-` @@@ @@@@7tI:&az` EN DB >     & . 6=Y?SQ   O& }  ]  s m 7  s  9 z h > p W-  \|M3C8 glz7b100IW Krieglstein2002X Krieglstein2003)Krishnamoorthy2000Krishnamoorthy2005 Krueger1980qKusuhara2006 Lachkar1998H Lam2003D Langham1989E Langham1989*Langhans199664Langhans19988 Lanzl2001 Lanzl2005( Lau2006 Le20040 LeBlanc2000 Lee2000+ Lesk20030, Lesk200320 Leske1995 Leske2002 Leske2003' LeVatte2004 Levene1980n Levin1997u Lexer1997mLiebmann2000r Lienert2003R Liu2002R Liu2002X Loebl1977t Logan2005+ Lovasik2003 Lubeck2001 Lung20050% Luscher1995 Lusky1995q Maeda2006i Maepea2001 Maggio19979W Maino2001J Manni2002 Mantyh19979} Mantyh20030 Mao1991Marchini20001 Mardin20033> Maren2006Marraffa2000 Martin19989g Martin2000p Martin2001ha Martin2002B Martini20052 Mashima2006{ Masini20000| Masini200409 Matthiessen2004> Matthiessen2006 Maumenee19801 Maunder1980 Mavroudis2006 McCarty Ph2004UMcCranor2004QMcKinnon2002h Melamed2003 Metheetrairut1994* Michelson19964 Michelson19981 Michelson2003 Migdal19988J Migliardi2002 Migliardi2003  Mikelberg1995 Miller20022 Milton1980Minckler1977 Morbio20000 Morgan2004 Morgan2005I Mori2001h Moroz2003Morrison1990 Morsman1995 Moster19944 Movaffaghy1998 Munch1995 Nagel2001 Nagel2002 Nagel2004 Nagel2005qNakamura2006 Narayan2005: Nascimbeni1997q Negi20066M Nelson1998P Nelson2003w Newby1999Nickells1995-Nicolela1996@Nicolela1996 Nie1996 Nishioka1977z Nyholt19979D O'Brien1989E O'Brien1989M O'Brien1998O O'Brien1998w O'Brien1999P O'Brien20032 Ohtake2006 Olsson1996 Onda1995 Orgul1996 Orgul1998A Orgul2000C Orgul2000" Orgul2001 Orgul2001 Orgul2002 Orgul2003< Orgul2004 Orgul2005 Orgul2006Orzalesi2002Orzalesi20030 Ozturk2003 Pache2001s Pache2002 Pache2002r Pache20031Papastathopoulos2003 Pappas2006lQ Paris2002 Parrish2002 Patel1996t Patterson2005p Pe'er1999 Pease1995Q Pena20022J Pesavento2002n Peter2006} Peters2003 Petrig19981 Picornell2003{ Pieri2000; Pieri2003Pillunat19973 Piltz-seymour2001Z Plange2001a Plange2002b Plange2003\ Plange2004] Plange2004d Plange20055 Plange20067 Plange20068 Plange2006O Poinoosawmy1998S Poinoosawmy2002 Polak2000v Polak2001 Polak2002 Pollack1980 Polska2000} Pomonis2003> Praga2006)Prasanna2000Prasanna20055 Predel20060G Price2003:Quaranta1997:Quaranta19979 Quigley1979 Quigley1990 Quigley1991 Quigley1995 Rainer2000K Rainer2004s Rainer20050 Rait20040@ Rankin19969t Rankin20055 Rassam1996Rechtman20033^Redbrake1999j Reim19939` Reim19955 Reim19966Reinhard2006' Reitsamer2004` Remky1995^ Remky1999_ Remky2000Z Remky2001a Remky2002b Remky2003 Remky2003\ Remky2004] Remky2004d Remky20055 Remky20067 Remky20068 Remky2006 Renard2002 Renard20030{ Renieri2000; Renieri2003| Renieri2004 Resch2004 Resch2005 Resink200119 Richard2004> Richard2006x Richardson1998 Riemer19999Rintalan2003 Riva19979 Riva19989 Riva2002e+ Rivard20030 Rogers1997} Rogers2003c Rosengarten2001 Rotenstreich20010W Ruggeri2001TRuokonen20022m Sample20000 Sanders1983Q Sanford20022 Sato2006[ Saxena20060Schachat1995DSchilder1989ESchilder1989 Schlingemann2001*Schmauss19966u Schmetterer1997L Schmetterer2000 Schmetterer2000v Schmetterer2001 Schmetterer2002K Schmetterer2004 Schmetterer2004 Schmetterer2005 Schmetterer2005 Schmetterer2005 Schmidt1994j Schulte1993` Schulte1995 Schulte1996ySchulzer2001G Schuman2003ASchumann2000XSchwartz1977YSchwartz1994dSchwartz2005s Schwarz2002n Scott2006Seifertl2002:Semeraro19977 Senff1995 Sergott1994 Serra2002 Serra2003 Setty1996 Shaffer1980 Shaw2005d Shields1991 Shields19952 Shinoda2006 Sibour19949U Siesky20040N Sihota20033[ Sihota2006D Silver19899E Silver1989 Simader2005 Singh1991N Singh2003[ Sinha2006{ Sodi20000; Sodi20030| Sodi20040 Sommer1991 Spaeth19944i Sperber2001j Sponsel1993Q Sponsel2002\ Sponsel2004 Stefansson20022 Stefansson2003 Stewart1991 Strobel1999n Strouthidis2006 Suburo20055 Suzuki19777 Taguchi2004[ Taneja2006q Tatsumi2006 Taylor20042 Tezel2004Thibault1995Thompson2003 Tielsch1991Tokunaga2004i Tomic2001. Tomita20000Topouzis2006+ Trabut20030'Tremblay20044 Trible1994Q Trigo2002Trinkaus2004 Trope1994 Tsukahara2004 Tsumura2004x Tunny1998{ Ucci20000; Ucci20030| Ucci20040 Van Buskirk1995 Van Buskirk1996 Van Buskirk2004 Van De Voorde2000 vanderWerf2001|Vannozzi2004 Varotto2000K Vass20040 Vass2005e[ Venkatesh2006WVetrugno2001 Vilser1995 Vilser19999 Vilser2001 Vilser20020 Vilser2004 Vilser2005 Vingerling1994 Vrensen2001 Vu20040> Wagenfeld2006&Waldmann1996/ Walker19879K Wally2004@ Walman19966 Wang2001 Wang20040~ Wang2006 Wax2004w Webb19999Q Weber2002o Weber20057 Weber2006 Weigert2005 Weinreb1994 Weinreb1995m Weinreb2000% Wenk19959^ Wenzel19999>Wiermann20066 Wijsman1995/ Wilson1987 Wilson19944 Wilson1996 Wilson20022 Wilson20060 Wintzer1999> Wlodarsch2006j Wolf1993` Wolf1995 Wolf19969 Wolfs2005G Wollstein2003 Wolter2003u Wolzt1997L Wolzt2000 Wong20040 Wu1995s Wuest2002I Yamaguchi2001?Yamazaki1997 Yan1994F Yang1997 Yee2003) Yorio2000 Yorio2005I Yoshida2001' Yu2004r' Yu20040 Yu20040 Yu2005 Yu2006- Yucel2003g Zacish20000 Zack19951mZangwill2000g Zarfati2000 Zawinka2004 Zawinka20069 Zeitz2004> Zeitz2006) Zhang2000) Zhang2000p Zimmerman19992004r' Yu200409 Zeitz2004> Zeitz2006) Zhang2000) Zhang2000SGEHO3hi~%oKWluvAj"S^ *)FC`g|<Ze0(=d8!1nxmtLDk'P+$r@ .?2B4#R6/N , Authors5"Journals .Keywords s                               Ћ q ,Agarwal, H. C. Akarsu, C.Akhalbedashvili, N. Aldinger, C. Alm, A. Amin, C. S.Amoako-Mensah, T.Anastasopoulos, E.Anderson, D. R. Aoki, S.Archibald, M. L. Arend, K. O. Arend, O. Arend, S. Armaly, M. F. Aydin, A. Azar, S. L. Baccini, M. Bachmann, K. Bacon, D. R.Balaratnasingam, C. Ball, A. K. Bathija, R.Batterbury, M. Becker, B.Bellezza, A. J.Ben Simon, G. J. Bengtsson, B. Berg, T. J. Berisha, F. Bernardi, P.Bilgili, M. Y.Bizzarro, R. L. Blum, M.Boles Carenini, B. Bonini, S. Bonomi, L. Bosem, M. E. Branca, F.Brauer-Burchardt, C.Breiteneder, H.Breteler, M. M.Brimage, P. J. Brun, A. M. Bucci, M. G. Buck, S.Buckley, A. R. Budde, W. M. Buehl, W. Bui, B. Bunce, C. Bunce, C. V. Bunt, A. H.Burgoyne, C. F. Campi, L. Cantatore, F. Cantor, L. B. Cardia, L.Carenini, A. B.Carlsson, A. M. Cassamali, M. Catton, M.Cavallini, G. M.Centofanti, M.Chakravarthy, U. Chamot, S. R. Chan, B. Chan, H. Chan, S. T.Chauhan, B. C. Chen, H. C. Cheng, C. Y.Childs-Shaw, K. Chou, J. C. Chung, H. S. Cioffi, G Cioffi, G. A. Ciulla, T. A. Clark, C. V.Clearkin, L. G. Cole, C. N.Coleman, A. L. Collignon, N.Collignon-Brach, J. Coloma, F. M.Connell, A. M. Costa, V. P.Cringle, S. J. Cull, G.Cunliffe, I. A.Curtain, R. P. Dallinger, S. Daneljan, L. Dang, M. Darhad, U.de Jong, P. T. de Voogd, S. Delaey, C. Demaster, E. Desai, D. Dewe, W. Dhanjil, S. Dichtl, A. Dielemans, I.Diestelhorst, M. Donato, F. Dong, J.Dorman-Pease, M. E. Dorner, G. Dorner, G. T.Douglas, G. R. Downs, J. C. Drance, S. Drance, S. M. Dubler, B. Duijm, H. F.Dunkelberger, G. R. Dupont, J. Eddy, D. M. Eddy, J. F.Eichler, H. G. Emre, M.Epstein, D. L. Ermis, S. S. Ethier, C. R. Evans, D.Farrell, R. A.Fechtner, R. D.Fercher, A. F. Feuer, W. J. Findl, O. Fisher, R. Flammer, J. Fontana, L. Formaz, F. Fortune, B.Fuchsjager-Mayrl, G. Fujioka, M. Galambos, P.  .Acta Ophthalmol Scand Acta Ophthalmol Scand SupplActa Ophthalmol SupplAm J OphthalmolArch OphthalmolBiomed Tech (Berl)Br J OphthalmolBrain Res BullClin Auton ResClin Exp Optom Clin Exp Pharmacol Physiol Clin Ther Curr Eye ResCurr Opin OphthalmolDoc OphthalmolEur J Ophthalmol Eur Neurol Exp Eye Res Exp NeurolEyeGer J OphthalmolGlia$ Graefes Arch Clin Exp OphthalmolIndian J OphthalmolInt OphthalmolInvest Ophthalmol Vis Sci J GlaucomaJ Hum HypertensJ Ocul Pharmacol TherJpn J OphthalmolKlin Monatsbl Augenheilkd Med Sci MonitNeuro-Ophthalmology NeurologyOphthalmic Res$Ophthalmic Surg Lasers Imaging Ophthalmologe Ophthalmology Optom Vis Sci Pharmacol ResProg Retin Eye Res Rev NeurosciSemin OphthalmolSurv OphthalmolTrans Am Ophthalmol SocUltrasound Med Biol  V X(#*African Continental Ancestry Group *Algorithms*Axonal Transport*Blood Circulation Time*Blood Flow Velocity*Blood Pressure,&*Blood Pressure Monitoring, Ambulatory*Blood-Brain Barrier*Capillary Permeability*Circadian Rhythm*Cold,(*Diagnostic Techniques, Ophthalmological*Disease Models, Animal($*European Continental Ancestry Group*Fluorescein Angiography,)*Fluorescein Angiography/*instrumentation *Genes$ *Glaucoma/classification/therapy*Heat*Hemodynamic Processes *Hemorheology *Homeostasis*Intraocular Pressure("*Intraocular Pressure/drug effects*Laser-Doppler Flowmetry *Lighting*Linkage (Genetics)*Online Systems*Ophthalmology*Ophthalmoscopes*Ophthalmoscopy *Optometry*Photic Stimulation*Polymorphism, Genetic *Posture*Pulsatile Flow *Rheology*Tilt-Table Test*Trabeculectomy$ *Ultrasonography, Doppler, Color,'*Ultrasonography, Doppler, Transcranial*Visual Fields(%Acetylcholine/administration & dosage Acute DiseaseAdministration, OralAdministration, Topical Adolescent,'Adrenergic alpha-Agonists/*pharmacology41Adrenergic alpha-Agonists/administration & dosage@:Adrenergic alpha-Agonists/administration & dosage/*adverseHBAdrenergic alpha-Agonists/administration & dosage/*therapeutic use,)Adrenergic beta-Antagonists/*pharmacology0,Adrenergic beta-Antagonists/*therapeutic use0+Adrenergic beta-Antagonists/therapeutic useAdult("African Continental Ancestry Group0+African Continental Ancestry Group/genetics Age FactorsAgedAged, 80 and overAging/*physiologyAging/pathologyAging/physiologyAlcohol Drinking Alleles Amino AcidsAnalysis of Variance41Angiography, Digital Subtraction/*instrumentation Animals Anthropometry<8Anti-Inflammatory Agents, Non-Steroidal/*therapeutic useAntibodies, Monoclonal Antigens, Surface/analysis,(Antihypertensive Agents/*therapeutic use@=Antihypertensive Agents/administration & dosage/*pharmacologyD@Antihypertensive Agents/administration & dosage/*therapeutic use<7Antihypertensive Agents/administration & dosage/adverse,'Antihypertensive Agents/therapeutic useApoptosis/*physiologyAqueous Humor/*chemistryAqueous Humor/metabolism Arteries Arteries/anatomy & histologyArteries/physiologyArteries/ultrasonography,&Arthritis, Rheumatoid/*blood/pathology Artifacts,)Asian Continental Ancestry Group/genetics CKeB 8(lC2 i#S"^6o@1*)DF/(|.'n+$r!vE, B!"0,0%2<GZ4=@"gRdBPCHON3+.W),h#Ng/L'k8?2CRK uA./6Ae S3F`08%m%'x jkt#B@tkLLit@AA`i xgh~815519534511n 2005 JaneXREffect of elevated intraocular pressure on endothelin-1 in a rat model16411100 244t8l 2006 Augl`YAsymmetric visual field loss and retrobulbar haemodynamics in primary open-angle glaucoma; 978-83|vPURPOSE: To investigate interocular differences in retrobulbar flow velocities in patients with asymmetric glaucomatous visual field loss. METHODS: Twenty-five patients with primary open-angle glaucoma (POAG) and asymmetric visual field loss were included in this study. Asymmetric visual field loss was defined as a difference of the global index mean deviation (MD) >6 dB between the two eyes. Flow velocities (peak systolic velocity PSV and end-diastolic velocity EDV) and resistive indices (RI) of the ophthalmic artery (OA), central retinal artery (CRA), and nasal and temporal posterior ciliary arteries were measured by means of colour Doppler imaging. RESULTS: MD of eyes with more severe glaucomatous visual field loss was -18.3+/-7.8 dB vs -6.8+/-5.5 dB (p<0.0001) in the less affected eyes. The PSV and the EDV of the CRA and the PSV of the OA were significantly decreased in eyes with more severe glaucomatous visual field loss (CRA PSV: 7.6+/-2.0 cm/s vs 8.3+/-1.7 cm/s, p=0.04; CRA EDV: 2.24+/-0.5 cm/s vs 2.55+/-0.6 cm/s, p<0.007; OA PSV: 29.7+/-9.9 cm/s vs 32.7+/-11.5 cm/s, p<0.02). None of the other differences in velocity or resistive index were significant. CONCLUSIONS: Patients with asymmetric glaucomatous visual field loss exhibit asymmetric flow velocities of the CRA and OA. Patients with more severe damage display reduced flow velocities in retrobulbar vessels in POAG.'ztDepartment of Ophthalmology, RWTH Aachen University, Pauwelsstrasse 30, 52057, Aachen, Germany, nplange@ukaachen.de..'Plange, N. Kaup, M. Arend, O. Remky, A. (!0721-832X (Print) Journal Articles& Graefes Arch Clin Exp Ophthalmollehttp://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=16411100lLUSIONS: Whereas risk factors for prevalence help select populations within which to screen for glaucoma, the factors that affect the rate of progression help decide the expected prognosis of the individual's untreated disease and thereby the frequency of follow-up and aggressiveness of the therapy to be undertaken.'<6Bascom Palmer Eye Institue, Miami, Fl 33101-6880, USA..'Drance, S. Anderson, D. R. Schulzer, M.(!0002-9394 (Print) Journal ArticleAm J OphthalmolAfrican Continental Ancestry Group/genetics Aged Asian Continental Ancestry Group/genetics Disease Progression Eye Hemorrhage/complications Female Glaucoma/complications/genetics/*physiopathology Humans *Intraocular Pressure Male Middle Aged Migraine Disorders/complications Optic Disk/blood supply Prognosis Reference Values Research Support, Non-U.S. Gov't Risk Factors Sex Characteristics Survival Analysis *Visual Fieldslehttp://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=11384564?  15288980 111e80 2004 AugeD=Detection of undiagnosed glaucoma by eye health professionals1508-142+PURPOSE: To examine the clinical features of undiagnosed open-angle glaucoma (OAG) in people who have attended an eye care provider within the previous 12 months and to suggest strategies to assist in the early detection of glaucoma. DESIGN: Population based cross-sectional study. PARTICIPANTS: Permanent residents aged 40 years and older at recruitment during 1992 through 1996. METHODS: A cluster-stratified random sample of 4744 participants from the urban and rural cohorts was studied. Structured standardized interviews and dilated ocular examinations were conducted in all eligible participants. Data on demographic characteristics, prior knowledge of eye disease, use of eye care services, intraocular pressures, cup-to-disc ratios, visual fields, and photography of optic discs were obtained. All suspected glaucoma cases were submitted to a panel of 6 ophthalmologists to determine glaucoma diagnosis. MAIN OUTCOME MEASURES: Clinical features of participants seen by eye health professionals within the previous 12 months who have previously undiagnosed OAG, previously diagnosed OAG, and no glaucoma. RESULTS: Thirty-five previously undiagnosed and 43 previously diagnosed participants had visited an optometrist or ophthalmologist or both in the previous 12 months. Age and gender were not significantly different between the undiagnosed and diagnosed glaucoma cases. After logistic regression, the type of eye professional seen (odds ratio [OR], 45.17; 95% confidence interval [95% CI], 5.89-346.17; P = 0.0002) and the presence of visual field defects (OR, 0.06; 95% CI, 0.01-0.69, P = 0.020) were the only statistically significant variables between the diagnosed and undiagnosed glaucoma groups. CONCLUSIONS: Raised intraocular pressure should not be relied on as the only triggering factor in glaucoma investigations.'RKCentre for Eye Research Australia, University of Melbourne, VIC, Australia.\VWong, E. Y. Keeffe, J. E. Rait, J. L. Vu, H. T. Le, A. McCarty Ph, D. C. Taylor, H. R.(!0161-6420 (Print) Journal Article OphthalmologyAdult Aged Aged, 80 and over Cross-Sectional Studies Diagnostic Techniques, Ophthalmological Female Glaucoma, Open-Angle/*diagnosis Humans Intraocular Pressure Male Middle Aged Ocular Hypertension/diagnosis *Ophthalmology Optic Disk/pathology Optic Nerve Diseases/diagnosis *Optometry Photography Research Support, Non-U.S. Gov't Rural Population Urban Population Vision Disorders/diagnosis Visual Fieldslehttp://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=152889809439354r 124=3e 1997 SepaxrThe relationship between progression of visual field defects and retrobulbar circulation in patients with glaucoma 287-95PURPOSE: To investigate whether lower blood flow velocities and higher resistive indices in the retrobulbar arteries are associated with progression of visual field defects in eyes with open-angle glaucoma with or without increased intraocular pressure. METHODS: Color Doppler imaging was performed in 16 eyes with progressive visual field defects in patients with normal-tension glaucoma, 15 eyes with practically stable visual field defects in patients with normal-tension glaucoma, 14 eyes with progressive visual field defects in glaucomatous patients with increased intraocular pressure, and 14 eyes with practically stable visual field defects in glaucomatous patients with increased intraocular pressure. Peak systolic velocity and end-diastolic velocity were measured, and resistive index was calculated in the central retinal artery, short posterior ciliary arteries, and the ophthalmic artery. RESULTS: Eyes with progressive visual field defects in patients with normal-tension glaucoma had statistically significantly lower blood flow velocities and higher resistive index in the central retinal artery and the short posterior ciliary arteries than did those with practically stable visual field defects, whereas, in the glaucomatous patients with increased intraocular pressure, such differences were not found. CONCLUSIONS: Eyes of patients with normal-tension glaucoma and progressive visual field defects have decreased blood flow velocities and increased resistive indices in their retrobulbar arteries, suggesting that these circulatory factors may be associated with the deterioration of visual field defects in patients with normal-tension glaucoma but may be less involved in the deterioration in glaucomatous patients with increased intraocular pressure.'VODepartment of Ophthalmology, University of British Columbia, Vancouver, Canada. Yamazaki, Y. Drance, S. M.RL0002-9394 (Print) Clinical Trial Journal Article Randomized Controlled TrialAm J OphthalmolBlood Circulation/*physiology Blood Flow Velocity/physiology Ciliary Arteries/physiology/ultrasonography Disease Progression Glaucoma, Open-Angle/drug therapy/*physiopathology Humans Intraocular Pressure Middle Aged Ophthalmic Artery/physiology/ultrasonography Orbit/*blood supply Retinal Artery/physiology/ultrasonography Ultrasonography, Doppler, Color Vision Disorders/*physiopathology *Visual Fieldsjdhttp://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=94393547918293p788_ 1994 AugJCDeformation of the lamina cribrosa by elevated intraocular pressureb 643-8a\UThe purpose of this study was to determine the mechanical response of the lamina cribrosa (LC) to elevated intraocular pressure (IOP) so as to identify possible mechanisms of optic nerve damage in early glaucoma. Ten pairs of normal human eyes were fixed after 24 hours' exposure to 50 mm Hg pressure (experimental eyes) or 5 mm Hg pressure (contralateral control eyes). Photomicrographs of the central region of the optic nerve head (ONH) were taken to examine the LC morphologically and to measure the dimensions of the LC. It was found that elevated IOP caused the LC to deflect posteriorly without affecting its thickness. The majority of the posterior displacement in the LC occurred near the periphery of the ONH. This shape change is consistent with a model of force distribution within the LC in which shear stresses are dominant; such stresses are maximal at the periphery and minimal at the centre of the ONH. These findings support a model in which mechanical forces, specifically shearing stresses within the peripheral lamina, play a direct role in the pathology of glaucomatous optic neuropathy.'JDDepartment of Ophthalmology, University of Toronto, Ontario, Canada.\VYan, D. B. Coloma, F. M. Metheetrairut, A. Trope, G. E. Heathcote, J. G. Ethier, C. R.(!0007-1161 (Print) Journal ArticleBr J OphthalmolAged Aged, 80 and over Aging/pathology Axons/pathology Humans Ocular Hypertension/*pathology Optic Disk/*pathology Research Support, Non-U.S. Gov't Sclera/*pathology Tissue Fixationrjdhttp://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=7918293X1985490i 1111 1991 Jan 15zsCorrelation between intraocular pressure control and progressive glaucomatous damage in primary open-angle glaucomaa 51-5Fifty-five patients with primary open-angle glaucoma and early glaucomatous damage who had medical therapy and laser trabeculoplasty were followed up for four to 11 years or until progressive glaucomatous damage was documented. Factors associated with the stability or progression of glaucoma were evaluated. Eyes with mean intraocular pressure higher than 21 mm Hg during the follow-up period uniformly had progressive glaucomatous c 9215759511 1977 NovyPIFluorescein angiographic defects of the optic disc in ocular hypertensione 1980-4~Fluorescein angiograms of the optic disc were studied in 23 normal and 29 ocular hypertensive eyes. Significant differences in the frequency distributions of areas of defects were obtained between normal and ocular hypertensive eyes. Increased areas of filling defects were noted in ocular hypertensive eyes as compared to normals. There were also significant correlations of the areas of filling defects with age and systolic blood pressure in the ocular hypertensive eyes that were not present in the normals. These observations support the concept that fluorescein angiography of the optic disc demonstrates localized areas of impaired circulation that increase with ocular pressure, age, and systolic blood pressure. This technique may be useful in separating normal from the ocular hypertensive patient who shows changes in the circulation of the optic disc with increased ocular pressure.Loebl, M. Schwartz, B.(!0003-9950 (Print) Journal ArticleArch OphthalmolAdolescent Adult Age Factors Aged Child Female *Fluorescein Angiography Humans *Intraocular Pressure Male Middle Aged Optic Disk/*pathology Research Support, U.S. Gov't, P.H.S.jchttp://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=921575 9Y,f,&Glaucoma, Open-Angle/blood/*metabolism0+Glaucoma, Open-Angle/blood/*physiopathology<9Glaucoma, Open-Angle/blood/complications/*physiopathology83Glaucoma, Open-Angle/complications/*physiopathology4/Glaucoma, Open-Angle/diagnosis/*physiopathology84Glaucoma, Open-Angle/diagnosis/*prevention & control82Glaucoma, Open-Angle/drug therapy/*physiopathology,)Glaucoma, Open-Angle/enzymology/*genetics0,Glaucoma, Open-Angle/epidemiology/*ethnology$Glaucoma, Open-Angle/pathology($Glaucoma, Open-Angle/physiopathology0-Glaucoma, Open-Angle/physiopathology/*surgery0,Glaucoma, Open-Angle/physiopathology/surgeryGlaucoma/*complications$!Glaucoma/*diagnosis/*epidemiology(#Glaucoma/*diagnosis/physiopathology,'Glaucoma/*drug therapy/*physiopathology,&Glaucoma/*drug therapy/physiopathologyGlaucoma/*etiology$Glaucoma/*metabolism/pathologyGlaucoma/*pathology($Glaucoma/*pathology/*physiopathology(#Glaucoma/*pathology/physiopathologyGlaucoma/*physiopathology41Glaucoma/*physiopathology/surgery/ultrasonography$Glaucoma/*prevention & control,'Glaucoma/chemically induced/*metabolism41Glaucoma/complications/*pathology/physiopathology,'Glaucoma/complications/*physiopathology4.Glaucoma/complications/diagnosis/*epidemiology40Glaucoma/complications/genetics/*physiopathology$ Glaucoma/diagnosis/*epidemiology Glaucoma/diagnosis/*pathology(#Glaucoma/diagnosis/*physiopathology,&Glaucoma/drug therapy/*physiopathology("Glaucoma/etiology/*physiopathology,'Glaucoma/etiology/pathology/radiography(#Glaucoma/pathology/*physiopathology("Glaucoma/pathology/physiopathologyGlaucoma/physiopathology,)Glaucoma/physiopathology/*ultrasonography0*Glial Fibrillary Acidic Protein/metabolism Glucose Transporter Type 1 GreeceHand Strength/*physiology HaplorhiniHealth Surveys Heart RateHeart Rate/drug effectsHeart Rate/physiologyHemodynamic Processes(#Hemodynamic Processes/*drug effects$!Hemodynamic Processes/*physiology$ Hemodynamic Processes/physiology Hemorrhage HomeostasisHomeostasis/*physiologyHomeostasis/physiologyHorseradish Peroxidase Humans Hypertension/complications0+Hypertension/complications/*physiopathology0*Hypertension/drug therapy/*physiopathologyHyperthermia, Induced84Hypertrophy/drug therapy/*metabolism/physiopathology Hypotension/*physiopathologyHypotension/complications Hypotension/physiopathologyHypothermia, Induced Hypothermia/physiopathology84Image Processing, Computer-Assisted/*instrumentation83Image Processing, Computer-Assisted/instrumentationImmunoenzyme TechniquesImmunohistochemistryIn Situ Nick-End Labeling Incidence Indomethacin/*therapeutic use Infusion Pumps, ImplantableInfusions, Intra-Arterial InjectionsInterferometryInterferometry/methodsIntraocular Pressure("Intraocular Pressure/*drug effects0-Intraocular Pressure/*drug effects/physiology$ Intraocular Pressure/*physiology$!Intraocular Pressure/drug effects0-Intraocular Pressure/drug effects/*physiology$Intraocular Pressure/physiologyIschemia/*diagnosis0,Ischemia/chemically induced/*physiopathologyIschemia/etiology<9Ischemic Attack, Transient/complications/*physiopathology$!Isometric Contraction/*physiology$ Isometric Contraction/physiologyItaly/epidemiologyKainic Acid/pharmacologyLaser Coagulation Laser SurgeryLaser-Doppler Flowmetry$ Laser-Doppler Flowmetry/*methods("Laser-Doppler Flowmetry/*standardsZ z9270610t492; 1997 AugpiMigraine association and linkage studies of an endothelial nitric oxide synthase (NOS3) gene polymorphisml 614-7eMigraine shows strong familial aggregation. However, the number of genes involved in the disorder is unknown and not identified. Nitric oxide is involved in the central processing of pain stimuli and plays an important role in the regulation of basal or stimulated vasodilation. Nitric oxide synthase, which controls the synthesis of nitric oxide, could possibly be a cause, or candidate gene, in migraine etiology. In this study, we detected a polymorphism for endothelial nitric oxide synthase by polymerase chain reaction and tested this for association and linkage to migraine. Results from the study did not show an association of the nitric oxide synthase microsatellite when tested in 91 affected and 85 unaffected individuals. Using the FASTLINK program for parametric linkage analysis, the polymorphism did not show significant linkage to migraine when tested in four migraine pedigrees composed of 116 individuals, 52 affected. Total LOD scores excluded linkage up to 8.5 cM between the nitric oxide synthase polymorphism and migraine. Results using the nonparametric affected pedigree member form of analysis also did not support a role for this gene in migraine etiology.d'\VSchool of Health Sciences-NHS, Griffith University, Gold Coast, Queensland, Australia.RKGriffiths, L. R. Nyholt, D. R. Curtain, R. P. Goadsby, P. J. Brimage, P. J. (!0028-3878 (Print) Journal Articlem NeurologyyAlleles Endothelium, Vascular/*enzymology *Genes Genotype Humans *Linkage (Genetics) Lod Score Migraine Disorders/*genetics Nitric Oxide Synthase/*genetics Pedigree *Polymorphism, Genetic Research Support, Non-U.S. Gov'tjdhttp://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=9270610126575944442 2003 AprinhChoroidal vascular reaction to hand-grip stress in subjects with vasospasm and its relevance in glaucoma1573-80 `ZPURPOSE: To assess the impact of vascular dysregulation on choroidal blood flow response to the hand-grip test and the relevance of this response to glaucoma. METHODS: Eighty healthy volunteers underwent a hand-grip test while choroidal blood flow was measured by means of laser Doppler flowmetry. Blood pressure, heart rate, and intraocular pressure (IOP) were monitored. Choroidal blood flow changes were compared between subjects with a positive history of cold hands and control subjects by means of analysis of variance. The relationship of the vascular response to the level of IOP at which progressive damage occurred was analyzed in 21 patients with primary open-angle glaucoma who had progressive damage despite normal or normalized IOP. RESULTS: Blood pressure and heart rate increased and IOP decreased in response to a hand-grip test. Healthy subjects with a positive history of cold hands (n = 36) demonstrated a decrease in choroidal blood flow during the hand-grip test (mean +/- SD: 13.5 +/- 5.8, 12.2 +/- 6.8, and 13.4 +/- 6.9 AU, at baseline, during the test, and 3 minutes after release, respectively), whereas control subjects (n = 44) demonstrated an inverse (12.5 +/- 8.3, 13.7 +/- 9.4, and 11.9 +/- 7.1 AU, respectively) response pattern (P = 0.039). Glaucoma patients with a decrease of at least 10% in choroidal blood flow during the hand-grip test had lower IOP (14.67 +/- 3.83 and 13.50 +/- 2.59 mm Hg in the right and the left eyes, respectively) compared (P = 0.032) with those without such a decrease (16.54 +/- 3.85 and 16.92 +/- 2.95 mm Hg in the right and the left eyes, respectively). CONCLUSIONS: A hand-grip test elicits a different blood flow response in subjects with vasospasm compared with control subjects. Damage by glaucoma in patients with a decrease in choroidal blood flow during a hand-grip test may progress at a relatively lower IOP.'0*University Eye Clinic, Basel, Switzerland.PJGugleta, K. Orgul, S. Hasler, P. W. Picornell, T. Gherghel, D. Flammer, J.(!0146-0404 (Print) Journal Article Invest Ophthalmol Vis ScitnAdult Blood Flow Velocity Blood Pressure/physiology Choroid/*blood supply Female Glaucoma, Open-Angle/*physiopathology Heart Rate/physiology Humans Hypotension/physiopathology Hypothermia/physiopathology Intraocular Pressure/physiology Isometric Contraction/physiology Laser-Doppler Flowmetry Male Middle Aged Research Support, Non-U.S. Gov't Stress/*physiopathologylehttp://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=1265759412472448833l 2000 May{d]Normal tension glaucoma: diagnostic features and comparisons with primary open angle glaucoma\161-172\yBACKGROUND: A significant proportion of patients diagnosed under the broad classification of open angle glaucoma actually has normal tension glaucoma (NTG). It has many clinical features that overlap with primary open angle glaucoma (POAG), yet there is a question of whether it has a different aetiology in which intraocular pressure plays less of a role. METHODS: The epidemiology and clinical features of normal tension glaucoma are reviewed with particular reference to possible differences from primary open angle glaucoma, which might permit differentiation. The pathophysiology is discussed, outlining recent research in cell death (apoptosis), axonal damage and neuroprotection. DISCUSSION AND CONCLUSION: There is considerable evidence that NTG develops with little contribution from the effect of intraocular pressure. However, the clinical diagnosis of NTG is often one of exclusion and the differentiation of NTG from POAG remains difficult because many clinical signs are suggestive but not definitive of NTG. More accurate diagnosis may be possible when individual patients exhibit a greater number of signs. Some evidence suggests that NTG with relatively high pressures (greater than 15 mmHg) is more likely to progress than NTG with relatively low pressures. Clinicians must be particularly alert to the possibility of NTG because IOP, a clinical marker for some glaucomas, is absent.'tnDepartment of Optometry and Vision Sciences, The University of Melboune, Parkville, Victoria, 3052, Australia.Gutteridge, I. F.(!0816-4622 (Print) Journal articleClin Exp Optomlehttp://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=12472448 9V ta($Diabetic Retinopathy/physiopathology,'Diagnostic Techniques, Ophthalmological<8Diagnostic Techniques, Ophthalmological/*instrumentation DiastoleDiastole/physiologyDisease Models, AnimalDisease ProgressionDNA Damage/physiology DNA/analysis$ Dose-Response Relationship, DrugDouble-Blind Method Drug Administration ScheduleDrug Therapy, Combinationeffects/*therapeutic use$Electrocardiography, AmbulatoryElectrophoresis, Agar GelEndothelin-1/*bloodEndothelin-1/*genetics(#Endothelin-1/*metabolism/physiology Endothelin-1/*pharmacologyEndothelin-1/*physiologyEndothelin-1/bloodEndothelin-1/geneticsEndothelin-1/pharmacologyEndothelins/*bloodEndothelins/*pharmacology("Endothelins/metabolism/*physiology0+Endothelium, Corneal/*enzymology/metabolism$!Endothelium, Vascular/*enzymology,&Endothelium, Vascular/*physiopathology$Endothelium, Vascular/chemistry$ Endothelium, Vascular/physiologyEnglish Abstract,)Enzyme Inhibitors/administration & dosage(#Epinephrine/administration & dosageEquipment DesignErythrocytes/pathologyEstrogens/physiologyEvaluation Studies Exercise TestExercise/*physiologyExercise/physiology4/Extracellular Matrix/*metabolism/ultrastructure40Eye Diseases/diagnosis/*etiology/physiopathology Eye Diseases/physiopathology Eye Hemorrhage/complications0*Eye Injuries, Penetrating/*physiopathologyEye/*blood supply4/Eye/*blood supply/*drug effects/physiopathology$Eye/*blood supply/drug effects Eye/*blood supply/metabolism$!Eye/*blood supply/ultrasonography($Eye/*physiopathology/ultrasonography(%Eye/anatomy & histology/*blood supplyEye/blood supplyFalse Negative Reactions FemaleFingers/*blood supplyFingers/blood supply Flicker Fusion/*physiologyFluorescein Angiography,(Fluorescein Angiography/*instrumentation$ Fluorescein Angiography/*methods$Fluorescein Angiography/methodsFluorescein/*metabolism83Fluorescein/administration & dosage/*diagnostic use,(Fluorescent Antibody Technique, IndirectFollow-Up StudiesForearm/blood supply Fundus OculiGene ExpressionGene Frequency Genotype82Glaucoma, Angle-Closure/*pathology/physiopathology Glaucoma, Open-Angle/*blood<8Glaucoma, Open-Angle/*blood/drug therapy/physiopathology84Glaucoma, Open-Angle/*complications/*physiopathology40Glaucoma, Open-Angle/*complications/epidemiology0-Glaucoma, Open-Angle/*complications/pathology$Glaucoma, Open-Angle/*diagnosis83Glaucoma, Open-Angle/*drug therapy/*physiopathology82Glaucoma, Open-Angle/*drug therapy/physiopathologyHBGlaucoma, Open-Angle/*drug therapy/physiopathology/ultrasonography("Glaucoma, Open-Angle/*epidemiology0+Glaucoma, Open-Angle/*epidemiology/etiology85Glaucoma, Open-Angle/*etiology/*pathology/radiography,'Glaucoma, Open-Angle/*etiology/genetics$Glaucoma, Open-Angle/*genetics$ Glaucoma, Open-Angle/*metabolism0*Glaucoma, Open-Angle/*metabolism/pathology4/Glaucoma, Open-Angle/*pathology/physiopathology(%Glaucoma, Open-Angle/*physiopathology4.Glaucoma, Open-Angle/*physiopathology/*surgery4.Glaucoma, Open-Angle/*physiopathology/*therapy0-Glaucoma, Open-Angle/*physiopathology/surgery0-Glaucoma, Open-Angle/*physiopathology/therapy85Glaucoma, Open-Angle/*physiopathology/ultrasonographyu 8646172g5J1H 1996 JanC@:Retinal hemodynamics during increased intraocular pressure9196381643 1997 Mar`ZThe effect of systemic nitric oxide-synthase inhibition on ocular fundus pulsations in man 305-12There is experimental evidence that endothelium derived nitric oxide is involved in the regulation of ocular vascular tone. The purpose of this study was to investigate the effects of NO-synthase inhibition by N-monomethyl-L-arginine (L-NMMA) on ocular fundus pulsations in young healthy volunteers. Three milligrams per kilograms L-NMMA were administered i.v. over 5 minutes. Protocol 1: Measurements of blood pressure, pulse rate, fundus pulsation amplitude, NO-exhalation, and cardiac output were performed at baseline and 10, 30, 60, 90, 150, and 300 minutes after L-NMMA infusion (n = 8). Fundus pulsation amplitude, which has been shown to estimate the pulsatile component of the choroidal blood flow, was recorded with a recently developed laser interferometer. Protocol 2: Measurements of blood pressure, pulse rate, fundus pulsation amplitude, NO-exhalation, and blood flow velocity in the ophthalmic artery were performed in a randomized, placebo controlled cross over study (n = 10). Ten minutes after L-NMMA administration fundus pulsation amplitude decreased by 23 +/- 2% (protocol 1) and 19 +/- 1% (protocol 2, P < 0.01 each), cardiac output by 12 +/- 2% (P < 0.01), and exhaled NO by 55 +/- 6% (protocol 1) and 41 +/- 6% (protocol 2, P < 0.01 each). All parameters returned to baseline values within the 300 minutes observation period, with a faster recovery of fundus pulsation amplitude than of cardiac output and exhaled NO. Blood pressure, pulse rate, and ophthalmic artery blood flow velocity showed only minor changes during and after administration of L-NMMA. Our results suggest that systemic NO-synthase inhibition reduces pulsatile choroidal and most likely total choroidal blood flow in humans. The recovery of vascular tone in choroidal vessels seems to be different from the cardiovascular response. Our findings indicate that reduced fundus pulsations after L-NMMA are caused by systemic factors as well as by local reactions of the choroidal vasculature.'JCDepartment of Clinical Pharmacology, University of Vienna, Austria.n|Schmetterer, L. Krejcy, K. Kastner, J. Wolzt, M. Gouya, G. Findl, O. Lexer, F. Breiteneder, H. Fercher, A. F. Eichler, H. G.RL0014-4835 (Print) Clinical Trial Journal Article Randomized Controlled Trial Exp Eye ResnAdult Blood Flow Velocity/drug effects Choroid/blood supply/*drug effects Cross-Over Studies Double-Blind Method Fundus Oculi Humans Male Nitric Oxide/metabolism Nitric Oxide Synthase/*antagonists & inhibitors Ophthalmic Artery/*drug effects/physiology/ultrasonography Pulse/drug effects Regional Blood Flow/drug effects Research Support, Non-U.S. Gov't omega-N-Methylarginine/*pharmacologyjdhttp://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=9196381$9270610t492; 15744136162 2005 AprBlood flow in glaucoma 79-83PURPOSE OF REVIEW: Glaucoma, one of the leading causes of blindness in the world, is characterized by progressive visual field loss and distinctive excavation of the optic nerve head. Although elevated intraocular pressure is the major risk factor, there is increasing evidence that the pathogenesis of glaucoma is also linked to altered ocular blood flow. This review summarizes the recent publications relevant to blood flow in glaucoma. RECENT FINDINGS: Several studies indicate that a perfusion instability, rather than a steady reduction of ocular blood flow, might contribute to glaucomatous optic neuropathy. The main cause of the instability is a disturbed autoregulation in the context of a general vascular dysregulation. The underlying mechanism of such a vascular dysregulation is not known. A dysfunction of both the autonomic nervous system and vascular endothelial cells is discussed. SUMMARY: The mechanical and vascular theories are not mutually exclusive; on the contrary, a vascular dysregulation increases the susceptibility to intraocular pressure. Therapeutically, therefore, both an intraocular pressure reduction and an improvement of the ocular blood flow might be considered.'0)University Eye Clinic Basel, Switzerland.$Grieshaber, M. C. Flammer, J..(1040-8738 (Print) Journal Article ReviewCurr Opin OphthalmolAnimals Biological Markers/blood Blood Flow Velocity/physiology Blood Pressure/physiology Endothelin-1/blood Eye/*blood supply Glaucoma, Open-Angle/blood/complications/*physiopathology Humans Intraocular Pressure/physiology Laser-Doppler Flowmetry Ophthalmic Artery/*physiology Optic Nerve Diseases/etiology/physiopathology Regional Blood Flow/physiology Ultrasonography, Doppler, Color Vasoconstriction/physiology Visual Fields/physiologylehttp://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=15744136Q 11755835 1331 2002 JanLatanoprost and brimonidine: therapeutic and physiologic assessment before and after oral nonsteroidal anti-inflammatory therapy 11-8 PURPOSE: To assess, before and during oral nonsteroidal anti-inflammatory drug coadministration, latanoprost's and brimonidine's hypotensive action in eyes at risk of glaucomatous progression, assessing the effect of each drug on ocular perfusion and visual function. METHODS: Twenty consenting adults with open-angle glaucoma or ocular hypertension underwent a double-masked, bilateral, randomized prospective study. Treatment started with either latanoprost 0.005% in the morning and placebo in the evening, or brimonidine 0.2% twice daily in one eye; after 1 week starting the other in the fellow eye. After another week, oral indomethacin 25 mg four times a day, commenced for 2 more weeks. Intraocular pressure, ocular circulation, and visual function were monitored pretreatment, after unilateral monotherapy (day 7), bilateral ocular therapy (day 14), and coadministered oral indomethacin (day 28). Intrasubject differences (interocular and intraocular relative to baseline) were determined by two-tailed paired t test. RESULTS: A loss of the significance of intraocular pressure reduction with brimonidine was noted after oral indomethacin coadministration (-14%; P =.004 for brimonidine alone versus -11%; P =.3 with indomethacin). Significant intraocular pressure reduction with latanoprost persisted despite indomethacin (-25%; P <.0001 for latanoprost alone versus -30%; P <.0001 with indomethacin). Pulsatile ocular blood flow increased 40% with latanoprost, but was unchanged with brimonidine (interdrug difference, P =.004). Midperipheral retinal microcirculation increased 23% (P =.03) with latanoprost. Humphrey perimetry and contrast sensitivity remained consistently at or above baseline with both latanoprost and brimonidine. Indomethacin had no significant effect on ocular perfusion or visual function measures. CONCLUSIONS: Circulatory and hydrodynamic findings differed substantially for the two drugs. The loss of significance of intraocular pressure reduction with brimonidine during indomethacin treatment may be clinically important.'South Texas Ocular Imaging Center, University of Texas Health Science Center at San Antonio, Department of Ophthalmology, San Antonio, Texas 78229-3900, USA. sponsel@uthscsa.eduTNSponsel, W. E. Paris, G. Trigo, Y. Pena, M. Weber, A. Sanford, K. McKinnon, S.RL0002-9394 (Print) Clinical Trial Journal Article Randomized Controlled TrialAm J Ophthalmol60Administration, Oral Adult Aged Anti-Inflammatory Agents, Non-Steroidal/*therapeutic use Antihypertensive Agents/administration & dosage/adverse effects/*therapeutic use Blood Flow Velocity/drug effects Comparative Study Contrast Sensitivity/drug effects Double-Blind Method Drug Therapy, Combination Female Glaucoma, Open-Angle/*drug therapy/physiopathology Humans Indomethacin/*therapeutic use Intraocular Pressure/*drug effects/physiology Laser-Doppler Flowmetry Male Middle Aged Ocular Hypertension/drug therapy/physiopathology Ophthalmic Solutions Prospective Studies Prostaglandins F, Synthetic/administration & dosage/adverse effects/*therapeutic use Quinoxalines/administration & dosage/adverse effects/*therapeutic use Research Support, Non-U.S. Gov't Retinal Vessels/drug effects Visual Fields/drug effectslehttp://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=11755835 @ N=\_da^ GhJ'!y e <#OK|;{T"C $z,+f.6lpw]Um1 %MP HD(0RXtBV94*Iq@-rs3857ZbS):}c2LuvAY[EQnixW&~o/`j?Fg>y of each clinical finding in the individuals who later developed visual field defects were determined, and none of the clinical findings was found to be a good predictive indicator.>7Kitazawa, Y. Horie, T. Aoki, S. Suzuki, M. Nishioka, K.(!0003-9950 (Print) Journal ArticleArch OphthalmolAdult Female Follo75532568610 1979 OctnhThe histology of human glaucoma cupping and optic nerve damage: clinicopathologic correlation in 21 eyes1803-30We have examined by light and electron microscopy the retina, optic nervehead, a16914471 2006 Aug 16b\Retrobulbar hemodynamics and morphometric optic disc analysis in primary open-angle glaucomaRLBACKGROUND: Previous studies confirmed reduced retrobulbar hemodynamics in primary open-angle glaucoma (POAG). To investigate a correlation between retrobulbar hemodynamics and morphometric neuroretinal rim analysis in patients with POAG. METHODS: Fifty-one patients with POAG (mean age 65 11 years) were included in this clinical study. Blood flow velocities (peak systolic (PSV) and end-diastolic (EDV) velocities) of the ophthalmic artery (OA), central retinal artery (CRA), posterior ciliary arteries (PCA), and central retinal vein were measured using colour Doppler imaging (Siemens Sonoline Sienna). Optic disc morphometry was performed using scanning laser tomography (Heidelberg Retinal Tomograph II). The stereometric parameters of the neuroretinal rim (rim area, rim volume, cup shape measure, and retinal nerve fibre layer (RNFL) cross sectional area) were used for analysis. RESULTS: The PSV of the CRA was significantly (p<0.001) correlated to rim area (r=0.50) and rim volume (r=0.51). The minimum velocities of the central retinal vein were significantly (p<0.001) correlated to rim volume (r=0.56) and RNFL cross sectional area (r=0.49). No correlations were found for the flow velocities of the OA and PCAs. CONCLUSION: Retrobulbar hemodynamics of the central retinal artery and vein are correlated to the neuroretinal rim damage in POAG.'>7RWTH Aachen University, Dept of Ophthalmology, Germany.A:4Plange, N. Kaup, M. Weber, A. Arend, K. O. Remky, A.(!0007-1161 (Print) Journal article Br J Ophthalmolllehttp://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=16914471  BE8[ 816840877837n 2006 Jul{Topography and fluorescein angiography of the optic nerve head in primary open-angle and chronic primary angle closure glaucoma 520-6{PURPOSE: The purpose of this study is to correlate optic nerve head topography with fluorescein angiography of the optic nerve head in patients with primary open-angle glaucoma (POAG), chronic primary angle closure glaucoma (CPACG), and normal controls. METHODS: This was an institution-based, cross-sectional, case-control study of 30 consecutive patients each with POAG or CPACG, which were compared with 30 age- and sex-matched controls. The fluorescein angiograms undertaken in one eye of each of the 90 subjects were then analyzed both qualitatively and quantitatively. RESULTS: The mean age of controls (group 1) was 51.73 +/- 9.6 years, patients with CPACG (group II) was 53.26 +/- 9.5 years, and patients with POAG (group III) was 54.5 +/- 10.4 years. The mean deviation and corrected pattern standard deviation on Humphrey visual field analyzer, respectively, were -1.51 +/- 2.01 dB and 2.09 +/- 1.04 dB the in control group, -9.4 +/- 9.3 dB and 5.32 +/- 4.02 dB in the CPACG group, and -11.27 +/- 7.7 dB and 7.57 +/- 5.34 dB in the POAG group. There was no significant difference in the disc areas between the three groups (analysis of variance [ANOVA], p = 0.157). All circulatory parameters were delayed in both glaucoma groups compared with controls with the disc filling time (ANOVA, p = 0.001) and the choroidal filling time being significantly delayed (ANOVA, p = 0.006). The Moorfield regression analysis showed good correlation with the pattern of disc fluorescence in all quadrants in cases of CPACG and POAG. CONCLUSION: The optic nerve head and choroidal circulation was delayed in both patients with POAG and those with CPACG, which correlates with loss of neuroretinal rim and retinal nerve fiber layer on the Heidelberg Retina Tomograph II (HRT). Patients with POAG showed diffuse damage with significant rim loss, whereas patients with CPACG showed marked sectorial abnormalities (superotemporal and the inferior-temporal) on fluorescein angiography and HRT. One possible reason for this discrepancy could be sectorial ischemia occurring in cases of CPACG as a result of a sudden rise of intraocular pressure causing disc and visual field damage.p'jdDr. R. P. Center for Ophthalmic Sciences, All India Institute of Medical Sciences, New Delhi, India.>8Sihota, R. Saxena, R. Taneja, N. Venkatesh, P. Sinha, A.(!1040-5488 (Print) Journal Article  Optom Vis ScitBlood Flow Velocity/physiology Choroid/*blood supply Chronic Disease Comparative Study Cross-Sectional Studies Disease Progression Female *Fluorescein Angiography Follow-Up Studies Fundus Oculi Glaucoma, Angle-Closure/*pathology/physiopathology Glaucoma, Open-Angle/*pathology/physiopathology Humans Male Middle Aged Optic Disk/*pathology Perimetry Retrospective Studies Severity of Illness Index Visual Fieldslehttp://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=168408772546363  191B 1989JCEstimation of pulsatile ocular blood flow from intraocular pressurea 25-9A relationship has been derived between intraocular pressure and pulsatile blood flow in the eye. Measurements of intraocular pressure show a time variation that is associated with the pulsatile component of arterial pressure. Experimental results provide a means of transforming intraocular pressure changes into ocular volume changes. The eye is represented by a chamber with elastic walls, a pulsatile incoming flow of incompressible fluid (blood), and a steady outgoing flow of blood. Under these conditions, the rate of pulsatile blood flow through the eye can be approximated from the instantaneous intraocular pressure measurements. Data from a healthy human eye are used to illustrate the analysis.'.(Johns Hopkins University, Baltimore, MD.JDSilver, D. M. Farrell, R. A. Langham, M. E. O'Brien, V. Schilder, P.Journal ArticleActa Ophthalmol SupplBlood Flow Velocity Comparative Study Eye/anatomy & histology/*blood supply Humans *Intraocular Pressure *Pulsatile Flow Research Support, U.S. Gov't, Non-P.H.S. Research Support, U.S. Gov't, P.H.S. *Rheology Time Factorsjdhttp://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=254636318675501 109.8f 1991 AugiRelationship between intraocular pressure and primary open angle glaucoma among white and black Americans. The Baltimore Eye Survey 1090-5 A detailed ocular examination, including perimetry, was conducted on 5308 black and white subjects aged 40 years and older in a population-based prevalence survey in east Baltimore, Md. Repeated, detailed examinations were carried out on selected subjects. Roughly half of all subjects with optic nerve damage from primary open angle glaucoma, regardless of race, were unaware that they had the condition. The average intraocular pressure (IOP) among black patients with glaucoma who were receiving treatment was virtually identical to that in those black patients who were not receiving treatment (median IOP, 20 mm Hg); treated eyes of white patients had a lower IOP than those eyes of white patients who were not receiving treatment (mean [+/- SD] IOP, 18.69 +/- 3.23 mm Hg vs 24.15 +/- 5.23 mm Hg; P less than .001). The risk of glaucomatous optic nerve damage increased with the height of the screening IOP, particularly at levels of 22 to 29 and 30 mm Hg and above (relative rate compared with IOP of 15 mm Hg or lower, 12.8 and 40.1 mm Hg, respectively). More than half of all glaucomatous eyes had a screening IOP below 21 mm Hg, whether these eyes were receiving treatment or not. The IOP in glaucomatous eyes tended to rise on follow-up, in contrast with nonglaucomatous eyes in which the IOP was as likely to rise as to fall. Results confirmed that IOP is an important factor in glaucoma, but did not support the traditional distinction between "normal" and "elevated" pressure, nor its corollaries, "low-tension" glaucoma and "high-tension" glaucoma.'XRDana Center for Preventive Ophthalmology, Johns Hopkins University, Baltimore, Md.\USommer, A. Tielsch, J. M. Katz, J. Quigley, H. A. Gottsch, J. D. Javitt, J. Singh, K.(!0003-9950 (Print) Journal ArticleArch Ophthalmol*African Continental Ancestry Group *European Continental Ancestry Group Glaucoma, Open-Angle/epidemiology/*ethnology Health Surveys Humans *Intraocular Pressure Maryland/epidemiology Prevalence Research Support, U.S. Gov't, P.H.S. Risk Factorsjdhttp://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=1867550d.\USommer, A. Tielsch, J. M. Katz, J. Quigley, H. A. Gottsch, J. D. Javitt, J. Singh, K.(!0003-9950 (Print) Journal ArticleArch Ophthalmol*African Continental Ancestry Group *European Continental Ancestry Group Glaucoma, Open-Angle/epidemiology/*ethnology Health Surveys Humans *Intraocular Pressure Maryland/epidemiology Prevalence Research Support, U.S. Gov't, P.H.S. Risk Factorsjdhttp://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=1867550d.\USommer, A. Tielsch, J. M. Katz, J. Quigley, H. A. Gottsch, J. D. Javitt, J. Singh, K.(!0003-9950 (Print) Journal ArticleArch Ophthalmol*African Continental Ancestry Group *European Continental Ancestry Group Glaucoma, Open-Angle/epidemiology/*ethnology Health Surveys Humans *Intraocular Pressure Maryland/epidemiology Prevalence Research Support, U.S. Gov't, P.H.S. Risk Factorsjdhttp://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=1867550  |11436940173  2001 JunRKEffect of brimonidine tartrate on ocular hemodynamics in healthy volunteers0199-205\While alpha2-adrenergic agonists, such as brimonidine tartrate, significantly reduce the intraocular pressure (IOP), the presence of vasoconstrictor postsynaptic alpha2 receptors on vascular smooth muscle raise the possibility that brimonidine could potentially compromise ocular blood flow. Consequently, the ocular hemodynamic effects of brimonidine were studied in normal subjects. Twelve healthy volunteers were included in this prospective, double-masked, placebo controlled, crossover-designed clinical trial. They received either brimonidine tartrate 0.2% or placebo b.i.d. for 2 weeks. Goldmann tonometry and color Doppler imaging (CDI) were performed at baseline, at 2 hr, 1 week, and 2 weeks after the treatment. Fundus angiography using a scanning laser ophthalmoscope was performed at baseline and 2 weeks after treatment to determine retinal arteriovenous passage time. Brimonidine lowered IOP at 2 hr, 1 week, and 2 weeks (p = 0.058, p = 0.031, and p = 0.022, respectively). Brimonidine did not affect the retrobulbar arterial velocities measured by CDI, nor retinal arteriovenous passage time. In conclusion, two-week treatment with brimonidine reduces IOP and does not reduce the bulk retinal or retrobulbar arterial perfusion in young healthy volunteers.'Glaucoma Research and Diagnostic Center, Department of Ophthalmology, Indiana University Medical Center, Indianapolis 46202, USA.lvoJonescu-Cuypers, C. P. Harris, A. Ishii, Y. Kagemann, L. Gazozi, H. J. Rotenstreich, Y. Chung, H. S. Martin, B.iRL1080-7683 (Print) Clinical Trial Journal Article Randomized Controlled TrialJ Ocul Pharmacol Thera Administration, Topical Adrenergic alpha-Agonists/*pharmacology Adult Blood Flow Velocity/drug effects Blood Pressure/drug effects Ciliary Arteries/*physiology/ultrasonography Cross-Over Studies Double-Blind Method Female Fluorescein Angiography Heart Rate/drug effects Humans Intraocular Pressure/*drug effects Male Ophthalmic Artery/*physiology/ultrasonography Ophthalmic Solutions Prospective Studies Quinoxalines/*pharmacology Retinal Artery/*physiology/ultrasonography Tonometry, Ocular Ultrasonography, Doppler, Colorilehttp://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=11436940d9613377822p 1998 FebsLFHeidelberg retinal flowmetry: factors affecting blood flow measurement 131-6oAIMS: To evaluate factors affecting Heidelberg retinal flowmeter (HRF) measurements of retinal and optic nerve head blood flow in human subjects. METHODS: The angle of incidence between laser beam and fundus, and camera distance from the eye, were evaluated for their effect upon measures of blood volume, velocity, and flow in a single 100 x 100 x 400 microns volume of temporal peripapillary retinal tissue in normal volunteers. Both intra and intersession reproducibility of these measures were studied. Intersession data were obtained by taking one image per week for 4 weeks. Finally, the intersession haemodynamic data were examined in the entire image (640 x 2560 x 400 microns), using histograms of pixel by pixel blood flow. RESULTS: Measures of blood volume, velocity, and flow from a single anatomical site were unaffected by laser beam to fundus angle of incidence (n = 12). As camera distance from the eye was increased (from 2 to 5 to 7 cm), flow measurements showed increasing individual changes, despite unaltered measured vessel lengths and constant overall mean flow (n = 14). The coefficient of variation for two intersession images of optic nerve head blood flow averaged 7% (n = 20); in contrast, the 4 week intersession coefficient of variation averaged 30% (n = 15). Intersession reproducibility was increased by using flow histograms from the entire image: the coefficients of variation averaged 16% for total flow and 17% for flow in the pixel of median flow. CONCLUSION: HRF measures of flow are independent of the laser beam to fundus angle of the incidence and dependent upon camera distance from the eye. Intersession reproducibility is best using pixel by pixel analysis of the entire image.'b\Department of Ophthalmology, Indiana University School of Medicine, Indianapolis 46202, USA.HBKagemann, L. Harris, A. Chung, H. S. Evans, D. Buck, S. Martin, B.(!0007-1161 (Print) Journal ArticleBr J Ophthalmol Blood Flow Velocity Hemodynamic Processes Humans Laser-Doppler Flowmetry/*methods Optic Disk/*blood supply Reproducibility of Results Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S. Retinal Diseases/*physiopathology Retinal Vessels/*physiologyjdhttp://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=961337774477699812 1980 DecfxqAlternative definitions of open-angle glaucoma. Effect on prevalence and associations in the Framingham eye study 2172-7\VFramingham Eye Study data were used to examine the effect of alternative definitions of open-angle glaucoma (OAG) on prevalence and on associations with selected variables from the Framingham Heart Study. Definitions were based on various combinations of history of glaucoma, types of visual field defects, and functions of intraocular pressure and cup-disc ratio. Visual field defect irrespective of blind spot enlargement is used as a standard for comparison. Prevalence of OAG by this definition is higher for men than for women and increases with age, more markedly than for most other definitions. Alcohol consumption is directly related to glaucoma defined either by the reference standard or by visual field defects including blind spot enlargement. Systemic blood pressure, ventricular rate, and diagnosis of diabetes are directly related to IOP. Kahn, H. A. Milton, R. C.(!0003-9950 (Print) Journal ArticleArch OphthalmolAged Alcohol Drinking Blood Pressure Female Glaucoma/complications/diagnosis/*epidemiology Humans Intraocular Pressure Male Massachusetts Middle Aged Papilledema/etiology Terminology Vision Disorders/etiology Visual Fieldsjdhttp://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=7447769R 123860778611 2002 Nov ztEffect of latanoprost 0.005% and brimonidine tartrate 0.2% on pulsatile ocular blood flow in normal tension glaucoma 1236-9~xAIM: To determine the effect of brimonidine tartrate 0.2% and latanoprost 0.005% on pulsatile ocular blood flow (POBF) in patients with normal tension glaucoma (NTG). METHOD: NTG patients with progressive optic neuropathy, new disc haemorrhage, or field defects that threatened fixation were enrolled into a randomised, investigator masked, crossover study. Group I patients received 4 weeks each of latanoprost, lubricant, and brimonidine, while group II patients received 4 weeks each of brimonidine, lubricant, and latanoprost. Diurnal POBF was measured at baseline and after each 4 week treatment. RESULTS: 25 patients completed the study and had reliable POBF measurement at each visit. There was no significant diurnal change in baseline POBF (p = 0.768). Latanoprost increased POBF by 213 (SD 257) micro l/min (22.8%, p <0.001) while brimonidine increased it by 97 (183) micro l/min (10.4%, p = 0.014). POBF increased at 8 am (p = 0.004), 12 noon (p = 0.002), and 4 pm (p <0.001) with latanoprost, while it increased only at 8 am (p = 0.016) with brimonidine. After adjusting for the factor of IOP, neither latanoprost nor brimonidine increased POBF significantly. CONCLUSIONS: Latanoprost increases the mean POBF that is related to its IOP lowering effect. The increase in POBF noted after brimonidine is within the range of long term variation and may not be attributable to the drug effect.'Department of Ophthalmology, Taipei Veterans General Hospital, Taipei, Taiwan National Yang-Ming University School of Medicine, Taipei, Taiwan. jlliu@vghtpe.gov.tw JCLiu, C. J. Ko, Y. C. Cheng, C. Y. Chou, J. C. Hsu, W. M. Liu, J. H.pRL0007-1161 (Print) Clinical Trial Journal Article Randomized Controlled TrialBr J OphthalmolaAdult Aged Antihypertensive Agents/administration & dosage/*pharmacology Cross-Over Studies Eye/*blood supply/drug effects Female Glaucoma/drug therapy/*physiopathology Humans Intraocular Pressure/drug effects Male Middle Aged Prostaglandins F, Synthetic/administration & dosage/*pharmacology Pulsatile Flow/*drug effects/physiology Quinoxalines/administration & dosage/*pharmacologynlehttp://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=12386077sh: ,15519534511n 2005 JaneXREffect of elevated intraocular pressure on endothelin-1 in a rat model of glaucoma 41-50aThe role of endothelin-1 (ET-1) a potent vasoactive peptide, in glaucoma pathogenesis is receiving increasing attention, particularly in astroglial activation in optic nerve damage. Our laboratory has also shown that ET-1 treatment causes proliferation of cultured human optic nerve head astrocytes to possibly initiate astrogliosis. ET-1 is distributed in retina, optic nerve, and ciliary epithelium, however the effects of elevated intraocular pressure (IOP) (as seen in glaucoma) on ET-1 and ET(B) receptors are not clearly understood. In the present study, the levels of immunoreactive ET-1 (ir-ET-1) in aqueous humour (AH) and optic nerve head (ONH) were determined in the Morrison elevated IOP model of glaucoma. Additionally in the ONH of these rats, immunohistochemical analyses of ET(B) receptors and glial fibrillary acidic protein (GFAP; a marker for astroglial cells and for astrogliosis) were performed. There was 2- to 2.5-fold increase in AH ir-ET-1 levels for rats subjected to elevated IOP, compared to their respective controls. In the Morrison rat model of glaucoma, elevated IOP increased optic nerve ir-ET-1 with concomitant increases in ir-ET(B) and ir-GFAP labelling (possibly indicative of astrogliosis and hypertrophy). As seen in brain astrocytes subjected to neurotrauma, the present findings are suggestive of ET-1's role in astroglial activation, particularly in response to elevated IOP in glaucoma.n'Department of Pharmacology and Neuroscience, University of North Texas Health Science Center, 3500 Camp Bowie Blvd., Fort Worth, TX 76107, USA. gprasann@hsc.unt.edulfPrasanna, G. Hulet, C. Desai, D. Krishnamoorthy, R. R. Narayan, S. Brun, A. M. Suburo, A. M. Yorio, T.(!1043-6618 (Print) Journal Article  Pharmacol Res :4Animals Comparative Study *Disease Models, Animal Endothelin-1/*metabolism/physiology Glaucoma/chemically induced/*metabolism Intraocular Pressure/drug effects/*physiology Male Rats Rats, Inbred BN Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S. Saline Solution, Hypertonic/pharmacologylehttp://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=15519534r9111259c 104r41 1997 Apr:lfColor Doppler imaging of ophthalmic artery blood flow velocity: a study of repeatability and agreement 653-8PURPOSE: Color Doppler imaging (CDI) is a relatively new technique that allows quantification of blood flow velocity in orbital and ocular vasculature. Despite the numerous clinical studies that have used CDI, repeatability of this technique and agreement between observers have not been documented. METHODS: The authors performed a prospective investigation of the repeatability and agreement between observers on ophthalmic artery blood flow velocity measurements in 35 patients (35 eyes). RESULTS: Results on the estimated error of measurement (variability between repeated readings on the same subject) indicate good repeatability of the measurements; in fact, the measurement variances were only 5.6% for the peak systolic velocity, 11.4% for the end diastolic velocity, and 6.2% for the mean envelope velocity. The statistical analysis of repeatability showed a very narrow 95% confidence interval for both observers. The measurement of agreement between the two observers demonstrated the existence of a good concordance of the measurements taken by each observer on each subject. CONCLUSIONS: Results suggest that CDI is a reliable tool for quantitative assessment of ophthalmic artery blood flow velocity.'RLCentro Glaucoma-Clinica Oculistica, Universita degli Studi di Brescia,Italy.piQuaranta, L. Harris, A. Donato, F. Cassamali, M. Semeraro, F. Nascimbeni, G. Gandolfo, E. Quaranta, C. A. (!0161-6420 (Print) Journal Article  OphthalmologymAged Analysis of Variance *Blood Flow Velocity Female Humans Male Middle Aged Observer Variation Ophthalmic Artery/*ultrasonography Reproducibility of Results *Ultrasonography, Doppler, Color jdhttp://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=9111259 5532568610 1979 OctnhThe histology of human glaucoma cupping and optic nerve damage: clinicopathologic correlation in 21 eyes1803-30We have examined by light and electron microscopy the retina, optic nervehead, and optic nerves of 21 human eyes from glaucoma patients in whom clinical information was available for comparison. In several cases it was possible to correlate the degree and distribution of optic nerve damage with the clinical appearance of the optic disc and visual field studies. There was no selective loss of astrocytes of the optic nervehead in early glaucoma cupping. Acquired increases in optic disc cup size prior to detectable visual field loss probably represent loss of ganglion cell axonal fibers which is not yet significant enough to produce field defects. It is unlikely that the mechanism of axonal damage in chronic human glaucoma involves early loss of astrocytic glial cells at the optic nervehead. At the level of the retrobulbar optic nerve, the ganglion cell axonal fibers of the superior and inferior quadrants seem to be lost earlier than the fibers of the nasal and temporal nerve periphery. Since the superior and inferior poles of the optic nerve may contain the fibers of arcuate area ganglion cells, these data confirm the presumption from visual field testing that arcuate area ganglion cell fibers are selectively more susceptible to damage in chronic glaucoma."Quigley, H. A. Green, W. R.4.0161-6420 (Print) Case Reports Journal Article OphthalmologyAdult Aged Female Glaucoma/diagnosis/*pathology Humans Intraocular Pressure Male Microscopy, Electron Middle Aged Optic Disk/*pathology/ultrastructure Optic Nerve/*pathology Research Support, U.S. Gov't, P.H.S. Visual Fieldsjchttp://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=553256 n f 67096165 1977 Mayd]Orthograde and retrograde axoplasmic transport during acute ocular hypertension in the monkey 426-41HBOrthograde and retrograde axoplasmic transport have been studied in the optic nerve heads of 37 Macaca fascicularis eyes with normal or elevated intraocular pressure (IOP) produced by cannulation of the anterior chamber. Orthograde transport was labeled by 3H-amino acids injected intravitreally and incorporated into retinal ganglion cell proteins. Retrograde transport was studied in the same eyes by injecting horseradish peroxidase (HRP) into one or both optic tracts and dorsal lateral geniculate nuclei (dLGN). Both tracers accumulated in the lamina scleralis (LS) of eyes maintained at pressures of 25 to 150 mm. Hg for 12 to 28 hours (pressure in normal controls = 10 to 14 mm. Hg) but the HRP technique was markedly more sensitive. The degree of retrograde transport obstruction in the LS appeared to be directly proportional to both the height and the duration of elevated IOP. In one experiment, the blockades of orthograde and retrograde transport induced at 50 mm. Hg were demonstrated to be reversible. Serial reconstructions of radioautographs and peroxidase-reacted sections of the optic nerve heads demonstrated that the orthograde and retrograde transport obstructions were coincidental anatomically by light microscopy in the LS and occurred most prominently in the temporal quadrants of the nerve head. These transport obstructions occurred at moderate elevations of IOP (25 TO 50 mm. Hg) despite (1) elevated arterial PO2 levels during inhalation of 100 percent oxygen and (2) intact nerve head capillary circulation, as demonstrated by perfusion with nucleated avian erythrocytes.2+Minckler, D. S. Bunt, A. H. Johanson, G. W.(!0146-0404 (Print) Journal Article Invest Ophthalmol Vis SciAcute Disease Amino Acids Animals Autoradiography *Axonal Transport Chickens Erythrocytes/pathology Glaucoma/*pathology Haplorhini Horseradish Peroxidase Intraocular Pressure Macaca fascicularis Optic Disk/pathology Optic Nerve/blood supply/pathology Perfusion Pressure Regional Blood Flow Research Support, U.S. Gov't, Non-P.H.S. Research Support, U.S. Gov't, P.H.S. Retina/pathology Sclera/innervationhbhttp://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=6709615288976 1118 2004 Augf@:Retinal venous pulsation in glaucoma and glaucoma suspects1489-94nPURPOSE: To determine whether changes in central retinal vein pulsation characteristics occur in glaucoma, and how these are related to indices of glaucoma severity. DESIGN: A large, consecutive, prospective, case-controlled study. PARTICIPANTS: Ninety-four consecutive glaucoma patients and 105 glaucoma suspects seen in a tertiary referral clinic were examined. Forty-one age-matched normal subjects also were examined. METHODS: The presence or absence of spontaneous venous pulsation was observed in these 3 groups. The ophthalmodynamometric force (ODF) required to induce venous pulsation at the optic disc was measured in those without spontaneous pulsation. Optic disc photographs were obtained and visual field testing was performed for all subjects. MAIN OUTCOME MEASURES: The prevalence of spontaneous venous pulsation between these 3 groups was compared. The relationship between ODF and visual field mean deviation, neuroretinal rim area, age, intraocular pressure (IOP), gender, and diagnosis of glaucoma was investigated using linear mixed models fitted by Gibb's sampling. RESULTS: Significantly fewer (chi-square, 27.7; P<0.001) glaucoma patients (54%) were observed to have spontaneous venous pulsation than suspects (75%) or normals (98%). A worse visual field mean deviation was shown to be the most significant predictor of a higher ODF (P<0.000), with younger age (P<0.000) also predictive of a higher ODF. A strong relationship between ODF and mean deviation was found in the glaucoma patients (r = 0.59; n = 52; P<0.001). CONCLUSIONS: Spontaneous venous pulsation is less common in glaucoma. The ODF required to induce venous pulsation is increased in glaucoma, and this ODF is greater in those with more severe field loss.'jcLions Eye Institute, University of Western Australia, Perth, Australia. whmorgan@cyllene.uwa.edu.aujcMorgan, W. H. Hazelton, M. L. Azar, S. L. House, P. H. Yu, D. Y. Cringle, S. J. Balaratnasingam, C.(!0161-6420 (Print) Journal Article OphthalmologyAged Blood Flow Velocity Case-Control Studies Comparative Study Female Glaucoma/*physiopathology Humans Intraocular Pressure/physiology Male Middle Aged Ocular Hypertension/physiopathology Ophthalmodynamometry Optic Disk/blood supply Photography Prospective Studies Pulsatile Flow/*physiology Research Support, Non-U.S. Gov't Retinal Vein/*physiology Visual Acuity/physiology Visual Fields/physiologylehttp://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=15288976Artery/innervation/*physiology Sympathetic Nervous System/physiologylehttp://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=11015035m8188062 2323 1994 MarxrReliability of intraocular pressure measurement with the Goldmann applanation tonometer in epidemiological studies 141-4(!The reproducibility of intraocular pressure (IOP) measurement with the Goldmann applanation tonometer was investigated as part of a population-based epidemiological study. Sixty-two subjects were examined in a first measurement session. The IOP was measured three times consecutively in both eyes according to a fixed protocol. The mean standard deviation (SD) of these measurements was 0.8 mmHg. The mean intraobserver variation for the first measurement was 1.64 (SD 2.07) mmHg. For the median of the three measurements the intra-observer variation was 1.50 (SD 1.96) mmHg. The mean inter-observer values were 1.79 (SD 2.41) mmHg for the first measurement and 1.60 (SD 2.15) mmHg for the median measurement. The correlation coefficient between the median values of the three measurements of both observers was 0.81. No systematic differences were found between the two observers. Using the median value of three consecutive measurements reduced the inter-observer variation by 11% and the intra-observer variation by 9% compared with a single measurement.'b[Department of Ophthalmology, Erasmus University Medical School, Rotterdam, The Netherlands.NHDielemans, I. Vingerling, J. R. Hofman, A. Grobbee, D. E. de Jong, P. T.(!0721-832X (Print) Journal Article& Graefes Arch Clin Exp OphthalmolAged Comparative Study Female Glaucoma/diagnosis/*epidemiology Humans *Intraocular Pressure Male Middle Aged Netherlands/epidemiology Observer Variation Reproducibility of Results Research Support, Non-U.S. Gov't Tonometry, Ocular/instrumentation/*methods jdhttp://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=8188062 a 211914213864  2002 ApruCapillary density and retinal diameter measurements and their impact on altered retinal circulation in glaucoma: a digital fluorescein angiographic studyc 429-33AIM: Normal pressure glaucoma (NPG) patients exhibit prolonged retinal arteriovenous passage times in fluorescein angiography and colour Doppler imaging suggests increased resistance downstream from the central retinal and posterior ciliary arteries. The aim of the study was to elucidate the morphological source of decreased perfusion and increased resistance of the ocular circulation in NPG. METHODS: Retinal arteriovenous passage time (AVP) and peripapillary arterial and venous diameters were measured in digital scanning laser fluorescein angiograms. For estimation of retinal capillary density the area of the foveal avascular zone (FAZ) and the perifoveal intercapillary area (PIA) was quantified. 36 patients with NPG (mean age 57 (SD 13) years) and 21 healthy subjects (mean age 51 (13) years) were enrolled in the comparative study. RESULTS: In NPG patients the AVP (2.55 (1.1) seconds) was significantly prolonged (p<0.001) when compared with healthy subject data (AVP: 1.70 (0.39) seconds). No differences for arterial or venous diameter, FAZ, and PIA were observed in NPG patients compared with healthy subjects. FAZ, PIA, arterial and venous diameter were not correlated with visual field indices (except venous diameter with PSD, r=0.35 (p<0.05)) or cup to disc ratios. AVP was significantly correlated (p<0.05) with the size of the optic nerve head (r=-0.28), visual field indices (MD: r=-0.3; PSD: r=0.3; CPSD: r=0.3), and contrast sensitivity (r=-0.34). CONCLUSION: AVP times are significantly prolonged in NPG. The slowing of the retinal transit does not result from capillary dropout, or changes of peripapillary arterial or venous diameters with increased vascular resistance.S'Department of Ophthalmology, Medical School of the Technical University of Aachen, Pauwelsstrasse 30, 52057 Aachen, Germany. oliver.arend@post.rwth-aachen.des>7Arend, O. Remky, A. Plange, N. Martin, B. J. Harris, A.t(!0007-1161 (Print) Journal ArticleiBr J OphthalmolaBlood Flow Velocity Capillaries/pathology Female Glaucoma, Open-Angle/*pathology/physiopathology Humans Male Middle Aged Prospective Studies Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S. Retinal Artery/pathology Retinal Vein/pathology Vascular Resistancelehttp://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=11914213n14510794815e 2003 OctnEvaluation of retinal haemodynamics and retinal function after application of dorzolamide, timolol and latanoprost in newly diagnosed open-angle glaucoma patients 474-90@:PURPOSE: The purpose of this prospective, randomized, cross-over study was to investigate and compare the microcirculatory effects of timolol, dorzolamide and latanoprost in newly diagnosed primary open-angle glaucoma (POAG) patients. Haemodynamics were assessed using fluorescein angiography by means of a scanning laser ophthalmoscope (SLO). Visual function and visual field indices were evaluated during all drug treatment phases. METHODS: Fourteen patients with newly diagnosed POAG (age 55 +/- 7 years; 10 male, four female) were recruited for the study. At baseline examination, blood pressure, heart rate, intraocular pressure (IOP), SLO angiograms, and contrast sensitivity (CS) were analysed. Patients then randomly received timolol, dorzolamide or latanoprost treatment for 4 weeks. Patients then returned and all procedures were repeated and assessed. Arteriovenous passage times (AVPs), peripapillary arterial and venous diameters were assessed from SLO angiograms, using digital image processing. Calculated ocular perfusion pressure was determined for each treatment phase. RESULTS: Intraocular pressure was significantly lowered by each drug compared to baseline (p < 0.0001). Arteriovenous passage times were significantly shortened after dorzolamide application compared to baseline (p = 0.009), whereas neither timolol nor latanoprost treatment resulted in significant AVP changes. Peripapillary arterial and venous diameters, systolic and diastolic blood pressure, heart rate and ocular perfusion pressures were not significantly altered during any treatment phase. Contrast sensitivity testing at 6 cycles/degree (c.p.d.) revealed a significant rise after dorzolamide compared to timolol (p = 0.007). CONCLUSION: Our results suggest that dorzolamide treatment significantly shortened AVP times in newly diagnosed open-angle glaucoma patients, whereas timolol and latanoprost had no significant effect. Given that prolonged AVP times have been associated with disease progression in glaucoma; dorzolamide treatment may benefit optic nervehead preservation by increasing ocular perfusion.'Department of Ophthalmology, Medical School, Technical University Aachen, Pauwelsstrasse 30, Aachen 52057, Germany. oliver.arend@web.de0)Arend, O. Harris, A. Wolter, P. Remky, A.RL1395-3907 (Print) Clinical Trial Journal Article Randomized Controlled TrialActa Ophthalmol Scand>8Adrenergic beta-Antagonists/*therapeutic use Arteries Blood Pressure/drug effects Carbonic Anhydrase Inhibitors/*therapeutic use Contrast Sensitivity/drug effects Cross-Over Studies Female Glaucoma, Open-Angle/*drug therapy/*physiopathology Humans Intraocular Pressure Male Microscopy, Confocal Middle Aged Ophthalmoscopy Prostaglandins F, Synthetic/*therapeutic use Regional Blood Flow/drug effects Research Support, Non-U.S. Gov't Retinal Vessels/*drug effects/*physiopathology Sulfonamides/*therapeutic use Thiophenes/*therapeutic use Timolol/*therapeutic use Veinslehttp://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=145107947Arend, O. Remky, A. Plange, N. Martin, B. J. Harris, A.t(!0007-1161 (Print) Journal ArticleiBr J OphthalmolaBlood Flow Velocity Capillaries/pathology Female Glaucoma, Open-Angle/*pathology/physiopathology Humans Male Middle Aged Prospective Studies Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S. Retinal Artery/pathology Retinal Vein/pathology Vascular Resistancelehttp://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=11914213n %88537023 2338 1995 Augb\Endothelin-1 plasma levels in normal-tension glaucoma: abnormal response to postural changes 484-8|BACKGROUND: Endothelin-1 (ET-1) is a potent vasoconstrictor peptide produced by vascular endothelial cells. ET-1 may have a role in the pathogenesis of various vascular diseases. There are reports in the literature that ET-1 plasma levels are raised in normal-tension glaucoma (NTG) patients. METHODS: ET-1 concentration, plasma renin activity, and 24-h blood pressure were measured in 21 high-tension glaucoma (HTG) patients, 19 NTG patients, and 20 non-glaucomatous controls in supine and upright positions. RESULTS: ET-1 plasma levels tended to be higher in NTG patients (3.2 +/- 2.2 pg/ml) than in HTG patients (2.2 +/- 0.6 pg/ml) and controls (2.6 +/- 0.7 pg/ml). The differences, however, were not statistically significant. The individual scatter was significantly greater in the NTG group, indicating that our NTG patients are a heterogeneous population. The physiological increase in ET-1 plasma level after changing from the supine to the upright position was absent in NTG patients. Plasma renin activities tended to be lower in NTG patients (1.2 +/- 1.2 ng/ml/h) than in HTG patients (1.3 +/- 0.8 ng/ml/h) and controls (2.0 +/- 1.7 ng/ml/h). This may explain why NTG patients had relatively low blood pressure despite high ET-1 levels. CONCLUSIONS: Our data support the hypothesis that vascular dysfunction may be involved in the pathogenesis of optic nerve damage in normal-tension glaucoma.'0*University Eye Clinic, Basel, Switzerland.4.Kaiser, H. J. Flammer, J. Wenk, M. Luscher, T.(!0721-832X (Print) Journal Article& Graefes Arch Clin Exp OphthalmolBlood Pressure Comparative Study Endothelins/*blood Female Glaucoma, Open-Angle/*blood Heart Rate Humans Intraocular Pressure Male Middle Aged Ocular Hypertension/*blood *Posture Radioimmunoassay Renin/blood Research Support, Non-U.S. Gov'tjdhttp://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=853702312049574 120S6, 2002 Jun@The Ocular Hypertension Treatment Study: a randomized trial determines that topical ocular hypotensive medication delays or prevents the onset of primary open-angle glaucomaO 701-13; discussion 829-30rBACKGROUND: Primary open-angle glaucoma (POAG) is one of the leading causes of blindness in the United States and worldwide. Three to 6 million people in the United States are at increased risk for developing POAG because of elevated intraocular pressure (IOP), or ocular hypertension. There is no consensus on the efficacy of medical treatment in delaying or preventing the onset of POAG in individuals with elevated IOP. Therefore, we designed a randomized clinical trial, the Ocular Hypertension Treatment Study. OBJECTIVE: To determine the safety and efficacy of topical ocular hypotensive medication in delaying or preventing the onset of POAG. METHODS: A total of 1636 participants with no evidence of glaucomatous damage, aged 40 to 80 years, and with an IOP between 24 mm Hg and 32 mm Hg in one eye and between 21 mm Hg and 32 mm Hg in the other eye were randomized to either observation or treatment with commercially available topical ocular hypotensive medication. The goal in the medication group was to reduce the IOP by 20% or more and to reach an IOP of 24 mm Hg or less. MAIN OUTCOME MEASURES: The primary outcome was the development of reproducible visual field abnormality or reproducible optic disc deterioration attributed to POAG. Abnormalities were determined by masked certified readers at the reading centers, and attribution to POAG was decided by the masked Endpoint Committee. RESULTS: During the course of the study, the mean +/- SD reduction in IOP in the medication group was 22.5% +/- 9.9%. The IOP declined by 4.0% +/- 11.6% in the observation group. At 60 months, the cumulative probability of developing POAG was 4.4% in the medication group and 9.5% in the observation group (hazard ratio, 0.40; 95% confidence interval, 0.27-0.59; P<.0001). There was little evidence of increased systemic or ocular risk associated with ocular hypotensive medication. CONCLUSIONS: Topical ocular hypotensive medication was effective in delaying or preventing the onset of POAG in individuals with elevated IOP. Although this does not imply that all patients with borderline or elevated IOP should receive medication, clinicians should consider initiating treatment for individuals with ocular hypertension who are at moderate or high risk for developing POAG.'zsDepartment of Ophthalmology and Visual Sciences, Washington University School of Medicine, St Louis, MO 63110, USA.Kass, M. A. Heuer, D. K. Higginbotham, E. J. Johnson, C. A. Keltner, J. L. Miller, J. P. Parrish, R. K., 2nd Wilson, M. R. Gordon, M. O.d^0003-9950 (Print) Clinical Trial Journal Article Multicenter Study Randomized Controlled TrialArch OphthalmolAdministration, Topical Adult Aged Aged, 80 and over Antihypertensive Agents/*therapeutic use Comparative Study Double-Blind Method Female Follow-Up Studies Glaucoma, Open-Angle/diagnosis/*prevention & control Humans Intraocular Pressure/*drug effects Male Middle Aged Ocular Hypertension/diagnosis/prevention & control Ophthalmic Solutions Optic Disk/pathology Patient Compliance Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S. Safety Treatment Outcome Visual Acuity Visual Fieldslehttp://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=12049574M J9683148 126p1l 1998 JulfhbA comparison of ocular blood flow in untreated primary open-angle glaucoma and ocular hypertension 42-51PURPOSE: To compare ocular blood flow in untreated primary open-angle glaucoma and ocular hypertension using scanning laser Doppler flowmetry and pulsatile ocular blood flow. METHOD: Fourteen ocular hypertensive subjects and 10 patients with primary open-angle glaucoma were matched for intraocular pressure, mean arterial blood pressure, and age. They had scanning laser Doppler flowmetry images taken centered on the optic disk. Pulsatile ocular blood flow readings were performed in sitting, standing, and supine positions. No subjects were receiving topical antiglaucoma treatment, systemic beta-blockers, calcium antagonists, or nitrates at the time of measurement. RESULTS: Laser Doppler flowmetry results showed a significant reduction in blood velocity, volume, and flow at the lamina cribrosa and the temporal neuroretinal rim in glaucoma compared to ocular hypertension (P < .05). No difference was found between the groups at the nasal neuroretinal rim or the nasal juxtapapillary retina. There was a significant increase in minimum velocity (P = .03) at the temporal juxtapapillary retina in glaucoma compared to ocular hypertension. The ocular pulse amplitude, pulse volume, and pulsatile ocular blood flow were significantly lower (P < .05) in the glaucoma group compared to ocular hypertension in sitting and standing positions. CONCLUSION: Having controlled for factors known to affect perfusion pressure, we found evidence of reduced ocular blood flow in primary open-angle glaucoma compared with ocular hypertension. Our findings indicate a reduction in choroidal and short posterior ciliary artery circulation in primary open-angle glaucoma. Whether these changes in blood flow are a cause or a consequence of glaucomatous optic atrophy is still unknown.i'LEPrincess Alexandra Eye Pavilion, Edinburgh, Scotland, United Kingdom.o&Kerr, J. Nelson, P. O'Brien, C.r(!0002-9394 (Print) Journal ArticlenAm J Ophthalmol Aged Blood Flow Velocity Blood Volume Choroid/blood supply/physiopathology Ciliary Arteries/physiopathology Cohort Studies Comparative Study Female Glaucoma, Open-Angle/*physiopathology Humans Intraocular Pressure Laser-Doppler Flowmetry Male Middle Aged Ocular Hypertension/*physiopathology Optic Disk/*blood supply Pulsatile Flow Research Support, Non-U.S. Gov't Retinal Vessels/physiopathologyjdhttp://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=9683148 &Y>k@ = 2 dB) showed a retinal perfusion lower than the 90% percentile of normal blood flow. We found no correlation between reduction of juxtapapillary or papillary blood flow and mean defect in POAG eyes. CONCLUSION: Glaucomatous eyes with no defects or borderline visual field defects as well as glaucomatous eyes in an advanced disease stage show significantly decreased optic nerve head and juxtapapillary retinal capillary blood flow.e'LFDepartment of Ophthalmology, University of Erlangen-Nurnberg, Germany.:4Michelson, G. Langhans, M. J. Harazny, J. Dichtl, A.(!0721-832X (Print) Journal ArticleB& Graefes Arch Clin Exp Ophthalmol^WBlood Flow Velocity Cross-Sectional Studies Glaucoma, Open-Angle/complications/*physiopathology Humans Intraocular Pressure Laser-Doppler Flowmetry Middle Aged Optic Atrophy/etiology/physiopathology Optic Disk/*blood supply Perfusion Research Support, Non-U.S. Gov't Retinal Vessels/*physiology Vision Disorders/*physiopathology *Visual Fieldsjdhttp://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=9498117' 814691166451 2004 JanD=Model of endothelin-1-induced chronic optic neuropathy in rat 144-52|vPURPOSE: To describe a model of chronic endothelin (ET)-1 administration to the optic nerve and evaluate its effect on retinal ganglion cell (RGC) and axon survival in rat. METHODS: Osmotic minipumps were surgically implanted in one eye of 113 Brown Norway rats to deliver 0.05, 0.10, 0.20, or 0.40 microg ET-1 per day (3.3, 6.7, 13.4, and 26.8 microM, respectively), or balanced salt solution (BSS) to the immediate retrobulbar optic nerve; the fellow untreated eye served as the control. Before pump implantation, RGCs were retrogradely labeled with fluorochrome. Animals were killed at 21, 42, or 84 days. RGC survival was expressed as the ratio of RGC counts in experimental versus control eyes in wholemounted retinas, whereas axon survival was expressed similarly from electron micrographs of the optic nerves. Serial optic disc changes were evaluated using scanning laser tomography. The effect of ET-1 (3 microL topical application of 10(-5) M) on blood flow in the surgically exposed optic nerve was measured using laser Doppler flowmetry in a separate group of five animals. RESULTS: ET-1 led to a mean reduction in optic nerve blood flow of 68%. There were no significant differences in RGC survival among the four ET-1 doses used in this study. Pooled across all ET-1 doses, RGC survival decreased incrementally at 21, 42, and 84 days (P < 0.001; mean +/- SD, 0.77 +/- 0.25, 0.60 +/- 0.27, and 0.50 +/- 0.26, respectively) and was statistically significantly lower at each time point than in the BSS-treated animals. The axon survival data also showed a similar time-dependent loss. Only one of 21 animals showed significantly increased disc cupping, and there was no relationship between RGC survival and change in cupping. CONCLUSIONS. Chronic administration of ET-1 to the rat optic nerve results in a time-dependent loss of RGCs and their axons without apparent change in optic disc topography.'pjRetina and Optic Nerve Research Laboratory, Dalhousie University, Halifax, Nova Scotia, Canada. bal@dal.ca~Chauhan, B. C. LeVatte, T. L. Jollimore, C. A. Yu, P. K. Reitsamer, H. A. Kelly, M. E. Yu, D. Y. Tremblay, F. Archibald, M. L.(!0146-0404 (Print) Journal Article Invest Ophthalmol Vis SciAnimals Axons/*drug effects/pathology Cell Survival/drug effects Chronic Disease Disease Models, Animal Endothelin-1/*pharmacology Infusion Pumps, Implantable Laser-Doppler Flowmetry Male Optic Disk/*blood supply Optic Nerve Diseases/*etiology/physiopathology Rats Rats, Inbred BN Regional Blood Flow/drug effects Research Support, Non-U.S. Gov't Retinal Ganglion Cells/*drug effects/pathologylehttp://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=14691166manifest visual field defect. Decreases in flow in glaucoma suspects were similar in magnitude to those of subjects with primary open-angle glaucoma. These data suggest that impaired optic nerve blood flow develops early in the glaucomatous process and does not develop solely as a result of glaucoma damage.'Scheie Eye Institute, University of Pennsylvania Health Systems, Philadelphia, Pennsylvania 19104, USA. piltz@mail.med.upenn.eduHAPiltz-seymour, J. R. Grunwald, J. E. Hariprasad, S. M. Dupont, J.(!0002-9394 (Print) Journal ArticleAm J OphthalmolTMBlood Flow Velocity Blood Pressure Cohort Studies Comparative Study Glaucoma, Open-Angle/*physiopathology Humans Intraocular Pressure Laser-Doppler Flowmetry Middle Aged Optic Nerve/*blood supply Prospective Studies Regional Blood Flow Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S. Visual Acuity Visual Fieldslehttp://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=11438055 V 9 mAstrocytes/*metabolism$ Astrocytes/*metabolism/pathology,(Astrocytes/chemistry/cytology/metabolism0,Astrocytes/cytology/drug effects/*metabolism82Autonomic Nervous System Diseases/*physiopathology@ or = 30 mmHg may be detrimental to retinal perfusion in normals as well as in patients with POAG, who may have compromised retinal perfusion to begin with.'F@Augenklinik der Medizinischen Fakultat der RWTH Aachen, Germany.B 25 mm Hg; "low-risk" OHT had IOP Aged Blood Flow Velocity Comparative Study Female Glaucoma, Open-Angle/*physiopathology Humans Intraocular Pressure Laser-Doppler Flowmetry Male Middle Aged Ocular Hypertension/physiopathology Optic Disk/*blood supply Prospective Studies Regional Blood Flow Research Support, Non-U.S. Gov't Retinal Vessels/*physiologylehttp://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=1464421210438154185_ 1999 SepoProgress in measurement of ocular blood flow and relevance to our understanding of glaucoma and age-related macular degeneration 669-87D>New technologies have facilitated the study of the ocular circulation. These modalities and analysis techniques facilitate very precise and comprehensive study of retinal, choroidal, and retrobulbar circulations. These techniques include: 1. Vessel caliber assessment; 2. Scanning laser ophthalmoscopic fluorescein angiography and indocyanine green angiography to image and evaluate the retinal circulation and choroidal circulation respectively; 3. Laser Doppler flowmetry and confocal scanning laser Doppler flowmetry to measure blood flow in the optic nerve head and retinal capillary beds; 4. Ocular pulse measurement; and 5. color Doppler imaging to measure blood flow velocities in the central retinal artery, the ciliary arteries and the ophthalmic artery. These technique have greatly enhanced the ability to quantify ocular perfusion defects in many disorders, including glaucoma and age-related macular degeneration, two of the most prevalent causes of blindness in the industrialized world. Recently it has become clear, in animal models of glaucoma, that retinal ganglion cells die via apoptosis. The factors that initiate apoptosis in these cells remain obscure, but ischemia may play a central role. Patients with either primary open-angle glaucoma or normal-tension glaucoma experience various ocular blood flow deficits. With regard to age-related macular degeneration, the etiology remains unknown although some theories include primary retinal pigment epithelial senescence, genetic defects such as those found in the ABCR gene which is also defective in Stargardt's disease and ocular perfusion abnormalities. As the choriocapillaris supplies the metabolic needs of the retinal pigment epithelium and the outer retina, perfusion defect in the choriocapillaris could account for some of the physiologic and pathologic changes in AMD. Vascular defects have been identified in both nonexudative and exudative AMD patients using new technologies. This paper is a comprehensive update describing modalities available for the measurement of all new ocular blood flow in human and the clinical use.'d^Department of Ophthalmology, Indiana University, Indianapolis 46202, USA. Alharris@indiana.edu82Harris, A. Chung, H. S. Ciulla, T. A. Kagemann, L..(1350-9462 (Print) Journal Article ReviewProg Retin Eye ResAnimals Blood Flow Velocity *Diagnostic Techniques, Ophthalmological Eye/*blood supply Glaucoma, Open-Angle/*physiopathology Humans Macular Degeneration/*physiopathology Regional Blood Flow Rheologylehttp://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=10438154ty to optic nerve damage. An enhanced understanding of the nature of the optic nerve damage in POAG and improved methods of study may result in earlier diagnosis or may allow us to distinguish among different pathological processes all currently grouped under the diagnosis of POAG. As we gain a better understanding of the neuropharmacology and cellular biology of injury and repair of the visual system we will undoubtedly refine the concepts of glaucomatous optic neuropathy.'ZTDepartment of Ophthalmology and Visual Sciences, University of Louisville, Kentucky.$Fechtner, R. D. Weinreb, R. N..(0039-6257 (Print) Journal Article ReviewSurv OphthalmolGlaucoma, Open-Angle/*complications/pathology Humans Intraocular Pressure Optic Disk/blood supply/pathology Optic Nerve/pathology Optic Nerve Diseases/*etiology/pathology Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S.jdhttp://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=7974188= 1296779714663592 242l2o 2004 Feb?JDColor Doppler imaging in ocular hypertension and open-angle glaucoma 125-9ePURPOSE: To quantify the retrobulbar hemodynamics of patients with ocular hypertension and open-angle glaucoma and to compare it with that of normal subjects. METHODS: Nineteen eyes of 19 ocular hypertensive patients, 19 eyes of 19 open-angle glaucoma patients and 19 eyes of 19 normal subjects were recruited from our clinic and underwent color Doppler imaging evaluation of the ophthalmic, posterior ciliary, and central retinal arteries. The peak systolic and end-diastolic blood flow velocities and resistivity indices of all retrobulbar vessels were measured. RESULTS: The retrobulbar blood flow velocities were lower and resistivity indices were higher in all retrobulbar vessels in ocular hypertensive patients than in normal subjects. The differences, however, did not reach statistical significance ( P>0.05). Glaucoma patients had lower end-diastolic velocities and higher resistivity indices than did normal subjects in the ophthalmic ( P=0.003 and P=0.003, respectively), posterior ciliary ( P=0.001 and P<0.001, respectively), and central retinal arteries ( P=0.03 and P=0.04, respectively). Glaucoma patients had significantly lower end-diastolic velocity and higher resistivity index than did patients with ocular hypertension in the posterior ciliary artery ( P=0.04 and P=0.001, respectively). CONCLUSIONS: This study suggests that ocular hypertensive patients have more normal blood flow than do glaucoma patients, because all retrobulbar homodynamic measurements in ocular hypertension range between glaucoma and normal subjects. On the other hand, glaucoma is associated with blood-flow velocity reduction and resistivity index elevation in all retrobulbar arteries.'nhDepartment of Ophthalmology, University of Kirikkale, Kirikkale, 71100, Turkey. cengizakarsu@hotmail.com Akarsu, C. Bilgili, M. Y.o(!0721-832X (Print) Journal Articleg& Graefes Arch Clin Exp Ophthalmol~wBlood Flow Velocity Blood Pressure Ciliary Arteries/*physiology/ultrasonography Comparative Study Female Glaucoma, Open-Angle/*physiopathology Heart Rate Humans Intraocular Pressure Male Middle Aged Ocular Hypertension/physiopathology Ophthalmic Artery/*physiology/ultrasonography Regional Blood Flow Retinal Artery/*physiology/ultrasonography Ultrasonography, Doppler, Colorulehttp://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=14663592/2021167p 111e5i 1991 May 15piBlood-cell velocity in the nailfold capillaries of patients with normal-tension and high-tension glaucoma 585-8We compared the capillary blood-cell velocity in the fingertips of 30 patients with high-tension glaucoma, 30 patients with normal-tension glaucoma, and 30 control subjects by nailfold capillaroscopy. There were no measurable differences in the morphologic findings. The blood-flow velocity, however, was reduced significantly in the patients with normal-tension glaucoma compared with the control subjects (P less than .05). This difference was especially pronounced after cold provocation (P less than .0005). After cooling, 25 of 30 patients with normal-tension glaucoma had a blood standstill of 12 seconds or more, whereas only three of 30 control subjects and four of 30 patients with high-tension glaucoma had a measurable blood standstill.c'LEDepartment of Internal Medicine, St. Claraspital, Basel, Switzerland.rGasser, P. Flammer, J.(!0002-9394 (Print) Journal Article7Am J Ophthalmol8Adult Aged Blood Flow Velocity Capillaries Comparative Study Female Fingers/*blood supply Glaucoma/*physiopathology Humans Hyperthermia, Induced Hypothermia, Induced Male Middle Aged Ocular Hypertension/*physiopathology Research Support, Non-U.S. Gov'tjdhttp://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=2021167 V@ 8610793 121e55 1996 May0b[Color Doppler imaging in patients with asymmetric glaucoma and unilateral visual field lossu 502-10PURPOSE: To determine whether lower blood velocities and high resistive index in the retrobulbar arteries are primary or secondary to glaucomatous damage in patients with open-angle glaucoma. METHODS: Color Doppler imaging was performed in 32 glaucomatous patients with unilateral visual field loss and in 31 control subjects. Peak systolic velocity and end diastolic velocity were measured, and resistive index was calculated in the central retinal artery and short posterior ciliary arteries. RESULTS: In patients with glaucoma, both the more affected and the contralateral eyes with normal visual fields had significantly lower peak systolic velocity and end diastolic velocity in their central retinal artery and short posterior ciliary arteries than did the control subjects of similar age (P < or = .03). The resistive index of the central retinal artery of both eyes of patients with glaucoma was also significantly higher than in the control subjects (P = .001). When considering the 16 patients who had the greatest visual field asymmetry, the more affected eyes had lower peak systolic velocity and end diastolic velocity in the central retinal artery than the contralateral eyes did (P = .02). CONCLUSIONS: Even eyes with normal visual fields in patients with asymmetric disease had decreased blood velocities in their retrobulbar vessels, suggesting that these circulatory changes probably precede detectable damage. Furthermore, the finding of lower central retinal artery blood velocities in the more affected eye of asymmetric patients suggests that low blood velocities may be one of the lateralizing factors in those patients and that they have a possible role in the pathogenesis of the disease.'VODepartment of Ophthalmology, University of British Columbia, Vancouver, Canada.NHNicolela, M. T. Drance, S. M. Rankin, S. J. Buckley, A. R. Walman, B. E.(!0002-9394 (Print) Journal ArticleAm J OphthalmolAged Arteries/ultrasonography Blood Flow Velocity Female Glaucoma, Open-Angle/*physiopathology/ultrasonography Humans Male Middle Aged Orbit/*blood supply/ultrasonography Ultrasonography, Doppler, Color/*methods Vision Disorders/*physiopathology/ultrasonography *Visual Fieldsjdhttp://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=86107938916291.7i3h 1996Jul-Sept,%Endothelin peptides in brain diseasesh 177-86Recently, scientists interested in diseases of the human brain have paid much attention to the endothelin group of peptides. Under normal conditions they are found in some types of neurons and in endothelial cells of microvessels but not in glial cells. This review focuses on the endothelin peptides and their involvement in various brain diseases. Particular attention is paid to their expression in reactive astrocytes seen in many pathological conditions of the human brain. Endothelin-1 is a very potent vasoconstrictor which may be involved in the vasospasm occurring in subarachnoid haemorrhage. Intracerebral injection or application to cerebral arteries in animals will cause a focal necrosis, apparently due to severe vasoconstriction. Reactive astrocytes occurring in cases with infarcts, lacunae, Alzheimer's disease, progressive multifocal leukoencephalopathy (PML) and subacute sclerosing panencephalitis (SSPE) express endothelin-like immunoreactivity. Astrocytes in vitro may produce, store and release endothelins. To some extent astrocytes grown in vitro mimic reactive astrocytes in vivo since in cultures astrocytes are removed from their natural environment which may trigger reactive responses. Therefore, in vivo reactive astrocytes may produce, store and release endothelins just as in vitro. If endothelins are released from reactive astrocytes they may act as mitogens and may influence microcirculation by inducing vasoconstriction of intracerebral arterioles. In such ways endothelins may contribute to the final lesions seen in cases with infarcts, lacunae, traumatic conditions, Alzheimer's disease and inflammatory diseases of the brain.'JCLaboratory of Neuropathology, University Hospital, Uppsala, Sweden.xNie, X. J. Olsson, Y.N.(0334-1763 (Print) Journal Article Review Rev NeurosciLFAnimals Astrocytes/*metabolism Blood-Brain Barrier/physiology Brain Diseases/metabolism/*physiopathology Cerebrovascular Disorders/physiopathology Endothelins/metabolism/*physiology Humans Neuropeptides/metabolism/*physiology Research Support, Non-U.S. Gov't Subarachnoid Hemorrhage/physiopathology Vasoconstriction/physiologyjdhttp://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=89162917611333 120f1  1995 Jul0)Microvasculature of the human optic nerveh 92-102 PURPOSE: Methyl methacrylate vascular corrosion casting techniques were used to examine the normal anterior optic nerve microvasculature in 18 human eye bank eyes. METHODS: Selective cannulation of the central retinal artery, the short posterior ciliary arteries, or both, allowed the methyl methacrylate to be injected into the anterior optic nerve circulation. Preflushing with tissue plasminogen activator greatly enhanced the filling of the fine microvasculature by dissolving the intraluminal clots. RESULTS: The superficial nerve fiber layer of the optic nerve received its primary blood supply from the central retinal artery. In 11 of 13 eyes injected with methyl methacrylate through the short posterior ciliary arteries, there was a perineural, circular arterial anastomosis (circle of Zinn-Haller) at the scleral level. Branches from this circle penetrated the optic nerve to supply the prelaminar and laminar regions and the peripapillary choroid. In the two eyes without this arterial circle, direct branches from the short posterior ciliary arteries supplied the anterior optic nerve. The venous drainage of the anterior optic nerve was almost entirely through the central retinal vein and its tributaries. CONCLUSIONS: This study demonstrates that the main arterial vascular supply to the anterior optic nerve is from the short posterior ciliary arteries. The contribution of the peripapillary choroid to the anterior optic nerve is minimal in comparison to the direct contribution from the short posterior ciliary arteries.'NGDepartment of Ophthalmology, Gifu University School of Medicine, Japan.<6Onda, E. Cioffi, G. A. Bacon, D. R. Van Buskirk, E. M.(!0002-9394 (Print) Journal ArticleAm J OphthalmolHBArteries Ciliary Body/blood supply/ultrastructure Corrosion Casting Humans Methylmethacrylate Methylmethacrylates Microcirculation Microscopy, Electron, Scanning Optic Nerve/*blood supply Research Support, U.S. Gov't, P.H.S. Retinal Artery/anatomy & histology/ultrastructure Retinal Vein/anatomy & histology/ultrastructurejdhttp://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=7611333e10433851692 1999 AugRLCentral and peripheral arteriovenous passage times of the retina in glaucoma 145-53 The purpose of this paper was to estimate arteriovenous passage (AVP) times, taking into account the non-uniform distribution of arrival times over the vessel diameter, and assessment of respective differences between 15 normal controls (N), 30 primary open-angle glaucoma (POAG) and 30 normal-pressure glaucoma (NPG) patients. Arrival times in retinal vessels were assessed from digitized scanning laser fluorescein angiograms. The arrival times were assessed as a function of position (juxtamural versus axial) in the vessel. This differentiation, based on the measurement position in the vessel, enabled the estimation of AVP times of the posterior pole and of the peripheral retina.The overall, juxtamural and axial AVP times were prolonged in POAG as compared to both N and NPG (P<0.03). The difference in axial AVP times between POAG and normal subjects was considerably larger than the juxtamural values. The distribution of AVP times was considerably larger in POAG patients than in N subjects and NPG patients.Retinal AVP times are prolonged in POAG patients as compared to N and NPG. The wider distribution of AVP times in POAG patients may point to a generalized microvascular alteration. Since the axial AVP times seem to provide the largest differences between NPG and POAG patients, this measurement may be preferred over more general AVP times. The axial AVP times may possibly reflect peripheral vascular changes, e.g. increased vascular resistance. The underlying mechanisms causing these differences are at present unknown.'f_Department of Ophthalmology, Academic Medical Center, University of Amsterdam, The Netherlands.,%Duijm, H. F. Berg, T. J. Greve, E. L.PJ0014-4835 (Print) Clinical Trial Controlled Clinical Trial Journal Article Exp Eye ResBlood Circulation/physiology Fluorescein Angiography Glaucoma/*physiopathology Humans Intraocular Pressure Retinal Vessels/*physiopathology Time Factorslehttp://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=10433851atous changes (P less than .05), but initial optic nerve head appearance, initial visual field findings, number of medicines used, medical history, and patient gender or race were not statistically associated with stability or progression of the glaucoma. These findings reinforce the importance of intraocular pressure control in primary open-angle glaucoma and the need to identify other markers that help determine the proper level of intraocular pressure for individual patients.'VPDepartment of Ophthalmology, Duke University Eye Center, Durham, North Carolina..(Mao, L. K. Stewart, W. C. Shields, M. B.(!0002-9394 (Print) Journal ArticlepAm J OphthalmolcAdult Aged Aged, 80 and over Female Follow-Up Studies Glaucoma, Open-Angle/*physiopathology/surgery Humans *Intraocular Pressure/drug effects Male Middle Aged Optic Disk/*physiopathology Tonometry, Ocular Trabeculectomy Visual Fieldsejdhttp://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=1985490N.12831143512 2003 Jun3`YPulsatile ocular blood flow among normal subjects and patients with high tension glaucoman 133-8df_PURPOSE: To estimate pulsatile ocular blood flow (POBF) among normal subjects and to compare various parameters in eyes of primary open angle glaucoma with high intraocular pressure (IOP). METHODS: POBF was estimated in 95 eyes of 95 normal subjects above the age of 40 years and in 35 eyes of 35 primary open angle glaucoma patients using the OBF system (OBF Labs Ltd., UK). Correlation of age, gender, IOP, pulse amplitude, pulse volume and pulse rate with POBF was studied. POBF values were measured in glaucomatous patients before IOP control and one month later after control of IOP to < 22 mmHg. RESULTS: The mean POBF among normal subjects was 1382.2 +/- 413 ml/min (range 636-2291 m/min). Females had a significantly higher mean POBF (1512 +/- 347 ml/min) than males (1193 +/- 312 ml/min). The mean IOP among normal subjects was 12.6 mmHg and in glaucoma patients, 29.1 mmHg. Mean POBF in glaucomatous eyes with initially elevated IOP was 718.9 +/- 322.6 ml/min, which improved after IOP control to 1129 +/- 291 ml/min. IOP had a strong (P < .01) negative correlation with POBF (r = -0.667) CONCLUSIONS: POBF among eyes of normal subjects in this study is higher than reported among Caucasian eyes. Primary open angle glaucoma eyes with high IOP have significantly reduced ocular blood flow. Therapy aimed at lowering IOP has a positive effect onocular haemodynamics.g'hbDr. R P Centre for Ophthalmic Sciences, All India Institute of Medical Sciences, New Delhi, India.4-Agarwal, H. C. Gupta, V. Sihota, R. Singh, K.a(!0301-4738 (Print) Journal ArticlegIndian J OphthalmoltAdult Case-Control Studies Eye/*blood supply Female Glaucoma, Open-Angle/*complications/*physiopathology Humans Male Middle Aged Ocular Hypertension/*complications/*physiopathology Pulsatile Flow Regional Blood Flow-lehttp://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=12831143Lterior ciliary artery from 0.75 to 0.91, and for the long posterior ciliary artery from 0.77 to 0.99 in both the groups. CONCLUSIONS: The ICCs of the repeated measurements reflect a good reproducibility for both the groups with assumed different retrobulbar perfusion. These findings are prerequisites for the use of CDI in clinical practice and research.4'Universitatsklinikum Hamburg-Eppendorf, Klinik und Poliklinik fur Augenheilkunde, Hamburg, Germany. e.matthiessen@uke.uni-hamburg.de82Matthiessen, E. T. Zeitz, O. Richard, G. Klemm, M.:40950-222X (Print) Evaluation Studies Journal Article Eyei*#Blood Flow Velocity Ciliary Arteries/physiopathology/*ultrasonography Glaucoma/physiopathology/*ultrasonography Humans Ophthalmic Artery/physiopathology/*ultrasonography Pulsatile Flow Regional Blood Flow Reproducibility of Results Ultrasonography, Doppler, Color/methods Vascular Resistanceylehttp://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=15069438D(16045909821 2006 JanXREffects of acute delivery of endothelin-1 on retinal ganglion cell loss in the rat 132-45  The vasoconstrictive peptide, Endothelin-1 (ET-1) has been found at elevated levels in glaucomatous eyes. In this study, a single 5mul intraocular injection of ET-1 was injected into the rat eye in order to characterize an in vivo retinal ganglion cell (RGC)-specific cell death model. The most effective concentration of ET-1 at inducing RGC loss at 2 weeks post-injection was determined using 5, 50 and 500mum concentrations of ET-1. The density of surviving RGCs was determined by counting Fluorogold labelled RGCs. A significant loss (25%) of RGCs was observed using only the 500mum concentration when compared to PBS-injected controls. GFAP immunohistochemistry revealed an increase in GFAP expression in Muller cell end-feet, as well as a total increase in GFAP expression (80%), following ET-1 treatment. These changes in GFAP expression are indicative of glial hyperactivity in response to stress. The specificity of ET-1 mediated cell death for RGCs was determined by measuring the changes in retinal thickness and TUNEL labeling. Retinal thickness was quantified using confocal and light microscopy. In confocal measurements, Yo Pro-1 was used to stain nuclear layers and the thickness of retinal layers determined from reconstructions. No significant loss in thickness was observed in any retinal layers. The same observations were seen in semi-thin sections when viewed by conventional transmitted light microscopy. The lack of significant thickness changes in the outer nuclear, outer plexiform or inner nuclear layer suggests that there was no significant cell loss in the retina other than in the RGC layer. Exclusive co-localization of TUNEL-labelled nuclei with Fluorogold-labelled cytoplasm provided additional evidence for RGC-specific death that most likely occurs via an apoptotic mechanism. A cell death time course was performed to determine RGC loss over time. RGC losses of 25, 25, 36 and 44% were observed at 1, 2, 3 and 4 weeks post-ET-1 injection, compared to PBS-injected controls. The total number of remaining RGC axons was determined by multiplying the number of optic nerve (ON) axons per unit area, by the cross-sectional area. There was a 31% loss in total ON axons in ET-1 treated eyes at 3 weeks post injection. Functional integrity of the visual system was determined by observing changes in the pupillary light reflex. ET-1 treatment resulted in a slowing of the pupil velocity by 31% and an average increase in the duration of contraction of 1.85sec (32% increase). These experiments provide evidence that acute ET-1 injections can produce RGC-specific cell death and many cellular changes that are similar to glaucoma. This potential glaucoma model leaves the optic nerve intact and may be used in subsequent experiments, which are involved in increasing RGC survival and functional recovery.'|Department of Pathology and Molecular Medicine, HSC Rm 1R1, McMaster University, 1200 Main St. West, Hamilton, Ont., Canada.0)Lau, J. Dang, M. Hockmann, K. Ball, A. K.(!0014-4835 (Print) Journal Article Exp Eye ResAnimals Axons/drug effects/pathology Cell Death/drug effects Dose-Response Relationship, Drug Endothelin-1/*pharmacology Female Glaucoma/*pathology In Situ Nick-End Labeling Injections Kainic Acid/pharmacology Microscopy, Confocal Models, Animal Neuroglia/drug effects/pathology Optic Nerve/drug effects/pathology Photic Stimulation Rats Rats, Sprague-Dawley Reflex, Pupillary/drug effects Research Support, Non-U.S. Gov't Retinal Ganglion Cells/drug effects/*pathology Time Factorslehttp://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=16045909>dgF 9211141r6t3p 1997 Jun3d^Pulsatile ocular blood flow measurements in healthy eyes: reproducibility and reference values 175-9o4.PURPOSE: To determine the reproducibility and the normal reference range of pulsatile ocular blood flow (POBF) values in healthy subjects using the Ocular Blood Flow Tonograph (OBF Laboratories, UK Ltd., Wiltshire, England). METHOD: Pulsatile ocular blood flow was measured in one eye of each of 83 patients. Coefficient of reliability was determined by calculation of intraclass correlation coefficient via one-way analysis of variance. Mean difference between measurements was calculated for bias and first exposure effects. Pulsatile ocular blood flow from 163 healthy individuals were analyzed to determine the distribution, mean, standard deviation (SD), range, and the 5th and 95th percentile values. The influence of age, blood pressure, pulse rate, and intraocular pressure on pulsatile ocular blood flow was determined by regression analysis. RESULTS: Reliability coefficient for pulsatile ocular blood flow values ranging from 290 microliters/min to 2,196 microliters/min was 0.92. Variation in bias and first exposure effect were not significant. Pulsatile ocular blood flow values were normally distributed. Mean values were 669.90 +/- 233.0 microliters/min in men and 841.90 +/- 254.6 microliters/min in women. Fifth and ninety-fifth percentile values were 364.75 microliters/min and 1,266.10 microliters/min in men and 397.18 microliters/min and 1,346.10 microliters/min in women. Pulsatile ocular blood flow was significantly influenced by pulse rate. CONCLUSION: This study confirms the reliability of the Ocular Blood Flow Tonograph in repeated measurements of POBF within individuals over short time intervals. The high interindividual variation in POBF may invalidate comparison of POBF between individuals, and the wide range of normal values may limit the value of using a low POBF as a possible indicator of disease.'.(St. Paul's Eye Unit, Liverpool, England.@9Yang, Y. C. Hulbert, M. F. Batterbury, M. Clearkin, L. G.s(!1057-0829 (Print) Journal Articleb J GlaucomaAdult Aged Aged, 80 and over Blood Pressure Eye/*blood supply Female Humans Male Middle Aged Observer Variation Pulsatile Flow/*physiology Reference Values Regression Analysis Reproducibility of Resultsjdhttp://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=9211141b[Zarfati, D. Harris, A. Garzozi, H. Zacish, M. Kagemann, L. Jonescu-Cuypers, C.P. Martin, B. 2000:4A review of ocular blood flow measurement techniquesNeuro-Ophthalmology3401-40916825276 2006 Jul 6itmGlaucoma progression is associated with decreased blood flow velocities in the short posterior ciliary arteryHBPURPOSE: An altered perfusion of the optic nerve head has been proposed as a pathogenic factor in glaucoma. The aim of the study was to investigate potential differences in ocular hemodynamics between glaucoma patients with progressive versus stable disease as well as healthy volunteers. METHODS: Peak systolic velocity (PSV), end- diastolic velocity (EDV) and resistivity index (RI) in the short posterior ciliary artery (SPCA), central retinal artery (CRA) and ophthalmic artery (OA) were recorded in 114 consecutive glaucoma patients with an intraocular pressure (IOP) i U21 mm Hg as well as 40 healthy volunteers by colour Doppler imaging (CDI). RESULTS: Out of 114 glaucoma patients, 12 showed glaucoma progression (follow-up period: 295i A18 days). CDI measurements in these patients demonstrated decreased PSV and EDV in the SPCA (p<0.001 and p<0.05, resptively) and decreased PSV in the CRA compared with stable glaucoma patients and healthy controls (p<0.05). No differences in flow velocities were found for the OA. IOP and systemic blood pressure were similar in all three groups. CONCLUSIONS: Progressive glaucoma is associated with decreased blood flow velocities in the small retrobulbar vessels supplying the optic nerve head. The detected difference could represent a risk factor for progression of glaucomatous optic neuropathy.'`ZUniversitatsklinikum Hamburg-Eppendorf, Klinik und Poliklinik fur Augenheilkunde, Germany.xrZeitz, O. Galambos, P. Wagenfeld, L. Wiermann, A. Wlodarsch, P. Praga, R. Matthiessen, E. T. Richard, G. Maren, K.(!0007-1161 (Print) Journal articlemBr J Ophthalmolklehttp://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=16825276  @ N=\_da^ GhJ'! ye <#OK|;{T"C $z,+f.6lpw]Um1 %MP HD(0RXtB94*Iq@-rs3857ZbS):}c2LuvAY[EQnixW&~o/`j?Fg> meFelaL $Aged, 80 and over RvG l12967797 136n3s 2003 SepM^WEvaluating pulsatile ocular blood flow analysis in normal and treated glaucomatous eyes 448-53PURPOSE: To evaluate pulsatile ocular blood flow (POBF) analysis in normal subjects and glaucoma patients by comparison of POBF measurements with functional (as determined by visual field [VF]) and structural (as determined by optical coherence tomography [OCT]) measures. DESIGN: Prospective, cross-sectional study. METHODS: Forty-one eyes of 24 consecutive glaucoma patients and 20 eyes of 10 healthy subjects were studied; POBF analysis was performed on all subjects at the same visit as VF testing and OCT retinal nerve fiber layer (NFL) thickness measurement. The mean results of normal and glaucomatous eyes were compared for each method. Correlation between measurements obtained with each modality and the discriminating power using receiver operator characteristic curves was tested. RESULTS: The mean POBF (standard deviation [SD]) in the normal group was 1,010.4 (292.8) microl/min and 989.3 (305.5) microl/min in the glaucoma group (P =.90). Significant differences between groups were found for VF mean deviation and pattern standard deviation (P =.02, P =.004, respectively) and OCT mean NFL thickness (P <.0001). No correlation was found between POBF parameters and intraocular pressure, VF, or OCT variables except for intraocular pressure in glaucoma group (r = -.43, P =.003). The area under the receiver operator characteristic curves was higher for VF indexes and OCT mean NFL thickness than POBF parameters for distinguishing between normal and glaucomatous eyes. CONCLUSIONS: The wide range of normal values and the low discriminating power of POBF between normal and glaucomatous eyes limits the clinical use of the device for glaucoma patients.'|uNew England Eye Center, Tufts-New England Medical Center, Tufts School of Medicine, Boston, Massachusetts 02111, USA.:3Aydin, A. Wollstein, G. Price, L. L. Schuman, J. S.(!0002-9394 (Print) Journal ArticleAm J OphthalmolAged Antihypertensive Agents/therapeutic use Blood Flow Velocity Choroid/blood supply Comparative Study Cross-Sectional Studies Eye/*blood supply Female Glaucoma/*drug therapy/*physiopathology Humans Interferometry Intraocular Pressure Male Middle Aged Nerve Fibers/pathology Optic Nerve/pathology Perimetry Prospective Studies Pulsatile Flow Regional Blood Flow Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S. Tomography Tonometry, Ocular Visual Fieldslehttp://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=1296779712472450833n 2000 Mayc("Optic nerve blood flow in glaucoma180-184gBACKGROUND: Glaucomatous optic neuropathy often occurs in the absence of elevated intraocular pressure and, conversely, elevated intraocular pressure may occur without associated damage of the optic nerve. These findings challenge the simple explanation of intraocular pressure being the sole cause of neural loss and have led to theories of ischaemic causes of the morbidity. This paper reviews the vascular anatomy of the optic disc, the factors that control its blood flow and the existing techniques for measurement of the blood flow. It also briefly discusses the possible role of apoptosis in glaucomatous visual loss. METHOD: Literature review. CONCLUSIONS: The posterior ciliary artery circulation is the main source of the blood supply to the optic nerve head with additional lesser supply via the central retinal artery and the choroidal circulation. There is considerable individual variation in the distribution of this circulation and complex regulatory systems govern its function. It is likely that microcirculatory changes in the vascular supply of the optic disc play a role in glaucoma, either as the primary abnormality or as a co-factor that increases susceptibility to damage from increased intraocular pressure through impaired auto-regulation. Clinical trials are currently in progress for the treatment of glaucoma with systemically administered agents that are antagonists of the receptors that mediate glutamine toxicity, a factor in the process of apoptosis. '~xGlaucoma Unit, The Royal Victorian Eye and Ear Hospital, 32 Gisbourne Street, East Melbourne, Victoria, 3002, Australia. Bathija, R.n(!0816-4622 (Print) Journal articletClin Exp Optomlehttp://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=12472450r12556392442t 2003 FebchaDeformation of the lamina cribrosa and anterior scleral canal wall in early experimental glaucoma 623-37 PURPOSE: To test the hypothesis that pathophysiologic deformation of the lamina cribrosa and anterior scleral canal wall underlies the onset of confocal scanning laser tomography (CSLT)-detected optic nerve head (ONH) surface change in early experimental glaucoma. METHODS: Both eyes of four normal (two normal eyes) monkeys and four with early glaucoma (one eye with laser-induced IOP elevation, observed until the onset of CSLT-detected ONH surface change) were enucleated immediately after death and immersion fixed at IOP 0 mm Hg. In an additional four normal monkeys and five with early glaucoma, both eyes were cannulated, and IOP set to 10 mm Hg in one normal eye and either 30 or 45 mm Hg in the other (normal or early-glaucoma) eye. After 15 to 80 minutes of acute IOP elevation, these nine monkeys were perfusion-fixed. Within images of serial sagittal sections of the ONH tissues in all 17 monkeys, anterior lamina cribrosa position, laminar thickness, and scleral canal diameter were measured. For each parameter, differences between the two eyes of each monkey and between treatment groups were assessed by ANOVA. RESULTS: Within the eyes of the eight monkeys with IOP 0 mm Hg, the lamina cribrosa was posteriorly displaced and thicker and the scleral canal was enlarged at Bruch's membrane and at the anterior laminar insertion in the early-glaucoma eyes compared with the contralateral normal eyes (plastic deformation). Within the high-IOP normal eyes, the lamina cribrosa was posteriorly displaced compared with that in the low-IOP normal eyes, but there were no significant differences in laminar thickness or scleral canal diameter (normal compliance). Within the high-IOP early-glaucoma eyes, the lamina cribrosa was posteriorly displaced and thicker and the scleral canal enlarged, compared with both low-IOP normal eyes and high-IOP normal eyes (hypercompliant deformation). Differences in laminar position between the high-IOP early-glaucoma eyes and the contralateral low-IOP normal eyes (hypercompliant plus plastic deformation) were more than eight times greater than the differences between the high-IOP normal eyes and the contralateral low-IOP normal eyes (normal compliance). CONCLUSIONS: Both plastic (permanent) and hypercompliant deformation of the lamina cribrosa and anterior scleral canal wall are present in young adult monkey eyes with early experimental glaucoma. These findings suggest that damage to the ONH connective tissues occurs early in the monkey model of experimental glaucoma.'\UDepartment of Biomedical Engineering, Tulane University, New Orleans, Louisiana, USA.^XBellezza, A. J. Rintalan, C. J. Thompson, H. W. Downs, J. C. Hart, R. T. Burgoyne, C. F.(!0146-0404 (Print) Journal Article Invest Ophthalmol Vis SciXRAnimals Connective Tissue/pathology Disease Models, Animal Glaucoma/*pathology Intraocular Pressure Laser Coagulation Macaca fascicularis Macaca mulatta Male Optic Disk/*pathology Optic Nerve Diseases/*pathology Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S. Sclera/*pathology Tomography Trabecular Meshwork/surgerylehttp://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=12556392y  Drance, S. 1972<6Some factors in the production of low tension glaucomaBr J Ophthalmol563e 229-42 Mar\5032759n~wAdult Age Factors Aged Blood Coagulation Disorders/complications Blood Pressure Circadian Rhythm Diabetes Complications Glaucoma/*etiology Hemorrhage Humans Hypotension/complications *Intraocular Pressure Middle Aged Ophthalmic Artery Optic Nerve Platelet Adhesiveness Serum Globulins Vascular Diseases/complications Vision Disorders/complications Visual Acuity Visual Fieldsl(!0007-1161 (Print) Journal Articlefjdhttp://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=503275911384564 131S6C 2001 Jund\URisk factors for progression of visual field abnormalities in normal-tension glaucomae699-708dB;PURPOSE: To uncover risk factors for the highly variable individual rates of progression in cases of untreated normal-tension glaucoma. METHODS: Visual field data were assembled from 160 subjects (160 eyes) enrolled in the collaborative normal-tension glaucoma study during intervals in which the eye under study was not receiving intraocular pressure-lowering treatment during prerandomization and postrandomization intervals. Analyses included multivariate analysis of time-dependent Cox proportional hazard, Kaplan-Meier analysis of "survival" without an increment of visual field worsening, and comparison of slopes of change in mean deviation global index over time. RESULTS: Most migraine occurred in women, but analysis demonstrated that gender and presence of migraine contribute separately to the overall risk. The risk ratio for migraine, adjusted for the other variables was 2.58 (P =.0058), for disk hemorrhage was 2.72 (P =.0036), and for female gender 1.85 (P =.0622). The average fall in the mean deviation index was faster in nonmigrainous women than in nonmigrainous men (P =.05). Suggesting genetic influence, Asians had a slower rate of progression (P =.005), and the few black patients enrolled had a tendency for faster progression. However, self-declared history of family with glaucoma or treated for glaucoma did not affect the rate of progression. Neither age nor the untreated level of intraocular pressure affected the rate of untreated disease progression, despite their known influence on prevalence. CONCLUSIONS: Whereas risk factors for prevalence help select populations within which to screen for glaucoma, the factors that affect the rate of progression help decide the expected prognosis of the individual's untreated disease and thereby the frequency of follow-up and aggressiveness of the therapy to be undertaken.'<6Bascom Palmer Eye Institue, Miami, Fl 33101-6880, USA..'Drance, S. Anderson, D. R. Schulzer, M.(!0002-9394 (Print) Journal ArticleAm J OphthalmolAfrican Continental Ancestry Group/genetics Aged Asian Continental Ancestry Group/genetics Disease Progression Eye Hemorrhage/complications Female Glaucoma/complications/genetics/*physiopathology Humans *Intraocular Pressure Male Middle Aged Migraine Disorders/complications Optic Disk/blood supply Prognosis Reference Values Research Support, Non-U.S. Gov't Risk Factors Sex Characteristics Survival Analysis *Visual Fieldslehttp://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=11384564 s>@F Sulfonamides/*therapeutic use85Sulfonamides/administration & dosage/*therapeutic use Sulfonamides/therapeutic useSurvival AnalysisSwitzerland/epidemiology(%Sympathetic Nervous System/physiology0*Sympathetic Nervous System/physiopathology Syndrome SystoleSystole/physiology Terminology Thiophenes/*therapeutic use83Thiophenes/administration & dosage/*therapeutic use Thiophenes/therapeutic use Time FactorsTimolol/*pharmacologyTimolol/*therapeutic use40Timolol/administration & dosage/*therapeutic use(%Timolol/pharmacology/*therapeutic useTimolol/therapeutic use Tissue DonorsTissue Fixation TomographyTomography/methodsTonometry, Ocular Tonometry, Ocular/*economics Tonometry, Ocular/*methods0*Tonometry, Ocular/instrumentation/*methods Trabecular Meshwork/surgeryTrabeculectomyTrabeculectomy/*methodsTreatment OutcomeUltrasonography, Doppler$Ultrasonography, Doppler, Color,(Ultrasonography, Doppler, Color/*methods,'Ultrasonography, Doppler, Color/methodsUrban Population$Vascular Diseases/complications0-Vascular Diseases/complications/*epidemiology@=Vascular Diseases/complications/drug therapy/*physiopathologyVascular Resistance$ Vascular Resistance/drug effects$Vascular Resistance/physiologyVasoconstriction Vasoconstriction/physiology VasodilationVasodilation/*physiologyVasodilation/physiology0*Vasodilator Agents/administration & dosage$ Vasomotor System/physiopathologyVeinsVeins/physiology Vision Vision Disorders/*diagnosis Vision Disorders/*etiology$!Vision Disorders/*physiopathology41Vision Disorders/*physiopathology/ultrasonography$Vision Disorders/complications Vision Disorders/diagnosisVision Disorders/etiology$ Vision Disorders/physiopathology Visual AcuityVisual Acuity/physiologyVisual Cortex/physiology Visual FieldsVisual Fields/*physiology Visual Fields/drug effectsVisual Fields/physiologyWales,'Wounds, Nonpenetrating/*physiopathology{`9695795172g 1998 Apro60Optic nerve blood-flow abnormalities in glaucoma 267-89Glaucoma can be defined as an optic nerve disease with typical morphological and functional changes. There are many risk factors associated with this neuropathy. The best known factor is an increased intraocular pressure. There are, however, many other risk factors. Among them, vascular factors play a major role. Although such vascular factors have been postulated more than hundred years ago, it is only recently that the physiology and pathophysiology of the optic nerve head circulation is, to some extent, understood. New instruments have bee11235526 232n 2000HAOcular haemodynamics and nitric oxide in normal pressure glaucomad 37-8XQThe authors studied the ocular haemodynamics by means of the Color Doppler Imaging (CDI) technique and the levels of cyclic guanosine monophosphate (cGMP), the intracellular mediator of NO action in plasma and the aqueous humour in a Normal Pressure Glaucoma group and in a normal group. They found significant alterations of both the velocities, systolic and diastolic, in the Ophthalmic Artery and lower cGMP levels in NPGs than in the controls. These data suggest that a disorder of NO regulation processes might be involved in blood supply to the optic nerve and in aqueous humour outflow.o'PIDepartment of Oto-Neuro-Ophthalmological Surgery, University of Florence.oD>Galassi, F. Sodi, A. Ucci, F. Renieri, G. Pieri, B. Masini, E.(!1395-3931 (Print) Journal Articlev"Acta Ophthalmol Scand Suppl,HAAged Aqueous Humor/metabolism Blood Flow Velocity Ciliary Arteries/*physiopathology/ultrasonography Cyclic GMP/blood Female Glaucoma, Open-Angle/blood/*physiopathology Humans *Intraocular Pressure Male Middle Aged Nitric Oxide/*metabolism Ophthalmic Artery/*physiopathology/ultrasonography Ultrasonography, Doppler, Colorslehttp://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=11235526s necessarily be associated with an increase in POBF.'XQGlaucoma Research Unit, Moorfields Eye Hospital, City Road, London, EC1V 2PD, UK.eNHPoinoosawmy, D. Indar, A. Bunce, C. Garway-Heath, D. F. Hitchings, R. A.(!0721-832X (Print) Journal Articlee& Graefes Arch Clin Exp OphthalmolAdministration, Topical Aged Antihypertensive Agents/*therapeutic use Betaxolol/therapeutic use Blood Flow Velocity Comparative Study Eye/*blood supply Female Glaucoma, Open-Angle/*physiopathology/therapy Humans Intraocular Pressure/*drug effects Male Ophthalmic Solutions Prostaglandins F, Synthetic/therapeutic use Pulsatile Flow Quinoxalines/therapeutic use Retrospective Studies Tonometry, Ocular Trabeculectomy/*methodslehttp://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=12271368fNGPrasanna, G. Krishnamoorthy, R. Hulet, C. Zhang, H. Zhang, X. Yorio, T.o 2000ngEndothelin-1 induces nitric oxide synthase-2 expression in human non-pigmented ciliary epithelial cellsr Exp Eye Resc715m 535-9y Novo11040089&Cells, Cultured Ciliary Body/*metabolism Colorimetry Endothelin-1/*physiology Gene Expression Humans Nitric Oxide Synthase/*metabolism Nitric Oxide Synthase Type II Pigment Epithelium of Eye/*metabolism Research Support, U.S. Gov't, P.H.S. Reverse Transcriptase Polymerase Chain Reaction0014-4835 (Print) Letterlehttp://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=11040089 >&smHEQuinoxalines/administration & dosage/adverse effects/*therapeutic use Quinoxalines/therapeutic use RabbitsRadioimmunoassayRandom AllocationRatsRats, Inbred BNRats, Sprague-DawleyReceptor, Endothelin B("Receptor, Endothelin B/*metabolismHCReceptors, Endothelin/agonists/antagonists & inhibitors/*metabolism0,Receptors, Endothelin/analysis/*biosynthesis$Receptors, Transferrin/analysis0,Recovery of Function/drug effects/physiologyReference StandardsReference Values$Reflex, Pupillary/drug effectsRefraction, OcularRegional Blood Flow$Regional Blood Flow/*physiology$ Regional Blood Flow/drug effects0+Regional Blood Flow/drug effects/physiology$Regional Blood Flow/physiologyRegression Analysis0,Regulatory Sequences, Nucleic Acid/*genetics Renin/blood("Reperfusion Injury/physiopathology Reproducibility of Results($Research Support, N.I.H., Extramural$ Research Support, Non-U.S. Gov't,(Research Support, U.S. Gov't, Non-P.H.S.($Research Support, U.S. Gov't, P.H.S.Retina/*physiologyRetina/*physiopathologyRetina/*radiation effectsRetina/pathology,)Retinal Artery Occlusion/*physiopathology(#Retinal Artery/*anatomy & histology Retinal Artery/*physiology0*Retinal Artery/*physiology/ultrasonography,)Retinal Artery/*physiology/ultrastructure$Retinal Artery/*physiopathology41Retinal Artery/*physiopathology/radiation effects4/Retinal Artery/*physiopathology/ultrasonography("Retinal Artery/anatomy & histology41Retinal Artery/anatomy & histology/ultrastructure@;Retinal Artery/drug effects/physiopathology/ultrasonography,&Retinal Artery/innervation/*physiologyRetinal Artery/pathologyRetinal Artery/physiology,)Retinal Artery/physiology/ultrasonography$Retinal Artery/physiopathology4.Retinal Artery/physiopathology/ultrasonography0+Retinal Diseases/*diagnosis/physiopathology$!Retinal Diseases/*physiopathology4.Retinal Ganglion Cells/*drug effects/pathology0-Retinal Ganglion Cells/*pathology/*physiology41Retinal Ganglion Cells/*physiology/ultrastructure4/Retinal Ganglion Cells/chemistry/ultrastructure4.Retinal Ganglion Cells/drug effects/*pathology$ Retinal Ganglion Cells/pathology,)Retinal Hemorrhage/complications/etiology$!Retinal Vein/*anatomy & histologyRetinal Vein/*physiology4/Retinal Vein/*physiopathology/radiation effects4/Retinal Vein/anatomy & histology/ultrastructureRetinal Vein/pathologyRetinal Vein/physiology0,Retinal Vein/physiopathology/ultrasonography($Retinal Vessels/*anatomy & histology4.Retinal Vessels/*drug effects/*physiopathology Retinal Vessels/*metabolism Retinal Vessels/*pathology0*Retinal Vessels/*pathology/physiopathology Retinal Vessels/*physiology4.Retinal Vessels/*physiology/*radiation effects$ Retinal Vessels/*physiopathology40Retinal Vessels/*physiopathology/ultrasonography4/Retinal Vessels/anatomy & histology/*physiology@1%/year, with significance level tailored according to series variability. Less stringent and stringent criteria were tested. Specificity was estimated by the proportions of control subjects with disease progression and significantly improving subjects (all). Agreement between disc and field progression in the subjects with OHT was assessed with specificities matched for both VF and HRT. RESULTS: Specificity for VF PLR was estimated to be 85.7% to 95.4% when standard criteria were used, and for RA/time to be 88.1% to 90.5% with the less-stringent criteria. In this comparison, 21.2% progressed by RA alone and 20.2% by VF alone, and 12.1% progressed by both RA and VF. Specificity was estimated to be 95.2% to 98.2% for both VF PLR and RA/time, using the three-omitting criteria and the stringent RA/time criteria, respectively. In this comparison, 8.6% progressed by RA alone, 15.1% by VF alone, and 3.5% by both RA and VF. CONCLUSIONS: A relatively high frequency of detected disease progression was observed with either method, with progression by VF occurring at least as frequently as progression by RA. Poor agreement between RA and VF progression was observed regardless of the specificity of the progression criteria. The results indicate that, in patients with ocular hypertension, monitoring of both VF and optic disc is necessary, as agreement between optic disc and VF progression is the exception rather than the rule.'NHGlaucoma Research Unit, Moorfields Eye Hospital, London, United Kingdom.D=Strouthidis, N. G. Scott, A. Peter, N. M. Garway-Heath, D. F.(!0146-0404 (Print) Journal Article Invest Ophthalmol Vis Sci@:Adult Aged Comparative Study Female Humans Male Middle Aged Ocular Hypertension/*diagnosis Optic Disk/*pathology Optic Nerve Diseases/*diagnosis Prospective Studies Reproducibility of Results Research Support, Non-U.S. Gov't Sensitivity and Specificity Tomography/methods Vision Disorders/*diagnosis *Visual Fieldslehttp://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=1679903214736786882s 2004 FebnRKAlterations in the morphology of lamina cribrosa pores in glaucomatous eyes 251-6AIMS: To determine alterations which occur in the size and shape of lamina cribrosa (LC) pores in glaucomatous eyes over a period of time. METHODS: Baseline and follow up optic disc photographs were retrospectively studied in 39 eyes of 39 patients with glaucoma. Only eyes with a vertical cup to disc ratio equal to or greater than 0.6 were included in the study. In addition, all selected eyes had to have serial optic disc photographs obtained at least 3 years apart allowing clear visualisation of LC surface. The association of the alterations in LC surface morphology with patient specific and eye specific characteristics was statistically analysed. RESULTS: During a mean study period of 3.90 (SD 0.7) years, individual pore size (mean pore area to disc area ratio) exhibited a significant decrease between baseline and follow up measurements of each eye (p<0.0001). However, during the study period, total pore area to disc area ratio did not change (p>0.05), and the change in pore shape in some eyes (from circular to more oval and elongated) was statistically insignificant (p = 0.12). Although a relation was detectable between the optic disc and lamina cribrosa parameters at a given time, which reflects cumulative effects, during the study period, there was no significant association between the changes of the LC parameters and neural tissue damage. The rate and the magnitude of the changes in individual pore size during the study period were not significantly different among the eyes exhibiting progressive neural rim damage and those staying stable (p>0.05). CONCLUSION: These findings demonstrate that the LC surface morphology exhibits changes along with the glaucomatous optic disc damage. However, the clinical appearance of LC surface in glaucomatous eyes may continue to change, even when the neural rim damage is clinically stable. These findings are probably associated with the chronic cellular events of tissue remodelling that occur in the glaucomatous optic nerve head.'Department of Ophthalmology and Visual Sciences, University of Louisville School of Medicine, Kentucky Lions Eye Center, 301 E. Muhammad Ali Boulevard, Louisville, KY 40202, USA. gulgun.tezel@louisville.edu(!Tezel, G. Trinkaus, K. Wax, M. B.(!0007-1161 (Print) Journal ArticleBr J OphthalmolAged Disease Progression Female Follow-Up Studies Glaucoma/*pathology Glaucoma, Open-Angle/pathology Humans Male Middle Aged Optic Disk/pathology Research Support, Non-U.S. Gov't Retrospective Studies Sclera/*pathologylehttp://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=147367869 |B 15751239151l 2005Jan-FebF?Ocular blood flow evaluation in injured and healthy fellow eyese 48-55r&PURPOSE: To assess if injured eyes develop ocular blood flow disturbances that may contribute to development of traumatic glaucoma. METHODS: Twenty-five eyes of 25 patients hospitalized from January 1997 to July 1999 for blunt (15) or penetrating (10) eye injury and elevated intraocular pressure (IOP) (>23 mm Hg) were controlled at least 24 months after the trauma and underwent visual field examination, pulsatile ocular blood flow (pOBF), and color Doppler imaging (CDI) analysis of ophthalmic artery, central retinal artery, nasal and temporal short posterior ciliary arteries. Uninjured healthy eye was used as control. RESULTS: IOP was significantly higher in injured eyes (15.1+/-3.3 vs 13.0+/-2.7 mmHg; p<0.01), but only 2 eyes (8%) were under medical treatment. pOBF values were significantly lower in injured eyes: 11.25+/-6.56 microL/sec in the trauma eyes and 15.40+/-7.29 in fellow eyes (p=0.002). Resistivity index of all investigated retrobulbar vessels was very significantly higher in injured eyes than in fellow eyes (p<0.0001). There is no significant correlation between IOP and ocular blood flow disturbance. CONCLUSIONS: Long-term follow-up (mean 39+/-12 months) of injured eyes shows, besides a slight but significant increase of IOP, a very significant impairment of ocular blood supply to injured eyes compared to healthy fellow eyes with reduction of pulsatile ocular blood flow and marked increase of resistance to flow in all retrobulbar vessels. These anomalies may be considered an independent risk factor to develop traumatic glaucoma.'xqDepartment of Neurosciences, Head-Neck and Rehabilitation, University of Modena and Reggio Emila, Modena - Italy.:3Martini, E. Guiducci, M. Campi, L. Cavallini, G. M.(!1120-6721 (Print) Journal ArticleEur J OphthalmolBlood Flow Velocity Ciliary Arteries/*physiology/ultrastructure Eye/*blood supply Eye Injuries, Penetrating/*physiopathology Female Follow-Up Studies Humans Intraocular Pressure Male Middle Aged Ophthalmic Artery/*physiology/ultrastructure Pulsatile Flow Regional Blood Flow Retinal Artery/*physiology/ultrastructure Ultrasonography, Doppler, Color Visual Fields Wounds, Nonpenetrating/*physiopathologylehttp://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=15751239i15069438184G 2004 Aprc^XReproducibility of blood flow velocity measurements using colour decoded Doppler imaging 400-5sB;BACKGROUND: It is taken for granted that glaucomatous damage is caused by changed haemodynamics of the retrobulbar vessel system besides other factors such as, for example, an elevated intraocular pressure. This was proven by various studies in which glaucoma patients were shown to have a changed retrobulbar blood flow velocity. In this study, the reliability of measurements of retrobulbar vessel perfusion by colour decoded Doppler imaging (CDI) was evaluated. PATIENTS AND METHODS: A total of 18 healthy volunteers and 15 patients with various glaucoma types were enrolled in this study. Using a CDI system, type Siemens Sonoline Elegra with a combined applicator (7.5L40), retrobulbar vessel perfusions of the ophthalmic artery, the short posterior ciliary arteries, and the long posterior ciliary arteries of each patient were measured six times. In each measurement, pulse amplitude, end-diastolic velocity, maximum systolic velocity, pulsatility index, and resistivity index of the vessels were determined. The reproducibility of measurements was evaluated by the calculation of the intraclass correlation coefficient (ICC) for each parameter. RESULTS: The ICCs for the ophthalmic artery varied from 0.89 to 0.98, for the short posterior ciliary artery from 0.75 to 0.91, and for the long posterior ciliary artery from 0.77 to 0.99 in both the groups. CONCLUSIONS: The ICCs of the repeated measurements reflect a good reproducibility for both the groups with assumed different retrobulbar perfusion. These findings are prerequisites for the use of CDI in clinical practice and research.4'Universitatsklinikum Hamburg-Eppendorf, Klinik und Poliklinik fur Augenheilkunde, Hamburg, Germany. e.matthiessen@uke.uni-hamburg.de82Matthiessen, E. T. Zeitz, O. Richard, G. Klemm, M.:40950-222X (Print) Evaluation Studies Journal Article Eyei*#Blood Flow Velocity Ciliary Arteries/physiopathology/*ultrasonography Glaucoma/physiopathology/*ultrasonography Humans Ophthalmic Artery/physiopathology/*ultrasonography Pulsatile Flow Regional Blood Flow Reproducibility of Results Ultrasonography, Doppler, Color/methods Vascular Resistanceylehttp://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=15069438D 15790877464 2005 AprleRetinal vessel diameters and incident open-angle glaucoma and optic disc changes: the Rotterdam study 1182-7~PURPOSE: It remains unclear whether reduced retinal blood flow and smaller arterioles, reported to exist in patients with open-angle glaucoma (OAG), are a cause or a consequence of ganglion cell loss. We examined whether baseline retinal vessel diameters were related to incident (i)OAG or incident optic disc changes in a population-based sample. METHODS: In the prospective population-based Rotterdam Study, baseline diameters of retinal arterioles and venules (1990-1993) were measured in digitized images of 3469 persons (aged 55 years and older) at risk for OAG. The follow-up examinations took place from 1997 to 1999. iOAG was based on the presence of incident glaucomatous visual field loss and/or incident glaucomatous optic neuropathy. Changes in neuroretinal rim, cup area, or vertical cup-to-disc ratio were calculated with a semiautomated image analyzer in 2782 persons. RESULTS: After a mean follow-up time of 6.5 years, 74 participants had iOAG. At baseline, the mean arteriolar diameter was 147.5 +/- 14.2 microm (SD) and the venular, 222.9 +/- 20.0 microm. Neither arteriolar diameters (odds ratio [OR] per SD decrease: 0.82; 95% confidence interval [CI]: 0.66-1.03) nor venular ones (OR per SD increase: 1.20; 95% CI: 0.95-1.53) were significantly related to iOAG. Baseline retinal vessel diameters did not predict changes in the optic disc. Additional adjustment for cardiovascular risk factors did not alter these results. CONCLUSIONS: The data show that baseline retinal vessel diameters did not influence the risk of iOAG or incident optic disc changes. These data provide no evidence for a retinal vascular role in the pathogenesis of OAG.'haDepartment of Epidemiology and Biostatistics, Erasmus Medical Center, Rotterdam, The Netherlands.f_Ikram, M. K. de Voogd, S. Wolfs, R. C. Hofman, A. Breteler, M. M. Hubbard, L. D. de Jong, P. T.(!0146-0404 (Print) Journal Article Invest Ophthalmol Vis SciAged Blood Pressure Female Glaucoma, Open-Angle/*epidemiology Humans Intraocular Pressure Male Middle Aged Optic Disk/*pathology Optic Nerve Diseases/*epidemiology Prospective Studies Research Support, Non-U.S. Gov't Retinal Vessels/*pathology Risk Factorslehttp://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=1579087712752054812d 2003 Apr |vThe effects of latanoprost and brimonidine on blood flow velocity of the retrobulbar vessels: a 3-month clinical trial 155-60ngOBJECTIVE: To investigate the effects of topical latanoprost 0.005% and topical brimonidine tartrate 0.2% on retrobulbar blood flow in patients with primary open-angle glaucoma (POAG) and ocular hypertension (OHT). METHODS: Forty-one consecutive patients with POAG and OHT were enrolled in this prospective, open-label, randomized, parallel study. Patients received either latanoprost 0.005% or brimonidine 0.2% for 3 months. Baseline retrobulbar blood flow measurements of the ophthalmic artery, central retinal artery and temporal short posterior ciliary artery were taken using colour Doppler imaging ultrasound, concurrently with systemic blood pressure, heart rate, ocular perfusion pressure and intraocular pressure (IOP) measurements. These measurements were repeated after 3 months. RESULTS: Both latanoprost and brimonidine significantly reduced IOP (p < 0.05). While there was a statistically significant increase in peak systolic velocity of the ophthalmic artery, no significant change was observed in the other vessels with latanoprost treatment (p < 0.05). Topical brimonidine did not significantly alter flow velocities or resistive indices in the retrobulbar vessels after 3 months. CONCLUSION: Topical latanoprost and brimonidine significantly reduced IOP in patients with POAG and OHT without causing significant haemodynamic alterations in the retrobulbar vessels.a'rkDepartment of Ophthalmology, Kocatepe University, School of Medicine, Afyon, Turkey. uuinan@superonline.comi4-Inan, U. U. Ermis, S. S. Yucel, A. Ozturk, F.fRL1395-3907 (Print) Clinical Trial Journal Article Randomized Controlled TrialActa Ophthalmol ScandfBlood Flow Velocity/*drug effects Ciliary Arteries/physiopathology/ultrasonography Eye/*blood supply Glaucoma, Open-Angle/*drug therapy/physiopathology/ultrasonography Humans Intraocular Pressure/drug effects Ocular Hypertension/*drug therapy/physiopathology/ultrasonography Ophthalmic Artery/physiopathology/ultrasonography Prostaglandins F, Synthetic/*therapeutic use Quinoxalines/*therapeutic use Retinal Artery/physiopathology/ultrasonography Ultrasonography, Doppler, Color Vascular Resistance/drug effectslehttp://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=127520545 b 12770971876_ 2003 JunjcColour Doppler imaging and fluorescein filling defects of the optic disc in normal tension glaucomaa 731-6AIM: To investigate the relation between blood flow parameters of the retrobulbar vessels measured by means of colour Doppler imaging (CDI) and fluorescein filling defects of the optic nerve head in patients with normal tension glaucoma (NTG) and control subjects. METHODS: 29 patients with NTG and 29 age and sex matched control subjects were included in this study. Blood flow velocities-peak systolic velocity (PSV), end diastolic velocity (EDV), and resistive indices (RI) of the ophthalmic artery (OA), the central retinal artery (CRA), and of the temporal and nasal short posterior ciliary arteries (TPCA, NPCA)-were measured with CDI. Fluorescein angiograms were performed with a scanning laser ophthalmoscope. The extent of absolute fluorescein filling defects of the optic nerve head in relation to the optic nerve head was assessed. RESULTS: The PSV of the OA, the PSV and EDV of the CRA, and of the TPCA and NPCA were significantly reduced in NTG (p<0.05). The RI of the CRA, the TPCA and NPCA were significantly increased in NTG (p<0.01). The optic nerve head fluorescein filling defects were significantly larger in NTG (p<0.01). The filling defects were significantly negatively correlated (p<0.05) with the PSV and EDV of the CRA (PSV(CRA): r = -0.41; EDV(CRA): r = -0.34), with the PSV and EDV of the NPCA (PSV(NPCA): r = -0.34; EDV(NPCA): r = -0.38), and with the EDV of the TPCA (r = -0.29). A significant positive correlation (p<0.05) was found with the RI of both PCAs (RI(NPCA): r = 0.28; RI(TPCA): r = 0.29). CONCLUSION: Patients with NTG had reduced blood flow velocities and higher resistive indices in most retrobulbar vessels. Optic nerve head fluorescein filling defects were larger compared to controls. The filling defects were correlated with end diastolic velocities and resistive indices of the PCAs and with blood flow velocities of the CRA. Capillary loss of the optic nerve head may be related to higher downstream resistance and reduced blood flow velocities of the retrobulbar vessels.'pjAugenklinik des Universitatsklinikum Aachen, Pauwelsstrasse 30, 52057 Aachen, Germany. nplange@ukaachen.de$Plange, N. Remky, A. Arend, O.(!0007-1161 (Print) Journal ArticlesBr J OphthalmolhBlood Flow Velocity Blood Pressure Case-Control Studies Diastole Fluorescein Angiography/methods Glaucoma/*diagnosis/physiopathology Humans Middle Aged Optic Disk/blood supply Retrospective Studies Systole Ultrasonography, Doppler, Color/methodsAlehttp://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=12770971a162398982020 2006 Feb f`24-h blood pressure monitoring in normal tension glaucoma: night-time blood pressure variability 137-42Systemic arterial hypotension, hypertension and altered ocular blood flow are known risk factors in glaucoma. In this study, 24-h ambulatory blood pressure monitoring was performed in patients with normal tension glaucoma (NTG) and controls to evaluate blood pressure variability. In all, 51 patients with NTG and 28 age-matched controls were included in this prospective study. A 24-h ambulatory blood pressure monitoring (SpaceLabs Medical Inc., Redmond, USA) was performed and systolic, diastolic and mean arterial blood pressures were measured every 30 min during daytime (0800-2000) and night time (0000-0600). To evaluate blood pressure variability a variability index was defined as the s.d. of blood pressure measurements. Night-time blood pressure depression ('dip') was calculated (in percent of the daytime blood pressures). Patients with NTG exhibited higher night-time diastolic (P = 0.01) and mean arterial blood pressure values (P = 0.02) compared to controls, whereas systolic blood pressure data were not significantly different. The variability indices of night-time systolic, diastolic and mean arterial blood pressure measurements were significantly increased in patients with NTG compared to controls (P < 0.05). The night-time blood pressure depression of systolic (P = 0.47), diastolic (P = 0.11) and mean arterial blood pressures (P = 0.28) was not significantly different between patients with NTG and controls. In conclusion, patients with NTG showed increased variability of night-time blood pressure measurements compared to controls. Increased fluctuation of blood pressure may lead to ocular perfusion pressure fluctuation and may cause ischaemic episodes at the optic nerve head.'PIAugenklinik des Universitatsklinikum Aachen, Germany. nplange@ukaachen.deHBPlange, N. Kaup, M. Daneljan, L. Predel, H. G. Remky, A. Arend, O.(!0950-9240 (Print) Journal ArticlehJ Hum HypertensKZTAged Blood Pressure/*physiology Blood Pressure Monitoring, Ambulatory Case-Control Studies Circadian Rhythm/*physiology Diastole/physiology Eye/blood supply Female Glaucoma/complications/*physiopathology Humans Hypertension/complications/*physiopathology Intraocular Pressure/*physiology Male Middle Aged Sleep/physiology Systole/physiologylehttp://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=16239898sLN Agarwal2003= Akarsu2004rAkhalbedashvili2003cAldinger20010i Alm2001J Amin2002K Amoako-Mensah2004Anastasopoulos20066Anderson1997yAnderson2001 Aoki19777' Archibald2004j Arend1993` Arend1995 Arend1996^ Arend1999^ Arend1999_ Arend2000Z Arend2001a Arend2002b Arend2003 Arend2003\ Arend2004] Arend2004d Arend20055 Arend20067 Arend20068 Arend2006  Armaly1980G Aydin2003 Azar20042; Baccini2003Bachmann1999 Bacon1995 Bacon1996Balaratnasingam2004Balaratnasingam2005( Ball20062 Bathija2000F Batterbury1997 Becker19800Bellezza2003h Ben Simon2003 Bengtsson2002 Bengtsson2003e Berg19999 Berisha2005Bernardi2000= Bilgili2004+Bizzarro2003,Bizzarro2003 Blum1999Boles Carenini1994J Bonini20020 Bonomi2000 Bosem1995 Branca2006u Breiteneder1997Breteler2005z Brimage1997 Brun20050J Bucci2002 Buck19988@ Buckley19961 Budde2003K Buehl2004 Bui2004O Bunce1998S Bunce2002 Bunt19771Burgoyne2003B Campi2005W Cantatore2001j Cantor19933_ Cantor2000 Cantor2001W Cardia20011Carenini1994Carlsson2000: Cassamali1997 Catton19979B Cavallini2005J Centofanti2002t Chakravarthy2005 Chamot19981H Chan2003H Chan2003H Chan2003 Chauhan2000' Chauhan2004 Chen19966R Cheng2002/ Childs-Shaw1987R Chou20022 Chung1998f Chung1999 Chung2001 Cioffi1995 Cioffi1996m Cioffi20000 Cioffi2001 Cioffi2004~ Cioffi20066f Ciulla1999x Clark1998FClearkin19979 Cole20032 Coleman2006! Collignon1998Collignon-Brach1992!Collignon-Brach1998 Coloma19940 Connell1995 Costa2002 Costa2003 Cringle2004 Cringle2005 Cull2001 Cull20040~ Cull20060Cunliffe2004z Curtain1997L Dallinger2000 Dallinger20055Daneljan2006( Dang2006q Darhad20060 de Jong1994 de Jong2005de Voogd2005 Delaey2000Demaster1997 Desai2005! Dewe1998 Dhanjil19984 Dichtl19988 Dielemans1994T Diestelhorst2002: Donato19979 Dong20040~ Dong20060 Dorman-Pease1990 Dorner2000 Dorner2004 Douglas1995 Downs2003  Drance1972 Drance1995- Drance19969@ Drance19969? Drance19979y Drance2001& Dubler19969A Dubler20000s Dubler20022r Dubler20033e Duijm1999 Dunkelberger19903 Dupont20012  Eddy1983 Eddy19839u Eichler1997L Eichler2000 Eichler2000K Eichler2004< Emre2004 Emre2005/ Epstein1987 Ermis2003 Ethier19949 Evans1998D Farrell1989E Farrell1989Fechtner1994u Fercher1997 Feuer1997u Findl1997L Findl2000 Findl2000 Findl2005T Fisher2002t Flammer1987 Flammer1991# Flammer1994% Flammer1995& Flammer1996 Flammer1998A Flammer2000C Flammer2000" Flammer2001 Flammer2001 Flammer2001 Flammer2002s Flammer2002 Flammer2002r Flammer2003 Flammer2003 Flammer2003< Flammer2004$ Flammer2005 Flammer2005 Flammer2006O Fontana1998 Formaz1997 Fortune2004~ Fortune2006KFuchsjager-Mayrl2004q Fujioka2006>Galambos2006{ Galassi2000; Galassi2003| Galassi2004:Gandolfo19979Garhofer2004Garhofer2005S Garway-Heath2002n Garway-Heath2006g Garzozi2000 Garzozi2003 Gasser1987 Gasser1991& Gasser19969 Gazozi20010 Geiser1997CGekkieva2000Gekkieva2001T Georgopoulos2002K Georgopoulos20042CGherghel2000"Gherghel2001Gherghel2001Gherghel20033Gherghel2004Ghilardi1997}Ghilardi2003z Goadsby1997h Goldenfeld2003 Gordon20022 Gottsch1991u Gouya1997 Graham19666  Graham1995 Green1979e Greve1999$ Grieshaber2005z Griffiths1997 Grobbee1994* Groh199693Grunwald2001A Gugleta2000C Gugleta2000" Gugleta2001 Gugleta2001 Gugleta2003< Gugleta2004BGuiducci2005! Guillaume1998N Gupta2003 Gutteridge2000` Haase1995+ Hafez2003, Hafez2003}Hagiwara2003* Harazny19964 Harazny19981 Harazny20033 Hariprasad20010o Harman2005 Harris19966: Harris19979 Harris19989^ Harris19999f Harris1999_ Harris2000g Harris20000 Harris2001pJ Harris20020a Harris2002 Harris2003 Harris2003 Harris2003U Harris2004n Harris20066 Hart20033 Hasler20033 Haufschild2005. Hayashi20006 Hayreh1995p Hayreh1999 Hayreh2001l Hayreh2001Hazelton2004Hazelton2005a Heathcote1994 Heijl2002 Heijl2003 Heijl2003 Henle1996w Henry1999/ Hertzmark1987  Hetherington1980 Heuer2002 Higginbotham2002I Hikichi2001O Hitchings1998S Hitchings2002- Hnik19961(Hockmann2006 Hofman19941 Hofman2001 Hofman20050 Hollows1966 Horie1977 Hosking2004 House2004 House2005 Hoyng2001R Hsu2002 Hubbard2005& Huber1996] Huber2004 Huemer20044t Hughes2005yF Hulbert1997) Hulet2000 Hulet2005 Hussein2002 Hussein20030 Hyman1995 Hyman2002 Hyman2003 Ikram2005 Inan2003S Indar2002 Ishii2001I Ishiko20010t Jackson2005 James1994U Januleviciene2004 Javitt19911Johanson1977m Johnson2000 Johnson2002' Jollimore20041 Jonas2003gJonescu-Cuypers2000Jonescu-Cuypers2001Jonescu-Cuypers2006 Joos19971Kagemann1998fKagemann1999gKagemann2000Kagemann2001rUKagemann2004  Kahn1980% Kaiser1995s Kaiser20022r Kaiser2003r Kappos20033c Kaps20012 Kashiwagi2004 Kass2002u Kastner1997 Katz19919 Katz19949cKaufmann20010d Kaup200505 Kaup200607 Kaup200608 Kaup20060 Keeffe2004' Kelly2004 Keltner2002+ Kergoat2003M Kerr1998P Kerr2003Kerrigan1995 Khurana19962 Kimura20066K Kircher2004 Kiss20000 Kiss20055 Kitazawa1977.Kitazawa20009 Klemm2004s Kloti2002Knighton1997R Ko20022 Kohner1996 Kolker1980nKomaroff20033I Konno2001Koskosas2006su Krejcy1997 Krieglstein2002T Krieglstein2002 d \ 815036566626l 2004 Feb 15Pathogenetic aspects of the glaucomatous optic neuropathy: fluorescein angiographic findings in patients with primary open angle glaucoma 517-24PURPOSE: To identify and quantify the role of retinal circulation, capillary leakage and/or nonperfusion of the optic nerve head in digital fluorescein angiography in normal subjects and patients with open angle glaucoma. METHODS: Eighteen patients with primary open angle glaucoma (POAG) and 18 healthy age matched subjects were included. Fluorescein angiograms were performed using the scanning laser ophthalmoscope. The arteriovenous passage time (AVP) was assessed by dye dilution technique and describes the shortest passage through a retinal vascular segment. Optic nerve head nonperfusion was marked manually in early angiographic images and is given as percentage of the optic disk area. The fluorescence of the optic nerve head (as measure of the disruption of the blood-brain barrier) and the surrounding retina (ratio of leakage) was measured using digital imaging analysis in the late phases of the angiogram (9-10min). RESULTS: The AVP time was significantly prolonged ( P=0.001) in patients with open angle glaucoma (AVP 2.29+/-0.32 s) compared to healthy subjects (AVP 1.37+/-0.42 s). The mean percentage of the optic nerve head nonperfusion was 16%. The ratio of optic nerve head fluorescence compared to retinal reference loci was significantly increased (P = 0.02) in patients with glaucoma (1.32+/-0.25) compared with normal subjects (1.32+/-0.19). CONCLUSIONS: Fluorescein angiography revealed altered retinal perfusion along with optic nerve head nonperfusion and increased vascular leakage in open angle glaucoma patients. These factors appear to influence each other, with ultrastructural changes of the lamina cribrosa accompanying changes in the vasculature and nerve fibers. Longitudinal and interventive studies should help better elucidate the relationship between circulatory and neural loss, adding vasoprotective therapeutic approaches to interfere with the glaucomatous neurodegenerative chain of events.'Universitatsklinikum Aachen, Augenklinik der Rheinisch Westfalischen Technischen Hochschule Aachen, Pauwelsstr. 30, 52057 Aachen, Germany. Oliver.Arend@post.rwth-aachen.deM4-Arend, O. Plange, N. Sponsel, W. E. Remky, A.G(!0361-9230 (Print) Journal Article2Brain Res BullB;Adult Aged Comparative Study Contrast Media/administration & dosage Fluorescein/administration & dosage/*diagnostic use Glaucoma/etiology/pathology/radiography Glaucoma, Open-Angle/*etiology/*pathology/radiography Humans Microscopy, Confocal/methods Middle Aged Optic Nerve Diseases/*etiology/pathology/*radiography.lehttp://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=15036566e15672253 243u7, 2005 Jul(LFFluorescein leakage of the optic disc in glaucomatous optic neuropathy 659-64yPURPOSE: To identify and quantify the role of capillary leakage of the optic nerve head in digital fluorescein angiography in normal subjects and patients with open-angle glaucoma. METHODS: We conducted a prospective cross-sectional study in the Department of Ophthalmology of the Technical University of Aachen. Thirty patients with primary open-angle glaucoma (POAG) and 30 healthy age-matched subjects were included. Fluorescein angiograms were performed using the scanning laser ophthalmoscope. The fluorescence of the optic nerve head and the surrounding retina (ratio of leakage) was measured using digital imaging analysis in the late phases of the angiogram (9-10 min). RESULTS: The ratio of optic nerve head fluorescence to retinal reference loci was significantly increased (p=0.01) in patients with glaucoma (POAG, 1.38+/-0.34) compared with normal subjects (1.20+/-0.19). Intraocular pressure (p=0.0001), visual field indices (mean deviation, p<0.0001; pattern standard deviation, p<0.0001; corrected pattern standard deviation, p<0.0001), and cup to disc ratios (p=0.02) differed significantly between the groups. Age and systolic and diastolic blood pressure showed no significant differences between groups. CONCLUSION: Fluorescein angiography revealed significantly increased vascular leakage of glaucomatous optic nerve heads. An endothelial disruption and fluorescein leakage might be the result of mechanical stress at the level of the lamina cribrosa and/or a sign of ischemic damage. This measurement approach might enable us to judge the severity of optic nerve head leakage, and it is a potential way to evaluate therapeutic regimens.n'b[Augenzentrum Alsdorf, Cacilienstr. 9, 52047 Alsdorf, Germany. arend@augenzentrum-alsdorf.deo:4Arend, O. Remky, A. Plange, N. Kaup, M. Schwartz, B.(!0721-832X (Print) Journal Articler& Graefes Arch Clin Exp Ophthalmol\VBlood-Retinal Barrier *Capillary Permeability Cross-Sectional Studies Female Fluorescein/*metabolism Fluorescein Angiography Glaucoma, Open-Angle/*metabolism Humans Intraocular Pressure Male Middle Aged Optic Disk/*blood supply Optic Nerve Diseases/*metabolism Prospective Studies Regional Blood Flow Retinal Vessels/*metabolism Visual Fieldslehttp://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=15672253 7447768t9812 1980 Dec;Biostatistical analysis of the collaborative glaucoma study. I. Summary report of the risk factors for glaucomatous visual-field defects2163-71^A prospective collaborative study was conducted in five centers during a 13-year period to identify factors that influence the development of visual-field defects (GVFDs) of open angle glaucoma. In 5,000 subjects, GVFDs developed in only 1.7% of eyes. Statistical analysis of 26 factors at first examination identified five that were significantly related to the development of GVFDs--outflow facility, age, applanation pressure, cup-disc ratio, and pressure change after water drinking. Their absolute initial value, and not its change with time, was the important predictor. Multivariate analysis showed their collective predictive power to be undesirably poor, indicating that other factors must play an important role in the development of GVFDs. Mortality-table analysis indicated that during a period of five years, 98.54% of eyes with initial pressure less than 20 mm Hg continued to be free from GVFDs as compared with 93.34% of those with pressure of 20 mm Hg or greater.Armaly, M. F. Krueger, D. E. Maunder, L. Becker, B. Hetherington, J., Jr. Kolker, A. E. Levene, R. Z. Maumenee, A. E. Pollack, I. P. Shaffer, R. N.(!0003-9950 (Print) Journal ArticleArch Ophthalmol&Aged Glaucoma/*complications Humans Male Middle Aged Perimetry Prospective Studies Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, Non-P.H.S. Research Support, U.S. Gov't, P.H.S. Risk Scotoma/etiology Sensory Thresholds Statistics Vision Disorders/*etiology *Visual Fieldsujdhttp://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=7447768 1179731399 2001:3The effect of trabeculectomy on ocular hemodynamics2 241-52PURPOSE: To evaluate the effects of chronic reduction of intraocular pressure (IOP) on ocular hemodynamics. METHODS: Multisite, prospective evaluation of patients requiring trabeculectomy for treatment of glaucoma. Patients were recruited from the glaucoma service of 2 university hospitals. Patients were evaluated prior to surgery and at 3, 6, and 12 months after trabeculectomy. Color Doppler imaging was used to measure blood flow in the ophthalmic artery, central retinal artery, and short posterior ciliary arteries. Heidelberg retinal flowmetry was used to evaluate perfusion in the peripapillary and optic disc capillary beds. IOP was measured at baseline and at each study visit. RESULTS: There were highly significant reductions in IOP from presurgical baseline measures. At 3 months, mean IOP reduction was 17.1 mm Hg (62.3%; P < .001). At the 6- and 12-month evaluations, the mean IOP reductions were 15.7 mm Hg (57.3%) and 15.5 mm Hg (56.5%), respectively, P < .001. Despite the significant reduction in IOP, there were no significant differences in any ocular blood flow parameters before and after trabeculectomy. CONCLUSIONS: The findings of this study suggest that chronic reduction of IOP does not alter ocular blood flow and that IOP may be an independent risk factor for progression of glaucoma. These findings also suggest that the eye has the ability to autoregulate to chronically increased IOP over time and that additional studies evaluating the long-term effects of IOP changes are needed to further define this relationship.o'@9Indiana University School of Medicine, Indianapolis, USA.M Cantor, L. B.f(!0065-9533 (Print) Journal ArticleeTrans Am Ophthalmol SocgAdult Aged Aged, 80 and over Blood Flow Velocity Ciliary Arteries/physiology/ultrasonography Eye/*blood supply Female Glaucoma, Open-Angle/*physiopathology/*surgery Humans Intraocular Pressure/physiology Laser-Doppler Flowmetry Male Middle Aged Ophthalmic Artery/physiology/ultrasonography Prospective Studies Retinal Artery/physiology/ultrasonography *Trabeculectomy Ultrasonography, Doppler, Color-lehttp://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=11797313y_ 10067331961y 1999 Janm[Retinal hemodynamics in patients with normal pressure glaucoma. Quantification with digital laser scanning fluorescein angiography] 24-9ZSChronic ischemia of th10966955849i 2000 Sepl~xAltitudinal visual field asymmetry is coupled with altered retinal circulation in patients with normal pressure glaucoma1008-12}AIM: To compare the effect of altitudinal asymmetric glaucomatous damage on retinal microcirculation in patients with normal pressure glaucoma (NPG). METHODS: In a prospective cross sectional study patients with NPG (washed out for antiglaucomatous therapy) and altitudinal asymmetric perimetric findings between the superior and inferior hemisphere (Humphrey 24-2) (n=18) were included and compared with 20 NPG patients with symmetrical field defects and 18 healthy subjects. Fluorescein angiograms were performed using a scanning laser ophthalmoscope. Using digital image analysis, arteriovenous passage time (AVP) and vessel diameters were assessed for comparison of corresponding affected and less affected temporal arcades. RESULTS: Both affected and less affected hemispheres showed significantly prolonged AVP times (p<0.001) when compared with healthy subject data. In hemispheres with more severe glaucomatous field loss the AVP times were significantly (p=0.04) prolonged compared with the less affected hemisphere (AVP affected 3.1 (SD 7) seconds v AVP less affected 2.61 (1.4) seconds). There was no asymmetry effect on arterial and venous diameter measurements. CONCLUSION: Altitudinal visual field defects are linked together with circulatory deficits of the retinal tissue. The attenuated circulation seems to be a considerable factor in the natural course of glaucomatous optic neuropathy.n'Department of Ophthalmology, Medical School of the Technical University of Aachen, Pauwelsstrasse 30, 52057 Aachen, Germany. oliver.arend@post.rwth-aachen.dec2,Arend, O. Remky, A. Cantor, L. B. Harris, A.(!0007-1161 (Print) Journal Article.Br J Ophthalmol XQCross-Sectional Studies Female Glaucoma/*pathology/physiopathology Humans Male Microcirculation/*pathology Middle Aged Prospective Studies Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S. Retinal Vessels/physiopathology Sensory Thresholds Vision Disorders/*etiology Visual Acuity/physiology Visual Fields/*physiologyllehttp://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=10966955IZ 11392265 218p4c 2001 Aprgxr[Absolute filling defects of the optic disc in fluorescein angiograms in glaucoma--a retrospective clinical study] 214-21f_BACKGROUND: Analysis of clinical importance of the size of filling defects in fluorescein angiograms in primary open-angle glaucoma (POAG), normal-tension glaucoma (NTG), ocular hypertension and subjects with physiological excavations in comparison to visual field loss, optic nerve head morphology and hemod11392265 218p4c 2001 Aprgxr[Absolute filling defects of the optic disc in fluorescein angiograms in glaucoma--a retrospective clinical study] 214-21f_BACKGROUND: Analysis of clinical importance of the size of filling defects in fluorescein angiograms in primary open-angle glaucoma (POAG), normal-tension glaucoma (NTG), ocular hypertension and subjects with physiological excavations in comparison to visual field loss, optic nerve head morphology and hemodynamics. PATIENTS AND METHODS: 75 patients (POAG, NTG, ocular hypertension) and 10 healthy subjects with physiological excavations were included in this study. In digitized video fluorescein angiograms (Scanning Laser Ophthalmoscope) the size of absolute filling defects of the optic disc was quantified in the early venous phase and expressed by percentage of the optic disc. Visual fields were obtained by conventional static perimetry (Humphrey 24-2) and graded in stages of glaucoma visual field defects (Aulhorn I-V). Optic disc excavations were evaluated as cup-to-disc-area-ratios. RESULTS: The filling defects correlated with the visual-field loss stages of Aulhorn and the visual field indices MD (mean deviation), PSD (pattern standard deviation) and CPSD (corrected pattern standard deviation). There was no correlation with the index SF (short-term fluctuation) and with systemic hemodynamics (blood pressure, perfusion pressure) or the IOP. Absolute filling defects correlated with the cup-to-disc-area-ratio in NTG. The absolute filling defects were larger in patients with glaucoma (POAG, NTG) in comparison to patients without glaucomatous visual field loss (ocular hypertension, glaucoma-like discs). No difference of filling defects was found in the glaucoma group (POAG, NTG). Patients with NTG had larger excavations and lower systolic blood pressures than patients with POAG. CONCLUSION: The size of fluorescein filling defects may be useful as a parameter for the evaluation of an ischemic lesion of the optic nerve head. Absolute filling defects may differentiate POAG from ocular hypertension and NTG from glaucoma-like discs without field defects. The results support the hypothesis that in POAG and NTG disturbances of the circulation result in similar filling defects of the optic disc and visual field loss.'NGUniversitats-Augenklinik der RWTH Aachen, Pauwelsstr. 30, 52057 Aachen.$Plange, N. Remky, A. Arend, O.(!0023-2165 (Print) Journal Article$nhPapillare Fullungsdefekte in Fluoreszein-Angiographien bei Glaukom--Eine retrospektive klinische Studie. Klin Monatsbl AugenheilkdXRAdult Aged Case-Control Studies Comparative Study English Abstract *Fluorescein Angiography Glaucoma/*physiopathology Glaucoma, Open-Angle/physiopathology Humans Intraocular Pressure Middle Aged Ocular Hypertension/*physiopathology Ophthalmoscopy Optic Disk/blood supply/*pathology Optic Neuropathy, Ischemic/physiopathology Visual Fieldslehttp://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=11392265 Y& e$Laser-Doppler Flowmetry/methodsLasers/*diagnostic useLasers/diagnostic useLevobunolol/*pharmacology Lod ScoreLongitudinal StudiesMacaca fascicularisMacaca mulatta(%Macular Degeneration/*physiopathologyMale ManometryMaryland/epidemiologyMass Screening/*economicsMass Screening/*methods Massachusetts$Membrane Glycoproteins/analysis$Membrane Potentials/physiologyMethylmethacrylateMethylmethacrylatesMicrocirculation Microcirculation/*pathology<8Microcirculation/drug effects/physiology/physiopathology Microcirculation/physiology$ Microcirculation/physiopathologyMicroelectrodes,'Microglia/chemistry/cytology/metabolismMicroscopic AngioscopyMicroscopy, Confocal Microscopy, Confocal/methodsMicroscopy, Electron$Microscopy, Electron, Scanning Microspheres Middle Aged Migraine Disorders/*genetics$ Migraine Disorders/complicationsModels, AnimalModels, BiologicalModels, Theoretical0*Monosaccharide Transport Proteins/analysis83Multiple Sclerosis/*physiopathology/ultrasonographyMultivariate Analysis($Muscle, Smooth, Vascular/innervation(#Muscle, Smooth, Vascular/physiology,(Muscle, Smooth, Vascular/physiopathologyD?Myocardial Ischemia/*complications/epidemiology/physiopathologyMyopia/complications Nerve Degeneration/physiologyNerve Fibers/drug effectsNerve Fibers/pathologyNerve Fibers/physiology0+Nerve Regeneration/drug effects/*physiologyNetherlands/epidemiology,(Neuroglia/*chemistry/cytology/metabolism$ Neuroglia/drug effects/pathologyNeuroglia/pathologyNeurons/pathology($Neuropeptides/metabolism/*physiology Nitric Oxide Synthase Type II$Nitric Oxide Synthase Type III4/Nitric Oxide Synthase/*antagonists & inhibitors$Nitric Oxide Synthase/*genetics$!Nitric Oxide Synthase/*metabolism4.Nitric Oxide Synthase/antagonists & inhibitorsNitric Oxide/*metabolismNitric Oxide/*physiologyNitric Oxide/metabolismNitrites/*analysis/blood(%Nitroprusside/administration & dosageObserver Variation Ocular Hypertension/*blood83Ocular Hypertension/*complications/*physiopathology$Ocular Hypertension/*diagnosis0+Ocular Hypertension/*diagnosis/drug therapyDAOcular Hypertension/*drug therapy/physiopathology/ultrasonography$Ocular Hypertension/*pathology($Ocular Hypertension/*physiopathology Ocular Hypertension/diagnosis0-Ocular Hypertension/diagnosis/physiopathology82Ocular Hypertension/diagnosis/prevention & control41Ocular Hypertension/drug therapy/*physiopathology40Ocular Hypertension/drug therapy/physiopathology,)Ocular Hypertension/epidemiology/etiology(#Ocular Hypertension/physiopathology Odds Ratio($Oligodendroglia/chemistry/metabolism($omega-N-Methylarginine/*pharmacology4.omega-N-Methylarginine/administration & dosageOphthalmic Artery@:Ophthalmic Artery/*drug effects/physiology/ultrasonography Ophthalmic Artery/*physiology0-Ophthalmic Artery/*physiology/ultrasonography0,Ophthalmic Artery/*physiology/ultrastructure("Ophthalmic Artery/*physiopathology82Ophthalmic Artery/*physiopathology/ultrasonography("Ophthalmic Artery/*ultrasonographyD>Ophthalmic Artery/drug effects/physiopathology/ultrasonography0,Ophthalmic Artery/physiology/ultrasonography$!Ophthalmic Artery/physiopathology82Ophthalmic Artery/physiopathology/*ultrasonography41Ophthalmic Artery/physiopathology/ultrasonographyOphthalmic SolutionsS: Inferior rim blood flow is less than superior rim blood flow in patients with superior hemifield defect, and superior rim blood flow is reduced compared to inferior in patients with inferior hemifield defect. The mean S/I ratios of the MBF in the patients with superior hemifield defect (1.46, n=37) was significantly higher than that in the patients with inferior hemifield defect (0.79, n=17; P<0.0001, Mann-Whitney U-test). CONCLUSIONS: The blood flow in the neuroretinal rim was found to correspond to the regional visual field defect in eyes with NTG. Reductions in flow were associated with reductions in function.'Department of Ophthalmology, Keio University School of Medicine, 35 Shinanomachi, Shinjuku-ku, Tokyo, 160-8582, Japan, kimura@sc.itc.keio.ac.jp.@9Sato, E. A. Ohtake, Y. Shinoda, K. Mashima, Y. Kimura, I.(!0721-832X (Print) Journal Article& Graefes Arch Clin Exp Ophthalmollehttp://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=16315043< n6422575283l 1983Nov-Dec282The value of screening for glaucoma with tonometry194-205JCThis paper estimates the value of performing Schiotz tonometry to detect glaucoma in an asymptomatic patient. About 9% of adults over 40 will be found on a single Schiotz tonometry test to have elevated intraocular pressure (IOP). On work-up, about 1 out of 50 of these individuals with high IOP will be found to have glaucoma. Tonometry, however, will miss about half of all patients with glaucoma because they do not have elevated IOPs at the time of the test. Pilocarpine or epinephrine are the most commonly used drugs to treat the disease, but they are not always effective in lowering a patient's IOP or in stopping the progression of field defects. From the available evidence it does not appear that earlier diagnosis makes a substantial difference in the patient's outcome. If all individuals over 40 years of age in a city of 1,000,000 were screened, the total cost of finding and treating about 484 people with chronic simple glaucoma would be on the order of $4,944,866 or about $13,000 per patient potentially benefited. Screening with tonometry does not appear to be warranted.,&Eddy, D. M. Sanders, L. E. Eddy, J. F.(!0039-6257 (Print) Journal ArticleSurv OphthalmolAdult Cost-Benefit Analysis Epinephrine/administration & dosage Evaluation Studies False Negative Reactions Follow-Up Studies Glaucoma, Open-Angle/diagnosis/*prevention & control Humans Intraocular Pressure Mass Screening/*economics Middle Aged Ocular Hypertension/*diagnosis/drug therapy Ophthalmic Solutions Pilocarpine/administration & dosage Research Support, Non-U.S. Gov't Sodium Chloride/administration & dosage Time Factors Tonometry, Ocular/*economicsjdhttp://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=642257515090420885r 2004 Mayi\VOcular blood flow alteration in glaucoma is related to systemic vascular dysregulation 662-6dAIMS: To investigate the source of ocular blood flow alterations in glaucoma. METHODS: In 56 patients with open angle glaucoma, blood flow parameters were obtained from both eyes in the ophthalmic and central retinal artery by means of colour Doppler imaging, as well as in the choroidal circulation and the neuroretinal rim of the optic nerve by means of laser Doppler flowmetry. Based on these haemodynamic parameters, a cluster analysis (two groups) was performed and differences with regard to risk factors were assessed between clusters. RESULTS: Ocular blood flow data in the two clusters indicated that the two groups (cluster 1 = 26 patient with higher blood flow values; cluster 2 = 30 patients with lower blood flow values) differed mainly in choroidal and optic nerve blood flow. No differences in sex distribution, propensity to have normal tension glaucoma, age, endothelin-1 plasma levels, visual field damage, intraocular pressure, or systemic blood pressure parameters were observed between the two clusters. However, 12 patients (46%) from the cluster with high ocular blood flow values showed a vasospastic response in nailfold capillaroscopy, while such a response was observed in 24 patients (80%) of the cluster with low ocular blood flow values. This difference in vasospastic propensity was statistically significant (p = 0.0121). CONCLUSIONS: Ocular blood flow alterations in glaucoma patients seem, at least partly, to be related to a systemic vascular dysregulation.'0*University Eye Clinic, Basel, Switzerland.0*Emre, M. Orgul, S. Gugleta, K. Flammer, J.(!0007-1161 (Print) Journal ArticlerBr J OphthalmolnxrAged Aged, 80 and over Blood Flow Velocity Blood Pressure Choroid/blood supply Endothelin-1/blood Eye/*blood supply Female Glaucoma, Open-Angle/*physiopathology Humans Intraocular Pressure Laser-Doppler Flowmetry Male Middle Aged Ophthalmic Artery/physiopathology Optic Nerve/blood supply Regional Blood Flow Retinal Artery/physiopathology Vasoconstriction Visual Fieldslehttp://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=15090420o15615748891d 2005 Jane\UIncreased plasma endothelin-1 levels in patients with progressive open angle glaucomar 60-3AIM: To compare the plasma levels of endothelin-1 (ET-1) between patients with primary open angle glaucoma with visual field progression despite normal or normalised intraocular pressure and patients with stabile visual fields in a retrospective study. METHODS: The progressive group consisted of 16 primary open angle glaucoma patients and the group with stable visual field consisted of 15 patients. After a 30 minute rest in a supine position, venous blood was obtained for ET-1 dosing. Difference in the plasma level of ET-1 between two groups was compared by means of analysis of covariance (ANCOVA), including age, sex, and mean arterial blood pressure as covariates. RESULTS: ET-1 plasma levels were found to be significantly increased in patients with deteriorating (3.47 (SD 0.75) pg/ml) glaucoma when compared to those with stable (2.59 (SD 0.54) pg/ml) visual fields (p = 0.0007). CONCLUSIONS: Glaucoma patients with visual field progression in spite of normal or normalised intraocular pressure have been found to have increased plasma endothelin-1 levels. It remains to be determined if this is a secondary phenomenon or whether it may have a role in the progression of glaucomatous damage. 'XRUniversity Eye Clinic Basel, Mittlere Strasse 91, PO Box, 4012 Basel, Switzerland.@9Emre, M. Orgul, S. Haufschild, T. Shaw, S. G. Flammer, J.i(!0007-1161 (Print) Journal ArticleoBr J OphthalmolaAged Analysis of Variance Blood Pressure/physiology Endothelin-1/*blood Female Glaucoma, Open-Angle/*blood/drug therapy/physiopathology Humans Intraocular Pressure/physiology Male Middle Aged Retrospective Studies Visual Fields/physiologylehttp://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=15615748 7974188o391. 1994Jul-Aug.F?Mechanisms of optic nerve damage in primary open angle glaucoma 23-42opjSeveral mechanisms have been postulated to explain the optic nerve damage that occurs in primary open angle glaucoma (POAG). No single mechanism can adequately explain the great variations in susceptibility to damage and the patterns of damage seen in this syndrome. The etiology of POAG is likely to be multifactorial. Mechanical, vascular and other factors may influence individual susceptibility to optic nerve damage. An enhanced understanding of the nature of the optic nerve damage in POAG and improved methods of study may result in earlier diagnosis or may allow us to distinguish among different pathological processes all currently grouped under the diagnosis of POAG. As we gain a better understanding of the neuropharmacology and cellular biology of injury and repair of the visual system we will undoubtedly refine the concepts of glaucomatous optic neuropathy.'ZTDepartment of Ophthalmology and Visual Sciences, University of Louisville, Kentucky.$Fechtner, R. D. Weinreb, R. N..(0039-6257 (Print) Journal Article ReviewSurv OphthalmolGlaucoma, Open-Angle/*complications/pathology Humans Intraocular Pressure Optic Disk/blood supply/pathology Optic Nerve/pathology Optic Nerve Diseases/*etiology/pathology Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S.jdhttp://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=7974188 10208262 237p4i 1999 AprfNGNoninvasive measurement of the Bayliss effect in retinal autoregulationd296-300s@9PURPOSE: The Bayliss effect describes the reaction of smooth muscle cells in the arterial wall to changes in blood pressure. A rise in mean arterial blood pressure (MAP) causes an autoregulatory myogenic vessel constriction by smooth muscle cells in the arterial wall. The responsiveness of retinal vessels to changes in MAP were analyzed using the Retinal Vessel Analyzer (RVA). METHODS: Continuous measurement of retinal arterial vessels was performed in 40 healthy volunteers (age 18-56 years.) over a 9-min period. After a 3-min baseline measurement (phase I), isometric exercise caused a rise in MAP over the next 3 min (phase II). During the last 3 min (phase III) recovery was observed. Blood pressure and ECG were documented simultaneously throughout the experiment. RESULTS: Exercise caused a significant rise of 22.8 (+/-6.0) mm Hg in MAP (phase II vs. phase I: P<0.001). Retinal arterioles showed 5.5% (+/-2.8%) vasoconstriction (P<0.001). During phase III vessel diameters returned to normal, with no difference from phase I (P = 0.179). CONCLUSION: Noninvasive measurement and quantitative analysis of the Bayliss effect in human retinal vessels by means of the RVA is possible. Analysis of retinal arterial autoregulation may provide valuable insight into pathologic conditions such as diabetic or hypertensive retinopathy.)'PIDepartment of Ophthalmology, Friedrich Schiller University Jena, Germany.rJCBlum, M. Bachmann, K. Wintzer, D. Riemer, T. Vilser, W. Strobel, J.n(!0721-832X (Print) Journal Articles& Graefes Arch Clin Exp OphthalmolpjAdolescent Adult Blood Pressure/physiology Comparative Study Diagnostic Techniques, Ophthalmological/*instrumentation Exercise/physiology Female *Homeostasis Humans Intraocular Pressure/physiology Male Middle Aged Muscle, Smooth, Vascular/physiology Reference Values Research Support, Non-U.S. Gov't Retina/*physiology Retinal Artery/*physiology Vasoconstrictionlehttp://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=1020826210889099 107y7t 2000 JultTNVascular risk factors for primary open angle glaucoma: the Egna-Neumarkt Study1287-93mHAOBJECTIVE: To assess the impact of vascular risk factors on the prevalence of primary open angle glaucoma. DESIGN: Population-based cross-sectional study. PARTICIPANTS: Four thousand two hundred ninety-seven patients more than 40 years of age underwent a complete ocular examination in the context of the Egna-Neumarkt Glaucoma Study. INTERVENTION: Ocular examinations were performed by trained, quality-controlled ophthalmologists according to a predefined standardized protocol including medical interview, blood pressure reading, applanation tonometry, computerized perimetry, and optic nerve head examination. MAIN OUTCOME MEASURES: Prevalences of ocular hypertension, primary open-angle glaucoma, normal-tension glaucoma, and other types of glaucoma were determined. Correlation coefficients were calculated for the association between systemic blood pressure and age-adjusted intraocular pressure (IOP) and between age and both intraocular and systemic blood pressures. Odds ratios were computed to assess the risk of primary open-angle glaucoma and normal-tension glaucoma in relation to systemic hypertension or antihypertensive medication, blood pressure levels, diastolic perfusion pressure, and a number of other cardiovascular risk factors. RESULTS: A positive correlation was found between systemic blood pressure and IOP, and an association was found between diagnosis of primary open-angle glaucoma and systemic hypertension. Lower diastolic perfusion pressure is associated with a marked, progressive increase in the frequency of hypertensive glaucoma. No relationship was found between systemic diseases of vascular origin and glaucoma. CONCLUSIONS: Our data are in line with those reported in other recent epidemiologic studies and show that reduced diastolic perfusion pressure is an important risk factor for primary open-angle glaucoma.r'JDClinica Oculistica, Universita degli Studi di Verona, Verona, Italy.NHBonomi, L. Marchini, G. Marraffa, M. Bernardi, P. Morbio, R. Varotto, A.(!0161-6420 (Print) Journal Articlei OphthalmologycngAdult Aged Aged, 80 and over *Blood Pressure Cross-Sectional Studies Female Glaucoma, Open-Angle/*epidemiology/etiology Humans *Intraocular Pressure Italy/epidemiology Male Middle Aged Ocular Hypertension/epidemiology/etiology Odds Ratio Optic Disk/blood supply Perimetry Prevalence Risk Factors Tonometry, Ocular Vascular Diseases/complications/*epidemiologymlehttp://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=10889099w16133034 244h4y 2006 Apr*PIRetinal vascular diameter in young subjects with a vasospastic propensityl 454-9.PURPOSE: Retinal vascular diameters have recently been shown not to be related to an increased risk of open-angle glaucoma. Because vasospastic propensity has been suggested to represent a risk factor for various ocular diseases, especially glaucoma, the steady-state retinal vascular diameter in subjects with a propensity for systemic vascular dysregulation was compared with a group of age-matched gender-matched controls. METHODS: Thirty healthy non-smoking individuals [female/male 26/4; mean +/- SD age 22.8+/-3.4 (range 18-31) years] were enrolled into the study. Subjects were classified as having vasospasm (15 subjects) if they related a clear history of frequently cold hands and as healthy subjects (15 subjects) if they denied such a history. Vasospastic propensity or the absence of it had to be confirmed by nail-fold capillaroscopy. Vascular diameter of retinal vessels was measured repeatedly on two days with the retinal vessel analyser and corrected for perfusion pressure, age, and refraction. RESULTS: Neither retinal arteriole diameter (P=0.30) or retinal venule diameter (P=0.49), nor retinal arteriole-to-venule ratio (P=0.96), differed between the two experimental groups. CONCLUSIONS: Although vasospastic propensity has been suggested to represent a risk factor in various ocular diseases, the steady-state retinal vessel diameters are not altered in healthy vasospastic subjects. It is probable that the steady-state retinal vessel diameters are no adequate risk indicators for the haemodynamic risk in diseases such as glaucoma.i'ngUniversity Eye Clinic of Basel, Mittlere Strasse 91, P.O Box 4012, Basle, Switzerland, sorguel@uhbs.ch.u@9Branca, F. Orgul, S. Zawinka, C. Reinhard, G. Flammer, J.i(!0721-832X (Print) Journal Article7& Graefes Arch Clin Exp Ophthalmollehttp://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=16133034uFujioka, M. Kusuhara, A. Maeda, H. Negi, A.(!0002-9394 (Print) Journal ArticleAm J Ophthalmol*$Adult Aged Aged, 80 and over Comparative Study Cornea/pathology Female Glaucoma/*physiopathology Humans Intraocular Pressure/*physiology Male Middle Aged Ocular Hypertension/physiopathology Reproducibility of Results Research Support, Non-U.S. Gov't Tonometry, Ocular/instrumentation/*methodslehttp://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=16876523p` *j8414416n 100r10 1993 OctfnhRetinal hemodynamics using scanning laser ophthalmoscopy and hemorheology in chronic open-angle glaucoma 1561-6hbPURPOSE: Recent studies suggest that elevated intraocular pressure is not the only causative factor for the development of visual field loss and optic nerve damage in glaucomatous eyes. The authors determine whether retinal hemodynamics or blood fluidity are alternated in eyes of patients with open-angle glaucoma compared with those of age- and sex-matched healthy subjects. METHOD: High-quality video fluorescein angiograms were obtained from single eyes of 51 patients with chronic open-angle glaucoma. From these angiograms, the arm-retina time, mean dye velocity, and arteriovenous passage time were quantified. The data from patients were compared with those of an age- and sex-matched group of healthy subjects. RESULTS: In patients with chronic open-angle glaucoma, an 11% reduction of the mean dye velocity (P < 0.05) and a 41% prolongation of the arteriovenous passage time (P < 0.01) was observed relative to the values obtained among the control subjects. Among hematocrit values, plasma viscosity, and erythrocyte aggregation, only plasma viscosity showed a significant increase (4%; P < 0.01) in patients with chronic open-angle glaucoma. CONCLUSION: These results indicate that a pronounced circulatory deficit exists within the retinal vasculature of glaucomatous eyes, which may coexist with, but cannot be fully attributed to, an increase in plasma viscosity.'lfAugenklinik der Medizinische Fakultat, Rheinisch-Westfalischen Technischen Hochschule Aachen, Germany.JDWolf, S. Arend, O. Sponsel, W. E. Schulte, K. Cantor, L. B. Reim, M.(!0161-6420 (Print) Journal Articlec Ophthalmology 0*Adult Aged Aged, 80 and over Chronic Disease Female Fluorescein Angiography Fundus Oculi Glaucoma, Open-Angle/*physiopathology/therapy Hemodynamic Processes *Hemorheology Humans Lasers/diagnostic use Male Middle Aged *Ophthalmoscopy Research Support, Non-U.S. Gov't Retinal Vessels/*physiopathologyjdhttp://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=84144167496338r4n5M 1995 SepsHARetinal hemodynamics in patients with chronic open-angle glaucoma- 279-82Recently it has been demonstrated that retinal hemodynamics are disturbed in patients with chronic open-angle glaucoma. As the underlying cause a reduction in perfusion pressure due to increased intraocular pressure (IOP) and deficiencies of retinal autoregulation has been discussed. The present study was undertaken to clarify the influence of filtering surgery on retinal hemodynamics in patients with chronic open-angle glaucoma. A total of 17 patients with chronic open-angle glaucoma aged between 37 and 86 years were included in this prospective study. All patients underwent digital fluorescein angiography before and 10 days after fistulating procedures. From the angiograms the arteriovenous passage time (AVP) and arterial mean dye-bolus velocity (MDV) were quantified by means of digital picture analysis. At baseline the AVP was significantly prolonged in the patients as compared with reference values (AVP, 2.5 +/- 0.8 versus 1.6 +/- 0.4 s; P < 0.01). After the fistulating procedure (IOP: before, 29 +/- 5 mmHg; after, 16 +/- 4 mmHg) the AVP was significantly reduced as compared with baseline values (AVP, 2.5 +/- 0.8 versus 2.0 +/- 0.4 s; P < 0.05), whereas the MDV showed only a slight increase (MDV, 5.70 +/- 0.89 versus 5.99 +/- 0.92 mm/s; P > 0.05). This study confirms a disturbance of retinal hemodynamics in patients with chronic open-angle glaucoma. The significant reduction in AVP observed after lowering of the IOP by fistulating procedures demonstrates the positive influence of IOP reduction on the retinal circulation. The improvement in retinal circulation may prevent the occurrence of further glaucomatous damage after fistulating procedures.a',%Augenklinik der RWTH Aachen, Germany.oB;Wolf, S. Arend, O. Haase, A. Schulte, K. Remky, A. Reim, M.i(!0941-2921 (Print) Journal ArticlerGer J OphthalmolAdult Aged Aged, 80 and over Chronic Disease Female Fluorescein Angiography Glaucoma, Open-Angle/*physiopathology *Hemodynamic Processes Humans Intraocular Pressure Male Middle Aged Research Support, Non-U.S. Gov't Retinal Vessels/*physiologyjdhttp://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=74963381 8537023 2338 1995 Augb\Endothelin-1 plasma levels in normal-tension glaucoma: abnormal response to postural changes 484-8|BACKGROUND: Endothelin-1 (ET-1) is a potent vasoconstrictor 12782846123O 2003 Jun yOptic disc morphometry correlated with confocal laser scanning Doppler flowmetry measurements in normal-pressure glaucoma  260-5tPURPOSE: To examine the relationship between morphologic optic disc parameters and hemodynamic parameters as measured by confocal laser scanning Doppler flowmetry in patients with normal-pressure glaucoma. METHODS: The study included 91 eyes of 54 patients with normal-pressure glaucoma (mean age: 57.7 +/- 9.8 years), and 136 eyes of 77 age-adjusted normal controls. Color stereo optic disc photographs were morphometrically examined, and confocal laser scanning flowmetry (Heidelberg Retinal Flowmeter) in the neuroretinal rim inside of the optic disc, and in the retina close to the temporal and nasal border of the optic nerve head was performed. RESULTS: Mean confocal laser scanning flowmetric measurements in the neuroretinal rim, temporal parapapillary retina, and nasal parapapillary retina were significantly (P<0.03) lower in the normal-pressure glaucoma group than in the age-adjusted control group. Correspondingly, mean confocal laser scanning flowmetric measurements within the neuroretinal rim decreased significantly, with relatively low correlation coefficients, decreasing neuroretinal rim area (P = 0.016; correlation coefficient r2 = 0.026), and increasing mean visual field defect (P = 0.011; r2 = 0.029). Measurements were statistically independent of alpha zone (P = 0.38; r2 = 0.004) and beta zone (P = 0.57; r2 = 0.002) of parapapillary atrophy. CONCLUSIONS: Confocal laser scanning flowmetric measurements within the neuroretinal rim were lower in eyes with normal-pressure glaucoma than in age-matched normal eyes. Confocal laser scanning flowmetric measurements decrease with increasing glaucomatous optic nerve damage. There is, however, a marked variability preventing a clear relationship between stage of glaucoma and decrease in confocal laser scanning flowmetric measurements. The correlation between parapapillary atrophy and confocal laser scanning flowmetric measurements is not statistically significant in normal-pressure glaucoma.'Department of Ophthalmology, Friedrich-Alexander University Erlangen-Nurnberg, Erlangen, Germany. Jost.Jonas@augen.ma.uni-heidelberg.de`YJonas, J. B. Harazny, J. Budde, W. M. Mardin, C. Y. Papastathopoulos, K. I. Michelson, G.(!1057-0829 (Print) Journal Article J GlaucomaAged Case-Control Studies Female Glaucoma/*pathology/*physiopathology Hemodynamic Processes Humans *Intraocular Pressure *Laser-Doppler Flowmetry Male Middle Aged Optic Disk/*pathology Research Support, Non-U.S. Gov't Retinal Vessels/physiopathology Visual Fieldslehttp://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=12782846ower in the nasal than the temporal circulation by 52.49% (p < 0.001). This is a consequence of both significantly smaller vessels (20.4%, p < 0.001) and slower blood velocity in the nasal circulation (24.64%, p = 0.003) compared with the temporal vessels. After breathing 60% oxygen for 10 minutes, there was significant vasoconstriction (temporal, 10.42 +/- 1.24%, p < 0.001; nasal, 7.66 +/- 1.48%, p < 0.001), slower red cell velocity (temporal, 27.10 +/- 3.92%, p < 0.001; nasal, 27.36 +/- 5.51%, p < 0.001) and a significant reduction in the volumetric flow rate (temporal, 41.16 +/- 3.64%, p < 0.001; nasal, 37.99 +/- 5.07%, p < 0.001). The reduction in the haemodynamic parameters was comparable in the temporal and nasal circulations, indicating similar autoregulatory capacity. Retinal vascular conductance was calculated from volume flow and retinal perfusion pressure. It was 53% larger in the temporal than the nasal circulations. This provides an index of the metabolic needs of the different regions of the retina.'LFDiabetic Retinopathy Unit, R.P.M.S., Hammersmith Hospital, London, UK.81Rassam, S. M. Patel, V. Chen, H. C. Kohner, E. M.(!0950-222X (Print) Journal Article EyeAdult Carbon Dioxide/blood Hemodynamic Processes/physiology *Homeostasis Humans Laser-Doppler Flowmetry Middle Aged Oxygen/blood Partial Pressure Regional Blood Flow Retinal Vessels/anatomy & histology/*physiologyjdhttp://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=8796158    & . 6=Y?SQ     & } +]f v m 7  9 z CXh > p W|: 3C8 glz  1 s O\{v- TM    7   ;b9R(p6 d7556490H613 1995 SepZTThe 1994 Von Sallman Lecture. The optic nerve head circulation in health and disease 259-72VOThis is a brief overview of multifaceted anatomical, experimental and clinical studies conducted by the author since 1955 on the optic nerve head circulation in health and disease. Conclusions, based on the accumulated information provided by these studies, are summarized. The studies on the pattern of blood supply of the optic nerve head have shown that: (a) its main source of blood supply is the posterior ciliary artery circulation, with retinal circulation supplying only the surface nerve fiber layer, (b) there is marked interindividual variation in the blood supply pattern, and (c) the blood supply in the optic nerve head has a sectorial distribution. The various factors which produce interindividual variation in the blood supply of the optic nerve head are discussed, particularly those in the posterior ciliary artery circulation; this is because all available evidence indicates that it is derangement in the posterior ciliary circulation in the optic nerve head that is primarily responsible for the common ischemic disorders of the optic nerve head, e.g. anterior ischemic optic neuropathy and glaucomatous optic neuropathy. Factors that may derange the blood flow in the optic nerve head include defective autoregulation of blood flow in it, vascular changes in its feeding arteries, hematologic abnormalities, systemic arterial hypertension and hypotension, and intraocular pressure; their roles are discussed. For better understanding and management of optic nerve head ischemic disorders, there is an urgent need for an accurate clinical method of assessment of blood flow in the posterior ciliary circulation in optic nerve head, since no satisfactory method is currently available. Redness or pallor of the optic disk on ophthalmoscopy is not a true guide to the optic nerve head vascularity as it gives no information about the state of the posterior ciliary circulation. Fluorescein fundus angiography, though far superior to the optic disk color for evaluation of optic nerve head vascularity, has a number of limitations. All these topics and various controversies about them are discussed briefly.'RKDepartment of Ophthalmology, University of Iowa, Iowa City 52242-1091, USA. Hayreh, S. S..(0014-4835 (Print) Journal Article Review Exp Eye Resd]Animals Arteries/anatomy & histology Ciliary Body/blood supply Homeostasis Humans Hypertension/complications Hypotension/complications Intraocular Pressure/physiology Ischemia/etiology Optic Disk/*blood supply Optic Nerve Diseases/etiology Regional Blood Flow Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S. Vascular Resistancejdhttp://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=75564901008427681n 1999 Feb}ZTMorphologic changes in chronic high-pressure experimental glaucoma in rhesus monkeys 56-71s | vPURPOSE: To investigate morphologic changes in the posterior segment of the eye and optic nerve head (ONH) in rhesus monkeys with experimental glaucoma, and to evaluate the effect of age and vascular disease on the glaucomatous damage. METHODS: This study was conducted in 36 eyes of rhesus monkeys 11 to 24 years of age. Experimental glaucoma was produced by laser photocoagulation of the anterior chamber angle in 28 eyes, and the remaining 8 eyes served as the nonglaucomatous group. Of the 28 glaucomatous eyes, 19 belonged to animals with experimental atherosclerosis and chronic arterial hypertension (A-H group); the remaining 9 had no A-H (non-AH group). Among the 8 eyes without glaucoma, 5 belonged to A-H animals and the remaining 3 to animals without A-H. All eyes underwent IOP measurements and fundus photography before laser photocoagulation and serially thereafter for 4 to 60 months (median 22.5 months). After enucleation, eyes were fixed in formalin for light microscopic studies. Morphologic abnormalities were evaluated and graded. Correlation analyses between morphologic parameters and clinical data were performed. RESULTS: The highest IOP ranged from 44 to 80 mmHg, but during the follow-up period median IOP was mostly 28 mmHg (mean 27+/-4.8 mmHg). On histopathologic examination, the eyes showed moderate to severe atrophy of the temporal peripapillary choroid (67%), choriocapillaris (70%), and RPE (12%); axonal atrophy in the retinal nerve fiber layer (85%), prelaminar region (69%), lamina cribrosa (66%), and retrolaminar region (82%); fibrous septal thickening in the lamina cribrosa (77%) and retrolaminar region (86%); bowing backward of the lamina cribrosa (77%); overall tissue atrophy in the prelaminar region (81%); and retinal ganglion cell atrophy (74%). The data showed a positive correlation between the ONH damage and atrophic changes in the temporal peripapillary choroid, and suggested greater damage in animals with A-H than in those without A-H. CONCLUSION: Vascular disease may influence glaucomatous damage in the ONH, as damage in the ONH was greater in animals with A-H than in those without A-H. A similar relationship also may exist between age and glaucomatous damage, but this needs to be investigated further in a larger study. It is postulated that the bowing back of the lamina cribrosa seen in optic disc cupping is produced by retrolaminar septal fibrosis and axonal loss. Although elevated IOP no doubt played an important role, the data suggest that the glaucomatous changes that were observed in this study are not simply mechanical in nature (due to the raised IOP), but may represent a multifactorial phenomenon.'piDepartment of Ophthalmology and Visual Sciences, College of Medicine, University of Iowa, Iowa City, USA..(Hayreh, S. S. Pe'er, J. Zimmerman, M. B.(!1057-0829 (Print) Journal Article J GlaucomaAging/pathology Animals Axons/pathology Choroid/pathology Chronic Disease Comparative Study Disease Models, Animal Disease Progression Follow-Up Studies Glaucoma/complications/*pathology/physiopathology *Intraocular Pressure Macaca mulatta Neuroglia/pathology Optic Nerve/pathology Optic Nerve Diseases/etiology/pathology Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S. Retinal Ganglion Cells/pathologylehttp://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=1008427611470451205i 2001 Sep}ZTThe blood supply of the optic nerve head and the evaluation of it - myth and reality 563-93Evidence has gradually emerged that there is vascular insufficiency in the optic nerve head (ONH) in both anterior ischemic optic neuropathy (AION) and glaucomatous optic neuropathy (GON); thus both represent ischemic disorders of the ONH. Together these diseases constitute a major cause of blindness or seriously impaired vision in man. Consequently there has recently been great interest in the ONH circulation in health and disease and in how to evaluate it. Many studies of the subject have been published, with conflicting interpretations and claims. The basis of the inconsistent information seems to be confusion on some fundamental issues concerning the ONH circulation itself. The objective of this paper is to differentiate myths and misconceptions from reality about the ONH blood supply; to elucidate the reasons for disagreement on the blood supply of the ONH; and to evaluate the reliability and validity of various methods currently used to measure ONH blood flow.'Department of Ophthalmology and Visual Sciences, University of Iowa College of Medicine, Iowa City, IA 52242-1091, USA. sohan-hayreh@uiowa.edu Hayreh, S. S..(1350-9462 (Print) Journal Article ReviewProg Retin Eye ResBlood Flow Velocity Ciliary Arteries/physiology Fluorescein Angiography Glaucoma/physiopathology Humans Optic Disk/*blood supply Optic Neuropathy, Ischemic/physiopathology Research Support, Non-U.S. Gov't Retinal Artery/physiology Retinal Vein/physiologylehttp://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=11470451a10090444221; 1998Ambulatory blood pressure monitoring in glaucoma patients. The nocturnal systolic dip and its relationship with disease progression 19-25@:PURPOSE: This study was designed to uncover a new sensitive and specific factor for predicting the progression of glaucoma. ME15477464 12210 2004 Oct^XChronic ischemia induces regional axonal damage in experimental primate optic neuropathy1517-25~OBJECTIVES: To evaluate the effects of chronic optic nerve ischemia in a nonhuman primate model and to evaluate the regional variability of axonal loss. METHODS: Unilateral ischemic optic neuropathy was induced by administration of endothelin-1 to the retrobulbar space via osmotic pumps in 12 primates for 6 to 12 months. The transversely cut sections were stained and divided into 16 regions. Average axonal density in each region was quantified and compared with the untreated contralateral control eyes. RESULTS: Mean axonal density was 208 310/mm(2) and 220 661/mm(2) in treated and control eyes, respectively (P = .03, 1-tailed paired t test), for the entire group. Two-way analysis of variance showed a significant effect of endothelin-1 on overall axonal density for the experimental group (P<.001). Among the nerves with significant axonal loss, the mean axonal loss was 11.6% (4%-21%). Regional mapping of the damage showed the axonal loss varied in the damaged nerves; the damaged regions often clustered within specific quadrants. CONCLUSION: Chronic ischemia induced by local administration of endothelin-1 causes significant loss of optic nerve axons with varying regional susceptibility.Clinical Relevance Localized damage occurs in other types of optic neuropathy, such as glaucoma, and may result from regional differences in anatomy, metabolism, or vasculature of the primate optic nerve.'jdDiscoveries in Sight, Devers Eye Institute, Portland, OR 97210, USA. gacioffi@discoveriesinsight.orgVOCioffi, G. A. Wang, L. Fortune, B. Cull, G. Dong, J. Bui, B. Van Buskirk, E. M. (!0003-9950 (Print) Journal ArticletArch Ophthalmole,%Animals Axons/*pathology Cell Count Chronic Disease Disease Models, Animal Endothelin-1/pharmacology Female Intraocular Pressure Macaca mulatta Optic Nerve/*pathology Optic Neuropathy, Ischemic/chemically induced/*pathology Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S.ulehttp://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=15477464E9924361n827i 1998 JulhjcPulsatile ocular blood flow investigation in asymmetric normal tension glaucoma and normal subjectso 731-6F@AIMS: This study was designed to investigate pulsatile ocular blood flow (POBF) in normal tension glaucoma (NTG) patients an12150988214\ 2002 Jul\2+The impact of ocular blood flow in glaucomar 359-93ngTwo principal theories for the pathogenesis of glaucomatous optic neuropathy (GON) have been described--a mechanical and a vascular theory. Both have been defended by various research groups over the past 150 years. According to the mechanical theory, increased intraocular pressure (IOP) causes stretching of the laminar beams and damage to retinal ganglion cell axons. The vascular theory of glaucoma considers GON as a consequence of insufficient blood supply due to either increased IOP or other risk factors reducing ocular blood flow (OBF). A number of conditions such as congenital glaucoma, angle-closure glaucoma or secondary glaucomas clearly show that increased IOP is sufficient to lead to GON. However, a number of observations such as the existence of normal-tension glaucoma cannot be satisfactorily explained by a pressure theory alone. Indeed, the vast majority of published studies dealing with blood flow report a reduced ocular perfusion in glaucoma patients compared with normal subjects. The fact that the reduction of OBF often precedes the damage and blood flow can also be reduced in other parts of the body of glaucoma patients, indicate that the hemodynamic alterations may at least partially be primary. The major cause of this reduction is not atherosclerosis, but rather a vascular dysregulation, leading to both low perfusion pressure and insufficient autoregulation. This in turn may lead to unstable ocular perfusion and thereby to ischemia and reperfusion damage. This review discusses the potential role of OBF in glaucoma and how a disturbance of OBF could increase the optic nerve's sensitivity to IOP.'F@University Eye Clinic, Basel, Switzerland. josef.flammer@uhbs.chrlFlammer, J. Orgul, S. Costa, V. P. Orzalesi, N. Krieglstein, G. K. Serra, L. M. Renard, J. P. Stefansson, E..(1350-9462 (Print) Journal Article ReviewProg Retin Eye ResEye/*blood supply Glaucoma/etiology/*physiopathology Humans Intraocular Pressure Regional Blood Flow Vascular Diseases/complicationslehttp://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=12150988p) Journal Articlei OphthalmologycngAdult Aged Aged, 80 and over *Blood Pressure Cross-Sectional Studies Female Glaucoma, Open-Angle/*epidemiology/etiology Humans *Intraocular Pressure Italy/epidemiology Male Middle Aged Ocular Hypertension/epidemiology/etiology Odds Ratio Optic Disk/blood supply Perimetry Prevalence Risk Factors Tonometry, Ocular Vascular Diseases/complications/*epidemiologymlehttp://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=10889099wology, Duke University Eye Center, Durham, North Carolina..(Mao, L. K. Stewart, W. C. Shields, M. B.(!0002-9394 (Print) Journal ArticlepAm J OphthalmolcAdult Aged Aged, 80 and over Female Follow-Up Studies Glaucoma, Open-Angle/*physiopathology/surgery Humans *Intraocular Pressure/drug effects Male Middle Aged Optic Disk/*physiopathology Tonometry, Ocular Trabeculectomy Visual Fieldsejdhttp://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=1985490\v.Ll10755098 14 ( Pt 1) 2000 FebiA comparison between laser interferometric measurement of fundus pulsation and pneumotonometric measurement of pulsatile ocular blood flow. 1. Baseline considerations 39-45e^XPURPOSE: Several methods have been proposed for the investigation of the human choroidal circulation. The aim of the present study was to compare laser interferometric measurements of cardiac synchronous fundus pulsations with pneumotonometric measurements of intraocular pressure pulse and pulsatile ocular blood flow in humans. METHODS: The association between fundus pulsation amplitude as assessed with laser interferometry and pulse amplitude (PA) and pulsatile ocular blood flow (POBF) as assessed with pneumotonometry was investigated in 28 healthy subjects. Additionally, we investigated the distribution of fundus pulsation amplitude (FPA) in a region of -15 degrees to +15 degrees around the macula (n = 18) and the influence of accommodation paralysis with cyclopentolate on FPA (n = 10). RESULTS: There was a high association between FPA and PA (r = 0.86, p < 0.001) and FPA and POBF (r = 0.70, p < 0.001). Fundus pulsations in the macula were significantly smaller than in the optic disc, but significantly larger than those in peripheral regions of the retina. Administration of cyclopentolate did not influence FPA. CONCLUSIONS: On the basis of the strong correlation between laser interferometric measurements of FPA and pneumotonometric measurements of PA and POBF, we conclude that the FPA is a valid index of pulsatile choroidal perfusion in humans.'jdDepartment of Clinical Pharmacology, University of Vienna, Austria. Leopold.Schmetterer@univie.ac.atF@Schmetterer, L. Dallinger, S. Findl, O. Eichler, H. G. Wolzt, M.(!0950-222X (Print) Journal Articleu Eye Adult Choroid/blood supply Comparative Study Eye/*blood supply Female Fundus Oculi Humans Lasers/*diagnostic use Male Pulsatile Flow Regional Blood Flow Retinal Vessels/physiology Tonometry, Ocular/*methodslehttp://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=10755098A11587919206. 2001 Nov1>8Role of nitric oxide in the control of ocular blood flow 823-47 In the recent years it has been recognized that nitric oxide is an important regulator of ocular blood flow. Nitric oxide is involved in the control of basal blood flow in the choroid, optic nerve and the retina. In addition, nitric oxide mediates a number of vasodilator responses in ocular vessels to agonists such as acetylcholine, bradykinin, histamine, substance P and insulin. Nitric oxide also plays a role in hypercapnia-induced vasodilation in the choroid and is a modulator of pressure autoregulation in this vascular bed. Abnormalities of the L-arginine/nitric oxide system have been observed in a variety of ocular diseases including glaucoma, diabetic retinopathy and retinopathy of prematurity. This makes the L-arginine/nitric oxide pathway an attractive target for therapeutic interventions. Additional research is required, particularly in characterizing the role of the three nitric oxide synthase isoforms in the control of ocular perfusion, to implement this concept into the clinical management of ocular diseases.'Department of Clinical Pharmacology, Vienna General Hospital, University of Vienna, Wahringer Gurtel 18-20, 1090, Vienna, Austria. leopold.schmetterer@univie.ac.at Schmetterer, L. Polak, K..(1350-9462 (Print) Journal Article ReviewProg Retin Eye Res"Animals Blood Flow Velocity Diabetic Retinopathy/physiopathology Endothelium, Vascular/physiology Eye/*blood supply Glaucoma, Open-Angle/physiopathology Humans Nitric Oxide/*physiology Regional Blood Flow/physiology Reperfusion Injury/physiopathology Research Support, Non-U.S. Gov't lehttp://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=11587919 8646172g5J1H 1996 JanC@:Retinal hemodynamics during increased intraocular pressure 1-5RThe pathogenesis of primary chronic open-angle glaucoma (POAG) remains uncertain. It has been proposed that some of these patients may present with a deficiency in retinal hemodynamic autoregulation. It is also thought that visual field loss in POAG could be related to poor retinal perfusion. The present study was undertaken to evaluate the capacity of retinal autoregulation to maintain constant retinal circulation despite an acute rise in intraocular pressure (IOP). A total of 22 healthy subjects were recruited to this study. Retinal hemodynamics were assessed by digital video fluorescein angiograms using a scanning laser ophthalmoscope at normal (13.8 +/- 1.5 mmHg) and increased IOP (33.8 +/- 3.4 mmHg). Suction cups were used for raising the IOPs. The angiograms were performed at baseline and after 1 min of increased IOP. To quantify retinal hemodynamics the arm-retina time (ART) and arteriovenous passage time (AVP) were evaluated. The ART increased significantly from 9.4 +/- 1.8 to 11.8 +/- 2.2 s (P < 0.05) during elevated IOP, and the AVP was significantly prolonged from 1.6 +/- 0.4 to 3.0 +/- 0.8 s (P < 0.01) with IOP elevation as well. The increase in ART and AVP indicates an insufficiency of retinal autoregulation after an acute rise in IOP, even in healthy subjects. It appears that IOP values of > or = 30 mmHg may be detrimental to retinal perfusion in normals as well as in patients with POAG, who may have compromised retinal perfusion to begin with.'F@Augenklinik der Medizinischen Fakultat der RWTH Aachen, Germany.BPeripheral endothelial dysfunction in normal pressure glaucoma 1710-4PURPOSE: To assess vascular endothelial function in patients with normal pressure glaucoma using forearm blood flow responses to intra-arterial infusions of endothelial-dependent and -independent vasoactive agents. METHODS: Eight patients with newly diagnosed and untreated normal pressure glaucoma and eight healthy age- and sex-matched control volunteers underwent measurement of forearm blood flow using venous occlusion plethysmography. Blood flow was assessed in response to incremental doses of sodium nitroprusside (an endothelial-independent vasodilator), acetylcholine (an endothelial-dependent vasodilator) and the vasoconstrictor N(G)-monomethyl-L-arginine (an inhibitor of nitric oxide synthase). RESULTS: Sodium nitroprusside caused a dose-related increase in forearm blood flow in patients and controls. Glaucoma patients appeared to have an increased vasodilatory response, but this was not significant (P = 0.23). Acetylcholine also induced vasodilatation in both groups, but the response was significantly reduced in the glaucoma group (P = 0.04). N(G)-monomethyl-L-arginine induced a similar degree of vasoconstriction in both groups (P = 0.76). CONCLUSIONS: This study has shown an impairment of peripheral endothelium-mediated vasodilatation in normal pressure glaucoma. These findings would support the concept of a generalized vascular endothelial dysfunction in patients with this condition.'2+Princess Alexandra Eye Pavilion, Edinburgh.i4.Henry, E. Newby, D. E. Webb, D. J. O'Brien, C.(!0146-0404 (Print) Journal Articleu Invest Ophthalmol Vis ScizJCAcetylcholine/administration & dosage Blood Flow Velocity/drug effects Brachial Artery/*physiopathology Dose-Response Relationship, Drug Endothelium, Vascular/*physiopathology Enzyme Inhibitors/administration & dosage Female Forearm/blood supply Glaucoma, Open-Angle/*physiopathology Humans Infusions, Intra-Arterial *Intraocular Pressure Male Middle Aged Nitric Oxide Synthase/antagonists & inhibitors Nitroprusside/administration & dosage Plethysmography Research Support, Non-U.S. Gov't Vasodilator Agents/administration & dosage omega-N-Methylarginine/administration & dosage lehttp://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=10393040d11274064425 2001 Apr`YLack of blood-brain barrier properties in microvessels of the prelaminar optic nerve head895-901ngPURPOSE: To define the blood-brain barrier (BBB) characteristics of microvessels in the optic nerve head (ONH). METHODS: Immunohistochemical staining of different regions of the ONH, retro-laminar optic nerve, and retina of human and monkey eyes was carried out, using antibodies against BBB markers (glucose transporter 1, transferrin receptor, and P-glycoprotein), the non-BBB marker PAL-E, and against plasma proteins fibrinogen and IgG, which serve as endogenous markers of nonspecific microvascular permeability. In the ONH of monkey eyes, the number of transport-related endothelial pinocytotic vesicles and their cellular distribution within the microvessels were determined by electron microscopy. RESULTS: In both human and monkey eyes, only microvessels in the prelaminar region of the ONH were positive for the PAL-E antigen. The prelaminar region microvessels showed either no or weak expression of the transferrin receptor and P-glycoprotein but stained positive for glucose transporter 1. In human ONH, fibrinogen and IgG were present around microvessels in the prelaminar region but not in other parts of the optic nerve or retina. By electron microscopy, endothelial cells of prelaminar region microvessels contained a higher number of pinocytotic vesicles, located at the luminal and abluminal side of the endothelial cell membrane, in contrast to a mainly abluminal localization in microvessels of the retina and other parts of the optic nerve. CONCLUSIONS: Microvessels in the prelaminar region of the ONH lack classical BBB characteristics and display nonspecific permeability, possibly mediated by vesicular transport.'f_Department of Ophthalmology, Academic Medical Center, University of Amsterdam, The Netherlands.LFHofman, P. Hoyng, P. vanderWerf, F. Vrensen, G. F. Schlingemann, R. O.(!0146-0404 (Print) Journal Article Invest Ophthalmol Vis Sci,%Animals Antibodies, Monoclonal Antigens, Surface/analysis Biological Markers/analysis Blood Proteins/analysis *Blood-Brain Barrier Capillaries/chemistry/*cytology *Capillary Permeability Comparative Study Endothelium, Vascular/chemistry Fluorescent Antibody Technique, Indirect Glucose Transporter Type 1 Humans Immunoenzyme Techniques Macaca mulatta Membrane Glycoproteins/analysis Monosaccharide Transport Proteins/analysis Optic Disk/*blood supply/chemistry P-Glycoprotein/analysis Receptors, Transferrin/analysis Research Support, Non-U.S. Gov'tlehttp://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=112740645954089.5010 1966 Oct TNIntra-ocular pressure, glaucoma, and glaucoma suspects in a defined population 570-86"Hollows, F. C. Graham, P. A.(!0007-1161 (Print) Journal ArticletBr J Ophthalmol XQAdult Aged Female Glaucoma/*diagnosis/*epidemiology Humans Male Middle Aged Wales jdhttp://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=595408915291936824n 2004 Aug Comparison of colour Doppler imaging and retinal scanning laser fluorescein angiography in healthy volunteers and normal pressure glaucoma patients 426-31PURPOSE: To correlate retinal circulatory measurements using scanning laser fluorescein angiography and flow velocities of retrobulbar vessels measured by means of colour Doppler imaging. METHODS: Fifteen patients with normal pressure glaucoma (NPG) and 15 healthy volunteers underwent colour Doppler imaging and fluorescein angiographic studies. Peak systolic velocities (PSVs), end-diastolic velocities (EDVs) and resistive indices (RIs) of the ophthalmic artery (OA) and central retinal artery were obtained. In the fluorescein angiograms arteriovenous passage time (AVP) was quantified by means of digital dye dilution curve analysis. RESULTS: Arteriovenous passage time was significantly prolonged in NPG patients compared to healthy subjects (p = 0.0026). In the central retinal artery PSV (p = 0.023) and EDV (p < 0.0001) were significantly decreased and RI was increased (p < 0.0001) in patients with NPG. The EDV of the central retinal artery showed a significant correlation with AVP (EDV: r = - 0.53, p = 0.0023). The RI of the central retinal artery correlated significantly to AVP (RI: r = 0.63, p < 0.0001). The AVP did not correlate to EDV or PSV, nor to the RI measured in the ophthalmic artery. CONCLUSION: Arteriovenous passage time, which represents blood flow in a vascular segment of artery, capillary bed and corresponding vein, was found to be correlated to the EDV and the RI of the central retinal artery. The combination of different techniques allows further interpretation of ocular circulatory responses.o'~wDepartment of Ophthalmology, University Hospital, Medical Faculty, Aachen University, Aachen, Germany. kkahuber@aol.coml.(Huber, K. Plange, N. Remky, A. Arend, O.(!1395-3907 (Print) Journal ArticlesActa Ophthalmol Scand 0*Adult Blood Flow Velocity Comparative Study Female Fluorescein Angiography/*methods Glaucoma, Open-Angle/*physiopathology Humans Laser-Doppler Flowmetry/*methods Male Middle Aged Ophthalmic Artery/*physiopathology Prospective Studies Regional Blood Flow Retinal Artery/*physiopathology Time Factorslehttp://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=15291936i 154520614510 2004 OctAbnormal systemic and ocular vascular response to temperature provocation in primary open-angle glaucoma patients: a case for autonomic failure?3546-54`ZPURPOSE: To assess systemic and ocular vascular reactivity in response to warm and cold provocation in untreated patients with primary open-angle glaucoma and normal control subjects. METHODS: Twenty-four patients with primary open-angle glaucoma and 22 normal control subjects were subjected to a modified cold pressor test involving immersion of the right hand in 40 degrees C warm water followed by 4 degrees C cold water exposure, and finger and ocular blood flow were assessed by means of peripheral laser Doppler flowmetry and retinal flowmetry, respectively. Finger and body temperature as well as intraocular pressure, systemic blood pressure, systemic pulse pressure, heart rate, and ocular perfusion pressure were also monitored. RESULTS: The patients with glaucoma demonstrated an increase in diastolic blood pressure (P = 0.023), heart rate (P = 0.010), and mean ocular perfusion pressure (P = 0.039) during immersion of the tested hand in 40 degrees C water. During cold provocation, the patients demonstrated a significant decrease in finger (P = 0.0003) and ocular blood flow (the parameter velocity measured at the temporal neuroretinal rim area; P = 0.021). Normal subjects did not demonstrate any blood flow or finger temperature changes during immersion of the tested hand in 40 degrees C water (P > 0.05); however, they exhibited increases in systolic blood pressure (P = 0.034) and pulse pressure (P = 0.0009) and a decrease in finger blood flow (P = 0.0001) during cold provocation. In normal subjects, the ocular blood flow was unchanged during high- and low-temperature challenge. CONCLUSIONS: Cold provocation elicits a different blood pressure, and ocular blood flow response in patients with primary open-angle glaucoma compared with control subjects. These findings suggest a systemic autonomic failure and ocular vascular dysregulation in POAG patients.'Neuroscience Research Institute, School of Life and Health Sciences, Aston University, Aston Triangle, Birmingham, United Kingdom.2+Gherghel, D. Hosking, S. L. Cunliffe, I. A.(!0146-0404 (Print) Journal Article Invest Ophthalmol Vis SciTNAged Autonomic Nervous System Diseases/*physiopathology Blood Flow Velocity Blood Pressure/*physiology Body Temperature *Cold Eye/*blood supply Female Fingers/blood supply Glaucoma, Open-Angle/*physiopathology Heart Rate/physiology *Heat Humans Intraocular Pressure/physiology Laser-Doppler Flowmetry Male Middle Aged Vasoconstrictionlehttp://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=154520617831043e 102n1 1995 Jan1JCAmbulatory blood pressure monitoring in glaucoma. The nocturnal dip& 61-9PURPOSE: Hypoperfusion of the optic nerve head may be among the significant factors relating to glaucoma damage. The physiologic nocturnal blood pressure "dip" may be exaggerated in some patients and may compromise local vascular supply. METHODS: Twenty-four-hour ambulatory blood pressure recording was performed on 38 patients with normal-tension glaucoma and on 46 with primary open-angle glaucoma. Eleven control subjects of similar age also were tested. The means of the systolic and diastolic blood pressures, mean arterial pressure, and pulse pressure for 24 hours, taken during the daytime (6 AM-10 PM) and night (10 PM-6 AM) periods were determined. The percentage nocturnal dip for each patient was calculated. A masked assessment of Humphrey visual fields for progression or stability was done on those 52 patients who had numerous fields plotted for more than 2 years. RESULTS: The results of the control subjects confirmed that the authors' technique produces values similar to cardiologic studies from large healthy populations. The mean results from all the authors' patients with glaucoma were within the ranges reported for control subjects in the literature. The blood pressure parameters of the normal-tension glaucoma and primary open-angle glaucoma groups did not differ significantly. All nocturnal pressure parameters (except pulse pressure) were lower in the 37 patients with progressive field defects compared with the 15 patients whose pressure parameters were stable, whereas the systolic, diastolic, and mean arterial pressure dips were significantly larger (systolic dip, P = 0.001). CONCLUSION: The nocturnal reduction in blood pressure may be an additional risk factor in patients with glaucoma.'VODepartment of Ophthalmology, University of British Columbia, Vancouver, Canada.NGGraham, S. L. Drance, S. M. Wijsman, K. Douglas, G. R. Mikelberg, F. S. (!0161-6420 (Print) Journal Article  Ophthalmologyo("Aged *Blood Pressure *Blood Pressure Monitoring, Ambulatory *Circadian Rhythm Comparative Study Female Glaucoma/*physiopathology Glaucoma, Open-Angle/physiopathology Humans Intraocular Pressure Male Middle Aged Research Support, Non-U.S. Gov't Vision Disorders/physiopathology Visual Fieldsjdhttp://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=7831043icance in POAG, as well as the association between NO(2)(-) and PP when glaucomas and controls were considered separately. CONCLUSIONS: The authors found alterations of NO markers in the plasma and aqueous humour of glaucoma patients. Primary or secondary impaired NO balance could alter ocular perfusion pressure.'Department of Oto-Neuro-Ophthalmological Sciences, University of Florence, Eye Unit II, Florence, Italy. fernando.galassi@unifi.itHAGalassi, F. Renieri, G. Sodi, A. Ucci, F. Vannozzi, L. Masini, E.n(!0007-1161 (Print) Journal ArticletBr J OphthalmolmLFAged Aqueous Humor/*chemistry Biological Markers/analysis/blood Case-Control Studies Chemotherapy, Cancer, Regional Perfusion Cyclic GMP/*analysis/blood Female Glaucoma, Open-Angle/blood/*metabolism Humans Intraocular Pressure Male Middle Aged Nitric Oxide/*metabolism Nitrites/*analysis/blood Research Support, Non-U.S. Gov'tlehttp://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=151482072jc } 12509808412. 2003 Jan 15zsEndothelin B receptors are expressed by astrocytes and regulate astrocyte hypertrophy in the normal and injured CNSe 180-90The ability of mammalian central nervous system (CNS) neurons to survive and/or regenerate following injury is influenced by surrounding glial cells. To identify the factors that control glial cell function following CNS injury, we have focused on the endothelin B receptor (ET(B)R), which we show is expressed by the majority of astrocytes that are immunoreactive for glial acid fibrillary protein (GFAP) in both the normal and crushed rabbit optic nerve. Optic nerve crush induces a marked increase in ET(B)R and GFAP immunoreactivity (IR) without inducing a significant increase in the number of GFAP-IR astrocytes, suggesting that the crush-induced astrogliosis is due primarily to astrocyte hypertrophy. To define the role that endothelins play in driving this astrogliosis, artificial cerebrospinal fluid (CSF), ET-1 (an ET(A)R and ET(B)R agonist), or Bosentan (a mixed ET(A)R and ET(B)R antagonist) were infused via osmotic minipumps into noninjured and crushed optic nerves for 14 days. Infusion of ET-1 induced a hypertrophy of ET(B)R/GFAP-IR astrocytes in the normal optic nerve, with no additional hypertrophy in the crushed nerve, whereas infusion of Bosentan induced a significant decrease in the hypertrophy of ET(B)R/GFAP-IR astrocytes in the crushed but not in the normal optic nerve. These data suggest that pharmacological blockade of astrocyte ET(B)R receptors following CNS injury modulates glial scar formation and may provide a more permissive substrate for neuronal survival and regeneration. 'lfMolecular Neurobiology Laboratory, Veterans Affairs Medical Center, Minneapolis, Minnesota 55455, USA.\URogers, S. D. Peters, C. M. Pomonis, J. D. Hagiwara, H. Ghilardi, J. R. Mantyh, P. W.f(!0894-1491 (Print) Journal Articlev GliapiAnimals Astrocytes/cytology/drug effects/*metabolism Brain Injuries/drug therapy/*metabolism/physiopathology Disease Models, Animal Hypertrophy/drug therapy/*metabolism/physiopathology Immunohistochemistry Male Nerve Regeneration/drug effects/*physiology Optic Nerve/cytology/drug effects/*metabolism Optic Nerve Injuries/drug therapy/*metabolism/physiopathology Rabbits Receptor, Endothelin B Receptors, Endothelin/agonists/antagonists & inhibitors/*metabolism Recovery of Function/drug effects/physiology Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, Non-P.H.S. Research Support, U.S. Gov't, P.H.S.plehttp://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=12509808 117507492711 2001 NovxqComparison of visually evoked peak systolic and end diastolic blood flow velocity using a control system approach^1499-503Transcranial Doppler sonography measures blood flow velocity in basal cerebral vessels with high accuracy. For quantification, time averaged mean blood flow velocities are used most because the peak systolic and end diastolic blood flow velocities mark the velocity extremes of one heart cycle. It is known, from hemodynamic measurements of the neurovascular coupling mechanism, that the end diastolic velocity is more sensitive for change in hemodynamics than the peak systolic velocity. Thus, we used a recently introduced control system approach to compare both indices for their use in functional transcranial Doppler tests focusing on hemodynamics of blood flow velocity change. We enrolled 65 healthy young volunteers without a medical history of cardiovascular risk factors, and performed a visual stimulation test. Peak systolic and end diastolic maximal blood flow velocities were used after transformation to relative data for control-system analysis. Due to Doppler artefacts, 95% of peak systolic and 86% of end diastolic data sets were analyzed. Results showed statistically significant differences for resting blood flow velocity and the control system parameter gain, attenuation and rate time, whereas the parameters' natural frequency and time delay were equal. Increase in relative blood flow velocity in the posterior cerebral artery due to visual-cortical stimulation was higher in end diastolic values than peak systolic data. Using a complex visual stimulation paradigm, the higher sensitivity of the end diastolic index is of no practical use. Being less influenced by Doppler artefacts, the peak systolic velocity index is more feasible for control-system analysis of dynamic blood flow regulation.'jdDepartment of Neurology, Faculty of Medicine, Justus-Liebig University of Giessen, Giessen, Germany.82Rosengarten, B. Aldinger, C. Kaufmann, A. Kaps, M.:40301-5629 (Print) Evaluation Studies Journal ArticleUltrasound Med BiolpAdult *Blood Flow Velocity Comparative Study Diastole Humans Posterior Cerebral Artery/physiology/*ultrasonography Sensitivity and Specificity Systole Time Factors *Ultrasonography, Doppler, Transcranial Visual Cortex/physiologylehttp://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=11750749r16315043 2447 2006 JulDecreased blood flow at neuroretinal rim of optic nerve head corresponds with visual field deficit in eyes with normal tension glaucoma^795-801PURPOSE: To determine the relationship between the blood flow parameters of the optic disc rim and the glaucomatous visual field changes. DESIGN: Observational cross-sectional study. METHODS: Tissue blood flow in the neuroretinal rim within the optic disc was determined with the Heidelberg retina flowmeter(HRF) in 54 eyes of 54 patients with normal tension glaucoma (NTG). Patients were selected whose visual field defects were confined to either the superior or inferior hemifield. Blood flow measurements were made in a 10 degrees x2.5 degrees area of the superior and inferior neuroretinal rim within the optic disc. The mean blood flow (MBF) was calculated by the automatic full-field perfusion image analyzer program, and the ratio of the MBF in the superior to the inferior rim areas (the S/I ratio) was calculated from the same HRF image in order to minimize the variation of measurement condition. RESULTS: Inferior rim blood flow is less than superior rim blood flow in patients with superior hemifield defect, and superior rim blood flow is reduced compared to inferior in patients with inferior hemifield defect. The mean S/I ratios of the MBF in the patients with superior hemifield defect (1.46, n=37) was significantly higher than that in the patients with inferior hemifield defect (0.79, n=17; P<0.0001, Mann-Whitney U-test). CONCLUSIONS: The blood flow in the neuroretinal rim was found to correspond to the regional visual field defect in eyes with NTG. Reductions in flow were associated with reductions in function.'Department of Ophthalmology, Keio University School of Medicine, 35 Shinanomachi, Shinjuku-ku, Tokyo, 160-8582, Japan, kimura@sc.itc.keio.ac.jp.@9Sato, E. A. Ohtake, Y. Shinoda, K. Mashima, Y. Kimura, I.(!0721-832X (Print) Journal Article& Graefes Arch Clin Exp Ophthalmollehttp://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=16315043/no ~ l16682595 124p5o 2006 Mayn\UEndothelin B receptor in human glaucoma and experimentally induced optic nerve damage 717-24OBJECTIVE: To assess endothelin B receptor (ETbR) expression in human glaucomatous optic nerves and the spatial relationship between ETbR and astrocytes. METHODS: Twenty-six eyes from 16 glaucoma patients and 10 normal control subjects were immunohistochemically labeled with antibodies to ETbR. The immunoreactivity was quantified and compared between normal and glaucomatous eyes with an image analysis system. Tissues were also double-labeled for ETbR and astrocytes. In addition, the optic nerve of a monkey with regional degeneration induced by laser coagulation was examined with the same techniques. RESULTS: The frequency of positive ETbR immunoreactivity was higher in human glaucomatous optic nerves as compared with age-matched controls (9/16 vs 1/10, P = .02). The ETbR immunoreactivity colocalized with astrocytic processes and was quantitatively higher in the glaucomatous eyes (P = .02). In the monkey, the regions of degeneration showed increased ETbR associated with reactive astrocytes and was highest at the borders between normal areas and degeneration. CONCLUSION: Increased ETbR immunoreactivity in diseased optic nerves and its association with astrocytes suggest that the glia-endothelin system may be involved in the pathologic mechanisms of neuronal degeneration.Clinical Relevance The study supports the clinical observation of endothelin involvement in glaucoma and provides direct evidence that the endothelin system is associated with glaucomatous pathologic abnormalities.l'JDDiscoveries in Sight, Devers Eye Institute, Portland, OR 97210, USA.:4Wang, L. Fortune, B. Cull, G. Dong, J. Cioffi, G. A.(!0003-9950 (Print) Journal ArticledArch OphthalmoloAged Aged, 80 and over Animals Astrocytes/*metabolism/pathology Axotomy *Disease Models, Animal Female Glaucoma, Open-Angle/*metabolism/pathology Glial Fibrillary Acidic Protein/metabolism Humans Immunoenzyme Techniques Macaca mulatta Male Optic Nerve/*metabolism/pathology Optic Nerve Diseases/*metabolism/pathology Receptor, Endothelin B/*metabolism Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't Tissue Donorsllehttp://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=16682595 16123419469i 2005 Sep b[Structure-function relations of parasol cells in the normal and glaucomatous primate retina3197-207PURPOSE: The purpose of this study was to examine the effect that chronic elevation of intraocular pressure has on the intrinsic and visual response properties of parasol cells in the primate retina. METHODS: A primate model of experimental glaucoma was combined with intracellular recording and staining techniques using an isolated retina preparation. Intrinsic electrical properties were examined by injection of depolarizing and hyperpolarizing currents. Visual responses were studied using drifting and counterphased gratings. Morphologic comparisons were made by injecting recorded cells with Neurobiotin and analyzing them quantitatively with a computer-based neuron reconstruction system. RESULTS: Structurally, parasol cells from glaucomatous eyes had smaller somata and smaller, less complex dendritic arbors, resulting in a significant reduction in total dendrite length and surface area. Functionally, these neurons did not differ from normal in their mean resting membrane potentials, input resistances, or thresholds to electrical activation, but did differ in membrane time constants and spike duration. Parasol cells from both normal and glaucomatous eyes preferred low-spatial-frequency stimuli, but significantly fewer glaucoma-related cells were driven visually-in particular, by patterned stimuli. Glaucomatous cells also did not respond as well to visual stimuli presented at increased temporal frequencies. CONCLUSIONS: Ganglion cells in the glaucomatous eye retain most of their normal intrinsic electrical properties, but are less responsive, both spatially and temporally, to visual stimuli. The reduction in visual responsiveness most likely results from significant changes in dendritic architecture, which affects their level of innervation by more distal retinal neurons.'~Department of Physiology and the Neuroscience Program, Michigan State University, East Lansing, MI 28824, USA. weberar@msu.edu Weber, A. J. Harman, C. D.(!0146-0404 (Print) Journal Article  Invest Ophthalmol Vis ScidAnimals Biotin/analogs & derivatives Cell Count Dendrites/pathology Disease Models, Animal Female Glaucoma/*physiopathology Intraocular Pressure Macaca mulatta Male Membrane Potentials/physiology Microelectrodes Neurons/pathology Optic Nerve Diseases/*physiopathology Research Support, N.I.H., Extramural Research Support, U.S. Gov't, P.H.S. Retinal Ganglion Cells/*pathology/*physiologynlehttp://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=16123419s3632414m 105989 1987 AugoB;A case-control study of risk factors in open angle glaucoma 1066-71 In a case-control study using an exploratory health questionnaire, we examined the relationship between primary open angle glaucoma (POAG) and a variety of personal characteristics and potential toxic exposures in patients in a general eye service. There were 83 patients with definite POAG, 121 POAG suspects, and 237 controls. Using multiple logistic regression analysis for simultaneous evaluation of potential risk factors, we found that black race (rate ratio = 6.8; 95% confidence interval [CI] = 2.8 to 16.0) and untreated systolic hypertension (rate ratio = 5.8; 95% CI = 2.2 to 15) were the most important risk factors. Current cigarette smoking was also associated with glaucoma (rate ratio = 2.9; 95% CI = 1.3 to 6.6). Suggestive associations were found with family history of glaucoma, definite or borderline diabetes, and myopia. The effects of many of these personal characteristics and exposures as risk factors were also noted for the glaucoma suspect group, though not as strongly as for the definite glaucoma cases.NHWilson, M. R. Hertzmark, E. Walker, A. M. Childs-Shaw, K. Epstein, D. L.(!0003-9950 (Print) Journal ArticleArch OphthalmolAfrican Continental Ancestry Group Alcohol Drinking Diabetes Complications Glaucoma, Open-Angle/*etiology/genetics Humans Hypertension/complications Myopia/complications Research Support, U.S. Gov't, P.H.S. Risk SmokingFjdhttp://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=3632414 89023176f4{ 1996 AugnXQThe value of the isometric hand-grip test--studies in various autonomic disorders0 211-82zTime-related methodological differences have confounded the value of isometric hand-grip (IHG) exercise as a test of sympathetic function. This study examines the blood pressure response to IHG in 71 normal subjects and 76 dysautonomic patients and compares it with the tilt table test. All participants were supine and performed IHG at 30% of maximum contraction for 5 min. Change in diastolic blood pressure (DBP) was the most sensitive and specific measurement in diagnosing abnormals. The multivariate group by time (1-5 min) effect was significant (F = 10.14, p < 0.001) with 5 min as the most important time measurement (Wilk's lambda = 0.70, p < 0.001). The DPB rise for normals was 25.15 +/- 1.31 mmHg (mean +/- SE), range 22.55-27.76 mmHg, with a sensitivity of 78.95% and a specificity of 71.83%. A multivariate analysis of variance showed intraindividual reproducibility of nine normals over four trials (F = 0.950, p > 0.25). Gender and grip strength were additional important variables. In comparison, the tilt table test demonstrated a sensitivity of 82.76% and a specificity of 73.68%. Isometric hand-grip is therefore a specific, sensitive, reproducible, simple and non-invasive test of sympathetic function with relatively well-studied reflex pathways. Its sensitivity and specificity compare favourably with the tilt table test. It should be incorporated in routine autonomic testing.'\UAutonomic Reflex Laboratory, Union Memorial Hospital, Baltimore, Maryland 21218, USA.tKhurana, R. K. Setty, A.600959-9851 (Print) Clinical Trial Journal ArticleClin Auton Res|Adolescent Adult Aged Aged, 80 and over Aging/physiology Autonomic Nervous System Diseases/diagnosis/*physiopathology Blood Pressure/physiology Comparative Study Female Hand Strength/*physiology Humans Isometric Contraction/*physiology Male Middle Aged Posture Reproducibility of Results Sex Characteristics Sympathetic Nervous System/physiopathology *Tilt-Table Test Time Factorsjdhttp://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=8902317 880076957d 1977 JuliB7Kitazawa, Y. Horie, T. Aoki, S. Suzuki, M. Nishioka, K.(!0003-9950 (Print) Journal ArticleArch OphthalmolAdult Female Follow-Up Studies *Glaucoma/classification/therapy Humans *Intraocular Pressure Male Middle Aged Prognosis Prospective Studies *Visual Fieldsjchttp://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=880076owmetry is used for the noninvasive evaluation of ocular microcirculation in diseases such as glaucoma. Because of the dual blood flow supply in the optic nerve and the limited penetration power of the laser, the instrument primarily measures the microcirculation on the surface of the optic nerve, which is largely supplied by the central retinal artery rather than the ciliary arteries.'^WDiscoveries in Sight, Devers Eye Institute 1225 NE Second Ave, Portland, OR 97232, USA..&Wang, L. Cull, G. Cioffi, G. A.o(!0003-9950 (Print) Journal Article Arch Ophthalmol NHAnimals Blood Flow Velocity Ciliary Arteries/*physiopathology Female Laser-Doppler Flowmetry/*methods Macaca mulatta Microcirculation Microspheres Nerve Fibers/physiology Optic Nerve/*blood supply Regional Blood Flow Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S. Retinal Artery Occlusion/*physiopathologylehttp://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=11735792n p#7940146F38 Suppl 1994 May-& The vascular concept of glaucoma S3-6The regulation of ocular perfusion is different for different parts of the eye. Observations on the retina can, therefore, not be extrapolated to the optic nerve head. Extraocular vessels, especially the short posterior ciliary arteries, might play a major role in regulation of ocular circulation, but additional regulation takes place in the eye itself. Dysregulation might be transient and, thus, not necessarily present and detectable at any one examination. Older patients with arteriosclerotic vessels may behave differently in this regard than do young, healthy animals. Not only the arterial but also the venous side of the circulation may be disturbed. Disk hemorrhages can not only be a sign of damage; they can also provoke ischemia. Besides hypoxia, diseased vessel walls might play a direct role in the pathogenesis of optic nerve head cupping. Finally, a relation between vascular dysregulation and aqueous-humor dynamics is conceivable. '0*University Eye Clinic, Basel, Switzerland. Flammer, J.L.(0039-6257 (Print) Journal Article ReviewSurv OphthalmolaBlood Flow Velocity Eye/*blood supply Glaucoma/*physiopathology Humans Intraocular Pressure Optic Disk/blood supply Optic Nerve Diseases/etiology Research Support, Non-U.S. Gov't Retinal Hemorrhage/complications/etiologyjdhttp://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=79401469695795172g 1998 Apro60Optic nerve blood-flow abnormalities in glaucoma 267-89Glaucoma can be defined as an optic nerve disease with typical morphological and functional changes. There are many risk factors associated with this neuropathy. The best known factor is an increased intraocular pressure. There are, however, many other risk factors. Among them, vascular factors play a major role. Although such vascular factors have been postulated more than hundred years ago, it is only recently that the physiology and pathophysiology of the optic nerve head circulation is, to some extent, understood. New instruments have been developed to measure ocular blood flow including blood flow in the optic nerve head. Although most of the studies indicate that circulation is changed in glaucoma patients, there is little association between glaucoma and arteriosclerosis. The main cause for the circulation disturbance in glaucoma seems rather to be a vascular dysregulation leading to local vasospasm and to systemic hypotension.'LFDepartment of Ophthalmology, University Eye Clinic Basel, Switzerland.Flammer, J. Orgul, S..(1350-9462 (Print) Journal Article ReviewProg Retin Eye Res("Animals Blood Flow Velocity Fluorescein Angiography Glaucoma/diagnosis/*physiopathology Homeostasis Humans Intraocular Pressure Laser-Doppler Flowmetry Optic Nerve/anatomy & histology/*blood supply Optic Nerve Diseases/diagnosis/*physiopathology Risk Factors Ultrasonography, Doppler, Colorjdhttp://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=969579511286896203s 2001 May1^XVasospasm, its role in the pathogenesis of diseases with particular reference to the eye 319-49>7Vasospasm can have many different causes and can occur in a variety of diseases, including infectious, autoimmune, and ophthalmic diseases, as well as in otherwise healthy subjects. We distinguish between the primary vasospastic syndrome and secondary vasospasm. The term "vasospastic syndrome" summarizes the symptoms of patients having such a diathesis as responding with spasm to stimuli like cold or emotional stress. Secondary vasospasm can occur in a number of autoimmune diseases, such as multiple sclerosis, lupus erythematosus, antiphospholipid syndrome, rheumatoid polyarthritis, giant cell arteritis, Behcet's disease, Buerger's disease and preeclampsia, and also in infectious diseases such as AIDS. Other potential causes for vasospasm are hemorrhages, homocysteinemia, head injury, acute intermittent porphyria, sickle cell disease, anorexia nervosa, Susac syndrome, mitochondriopathies, tumors, colitis ulcerosa, Crohn's disease, arteriosclerosis and drugs. Patients with primary vasospastic syndrome tend to suffer from cold hands, low blood pressure, and even migraine and silent myocardial ischemia. Valuable diagnostic tools for vasospastic diathesis are nailfold capillary microscopy and angiography, but probably the best indicator is an increased plasma level of endothelin-1. The eye is frequently involved in the vasospastic syndrome, and ocular manifestations of vasospasm include alteration of conjunctival vessels, corneal edema, retinal arterial and venous occlusions, choroidal ischemia, amaurosis fugax, AION, and glaucoma. Since the clinical impact of vascular dysregulation has only really been appreciated in the last few years, there has been little research in the according therapeutic field. The role of calcium channel blockers, magnesium, endothelin and glutamate antagonists, and gene therapy are discussed.'lfUniversity Eye Clinic Basel, Mittlere Strasse 91, CH-4012, Basel, Switzerland. josef.flammer@unibas.ch& Flammer, J. Pache, M. Resink, T..(1350-9462 (Print) Journal Article ReviewProg Retin Eye ResConstriction, Pathologic Eye/*blood supply Eye Diseases/diagnosis/*etiology/physiopathology Humans Peripheral Vascular Diseases/*complications/diagnosis/physiopathologylehttp://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=11286896 7706025365 1995 Aprx`ZRetinal ganglion cell death in experimental glaucoma and after axotomy occurs by apoptosis 774-86VPPURPOSE. To investigate whether retinal ganglion cell death in experimental glaucoma and after axotomy occurs by apoptosis. METHODS. Chronic elevated eye pressure was produced in 20 monkey eyes, and the optic nerve was transected unilaterally in the orbit of 10 monkeys and 14 rabbits. Sixteen monkey and 14 rabbit eyes were studied as normal controls. Analytic methods included light and electron microscopy, histochemistry for DNA fragmentation (TUNEL method), and DNA electrophoresis in agarose gels. RESULTS. Dying ganglion cells in the experimental retinas exhibited morphologic features of apoptosis, including chromatin condensation and formation of apoptotic bodies. Cells with a positive reaction for DNA fragmentation were observed in eyes subjected to axotomy and experimental glaucoma but were only rarely encountered in control eyes. No evidence of internucleosomal fragmentation was detected electrophoretically, possibly because of the small proportion of cells that were dying at any given time. CONCLUSION. Some retinal ganglion cells injured by glaucoma and by axotomy die by apoptosis.'{Department of Ophthalmology, Wilmer Institute, Johns Hopkins University School of Medicine, Baltimore, Maryland 21287, USA.^WQuigley, H. A. Nickells, R. W. Kerrigan, L. A. Pease, M. E. Thibault, D. J. Zack, D. J.(!0146-0404 (Print) Journal Article Invest Ophthalmol Vis Sci Animals Apoptosis/*physiology Axons/*physiology Cell Death DNA/analysis DNA Damage/physiology Disease Models, Animal Electrophoresis, Agar Gel Female Glaucoma/pathology/*physiopathology Macaca fascicularis Male Nerve Degeneration/physiology Optic Nerve/surgery Rabbits Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S. Retinal Ganglion Cells/*physiology/ultrastructurejdhttp://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=77060258796158n 10 ( Pt 3) 1996>7Regional retinal blood flow and vascular autoregulationi 331-7t82The temporal retina is larger than the nasal retina and contains the metabolically active fovea. The variation in the distribution of blood between the temporal and nasal retinal circulations was investigated in 15 healthy volunteers, and the autoregulatory capacity of the temporal and nasal circulations was quantitated using 60% oxygen in the inspired air. Retinal blood flow was determined from red cell velocity using laser Doppler velocimetry and retinal vessel diameter from retinal photographs using a digital image analysis system. Volume flow was lower in the nasal than the temporal circulation by 52.49% (p < 0.001). This is a consequence of both significantly smaller vessels (20.4%, p < 0.001) and slower blood velocity in the nasal circulation (24.64%, p = 0.003) compared with the temporal vessels. After breathing 60% oxygen for 10 minutes, there was significant vasoconstriction (temporal, 10.42 +/- 1.24%, p < 0.001; nasal, 7.66 +/- 1.48%, p < 0.001), slower red cell velocity (temporal, 27.10 +/- 3.92%, p < 0.001; nasal, 27.36 +/- 5.51%, p < 0.001) and a significant reduction in the volumetric flow rate (temporal, 41.16 +/- 3.64%, p < 0.001; nasal, 37.99 +/- 5.07%, p < 0.001). The reduction in the haemodynamic parameters was comparable in the temporal and nasal circulations, indicating similar autoregulatory capacity. Retinal vascular conductance was calculated from volume flow and retinal perfusion pressure. It was 53% larger in the temporal than the nasal circulations. This provides an index of the metabolic needs of the different regions of the retina.'LFDiabetic Retinopathy Unit, R.P.M.S., Hammersmith Hospital, London, UK.81Rassam, S. M. Patel, V. Chen, H. C. Kohner, E. M.(!0950-222X (Print) Journal Article EyeAdult Carbon Dioxide/blood Hemodynamic Processes/physiology *Homeostasis Humans Laser-Doppler Flowmetry Middle Aged Oxygen/blood Partial Pressure Regional Blood Flow Retinal Vessels/anatomy & histology/*physiologyjdhttp://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=87961589184120 1451 1997 MayvoExpression of endothelin-B receptors by glia in vivo is increased after CNS injury in rats, rabbits, and humans 180-95zsPrevious studies have demonstrated that neonatal cultures of astrocytes express functional endothelin (ET) receptors. To determine if similar ET receptors are expressed by adult glia we used 125I-ET-1 to examine the expression of ET receptors both in vivo in the normal and transected optic nerves of the rabbit and rat and in vitro in cultures of astrocytes, microglia, or oligodendrocytes. Additionally, we examined the expression of ET receptors in the human optic nerve. Moderate levels of ET(B) receptors were identified in the rabbit and rat forebrain, whereas in the normal rabbit, rat, and human optic nerves a low density of ET(B) receptors was observed, mainly in association with glial fibrillary acidic protein + (GFAP+) astrocytes. After unilateral optic nerve transection, or damage to the retina, the density of glial ET(B) receptors in the optic nerve is significantly increased in all species examined. Thus, at 7 days posttransection there is a significant increase in ET(B) receptors, and by 90 days posttransection the density of ET(B) receptors in the rabbit or rat optic nerve was among the highest of any area in the central nervous system (CNS). Primary cultures of astrocytes or microglia, but not oligodendrocytes, express 125I-ET-1 binding sites. These data demonstrate that in the normal CNS, astrocytes express low but detectable levels of ET(B) receptors, and, after CNS injury, both astrocytes and microglia express high levels of ET(B) receptors. ET(B) receptors provide a therapeutic target for regulating glial proliferation and the release of neurotrophic factors from glia that occur in response to neuronal injury.'rlMolecular Neurobiology Laboratory (151), Veterans Affairs Medical Center, Minneapolis, Minnesota 55417, USA.d^Rogers, S. D. Demaster, E. Catton, M. Ghilardi, J. R. Levin, L. A. Maggio, J. E. Mantyh, P. W.(!0014-4886 (Print) Journal Article Exp Neurol`ZAged Aged, 80 and over Animals Astrocytes/chemistry/cytology/metabolism Autoradiography Axons/chemistry Cells, Cultured Denervation Female Humans Immunohistochemistry Male Microglia/chemistry/cytology/metabolism Middle Aged Neuroglia/*chemistry/cytology/metabolism Oligodendroglia/chemistry/metabolism Optic Nerve/chemistry/cytology/*surgery Rabbits Rats Rats, Sprague-Dawley Receptor, Endothelin B Receptors, Endothelin/analysis/*biosynthesis Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, Non-P.H.S. Research Support, U.S. Gov't, P.H.S. Retinal Ganglion Cells/chemistry/ultrastructurejdhttp://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=9184120n, Switzerland.nGasser, P. Flammer, J..(0012-4486 (Print) Journal Article ReviewDoc Ophthalmol("Calcium Channel Blockers/therapeutic use Eye/blood supply Humans Ischemic Attack, Transient/complications/*physiopathology Models, Theoretical Regional Blood Flow Research Support, Non-U.S. Gov't Syndrome Vascular Diseases/complications/drug therapy/*physiopathology Vasoconstriction Visionjdhttp://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=3322745. 12635671131 2003Jan-Feb}Comparative analysis of the effects of dorzolamide and latanoprost on ocular hemodynamics in normal tension glaucoma patients  24-31  PURPOSE: To compare the effects of latanoprost (Xalatan) and dorzolamide (Trusopt) on ocular hemodynamics in normal-tension glaucoma patients. METHODS: A randomized, single-masked, parallel design study was conducted. After a 4-week washout period, 20 normal tension glaucoma patients, recruited from a single university-based ophthalmology clinic, received either latanoprost once daily or dorzolamide 3 times daily for 4 weeks. The subjects were examined at baseline and post-treatment. Outcome measures included heart rate (HR), blood pressure (BP), logMar visual acuity (VA), contrast sensitivity (CS), intraocular pressure (IOP), color Doppler imaging (CDI), and fluorescein angiography with the Rodenstock scanning laser ophthalmoscope (SLO). CDI measurements of the retrobulbar vessels included peak systolic velocity, end diastolic velocity, and the calculated resistance index. Arterio-venous passage time (AVP) in the superior and inferior temporal retina was calculated from the SLO angiograms. RESULTS: Neither dorzolamide nor latanoprost had any statistically significantly effect on HR or BP. Both drugs significantly lowered IOP without altering calculated ocular perfusion pressure (p<0.05). There was no statistically significant difference in any CDI measurement. Dorzolamide significantly decreased AVP time in the superior retina (p=0.011), while latanoprost did not (p=0.62). CONCLUSIONS: Dorzolamide, unlike latanoprost, significantly reduced AVP times in the superior temporal retina in normal tension glaucoma (NTG) patients.'xqDepartment of Ophthalmology, Indiana University School of Medicine, Indianapolis 46202, USA. alharris@indiana.eduRKHarris, A. Migliardi, R. Rechtman, E. Cole, C. N. Yee, A. B. Garzozi, H. J.RL1120-6721 (Print) Clinical Trial Journal Article Randomized Controlled TrialEur J Ophthalmolb\Adult Antihypertensive Agents/*therapeutic use Blood Flow Velocity Blood Pressure/drug effects Ciliary Arteries/physiology/ultrasonography Comparative Study Eye/*blood supply Glaucoma, Open-Angle/*drug therapy/*physiopathology Heart Rate/drug effects Humans Intraocular Pressure/drug effects Ophthalmic Artery/physiology/ultrasonography Prostaglandins F, Synthetic/*therapeutic use Regional Blood Flow Research Support, Non-U.S. Gov't Retinal Artery/physiology/ultrasonography Single-Blind Method Sulfonamides/*therapeutic use Thiophenes/*therapeutic use Tonometry, Ocular Ultrasonography, Doppler, Colorlehttp://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=1263567111033151445. 2000 Sep 1lf_Optic Disc Blood Flow Measured by Scanning Laser-Doppler Flowmetry Using a New Analysis Programl573-574ePurpose: Using a new analysis program for scanning laser-Doppler flowmetry (SLDF) by a Heidelberg retina flowmeter (HRF), we studied the relation between flow and visual field or disc morphology.Subjects and Methods: In 42 eyes of 21 patients with normal tension glaucoma (NTG) the mean-flow of the HRF blood flow parameters at the disc rim was measured and analyzed by a new analysis program for perfusion maps (the SLDF analysis tool), to minimize the influence of large vessels or/and artifacts caused by small eye movements. We investigated whether difference of the mean-flow between a pair of eyes had any relation to differences between a pair of eyes in visual field indices and those in disc morphological measurements of the Heidelberg retina tomograph.Results: We found statistically significant correlations between the mean-flow and optic disc parameters (Disk Area, Cup Area, Height Variation Contour, Cup Volume, Rim Volume, Mean RNFL Thickness). We found no statistically significant correlations between the mean-flow and visual field parameters (mean deviation, corrected pattern standard deviation).Conclusion: The results suggested that eyes with less flow in the optic disc rim have more advanced glaucomatous morphological changes.'TNDepartment of Ophthalmology, Self Defense Forces Central Hospital, Gifu, Japan*#Hayashi, N. Tomita, G. Kitazawa, Y.(!0021-5155 (Print) Journal articleJpn J Ophthalmollehttp://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=11033151 &88970495 234v10 1996 OcteB8Waldmann, E. Gasser, P. Dubler, B. Huber, C. Flammer, J.(!0721-832X (Print) Journal Article& Graefes Arch Clin Exp OphthalmolAged Cataract/*complications/epidemiology Electrocardiography, Ambulatory Exercise Test Female Glaucoma, Open-Angle/*complications/epidemiology Humans Incidence Male Middle Aged Myocardial Ischemia/*complications/epidemiology/physiopathology Risk Factors Switzerland/epidemiologyjdhttp://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=889704911735792 119i12 2001 DecEZSDepth of penetration of scanning laser Doppler flowmetry in the primate optic nerve 1810-4OBJECTIVES: To estimate the measuring depth of the blood flow and to establish the vascular contributions to these measurements with scanning laser Doppler flowmetry (SLDF) of the primate anterior optic nerve. METHODS: Optic nerve blood flow in each eye of 8 monkeys was measured using SLDF before and following surgical occlusion of the central retinal artery (n = 4) or posterior ciliary arteries (n = 4). The regional blood flow in both eyes was determined using a nonradioactive microsphere method. RESULTS: The blood flow in the nerve fiber layer (NFL), including the prelaminar region, was measured with microspheres after central retinal artery occlusion; it was significantly reduced (-83%) with no significant change in the combined laminar and retrolaminar regions. The blood flow measured with SLDF had a 51% reduction. After posterior ciliary artery occlusion, the blood flow in the NFL was measured with microspheres and was not significantly affected (+2%); neither was that measured with SLDF (-12%). However, there was a 51% reduction in the laminar and retrolaminar regions when microspheres were used. The mean +/- SD tissue thickness of the NFL was 359 +/- 16 microm and 353 +/- 54 microm in each group. CONCLUSIONS: Scanning laser Doppler flowmetry measures blood flow principally in the NFL of the anterior optic nerve, which is primarily supplied by the central retinal artery. Blood flow in the laminar and retrolaminar regions makes a small contribution to the SLDF measurement, with an NFL thickness between 300 and 400 microm. CLINICAL RELEVANCE: Scanning laser Doppler flowmetry is used for the noninvasive evaluation of ocular microcirculation in diseases such as glaucoma. Because of the dual blood flow supply in the optic nerve and the limited penetration power of the laser, the instrument primarily measures the microcirculation on the surface of the optic nerve, which is largely supplied by the central retinal artery rather than the ciliary arteries.'^WDiscoveries in Sight, Devers Eye Institute 1225 NE Second Ave, Portland, OR 97232, USA..&Wang, L. Cull, G. Cioffi, G. A.o(!0003-9950 (Print) Journal Article Arch Ophthalmol NHAnimals Blood Flow Velocity Ciliary Arteries/*physiopathology Female Laser-Doppler Flowmetry/*methods Macaca mulatta Microcirculation Microspheres Nerve Fibers/physiology Optic Nerve/*blood supply Regional Blood Flow Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S. Retinal Artery Occlusion/*physiopathologylehttp://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=11735792n 8115155m 10102A 1994 Febhb[Trabeculectomy is associated with retrobulbar hemodynamic changes. A color Doppler analysis 340-512,PURPOSE: To determine whether color Doppler hemodynamic changes occur in the retrobulbar circulation after trabeculectomy. METHODS: The authors prospectively enrolled 20 patients undergoing trabeculectomy and performed color Doppler imaging of both eyes before surgery and then at approximately 2-, 5-, and 14-week intervals after surgery. The systolic maximum velocity, mean velocity, end-diastolic velocity, and vascular resistance (resistance index) of the central retinal artery, nasal and temporal short posterior ciliary arteries, and ophthalmic arteries were determined. Statistical comparison of the preoperative and postoperative measures were performed on both the operative and nonoperative eye using the paired Student's t test. RESULTS: A statistically significant increase was observed in the mean and end-diastolic velocity and a significant decrease in the vascular resistance of the central retinal artery and both short posterior ciliary arteries at nearly all postoperative intervals (25 of 27 preoperative and postoperative comparisons; P < 0.05) The ophthalmic artery, while showing an increased velocity at all intervals, only attained a statistically significant increase in one of three postoperative intervals for mean velocity and two of three intervals for end-diastolic velocity (P < 0.05). There were no notable changes in resistance. The nonoperative eye did not show a statistically significant change in velocity or in resistance in the central retinal artery or either nasal or temporal short posterior ciliary artery at any interval (0 of 27 preoperative and postoperative comparisons for mean velocity, end-diastolic velocity, and resistance index.) CONCLUSION: Sustained increases in mean velocity and end-diastolic velocity and decreases in resistance index were observed in the central retinal artery and the short posterior arteries with clinically attainable reductions in intraocular pressure after trabeculectomy in patients with chronic glaucoma. These findings are consistent with, but not diagnostic of, increased blood flow through these vessels.'JDNeuro-Ophthalmology Service, Wills Eye Hospital, Philadelphia 19107.haTrible, J. R. Sergott, R. C. Spaeth, G. L. Wilson, R. P. Katz, L. J. Moster, M. R. Schmidt, C. M.(!0161-6420 (Print) Journal Article OphthalmologyAdult Aged Blood Flow Velocity/physiology Eye/*blood supply/ultrasonography Female Glaucoma/*physiopathology/surgery/ultrasonography Humans Intraocular Pressure/physiology Male Middle Aged Ocular Hypertension/physiopathology Ophthalmic Artery/physiology/ultrasonography Prospective Studies Regional Blood Flow Retinal Artery/physiology/ultrasonography *Trabeculectomy Vascular Resistance/physiologyjdhttp://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=8115155 t @16123422469 2005 Sep|vEvidence for association of endothelial nitric oxide synthase gene in subjects with glaucoma and a history of migraine 3221-6PURPOSE: There is evidence to suggest that vasospasm and vascular dysregulation play a role in the etiology of glaucoma. This effect may be particularly relevant in patients with glaucoma who have a history of migraine or vasospastic tendencies. This study was conducted to investigate the role of genes with products that regulate blood flow to ocular tissues. The candidate genes were the two isoforms of nitric oxide synthase (NOS), NOS3 and -2A, and endothelin (ET)-l. The frequency of the T786C mutation in NOS3 was also examined. METHODS: DNA was obtained from 58 patients with primary open-angle glaucoma (POAG), 76 with normal tension glaucoma (NTG), and 38 control subjects. Polymerase chain reactions (PCR) were used to compare the frequency of the alleles between the subjects with glaucoma and the control subjects and the subjects with glaucoma with vasospasm or migraine. The PCR product was sequenced to identify the frequency of the T786C mutation. RESULTS: The distribution of the NOS3 repeat alleles in subjects with glaucoma and control subjects just failed to reach statistical significance (P = 0.06). The distribution in subjects with NTG or POAG did not differ significantly. A significant difference was found (P < 0.001) in the distribution of allele frequencies of the NOS3 marker in subjects who had glaucoma with migraine versus control subjects. There were no differences in the distribution of the NOS2A or ET-1 markers between the subjects with glaucoma and the control subjects. CONCLUSIONS: This study provides evidence of an association between the NOS3 gene and subjects with glaucoma who have a history of migraine. Unlike in other studies, no evidence was found of an association between ET-1 and glaucoma.'}Department of Ophthalmology, The Royal Group of Hospitals, Belfast, N. Ireland, United Kingdom. joanne.logan1@btopenworld.com`YLogan, J. F. Chakravarthy, U. Hughes, A. E. Patterson, C. C. Jackson, J. A. Rankin, S. J.(!0146-0404 (Print) Journal Article Invest Ophthalmol Vis SciAged Endothelin-1/genetics Female Gene Frequency Glaucoma, Open-Angle/*genetics Humans Intraocular Pressure Male Middle Aged Migraine Disorders/*genetics Nitric Oxide Synthase/*genetics Nitric Oxide Synthase Type II Nitric Oxide Synthase Type III Polymerase Chain Reactionlehttp://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=1612342211219633101, 2001 Feb9Effect of timolol on anterior optic nerve blood flow in patients with primary open-angle glaucoma as assessed by the Heidelberg retina flowmeter 13-7PURPOSE: To evaluate the effect of 0.5% timolol maleate on the capillary circulation of the anterior optic nerve head in patients with primary open-angle glaucoma and to compare the results with those obtained in a healthy control group. PATIENTS AND METHODS: Twelve patients with nonprogressive glaucoma and 12 age- and sex-matched healthy volunteers were included in this prospective study. Optic nerve head perfusion was examined by the Heidelberg Retina Flowmeter (HRF) in both groups. A 3-week washout period preceded the baseline measurement in the glaucoma group, and ONH blood flow was assessed again after 3 weeks of bilateral topical timolol treatment and 2 hours after timolol application. RESULTS: Intraocular pressure decreased significantly with timolol (P < 0.001). The HRF flow values for patients with glaucoma were comparable to those for a control group at baseline (P = 0.25), 3 weeks after timolol therapy (P = 0.09), and 2 hours after timolol instillation (P = 0.15). The glaucoma group showed no statistically significant change in the HRF parameter flow as compared with baseline, either after 3 weeks of timolol treatment or 2 hours after timolol instillation (P = 0.40). The heart rate and arterial systolic and diastolic blood pressure values showed no alteration after timolol therapy. CONCLUSIONS: Patients with nonprogressive glaucoma seem not to have an altered optic nerve blood flow as assessed by the HRF, and timolol treatment does not seem to alter the latter blood flow parameter in such patients.'0*University Eye Clinic, Basel, Switzerland.LFLubeck, P. Orgul, S. Gugleta, K. Gherghel, D. Gekkieva, M. Flammer, J.RL1057-0829 (Print) Clinical Trial Journal Article Randomized Controlled Trial J Glaucoma~wAdrenergic beta-Antagonists/*therapeutic use Aged Blood Flow Velocity/drug effects Comparative Study Female Glaucoma, Open-Angle/drug therapy/*physiopathology Humans Intraocular Pressure/drug effects Laser-Doppler Flowmetry Male Middle Aged Ophthalmic Solutions Optic Disk/*blood supply Optic Nerve/*blood supply Prospective Studies Timolol/*therapeutic use Tonometry, Ocularolehttp://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=11219633N1985490i 1111 1991 Jan 15zsCorrelation between intraocular pressure control and progressive glaucomatous damage in primary open-angle glaucomaa 51-5Fifty-five patients with primary open-angle glaucoma and early glaucomatous damage who had medical therapy and laser trabeculoplasty were followed up for four to 11 years or until progressive glaucomatous damage was documented. Factors associated with the stability or progression of glaucoma were evaluated. Eyes with mean intraocular pressure higher than 21 mm Hg during the follow-up period uniformly had progressive glaucomatous changes. Conversely, eyes with mean intraocular pressure less than 17 mm Hg remained stable, and approximately half of the eyes with mean intraocular pressure between 17 and 21 mm Hg had progressive glaucomatous changes. Patients who remained stable were slightly younger than those with progressive glaucomatous changes (P less than .05), but initial optic nerve head appearance, initial visual field findings, number of medicines used, medical history, and patient gender or race were not statistically associated with stability or progression of the glaucoma. These findings reinforce the importance of intraocular pressure control in primary open-angle glaucoma and the need to identify other markers that help determine the proper level of intraocular pressure for individual patients.'VPDepartment of Ophthalmology, Duke University Eye Center, Durham, North Carolina..(Mao, L. K. Stewart, W. C. Shields, M. B.(!0002-9394 (Print) Journal ArticlepAm J OphthalmolcAdult Aged Aged, 80 and over Female Follow-Up Studies Glaucoma, Open-Angle/*physiopathology/surgery Humans *Intraocular Pressure/drug effects Male Middle Aged Optic Disk/*physiopathology Tonometry, Ocular Trabeculectomy Visual Fieldsejdhttp://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=1985490J z t 794013338 Suppl 1994 Mayd^Differences in the longterm effect of timolol and betaxolol on the pulsatile ocular blood flowS118-24In the past several years the effect of longterm glaucoma therapy on ocular hemodynamics has taken on increased interest. This interest has been sparked by studies demonstrating differential effects of various beta-blockers on visual function, and the possible contributory role of ocular blood flow. In the present study, the pulsatile ocular blood flow (POBF), as derived by the Langham OBF system, was measured prior to treatment and then tracked throughout a one-year period of beta-blocker therapy (betaxolol 0.5% or timolol 0.5%) in 25 glaucoma patients. Results of the two treatments were compared, and indicated that, whereas both betaxolol- and timolol-treated patients had similar significant reductions in the IOP, the effect of the two treatments on the POBF differed. In timolol-treated patients, the POBF decreased significantly over the 12-month observation period, whereas in betaxolol-treated patients it remained stable.'>7Clinica Oculistica, Universita di Torino, turin, Italy.4-Carenini, A. B. Sibour, G. Boles Carenini, B.RL0039-6257 (Print) Clinical Trial Journal Article Randomized Controlled TrialSurv OphthalmolrlAdult Aged Aged, 80 and over Betaxolol/pharmacology/*therapeutic use Blood Flow Velocity/drug effects/physiology Comparative Study Female Glaucoma, Open-Angle/*drug therapy/physiopathology Humans Intraocular Pressure Longitudinal Studies Male Middle Aged Pulsatile Flow/drug effects/physiology Research Support, Non-U.S. Gov't Timolol/pharmacology/*therapeutic usejdhttp://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=794013310704543 129t3t 2000 Marpd]The effect of brimonidine tartrate on retinal blood flow in patients with ocular hypertensionn297-3017>8PURPOSE:To study the effects of topical brimonidine tartrate 0.2%, an alpha(2)-agonist ocular hypotensive drug, on retinal capillary blood flow in patients with ocular hypertension.METHODS:The study was a double-masked, randomized, placebo-controlled trial set in a tertiary eye center. Ocular hypertensive patients with repeatable intraocular pressures greater than 21 mm Hg and normal visual fields and optic disks were consecutively recruited. After an eye examination, baseline retinal blood flow measurements were made with confocal scanning laser Doppler flowmetry in one study eye. Patients were then randomly assigned to receive either brimonidine or placebo (saline) twice daily for 8 weeks. Blood flow and intraocular pressure measurements were then repeated after 4 and 8 weeks. RESULTS:Seventeen patients were randomly assigned to receive brimonidine, and 14 received placebo. One patient in each group failed to complete the study. The mean group differences in baseline age and intraocular pressure were not statistically significant (59. 23 [+/-10.24] and 52.23 [+/-16.46] years, respectively, and 24.84 [+/-2.08] and 24.56 [+/-2.85] mm Hg, respectively). Brimonidine reduced intraocular pressure by 17.90% and 16.17% at 4 and 8 weeks, respectively, with a significant difference in treatment effect compared with the placebo group (P <.007). The group difference in treatment effect in any of the three hemodynamic parameters velocity, volume, and flow was within 8% and not significantly different at 4 or 8 weeks (P.360). Based on a type I error of 0.05, our study had a power greater than or equal to 75% to detect group differences in treatment effect of greater than or equal to 15% to 20%. CONCLUSIONS:Brimonidine reduces intraocular pressure without altering retinal capillary blood flow in patients with ocular hypertension.'NHFaculty of Medicine, Dalhousie University, Halifax, Nova Scotia, Canada.>8Carlsson, A. M. Chauhan, B. C. Lee, A. A. LeBlanc, R. P.tn0002-9394 (Print) Clinical Trial Corrected and Republished Article Journal Article Randomized Controlled TrialAm J Ophthalmol Adrenergic alpha-Agonists/administration & dosage/*therapeutic use Antihypertensive Agents/administration & dosage/*therapeutic use Blood Flow Velocity/physiology Double-Blind Method Female Humans Intraocular Pressure/*drug effects Laser-Doppler Flowmetry Male Middle Aged Ocular Hypertension/drug therapy/*physiopathology Ophthalmic Solutions/administration & dosage/therapeutic use Quinoxalines/administration & dosage/*therapeutic use Regional Blood Flow Retinal Vessels/*physiopathology Visual Acuity Visual Fieldslehttp://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=10704543r122199961242 2002Jul-Aug2,Pulsatile ocular blood flow during pregnancy 276-80PURPOSE: To study pulsatile ocular blood flow (POBF) throughout pregnancy. METHODS: We enrolled twenty-seven healthy women in the first trimester of gestation, only ten of which were followed through the second trimester, and fourteen non pregnant healthy women. In each subject we measured POBF with the POBF pneumotonometer (OBF Ltd. UK), IOP, blood pressure (BP) and heart rate (HR). An unpaired Student t-test was used to compare pregnant women with non-pregnant women, and a two-tailed paired Student t-test was used to compare the same women in the first and second trimester of pregnancy. p <0.05 is considered statistically significant. RESULTS: Results are presented as means +/- SD. In the first trimester of pregnancy the age was 32 +/- 6, POBF 1516.4 +/- 382 ml/min, IOP 13 +/- 3 mmHg, BP 92 +/- 6 mmHg, and HR 86 +/- 14 beats/min. In the second trimester POBF was 1629.11 +/- 352.4 ml/min, intraocular pressure (IOP) 12 +/- 3 mmHg, BP 96 +/- 3 mmHg, and HR 93 +/- 10 beats/min. In the control group the age was 27 +/- 9, POBF 972.23 +/- 329.3 ml/min, BP 88 +/- 4.3 mmHg, and HR 80 +/- 14 beats/min. POBF increases during the first trimester (p = 0.00008). In the second trimester POBF was higher compared to the first trimester (p = 0.0008). Non significant differences were observed for the other parameters. CONCLUSIONS: The POBF increases throughout gestation. During pregnancy there is an increase in estrogen which induces endothelial-dependent vasodilatation in several tissues. The estrogen changes may influence POBF.'rkOphthalmology Clinic, Tor Vergata University, Roma, Fondazione G.B. Bietti per l'Oftalmologia Onlus, Italy.lfCentofanti, M. Migliardi, R. Bonini, S. Manni, G. Bucci, M. G. Pesavento, C. B. Amin, C. S. Harris, A.(!1120-6721 (Print) Journal ArticleEur J OphthalmoltnAdolescent Adult Blood Flow Velocity Blood Pressure/physiology Comparative Study Endothelium, Vascular/physiology Estrogens/physiology Eye/*blood supply Female Heart Rate/physiology Humans Intraocular Pressure/physiology Pregnancy/*physiology Pregnancy Trimester, First Pregnancy Trimester, Second Pulsatile Flow/*physiology Tonometry, Ocular Vasodilation/physiologylehttp://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=122199963 4 Pr12646761493 2003`YExtraocular blood flow and endothelin-1 plasma levels in patients with multiple sclerosis 164-8NGIn order to evaluate whether plasma levels of the potent vasoconstrictor endothelin-1 (ET-1) are increased in patients with multiple sclerosis (MS) and whether these patients exhibit an ET-1-mediated vascular dysregulation, ET-1 plasma levels were measured in 30 patients with MS. Blood flow velocities in the ophthalmic artery, central retinal artery, central retinal vein, short lateral posterior ciliary artery, and short medial posterior ciliary artery were assessed in parallel. ET-1 plasma levels were significantly increased in MS patients when compared to sex- and age-matched healthy controls (2.0 +/- 0.4 pg/ml, range 1.1-2.8 vs. 1.5 +/- 0.2 pg/ml, range 0.9-2.0; p < 0.001). Moreover, the patients exhibited significant alterations of extraocular blood flow. The role of ET-1 in the inflammatory process remains to be clarified.'RKUniversity Eye Clinic Basel, University Hospital Basel, Basel, Switzerland.`YPache, M. Kaiser, H. J. Akhalbedashvili, N. Lienert, C. Dubler, B. Kappos, L. Flammer, J.(!0014-3022 (Print) Journal Article Eur NeurolAdult Blood Flow Velocity Ciliary Arteries/*physiopathology/ultrasonography Endothelin-1/*blood Female Humans Male Middle Aged Multiple Sclerosis/*physiopathology/ultrasonography Ophthalmic Artery/*physiopathology/ultrasonography Regional Blood Flow Retinal Artery/physiopathology/ultrasonography Retinal Vein/physiopathology/ultrasonography Retinal Vessels/*physiopathology/ultrasonography Ultrasonography, Doppler, Colorlehttp://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=126467619245904645 1997 MayhbAutoregulation of human optic nerve head circulation in response to increased intraocular pressure 737-44The following experiments were undertaken to determine if blood flow is maintained by autoregulation in the human optic nerve head when circulation is challenged by elevated intraocular pressure, and to determine if the presence or absence of autoregulation is universal. Laser Doppler flowmetry was used to determine the average velocity, the number of moving erythrocytes, and the volume of flow in the capillary bed of the optic disc. These parameters were measured in 10 subjects at spontaneous levels of intraocular pressure (IOP), and at pressures artificially elevated to 25, 35, 45 and 55 mm Hg with a scleral suction cup. Four subjects (two who showed autoregulation and two who did not) were studied on six additional occasions to determine consistency of the findings. In these same four subjects a second location on the disc was also measured on six occasions to determine if the IOP-effect on blood flow varied by location. Of the 10 subjects initially studied, seven maintained the baseline level of blood flow over the lower part of the range of elevated intraocular pressure (evidence of autoregulation), but showed a decline in flow by the time IOP reached 45 or 55 mm Hg. Two subjects showed a linear decline in blood flow beginning with the smallest increment of elevation of IOP (no autoregulation), and one showed an uninterpretable result. The two individuals who showed the linear decline and two of those who showed efficient autoregulation were remeasured, and each showed consistently the same pattern as before when restudied on six different occasions each. However, at a different location on their discs, autoregulation was manifest in all of these four individuals. When challenged by elevated IOP, the optic nerve head typically maintains a steady-blood flow over a range of IOP, but fails to maintain the same flow by the time IOP reaches 45 or 55 mm Hg. Some disc locations, at least in some individuals, do not show this autoregulation, but exhibit a decline in blood flow linearly related to IOP, even with the modest elevation of IOP.'|uDepartment of Ophthalmology, Bascom Palmer Eye Institute, University of Miami School of Medicine, Florida 33101, USA.NHPillunat, L. E. Anderson, D. R. Knighton, R. W. Joos, K. M. Feuer, W. J.(!0014-4835 (Print) Journal Article Exp Eye ResAdult Blood Flow Velocity Female Homeostasis/physiology Humans Intraocular Pressure/*physiology Laser-Doppler Flowmetry Male Middle Aged Optic Nerve/*physiology Regression Analysis Reproducibility of Results Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S.jdhttp://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=924590411438055 13281l 2001 JulbZTOptic nerve blood flow is diminished in eyes of primary open-angle glaucoma suspects 63-9 PURPOSE: The purpose of this study was to evaluate optic nerve blood flow in primary open-angle glaucoma suspect eyes with normal automated visual fields, in an attempt to elucidate how early in the glaucomatous disease process changes in optic nerve blood flow become apparent. METHODS: Twenty-one eyes (21 patients) suspected of having primary open-angle glaucoma were studied prospectively and compared with a previously reported cohort of 22 eyes (22 patients) with primary open-angle glaucoma and 15 eyes (15 subjects) of age-matched controls. Primary open-angle glaucoma suspect eyes had untreated intraocular pressure greater than 21 mm Hg and normal visual fields using Humphrey program 24-2 or 30-2 with a full threshold strategy. Laser Doppler flowmetry was used to measure optic nerve head blood velocity, volume, and flow at four quadrants in the optic nerve, in the cup, and in the foveola of one eye of each patient. The mean flow from the superotemporal rim, inferotemporal rim, and cup was calculated (Flow(3)) and identified as the main outcome measure. Measurements from primary open-angle glaucoma suspect eyes were compared with corresponding measurements from controls and eyes with primary open-angle glaucoma; a Student t test was employed with a Bonferroni corrected P value of.025 to account for comparisons of primary open-angle glaucoma suspects both to controls and to eyes with primary open-angle glaucoma. RESULTS: Compared with controls, Flow(3) was 24% lower in primary open-angle glaucoma suspect eyes (P <.0003). In primary open-angle glaucoma suspect eyes, flow was 16% lower in the superotemporal rim (P <.007), 35% lower in the cup (P <.007), and 22% lower in the inferotemporal neuroretinal rim (P <.029) compared with controls. No significant difference between primary open-angle glaucoma suspect and control eyes was seen in the inferonasal rim, superonasal rim, or foveola. No significant difference was detected at any location between primary open-angle glaucoma suspect eyes and eyes with primary open-angle glaucoma. CONCLUSIONS: Laser Doppler flowmetry detected circulatory abnormalities in primary open-angle glaucoma suspects who did not have any manifest visual field defect. Decreases in flow in glaucoma suspects were similar in magnitude to those of subjects with primary open-angle glaucoma. These data suggest that impaired optic nerve blood flow develops early in the glaucomatous process and does not develop solely as a result of glaucoma damage.'Scheie Eye Institute, University of Pennsylvania Health Systems, Philadelphia, Pennsylvania 19104, USA. piltz@mail.med.upenn.eduHAPiltz-seymour, J. R. Grunwald, J. E. Hariprasad, S. M. Dupont, J.(!0002-9394 (Print) Journal ArticleAm J OphthalmolTMBlood Flow Velocity Blood Pressure Cohort Studies Comparative Study Glaucoma, Open-Angle/*physiopathology Humans Intraocular Pressure Laser-Doppler Flowmetry Middle Aged Optic Nerve/*blood supply Prospective Studies Regional Blood Flow Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S. Visual Acuity Visual Fieldslehttp://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=11438055p:4Morsman, C. D. Bosem, M. E. Lusky, M. Weinreb, R. N. 1995\VThe effect of topical beta-adrenoceptor blocking agents on pulsatile ocular blood flow Eye  9 ( Pt 3)  344-77556745rlAdrenergic beta-Antagonists/*pharmacology Betaxolol/*pharmacology Comparative Study Eye/*blood supply Female Glaucoma, Open-Angle/*physiopathology Humans Intraocular Pressure/drug effects Levobunolol/*pharmacology Male Middle Aged Ocular Hypertension/*physiopathology Pulsatile Flow/*drug effects Research Support, Non-U.S. Gov't Time Factors Timolol/*pharmacology Thirty-three ocular hypertensive patients (21 with primary open angle glaucoma and 12 glaucoma suspects) were randomly assigned to receive either timolol, levobunolol or betaxolol in one eye. Pulsatile ocular blood flow (POBF) was measured before treatment (baseline) and 2 hours after drop administration. After 1 week of regular twice-daily dosage, POBF was measured again both immediately before and 2 hours after drop instillation. All measurements were made by an investigator masked to treatment. POBF increased by 11% (p = 0.09) at week 0 after levobunolol administration, and by 22% (p = 0.20) at week 1 before drop administration compared with baseline. It dropped by 23% and 25% (p = 0.04 and 0.06, respectively) before and after betaxolol administration at week 1. Although POBF was reduced in the timolol group, this change was not significant. These results can not be explained uniformly by changes in intraocular pressure or blood pressure. The relevance of these measurements to visual function in glaucoma is not known.RL0950-222X (Print) Clinical Trial Journal Article Randomized Controlled Trialjdhttp://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=7556745'ZTGlaucoma Center and Research Laboratories, University of California, San Diego, USA.; v15226664134; 2004 Aug{lfResponse of retinal vessel diameters to flicker stimulation in patients with ear14662590 121h12 2003 DechPIOcular hemodynamics and glaucoma prognosis: a color Doppler imaging studya 1711-5OBJECTIVE: To evaluate the effect of optic nerve circulation, using color Doppler imaging (CDI), on the progression of visual field damage in primary open-angle glaucoma. METHODS: The relationship between the results of retrobulbar CDI, performed shortly after the diagnosis of primary open-angle glaucoma, and the progression of visual field loss for 7 years was evaluated in 44 glaucoma patients. Color Doppler imaging variables in patients with a stable and deteriorating clinical course were compared, and the pattern of increasing risk for different CDI values was analyzed using an additive logistic model. Based on this nonparametric analysis, we arrived at a discriminant CDI value identifying glaucoma patients with a poor prognosis. On the basis of the discriminant value, patients were divided into 2 groups, and the odds ratio of visual field loss for each group was then estimated. RESULTS: Patients with a stable visual field had a higher diastolic velocity and a lower resistivity index in the ophthalmic artery (P<.001 for both) compared with those with a deteriorating visual field during the study. The odds of visual field deterioration in patients with an ophthalmic artery resistivity index of 0.78 or higher was about 6 times that of patients with an ophthalmic artery resistivity index lower than 0.78. CONCLUSION: Color Doppler imaging variables of the ophthalmic artery correlate with the risk of visual field deterioration in patients with primary open-angle glaucoma.'zDepartments of Oto-Neuro-Ophthalmological Surgery and Statistics, University of Florence, Italy. fernando.galassi@unifi.itF?Galassi, F. Sodi, A. Ucci, F. Renieri, G. Pieri, B. Baccini, M. (!0003-9950 (Print) Journal ArticleeArch Ophthalmol Aged Blood Flow Velocity Ciliary Arteries/physiology/ultrasonography Comparative Study Disease Progression Eye/*blood supply Female Glaucoma, Open-Angle/*physiopathology Humans Male Middle Aged Odds Ratio Ophthalmic Artery/physiology/ultrasonography Prognosis Regional Blood Flow Retinal Artery/physiology/ultrasonography Ultrasonography, Doppler, Color Vision Disorders/*physiopathology *Visual Fieldslehttp://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=14662590Mhritis.'0*University Eye Clinic, Basel, Switzerland.XQPache, M. Schwarz, H. A. Kaiser, H. J. Wuest, P. Kloti, M. Dubler, B. Flammer, J.(!1234-1010 (Print) Journal Article Med Sci MonitAdult Aged Arthritis, Rheumatoid/*blood/pathology Case-Control Studies Endothelin-1/*blood Female Humans Male Microscopic Angioscopy Middle Aged Radioimmunoassay Regional Blood Flow Time Factorslehttp://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=12218941 q5  Galassi, F. Gandolfo, E. Garhofer, G.Garway-Heath, D. F. Garzozi, H.Garzozi, H. J. Gasser, P. Gazozi, H. J. Geiser, M. Gekkieva, M.Georgopoulos, G. T.Georgopoulos, M. Gherghel, D.Ghilardi, J. R.Goadsby, P. J.Goldenfeld, M. Gordon, M. O.Gottsch, J. D. Gouya, G. Graham, P. A. Graham, S. L. Green, W. R. Greve, E. L.Grieshaber, M. C.Griffiths, L. R.Grobbee, D. E. Groh, M. J.Grunwald, J. E. Gugleta, K. Guiducci, M. Guillaume, S. Gupta, V.Gutteridge, I. F. Haase, A. Hafez, A. S. Hagiwara, H. Harazny, J.Hariprasad, S. M. Harman, C. D. Harris, A. Hart, R. T. Hasler, P. W.Haufschild, T. Hayashi, N. Hayreh, S. S.Hazelton, M. L.Heathcote, J. G. Heijl, A. Henle, C. Henry, E. Hertzmark, E.Hetherington, J., Jr. Heuer, D. K.Higginbotham, E. J. Hikichi, T.Hitchings, R. A. Hnik, P. Hockmann, K. Hofman, A. Hofman, P.Hollows, F. C. Horie, T.Hosking, S. L. House, P. H. Hoyng, P. Hsu, W. M.Hubbard, L. D. Huber, C. Huber, K. Huemer, K. H. Hughes, A. E.Hulbert, M. F. Hulet, C. Hussein, M. Hyman, L. Hyman, L. G. Ikram, M. K. Inan, U. U. Indar, A. Ishii, Y. Ishiko, S.Jackson, J. A. James, C. B.Januleviciene, I. Javitt, J.Johanson, G. W. Johnson, CJohnson, C. A.Jollimore, C. A. Jonas, J. B.Jonescu-Cuypers, C.Jonescu-Cuypers, C. P.Jonescu-Cuypers, C.P. Joos, K. M. Kagemann, L. Kahn, H. A. Kaiser, H. J. Kappos, L. Kaps, M. Kashiwagi, K. Kass, M. A. Kastner, J. Katz, J. Katz, L. J. Kaufmann, A. Kaup, M. Keeffe, J. E. Kelly, M. E.Keltner, J. L. Kergoat, H. Kerr, J.Kerrigan, L. A.Khurana, R. K. Kimura, I. Kircher, K. Kiss, B. Kitazawa, Y. Klemm, M. Kloti, M.Knighton, R. W. Ko, Y. C. Kohner, E. M. Kolker, A. E. Komaroff, E. Konno, S. Koskosas, A. Krejcy, K.Krieglstein, G. K.Krishnamoorthy, R.Krishnamoorthy, R. R.Krueger, D. E. Kusuhara, A. Lachkar, Y. Lam, A. K.Langham, M. E.Langhans, M. J. Lanzl, I. Lanzl, I. M. Lau, J. Le, A.LeBlanc, R. P. Lee, A. A. Lesk, M. R. Leske, M. C.LeVatte, T. L. Levene, R. Z. Levin, L. A. Lexer, F. Liebmann, J Lienert, C. Liu, C. J. Liu, J. H. Loebl, M. Logan, J. F.Lovasik, J. V. Lubeck, P. Lung, S. Luscher, T. Lusky, M. Maeda, H. Maepea, O. Maggio, J. E. Maino, A. Manni, G. Mantyh, P. W. Mao, L. K. Marchini, G. Mardin, C. Y. Maren, K. Marraffa, M. Martin, B. Martin, B. J. Martini, E. Mashima, Y. Masini, E.Matthiessen, E. T.Maumenee, A. E. Maunder, L. Mavroudis, L.McCarty Ph, D. C. McCranor, L. McKinnon, S. Melamed, S.Metheetrairut, A. Michelson, G. Migdal, C. Migliardi, R.Mikelberg, F. S. Miller, J. P. Milton, R. C.Minckler, D. S. Morbio, R. Morgan, W. H. Mori, F. Moroz, I.Morrison, J. C.Morsman, C. D. Moster, M. R.Movaffaghy, A. Zi & 15295667484n 2004Jul-Aug\Association between nocturnal blood pressure reduction and progression of visual field defect in patients with primary open-angle glaucoma or normal-tension glaucoma 380-5}PURPOSE: To assess prospectively the relationship between nocturnal blood pressure reduction (dip) and progression of the visual field defect in patients with normal-tension glaucoma (NTG) or primary open-angle glaucoma (POAG). PATIENTS AND METHODS: The subjects studied were 38 patients with glaucoma (23 patients with NTG, 15 patients with POAG), in whom 48-h ambulatory blood pressure monitoring was conducted, who were followed for at least 4 years, and in whom reliable visual field tests were performed at least 5 times. The progression was determined by the mean deviation (MD) slope analysis system installed in the Humphrey field analyzer Statpac program. Glaucoma patients with a dip of <10% were assigned to the nondipper group, those with a dip of 10%-20% to the tipper group, and those with a dip of >20% to the extreme dipper group. The dipper group was defined as physiologic dippers, while the nondipper and the extreme dipper groups were defined as nonphysiologic dippers, to study the relationship between the disturbance of the dip and progression of the visual field defect. RESULTS: Thirteen patients showed significant progression, while 25 patients did not. There were no significant differences in the mean intraocular pressure and follow-up period between the patients with progression and those without progression. Half (7/14) of the nondippers, 20% (4/20) of the dippers, and 50% (2/4) of the extreme dippers showed progression, indicating a tendency of progression in the nondipper and the extreme dipper groups. The nonphysiologic dippers had a higher incidence of progression compared with the physiologic dippers (P = 0.05). Among the glaucoma patients in the nondipper and dipper categories only, those with progression had significantly smaller dips (P = 0.02). CONCLUSION: These results suggest that disturbance in the physiologic dip may be involved in the progression of glaucoma.'b\Department of Ophthalmology, University of Yamanashi, Faculty of Medicine, Yamanashi, Japan.F@Tokunaga, T. Kashiwagi, K. Tsumura, T. Taguchi, K. Tsukahara, S.(!0021-5155 (Print) Journal ArticleJpn J Ophthalmol*Blood Pressure Blood Pressure Monitoring, Ambulatory Circadian Rhythm Disease Progression Female Glaucoma, Open-Angle/*physiopathology Humans Hypotension/*physiopathology Intraocular Pressure Male Middle Aged Prospective Studies Vision Disorders/*physiopathology *Visual Fieldslehttp://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=1529566711222537423l 2001 Mar TNComparison of retinal transit times and retinal blood flow: a study in monkeys 752-5(JCPURPOSE. To determine the correlation between transit times of retinal blood flow calculated from fluorescein angiograms and retinal blood flow determined by the microsphere method. METHODS. Two fluorescein angiograms were obtained in each eye of six monkeys, followed by determination of retinal blood flow with labeled microspheres. Angiograms in 10 eyes were analyzed for mean transit time (MTT) and arteriovenous passage time (AVP). MTT was determined in two ways: from dye curves reconstructed by extrapolation of semilogarithmic plots of the recorded curves (MTT(slope)) and by a new technique based on an impulse-response analysis (MTT(ir)). RESULTS. Mean values (+/-SD) for retinal blood flow in 10 eyes were 23.2 +/- 6.9 mg/min. Corresponding values for MTT(ir), MTT(slope), and AVP were 2.22 +/- 0.38, 4.89 +/- 5.89, and 1.08 +/- 0.14 seconds. There was a weak, but not statistically significant, correlation between retinal blood flow and MTT(ir) (r = -0.60, P = 0.06) but no useful correlation between retinal blood flow and either MTT(slope) or AVP. CONCLUSIONS. The relationship between retinal blood flow and transit times determined from fluorescein angiograms is weak. Of the three transit parameters tested, MTT(ir), determined with the recently developed impulse-response technique, had the best correlation with retinal blood flow. Further studies are needed to determine the ability of these transit parameters to detect a change in retinal blood flow and the possibility that transit times may provide useful clinical information unrelated to absolute values of retinal blood flow.'haDepartment of Neuroscience, Ophthalmology, Uppsala University Hospital, S-701 85 Uppsala, Sweden.2+Tomic, L. Maepea, O. Sperber, G. O. Alm, A.(!0146-0404 (Print) Journal Article Invest Ophthalmol Vis SciAnimals *Blood Circulation Time Blood Flow Velocity/physiology Comparative Study Female Fluorescein Angiography Macaca fascicularis Male Microspheres Regional Blood Flow Research Support, Non-U.S. Gov't Retinal Vessels/*physiology Time Factorslehttp://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=1122253716815251 1421 2006 Jul~wAssociation of blood pressure status with the optic disk structure in non-glaucoma subjects: the Thessaloniki eye study 60-67PURPOSE: To study the association of blood pressure (BP) status on the optic disk structure as measured with the Heidelberg Retina Tomograph (HRT) in people without glaucoma. DESIGN: Cross-sectional population-based setting study. METHODS: Consecutive participants in the Thessaloniki Eye Study were included in this study. HRT images of the optic disk and BP measurements were taken. Hypertension was defined as a systolic BP (SBP) > or =140 mm Hg, diastolic BP (DBP) >/=90 mm Hg, or both. Subjects were classified in three groups by SBP and DBP. The Kruskal-Wallis test was used to compare the three groups with respect to the HRT parameters. Regression models adjusted for age, gender, height, disk size, intraocular pressure, cardiovascular disease, diabetes, and duration of antihypertensive treatment were used for each HRT parameter to compare values among the different groups. The P value was considered significant at <.05. RESULTS: A total of 232 subjects were included in the analysis. Rim area was significantly different among groups when DBP was considered as the criterion to classify subjects (P = .005). In regression models, cup area, and cup-to-disk (c/d) ratio were increased in subjects with normal DBP that was the result of treatment, as compared with both the high DBP and untreated normal DBP groups. CONCLUSIONS: In patients without glaucoma, the DBP <90 mm Hg that results from antihypertensive treatment is associated with increased cupping and decreased rim area of the optic disk. This information should be considered in research aiming to define the role of the BP status as an independent factor initiating optic disk changes and/or as a contributing factor to glaucoma damage.'voII Department of Ophthalmology, Aristotle University of Thessaloniki, Thessaloniki, Greece. ftopouzis@otenet.grTopouzis, F. Coleman, A. L. Harris, A. Jonescu-Cuypers, C. Yu, F. Mavroudis, L. Anastasopoulos, E. Pappas, T. Koskosas, A. Wilson, M. R.(!0002-9394 (Print) Journal ArticleAm J Ophthalmol6/Aged Antihypertensive Agents/therapeutic use Blood Pressure/*physiology Blood Pressure Determination Cross-Sectional Studies Diastole Female Greece Humans Hypertension/drug therapy/*physiopathology Male Middle Aged Nerve Fibers/drug effects Optic Disk/*pathology Research Support, Non-U.S. Gov't Systolelehttp://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=16815251rZY8A 10926980 129f6  2000 JunztInterocular difference in progression of glaucoma correlates with interocular differences in retrobulbar circulation 728-33B;PURPOSE:To evaluate the correlation between interocular difference in progression of glaucomatous damage and interocular differences in retrobulbar blood flow. METHODS:On the basis of a retrospective analysis of visual fields, progressive damage was identified in 20 patients with primary open-angle glaucoma. As a parameter of interocular difference in progression of visual field damage, the angle (gamma) between the regression lines of the visual field index mean defect over time per eye was calculated for each subject. The relationship between the angle gamma and interocular differences in intraocular pressure and retrobulbar color Doppler imaging parameters was analyzed by a multiple linear regression analysis in a stepwise forward approach. RESULTS:With larger interocular differences in progression of glaucomatous damage, lower mean blood flow velocities in the ophthalmic artery (partial r = -.69; P <. 0016), higher resistivity indices in the central retinal artery (partial r =.48; P <.0456), and higher peak systolic velocities in the ophthalmic artery (partial r =.52; P <.0285) were noted in the eyes with more marked progression of damage (multiple r =.71; P <. 0099). Interocular differences in progression of visual field damage were not related to intraocular pressure or extent of visual field damage. CONCLUSION:Independent of the extent of the interocular difference in glaucomatous damage and intraocular pressure, interocular difference in progression of glaucomatous visual field damage correlates with interocular difference in retrobulbar hemodynamic parameters.'0*University Eye Clinic, Basel, Switzerland.@9Schumann, J. Orgul, S. Gugleta, K. Dubler, B. Flammer, J.(!0002-9394 (Print) Journal ArticleAm J OphthalmolBlood Circulation Blood Flow Velocity Disease Progression Eye/*physiopathology/ultrasonography Glaucoma, Open-Angle/*physiopathology/ultrasonography Humans Intraocular Pressure Middle Aged Ophthalmic Artery/*physiopathology/ultrasonography Orbit/*blood supply/ultrasonography Retinal Artery/*physiopathology/ultrasonography Ultrasonography, Doppler, Color Vision Disorders/physiopathology Visual Fieldslehttp://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=10926980 7940145L38 Suppl 1994 MayDtmCirculatory defects of the optic disk and retina in ocular hypertension and high pressure open-angle glaucoma S23-34Studies using fluorescein angiography have shown that two types of circulatory defects occur in the optic disk and retina of open-angle glaucomatous eyes. The first is a defect of the microcirculation of the optic disk characterized as a fluorescein defect. Such defects begin as small areas of relatively little filling of the small vessels of the disk with fluorescein. The areas of defect show leakage for both fluorescein and indocyanine green. These defects increase in size and number with the progression of the disease. Fluorescein defects are significantly correlated with visual field loss and retinal nerve fiber layer loss. The second circulatory defect is a decrease of flow of fluorescein in the retinal vessels, especially the retinal veins, so that the greater the age, diastolic blood pressure, ocular pressure and visual field loss, the less the flow. Both the optic disk and retinal circulation defects occur in untreated ocular hypertensive eyes. These observations indicate that circulatory defects in the optic disk and retina occur in ocular hypertension and open-angle glaucoma and increase with the progression of the disease.'B;Tufts University School of Medicine, Boston, Massachusetts. Schwartz, B..(0039-6257 (Print) Journal Article ReviewSurv OphthalmolBlood Flow Velocity Glaucoma, Open-Angle/*physiopathology Humans *Intraocular Pressure Microcirculation Ocular Hypertension/*physiopathology Optic Disk/blood supply/*physiopathology Research Support, Non-U.S. Gov't Retinal Vessels/*physiopathology jdhttp://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=79401451246527247 Suppl 1 Pt 2 200282Retinal Vessel Analyzer (RVA)--design and function 678-81The Retinal Vessel Analyzer (RVA) is a measuring device for online measurement of the diameter of retinal vessels in relation to time and locations along the vessel. It is furthermore provided with several tools for analyzing the measured data. The fundamental components consist of a fundus camera with CCD measuring camera attached and an advanced image-processing unit. The measurement range is from 90 microns, temporal resolution is 40 ms and measurement resolution is less than 1 micron. Systematic error of non-linearity is S < or = 1.6%, reproducibility is given by variation coefficient: short term vcs = 1.5%, long term vcl = 2.8%.'81IMEDOS GmbH, Weimar, Germany. b.seifert@imedos.de Seifertl, B. U. Vilser, W.(!0013-5585 (Print) Journal ArticleBiomed Tech (Berl)ZSArtifacts Equipment Design *Fluorescein Angiography/*instrumentation Humans Image Processing, Computer-Assisted/*instrumentation Microcirculation/physiopathology Reproducibility of Results Research Support, Non-U.S. Gov't Retinal Diseases/*diagnosis/physiopathology Retinal Vessels/*pathology/physiopathology Vascular Resistance/physiologylehttp://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=124652728540553  120 6 1995 Deci.'The challenge of screening for glaucoma 793-5Shields, M. B.*#0002-9394 (Print) Comment EditorialAm J Ophthalmol^D=Glaucoma/*prevention & control Humans Mass Screening/*methodsAjdhttp://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=8540553) S 12271368 24029e 2002 Sep.~Effect of treatment by medicine or surgery on intraocular pressure and pulsatile ocular blood flow in normal-pressure glaucoma 721-6PURPOSE: To study the effect of trabeculectomy and monotherapy with topical betaxolol, brimonidine and latanoprost on intraocular pressure (IOP) and pulsatile ocular blood flow (POBF) in patients with normal-pressure glaucoma (NPG). METHODS: In this retrospective study NPG patients attending the glaucoma research unit at Moorfields Eye Hospital were reviewed. Patients treated by surgery or topical medication (betaxolol, brimonidine or latanoprost) who had pre- and post-treatment IOP and POBF measurements were studied. For those patients who were having treatment to both eyes, one eye was selected at random for analysis. RESULTS: A total of 147 patients were reviewed. Forty-three eyes were receiving betaxolol 0.5%, 58 eyes latanoprost 0.005%, 23 eyes brimonidine 0.2% and 23 eyes had undergone trabeculectomy surgery. There were more female than male patients in all four groups, and the groups were similar with regards age. Pre-treatment IOP and POBF values were similar among the groups ( P=0.27, P=0.08 respectively). Post-treatment IOP values tended to be lower than pre-treatment values for all four groups. All groups had an increased POBF except for betaxolol, where POBF decreased. CONCLUSION: Patients treated by trabeculectomy and those receiving topical latanoprost and brimonidine had lower IOP and higher POBF following treatment. The betaxolol-treated group, despite a slight decrease in IOP, had a decreased POBF. Lowering IOP by treatment may not necessarily be associated with an increase in POBF.'XQGlaucoma Research Unit, Moorfields Eye Hospital, City Road, London, EC1V 2PD, UK.eNHPoinoosawmy, D. Indar, A. Bunce, C. Garway-Heath, D. F. Hitchings, R. A.(!0721-832X (Print) Journal Articlee& Graefes Arch Clin Exp OphthalmolAdministration, Topical Aged Antihypertensive Agents/*therapeutic use Betaxolol/therapeutic use Blood Flow Velocity Comparative Study Eye/*blood supply Female Glaucoma, Open-Angle/*physiopathology/therapy Humans Intraocular Pressure/*drug effects Male Ophthalmic Solutions Prostaglandins F, Synthetic/therapeutic use Pulsatile Flow Quinoxalines/therapeutic use Retrospective Studies Tonometry, Ocular Trabeculectomy/*methodslehttp://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=12271368f110499568411 2000 Nov6/Evaluation of the Zeiss retinal vessel analyser 1285-90 ngAIM: To investigate the reproducibility and sensitivity of the Zeiss retinal vessel analyser, a new method for the online determination of retinal vessel diameters in healthy subjects. METHODS: Two model drugs were administered, a peripheral vasoconstrictor (the alpha receptor agonist phenylephrine) and a peripheral vasodilator (the nitric oxide donor sodium nitroprusside) in stepwise increasing doses. Nine healthy young subjects were studied in a placebo controlled double masked three way crossover design. Subjects received intravenous infusions of either placebo or stepwise increasing doses of phenylephrine (0.5, 1, or 2 microg/kg/min) or sodium nitroprusside (0.5, 1, or 2 microg/kg/min). Retinal vessel diameters were measured with the new Zeiss retinal vessel analyser. Retinal leucocyte velocity, flow, and density were measured with the blue field entoptic technique. The reproducibility of measurements was assessed with coefficients of variation and intraclass correlation coefficients. RESULTS: Placebo and phenylephrine did not influence retinal haemodynamics, although the alpha receptor antagonist significantly increased blood pressure. Sodium nitroprusside induced a significant increase in retinal venous and arterial diameters (p<0.001 each), leucocyte density (p=0.001), and leucocyte flow (p=0.024) despite lowering blood pressure to a significant degree. For venous and arterial vessel size measurements short term coefficients of variation were 1.3% and 2.6% and intraclass correlation coefficients were 0.98 and 0.96, respectively. The sensitivity was between 3% and 5% for retinal veins and 5% and 7% for retinal arteries. CONCLUSIONS: These data indicate that the Zeiss retinal vessel analyser is an accurate system for the assessment of retinal diameters in healthy subjects. In addition, nitric oxide appears to have a strong influence on retinal vascular tone.'RKDepartment of Clinical Pharmacology, University of Vienna, Vienna, Austria.ib\Polak, K. Dorner, G. Kiss, B. Polska, E. Findl, O. Rainer, G. Eichler, H. G. Schmetterer, L.RL0007-1161 (Print) Clinical Trial Journal Article Randomized Controlled TrialBr J Ophthalmol yAdrenergic alpha-Agonists/administration & dosage Adult Cross-Over Studies Humans Male Nitroprusside/administration & dosage Ophthalmology/*instrumentation Phenylephrine/administration & dosage Placebos Regional Blood Flow/drug effects/physiology Reproducibility of Results Retinal Vessels/anatomy & histology/drug effects/*physiology Vasodilator Agents/administration & dosage lehttp://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=11049956d12147608438r 2002 AugZTInfluence of flicker frequency on flicker-induced changes of retinal vessel diameter 2721-6TNPURPOSE: To investigate the effect of diffuse luminance flicker of different frequencies on retinal vessel diameter in the human eye. METHODS: Nine healthy subjects participated in the study. A retinal vessel analyzer (RVA; Zeiss, Jena, Germany) was modified to allow for continuous measurement of vessel diameter during flicker stimulation. With this technique, the light used for measurement of vessel diameter consists of wavelengths between 567 and 587 nm, whereas the spectrum of the stimulation is low-pass, with a cutoff wavelength at 550 nm. Flicker frequencies ranged from 2 to 64 Hz. RESULTS: In retinal arteries an increase was observed at all flicker frequencies, with a less-pronounced effect at 64 Hz. In retinal veins, all flicker frequencies except 2 and 64 Hz induced vasodilation. Generally, the flicker-induced diameter response was less pronounced in retinal veins than in arteries. CONCLUSIONS: The flicker-induced diameter response of the larger retinal arteries and veins can be continuously measured with a modified RVA system that spectrally separates the flicker stimulation from the fundus illumination light. Vasodilation of retinal arteries was observed in response to short wavelength flicker with frequencies between 2 and 64 Hz, indicating that the parvo- and magnocellular neural pathways are activated with this stimulation.'@:Institute of Research in Ophthalmology, Sion, Switzerland.,%Polak, K. Schmetterer, L. Riva, C. E. (!0146-0404 (Print) Journal Articled Invest Ophthalmol Vis SciaAdult Female Flicker Fusion/*physiology Humans Male Photic Stimulation Research Support, Non-U.S. Gov't Retinal Vessels/*physiology/*radiation effects Time Factors Vasodilation/*physiologylehttp://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=12147608LNGPrasanna, G. Krishnamoorthy, R. Hulet, C. Zhang, H. Zhang, X. Yorio, T.o 2000ngEndothelin-1 induces nitric oxide synthase-2 expression in human non-pigmented ciliary epithelial cellsr Exp Eye Resc715m 535-9y Novo11040089&Cells, Cultured Ciliary Body/*metabolism Colorimetry Endothelin-1/*physiology Gene Expression Humans Nitric Oxide Synthase/*metabolism Nitric Oxide Synthase Type II Pigment Epithelium of Eye/*metabolism Research Support, U.S. Gov't, P.H.S. Reverse Transcriptase Polymerase Chain Reaction0014-4835 (Print) Letterlehttp://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=11040089s  8759355379 1996 AugJCAn endothelin-1 induced model of optic nerve ischemia in the rabbit 1860-9jcPURPOSE. To evaluate blood flow reduction and topographic optic nerve changes after the local administration of endothelin-1 in vivo, delivered to the perineural region of the anterior optic nerve in the rabbit. METHODS. Endothelin-1 (five rabbits) in a dosage of 0.1 microgram/day or balanced salt solution (two rabbits) was delivered to the perineural region of the anterior optic nerve with osmotically driven minipumps. Optic nerve blood flow was determined by the colored microspheres technique after 14 days of local endothelin-1 or balanced salt solution administration to the microvasculature of the optic nerve. In addition, optic nerve blood flow was determined in two rabbits that had no minipump implants. The morphologic changes induced by reduction of blood flow were assessed in five additional rabbits implanted with osmotically driven minipumps containing endothelin-1 (0.1 microgram/day). These rabbits were observed for 8 weeks, and the morphologic optic nerve changes were monitored with a confocal scanning laser ophthalmoscope. RESULTS. Independent of intraocular pressure, endothelin-1 induced a decrease in blood flow of approximately 38% in the experimental eye, compared to the decrease induced by balanced salt solution or to the decrease in rabbits without minipumps (analysis of covariance, P = 0.0092). Multivariate statistical analysis showed a significant change in topometric parameters (cup area, cup depth, rim volume) obtained with a confocal scanning laser ophthalmoscope, indicating an increase in optic nerve cupping and a decrease of the perineural rim volume in the experimental eyes (P = 0.017). CONCLUSIONS. The current results suggest that morphologic optic nerve alterations can be induced experimentally in the rabbit model after ischemia produced by the local administration of endothelin-1 to the perineural region of the anterior optic nerve.'D=Devers Eye Institute, Legacy Portland Hospitals, Oregon, USA.LEOrgul, S. Cioffi, G. A. Wilson, D. J. Bacon, D. R. Van Buskirk, E. M.(!0146-0404 (Print) Journal Article Invest Ophthalmol Vis Sci~xAnimals Endothelins/*pharmacology Female Ischemia/chemically induced/*physiopathology Male Microcirculation/drug effects/physiology/physiopathology Microscopy, Confocal Microspheres Multivariate Analysis Optic Nerve/*blood supply/cytology/*drug effects Polystyrenes Rabbits Regional Blood Flow/drug effects Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S.jdhttp://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=8759355122189418t9m 2002 SepNjdElevated plasma endothelin-1 levels and vascular dysregulation in patients with rheumatoid arthritisCR616-9^voBACKGROUND: Contradictory results on plasma endothelin-1 (ET-1) levels in patients with rheumatoid arthritis have been reported in previous studies. We therefore evaluated whether plasma ET-1 levels in patients with rheumatoid arthritis differ from those of normal controls. Since systemically increased levels of ET-1 are known to occur in tandem with primary or secondary vascular dysregulation, we also measured peripheral blood flow by means of nailfold capillaroscopy combined with a cold provocation test. MATERIAL/METHODS: We measured plasma levels of ET-1 in twelve patients with different stages of rheumatoid arthritis by means of a specific radioimmunoassay, and compared ET-1 values to those of healthy controls. Capillary blood flow and the frequency of cold-induced vasospasm were studied in parallel, using nailfold capillaroscopy combined with a cold provocation test. RESULTS: Plasma ET-1 levels were significantly increased in patients with rheumatoid arthritis (p = 0.01) when compared to controls (2.38+/-0.95 pg/ml vs. 1.53+/-0.38 pg/ml). Capillary blood flow was reduced when compared to our own normal values, and a cold-induced blood standstill was seen in 58% of the patients. CONCLUSIONS: Patients with rheumatoid arthritis exhibit significantly elevated levels of ET-1, which may be associated with the symptoms of vascular dysregulation observed in nailfold capillaroscopy. Even though the clinical conclusions should be drawn from this study with caution, additional therapy with calcium channel blockers or, possibly in the future, with ET-1 receptor blockers, may be beneficial in patients with rheumatoid arthritis.'0*University Eye Clinic, Basel, Switzerland.XQPache, M. Schwarz, H. A. Kaiser, H. J. Wuest, P. Kloti, M. Dubler, B. Flammer, J.(!1234-1010 (Print) Journal Article Med Sci MonitAdult Aged Arthritis, Rheumatoid/*blood/pathology Case-Control Studies Endothelin-1/*blood Female Humans Male Microscopic Angioscopy Middle Aged Radioimmunoassay Regional Blood Flow Time Factorslehttp://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=12218941&Pache, M. Nagel, E. Flammer, J.a 2002`YReproducibility of measurements with the retinal vessel analyzer under optimal conditionse Klin Monatsbl Augenheilkd  219b7 523-7 Julc$`ZReproduzierbarkeit der Messungen mit dem Retinal Vessel Analyzer unter Optimalbedingungen.12195319Adult English Abstract Female Homeostasis/physiology Humans Image Processing, Computer-Assisted/*instrumentation Male *Online Systems *Ophthalmoscopes Oxygen/blood Reference Values Retinal Artery/*anatomy & histology Retinal Vein/*anatomy & histologyBACKGOUND: To evaluate the reproducibility of measurements with the Retinal Vessel Analyzer (RVA) in healthy subjects and to describe which measuring conditions should be guaranteed to obtain optimal results. METHODS: The diameter of retinal arteries and veins of 20 healthy subjects (M : F = 11 : 9; mean age: 33 +/- 12 years) were measured with the RVA at baseline, after 2 hours, and after 2 weeks. RESULTS: No statistically significant differences in the diameter of retinal arteries and veins between the single measurements were present. Short-term variability of arterial diameter was 1 %, and the intraclass correlation coefficient kappa was 0.96. Long-term variability was 1.8 %, kappa was 0.98. In retinal veins, a short-term variability of 1 % was calculated, with a kappa of 0.97. Long-term variability was 1.5 %, with a kappa of 0.98. CONCLUSION: Due to the high reproducibility of its measurements, the RVA appears to be a useful device for both analysis and follow-up of retinal vessel diameters.o(!0023-2165 (Print) Journal Articleolehttp://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=12195319r'.(Universitats-Augenklinik Basel, Germany.qb P :14648137 242n1s 2004 Jan.rlAutoregulative behavior of retinal arteries and veins during changes of perfusion pressure: a clinical study 13-7&PURPOSE: To investigate the autoregulative response of large retinal vessels to artificial reduction of perfusion pressure. METHODS: The diameters of a venous and an arterial segment (each approx.1.5 mm in length) in one eye of each of 13 healthy volunteers (age 54.5+/-18 years) were measured continuously using the Retinal Vessel Analyzer (Imedos, Weimar, Germany). The intraocular pressure (IOP; mean before examination 13.7+/-2.9 mmHg) was increased by 21.2+/-3.5 mmHg by means of a suction cup in order to produce a temporary reduction of the retinal perfusion pressure. The RVA measurements were taken for 2 min without artificial intervention (baseline), for 100 s during IOP elevation, and for up to 10 min after removal of the suction cup. RESULTS: A significant response of arterial and venous diameters to the provocation was found ( P<0.02, ANOVA). The arterial and venous responses were opposite: Whereas the artificially elevated IOP increased the arterial diameter by +1.9+/-4.5%, the venous vessel diameter decreased by -2.6+/-3.5% ( P<0.02, Mann-Whitney U-test). After normalization of the IOP the arterial diameter fell slightly below the baseline value, while the veins underwent temporary dilation by +5.9+/-3.3% ( P<0.001). The mean systemic blood pressure did not change significantly during the investigation. CONCLUSION: Retinal arteries and veins of healthy volunteers exhibited opposite autoregulative behavior in response to perfusion pressure changes. This is believed to be due to the different regulative functions of arteries and veins.'rlRudolstadt Ophthalmology Practice, Anton-Sommer-Strasse 55, 07407 Rudolstadt, Germany. e_a_nagel@t-online.deNagel, E. Vilser, W.(!0721-832X (Print) Journal Article& Graefes Arch Clin Exp OphthalmolBlood Pressure/physiology Diagnostic Techniques, Ophthalmological Female Homeostasis/*physiology Humans Intraocular Pressure/physiology Male Middle Aged Perfusion Pressure Regional Blood Flow/physiology Retinal Artery/*physiology Retinal Vein/*physiology Vasodilation/physiologylehttp://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=14648137n15814471302t 2005 FebpDorzolamide influences the autoregulation of major retinal vessels caused by artificial intraocular pressure elevation in patients with POAG: a clinical study 129-37PURPOSE: The study investigated whether dorzolamide influences the autoregulatory behavior of major retinal arterioles in glaucoma patients via a moderate perfusion pressure reduction. METHODS: The study included one eye each of 12 untreated patients with a primary open-angle glaucoma (POAG) (age 60.8 +/- 8.3, IOP 22.3 +/- 6.5 mmHg). Changes in the diameter of a retinal artery segment before (120 s), during (100 s), and after (380 s) artificial IOP elevation to 38 mmHg for 100 s were recorded continuously by means of a Retinal Vessel Analyzer. The measurement was repeated after 4-week treatment with dorzolamide eye drops t.i.d. RESULTS: Ocular perfusion pressure (mmHg) was reduced by the intraocular pressure (IOP) elevation from 58 (+/- 10) to 41 (+/- 11) in the pretreatment examination and from 60 (+/- 8) to 40 (+/- 8) posttreatment (differences between the examinations n.s.). Before IOP elevation, the arterial diameter was found to be +1.7 +/- 3.5% greater in the posttreated eyes than in the pretreated eyes (p < 0.02). During IOP elevation, the arterial diameter decreased by -1.8% +/- 3.8 in the pretreated eyes, whereas dilatation by +1.4% +/- 2.5 was observed in the posttreated eyes (p = 0.02). At the end of the observation period following IOP elevation, the vessel diameter in the pretreated eyes had increased by +1.8% +/- 4.2, whereas in the posttreated eyes it had decreased by -1.7% +/- 3.0. On average, dorzolamide reduced IOP by -5.6 mmHg (p = 0.001). CONCLUSIONS: The arterial diameter dilatation during IOP elevation in dorzolamide-treated eyes could be an accelerated counter-regulation on the induced elevated IOP and could constitute an additional therapeutic effect.'TNRudolstadt Ophthalmologic Practice, Rudolstadt, Germany. e_a_nagel@t-online.de$Nagel, E. Vilser, W. Lanzl, I.600271-3683 (Print) Clinical Trial Journal Article Curr Eye ResAged Blood Pressure Carbonic Anhydrase Inhibitors/*therapeutic use Female Glaucoma, Open-Angle/*drug therapy/*physiopathology Homeostasis/physiology Humans *Intraocular Pressure Male Middle Aged Muscle, Smooth, Vascular/physiopathology Ocular Hypertension/physiopathology Ophthalmic Solutions Retinal Artery/*physiopathology Sulfonamides/*therapeutic use Thiophenes/*therapeutic use Vasodilationilehttp://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=15814471t16876523 142 2o 2006 AugtrkAgreement of rebound tonometer in measuring intraocular pressure with three types of applanation tonometersn 332-4PURPOSE: To evaluate the agreement of iCare rebound tonometer in measuring intraocular pressure (IOP) with Goldmann applanation tonometer (GAT), Tonopen XL, and noncontact tonometer, and the influence of the central corneal thickness (CCT) on IOP measurements made with these four tonometers in 45 (12 control and 33 glaucomatous or ocular hypertensive) eyes. DESIGN: Clinically relevant experimental study. METHODS: Tonometer intermethod agreement was assessed by the Bland-Altman method. The relations of CCT with absolute IOP values and intertonometer differences were analyzed by linear regression. RESULTS: The mean differences (95% limits of agreement) in IOP readings between iCare and GAT, Tonopen XL, and noncontact tonometer were 1.40 +/- 4.29, 0.00 +/- 4.78, and 2.22 +/- 4.19 mm Hg, respectively. All tonometries had a marked association with CCT. As the CCT got thicker, iCare considerably overestimated GAT and Tonopen XL. CONCLUSIONS: Although influenced by CCT, iCare agrees well with applanation tonometers.'~wDivision of Ophthalmology, Department of Organs Therapeutics, Kobe University Graduate School of Medicine, Kobe, Japan.VONakamura, M. Darhad, U. Tatsumi, Y. Fujioka, M. Kusuhara, A. Maeda, H. Negi, A.(!0002-9394 (Print) Journal ArticleAm J Ophthalmol*$Adult Aged Aged, 80 and over Comparative Study Cornea/pathology Female Glaucoma/*physiopathology Humans Intraocular Pressure/*physiology Male Middle Aged Ocular Hypertension/physiopathology Reproducibility of Results Research Support, Non-U.S. Gov't Tonometry, Ocular/instrumentation/*methodslehttp://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=16876523p 98782181675 1998 NovHBBlood flow in the human optic nerve head during isometric exercise 561-8RLInvestigating blood flow autoregulation in the optic nerve is important to understand the physiopathology of various ocular diseases such as glaucoma. This investigation requires that one establishes the relationship between optic nerve blood flow and perfusion pressure. Previous work has documented the effect of lowering the perfusion pressure on optic nerve blood flow. The purpose of the present study was to investigate the effect of elevated perfusion pressure on blood flow in this tissue. Laser Doppler flowmetry was applied to measure relative mean velocity, volume and flux of red blood cells in the tissue of the optic nerve head. These parameters were measured in 13 subjects during isometric exercise consisting of squatting. In the range of perfusion pressures from 56+/-4 to 80+/-5 mmHg (30+/-8%), there was no significant variation of mean velocity, volume and flux of red blood cells, but vascular resistance increased by about 50%. Intraocular pressure was increased significantly above baseline at the end of squatting and decreased during recovery. The results suggest that the maintenance of constant blood flow is achieved by an increase in vascular resistance taking place either at the arterioles feeding or at the veins draining the blood from the ONH or at the ophthalmic artery and/or vessels between this artery and the site of LDF measurements. Combining the results of this study with those of a previous one where perfusion pressure was decreased by increasing the intraocular pressure, we show the entire relationship between perfusion pressure and optic nerve blood flow in man.'@:Institut de Recherche en Ophtalmologie, Sion, Switzerland.<6Movaffaghy, A. Chamot, S. R. Petrig, B. L. Riva, C. E.(!0014-4835 (Print) Journal Article Exp Eye ResAdolescent Adult Exercise/*physiology Homeostasis/physiology Humans Intraocular Pressure/physiology Laser-Doppler Flowmetry Middle Aged Optic Disk/*blood supply Pulsatile Flow/physiology Regional Blood Flow Research Support, Non-U.S. Gov't Vascular Resistance/physiologyjdhttp://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=9878218$Munch, K. Vilser, W. Senff, I. 1995PIAdaptive algorithm for automatic measurement of retinal vascular diameter Biomed Tech (Berl)4011 322-5 Nov$RKAdaptive Algorithmen zur automatischen Messung retinaler Gefassdurchmesser.8580285*Algorithms English Abstract Humans Image Processing, Computer-Assisted/*instrumentation *Ophthalmoscopes Reference Standards Reproducibility of Results Research Support, Non-U.S. Gov't Retinal Artery/anatomy & histology Retinal Vessels/*anatomy & histology,A new adaptive computer-aided method for the measurement of blood vessel diameters has been developed. Within areas of interest in the image, the algorithm detects, line-wise, the edges of the vessels, which are then used for image-wise approximation and noise filtration. A high level of adaptivity with respect to numerous measuring parameters ensures its use in a wide range of applications. Thus, it has been shown to significantly improve clinically relevant reproducibility in the area of follow-up observations. The standard deviation for vessel diameter was (2.2 +/- 0.7)% in the case of arteries and (1.8 +/- 0.5)% in the case of veins. Testing the algorithm in images of poor quality revealed its high level of reliability and sensitivity.R(!0013-5585 (Print) Journal Article jdhttp://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=8580285'F?Augenklinik des Klinikums, Friedrich-Schiller-Universitat Jena.211820304114 2001Oct-Decf`Retinal vessel reaction to short-term IOP elevation in ocular hypertensive and glaucoma patients 338-44PURPOSE: Regulation of ocular blood flow might be impaired in glaucoma patients. We compared the reaction of retinal vessels to a short-term increase of intraocular pressure (IOP), using a retinal vessel analyzer (RVA), in normal volunteers, ocular hypertensive patients (OH) and primary open angle glaucoma patients (POAG). METHODS: Ten healthy subjects (56+/-8 years, IOP 13.7+/-1.6 mmHg), 10 OH patients (55+/-12 years, IOD 23.4+/-4.1 mmHg) and 11 POAG patients (60+/-11 years, IOP 23.3+/-1.95 mmHg) were evaluated. Arterial and venous retinal vessel diameter was measured continuously before, during and after raising IOP to suprasystolic values by the suction cup method, described as ocular oscillo-dynamography. RESULTS: The change in vessel diameter after the IOP rise differed in its temporal sequence and in absolute values depending on the group examined. In the retinal branch veins the reduction of vessel diameter during the IOP rise was significantly different in POAG (0%+/-6.7) and volunteers (-6.7%+/-8.5; p = 0.06) and in POAG and OH (-6.7%+/-7.0; p = 0.04). At 70-130 sec after IOP increase a dilatation occurred, again differing significantly in POAG (+5.8%+/-3.9) and volunteers (+9.7%+/-4.3; p = 0.03). Systemic blood pressure did not show any significant differences between groups or during the course of the examination. DISCUSSION: At short-term rise in IOP leads to less retinal vessel reaction in POAG patients than in volunteers and OH. This might be due to impaired autoregulation to ocular perfusion changes in POAG patients.'D=Technical University, Ilmenau, Germany. e_a_nagel@t-online.de(!Nagel, E. Vilser, W. Lanzl, I. M.(!1120-6721 (Print) Journal ArticleEur J OphthalmolBlood Flow Velocity Blood Pressure Comparative Study Glaucoma, Open-Angle/*physiopathology Homeostasis Humans *Intraocular Pressure Middle Aged Ocular Hypertension/physiopathology Ophthalmodynamometry Retinal Vessels/*physiopathologylehttp://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=11820304P4 H1559386u111a 1992 JaneLong-term effect of ophthalmic beta-adrenoceptor antagonists on intraocular pressure and retinal sensitivity in primary open-angle glaucoma 1-3^Timolol (TIM) and betaxolol (BET) were evaluated for their effects on both intraocular pressure and retinal sensitivity as determined from visual fields in a randomized two-year parallel study in 20 patients with primary open-angle glaucoma. All treatments were twice-daily in both eyes. TIM was more effective than BET as an ocular hypotensive agent throughout the two year period. With regard to retinal sensitivity as measured by automated visual fields, there was a decrease in retinal sensitivity in the first six months in the TIM and BET treatment groups by 0.5-0.6 dB, and 0.2-0.3 dB, respectively. However, at the one and two year visits, retinal sensitivity increased 0.8-0.9 dB in the BET treatment group only. It appears that ocular hypotensive efficacy may not relate to retinal sensitivity within a period of two years or less in patients with mildly to moderately elevated intraocular pressure. Further work may reveal the reliability of this observation, and its clinical relevance.'>7Service of Ophthalmology, University of Liege, Belgium.Collignon-Brach, J.RL0271-3683 (Print) Clinical Trial Journal Article Randomized Controlled Trial Curr Eye Resf_Aged Betaxolol/*therapeutic use Comparative Study Female Glaucoma, Open-Angle/*drug therapy/physiopathology Humans Intraocular Pressure/*drug effects Longitudinal Studies Male Middle Aged Random Allocation Research Support, Non-U.S. Gov't Retina/*physiopathology Sensory Thresholds Timolol/*therapeutic use Tonometry, Ocular Visual Fields/drug effects8jdhttp://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=155938614575724226 2003 NovPIThe effects of antiglaucoma and systemic medications on ocular blood flow769-805B;Based on the body of evidence implicating ocular blood flow disturbances in the pathogenesis of glaucoma, there is great interest in the investigation of the effects of antiglaucoma drugs and systemic medications on the various ocular vascular beds. The primary aim of this article was to review the current data available on the effects of antiglaucoma drugs and systemic medications on ocular blood flow. We performed a literature search in November 2002, which consisted of a textword search in MEDLINE for the years 1968-2002. The results of this review suggest that there is a severe lack of well-designed long-term studies investigating the effects of antiglaucoma and systemic medications on ocular blood flow in glaucomatous patients. However, among the 136 articles dealing with the effect of antiglaucoma drugs on ocular blood flow, only 36 (26.5%) investigated the effects of medications on glaucoma patients. Among these 36 articles, only 3 (8.3%) were long-term studies, and only 16 (44.4%) were double-masked, randomized, prospective trials. Among the 33 articles describing the effects of systemic medications on ocular blood flow, only 11 (33.3%) investigated glaucoma patients, of which only one (9.1%) was a double-masked, randomized, prospective trial. Based on this preliminary data, we would intimate that few antiglaucoma medications have the potential to directly improve ocular blood flow. Unoprostone appears to have a reproducible antiendothelin-1 effect, betaxolol may exert a calcium-channel blocker action, apraclonidine consistently leads to anterior segment vasoconstriction, and carbonic anhydrase inhibitors seem to accelerate the retinal circulation. Longitudinal, prospective, randomized trials are needed to investigate the effects of vasoactive substances with no hypotensive effect on the progression of glaucoma.'piGlaucoma Service, University of Campinas, Rua Bauru, 40, Sao Paulo 01248-010, Brazil. vp.costa@uol.com.br~wCosta, V. P. Harris, A. Stefansson, E. Flammer, J. Krieglstein, G. K. Orzalesi, N. Heijl, A. Renard, J. P. Serra, L. M..(1350-9462 (Print) Journal Article ReviewProg Retin Eye ResEye/*blood supply/metabolism Glaucoma/*drug therapy/physiopathology Humans Pharmacokinetics Pharmacology Regional Blood Flow/drug effectslehttp://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=1457572411015035326. 2000Nov-Dec{D>Regulatory mechanisms in the retinal and choroidal circulation 249-56The retina receives its nutrients from two separate circulations: retinal and choroidal circulation. This short overview describes the determinants in the regulation of these circulations. Retinal circulation is characterized by a low blood flow while flow in the choroid is high. The choroidal circulation is mainly controlled by sympathetic innervation and is not autoregulated. Retinal circulation lacks autonomic innervation, shows an efficient autoregulation and is mainly influenced by local factors. Local mediators released by endothelial cells and surrounding retinal tissue also have a substantial role in the regulation of retinal circulation.'PJDepartment of Physiology and Physiopathology, University of Gent, Belgium."Delaey, C. Van De Voorde, J..(0030-3747 (Print) Journal Article ReviewOphthalmic ResAnimals Arteries/physiology Blood Circulation/physiology Choroid/*blood supply Homeostasis Humans Muscle, Smooth, Vascular/innervation Regional Blood Flow/physiology Retinal Artery/innervation/*physiology Sympathetic Nervous System/physiologylehttp://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=11015035m8188062 2323 1994 MarxrReliability of intraocular pressure measurement with the Goldmann applanation tonometer in epidemiological studies 141-4(!The reproducibility of intraocular pressure (IOP) measurement with the Goldmann applanation tonometer was investigated as part of a population-based epidemiological study. Sixty-two subjects were examined in a first measurement session. The IOP was measured three times consecutively in both eyes according to a fixed protocol. The mean standard deviation (SD) of these measurements was 0.8 mmHg. The mean intraobserver variation for the first measurement was 1.64 (SD 2.07) mmHg. For the median of the three measurements the intra-observer variation was 1.50 (SD 1.96) mmHg. The mean inter-observer values were 1.79 (SD 2.41) mmHg for the first measurement and 1.60 (SD 2.15) mmHg for the median measurement. The correlation coefficient between the median values of the three measurements of both observers was 0.81. No systematic differences were found between the two observers. Using the median value of three consecutive measurements reduced the inter-observer variation by 11% and the intra-observer variation by 9% compared with a single measurement.'b[Department of Ophthalmology, Erasmus University Medical School, Rotterdam, The Netherlands.NHDielemans, I. Vingerling, J. R. Hofman, A. Grobbee, D. E. de Jong, P. T.(!0721-832X (Print) Journal Article& Graefes Arch Clin Exp OphthalmolAged Comparative Study Female Glaucoma/diagnosis/*epidemiology Humans *Intraocular Pressure Male Middle Aged Netherlands/epidemiology Observer Variation Reproducibility of Results Research Support, Non-U.S. Gov't Tonometry, Ocular/instrumentation/*methods jdhttp://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=8188062ber of patients with etiologically unexplained visual field loss, a vasospastic syndrome could be found with the help of a capillaroscopic local cooling test on the fingers. In the patients with proven vasospastic syndrome, the visual field defects were increased after a cold water test and decreased after a therapy with calcium entry blockers. General aspects of the physiology and pathophysiology of the circulation and especially of the circulation in the eye are presented.t'0)University Eye Clinic, Bern, Switzerland.nGasser, P. Flammer, J..(0012-4486 (Print) Journal Article ReviewDoc Ophthalmol("Calcium Channel Blockers/therapeutic use Eye/blood supply Humans Ischemic Attack, Transient/complications/*physiopathology Models, Theoretical Regional Blood Flow Research Support, Non-U.S. Gov't Syndrome Vascular Diseases/complications/drug therapy/*physiopathology Vasoconstriction Visionjdhttp://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=3322745| | j151482078860 2004 JunfXQNitric oxide proxies and ocular perfusion pressure in primary open angle glaucomai 757-60 BACKGROUND: To investigate the levels of nitric oxide (NO) markers in plasma and aqueous humour of patients with primary open angle glaucoma (POAG) and their relation to ocular perfusion pressure. METHODS: Cyclic guanosine monophosphate (cGMP) and nitrite (NO(2)(-)) were determined in plasma and aqueous humour of 38 patients with POAG and 46 controls. Blood pressure and IOP were measured to calculate ocular perfusion pressure (PP). RESULTS: cGMP and NO(2)(-) plasma levels were significantly decreased in glaucoma patients compared with controls (p = 0.001 v p = 0.004). In the aqueous humour of subjects with POAG, cGMP and NO(2)(-) concentrations were also lower than in normal eyes (p = 0.0001 v p = 0.001). There was a linear association between cGMP in plasma and aqueous humour in glaucomas and controls (r = 0.514, p = 0.029 and r = 0.558, p = 0.004) and this relation differed in the two groups (p = 0.003). Considering glaucoma patients with controls, a positive correlation was found between cGMP and PP (r = 0.379, p = 0.01) and between NO(2)(-) and PP (r = 0.339, p = 0.040). The cGMP/PP correlation was of borderline statistical significance in controls (p = 0.050), whereas it did not attain statistical significance in POAG, as well as the association between NO(2)(-) and PP when glaucomas and controls were considered separately. CONCLUSIONS: The authors found alterations of NO markers in the plasma and aqueous humour of glaucoma patients. Primary or secondary impaired NO balance could alter ocular perfusion pressure.'Department of Oto-Neuro-Ophthalmological Sciences, University of Florence, Eye Unit II, Florence, Italy. fernando.galassi@unifi.itHAGalassi, F. Renieri, G. Sodi, A. Ucci, F. Vannozzi, L. Masini, E.n(!0007-1161 (Print) Journal ArticletBr J OphthalmolmLFAged Aqueous Humor/*chemistry Biological Markers/analysis/blood Case-Control Studies Chemotherapy, Cancer, Regional Perfusion Cyclic GMP/*analysis/blood Female Glaucoma, Open-Angle/blood/*metabolism Humans Intraocular Pressure Male Middle Aged Nitric Oxide/*metabolism Nitrites/*analysis/blood Research Support, Non-U.S. Gov'tlehttp://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=1514820715226664134; 2004 Aug{lfResponse of retinal vessel diameters to flicker stimulation in patients with early open angle glaucoma 340-4_JCINTRODUCTION: Diffuse luminance flicker increases retinal vessel diameters in animals and humans, indicating the ability of the retina to adapt to different metabolic demands. The current study seeks to clarify whether flicker-induced vasodilatation of retinal vessels is diminished in glaucoma patients. METHODS: Thirty-one patients with early stage glaucoma (washout for antiglaucoma medication) and 31 age- and sex- matched healthy volunteers were included in the study. Retinal vessel diameters were measured continuously with a Retinal Vessel Analyzer. During these measurements three episodes of square wave flicker stimulation periods (16, 32, and 64 secs; 8 Hz) were applied through the illumination pathway of the retinal vessel analyser. RESULTS: Flicker-induced vasodilatation in retinal veins was significantly diminished in glaucoma patients as compared with healthy volunteers (ANOVA, P < 0.01). In healthy volunteers, retinal venous vessel diameters increased by 1.1 +/- 1.8% (16 seconds, P < 0.001), 2.0 +/- 2.6 (32 seconds, P < 0.001), and 2.1 +/- 2.1% (64 seconds, P < 0.001) during flicker stimulation. In glaucoma patients, venous vessel diameters increased by 0.2 +/- 1.7% (16 seconds, P < 0.6), 1.1 +/- 2.1% (32 seconds, P < 0.01), and 0.8 +/- 2.5 (64 seconds, P < 0.09). In retinal arteries, no significant difference in flicker response was noticed between the two groups (ANOVA, P < 0.6). In healthy controls, flicker stimulation increased retinal arterial vessel diameters by 1.0 +/- 2.4% (P < 0.03), 1.6 +/-3.2% (P < 0.004) and 2.4 +/- 2.6% (P < 0.001) during 16, 32, and 64 seconds of flicker, respectively. In glaucoma patients, flickering light changed arterial vessel diameters by 0.3 +/-2.6% (16 seconds, P = 0.4), 1.3 +/-3.1% (32 seconds, P = 0.03), and 1.8 +/- 3.8% (64 seconds, P = 0.005). CONCLUSION: Flicker-induced vasodilatation of retinal veins is significantly diminished in patients with glaucoma compared with healthy volunteers. This indicates that regulation of retinal vascular tone is impaired in patients with early glaucoma, independently of antiglaucoma medication.o'd]Department of Clinical Pharmacology, University of Vienna, Austria. guido.dorner@univie.ac.atrTNGarhofer, G. Zawinka, C. Resch, H. Huemer, K. H. Schmetterer, L. Dorner, G. T.(!1057-0829 (Print) Journal Articlec J GlaucomahbAged Blood Pressure Diagnostic Techniques, Ophthalmological Female Glaucoma, Open-Angle/*physiopathology Humans Intraocular Pressure Male Photic Stimulation/*methods Research Support, Non-U.S. Gov't Retinal Artery/*physiopathology/radiation effects Retinal Vein/*physiopathology/radiation effects Vasodilation/*physiology Vasomotor System/physiopathologylehttp://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=15226664i15851574465g 2005 MayShort-term increase of intraocular pressure does not alter the response of retinal and optic nerve head blood flow to flicker stimulation_ 1721-5XRPURPOSE: It has been shown that stimulation with diffuse luminance flicker induces vasodilatation in the human retina and increases optic nerve head (ONH) blood flow. The present study was designed to investigate the influence of a short-term increase in intraocular pressure on flicker-induced changes in ONH blood flow and retinal vessel diameters. METHODS: In a group of 15 healthy volunteers, IOP was increased by the episcleral suction cup technique. ONH blood flow was assessed with a laser Doppler flowmeter, and retinal vessel diameters were measured with the retinal vessel analyzer. Flicker responses of retinal vessel diameters and ONH blood flow were determined at baseline conditions and during suction of 70 and 140 mm Hg. Flicker light consisted of 8-Hz square-wave flashes at a wavelength below 550 nm and produced a retinal irradiance of 140 muW/cm(2). RESULTS: Suction increased IOP from 12 +/- 2 to 27 +/- 4 mm Hg and 43 +/- 4 mm Hg. Stimulation with diffuse luminance flicker induced an increase in ONH blood flow of +24.0% +/- 20.7%. Increased IOP did not significantly change the flicker response in the ONH (+19.3% +/- 26.6% and +22.1% +/- 25.1%). In retinal veins, flicker induced an increase in vessel diameter of +3.0% +/- 2.0%. Flicker responses in retinal veins were not significantly altered after the IOP was increased, compared with those recorded at baseline IOP (+2.8% +/- 2.5% and +3.2% +/- 2.2%). The flicker response in retinal arteries at baseline IOP was +3.5% +/- 2.0%. Again, the increase in IOP did not significantly alter this flicker response (+2.8% +/- 1.6% and +3.1% +/- 2.4%). CONCLUSIONS: A short-term increase in IOP does not alter the response of retinal vessel diameters and ONH blood flow to diffuse luminance flicker, which indicates that increased IOP does not alter retinal or ONH regulation during neuronal stimulation.'zsDepartments of Clinical Pharmacology, Medical University of Vienna, Wahringer Gurtel 18-20, A-1090 Vienna, Austria.NGGarhofer, G. Resch, H. Weigert, G. Lung, S. Simader, C. Schmetterer, L.(!0146-0404 (Print) Journal Article Invest Ophthalmol Vis Sci Blood Flow Velocity Blood Pressure Hemodynamic Processes Humans *Intraocular Pressure Laser-Doppler Flowmetry Male Ocular Hypertension/*physiopathology Optic Disk/*blood supply *Photic Stimulation Regional Blood Flow/physiology Retina/*radiation effects Retinal Vessels/*physiologylehttp://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=158515743322745t661i 1987 Mayd0)Influence of vasospasm on visual functionm 3-18In a number of patients with etiologically unexplained visual field loss, a vasospastic syndrome could be found with the help of a capillaroscopic local cooling test on the fingers. In the patients with proven vasospastic syndrome, the visual field defects were increased after a cold water test and decreased after a therapy with calcium entry blockers. General aspects of the physiology and pathophysiology of the circulation and especially of the circulation in the eye are presented.t'0)University Eye Clinic, Bern, Switzerland.nGasser, P. Flammer, J..(0012-4486 (Print) Journal Article ReviewDoc Ophthalmol("Calcium Channel Blockers/therapeutic use Eye/blood supply Humans Ischemic Attack, Transient/complications/*physiopathology Models, Theoretical Regional Blood Flow Research Support, Non-U.S. Gov't Syndrome Vascular Diseases/complications/drug therapy/*physiopathology Vasoconstriction Visionjdhttp://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=3322745mU n78489757811 1994 Novd>7Effect of trabeculectomy on pulsatile ocular blood flowc 818-22Trabeculectomy, despite producing an effective reduction in intraocular pressure, may not prevent continued visual field loss. This may be because of the presence of other factors in the pathogenesis of glaucoma. Vascular factors have been suggested as being particularly important. To study the effect of trabeculectomy on ocular blood flow the technique of ocular pulse analysis has been used to derive a measure of pulsatile ocular blood flow in 17 patients (average age 65.6 (SD 1.8) years) undergoing trabeculectomy. A significant increase in pulsatile ocular blood flow of 29% was observed in the group as a whole in the standing position following operation but in some individuals blood flow changed only slightly despite a large reduction in intraocular pressure. The significance of these findings in relation to the prognosis of visual field preservation following trabeculectomy is discussed.'leDivision of Pharmacological Sciences and Toxicology, United Medical School of Guy's Hospital, London.u James, C. B.(!0007-1161 (Print) Journal ArticleoBr J Ophthalmols<5Aged Blood Flow Velocity Blood Pressure Eye/*blood supply Female Glaucoma, Open-Angle/physiopathology/surgery Heart Rate Humans Intraocular Pressure/physiology Male Middle Aged Postoperative Period Posture/physiology Pulsatile Flow/*physiology Pulse/physiology Research Support, Non-U.S. Gov't *Trabeculectomy jdhttp://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=784897515606472826 2004 DecA comparison of the effects of dorzolamide/timolol fixed combination versus latanoprost on intraocular pressure and pulsatile ocular blood flow in primary open-angle glaucoma patientsi 730-7t PURPOSE: To evaluate the effects of dorzolamide/timolol fixed combination (D/T) compared to latanoprost on intraocular pressure (IOP) and pulsatile ocular blood flow (POBF) in primary open-angle glaucoma (POAG) patients. METHODS: Thirty patients with POAG were randomized in an open-label, cross-over study. Intraocular pressure reduction was achieved by 4 weeks medical therapy with D/T twice daily or latanoprost 0.005% dosed once in the evening. During a 4-week run-in and a 4-week wash-out period between study arms, patients ceased use of all other glaucoma medications and used timolol maleate 0.5% twice daily. Primary efficacy variables were IOP and POBF. RESULTS: There was no difference in baseline IOP and POBF parameters between the two study arms. Both D/T and latanoprost statistically significantly reduced IOP by 4.6 mmHg (p < 0.0001) and 3.75 mmHg (p < 0.0001) and increased POBF by 2.048 microl/second (p = 0.0030) and 2.147 microl/second (p = 0.0009), respectively. Repeated measures anova detected significant changes in POBF with treatment (p = 0.0361). Dorzolamide/timolol fixed combination statistically significantly increased pulse volume by 0.767 microl (p = 0.0087), while latanoprost therapy had no significant effect (p = 0.2407). CONCLUSIONS: Both drugs had similar effects in terms of IOP reduction. Dorzolamide/timolol significantly increased pulse volume while latanoprost had no effect. Further studies are necessary to establish whether the enhancement of choroidal blood flow can prevent glaucoma progression.k'TNEye Clinic of Kaunas University of Medicine, Kaunas, Lithuania. ingrida@kmu.ltHAJanuleviciene, I. Harris, A. Kagemann, L. Siesky, B. McCranor, L.rRL1395-3907 (Print) Clinical Trial Journal Article Randomized Controlled TrialActa Ophthalmol ScandnAdult Aged Antihypertensive Agents/administration & dosage/*therapeutic use Blood Flow Velocity/drug effects Comparative Study Cross-Over Studies Drug Therapy, Combination Eye/*blood supply Glaucoma, Open-Angle/drug therapy/*physiopathology Humans Intraocular Pressure/*drug effects Middle Aged Prostaglandins F, Synthetic/administration & dosage/*therapeutic use Pulsatile Flow Regional Blood Flow/drug effects Research Support, Non-U.S. Gov't Sulfonamides/administration & dosage/*therapeutic use Thiophenes/administration & dosage/*therapeutic use Timolol/administration & dosage/*therapeutic use Tonometry, Ocular Ultrasonography, Dopplerlehttp://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=15606472 HAJohnson, C Cioffi, G Liebmann, J Sample, P Zangwill, L Weinreb, Ru 2000ZTThe relationship between structural and functional alterations in glaucoma: a reviewSemin Ophthalmol84993-998 ~h12757105343 2003May-JunpiScanning laser Doppler flowmetry of nonperfused regions of the optic nerve head in patients with glaucoma 245-50BACKGROUND AND OBJECTIVE: To examine the reliability of scanning laser Doppler flowmetry in measuring capillary flow in regions of the optic nerve head, which are manifested differently by confocal tomographic angiography. PATIENTS AND METHODS: Capillary blood flow of the optic nerve head was measured in 16 eyes of 13 patients who had glaucoma with moderate to severe visual field defects. Blood flow measurements were taken by the scanning laser Doppler flowmeter and analyzed using the automatic full-field perfusion image analyzer (AFFPIA). Flow values were compared between perfused and nonperfused halves of the optic nerve head. Vascular anatomy of the optic nerve head was evaluated by confocal laser tomography with indocyanine green injection, and visual field tests by a standard visual field analyzer. RESULTS: Analysis of laser capillary flow parameters by the AFFPIA disclosed a mean lower flow value in nonperfused compared with perfused discs (426 +/- 310 vs 547 +/- 306; P = .006). There was also a positive correlation between visual field defect and capillary angiography of the optic nerve head. CONCLUSIONS: Flow measurements of the optic nerve head by scanning laser Doppler flowmetry using the AFFPIA revealed a mean lower flow value in nonperfused discs of patients who had glaucoma with severe visual field defect. Capillary angiography demonstrated by Heidelberg retina angiography has a good correlation with the pattern of visual field defect.'NGGoldschleger Eye Institute, Sheba Medical Center, Tel-Hashomer, Israel.<5Ben Simon, G. J. Moroz, I. Goldenfeld, M. Melamed, S.(!1542-8877 (Print) Journal Article$Ophthalmic Surg Lasers Imaging("Aged Aged, 80 and over Blood Flow Velocity Capillaries Female Glaucoma, Open-Angle/*physiopathology Humans *Laser-Doppler Flowmetry Lasers/diagnostic use Male Middle Aged Optic Disk/*blood supply Reproducibility of Results Tomography/methods Vision Disorders/*physiopathology *Visual Fieldslehttp://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=1275710515665350892e 2005 Feb{4-Effect of trabeculectomy on ocular blood flowi 185-8l6/BACKGROUND/AIM: Current evidence suggests that vascular insufficiencies in the optic nerve head play an important part in the pathogenesis of glaucomatous optic neuropathy. Trabeculectomy is the most common operative procedure for the treatment of medically uncontrolled glaucoma. This study was conducted to investigate whether trabeculectomy may improve ocular haemodynamics. METHODS: 30 patients with primary open angle glaucoma about to undergo trabeculectomy were included in the study. Patients were evaluated before surgery and at 2 and 10 weeks after trabeculectomy. Optic nerve head blood flow (OnhBF) was assessed with scanning laser Doppler flowmetry. Fundus pulsation amplitude (FPA) measurements were obtained with laser interferometry. RESULTS: Because of the decrease in intraocular pressure there was a significant increase in ocular perfusion pressure (OPP) following trabeculectomy (18.5% (SD 12.0%) and 19.0% (17.1%) at 2 and 10 weeks postoperatively; p <0.001). A significant increase in OnhBF was observed after trabeculectomy (11.6% (16.4%) and 16.2% (20.2%) for each postoperative visit, respectively; p <0.001). FPA was also significantly higher compared with baseline values (17.2% (17.3%) and 17.4% (16.3%), respectively; p <0.001). A significant association between the increase in OPP and the increase in OnhBF and FPA was observed 10 weeks after surgery (r = 0.47; p = 0.009, and r = 0.50; p = 0.005, respectively). CONCLUSION: The results of this study suggest that trabeculectomy improves ocular blood flow in patients with chronic open angle glaucoma.0'Department of Clinical Pharmacology, Medical University of Vienna, Allgemeines Krankenhaus Wien, Wahringer Gurtel 18-20, A-1090 Vienna, Austria.f`Berisha, F. Schmetterer, K. Vass, C. Dallinger, S. Rainer, G. Findl, O. Kiss, B. Schmetterer, L.(!0007-1161 (Print) Journal Article0Br J Ophthalmol.'Aged Analysis of Variance Blood Pressure/physiology Female Fundus Oculi Glaucoma, Open-Angle/physiopathology/*surgery Humans Interferometry/methods Intraocular Pressure/physiology Laser-Doppler Flowmetry/methods Male Middle Aged Optic Disk/*blood supply Trabeculectomy/*methods Treatment OutcomeUlehttp://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=15665350a!10090444221; 1998Ambulatory blood pressure monitoring in glaucoma patients. The nocturnal systolic dip and its relationship with disease progression 19-25@:PURPOSE: This study was designed to uncover a new sensitive and specific factor for predicting the progression of glaucoma. METHODS: The 24-ho10090444221; 1998Ambulatory blood pressure monitoring in glaucoma patients. The nocturnal systolic dip and its relationship with disease progression 19-25@:PURPOSE: This study was designed to uncover a new sensitive and specific factor for predicting the progression of glaucoma. METHODS: The 24-hour ambulatory blood pressure and diurnal curve of intra-ocular pressure were recorded in seventy patients: 51 primary open angle glaucoma (POAG) and 19 normal tension glaucoma (NTG). The mean systolic, diastolic and average arterial blood pressure were calculated, along with the nocturnal dip of systolic pressure and diastolic blood pressure. Two-year disease progression was assessed for all patients by means of retrospective analysis of visual fields defects on repeated perimetries. RESULTS: Abnormal (absence or increased) nocturnal dip of systolic blood pressure was found to be correlated with disease progression in POAG and NTG patients with a sensitivity of 86% and a specificity of 85%, whereas no significant correlation was found for the other risks factors envisaged. Furthermore, a significant relationship between stable visual field defects and the use of diuretics/laser procedure was evidenced. CONCLUSION: The nocturnal dip of systolic blood pressure should be considered as a predictive factor of disease progression in NTG and POAG. Further prospective studies are needed to ascertain whether dip normalization could help slow down the visual field loss in these patients.'`ZDepartment of Ophthalmology, Glaucoma Unit, University of Liege, CHU Sart Tilman, Belgium.>8Collignon, N. Dewe, W. Guillaume, S. Collignon-Brach, J.(!0165-5701 (Print) Journal Article Int Ophthalmolf`Aged Aged, 80 and over Blood Pressure/*physiology *Blood Pressure Monitoring, Ambulatory Chronic Disease Circadian Rhythm/*physiology Comparative Study Disease Progression Female Follow-Up Studies Glaucoma, Open-Angle/*physiopathology Humans *Intraocular Pressure Male Middle Aged Predictive Value of Tests ROC Curve Retrospective Studies Visual Fieldslehttp://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=10090444