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Diabetes elevates endothelin-1 (ET-1) in the vitreous and enhances constriction of retinal venules to this peptide. However, mechanisms contributing to ET-1-induced constriction of retinal venules are incompletely understood. We examined roles of sodium-hydrogen exchanger 1 (NHE1), protein kinase C (PKC), mitogen-activated protein kinases (MAPKs), and extracellular calcium (Ca 2+ ) in retinal venular constriction to ET-1 and the impact of diabetes on these signaling molecules. Retinal venules were isolated from control pigs and pigs with streptozocin-induced diabetes for in vitro studies. ET-1-induced vasoconstriction was abolished in the absence of extracellular Ca 2+ and sensitive to c-Jun N-terminal kinase (JNK) inhibitor SP600125 but unaffected by extracellular signal-regulated kinase (ERK) inhibitor PD98059, p38 kinase inhibitor SB203580, or broad-spectrum PKC inhibitor Gö 6983. Diabetes (after 2 weeks) enhanced venular constriction to ET-1, which was insensitive to PD98059 and Gö 6983 but was prevented by NHE1 inhibitor cariporide, SB203580, and SP600125. In conclusion, extracellular Ca 2+ entry and activation of JNK, independent of ERK and PKC, mediate constriction of retinal venules to ET-1. Diabetes activates p38 MAPK and NHE1, which cause enhanced venular constriction to ET-1. Treatments targeting these vascular molecules may lessen retinal complications in early diabetes., (© 2021 by the American Diabetes Association.)

The aryl hydrocarbon receptor (AHR) has endogenous functions in mammalian vascular development and is necessary for mediating the toxic effects of a number of environmental contaminants. Studies in mice have demonstrated that AHR is necessary for the formation of the renal, retinal, and hepatic vasculature. In fish, exposure to the prototypic AHR agonist 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) induces expression of the AHR biomarker cyp1a throughout the developing vasculature and produces vascular malformations in the head and heart. However, it is not known whether the vascular structures that are sensitive to loss of AHR function are also disrupted by aberrant AHR activation. Here, we report that TCDD-exposure in zebrafish disrupts development of 1) the subintestinal venous plexus (SIVP), which vascularizes the developing liver, kidney, gut, and pancreas, and 2) the superficial annular vessel (SAV), an essential component of the retinal vasculature. Furthermore, we determined that TCDD exposure increased the expression of bmp4, a key molecular mediator of SIVP morphogenesis. We hypothesize that the observed SIVP phenotypes contribute to one of the hallmarks of TCDD exposure in fish - the failure of the yolk sac to absorb. Together, our data describe novel TCDD-induced vascular phenotypes and provide molecular insight into critical factors producing the observed vascular malformations., (Copyright © 2021. Published by Elsevier B.V.)

As all the structures of the human eye are characterized by sex hormone receptors, this study tested the hypothesis that assisted reproductive technology (ART) treatment influences visual function and ocular morphology in women who have undergone ART treatment and children born as a result of ART treatment. A systematic literature search of all original articles published up to August 2018 was performed using the PubMed database, including all original studies available in the literature. Review articles, studies in which participants underwent mixed interventions (i.e. other than ART treatment), studies reporting data on ocular malformations in ART offspring, and studies written in languages other than English were excluded. All selected articles were analysed to assess the level of evidence according to the Oxford Centre for Evidence-Based Medicine 2011 guidelines, and the quality of evidence according to the Grading of Recommendations Assessment, Development and Evaluation system. Although sparse data suggest that ART treatment can influence visual function and ocular morphology in women who have undergone ART treatment and children born as a result of ART treatment, the available evidence is inconclusive given its low level and quality. More high-quality research is needed to assess the potential interaction between ART treatment and the eye., (Copyright © 2018 Reproductive Healthcare Ltd. Published by Elsevier Ltd. All rights reserved.)

Importance: Checkpoint inhibition in cancer immunotherapy related to T-cell-driven mechanisms of action associated with acute macular neuroretinopathy (AMN) and diffuse retinal venulitis, an adverse event not previously described, is reported here., Objective: To describe 2 patients who developed ophthalmologic events after treatment with the programmed death 1 axis inhibitor, atezolizumab., Design, Setting, and Participants: Retrospective review of 2 patients treated with atezolizumab for metastatic breast cancer and colon cancer, respectively, who presented with AMN and diffuse retinal venulitis conducted at 2 tertiary medical centers., Main Outcomes and Measures: Multimodal imaging including near infrared, optical coherence tomography, and fluorescein angiography were used to characterize retinal vascular abnormalities., Results: Based on optical coherence tomography and multimodal imaging findings, the clinical diagnosis of AMN associated with diffuse retinal venulitis was made in these 2 patients receiving atezolizumab., Conclusions and Relevance: While only 2 cases of patients receiving the programmed death ligand 1 inhibitor atezolizumab who experienced AMN and diffuse retinal venulitis are described here, these findings suggest that patients receiving programmed death 1 axis inhibitor therapies may need to be monitored for unexpected immune-related ocular toxicity including abnormalities of the microvasculature and large retinal vessels. Further studies might investigate the potential mechanisms of retinal vascular changes associated with these therapies.

Purpose: To evaluate the efficacy of switching treatment from intravitreal ranibizumab to intravitreal aflibercept on the treatment of refractory macular edema secondary to central retinal vein occlusion (CRVO)., Methods: In this retrospective study; 12 eyes with refractory macular edema secondary to CRVO after multiple monthly repeated intravitreal 0.5mg/0.05mL ranibizumab injections prior to switching therapy to intravitreal 2mg/0.05mL aflibercept, between March 2012 and April 2016 were reviewed. The follow-up time was 12 months. Changes in best-corrected visual acuity (BCVA), central macular thickness (CMT), central retinal volume (CRV) and injection interval between baseline and month 1, 3, 6 and 12 after switching therapy to aflibercept were reviewed and evaluated., Results: Mean baseline CRT decreased from 516±101 mic. to 252±114 mic. at month 12 (P=0.008). Mean baseline CRV decreased from 8.74±2.13 mm 3 to 6.82±1.64 mm 3 at month 12 (P=0.005). Baseline BCVA improved from 0.73±0.21 to 0.53±0.17 logMAR at month 12 (P=0.004). Mean BCVA gain was two logMar lines (10 letters) at month 12. After switching therapy to aflibercept; the mean injection interval increased significantly from 1.34 months at baseline to 1.86 months at month 12, by an increase of 0.52 months (P=0.02)., Conclusion: Intravitreal aflibercept is evaluated to be presenting significant visual and anatomical improvements in patients with persistent macular edema due to CRVO despite previous intravitreal ranibizumab., (Copyright © 2018 Elsevier Masson SAS. All rights reserved.)

Purpose: The goal of this study was to assess the effects of a single injection of intravitreal ranibizumab (RAN) or bevacizumab (BEV) on the retinal vessel size in eyes with diabetic macular edema., Materials and Methods: In total, 32 patients were enrolled in the RAN group, and 30 patients were included in BEV group. Each of these groups was also subdivided into two others groups: a study group and a control group. The study groups were composed of the injected eyes, whereas the noninjected fellow eyes served as the control groups. The patients underwent complete ophthalmic examinations, including optical coherence tomography and fundus fluorescein angiography, and the primary outcome measures included the central retinal artery equivalent, central retinal vein equivalent, and artery-to-vein ratio., Results: In the RAN study group (n = 32), the preinjection mean central retinal artery equivalent (175.42 μm) decreased to 169.01 μm after 1 week, and to 167.47 μm after 1 month (P < 0.001), whereas the baseline central retinal vein equivalent (235.29 μm) decreased initially to 219.90 μm after 1 week, and to 218.36 μm after 1 month (P < 0.001). In the BEV study group (n = 30), the preinjection central retinal artery equivalent (150.21 μm) decreased to 146.25 μm after 1 week, and to 145.89 μm after 1 month (P < 0.001); whereas the baseline central retinal vein equivalent (211.87 μm) decreased initially to 204.59 μm after 1 week and was 205.24 μm after 1 month (P < 0.001). The preinjection artery-to-vein ratio values changed significantly (P = 0.001) after 1 week and after 1 month in the RAN group, but no significant alteration in the artery-to-vein ratio was observed in the BEV group (P = 0.433). In both the RAN (n = 32) and BEV (n = 30) control groups, none of the 3 parameters changed throughout the study period, when compared with the baseline., Conclusion: The results of this study showed that both RAN and BEV injections significantly constricted the retinal blood vessel diameters.

PurposeTo detect and compare the vessel diameter effect of intravitreal vs subtenon injection of triamcinolone for diabetic macular edema (DME).MethodsSixty patients with DME who underwent triamcinolone injection either intravitreally (N=30) or under the tenon capsule (N=30) were included. Non-injected fellow eyes served as control. The main outcome measures were central retinal artery equivalent (CRAE), central retinal vein equivalent (CRVE), and artery-vein ratio (AVR).ResultsIn the intravitreal group, pre-injection mean CRAE (147.07 μ) decreased to 141.03 μ at 1 week and to 139.43 μ at 1 month (P<0.001) while baseline CRVE (209.61 μ) decreased initially to 198.85 μ at 1 week then to 198.49 μ at 1 month (P<0.001). In the subtenon group, pre-injection CRAE (152.18 μ) decreased to 149.49 μ at 1 week and to 147.47 μ at 1 month (P=0.017), while baseline CRVE (215.60 μ) decreased initially to 208.69 μ at 1 week then to 207.25 μ at 1 month (P=0.003). Pre-injection AVR values did not change at 1 week and at 1 month in both injection groups (P=0.66 and P=0.196, respectively). In the control group, none of the 3 parameters changed throughout the study period compared to the baseline (P>0.28).ConclusionIn eyes with DME, both intravitreal and subtenon triamcinolone injection led to a significant constriction of retinal arteries and veins.

Purpose: Niacin, a treatment for dyslipidemia, is known to induce vasodilation as a secondary effect. Previous instances of patients with chronic central retinal vein occlusion (CRVO) and cystoid macular edema (CME) have been observed to spontaneously improve when placed on systemic niacin for hypercholesterolemia. The purpose of this study was to evaluate the effects of niacin on CRVO and associated ocular complications., Methods: A prospective, single-center, non-randomized, interventional case series of niacin for CRVO was conducted. Best-correct visual acuity (BCVA), central macular thickness (CMT), and ocular complications were analyzed in 50 patients over 1 year. Eight patients were controls., Results: The mean initial logMAR BCVA was 0.915, and improved with niacin to 0.745 (P = 0.12), 0.665 (P = 0.02) and 0.658 (P = 0.03) after 3, 6, and 12 months of follow-up, respectively. At baseline, mean CMT was 678.9 μm, and improved to 478.1 μm (P = 0.001), 388.6 μm (P < 0.001), and 317.4 μm (P < 0.001) for the same time points. The control group had a mean initial logMAR BCVA of 1.023, which gradually deteriorated to 1.162 (P = 0.36) after 12 months, and baseline CMT of 700.0 μm at baseline, which gradually improved to 490.9 μm (P = 0.06) after 12 months. Panretinal photocoagulation for neovascularization was required in 5 patients (13.2%) receiving niacin and 3 (37.5%) controls., Conclusions: These data suggest that niacin may be associated with functional and anatomic improvements in eyes with CRVO. Future investigations will help ascertain whether there is a role for niacin as an adjunct therapy to intravitreal injections in the management of CRVO.

Purpose: To evaluate changes of vascular flow of patients treated with intravitreal injections of anti-vascular endothelial growth factor for macular edema secondary to retinal vein occlusion (RVO) with optical coherence tomography angiography (OCTA)., Methods: Patients with RVO with macular edema and treated with intravitreal injections of anti-vascular endothelial growth factors were retrospectively evaluated. The following examinations were performed before and after treatment: best-corrected visual acuity, spectral domain optical coherence tomography, fluorescein angiography, and OCTA (Optovue, Inc). Automatic measurement of vascular density of the superficial and deep capillary plexus was also performed and compared with age- and sex-matched healthy subjects., Results: Twenty-eight eyes of 28 patients (mean age 66.2 years; males 19%) were evaluated, including 13 central RVO, 11 branch RVO, and 4 hemicentral RVO. After treatment, mean central macular thickness significantly decreased from 644 μm to 326 μm and best-corrected visual acuity increased from 20/125 to 20/63 (P < 0.01 for both results). On OCTA, perifoveal capillary disruption (P = 0.029) and the number of cysts in the superficial capillary plexus and deep capillary plexus (P < 0.002) significantly decreased after treatment. The mean vascular density in the superficial capillary plexus slightly decreased during follow-up from 46.44% to 45.01% (not significantly). These densities were significantly less than those observed in healthy controls (P < 0.001)., Conclusion: Optical coherence tomography angiography showed regression of macular edema, reduced capillary disruption and cysts, and slight decrease in mean macular vascular density with time and despite treatment. Thus, OCTA enables qualitative and quantitative evaluation during follow-up of patients treated for RVO.

Retinal vein occlusion is a common and important cause of vision loss. In general, knowledge about this condition is scant within an internist's practice but the condition is relevant because of its association with other chronic ailments. A diagnosis of RVO should prompt the investigation of conditions needing chronic management in these patients. In this review we summarize the clinical presentation of RVO, its classification, associated risk factors, and treatment focused in the internist's scope of practice., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

Retinal vein occlusions may decrease visual acuity. There is no known therapy to treat ocular thrombosis. The authors used fondaparinux, an ultra-low-molecular-weight heparin, to treat 13 consecutive cases of recent-onset retinal vein occlusions. Two patients with renal insufficiency were not included. Eight central retinal vein occlusions and 5 branch retinal vein occlusions in 13 patients were treated with subcutaneous fondaparinux 2.5 mg once a day. The patients were seen every 2 weeks. Macular edema was treated with intravitreal injections of anti-vascular endothelial growth factor or steroids. Two patients elected to discontinue treatment. Of the remaining 11, 9 occlusions resolved in 1.5 to 13.5 months with rapid resolution of retinal edema and hemorrhage as soon as the occlusions resolved. One patient had a retinal vein that was still occluded after 8 months of therapy and 1 had retinal vein occlusion that partially resolved after 15 months of treatment. Of the 9 eyes with occlusions that resolved, visual acuity improved in 7. In 2, visual acuity decreased due to macular ischemia. Occlusion recurred in 1 2.5 months after the suspension of initial treatment. This patient is again being treated with fondaparinux 2.5 mg. No hemorrhaging occurred. Fondaparinux 2.5 mg can be given subcutaneously once a day to patients with recent-onset retinal vein occlusions without renal insufficiency. An occlusion may take a number of months to resolve. Once the vein occlusion has resolved, retinal edema and hemorrhage rapidly resolve and vision improves. Macular edema should be treated while waiting for the vein occlusion to resolve.

Purpose: To update the surgical technique in which a vitrectomy is performed and a retinal branch vein is cannulated and infused with recombinant tissue plasminogen activator (RTPA) to treat central retinal vein occlusion (CRVO) in patients who present with very low visual acuity (VA)., Methods: Twelve consecutive patients (12 eyes) with CRVO and low VA (logMAR >1.00) at presentation were treated using this method., Results: Cannulation of a peripapillary retinal vein and stable injection of RTPA was successfully performed without surgery-related complications in all 12 eyes. At 12 months after surgery, 8 of the 12 patients (67%) experienced at least one line of improvement in best corrected visual acuity; 6 of the 12 (50%) improved ≥5 lines and 2 (17%) improved ≥8 lines. After additional grid laser and/or subconjunctival or intravitreal corticosteroids, the mean decrease in central foveal thickness was 260 μm, and the mean total macular volume decreased from 12.10 mm(3) to 9.24 mm(3) . Four patients received panretinal photocoagulation to treat either iris neovascularization (n = 2) or neovascularization of the retina and/or disc (n = 2)., Conclusion: Administration of RTPA via a peripapillary vein using this updated technique provides an alternative or additional treatment option for patients with very low VA after CRVO., (© 2015 Acta Ophthalmologica Scandinavica Foundation. Published by John Wiley & Sons Ltd.)

Objective: To investigate the effects of intracameral carbachol in phacoemulsification surgery on central macular thickness (CMT), total macular volume (TMV) and retinal vessel caliber (RVC)., Materials and Methods: In this prospective consecutive case series, 82 patients underwent uneventful phacoemulsification and in-the-bag intraocular lens implantation. Unlike patients in the control group (43 eyes), patients in the study group (42 eyes) were injected with intracameral 0.01% carbachol during surgery. Spectral-domain optical coherence tomography (OCT) was used to analyze the parameters of CMT, TMV and RVC., Results: On the first postoperative day, mean CMT and TMV decreased markedly in the carbachol group, though these values did not change significantly in the control group. During follow-up visits, no statistically significant differences between the groups occurred regarding changes in mean CMT (p = 0.25, first day; p = 0.80, first week; p = 0.95, first month). However, change in mean TMV between groups on the first postoperative day was statistically significant (p = 0.01, first day; p = 0.96, first week; p = 0.68, first month). RVC values were similar on the preoperative and postoperative first days in both groups (p > 0.05)., Discussion: Results suggest that the effect of intracameral carbachol on macular OCT is related to pharmacological effects, as well as optic events (e.g. miosis)., Conclusion: Intracameral carbachol given during cataract surgery decreases macular thickness and volume in the early postoperative period but does not exert any gross effect on RVC.

This case describes the reversal of early central retinal vein occlusion (CRVO) with disc swelling after intravitreal dexamethasone implant (Ozurdex) injection. A 44-year-old female presented with sudden-onset intermittent blurred vision in her left eye. Fundus examination revealed multiple retinal hemorrhages without macular edema (ME). Two weeks later, an increased number of retinal hemorrhages with severe disc swelling were noted with still no sign of ME. An intravitreal dexamethasone implant was injected. Five days later, there were improvements in disc swelling and retinal hemorrhage. One month later, her subjective visual symptoms were completely improved, and fundus examination revealed marked improvement along with almost complete resolution of disc swelling. Intravitreal dexamethasone implant injection may potentially change the natural course of CRVO progression and its various subsequent complications.

Purpose: To assess retinal vascular calibre changes in eyes with neovascular age-related macular degeneration (AMD), treated with intravitreal anti-vascular endothelial growth factor agents, over a 1-year period and compare any such changes to untreated fellow eyes., Methods: Treatment naïve patients with neovascular AMD received three consecutive intravitreal injections of ranibizumab, followed by a pro re nata dosing regimen up to 1 year, with the aim of maintaining a 'fluid-free' macula. Retinal arteriolar and venular calibre was measured from digital fundus photographs at baseline and at three monthly intervals to 1 year, and summarised as central retinal artery equivalent (CRAE) and central retinal venular equivalent (CRVE), respectively., Results: A total of 53 injected eyes and 41 fellow, non-injected eyes were analysed. At baseline, there were no differences in retinal vascular calibre between injected and non-injected eyes (mean CRAE (SD) 144.93 (14.07) vs 145.74 (13.10) μm, P=0.80 and mean CRVE (SD) 216.23 (25.93) vs 219.91 (22.82) μm, P=0.53). Over a 12-month period, retinal venular calibre dilatation occurred in injected eyes (mean CRVE change +5.71 (14.71) μm, P=0.007), with no change in retinal arterioles, +0.69 (14.71) μm, P=0.68. In non-injected eyes, arteriolar narrowing occurred as a whole, mean CRAE change -4.20 (7.00) μm, P=0.001, over 12 months, with a trend for narrowing in venules, -2.16 (11.56) μm, P=0.28. In injected eyes, after controlling for covariates, the changes in CRVE over 12 months mirrored improvements in macular thickness, -0.06 (-0.005, -0.11) μm, P=0.04, and visual acuity, +9.66 (-0.30, +19.32) μm, P=0.06., Conclusion: Intravitreal ranibizumab significantly dilated retinal venules after a 1-year period.

Purpose: Recent studies suggest that the cannulation of retinal vessels may provide a potential access route for the administration of thrombolytic agents in retinal vessel occlusion. However, the major problem with available techniques is the limited visualization of retinal vessels with conventional surgical microscopes, making it difficult to effectively control the targeted injection of drugs., Methods: The authors developed a novel single-piece catheter system for the endoscopically guided puncture of microvessels. Experimental punctures of retinal vessels with injection of fluid were performed in porcine cadaver eyes using a standard high-resolution gradient index microendoscope introduced through the pars plana., Results: Endoscopically guided punctures were successfully performed in porcine branch retinal veins at various distances from the optic disc. Injection of recombinant tissue plasminogen activator (rt-PA), hypertonic solution (hyper HES), or normal saline solution into the vessel lumen was accomplished under direct endoscopic view in a safe and reliable manner., Conclusions: Endoscopically guided puncture of retinal microvessels is feasible and can be performed through a pars plana entry without additional micromanipulation devices. This novel technique may be a safe and effective approach to catheter-directed endovascular thrombolysis in retinal vascular occlusive diseases.

Purpose: The purpose of this article was to evaluate the efficacy and safety of intravitreal bevacizumab (Avastin) in eyes with macular edema secondary to central retinal vein occlusion (CRVO)., Methods: Forty-five consecutive eyes with macular edema secondary to CRVO were included in a prospective clinical trial. Eyes were treated with 3 initial intravitreal bevacizumab injections of 1.25 mg at monthly intervals. Retreatment was based on central retinal thickness (CRT) measured by optical coherence tomography (OCT). OCT was performed monthly; fluorescein angiography was performed every 3 months. Main outcome parameters were visual acuity (VA, using the Early Treatment of Diabetic Retinopathy Study protocol) and CRT in an 18-month follow-up period., Results: After 18 months of follow-up, mean VA increased from 40.9 letters at baseline to 61.9 letters (+21 letters; P<0.001) at month 18; CRT decreased from 572.3 μm at baseline to 273.2 μm at month 18 (-299.1 μm; P<0.001). Neither age, duration of CRVO, baseline VA, nor baseline CRT was correlated with the change in VA. No drug-related systemic or ocular side effects were observed following intravitreal bevacizumab treatment., Conclusions: Intravitreal bevacizumab is generally well tolerated and may improve VA and decrease CRT in patients with macular edema secondary to CRVO over a period of 18 months.

Purpose: To examine the intraocular distribution of bevacizumab at four weeks after intravitreal bevacizumab (IVB) injection and to investigate the effects of IVB on apelin and vascular endothelial growth factor (VEGF) in the central retinal vein occlusion (CRVO) of monkey eyes., Methods: Direct laser coagulation was performed on all branch retinal veins in the right eyes of six Rhesus monkeys to establish a CRVO model. The eyes of the first three monkeys were enucleated one week, two weeks, and 24 weeks after the establishment of the CRVO model; this was the CRVO group. Subsequently, IVB was injected into the eyes of the last three monkeys one week, two weeks, and 24 weeks after laser coagulation; this was the IVB group. The left eye of the first monkey was used as normal control. Immunohistochemistry and reverse-transcription PCR was used to examine the expression of apelin and VEGF. The penetration of bevacizumab into the retina and iris was investigated by fluorescence immunostaining., Results: Immunoreactivity for bevacizumab could be detected in the vessel walls of the iris and choroid on day 28 after injecting IVB: apelin and VEGF staining had been more prominent than normal in the CRVO eye, but these decreased following IVB injection. Expression of apelin mRNA (p<0.01) was lower in the IVB group than the CRVO group and did not vary significantly between groups., Conclusions: Bevacizumab could be detected in the iris and choroid after four weeks of intravitreal injection. Apelin may be partially suppressed by bevacizumab, and it may play a role in retinal neovascularization during the development of CRVO.

The novel therapeutic principle of intravitreal drug therapy for retinal vein occlusion has become an integrated constituent of clinical practice over the last years. The two substance classes that have been evaluated in large randomised clinical trials so far are corticosteroids and inhibitors of vascular endothelial growth factor (VEGF). The reported treatment success of these intravitreally administered substances has lead not only to a paradigm shift in clinical care but has also advanced our understanding of the underlying pathophysiological principles of retinal vein occlusions. In this review the different substances are discussed, their mechanisms of action are analysed and the results of the large clinical trials available to date are critically evaluated. Furthermore, an approach to integrate these novel treatment options into the existing treatment regimes for retinal vein occlusions is suggested., (© Georg Thieme Verlag KG Stuttgart · New York.)

The aim of this study was to investigate the effects of intravenous administration of flunarizine on the diameter of retinal blood vessels and blood pressure in anesthetized rats and to compare the effects of this antagonist with those of nicardipine and nifedipine. Retinal vascular images were captured with a fundus camera system for small animals and the diameter of retinal blood vessels contained in the images was measured using image-processing softwares on a personal computer. Blood pressure was continuously measured. Flunarizine [1-30 microg/kg, intravenously (i.v.)] dose-dependently increased the diameter of retinal blood vessels without significantly changing systemic blood pressure. Nicardipine (1-30 microg/kg, i.v.) increased the retinal blood vessel diameter but decreased blood pressure in a dose-dependent manner. Nifedipine (10-100 microg/kg, i.v.) failed to dilate the retinal blood vessels, although it produced comparable depressor responses as those to nicardipine. These results suggest that flunarizine selectively acts on the retinal blood vessels rather than on the peripheral resistance vessels. Flunarizine could therefore be considered as a candidate for therapeutic drugs to treat diseases associated with disorders of retinal circulation without severe cardiovascular side-effects.

Purpose: To compare the surgical outcomes and evaluate the effectiveness of two treatments for central retinal vein occlusion: radial optic neurotomy (RON) and cannulation of tissue plasminogen activator (tPA) into the retinal vein (tPA)., Methods: This study consisted of 22 eyes. The inclusion criterion was a best-corrected visual acuity of < or =20/60 due to central retinal vein occlusion. The exclusion criteria were previous treatment and the presence of ocular neovascularization. Patients were randomized into RON or tPA groups (n = 11 each). Best-corrected visual acuity, macular thickness, and complications were recorded., Results: The mean best-corrected visual acuity changed from 16/200 at baseline to 20/167 at 12 months in RON (P = 0.217) and from 10/200 to 20/200 in tPA (P = 0.051). The preoperative macular thicknesses decreased from 1,059 microm to 406 microm 12 months postoperatively in RON (P < 0.001) and from 1,121 microm to 271 microm (P < 0.001) in tPA. Neovascular glaucoma developed in 2 eyes (18%) in RON and in 4 eyes (40%) in tPA. Visual field defects associated with surgery were seen in 2 eyes (18%) in RON., Conclusion: There was no significant difference in surgical outcomes between the two procedures. Although best-corrected visual acuity and macular edema improved, the incidence of neovascular glaucoma was high. It is, therefore, still uncertain whether these treatments are effective.

Retinal blood flow has been reported to decrease early in human diabetes as well as in diabetic animal models. The purpose of the present study is to investigate the role of thromboxane receptor binding in the decrease of flow. C57BL/6 mice were injected with streptozotocin (STZ) at 11-12 weeks of age and remained hyperglycemic for 4 weeks. The mice were treated with a selective thromboxane receptor antagonist, GR32191B (vapiprost), in drinking water for the final three weeks at a dose of 1mg/kg/day. In separate experiments, vapiprost was administered only once, as an acute injection 25min prior to the experimental measurements. The measurements included retinal arteriolar and venular diameters and red blood cell (RBC) velocities, from which retinal blood flow was calculated. STZ induced decreases in vascular diameters and RBC velocities, resulting in an approximate 30% decrease in overall retinal blood flow. However, these decreases were not seen in mice given the three-week administration of vapiprost. Acute administration to diabetic mice of 1mg/kg vapiprost, but not 0.1mg/kg, induced arteriolar vasodilation, with the dilation more substantial in smaller feed arterioles. In summary, STZ-induced decreases in retinal blood flow can be attenuated by the thromboxane receptor antagonist vapiprost.

Background: Dietary fiber appears to decrease the risk of cardiovascular morbidity and mortality. Microvascular abnormalities can be observed by retinal examination and contribute to the pathogenesis of various cardiovascular diseases. The impact of dietary fiber on the retinal microvasculature is not known., Objective: We aimed to examine the association between dietary fiber intake and retinal vascular caliber., Design: At the third visit (1993-1995) of the Atherosclerosis Risk in Communities (ARIC) Study, a population-based cohort of adults in 4 US communities, the retinal vascular caliber of 10,659 participants was measured and summarized from digital retinal photographs. Usual dietary intake during the same period was assessed with a 66-item food-frequency questionnaire., Results: After control for potential confounders including hypertension, diabetes, lipids, demographic factors, cigarette smoking, total energy intake, micronutrients intake, and other cardiovascular disease risk factors, higher intake of fiber from all sources and from cereal were significantly associated with wider retinal arteriolar caliber and narrower venular caliber. Participants in the highest quintile of fiber intake from all sources had a 1.05-microm larger arteriolar caliber (P for trend = 0.012) and a 1.11-microm smaller venular caliber (P for trend = 0.029)., Conclusions: Dietary fiber was related to wider retinal arteriolar caliber and narrower venular caliber, which are associated with a lower risk of cardiovascular disease. These data add to the growing evidence of the benefits of fiber intake on various aspects of cardiovascular pathogenesis.

We examined the effects of vasodilatory prostaglandins (prostacyclin and prostaglandin E(2)) and selective agonists for prostanoid EP(2) and EP(4) receptor on the diameters of retinal blood vessels and fundus (retinal/choroidal) blood flow in rats. Male Wistar rats (8- to 10-week-old) were treated with tetrodotoxin (50 microg/kg, i.v.) to eliminate any nerve activity and prevent movement of the eye and infused with a mixture solution of norepinephrine and epinephrine (1:9) to maintain adequate systemic circulation under artificial ventilation. Fundus images were captured with a digital camera that was equipped with the special objective lens for small animals, and the diameters of retinal arterioles and venules were measured on a personal computer. Fundus blood flow was estimated using a laser Doppler flowmetry. Intravenous infusions of prostacyclin and prostaglandin E(2) dilated retinal blood vessels, increased fundus blood flow and decreased systemic blood pressure in a dose-dependent manner. The effects of vasodilatory prostaglandins on retinal arterioles were greater than those on retinal venules. Similarly, a prostanoid EP(2) receptor agonist (ONO-AE1-259-01) dilated retinal blood vessels, and increased fundus blood flow and decreased systemic blood pressure. However, a prostanoid EP(4) receptor agonist (ONO-AE1-329) failed to increase fundus blood flow, despite its comparable depressor response with those to vasodilatory prostaglandins and the prostanoid EP(2) receptor agonist. The responses to forskolin, an activator of adenylyl cyclase, were very similar to those to prostacyclin and the prostanoid EP(2) receptor agonist. These results suggest that prostacyclin and prostaglandin E(2) act as vasodilators in retinal and choroidal circulation, and prostanoid IP and EP(2) receptors play an important role in the regulation of ocular hemodynamics in rats.

Aim: To investigate the effect of dopamine on retinal and choroidal blood flow in humans., Methods: We investigated the effect of two doses of intravenous dopamine (5 and 10 microg/kg/min) via a randomised double-masked crossover study in 12 healthy subjects chosen from a total of 16. Blood flow parameters in retina, optic nerve head and choroid were assessed with bi-directional laser Doppler velocimetry, laser Doppler flowmetry and laser interferometric measurement of fundus pulsation amplitude, respectively., Results: Intravenous dopamine dose-dependently increased retinal blood cell velocity and fundus pulsation amplitude (p<0.001). At the highest administered dose red blood cell velocity in retinal vessels increased by 37% and fundus pulsation amplitude by 24%. By contrast, optic nerve head blood flow did not change with dopamine administration., Conclusions: Our data indicate that dopamine has a pronounced enhancing effect on the retinal perfusion in humans. Further studies are required to establish the exact role of dopamine in the regulation of choroidal and optic nerve head blood flow.

Purpose: Retinal endovascular lysis is a new therapeutic option for patients with central retinal vein occlusion (CRVO). In this procedure, a fibrinolytic agent is injected directly into a cannulated retinal vein after pars plana vitrectomy., Design: Prospective interventional case series., Participants: Thirteen strictly defined patients with ischemic CRVO., Methods: Patients with a decimal visual acuity (VA) of 0.2 or worse were scheduled for surgery within the first 5 months after onset of CRVO. A full ocular examination, determination of VA (Early Treatment Diabetic Retinopathy Study charts), and fluorescein angiography were done preoperatively and 6, 12, 26, and 52 weeks postoperatively., Main Outcome Measure: Visual acuity 1 year after retinal endovascular lysis. Secondary study end points were (1) correlation of VA and successful recombinant tissue plasminogen activator injection into a retinal vein, (2) complication rate, and (3) number of additional surgical procedures within the first year after retinal endovascular lysis., Results: All patients had an ischemic CRVO and completed the 1-year follow-up visit. Preoperative decimal VA was 0.063 +0.025/-0.018 (VA range, light perception [LP]-0.2); 6-week postoperative VA, 0.049 +0.024/-0.016 (LP-0.4); 3-month postoperative VA, 0.043 +0.019/-0.014 (LP-0.3); 6-month postoperative VA, 0.035 +0.022/-0.013 (blindness-0.4); and 12-month postoperative VA, 0.04 +0.026/-0.016 (blindness-0.4). Visual acuity changed 1 year after retinal endovascular lysis by -1.923+/-1.619 lines (+6 to -16 lines; P = 0.258). We considered the retinal endovascular lysis procedure to have been technically successful in 10 eyes. Visual changes did not depend on successful lysis. Six eyes developed neovascular glaucoma, of which 2 globes ended up with painful phthisis and had to be removed. Retinal detachment was found in 3 eyes and cataract in 4. Together, the 13 eyes needed 22 additional surgical procedures. Preoperative and postoperative angiographic examinations showed no significant changes., Conclusion: Ischemic CRVO patients did not profit from retinal endovascular lysis in this pilot study. Visual results and the risk of developing iris neovascularization and neovascular glaucoma took the natural course. Although these results may be due to the overall bad prognosis of these particular ischemic eyes, the number of postoperative complications is unacceptably high.

The aim of the present study was to investigate the effect of sildenafil citrate (viagra) on retinal venous diameter in patients with age-related macular degeneration (AMD). We investigated 14 male patients in a double-masked, randomized, placebo-controlled, crossover study. In each subject, one eye with typical non-exudative AMD fundus features was studied. Each of the subjects received 100 mg dose of sildenafil or matching placebo on two separate study visits. Monochromatic fundus photographs were obtained in the study eye before dosing and then 30, 90, 180 and 300 min later. Measurements of the diameter of the major retinal veins from digitized negatives were carried out using "Vessel map" static vessel analysis program (IMEDOS GmbH, Weimar, Germany). Statistical analysis of the data comparing the effect of sildenafil and placebo on venous diameters was performed using analysis of variance (ANOVA) for repeated measures. An analysis of variance (ANOVA) comparing the effects of sildenafil citrate and placebo on retinal vein diameters showed a significant interaction between time and treatment (P = 0.03). In comparison to placebo, sildenafil citrate produced a statistically significant vasodilatation of major retinal veins of 4.7% at 90 min (P = 0.004), 5.5% at 180 min (P < 0.0001) and 5.8% at 300 min (P < 0.0001). At 30 min there was a 2.2% difference, which was not statistically significant (P=0.14). Our results suggest that in patients with age-related macular degeneration, sildenafil citrate (viagra) produces a statistically significant vasodilatation of major retinal veins that is similar to what has been reported in normal subjects. Whether this vasodilatation is associated with changes in retinal blood flow needs to be further investigated.

The use of cyclosporin has been associated with the development of cholelithiasis in transplant recipients. Cholelithiasis in turn enhances the effects of cyclosporin on increased platelet aggregation. In this report, a patient who had undergone a renal transplantation as a result of malignant hypertension, and who was on immunosuppressive therapy consisting of cyclosporin, prednisone and azathioprine, developed thrombosis of the central retinal vein 5 years following the transplantation. Seven years after the transplantation, cholelithiasis, cholecystitis, cholangitis and subsequently secondary chronic biliary sclerosis were detected. Latero-lateral anastomosis between the common bile duct and duodenum was performed during explorative laparotomy and ursodeoxycholic acid treatment was introduced. The possible inter-relationship of the cholestatis, central retinal vein thrombosis and immunosuppression are discussed.

Purpose: To evaluate the feasibility, safety, and efficacy of local thrombolytic agents directly injected into occluded retinal veins in an experimental animal model., Design: Experimental animal study., Methods: This experimental study was performed in two phases. In phase 1, 15 enucleated porcine eyes and 8 in vivo canine eyes were used for the development of the instrumentation and surgical technique required for retinal vein cannulation with prolonged intravascular infusion. In phase 2 of this study, experimental branch retinal vein occlusion was photo-chemically created using an intravenous injection of rose bengal followed by diode laser photocoagulation in eight eyes of eight dogs. Four eyes were treated by retinal vein cannulation and an injection of tissue plasminogen activator (t-PA) using a specifically designed microcatheter, while the remaining four eyes were untreated (control group). The total amount of t-PA injected intravenously ranged from 400 to 1000 mug, infused over a period ranging from 25 to 45 minutes with a mean pressure of 40 psi, resulting in a mean injection flow rate of 0.05 ml/min. The dogs underwent clinical examination, fluorescein angiography, and histologic examination. Main outcome measures were: Achievement of prolonged intravascular infusion of t-PA, changes in fundus appearance, fluorescein angiography, and histology., Results: A microcatheter instrument and a surgical technique for retinal vein cannulation with prolonged intravascular infusion were developed. Cannulation and t-PA infusion for a period of at least 30 minutes was achieved in all four treated eyes with experimental branch retinal vein occlusion. No complications were recorded in all treated eyes. One week and 1 month postoperatively, treated eyes exhibited marked decreases in retinal hemorrhages, retinal vein dilation, and tortuosity, whereas nontreated eyes exhibited persistence of these findings. Fluorescein angiography demonstrated improved circulatory flow in treated relative to nontreated eyes. Histologic analysis confirmed the presence of thrombi in nontreated eyes only., Conclusions: Retinal vein cannulation with prolonged intravascular injection of t-PA is feasible and safe, and this may offer a new treatment option for retinal vein occlusion.

Objective: To describe development of retinal vein occlusion (RVO) in patients anticoagulated with warfarin., Design: Retrospective, observational case series., Participants: Thirteen patients drawn from a private retina practice., Methods: Review of clinical records, laboratory results, color fundus photographs, and fluorescein angiograms., Main Outcome Measures: Primary measures were international normalized ratio (INR), visual acuity, and concurrent systemic disease., Results: The female-to-male ratio was 7 to 6. Age range was 44 to 86 years, with a median age of 73 years. Two patients had systemic lupus erythematosus, 7 had hypertension, and 2 had primary open-angle glaucoma. Two had laboratory abnormalities: 1 with a combination of lupus anticoagulant and anticardiolipin antibodies and 1 with a combination of hyperhomocystinemia and low antithrombin III. Three patients were taking acetylsalicylic acid in addition to warfarin at the time of the RVO. The INRs at the time of RVO were 0.9 to 3.8, with 9 of 13 <==2.0., Conclusions: Anticoagulation with warfarin does not preclude RVO in predisposed patients, nor does combination therapy with warfarin and acetylsalicylic acid. Attention to keeping the INR >2.0 may be helpful.

Purpose: To report the results of retinal endovascular surgery and intravitreal triamcinolone acetonide on two eyes of two patients younger than 40 years of age with central vein occlusion., Design: Interventional case reports from a study approved by the Institutional Review Board of North Broward Medical Center, Pompano Beach, Florida., Methods: Two men, ages 37 and 39, with unilateral central vein occlusion were treated with retinal endovascular surgery and intravitreal triamcinolone acetonide. The main outcome measure was recovery of visual acuity., Results: One patient recovered 8 lines of visual acuity, the other recovered 11 lines. There was rapid clearance of intraretinal hemorrhage and edema in both cases., Conclusions: Retinal endovascular surgery and intravitreal triamcinolone acetonide may promote recovery of visual acuity in eyes of young adults with central vein occlusion., (Copyright 2003 by Elsevier Science Inc.)

Case Report: A 20-year-old male with no history of any systemic or eye disease developed loss of visual acuity in both eyes. White exudates surrounding the retinal veins from the posterior pole to the periphery, retinal edema and hemorrhages in both eyes were evident on ophthalmoscopy. Fluorescein angiography showed leakage of the dye from the veins and extensive staining of the vein walls. A diagnosis of acute frosted branch angiitis was made. Systemic examination revealed axillary, submandibular and inguinal lymphadenopathies. VCA IgM antibody for Epstein-Barr virus was negative and IgG positive. Biopsy was taken of an axillary lymph node; a non-specific inflammatory reaction was found on anatomopathologic study. The patient was started on 90 mg prednisolone daily. After two weeks retinal vasculitis had improved and the lymphadenopathies soon resolved. Small, hard exudates were present in the posterior pole during absorption of the retinal edema and resolution of the vascular inflammation. Systemic prednisolone were reduced progressively and definitively withdrawn two months later. The patient's visual acuity was 20/25 in both eyes. No fibrotic scar tissue or atrophic lesions were noted in either fundus., Conclusions: We report a new case of acute frosted branch angiitis with an onset and favorable clinical course similar to previous reports. We found the additional presence of lymphadenopathies but have been unable to establish a possible causal agent. To our knowledge, apart from a recent case of frosted branch angiitis-like response in Greece, the present case is the first reported in western Europe.

Background: The cardiovascular effects of sildenafil (Viagra), a selective inhibitor of phosphodiesterase type 5 (PDE5), have been extensively studied. However, its effect on human retinal arteries and veins has not yet been investigated. The effect of a single dose administration of sildenafil on the retinal vessel diameters of healthy subjects was evaluated., Methods: Sildenafil 50 mg was administered to 10 healthy subjects (male:female = 4:6; mean age 31 (SD 6) years). The diameters of retinal arteries and veins were measured by means of a retinal vessel analyser (RVA) immediately before and at 30, 60, 90, and 120 minutes after sildenafil uptake. Blood pressure, heart rate, and intraocular pressure were monitored in parallel., Results: A significant increase of 5.8% (p<0.001) in both retinal arterial and venous diameters was found 30 minutes after sildenafil uptake. The diameters returned to baseline after 120 minutes. A mild systemic hypotensive response was seen. Changes in heart rate and intraocular pressure were not observed., Conclusion: Sildenafil causes a significant dilatation of retinal arteries and veins in healthy subjects. A possible role for PDE5 in the regulation of retinal blood flow is implicated.

The aim of this study was to evaluate PXF (pentoxifylline; 1600 mg daily vs placebo) in patients with retinal vein thrombosis (RVT) in a 4-week trial, evaluating clinical outcome and retinal flow. Inclusion criteria were sudden loss of vision (SLV); retinal vein thrombosis (RVT); decrease in retinal vein flow; asymmetry between retinal veins (>40%) documented by duplex scanning (retinal vein thrombosis flow = RVTF). All 18 included patients completed the study. The groups were comparable. No side effect was observed. An improvement in arterial flow (p<0.05) and a decrease in analogue score (p<0.05) were observed in both groups (due to the spontaneous evolution with partial thrombus lysis in 4 weeks). The increase in arterial flow (PSF and EDF) were greater (p<0.05) in the PXF group. The RVFV increase was better in the PXF group (350% increase vs 200% increase in the placebo group; p<0.05). There was a significant difference in the analogue score decrease (4 vs 7) in the PXF group (p<0.05). In conclusion, PXF improved retinal flow after RVT better than placebo. It should be considered as an important treatment option.

The purpose of the present study was to study the effect of topical unoprostone on the circulation of human optic nerve head (ONH) and retina in normal subjects. Using laser-speckle tissue blood flow analysis, normalized blur (NB), a quantitative index of tissue blood velocity, was measured every 0.125 sec at a temporal ONH site, free of visible surface vessels. Measurements were averaged for 3 cardiac cycles (NB(ONH)). Color Doppler imaging (CDI) was also used to evaluate peak systolic blood velocity (PSV), end-diastolic velocity (EDV), and resistive index (RI) in the central retinal artery (CRA) and mean blood velocity (MV) in the central retinal vein (CRV). For baseline comparison (Day 0), recordings of bilateral NB(ONH) and intraocular pressure (IOP), blood pressure (BP), and pulse rate (PR) were recorded in healthy volunteers before, and 45, 90, 180, and 270 min after instillation of one drop of unoprostone vehicle. On Day 1 (the day after baseline measurements), and twice daily for 7 days, one drop of 0.12% unoprostone was instilled into one eye and its vehicle into the other in a double-blinded manner. Measurements as on Day 0 were recorded on Days 1 and 7. CDI measurements were performed before and at 45 and 180 min after morning instillation on Days 1 and 7. During baseline recordings, there were no significant changes in any parameters. After administration of topical unoprostone, IOP was significantly lower bilaterally with more reduction in the unoprostone-treated eyes on Day 7. On Day 7, the NB(ONH) of the unoprostone-treated eyes was significantly higher 45 min after instillation than baseline (P = 0.035 with Bonferroni's correction). Analysis of variance for repeated measurements also revealed significant difference between Day 0 and Day 7 (P = 0.0017). BP, PR, NB(ONH) in the eye that received only the vehicle, PSV, EDV, and RI in the CRA in both eyes, and MV in the CRV in both eyes changed little. Tissue blood velocity in the ONH increased, at least temporarily, following instillation of unoprostone twice daily for 7 days. Although the clinical implication of the increase is unclear, the effects of topical unoprostone on human ONH circulation deserve further consideration.

Purpose: Central retinal vein occlusion (CRVO) often produces significant and permanent loss of vision in the affected eye. The purpose of this study was to determine if patients with vision loss secondary to CRVO treated with retinal vein cannulation and infusion of tissue plasminogen activator (t-PA) experienced recovery of visual acuity., Design: Prospective, noncomparative, interventional case series., Participants: Thirty eyes of 30 consecutive patients with CRVO underwent the procedure, but two were subsequently excluded. The remaining 28 eyes of 28 patients with CRVO for an average of 4.9 months before intervention (range, 0.25-30 months) and best-corrected visual acuity 20/63 or worse were included in the study., Intervention: All patients underwent pars plana vitrectomy with cannulation and infusion of t-PA into a branch retinal vein., Main Outcome Measures: Change in visual acuity and the development of complications such as vitreous hemorrhage and neovascular glaucoma were monitored., Results: Twenty-two of 28 patients (79%) experienced at least one line of visual improvement during the follow-up period (average, 11.8 months; range, 3-24 months), and the same number had this level of improvement at the last follow-up examination. Fifteen patients (54%) gained 3 or more lines of acuity within 6 months after the procedure, and 14 (50%) had acuity at last follow-up at least 3 lines better than baseline acuity (average, 6.8 lines). Seven patients had postoperative vitreous hemorrhages ranging from 1 week to 11 months after the procedure; two cleared spontaneously. One patient had a postoperative retinal detachment from a peripheral retinal break that was repaired successfully with pneumatic retinopexy. No other serious intraoperative or early postoperative complications were noted., Conclusions: Vitrectomy with retinal vein cannulation and infusion of t-PA is a relatively safe procedure that may improve vision in eyes with CRVO.

Background: Frosted branch angiitis usually occurs in children, and has a good prognosis. We report two cases of unilateral frosted branch angiitis in adults. Both had poor visual outcomes because of associated central retinal vein occlusion and neovascular glaucoma., Cases: Case 1 was a 36-year-old woman. Almost all retinal veins and some retinal arteries showed vasculitis in her right eye, and veins were slightly dilated and sheathed. Case 2 was a 23-year-old woman. Angle hypopyon was observed in her left eye. Retinal veins were dilated, meandering, and sheathed. Retinal hemorrhages were also observed. In both cases, after systemic steroid therapy the retinal vasculitis gradually decreased, but central retinal vein occlusions gradually developed. Despite systemic administration of urokinase and panretinal photocoagulation, neovascular glaucoma developed, and visual acuity diminished in both cases., Conclusions: Two cases of frosted branch angiitis complicated by retinal vein occlusion are reported. Careful observation of retinal blood flow is necessary in frosted branch angiitis in adults.

Purpose: Ticlopidine inhibits adenosine diphosphate (ADP)-induced platelet aggregation and may be effective in patients with retinal vein occlusions (RVO). This study tests the efficacy of ticlopidine in an animal model of RVO., Methods: Rose bengal-mediated argon laser photothrombosis of retinal veins was created in rabbits pretreated with oral ticlopidine, aspirin, or saline. The number of laser spots necessary to produce a partial or complete RVO was recorded and tabulated., Results: Pretreatment with ticlopidine significantly increased the number of laser spots needed to produce a partial (P =.02), or a complete (P =.002) RVO as compared to the control group. Pretreatment with ticlopidine significantly increased the number of laser spots needed to produce a partial RVO (P =.02). Pretreatment with aspirin significantly increased the number of laser spots needed to produce a complete RVO (P =.002)., Conclusion: Ticlopidine may be a useful antiplatelet agent for the treatment of patients with RVO. Patients treated with ticlopidine should be monitored for the possible development of hematologic disorders.

Purpose: To investigate the later pathohistological changes in experimental retinal venous obstruction in rabbits., Methods: Experimental retinal venous obstruction was produced in retinal blood vessels of rabbits by trans-adventitial dropping of thrombin. Fundus observation was performed 3 months and 1 year thereafter. Retinal histological examinations were performed by fluorescein microscopy, light microscopy, and transmission electron microscopy., Results: Vessels with a rete mirabile and arteriovenous anastomosis were observed after 3 months. On a flat gelatin-fluorescein preparation, regions with no perfusion, thought to be areas of vascular occlusion in the periphery, were observed extensively. Clear leakage of gelatin-added fluorescein was noted from vessels in the periphery, and minute neovascularization with a rete mirabile from these vessels was confirmed. Newly formed retinal vessels were also observed by transmission electron microscopy. The endothelial cells of these newly formed vessels had a large nucleus, a number of ribosomes, and thin basement membrane. Proliferative changes included glial cells that had penetrated into the basement membrane of ghost vessels., Conclusion: Our long-term observations confirmed that proliferative changes and neovascularization occurred in this model of retinal venous obstruction.