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Tractional retinal detachment after branch retinal vein occlusion. Influence of disc neovascularization on the outcome of vitreous surgery.

OBJECTIVE: This study aimed to investigate the influence of disc neovascularization on the outcome of vitreous surgery for tractional retinal detachment (TRD) after branch retinal vein occlusion (BRVO). DESIGN: The study design was a retrospective case series. PARTICIPANTS: Twenty-two eyes of 22 patients who had undergone vitrectomy for TRD after BRVO at the Osaka National Hospital (Osaka, Japan) or the Surugadai Hospital of Nihon University (Tokyo, Japan) between 1985 and 1995 participated. Seven (32%) of 22 eyes had a TRD secondary to neovascularization of the optic disc (NVD) and neovascularization elsewhere (NVE; group I), and 15 (68%) had a TRD with NVE without NVD (group II). MAIN OUTCOME MEASURES: Visual acuities and retinal reattachment rates were measured. RESULTS: Sixteen (73%) of the 22 study eyes showed severe vitreous hemorrhage before surgery, and 11 eyes (50%) had received laser photocoagulation treatment before surgery. Fourteen (64%) of the study eyes achieved total retinal reattachment after initial vitrectomy, and 19 eyes (86%) were reattached completely at final examination. Thirteen eyes (59%) achieved a visual acuity of better than 0.1. Group I patients had a significantly higher rate of recurrent combined traction rhegmatogenous retinal detachment (P = 0.01) and a significantly worse final visual outcome (P = 0.01). CONCLUSIONS: Better surgical results are expected in eyes without NVD than with NVD among patients who undergo vitrectomy for TRD after BRVO. Although the authors were unable to determine the reason for this difference in the current study, they speculate that the degree of retinal nonperfusion, diffusible angiogenic factors, and distance of the site of occlusion from the disc may each affect visual and anatomic outcomes in these eyes.

Aged↗

Pigment epithelium-derived factor inhibits leptin-induced angiogenesis by suppressing vascular endothelial growth factor gene expression through anti-oxidative properties.

Leptin, a circulating hormone secreted mainly from adipose tissues, is involved in the control of body weight. Recently, leptin was found to be an angiogenic factor, and its vitreous levels are associated with angiogenic eye diseases such as proliferative diabetic retinopathy. However, the molecular mechanism for leptin-elicited angiogenesis remains to be elucidated. Pigment epithelium-derived factor (PEDF) has been shown to be the most potent natural inhibitor of angiogenesis in the mammalian eye, and its levels in the vitreous were decreased in angiogenic eye diseases. In this study, we investigated whether and how PEDF could inhibit the leptin-induced DNA synthesis in microvascular endothelial cells (EC), a key step of angiogenesis. Leptin significantly increased intracellular reactive oxygen species (ROS) generation in microvascular EC. PEDF was found to inhibit the leptin-induced ROS generation in EC. An anti-oxidant, N-acetylcysteine, or PEDF completely prevented the leptin-induced upregulation of vascular endothelial growth factor (VEGF) mRNA levels as well as any increase in DNA synthesis in microvascular EC. Polyclonal antibodies against human VEGF were also found to completely inhibit DNA synthesis in leptin-exposed EC. The present study suggests that leptin could elicit angiogenesis through autocrine VEGF production via intracellular ROS generation. PEDF may block the angiogenic effects of leptin through its anti-oxidative properties.

Acetylcysteine↗

Central retinal vein occlusion and iris neovascularization hemorrhage.

Although there have been few direct observations, the etiology of spontaneous hyphema in patients with retinal or ocular hypoxia is assumed to be hemorrhage from a neovascular iris vessel. This paper reports observed hemorrhage from such a rubeotic iris in a patient with central retinal vein occlusion, diabetes, hypertension, peripheral vascular disease and chronic open-angle glaucoma. Bleeding was spontaneous with dilation, but stopped within 24 hours without treatment, leaving only traces of inferior angle blood staining. The two types of central retinal vein occlusion, and suggestions for their management, are also discussed.

Humans↗

Clinicopathologic correlation of intraretinal microvascular abnormalities.

PURPOSE: To define the cross-sectional morphology of intraretinal microvascular abnormalities, which previously have been described only in terms of trypsin digestion. MATERIAL/METHODS: Fourteen vascular lesions of five patients with diabetic retinopathy were identified on fundus photographs and/or fluorescein angiograms and classified as intraretinal microvascular abnormalities. Eyes of these patients were obtained after the patients' deaths. The period between the time at which the photographs were taken and that at which enucleation was performed was 3-20 months. The duration of autolysis before fixation was 5 hours or less. The embedded tissue was evaluated by light and electron microscopy, and these findings were correlated with the clinical appearance. RESULTS: The lesions consisted of multiple, closely spaced, thin-walled vascular lumina with a caliber of 20-70 microns. They were located in the inner retina and surrounded by a wide cuff containing randomly oriented collagen fibers. Endothelial cell nuclei were numerous. Pericyte degeneration and multiplication of the endothelial and pericyte basement membrane had occurred. Endothelial junctions were short, and gaping of junctions was not seen. However, occasional fenestrations were present. CONCLUSION: The cross-sectional morphology of intraretinal microvascular abnormalities is consistent with vascular pathology typical for intraretinal diabetic microangiopathy, but also includes features usually seen in new vessels. This supports the concept that intraretinal microvascular abnormalities have the particular potential for neovascularization.

Adult↗

Treatment of macular subretinal neovascularization with the red-light krypton laser in presumed ocular histoplasmosis syndrome.

A patient with presumed ocular histoplasmosis and decreased visual acuity in one eye had subretinal neovascularization and retinal hemorrhage in the macular area. Argon-laser treatment to eradicate the subretinal neovascular membrane was contraindicated because of the proximity of the hemorrhagic lesion to the fovea. We used a red-light krypton laser (647 nm) because the light is not absorbed by the hemoglobin in the retinal hemorrhage or by the macular luteal pigment (xanthophyll), and because it is transmitted into the choroid, allowing treatment within the macular zone with less damage to the internal retinal elements. After treatment, the subretinal neovascular membrane completely disappeared and the macular hemorrhage cleared. To the best of our knowledge, this is the first time that a histoplasmic macular subretinal neovascular membrane has been treated with the red-light krypton laser.

Eye Diseases↗

Photodynamic therapy for neovascular age-related macular degeneration.

BACKGROUND: In neovascular age-related macular degeneration, new vessels grow under the retina, distorting vision and leading to scarring. This is further exacerbated if the blood vessels leak. Photodynamic therapy, originally used in cancer treatment, has been investigated as a way to treat the neovascular membranes without affecting the retina. OBJECTIVES: The aim of this review is to examine the evidence for the safety and effectiveness of photodynamic therapy in the treatment of neovascular age-related macular degeneration. SEARCH STRATEGY: We searched for trials in the Cochrane Eyes and Vision Group trials register (available in the Cochrane Controlled Trials Register), the Cochrane Controlled Trials Register, Medline and Embase. We used the Science Citation Index to search for reports that cited identified relevant study reports. We contacted experts in the field for further trials information, and we searched the reference lists of identified relevant studies for further trial reports. Searches were conducted in December 1999. SELECTION CRITERIA: We included randomised trials of photodynamic therapy in people with choroidal neovascularisation due to age-related macular degeneration. DATA COLLECTION AND ANALYSIS: Two reviewers extracted the data independently. Meta analysis was not performed. MAIN RESULTS: One published trial was identified. Outcome data were available at 12 months after the first treatment. Patients received an average of 3.7 treatments. The relative risk of losing three or more lines of visual acuity at 12 months comparing the intervention with the control group was 0.72 (95% confidence interval 0.61 to 0.86). The relative risk of losing six or more lines of visual acuity at 12 months comparing the intervention with the control group was 0.62 (95% confidence interval 0.44 to 0.87). Subgroup analyses suggest that the benefits may be confined to people with no occult choroidal neovascularisation. REVIEWER'S CONCLUSIONS: Photodynamic therapy in people with classic choroidal neovascularisation due to age-related macular degeneration is effective in preventing visual loss. This evidence is drawn from a subgroup analysis of 143 participants in one trial. Outcomes and potential adverse effects of this treatment should be monitored closely. There is no evidence that photodynamic therapy is beneficial for people with evidence of occult choroidal neovascularisation. These people should be offered treatment in the context of a randomised trial.

Humans↗

Reperfusion of occluded capillary beds in diabetic retinopathy.

PURPOSE: To demonstrate the reperfusion of nonperfused capillary beds in diabetic retinopathy. METHODS: In a retrospective study, we reviewed 292 fluorescein angiograms of 94 eyes of 74 patients (mean age, 52 years; range, 20 to 68 years) with diabetic retinopathy. Fluorescein angiography was performed repeatedly (mean, three times; range, two to eight times) during a mean follow-up period of 2 years (range, 3 months to 12 years). None of the 94 eyes received laser photocoagulation. RESULTS: Reperfusion of occluded capillary beds was observed in 65 (69%) of 94 eyes. Reperfusion was characterized by recanalization in 22 (34%) of the 65 eyes or by intraretinal neovascularization in 54 (83%) of the 65 eyes. The former took place in small nonperfused areas and the latter in larger nonperfused areas. Reperfusion occurred throughout the entire fundus in six of 94 eyes, resulting in resolution of diabetic retinopathy. Reperfused capillary beds with intraretinal neovascularization left vascular remodeling, which was seen as twisted or kinked abnormal vessels. CONCLUSIONS: In diabetic retinopathy, occluded capillary beds may be reperfused. Twisted abnormal vessels may represent the reperfusion process through intraretinal neovascularization.

Adult↗

Photodynamic therapy and intravitreal triamcinolone for a subretinal neovascularization in bilateral idiopathic juxtafoveal telangiectasis.

PURPOSE: To report combined treatment of photodynamic therapy (PDT) with verteporfin and intravitreal triamcinolone acetonide injection for subfoveal neovascularization secondary to bilateral idiopathic juxtafoveal telangiectasis. DESIGN: Interventional case report. METHOD: A patient with a subfoveal neovascularization secondary to bilateral idiopathic juxtafoveal telangiectasis was treated with PDT plus an intravitreal injection of 4 mg of triamcinolone acetonide. RESULTS: Leakage in the late-phase of fluorescein angiography resolved with attenuation of telangiectatic vessels and improvement in visual acuity from 20/200 to 20/50. At 9 months post-treatment, recurrent leakage was treated with repeat PDT and intravitreal triamcinolone. One year after initial presentation, visual acuity was 20/60 with no leakage on fluorescein. CONCLUSION: Combined treatment with PDT and intravitreal triamcinolone acetonide resulted in regression of a subfoveal neovascular membrane and improvement in visual acuity during the course of follow-up.

Drug Therapy, Combination↗

Hypercapnia prevents neovascularization via nitrative stress.

Neovascularization after an ischemic insult is a beneficial attempt to salvage the injured tissue. Yet, despite the production of angiogenic factors within ischemic tissues, compensatory growth of new vessels fails to provide adequate vascularization. Thus, we hypothesized that local factors counter efficient revascularization. Whereas ischemia is often considered to be synonymous with an oxygen deficit, it is also associated with a concomitant local elevation of carbon dioxide (CO2). Although studies suggest that hypercapnia impacts tissue neovascularization, its significance relative to the abundantly described effects of hypoxia and its underlying mechanisms have yet to be elucidated. Therefore, we investigated the effects of hypercapnia on blood vessel growth in models of developmental and ischemic neovascularization. Acute and prolonged CO2 exposure inhibited developmental neovascularization of the rodent retina, as well as revascularization of the ischemic retina. Hypercapnia induced early increases in endothelial nitric oxide synthase and nitrative stress, associated with astrocyte impairment and endothelial cell death, as well as downregulation of the proangiogenic prostaglandin E2 receptor EP3. These results establish a previously unexplored means by which hypercapnia hinders efficient neovascularization, a mechanism that may contribute to ischemic tissue injury.

Animals↗

Photodynamic therapy of subretinal neovascularization in the monkey eye.

Experimental subretinal neovascularization in the monkey eye was treated by photodynamic therapy with rose bengal. Following intravenous injection of rose bengal, the subretinal vessels were irradiated with filtered light. Successful treatment was achieved, provided the subretinal vessels were irradiated during the period in which the dye was present in and around the subretinal vessels but had already cleared from the retinal vasculature. The successfully treated lesions demonstrated replacement of the leaking and pooling subretinal vessels with a non-leaky scar. Morphologic evaluation revealed immediate destruction of the subretinal plexus, with minimal damage to the overlying retina. The destroyed subretinal tuft was replaced by a scar containing mainly fibroblasts embedded in collagen fibers. Our results suggest that photodynamic therapy is potentially useful for destruction of subretinal vessels without damaging the overlying retina.

Animals↗

Neovascular glaucoma as a complication of retinal vasculitis in Crohn disease.

PURPOSE: To report a case of neovascular glaucoma as a complication of retinal vasculitis in Crohn disease. METHODS: Case report with fluorescein angiogram. RESULTS: A 62-year-old man with biopsy-proven Crohn disease presented with bilateral uveitis, bilateral iris new vessels, and neovascular glaucoma in the left eye. Fluorescein angiography revealed signs of retinal vasculitis and capillary nonperfusion in both eyes. CONCLUSION: Crohn disease may be associated with retinal vasculitis and, thus, neovascular glaucoma. A satisfactory result can be achieved by using corticosteroids to control the retinal vascular inflammation, by applying panretinal photocoagulation and by controlling the increased intraocular pressure surgically.

Administration, Topical↗

Subretinal neovascular membrane associated with type 2a idiopathic juxtafoveolar telangiectasis in pseudoxanthoma elasticum.

BACKGROUND: The objective was to report a case of pseudoxanthoma elasticum associated with type 2A idiopathic juxtafoveolar telangiectasis (T2AIJT) complicated by bilateral subretinal neovascular membranes (SRNVM). METHODS: The right eye with juxtafoveal SRNVM and the left eye with subfoveal SRNVM underwent laser photocoagulation and photodynamic therapy respectively. The follow-up duration was 48 months. RESULTS: Best corrected visual acuity was 20/32 in both eyes at baseline, and 20/32 in the right eye and 20/200 in the left eye at the end of the follow-up. Atrophic changes in the retinal pigment epithelium developed around the SRNVM treated with photodynamic therapy (PDT). CONCLUSIONS: Pseudoxanthoma elasticum may be associated with T2AIJT complicated by bilateral SRNVM. Further studies are needed to assess both efficacy and appropriate PDT regime in T2AIJT-related SRNVM, especially if associated with other conditions.

Coloring Agents↗

[What is the etiology of diabetic retinopathy?].

Recent experimental and clinical investigations suggest several pathogenetic mechanisms for diabetic retinopathy. The pathogenesis of diabetic retinopathy can best be understood by a concerted action of biochemical, hemodynamic and endocrine or cytokinetic factors. Biochemical factors such as nonenzymatic glycosylation and induction of the aldose reductase pathway seem to be of importance for the genesis of nonproliferative diabetic retinopathy, characterized by pericyte loss, basal membrane thickening and formation of microaneurysms. The development of the proliferative form, characterized by ocular neovascularization, is the response to chronic hypoxia and is probably due to the angiogenetic influence of hormones and growth factors. The most important therapeutic approach is strict control of hyperglycemia.

Aldehyde Reductase↗

Radiotherapy treatment of age-related subfoveal neovascular membranes in patients with good vision.

This prospective study investigated whether low-dose ionising radiotherapy preserved vision and caused membrane regression in patients with age-related subfoveal neovascular membranes (SFNVMs) or vascularised pigment epithelial detachments (PEDs) and relatively good initial visual acuities. Twenty-five patients with initial Snellen acuities of 6/24 or better were treated with low-dose external beam radiotherapy. Of the patients with SFNVMs, visual acuities were maintained or improved in 58% at 6 months and 53% at 1 year. Neovascular membrane size was assessed by image analysis and showed some regression in 47% and 41% at 6 and 12 months respectively. These results suggest that patients with SFNVMs and good vision may benefit from radiotherapy, faring better than previous reports of the natural history of this condition. Conversely, patients with vascularised PEDs did not appear to benefit from radiotherapy. Only 17% maintained their vision at 1 year and 33% suffered retinal pigment epithelial tears. The results from patients with SFNVMs and good initial vision, excluding those with vascularised PEDs, are encouraging however, any benefit from this treatment needs to be proven by controlled trials with long follow-up.

Aged↗

[Intraocular neovascularization].

To investigate the mechanism of intraocular neovascularization, we studied how vascular endothelial growth factor (VEGF) and interleukin-8 (IL-8) are expressed in the ocular tissues under hypoxic conditions. Prior to proliferation of vascular endothelial cells resulting in neovascularization, the retinal tissues such as pericytes, retinal glial cells, ganglion cells, and ciliary epithelium react directly to hypoxia expressing VEGF and/or IL-8 and stimulate endothelial cell proliferation in a paracrine manner. We demonstrated that transcription factor activator protein-1 (AP-1) is activated for expression of VEGF messenger ribonuculeic acid (mRNA) and in a similar way nuclear factor kappa B (NF-kappa B) is activated for expression of IL-8 mRNA. However, hypoxia-induced expression of VEGF and/ or IL-8 is only one aspect of the complicated processes in intraocular neovascularization. We hope that further detailed analysis of the mechanism will make it possible to inhibit and treat clinically intraocular neovascularization in the near future.

Adult↗