Peripheral Retinal Neovascularization Research Articles

Diabète et ischémie des membres inférieurs : bénéfice potentiel des stratégies d'angiogenèse thérapeutique

Cardiovascular complications are the leading cause of morbidity and mortality in patients with diabetes mellitus; up to 80% of deaths in patients with diabetes are closely associated with vascular disease. The ability of the organism to form a collateral network of blood vessels constitutes an important response to vascular occlusive disease and determines to a large part the clinical consequences and severity of tissue ischemia. The development of new vessels is significantly reduced in diabetic patients with coronary or peripheral artery disease. This probably contributes to the severe course of limb ischemia in diabetic patients, in which peripheral artery disease often results in foot ulceration and lower extremity amputation. Diabetic retinopathy remains one of the major causes of acquired blindness in developed nations. This is true despite the development of laser treatment, which can prevent blindness in the majority of those who develop macular edema or proliferative diabetic retinopathy. The hallmark of diabetic retinopathy is the lack of microvessels in the macula, leading to hypoxia, associated with peripheral retinal neovascularization that may ultimately cause severe vitreous cavity bleeding and/or retinal detachment. The factors that stimulate retinal blood vessel growth have not been fully defined, but there is accumulating evidence that the renin-angiotensin-bradykinin system may be involved in a number of retinal vascular disorders, including retinopathy of prematurity and proliferative diabetic retinopathy. Only a few studies have specifically evaluated the effect of diabetes on angiogenesis in ischemic vascular disease and in the retina. Moreover, the mechanisms by which diabetes could both limit the formation of new blood vessels in most organs and simultaneously induce proliferative diabetic retinopathy remain largely undefined. In the present review, we aimed to briefly describe the main molecular mechanisms involved in the ischemia-induced angiogenesis, and their alterations in diabetes. Possible therapeutic strategies to restore angiogenesis in diabetic patients are also listed.

Molecular Basis of Angiopathy in Diabetes Mellitus

See related article, pages 55–62 Cardiovascular complications are the leading cause of morbidity and mortality in patients with diabetes mellitus; up to 80% of deaths in patients with diabetes are closely associated with vascular disease. The ability of the organism to form a collateral network of blood vessels constitutes an important response to vascular occlusive disease and determines to a large part the clinical consequences and severity of tissue ischemia. The development of new vessels is significantly reduced in diabetic patients with coronary or peripheral artery disease.1,2 This probably contributes to the severe course of limb ischemia in diabetic patients, in which peripheral artery disease often results in foot ulceration and lower extremity amputation. Diabetic retinopathy remains one of the major causes of acquired blindness in developed nations. This is true despite the development of laser treatment, which can prevent blindness in the majority of those who develop macular edema or proliferative diabetic retinopathy. The hallmark of diabetic retinopathy is the lack of microvessels in the macula, leading to hypoxia, associated with peripheral retinal neovascularization that may ultimately cause severe vitreous cavity bleeding and/or retinal detachment. The factors that stimulate retinal blood vessel growth have not been fully defined, but there is accumulating evidence that the renin-angiotensin-bradykinin system (RAKS) may be involved in a number of retinal vascular disorders, including retinopathy of prematurity and proliferative diabetic retinopathy3,4 Only a few studies have specifically evaluated the effect of diabetes on angiogenesis in ischemic vascular disease and in the retina. Moreover, the mechanisms by which …

Surgical management of retinal detachment secondary to acute retinal necrosis: clinical features, surgical techniques, and long-term results

Purpose: To describe the clinical features of complicated retinal detachment secondary to acute retinal necrosis (ARN) and to present the long-term results of vitreous surgery in these cases. Methods: A retrospective study was conducted on 16 immunocompetent patients (18 eyes). The average follow-up period was 60 months. Results: Proliferative vitreoretinopathy (PVR) grade C, with the predominance of anterior PVR, and characteristic changes in the vitreous base area were present in all cases before surgery. All eyes underwent vitrectomy, membrane peeling, endolaser photocoagulation, and intraocular tamponade without scleral buckling. Additional procedures were performed in 13 eyes. Retinal reattachment was achieved in the 18 eyes (100%) in the short term. Variable degrees of reproliferation occurred in all cases after surgery. Other delayed complications included ocular hypotony, macular pucker, peripheral retinal neovascularization, and severe preretinal fibrosis. Improvement of visual acuity occurred in 13 eyes (72.2%). Eleven eyes (61.1%) achieved final ambulatory visual acuity of 5/200 or better. Conclusions: Rhegmatogenous retinal detachment secondary to ARN has characteristic clinical features. Severe proliferative vitreoretinopathy with the predominance of anterior PVR develops rapidly. Reproliferation is the most important late postvitrectomy complication necessitating multiple surgical procedures in these cases. The visual results remain unfavorable due to the destructive nature of ARN.

Idiopathic polypoidal choroidal vasculopathy and sickle cell retinopathy

PURPOSE: To report a patient who had concomitant idiopathic polypoidal choroidal vasculopathy and sickle cell retinopathy. METHOD: Case report. A 46-year-old black woman presented with sudden onset of “blurring” in the left eye. Her ocular history was unremarkable, and her medical history was relevant for sickle cell disease with yearly episodes of sickle cell crises. RESULTS: Both eyes had evidence of idiopathic polypoidal choroidal vasculopathy and peripheral retinal neovascularization secondary to sickle cell disease. The left eye had hemorrhagic retinal pigment epithelial detachments secondary to idiopathic polypoidal choroidal vasculopathy. CONCLUSION: We present this case as an example of concomitant sickle cell retinopathy and idiopathic polypoidal choroidal vasculopathy. We are unaware of previous reports with these findings.

Diseases of the Retina and Vitreous.

Anatomy. How to Examine the Fundus. Fluorescein Angiography. Indocyanine Green Angiography. B-Scan Ultrasonography. Hereditary Chorioretinal Dystrophies. Pediatric Retinal Diseases. Retinal Vascular Occlusive Disease. Diabetic Retinopathy. Treatment of Choroidal Neovascularization. Aneurysms and Telangiectasis. Retinal and Choroidal Manifestations of AIDS. White Dot Syndromes. Traction Maculopathies. Sickle Cell Retinopathy and Other Causes of Peripheral Retinal Neovascularization. Central Serous Chorioretinopathy. Tumours of the Ocular Fundus. Vitreoretinal Complications of Cataract Surgery. Laser Photocoagulation. Rhegmatogenous Retinal Detachment: Diagnosis and Management. Pars Plana Vitrectomy.

Macular fibrosis associated with talc retinopathy

PURPOSE: To investigate a patient with talc retinopathy who developed macular fibrosis with resultant visual loss. METHODS: A 64-year-old intravenous drug abuser was evaluated for bilateral peripheral retinal neovascularization. He admitted to abusing oral methylphenidate intravenously. Funduscopy showed numerous intravascular talc particles in the macular area of both eyes. Over a period of next 4 years, visually significant macular fibrosis gradually developed in both eyes, the left eye more than the right eye. RESULTS: Fluorescein angiography confirmed the presence of bilateral peripheral retinal neovascularization with adjacent areas of ischemic retina. The patient was treated with peripheral laser treatment to the ischemic retina with resultant regression of peripheral retinal neovascularization. Bilateral macular fibrosis accounted for the reduced vision in our patient. CONCLUSION: Talc retinopathy can be associated with macular fibrosis with resultant visual loss.

Peripheral retinal neovascularization (Eales disease) associated with the factor V Leiden mutation

Purpose: To illustrate a case of peripheral retinal neovascularization (Eales disease) in a patient who tested positive for the factor V Leiden mutation. Methods: A 42–year–old woman had a 1-week history of blurred vision in her right eye. Her medical history was remarkable for a cerebrovascular accident. Ophthalmoscopy of the right eye disclosed a mild vitreous hemorrhage and a ridge of retinal neovascularization in the temporal periphery. The left fundus showed evidence of temporal retinal ischemia. A laboratory evaluation for hypercoagulability was positive for factor V Leiden mutation. Results: Peripheral scatter laser photocoagulation was applied to the ischemic retina, and the neovascularization regressed. The patient began taking warfarin sodium to prevent further thrombotic events. Conclusion: A laboratory evaluation for coagulopathy, including the factor V Leiden mutation, should be added to the examination of patients with Eales disease, especially individuals with a history of a previous thrombotic event.

Peripheral Retinal Neovascularization and Retinal Vascular Occlusion Associated With Activated Protein C Resistance

To describe a patient with peripheral retinal neovascularization and vascular occlusion associated with activated protein C resistance. Case report. A 63-year-old woman was examined for acute loss of vision in both eyes. She was noted to have macular edema in both eyes as well as a macular branch vein occlusion in the right eye and a central retinal vein occlusion in the left eye. Peripheral retinal neovascularization was present in both eyes. Extensive systemic evaluation disclosed a heterozygous state for the factor V Leiden indicating activated protein C resistance. Activated protein C resistance may be associated with peripheral retinal neovascularization.

Bilateral Bullous Exudative Retinal Detachment Complicating Idiopathic Central Serous Chorioretinopathy during Systemic Corticosteroid Therapy

To present evidence that systemic corticosteroid therapy may cause bilateral bullous serofibrinous exudative retinal detachment in some patients with idiopathic central serous chorioretinopathy. Idiopathic central serous chorioretinopathy usually causes mild, transient loss of central vision, usually in otherwise healthy men with a type A personality. A few patients have permanent visual loss because of chronic and recurrent retinal detachment. The clinical findings in these patients may lead to incorrect diagnoses and use of corticosteroid therapy. The clinical and photographic records of three patients in whom bilateral bullous serofibrinous exudative retinal detachment associated with idiopathic central serous chorioretinopathy developed after treatment with systemic corticosteroids were reviewed. Systemic corticosteroid treatment was instituted (1) as a prophylaxis to prevent exacerbation of the disease while undergoing surgery in the fellow eye, and (2) as the result of misdiagnoses of multifocal choroiditis and retinal vasculitis (Eales disease). Two of the patients had a history of chronic recurrent retinal detachments before institution of corticosteroid treatment. In one of these patients, bilateral chronic inferior retinal detachment developed, causing peripheral retinal vascular nonperfusion, retinal neovascularization, and vitreous hemorrhage. All three patients had severe permanent visual loss in one or both eyes. The findings in these patients provide further evidence that systemic corticosteroid treatment may cause severe exacerbation of retinal detachment and lasting visual loss in some patients with idiopathic central serous retinopathy. Recognition of the atypical presentations of this disorder is important to avoid incorrect diagnoses and treatment.

Retinopathy Associated With Hemoglobin AC

Peripheral retinal neovascularization is a well-studied complication of sickle cell hemoglobinopathy and has been recognized in hemoglobin SC disease, hemoglobin SS disease, and sickle cell—β-thalassemia and occasionally in hemoglobin AS disease (sickle cell trait). 1 There are only a few reports in the literature of retinal vascular changes associated with hemoglobin AC disease (C trait), 1-3 a condition that generally has limited clinical manifestations. We report herein a case of subhyaloid hemorrhage and peripheral retinal neovascularization in the setting of hemoglobin AC disease. Report of a Case. A 57-year-old black man with a history of systemic hypertension and coronary artery disease presented in April 1988 with a complaint of central scotoma in the left eye. Best corrected visual acuities were 20/20 OD and 20/400 OS, and the findings on slit-lamp examination were normal in both eyes. Ophthalmoscopic examination of the right eye revealed a few, small, peripheral intraretinal hemorrhages. Ophthalmoscopic

Severe Periphlebitis, Peripheral Retinal Ischemia, and Preretinal Neovascularization in Patients With Multiple Sclerosis

Two patients with definite multiple sclerosis and marked retinal periphlebitis developed occlusive peripheral retinal vasculitis, which resulted in peripheral retinal ischemia and peripheral retinal neovascularization. Results of investigation for other causes of peripheral proliferative retinopathies were negative in both patients although one patient had a positive anticardiolipin antibody. Both patients have been followed up for over seven years and have maintained good visual acuity with mild regression of the preretinal neovascularization without laser intervention. An analysis of these two cases and six other reported cases indicates that severe periphlebitis can evolve into occlusive peripheral vasculitis, which results in peripheral retinal neovascularization in patients with multiple sclerosis.

Correlation of Electroretinographic Findings and Peripheral Retinal Nonperfusion in Patients With Sickle Cell Retinopathy

This study examined the relationship between the proportion of peripheral retinal nonperfusion and electroretinogram measures in one untreated eye of 44 patients with sickle cell retinopathy. The proportion of peripheral retinal nonperfusion was derived from fluorescein angiographic frames covering 180 degrees of the temporal periphery. The extent of peripheral retinal capillary nonperfusion was greater in patients with peripheral retinal neovascularization compared with those without neovascularization. Reductions in electroretinogram a- and b-wave amplitudes were found in patients with and without neovascularization. However, such reductions were of greater frequency and magnitude in patients with neovascularization. Electroretinogram abnormalities were restricted to reductions in amplitude; implicit times were generally normal. In terms of the variables of the b-wave luminance-response function, abnormalities were restricted to reductions in the amplitude variable Rmax; values of logK and n were generally within the normal range. Across all patients, there was a significant negative correlation between electroretinogram amplitude measures and capillary nonperfusion, indicating that the electroretinogram provides information about the functional consequences of peripheral capillary nonperfusion in sickle cell retinopathy.

OPTIC DISC NEOVASCULARIZATION IN DOMINANT EXUDATIVE VITREORETINOPATHY

Dominant exudative vitreoretinopathy (DEVR) is inherited retinal vascular disorder which is characterized by peripheral retinal neovascularization, tractional retinal detachment, subretinal, exudation, and vitreous fibrosis. A milder form of involvement characterized by capillary nonperfusion and straightening of the retinal vessels may be present in asymptomatic individuals. We describe a 15-year-old patient who presented with optic disc neovascularization, a finding not previously reported in association with DEVR. Angiographic evidence of DEVR in successive generations confirmed the diagnosis. The findings in mild and advanced DEVR are reviewed, and the pathogenesis of the capillary nonperfusion is discussed.

Oxygen-Induced Retinopathy in Newborn Rats: Effects of Prolonged Normobaric and Hyperbaric Oxygen Supplementation

An experimental study was conducted to verify the effects of prolonged normobaric and hyperbaric oxygen supplementation on retinal vessels in newborn animals. Nine litters of newborn Wistar rats were used in the following way. Two litters were used as controls. Two other litters received normobaric oxygen supplementation (FiO2 80%) for five days after birth. These rats were then removed and kept for five more days in room air. Retinopathy with marked peripheral retinal neovascularization was seen in these litters. Three other litters were exposed to the same treatment for ten days after birth, removed from oxygen, and kept for 15 more days in room air. Severe retinopathy with extraretinal proliferation and, in some cases, retinal detachment developed in these animals. Two other litters received hyperbaric (1.80 atm) oxygen supplementation (FiO2 80%) for ten days after birth and were then kept for 15 days in normobaric room air. These animals showed no evidence of peripheral retinopathy. It is possible that moderate hyperbarism exerts, in the newborn rat, a protective action against the toxic effects of oxygen supplementation on immature retinal vessels.

Electroretinographic Findings in Sickle Cell Retinopathy

We obtained electroretinograms (ERGs) from normal subjects and from patients with sickle cell disease. The ERG components (a-wave, b-wave, and oscillatory potentials) obtained from normal subjects and patients without peripheral retinal neovascularization did not differ in either amplitude or implicit time. However, ERG components obtained from patients with peripheral retinal neovascularization were reduced in amplitude compared with those obtained from normal subjects or patients without neovascularization. The reduced a-wave, b-wave, and oscillatory potential amplitudes may have been due to photoreceptor dysfunction secondary to choroidal ischemia or possibly increased oxygen demands by the inner retina. Ischemia of the inner retina may also have contributed to the altered b-wave and oscillatory potentials. These results suggest that ERG provides a means of assessing the consequence of peripheral retinal ischemia to retinal cell function and could be of value in monitoring patients with sickle cell disease for the development of clinically significant peripheral retinal neovascularization.

Retinitis Pigmentosa and Retinal Neovascularization

Four patients with retinitis pigmentosa and either disc or peripheral retinal neovascularization with recurrent vitreous hemorrhage are described. One patient with peripheral retinal neovascularization also had rubeosis and neovascular glaucoma. The effects of relative hyperoxia on the retinal microcirculation in retinitis pigmentosa as well as intraocular inflammation may account for such changes. Laser photocoagulation appears effective in preventing vitreous hemorrhage in these patients, but systemic administration of corticosteroids did not cause the new vessels to regress.

Prophylactic laser photocoagulation in hereditary snowflake vitreoretinal degeneration. A family report.

Examination of 37 members of a family revealed that 17 had snowflake vitreoretinal degeneration. All those affected showed some evidence of vitreous degeneration and 13 had retinal changes with differing degrees of severity. Vitreal changes may thus present as an early stage when hardly any retinal pathology is apparent. Peripheral retinal neovascularization was seen in four patients. Rhegmatogenous retinal detachment developed in two eyes and retinal breaks in six additional eyes. Because of the poor surgical prognosis in such cases, prophylactic treatment with argon laser photocoagulation is recommended for any type of retinal break.

Indirect Treatment of Peripheral Retinal Neovascularization

Indirect (scatter) cryotherapy and photocoagulation treatments successfully obliterated peripheral neovascularization in patients with sickle cell retinopathy and talc retinopathy. Fifteen of 17 neovascular fronds in seven eyes of five patients were obliterated. This type of treatment is analogous to panretinal photocoagulation for diabetic retinopathy. Because low energy levels are used, indirect treatment of peripheral neovascularization may be a safe and effective alternative to focal treatment of feeder vessels.

Indentation laser photocoagulation of peripheral retinal neovascularization.

The treatment of peripheral retinal neovascularization by laser photocoagulation is an accepted technique. One of its limitations is the difficulty in photocoagulating retinal neovascularization that has become even slightly elevated from the underlying pigment epithelium. The failure to close the neovascular frond and the production of a vitreous hemorrhage are the complications from the direct photocoagulation of elevated neovascularization. The currently accepted method of treating the feeding retinal arteriole and venule, although successful, requires multiple treatment sessions. The use of a scleral indentation funnel at the time of laser photocoagulation permits the direct photocoagulation of elevated neovascularization in some cases. This technique increases the number of neovascular fronds that are amenable to direct laser photocoagulation, improves the rate of success of closure of the neovascularization by photocoagulation, decreases the necessary number of treatment sessions, and decreases the risks from treatment.

Platelet-Induced Retinal Neovascularization in Leukemia

Retinal changes resembling those of background diabetic or hypertensive retinopathy commonly occur in leukemia, whereas retinal neovascularization is rare. When neovascularization does occur, it is usually the result of hyperviscosity caused by a greatly increased number of circulating leukocytes. A 42-year-old woman with diabetes mellitus developed chronic myelocytic leukemia and peripheral retinal neovascularization. The hyperviscosity leading to the neovascularization was probably caused by an increased number of circulating platelets.