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Sudden painless visual loss: retinal causes.

Sudden painless visual loss occurs in retinal disorders that reflect primary ocular disease, as well as systemic disease. This article reviews vitreous and retinal detachment and macular degeneration as ocular causes of sudden visual loss. Retinal changes that are caused by systemic disease, including infectious retinitis, occlusion of retinal vessels, and proliferative new vessel formation, are reviewed. In each instance, the retinal examination should provide the ocular or systemic diagnosis or lead to the diagnosis.

Aged↗

Analysis of vessel absorption profiles in retinal oximetry.

The optical densities of vessel absorption features in small bandwidth fundus photographs have been used by many people for finding the oxygenation of the blood in retinal vessels. The purpose of this article is to show that the information found in this way can be made more accurate, and more information can be found by considering the details of the absorption profile (intensity as a function of distance across the vessel). The "wings" of the profile are primarily determined by the line-spread function of the video camera or film. A four-parameter curve fitting procedure using the line-spread function and an "ideal" vessel profile can be used to eliminate the effects both of the line-spread function and of any central reflection (vessel reflex) that may be present, yielding estimates of the vessel diameter and central absorption. The conclusions concerning the reflection are supported by studies of reflections from capillary tubes and wires in a model eye.

Biophysical Phenomena↗

Impaired retinal autoregulation in small retinal arterioles before and after focal laser treatment for diabetic maculopathy.

AIMS: To study the effect of an acute increase in the arterial blood pressure on the diameter response of retinal arterioles supplying areas with focal diabetic macular oedema before and after laser photocoagulation, and control arterioles supplying areas without oedema. METHODS: In 17 diabetic patients the diameter response of arterioles after an increase in the arterial blood pressure induced by isometric exercise was studied using the retinal vessel analyser (RVA). In each patient a study arteriole supplying a focal area of macular oedema as well as a control arteriole supplying a retinal area without retinopathy lesions was selected, and the diameter response of these vessels was performed immediately before, and 1 hour and 3 months after focal laser photocoagulation of the focal oedema area. RESULTS: The diameter response was impaired in both study arterioles and control arterioles before focal laser photocoagulation. The treatment induced regression of the focal retinal oedema, but did not affect the diameter response in the arteriole supplying this area (p = 0.85). CONCLUSION: Impairment of the diameter response in small arterioles from diabetic patients does not parallel the regional distribution of retinopathy lesions. Other factors than disturbed autoregulation are probably involved in generating flow disturbances and oedema in diabetic maculopathy.

Adult↗

Evolution of neovascularization in mice with overexpression of vascular endothelial growth factor in photoreceptors.

PURPOSE: To determine the earliest changes that occur in the retina after the onset of ectopic expression of vascular endothelial growth factor (VEGF) by photoreceptors in transgenic mice, to characterize the development of neovascularization (NV), and to determine the feasibility of using these mice to test the efficacy of antiangiogenic agents. METHODS: The time course of expression of VEGF transgene mRNA was determined by reverse transcription-polymerase chain reaction (RT-PCR). Histopathologic changes in the retina were investigated by light and electron microscopy and immunocytochemistry. Standard and confocal fluorescence microscopy and image analysis were used to evaluate NV in retinal whole mounts. RESULTS: VEGF transgene mRNA was first detected in the retina by RT-PCR on postnatal day 6 (P6) and increased over the next several days to reach a constant steady-state level between P14 and P21. Abnormal cells were seen in the outer nuclear layer on P10 and among photoreceptors on P14; by P18 there were cell aggregates in the subretinal space with evidence of lumen formation. The invading cells were demonstrated to be endothelial cells by staining with an endothelial cell-specific lectin. Whole mounts of retinas perfused with fluorescein-labeled dextran showed a similar sequence of events, with sprouts from retinal vessels in the deep capillary bed seen on P14 and vessels reaching the subretinal space by P18. Confocal and standard fluorescence microscopy and changes in the number and area of neovascular lesions in the subretinal space over time measured by image analysis suggest gradual enlargement and coalescence of vascular complexes. The subretinal NV was progressively engulfed by the retinal pigmented epithelium. Invasion of blood vessels from the choroid was not identified in any specimen. CONCLUSIONS: These data support the feasibility of using rhodopsin-VEGF transgenic mice to study tissue-specific aspects of NV in the retina and to test antiangiogenic agents for inhibition of intraretinal and subretinal NV.

Animals↗

Subretinal neovascularization in the rat induced by IRBP synthetic peptides.

The present study was undertaken to develop a new animal model of subretinal neovascularization that does not involve traumatic manipulation of the eye. Using this model, the mechanism of subretinal neovascularization and its penetration through Bruch's membrane, and the various factors that contribute to this process were then examined. Male Lewis rats were immunized with interphotoreceptor retinoid binding protein (IRBP) peptide R-4, and the eyes histologically examined at various times up to 45 days after immunization. On day 12 after immunization, inflammatory cells were identified primarily in the anterior segment of the eye, with scattered cells in the retina and choroid. The inflammation was most prominent on day 14, by which time many eyes showed serous retinal detachment. By day 18 the inflammation had declined in intensity, but branches of the retinal vessels were seen extending into the choroid. Examination on day 30 revealed even fewer inflammatory cells but an accumulation of retinal pigment epithelial cells and mononuclear cells was present in the subretinal space. Examination on day 45 revealed no appreciable inflammation, but typical new vessels were found in the eyes from five of the 13 rats (38%) examined at that point. Mild inflammation of the retinochoroidal tissue can induce subretinal new vessels in rats, and this model will be useful for further study of subretinal new vessel formation.

Amino Acid Sequence↗

Vascular endothelial growth factor and vascular permeability changes in human diabetic retinopathy.

PURPOSE: The authors used histochemical analysis to determine whether increased vascular endothelial growth factor (VEGF) immunoreactivity in diabetic retinal vessels is related to increased vascular permeability, as indicated by human serum albumin (HSA) immunostaining, or to presumed retinal hypoxia as demonstrated by decreased vascularity. A correlation between VEGF and HSA in cryosections with angiopathic changes in the adenosine diphosphatase (ADPase) flat-embedded fellow retinas was sought. Because VEGF is a heparin-binding protein, the relation between VEGF and heparan sulfate proteoglycan (HSPG) immunoreactivities was also investigated. METHODS: Cryopreserved eyes from 18 diabetic and 9 nondiabetic subjects removed after death were sectioned and immunohistochemical analysis was performed with antibodies against VEGF, HSA, HSPG, vWf (von Willebrand factor), and collagen IV. The fellow retinas were prepared by our ADPase flat-embedding technique to determine the degree of diabetic retinopathy. The number of positive vessels for each antibody and antibody localizations were determined by light microscopy. RESULTS: The average number of VEGF-stained vessels in diabetic retinas was significantly higher than in nondiabetic retinas (P = 0.04). In diabetic retinas, there was a positive correlation between the distribution of VEGF-positive vessels and the distribution of HSA- and HSPG-positive vessels. No such correlation was observed in nondiabetic eyes. In many cases, HSPG immunoreactivity appeared colocalized with VEGF immunoreactivity, suggesting VEGF binding to HSPG. The comparison with the ADPase flat-embedded fellow retinas suggested that increased VEGF immunoreactivity and vascular permeability may occur before morphologic changes in the vasculature. CONCLUSIONS: Vascular endothelial growth factor immunoreactivity was correlated with increased vascular permeability to macromolecules and appears to be increased in diabetic subjects before the onset of retinopathy.

Adult↗

Increased blood pressure induces a diameter response of retinal arterioles that increases with decreasing arteriolar diameter.

PURPOSE: To study the diameter response of retinal arterioles as a function of the arteriolar diameter. METHODS: Ten healthy young volunteers aged 22 to 33 years were subjected to diameter measurement of four successive segments of a retinal arteriole with a retinal vessel analyzer (RVA). At each of the segments, the diameter response during an increase in the systemic blood pressure (mean arterial pressure [MAP]) induced by isometric exercise was compared to the diameter of the arterioles during rest. RESULTS: The isometric exercise induced a significant contraction of the studied vessel segments averaging 2.5% +/- 0.4% (P < 0.0001, n = 40). There was a significant negative correlation between the baseline diameter of the studied vessel segments and the diameter response induced by isometric exercise (P = 0.02). CONCLUSIONS: The blood pressure-induced diameter response of retinal arterioles increased with decreasing diameter of the vessels. The results indicate that the distal retinal arterioles play a major role in the regulation of retinal blood flow.

Adult↗

Luminal vesicles in endothelial cells of retinal and iridial vessels of the rat.

Endothelial vesicles on the luminal front of retinal and iridial vessels were studied by perfusion fixation after intravenous injection of peroxidase, and by perfusion fixation of glutaraldehyde with tannic acid or ruthenium red. Many luminal vesicles contained peroxidase reaction product after intravenous injection of peroxidase, but were virtually empty after perfusion fixation. Both tannic acid and ruthenium red delineated the majority of luminal vesicles, singular or in clusters, surface-associated or "free" in the cytoplasm. Only a few free vesicles were unlabeled by the dye. No transendothelial channels were seen. The results suggest that most of the vesicles on the luminal front of endothelial cells are continuous with the cell surface at the time of fixation. The function of these vesicles is not fully understood; some appear to be involved in endocytosis of macromolecules from the vascular lumen.

Animals↗

Attenuation of retinal vascular development and neovascularization in transgenic mice over-expressing thrombospondin-1 in the lens.

Thrombospondin-1 (TSP1) is an endogenous inhibitor of angiogenesis and induces endothelial cell (EC) apoptosis. To study the role TSP1 plays during vascular development and neovascularization, we assessed the effects of ectopic TSP1 expression in the lens on retinal vascularization in transgenic mice. The TSP1 over-expressing mice showed abnormalities in the development of retinal vasculature. There was a dramatic decrease in the density of superficial and deep vascular plexuses of the retina in transgenic mice. The retinal vessels in TSP1 transgenic mice also appeared nonuniform and abnormal in maturation. We detected an increase in the number of EC undergoing apoptosis, which was compensated, in part, by an increase in cell proliferation in retinal vasculature of TSP1 transgenic mice. The TSP1 transgenic mice also exhibited increased levels of vessel obliteration and a limited preretinal neovascularization during oxygen-induced ischemic retinopathy (OIR). Our results indicate increased expression of TSP1 attenuates normal retinal vascularization and preretinal neovascularization during OIR. Therefore, modulation of TSP1 expression may provide an effective mechanism for regulation of ocular angiogenesis.

Animals↗

[Hereditary retinal macrovessel. Report of 2 cases].

PURPOSE: We report two cases of hereditary retinal macrovessel an uncommon condition where an anomalous retinal vessel crosses the macula. CASE REPORT: A 45-year-old woman complained of fluctuating visual acuity in the right eye for 10 years. A 24-year-old man was seen at a routine ophthalmic examination. In both patients, dilated fundus examination and fluorescein angiogram confirmed the diagnosis. DISCUSSION: Hereditary retinal macrovessel is a rare condition. The anomalous vessel is remarkably stable and complications only occur exceptionally as described in the literature.

Adult↗

Implication of the hypoxia response element of the Vegf promoter in mouse models of retinal and choroidal neovascularization, but not retinal vascular development.

Retinal neovascularization (NV) and macular edema, resulting from blood-retinal barrier (BRB) breakdown, are major causes of visual loss in ischemic retinopathies. Choroidal NV (CNV) occurs in diseases of the retinal pigmented epithelium/Bruch's membrane complex and is another extremely prevalent cause of visual loss. We used mice in which the hypoxia response element (HRE) is deleted from the vascular endothelial growth factor (vegf) promoter (Vegf(delta/delta) mice) to explore the role of induction of VEGF through the HRE in these disease processes. Compared to wild type (Vegf+/+) mice with oxygen-induced ischemic retinopathy (OIR) in which vegf mRNA levels were increased and prominent retinal NV and BRB breakdown occurred, Vegf(delta/delta) littermates with OIR failed to increase vegf mRNA levels in the retina and had significantly less retinal NV and BRB breakdown, but showed prominent dilation of some superficial retinal vessels. Vegf(+/delta) littermates with ischemic retinopathy developed comparable retinal NV to Vegf+/+ mice, exhibited intermediate levels of BRB breakdown, and did not show vasodilation. In a mouse model of CNV, due to laser-induced rupture of Bruch's membrane, the area of CNV at Bruch's membrane rupture sites was more than tenfold greater in Vegf+/+ mice than in Vegf(delta/delta) littermates. In contrast to these dramatic differences in pathologic ocular NV, Vegf(delta/delta) mice showed subtle differences in retinal vascular development compared to Vegf+/+ mice; it was slightly delayed, but otherwise normal. These data suggest that induction of VEGF through the HRE in its promoter is critical for retinal and CNV, but not for retinal vascular development.

Animals↗

Oxidative stress in diabetic retina.

The authors describe the alterations usually associated with diabetic retinopathy. They concern the classical thickening of the basal membrane of retinal capillaries and the associated modification of retinal vessel permeability. These alterations correspond to the blood-retinal barrier disruption. The authors then discuss the participation of oxygenated free radicals in the pathogenesis of diabetic retinopathy. They report several experimental studies establishing such a participation and finally describe their own results obtained on a model of retinas isolated from alloxan-induced diabetic rats. After one month of evolution, the electroretinograms (ERG) recorded on isolated retinas from diabetic rats had an amplitude about 20% lower than the controls, whereas after two months of diabetes, this decrease was about 60%. Under these conditions, the authors tested the protective properties of Ginkgo biloba extract (EGb 761) on their model. They observed that in EGb-treated animals (100 mg/kg/day), the ERG had a significantly (p less than 0.001) greater amplitude than untreated animals after two months of diabetes evolution. In conclusion, the authors discuss the possible utilization of a free radical scavenger, such as EGb 761, in the prevention of the retinal impairment in diabetes.

Animals↗

In vivo retinal vascular cannulation in rabbits.

PURPOSE: To perform in vivo cannulation of retinal vessels for local application of pharmacotherapy to treat central retinal vein occlusion (CRVO), a new method was tested using rabbits. Changes following cannulation were studied histologically. METHODS: The micropipette used for cannulation was constructed from a glass tube. The outer diameter of the tip was 30-40 microm. Rabbits for the experiment were anesthetized; each had its head stabilized with fixing equipment designed for that purpose. After preparing a port for infusion of balanced salt solution (BSS), the specially designed micropipette was inserted at the pars plana of the ciliary body to puncture the major retinal vein, through which BSS was injected. RESULTS: We were able to puncture the major retinal vein with the micropipette without causing any serious incident, after which we injected approximately 100 microl of BSS. A small amount of vitreous hemorrhage that appeared after removing the micropipette could be stopped by increasing intraocular pressure by elevating the infusion bottle. Postoperative observation by indirect ophthalmoscopy showed no obstruction in the vein at the puncture site. Light microscopy showed only a slight narrowing of the venous lumen at the site. CONCLUSION: Cannulation into the retinal vein of rabbits was possible, and invasion was not significant, as determined histologically. Our findings endorse a method of restoring blood flow that involves direct injection of tissue plasminogen activator into the retinal vein of patients with CRVO to dissolve a thrombus.

Animals↗

Retinal vasculitis due to secondary syphilis.

BACKGROUND: Retinal vasculitis is one of the manifestations of ocular syphilis. CASE: A 29-year-old man was referred to our hospital with the complaint of sudden visual loss in the left eye lasting more than three weeks. OBSERVATIONS: Ophthalmoscopic examination showed retinal hemorrhages, edema, and sheathing of large retinal arteries and veins. Fluorescein angiography revealed extensive occlusion of the affected retinal arteries, veins, and capillaries. Little evidence of uveitis or vitritis was observed. The fluorescent treponemal antibody-absorption test was positive, and the Treponema pallidum hemagglutination titer was 1:10,240. The treatment with penicillin was effective, leading to resolution of the retinal hemorrhages and edema, although occlusion of the retinal vessels persisted. CONCLUSIONS: Vascular occlusion occurred simultaneously in large retinal arteries, arterioles, and capillaries as well as in segments of retinal veins, resulting in irreversible changes in the vascular walls.

Adult↗

Congenital retino-pigment epithelial malformation, previously described as hamartoma.

Six patients with a congenital malformation of the retina and pigment epithelium had a slightly elevated greenish-blue or gray lesion in the macular area or fundus periphery composed of a flat, outer pigmented portion consisting of a layer of hyperpigmented, presumably hypertrophied retinal pigment epithelium and a prominent, unpigmented inner portion consisting of malformed thickened retina. Marked tortuosity of the retinal vessels was explained by an intraretinal disturbance of the retinal layering and the presence of preretinal membranes. Angiography revealed blockage of the background fluorescence caused by the abnormal retinal pigment epithelium and leakage from dilated, abnormal capillaries. Typically, the lesion was unilateral and was found in children or young adults who had monocular strabismus, reduced visual acuity, and often hyperopia. Most of the patients were males, and their cases were frequently misdiagnosed as tumors.

Adolescent↗

Prevalence of myopia at 9 months in infants with high-risk prethreshold retinopathy of prematurity.

PURPOSE: To examine the prevalence of myopia and high myopia at 9 months corrected age in premature infants who participated in the multicenter randomized trial of Early Treatment for Retinopathy of Prematurity (ETROP). DESIGN: Randomized, controlled clinical trial. PARTICIPANTS: Four hundred one infants with birth weights of <1251 g in whom prethreshold ROP developed in one or both eyes and who were determined to have a significant risk (> or =15%) of poor structural outcomes without treatment, based on the risk management for ROP program. INTERVENTION: Infants with bilateral high-risk prethreshold ROP (n = 317) had 1 eye randomized to early treatment, and the fellow eye was managed conventionally. In asymmetric cases (n = 84), the eye with high-risk prethreshold ROP was randomized to early treatment or conventional management (control). Eyes randomized to early treatment at high-risk prethreshold ROP and eyes randomized to conventional management in which threshold ROP developed received peripheral retinal photocoagulation or cryotherapy. Conventionally managed eyes in which threshold ROP did not develop were observed. Cycloplegic retinoscopy data were obtained at 9 months corrected age from 321 eyes treated early and 307 eyes managed conventionally. MAIN OUTCOME MEASURES: Prevalence of myopic (spherical equivalent > or = 0.25 diopters [D]) and highly myopic (> or =5.00 D) eyes in each group. RESULTS: The prevalence of myopia (64.5% vs. 69.4%; P = 0.06) and high myopia (25.5% vs. 28.3%; P = 0.20) was similar between eyes treated at high-risk prethreshold and high-risk prethreshold eyes managed conventionally. Among high-risk eyes managed conventionally, the prevalence of myopia (78.2% vs. 53.3%) and high myopia (37.6% vs. 11.2%) was higher when threshold ROP developed than when regression without treatment occurred. Among eyes treated at high-risk prethreshold ROP, the prevalence of myopia (93.3% vs. 91.7% vs. 60.6%) and of high myopia (53.3% vs. 33.3% vs. 20.8%) was higher in eyes with abnormal angle of temporal retinal vessels or macular ectopia than in eyes with no retinal residua. This also held true for conventionally managed eyes. CONCLUSIONS: Early treatment at high-risk prethreshold did not place eyes at greater risk of myopia and high myopia than did conventional management of eyes with high-risk prethreshold ROP.

Cryotherapy↗

A prospective study of dense spontaneous vitreous hemorrhage.

PURPOSE: We studied the incidence of vitreous hemorrhage in a well-defined population to determine the underlying causes of such hemorrhages. METHODS: We prospectively studied all eyes with dense spontaneous first-time vitreous hemorrhage during a 2 1/2-year period in the greater Göteborg area (542,000 inhabitants). Follow-up time was one year. RESULTS: Ninety-four patients (95 eyes) were included, corresponding to a yearly incidence of seven cases per 100,000 inhabitants. Because of demographic factors and the organization of Swedish ophthalmologic care, we believe that this is close to the true incidence. The cause of vitreous hemorrhage could be verified in all but four eyes but frequently not until late in the follow-up period. The most common underlying cause was vitreous detachment and traction to a retinal vessel (39 eyes). In 28 of these eyes a retinal tear was also present. Five of these eyes developed a retinal detachment. In 19 eyes, bleeding was caused by proliferative diabetic retinopathy. This figure was relatively smaller than in previous studies. Retinal vein occlusion was the cause of hemorrhage in 15 eyes. Retinal macroaneurysm (seven eyes) was an easily overlooked cause, often diagnosed late in the follow-up period. CONCLUSIONS: Because of the common diagnostic difficulties and the frequent need for laser treatment, vitrectomy, or both, it is recommended that eyes with vitreous hemorrhage be followed up in centers with ultrasonographic and surgical expertise.

Adult↗

[Carcinoma-associated retinopathy: a review with clinical examples].

Cancer-associated retinopathy (CAR) is a rare paraneoplastic syndrome. In this survey we report about two further patients with CAR, who were referred to the University Eye Hospital of Tuebingen within a few months. The most common primary tumor associated with CAR is small cell carcinoma of the lung. Case reports about rhabdomyosarcoma, carcinoma of the endometrium, prostate and mamma were also described. The exact pathogenesis of CAR is still unknown. Specific autoantibodies were found against the photoreceptor protein recovering (23-kd retinal CAR antigen). However, this reaction is not present in all patients, and probably other antigens are also involved. Most of the patients experience symptoms of CAR before the primary tumor is detected. Besides glare sensitivity and flashing lights, a rapidly progressive, often asymmetric visual loss may occur. Although paracentral and mid-peripheral scotomas can be found frequently, visual field defects are often quite heterogeneous. Typically, the responses in the electroretinogram (ERG) are markedly reduced, but normal ERGs were also described. The fundus picture in CAR shows sheathing of the retinal vessels, narrowing of the arterioles and clumbing of the retinal pigment epithelium. The prognosis is poor. Frequently there is progression to bilateral loss of vision within a few months. Treatment of the primary tumor does not seem to alter the ocular prognosis. Systemic corticosteroids may be helpful in some patients. Nevertheless, no proven therapeutic regimen is currently available.

Aged↗