Capillary Nonperfusion Research Articles

Radiation retinopathy in patients treated for sinus and epipharingeal malignancies

Radiation retinopathy is vasculopathy induced by ionising radiation delivered by either brachytherapy or teletherapy for ocular and nonocular malignancies. The first signs of radiation retinopathy typically occur a few months to a few years after the exposure to ionizing radiation. In the 3 of our patients, changes like capillary telangiectasia, microaneurysms, intraretinal hemorrhages, hard exudation, and capillary nonperfusion showed a clinical picture of macular edema. Two of the patients were suspected of diabetic retinopathy, and 1 patient had optic neuropathy. In our group of patients a latent period was between 3 and 8 years. The incidence of radiation retinopathy increases significantly with the total doses of radiation above 45 Gy, and, thus, it has not been found in the lower doses. Radiation retinopathy is a diagnostical and therapentical problem. Clinical picture can be identical to that of diabetic retinopathy suggesting a common pathophysiologic mechanism of the damage to capillary endothelial cells, and the importance of clinical examination, anamnesis and fluorescein angiography.

Spontaneous Resolution of Macular Exudation with Good Visual Recovery in Idiopathic Retinal Vasculitis, Aneurysms, and Neuroretinitis (IRVAN): A Case Report

A 14-year-old boy presented with decreased visual acuity in both eyes of three-months duration. Fundus examination revealed macular exudation in both eyes with aneurysmal changes at the arteriolar bifurcations. Fluorescein angiography confirmed the presence of numerous aneurysmal dilatations of the retinal arterioles and extensive peripheral capillary nonperfusion areas. A provisional diagnosis of idiopathic retinal vasculitis, aneurysms, and neuroretinitis (IRVAN) was made. Scatter photocoagulation was advised in view of the extensive capillary nonperfusion areas. The patient was then lost to follow-up. He presented a year later with bilateral nonresolving vitreous hemorrhage, more severe in the right eye. He underwent right pars plana vitrectomy. Intraoperatively, the fundus features were similar to those at the initial presentation, but with the absence of any macular exudation. IRVAN represents an evolving clinical condition, with ill-defined clinical aspects, particularly with respect to management. In view of the spontaneous absorption of the macular exudates, we would like to suggest a cautious approach to applying photocoagulation of the retinal aneurysms.

Ocular structure and function in an aged monkey with spontaneous diabetes mellitus

Diabetes mellitus develops spontaneously in middle-aged, obese rhesus monkeys, thus making them a good model for examining the effects of co-morbid factors on the development of end-organ damage. Changes in structure and function in the eyes of one monkey who spontaneously developed type 2 diabetes are reported here. This animal had concomitant hypertension, high levels of triglycerides and serum cholesterol, and a low fraction of high-density lipoprotein. The eyes showed intraretinal hemorrhages and large areas of retinal capillary nonperfusion. Indo-cyanin green (ICG) angiography revealed a large area of non- or poorly perfused choriocapillaris in one eye, and immunohistochemistry showed loss of viable choriocapillaries in this region. Both basal laminar deposits and hard drusen were present on areas of Bruch's membrane adjacent to nonviable choriocapillaris. Blood flow via the nasal posterior ciliary arteries to this section of choroid was not detectable by color duplex Doppler ultrasound, indicating contribution of extraocular vascular disease to ischemia in this eye. There was a severe decline in number of photoreceptor inner and outer segments, and corresponding reductions in the multifocal electroretinogram (ERG), in the areas of choriocapillaris loss.The ganzfeld ERG indicated loss in both inner and outer retinal function. Much of the ganglion cell layer was absent throughout the retina, possibly reflecting the effect of diabetes as well as chronic open angle glaucoma; the latter diagnosis supported by elevated intraocular pressures and excavated optic disks. In summary, high resolution, enzyme histochemical and histopathological analyses of a diabetic hypertensive monkey retina and choroid after serial functional in vivo analyses have demonstrated the relationship between vascular dysfunction and visual function loss. Choroidal vascular dysfunction in both large and small vessels was associated with age-related macular degeneration-like changes in Bruch's membrane and photoreceptor degeneration.

A central role for inflammation in the pathogenesis of diabetic retinopathy.

Diabetic retinopathy is a leading cause of adult vision loss and blindness. Much of the retinal damage that characterizes the disease results from retinal vascular leakage and nonperfusion. Diabetic retinal vascular leakage, capillary nonperfusion, and endothelial cell damage are temporary and spatially associated with retinal leukocyte stasis in early experimental diabetes. Retinal leukostasis increases within days of developing diabetes and correlates with the increased expression of retinal intercellular adhesion molecule-1 (ICAM-1) and CD18. Mice deficient in the genes encoding for the leukocyte adhesion molecules CD18 and ICAM-1 were studied in two models of diabetic retinopathy with respect to the long-term development of retinal vascular lesions. CD18-/- and ICAM-1-/- mice demonstrate significantly fewer adherent leukocytes in the retinal vasculature at 11 and 15 months after induction of diabetes with STZ. This condition is associated with fewer damaged endothelial cells and lesser vascular leakage. Galactosemia of up to 24 months causes pericyte and endothelial cell loss and formation of acellular capillaries. These changes are significantly reduced in CD18- and ICAM-1-deficient mice. Basement membrane thickening of the retinal vessels is increased in long-term galactosemic animals independent of the genetic strain. Here we show that chronic, low-grade subclinical inflammation is responsible for many of the signature vascular lesions of diabetic retinopathy. These data highlight the central and causal role of adherent leukocytes in the pathogenesis of diabetic retinopathy. They also underscore the potential utility of anti-inflammatory treatment in diabetic retinopathy.

A new staging system for idiopathic retinal periphlebitis.

To develop and standardize a universally acceptable new staging system for idiopathic retinal periphlebitis (Eales disease). A new staging system was established and standardized based on standard terminology and features. Idiopathic retinal periphlebitis was classified as peripheral and central types. Peripheral disease consisted of four stages. Stage 1 is periphlebitis of small (1a) and large (1b) caliber vessels with superficial retinal hemorrhages. Stage 2a denotes capillary nonperfusion and 2b neovascularization elsewhere/of the disc. Stage 3a is classified as fibrovascular proliferation and 3b vitreous hemorrhage. Stage 4a is traction/combined rhegmatogenous retinal detachment whereas 4b is rubeosis iridis, neovascular glaucoma, complicated cataract, and optic atrophy. A total of 253 cases of idiopathic retinal periphlebitis (mean age, 24.7 +/- 4.7 years, all male) presenting at this tertiary care center were classified prospectively according to the new staging system, by two independent observers (interobserver correlation = 0.7). The new staging system was consistent, simple, and easy to recall. Peripheral and central types of idiopathic retinal periphlebitis were found in 94.07% and 5.93% of cases, respectively. The new staging system also defined the severity of the disease. Vitreous hemorrhage was found to be the commonest presenting feature (51.68%), whereas traction/combined rhegmatogenous detachment was found in 5.88% of cases. The new staging system is useful in classifying and assessing the severity of disease. Management strategy can also be defined according to the stage of the disease. It is designed to promote the use of standard assessment with applications to clinical management and research.

Clinical and Angiographic Features in Nasal Branch Retinal Vein Occlusion

Purpose: To analyse the epidemiological and clinical characteristics of nasal branch retinal vein occlusion (NBRVO). Methods: Patients affected by branch retinal vein occlusion observed in the out-patient departments of the Eye Clinic of Trieste between January 1995 and January 1999 were enrolled. Results: Out of 144 patients with branch retinal vein occlusion, 128 (88.9%) were affected by temporal branch retinal vein occlusion (TBRVO), and 16 patients were affected by NBRVO (11.1%). The two groups did not differ as far as systemic hypertension, diabetes mellitus, glaucoma and ischaemic heart disease were regarded. NBRVO cases were characterized by better visual acuity and greater figures of capillary non-perfusion, retinal neovascularization and vitreous haemorrhage. Conclusions: NBRVO, even though infrequent, shares the same epidemiological characteristics as TBRVO. The higher prevalence of ischaemic cases in the NBRVO group could depend on a bias during the enrolment of patients, because especially symptomatic patients may have been examined in our out-patient departments. The relatively high percentage of epiretinal membrane formation after laser photocoagulation suggests particular caution, especially in cases presenting with vitreous haemorrhage.

Radiation retinopathy after fractionated stereotactic radiotherapy for optic nerve sheath meningioma

Purpose To report a patient with radiation retinopathy after fractionated stereotactic radiotherapy for treatment of optic nerve sheath meningioma (ONSM). Design Interventional case report. Methods The clinical presentation, radiation treatment, and subsequent visual complications of a patient with ONSM are described. Main outcome measures Development of radiation retinopathy and Snellen visual acuity. Results A 36-year-old man presented with a left optic neuropathy. Magnetic resonance imaging studies showed abnormalities consistent with ONSM. Because of progressive vision loss, the patient underwent fractionated stereotactic radiotherapy for the lesion. Vision initially improved after treatment, but 22 months later, retinal abnormalities consistent with radiation retinopathy were noted in the left eye. Visual acuity worsened over the next 24 months in association with the development of retinal hemorrhages, lipid, and retinal edema predominantly within the nasal portion of the posterior pole. Fluorescein angiography showed edema associated with microaneurysms, retinal telangiectasia, and capillary nonperfusion. Laser photocoagulation was performed on several occasions in areas of microaneurysms and retinal telangiectasia; however, the retinal edema and lipid remained, associated with persistent decreased vision. Conclusions Radiation retinopathy and vision loss may occur after fractionated stereotactic radiotherapy for ONSM and should be discussed as a potential complication.

Ocular Manifestations in Dengue Fever

Purpose: To report a case of Dengue fever resulting in permanent visual loss in both eyes due to retinal capillary occlusion. Methods: Case report. Results: Severe permanent visual loss occurred in a patient with Dengue fever. Dilated fundus exam showed vascular sheathing with associated retinal hemorrhages at the equator and cotton wool spots in the maculae of both eyes. Fluorescein angiography revealed areas of capillary nonperfusion at the equator and in the macula. The diagnosis of Dengue fever was confirmed by serology detecting IgM antibodies to the Dengue virus. Conclusion: Ocular abnormalities may be seen in patients with Dengue fever, therefore ophthalmoscopy should be performed in patients presenting with severe forms of the disease.

Intravitreal tissue plasminogen activator in the management of central retinal vein occlusion.

To evaluate the role of intravitreal tissue plasminogen activator (tPA) in the management of central retinal vein occlusion (CRVO) in patients with symptoms for <3 days. We evaluated the visual outcome of a consecutive series of patients with CRVO following intravitreal tPA injection. All patients presented with visual acuity worse than 20/50 within 3 days from the onset of symptoms. Main outcome measures included percentage of patients whose final vision improved to 20/50 or better and change in percentage of patients with vision of 20/200 or worse before and after treatment. Twelve patients received intravitreal tPA for CRVO. Nine patients (75%) had best-corrected visual acuity of 20/200 or worse at presentation compared with 4 patients (33%) at the last follow-up after treatment. Five (55%) of these 9 patients had final visual acuity that improved to 20/50 or better. The remaining four patients did not have improvement or their vision continued to worsen. All 4 patients had fluorescein angiographic evidence of >10 disk areas of capillary nonperfusion at presentation. Overall, 8 (67%) of 12 patients had final visual acuity of 20/50 or better. No side effects related to tPA injection were observed. Our data suggest that intravitreal tPA injection may have a beneficial role in the management of CRVO when used within a few days of the onset of symptoms in patients with no angiographic evidence of severe capillary nonperfusion even if initial visual acuity is 20/200 or worse.

Presumed combined hamartoma of the retina and retinal pigment epithelium with preretinal neovascularization

Purpose To describe a case of presumed combined hamartoma of the retina and retinal pigment epithelium associated with preretinal neovascularization. Design Observational case report. Methods We report clinical and angiographic findings of a 26-year-old woman. Results The patient presented with mild vitreous hemorrhage and slowly decreasing vision in the right eye. A combined hamartoma of the midperipheral retina and retinal pigment epithelium with an epiretinal membrane causing traction to the macula was found. Fluorescein angiography showed areas of capillary nonperfusion and a large preretinal neovascularization peripheral to the hamartoma. Conclusions A combined hamartoma may be associated with retinal capillary nonperfusion and preretinal neovascularization, suggesting that significant retinal ischemia can occur with a combined hamartoma.

Retinal Neovascularization in Eales Disease

A study was undertaken, using fluorescein angiography, to correlate the area of capillary nonperfusion (CNP) with the occurrence of retinal neovascularization in 20 cases of Eales disease. Neovascularization elsewhere and neovascularization of the disc were found in eyes with greater than 20 and 60 disc areas CNP, respectively. The role of lipid peroxides in neovascularization was also studied biochemically. A significant increase in platelet malondialdehyde levels was observed in cases with neovascularization.

Correlation of increased vascular endothelial growth factor with neovascularization and permeability in ischemic central vein occlusion.

To establish a role for vascular endothelial growth factor (VEGF) during the onset and clinical course of neovascularization of the iris (NVI) in ischemic central retinal vein occlusion. Sixteen patients with ischemic central retinal vein occlusion were followed up for 12 months by clinical examination, retinal and iris angiography, and serial anterior chamber sampling of aqueous humor. Aqueous VEGF level was determined by enzyme-linked immunoassay, and permeability changes were estimated by capillary zone electrophoretic assessment of aqueous albumin. A correlation was found between aqueous VEGF concentrations and the onset, persistence, and regression of NVI; extent of retinal capillary nonperfusion; and vascular permeability. The NVI occurred when aqueous VEGF concentrations were 849 to 1569 pg/mL and regressed fully when they fell below 550 pg/mL. Aqueous concentrations of serum albumin, a marker of increased permeability, correlated with increased VEGF. Placental growth factor was found at low levels only when VEGF levels exceeded 330 pg/mL. The NVI remained VEGF-dependent during the course of the disease, regressing only if VEGF concentrations were reduced after laser ablation of hypoxic retina. The close temporal correlation between aqueous VEGF levels and the course of neovascularization and permeability in human ischemic central retinal vein occlusion indicates that increased aqueous VEGF level may predict the need for treatment, and that anti-VEGF therapy at an early stage of ischemic central retinal vein occlusion may be therapeutically beneficial.

Rheumatoid hyperviscosity syndrome: reversibility of microvascular abnormalities after treatment

PURPOSE: To report a case of rheumatoid hyperviscosity syndrome involving both retinal and choroidal circulation that resolved after treatment.DESIGN: Interventional case report.METHODS: A 58-year-old woman with clinical and serologic evidence of an inflammatory connective tissue disease without any visual complaints was referred for a funduscopic evaluation.RESULTS: Funduscopic examination revealed marked dilation and beading of the venous system, microaneurysms, and telangiectatic capillary beds in the posterior pole. Fluorescein angiography disclosed delayed choroidal filling, prolonged arteriovenous transit time, and areas of capillary nonperfusion. These findings were accompanied by a severe polyclonal hypergammaglobulinemia and a 10-fold increase in serum viscosity. The ocular findings were reversible after plasmapheresis and steroid treatment.CONCLUSION: Rheumatoid hyperviscosity syndrome can involve both retinal and choroidal circulation. The prominent microvasculopathy is reversible after appropriate treatment.

The pathogenesis of diabetic retinopathy: old concepts and new questions.

Hyperglycaemia appears to be a critical factor in the aetiology of diabetic retinopathy and initiates downstream events including: basement membrane thickening, pericyte drop out and retinal capillary non-perfusion. More recently, focus has been directed to the molecular basis of the disease process in diabetic retinopathy. Of particular importance in the development and progression of diabetic retinopathy is the role of growth factors (eg vascular endothelial growth factor, placenta growth factor and pigment epithelium-derived factor) together with specific receptors and obligate components of the signal transduction pathway needed to support them. Despite these advances there are still a number of important questions that remain to be answered before we can confidently target pathological signals. How does hyperglycaemia regulate retinal vessels? Which growth factors are most important and at what stage of retinopathy do they operate? What is the preferred point in the growth factor signalling cascade for therapeutic intervention? Answers to these questions will provide the basis for new therapeutic interventions in a debilitating ocular condition.

Incidence of radiation retinopathy after high-dosage single-fraction gamma knife radiosurgery for choroidal melanoma

Objective To investigate the incidence and clinical findings of radiation retinopathy after single-fraction high-dose gamma knife radiosurgery for choroidal melanoma. Design Retrospective noncomparative interventional case series. Participants Thirty-two patients with choroidal melanoma. Methods Review of charts, color fundus photographs, and fluorescein angiograms of 32 choroidal melanoma patients after radiosurgery. All patients were treated with the Leksell gamma knife in one fraction with a marginal dose between 40 and 80 Gy (median, 50 Gy) and were followed for at least 24 months (or until enucleation because of complications secondary to radiation). Main outcome measures Any clinical feature of radiation retinopathy and neovascular glaucoma. Results During a mean follow-up of 38 months (range, 6–81 months) we found radiation retinopathy in 84% of our patients. The most common findings in these patients were intraretinal hemorrhages with an incidence of 70%, macular edema and capillary nonperfusion in 63%, and hard exudates in 52% of the patients. Less common were microaneurysms in 30% and retinal neovascularization in 22%. The time of onset of the various radiation-associated retinal findings ranged between 1 and 22 months. Forty-seven percent of all patients developed neovascular glaucoma. In our study there was no correlation between radiation dosage applied and clinical findings. Conclusions Single-fraction high-dose Leksell gamma knife radiosurgery of choroidal melanomas with a median marginal dose of 50 Gy is highly associated with early radiation retinopathy and with neovascular glaucoma.

Increased prevalence of micro thromboses in retinal capillaries of diabetic individuals. Daria B, Maiello M, Lorenzi M. Diabetes 2002;50:1432–1439

In diabetic retinopathy, capillary nonperfusion and eventual obliteration leads to retinal ischemia and neovascularization. The occurrence of retinal microthrombosis in human diabetes has long been suspected and occasionally observed but never systematically demonstrated. The authors used trypsin digestion to isolate the intact vascular network from retinas obtained postmortem from nine diabetic donors (age 64 ± 11 years, duration of diabetes 6 ± 4 years; mean ± SD) and eight age-matched nondiabetic donors. Topographically matched sectors (each one-sixth of retina) of diabetic and nondiabetic retinas were tested sequentially with antibodies to fibrin cross-linking factor XIII and platelet glycoprotein (GP)-IIIa to identify fibrin-platelet thrombi. In some trypsin digests, they also examined vascular cell apoptosis. The retina from a nondiabetic donor, 24 years of age, who had died of trauma, was used to exclude confounding influences caused by the postmortem period. When compared with those of nondiabetic donors, the retinas of diabetic donors showed double the number of capillary segments with colocalized immunostaining for factor XIII and GPIIIa (P = 0.02). The total area of the positive segments was fourfold greater in the diabetic than in the nondiabetic donors (P = 0.02) and correlated with the duration of diabetes. Large thrombi were six times more frequent in the diabetic donors (P = 0.03), and there was a significant topographical association of microthrombosis with apoptotic cells in both diabetic and nondiabetic vessels (P = 0.0001). Diabetes of short duration was found to be associated with a greater than normal number and size of platelet-fibrin thrombi in the retinal capillaries. These thrombi can contribute to capillary obliteration and retinal ischemia and may be a practical target for early drug intervention.—Thomas J. Liesegang

Pathologic features of vascular endothelial growth factor-induced retinopathy in the nonhuman primate

PURPOSE: Vascular endothelial growth factor (VEGF) is a potent ischemia-upregulated angiogenic protein that has been implicated in diabetic retinopathy. Intravitreal VEGF injections have not previously been shown to produce preretinal neovascularization. The purpose of this study was to further characterize the angiopathic changes that occur after intravitreal injections in a nonhuman primate and determine if preretinal neovascularization develops. DESIGN: Experimental animal study. METHODS: Vascular endothelial growth factor 165 was injected into the eyes of normal cynomolgus monkeys at regular intervals. As a control, normal eyes were injected with phosphate buffered saline. Color photography and fluorescein angiography were performed at regular intervals. The retinas were incubated for adenosine diphosphatase (ADPase) activity to visualize retinal vessels. The retinas were flat-embedded and areas of potential preretinal neovascularization were identified en bloc and serially sectioned. RESULTS: Areas of capillary nonperfusion and vessel dilation and tortuousity were seen by angiography. In serial sections, the nonperfused areas were found to be associated with endothelial cell hyperplasia in vessel lumens. Preretinal neovascularization originating only from superficial veins and venules was observed throughout peripheral retina, but was not seen in the posterior pole. Lacunae-like veins were subdivided by the process of intussusception and endothelial cell bridging. Arterioles demonstrated endothelial cell hyperplasia and microaneurysms. CONCLUSION: Intraocular injections of VEGF were sufficient to produce preretinal neovascularization in the nonhuman primate. Most vasculopathic structures were associated with endothelial cell hyperplasia. These results demonstrate that VEGF alone can produce many features of both nonproliferative and proliferative diabetic retinopathy including the previously undescribed development of preretinal neovascularization. This well-characterized VEGF-induced primate model of retinal neovascularization may be useful as a means of testing new treatments for retinal neovascularization.

Retinal Vascular Endothelial Growth Factor Induces Intercellular Adhesion Molecule-1 and Endothelial Nitric Oxide Synthase Expression and Initiates Early Diabetic Retinal Leukocyte Adhesion in Vivo

Leukocyte adhesion to the diabetic retinal vasculature results in early blood-retinal barrier breakdown, capillary nonperfusion, and endothelial cell injury and death. Previous work has shown that intercellular adhesion molecule-1 (ICAM-1) and CD18 are required for these processes. However the relevant in vivo stimuli for ICAM-1 and CD18 expression in diabetes remain unknown. The current study investigated the causal role of endogenous vascular endothelial growth factor (VEGF) and nitric oxide in initiating these events. Diabetes was induced in Long-Evans rats with streptozotocin, resulting in a two- to threefold increase in retinal leukocyte adhesion. Confirmed diabetic animals were treated with a highly specific VEGF-neutralizing Flt-Fc construct (VEGF TrapA(40)). Retinal ICAM-1 mRNA levels in VEGF TrapA(40)-treated diabetic animals were reduced by 83.5% compared to diabetic controls (n = 5, P < 0.0001). VEGF TrapA(40) also potently suppressed diabetic leukocyte adhesion in retinal arterioles (47%, n = 11, P < 0.0001), venules (36%, n = 11, P < 0.0005), and capillaries (36%, n = 11, P < 0.001). The expression of endothelial nitric oxide synthase (eNOS), a downstream mediator of VEGF activity, was increased in diabetic retina, and was potently suppressed with VEGF TrapA(40) treatment (n = 8, P < 0.005). Further, VEGF TrapA(40) reduced the diabetes-related nitric oxide increases in the retinae of diabetic animals. The inhibition of eNOS with N-omega-nitro-L-arginine methyl ester also potently reduced retinal leukocyte adhesion. Although neutrophil CD11a, CD11b, and CD18 levels were increased in 1-week diabetic animals, VEGF TrapA(40) did not alter the expression of these integrin adhesion molecules. Taken together, these data demonstrate that VEGF induces retinal ICAM-1 and eNOS expression and initiates early diabetic retinal leukocyte adhesion in vivo. The inhibition of VEGF bioactivity may prove useful in the treatment of the early diabetic retinopathy.

Nonsteroidal anti-inflammatory drugs prevent early diabetic retinopathy via TNF-alpha suppression.

Leukocyte adhesion to the diabetic retinal vasculature results in blood-retinal barrier breakdown, capillary nonperfusion, and endothelial cell injury and death. Intercellular adhesion molecule-1 (ICAM-1) and the leukocyte integrin CD18 are required for these processes. Diabetes was induced in Long Evans rats, resulting in a two- to threefold increase in retinal leukocyte adhesion. Following one week of diabetes, neutrophil CD11a, CD11b, and CD18 expression was increased significantly, as were retinal ICAM-1 levels. Animals were treated with aspirin, a cyclooxygenase 2 (COX-2) inhibitor (meloxicam), or a soluble tumor necrosis factor alpha (TNF-alpha) receptor/Fc construct (TNFR-Fc, etanercept). High-dose aspirin, etanercept, and high-dose meloxicam each reduced leukocyte adhesion and suppressed blood-retinal barrier breakdown. High-dose aspirin also reduced the expression of CD11a, CD11b, and CD18, whereas meloxicam and etanercept did not. High-dose aspirin, etanercept, and high-dose meloxicam each reduced retinal ICAM-1 expression. Aspirin and meloxicam both lowered retinal TNF-alpha levels. Notably, aspirin, meloxicam, and etanercept did not change retinal vascular endothelial growth factor levels. High-dose aspirin, etanercept and high-dose meloxicam, each suppressed the retinal expression of eNOS and the DNA-binding capacity of retinal nuclear factor-kappaB. High-dose aspirin also suppressed Erk kinase activity, which is involved in CD18 up-regulation. Taken together, these data identify COX-2 and TNF-alpha as operative in the early signature pathologies of diabetic retinopathy, a newly recognized inflammatory disease.

Multiple retinal vein occlusions in essential thrombocythemia

PURPOSE: To report the ophthalmoscopic and angiographic evidence of both temporally and spatially independent multiple occlusions of the retinal veins in a patient with essential thrombocythemia. METHODS: Observational case report. Ophthalmic examinations, including fluorescein fundus angiogram, were performed on a 77-year-old male, who was found to have essential thrombocythemia. RESULTS: An acute impending central retinal vein occlusion in the left eye was diagnosed with coexisting old retinal vein occlusions evidenced by white vessels and capillary nonperfusion in both eyes. Peripheral retinal capillary dropout was also found angiographically in the right eye. CONCLUSION: Bilateral multiple occlusions of retinal veins in the present case suggest a prothrombotic tendency in retinal circulation in essential thrombocythemia.