Eales Disease Research Articles

Involvement of oxidative and nitrosative stress in promoting retinal vasculitis in patients with Eales’ disease

Objectives Eales’ disease (ED) is an idiopathic retinal vasculitis condition, which affects retina of young adult males. The histopathological hallmark in ED is the adhesion of leukocytes to the endothelium and the infiltration of these cells into the retinal parenchyma. Phagocyte generated free radicals have been implicated in mediating tissue damage associated with various inflammatory vasculopathies. In the present study, we have investigated the possible role of reactive oxygen species (ROS) and reactive nitrogen species (RNS) in causing retinal tissue damage in ED. Design and methods 35 patients with ED and 20 healthy control subjects were included in the study. Monocytes (MC) were separated from peripheral blood of the respective study participants. Inducible nitric oxide synthase (iNOS) protein expression was assessed using Western blot and 3 nitrotyrosine (3NTYR) by reversed phase high performance liquid chromatography (RP HPLC). Thiobarbituric acid reactive substances (TBARS) were determined by measuring malondialdehyde (MDA) formed. Superoxide dismutase (SOD) activity was assayed based on the ability of SOD to inhibit auto-oxidation of epinephrine. Iron, copper and zinc content were determined using Atomic Absorption Spectrophotometer. Immunolocalization of iNOS and 3NTYR was performed on the surgically excised epiretinal membranes (ERM) from patients with ED. Results There was a significant increase in the expression of iNOS, as well as 3NTYR accumulation, diminished SOD activity, elevated lipid peroxides, iron, copper and decreased zinc content in the MC of patients with ED when compared with healthy control subjects. The elevated levels of ROS and RNS products correlated with diminished antioxidant status in patients with ED. Strong immunoreactivity for iNOS and 3NTYR was observed in inflammatory cells and endothelial cells in ERM obtained from patients with ED. Conclusions Our findings from this study clearly reveal the involvement of RNS and ROS in the development of retinal vasculitis in ED. Based on our present study and earlier studies we confirm the role of free radicals in mediating retinal tissue damage in ED. Hence we believe selective inhibition of iNOS or supplementation with antioxidants vitamin E and C might be beneficial in controlling retinal vasculitis in patients with ED.

Accumulation of 8-hydroxydeoxyguanosine and its relationship with antioxidant parameters in patients with Eales’ disease: Implications for antioxidant therapy

Purpose. Eales’ disease (ED) is an idiopathic retinal inflammatory disease, which affects the retina of young adult males. Oxidative stress has been associated with the development of various inflammatory diseases. Accumulation of DNA oxidation products has been considered as an early biomarker for assessing oxidative tissue damage. To our knowledge there are no human clinical reports available on the accumulation of DNA adducts in ocular inflammatory diseases. Hence the aim of the present study was to determine the levels of 8-hydroxy-2'deoxyguanosine (8-OHdG) and to correlate it with the antioxidant and oxidant parameters in patients with ED and healthy control subjects. Methods. Twenty-two patients with ED [12 in active perivasculitis (AV) and 10 in healed vasculitis stages (HV)] were recruited for the study. 14 healthy volunteers were included as control. 8-OHdG was determined in their leukocytes by Gas chromatography-Mass Spectrometry (GC/MS) technique. Glutathione levels were determined in plasma, while Superoxide dismutase (SOD) activity and thiobarbituricacid reactive substances (TBARS) content were determined in their erythrocytes. Results. Our results indicated that 8-OHdG levels were elevated by 3 and 1.9 folds respectively in AV and HV stages of patients with ED, when compared with healthy control subjects. Increased 8-OHdG levels correlated with diminished SOD activity and decreased GSH content in patients with ED. Conclusions. To our knowledge, this is the first report of DNA adduct accumulation in patients with ED. Increased DNA adduct accumulation correlated with the severity of the disease, and they lie in parallel with diminished antioxidant capacity observed in patients with ED. Based on the observations from our present work and our earlier studies, we reiterate that oxidative stress is involved in the disease process. Hence we believe antioxidant vitamin E and C supplementation might be beneficial to patients with ED.

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.

C-reactive protein in eales disease

C-reactive protein (CRP) is an acute-phase reactant. A study was undertaken to estimate CRP, by rapid slide latex test, in 32 consecutive cases of Eales disease and 32 matched healthy controls. Elevated levels of CRP were detected in 11 (84.6%) of 13 cases of active disease. The CRP titers ranged from 0.6 to 2.4 mg%. Sensitivity and specificity of this test were 84% and 100%. After oral methotrexate pulsed therapy, elevated levels of CRP returned to normal.

Visual outcome of patients with central eales disease

A retrospective study was undertaken to evaluate visual outcome of 11 patients (13 eyes) with central Eales disease (median age, 22 years). All patients had raised erythrocyte sedimentation rates. Nonischemic disease developed in 11 eyes, and 2 eyes had ischemic disease. All patients were administered systemic corticosteroid therapy. One patient with ischemic disease also received panretinal photocoagulation. Final visual acuity of 6/6 was achieved in 7 eyes in the nonischemic group.

The plasma blade in vitreoretinal surgery

The Plasma Blade (Fugo Blade) was used to treat a traumatic retinal detachment, a case of Eales disease, and a case of proliferative diabetic retinopathy. Using this new battery-powered radiofrequency electrosurgical device, the authors were able to perform retinotomy and dissolve dense fibrovascular bands, with minimal bleeding and no tractional tears. The Plasma Blade appears, to have other clinical applications besides capsulotomy.

Enhanced oxidative stress in eales disease

A study was undertaken to evaluate oxidative stress and oxidative defense mechanisms in 14 cases of Eales disease with retinal periphlebitis and 10 controls. Alterations in activity of the enzymes sueeroxide dismutase and catalase in platelets and the lipid peroxidation product malondialdehyde were estimated biochemically. Enhanced oxidative stress (significantly increased malondialdehyde levels and decreased superoxide dismutase enzyme activity) was detected. Results suggest involvement of free radicals in the pathogenesis of Eales disease.

Macular involvement in eales disease

Aretrospective study of macular involvement was undertaken in 112 cases (175 eyes) of Eales disease. One or more macular lesions were observed in 51 eyes (28.1%). Macular edema (12.57%), intraretinal hemorrhages (10.85%), retinal pigment epithelial abnormalities (9.14%), hard exudates (8.57%), microaneurysms (7.42%), traction macular detachment (7.42%), macular nonperfusion (1.71%), and epiretinal membrane (1.71%) were observed. Macular involment in Eales disease is not uncommon.

Efficacy of oral methotrexate pulsed therapy in eales disease

A prospective study was undertaken to evaluate oral methotrexate pulsed therapy in 6 cases of Eales disease presenting with perivasculitis. Methotrexate was administered (7.5 mg weekly) for 3 months. The therapy was tolerated well, and retinal perivasculitis subsided in all cases. Five patients achieved excellent visual acuity—6/6 (20/20) or better. Elevated titers of C-reactive protein returned to normal after therapy. Six-month follow-up revealed no recurrence of the disease.

EALES DISEASE: Clinical Features, Pathophysiology, Etiopathogenesis

Eales disease is a clinical entity, classically presenting with repeated vitreous hemorrhage in young adult men. The underlying pathology is retinal phlebitis, predominantly in the peripheral fundus. The clinical manifestations are those of inflammatory retinal vein occlusion, usually multiple branch retinal vein occlusion (BRVO), but sometimes central retinal vein occlusion (CRVO). Phlebitis may or may not be associated with choroiditis, pars planitis, iridocyclitis, arteritis, or papillitis. There seem to be multiple causes with several possible pathologic and immunopathologic processes, which could explain the variability in the acuteness of onset and course of disease. Although in some cases the possible cause can be identified by association, in most cases the cause remains obscure. The management of Eales disease can be highly satisfactory when appropriate treatment is used at the appropriate stage of disease development. Proper management requires a proper understanding of the pathophysiology of Eales disease. Henry Eales (1880–1882) 23,24 was the first to describe a clinical syndrome of recurrent retinal and vitreous hemorrhages in apparently healthy young men. He had not, however, noticed any association with vasculitis or phlebitis. Wadsworth (1887) 73 associated perivasculitis with vitreous hemorrhage. Axenfeld and Stock (1909–1911) 5 were the ones who associated periphlebitis with Eales disease. Duke-Elder et al 22 consider Eales disease to be a clinical entity that is a manifestation of retinal perivasculitis of different causes. There is considerable confusion in terminology and nomenclature involving the pathology of Eales disease. It has been variously described as retinal perivasculitis, 16,43,44,73 obliterative vasculopathy, 34 and periphlebitis. 28 It is clear, however, that Eales disease is a clinical manifestation of inflammatory retinal vein occlusion or phlebitis. The associated arteritis in some cases is not relevant to the development of typical Eales disease. Because retinal vein inflammation can be in the form of massive exudation, obliterating the lumen completely or mildly cuffing vein segments with minimal changes in the venous lumen, it would be inappropriate to describe all cases as periphlebitis. It may be adequate to describe the basic pathology of Eales disease as simply retinal phlebitis, rather than blundering into the realm of pathology.

EALES DISEASE: Medical, Laser, and Surgical Treatments

Eales disease is an idiopathic retinal vasculitis that affects predominantly young men. The major manifestations of Eales disease are the inflammation of retinal veins with or without arteritis papillitis anterior posterior uveitis or pars planitis. The prognosis usually depends on the degree of vitreous macular circulatory failure proliferative retinopathy. The involvement is mostly bilateral at the peripheral retina. The fundus lesions that can be observed vary among retinal neovascularization (fig.1) vascular sheathing (fig.2) retinal vitreous hemorrhage retinitis proliferans (fig.3) disc neovascularization (fig.4) branch central retinal vein occlusion tractional retinal etachment rubeosis iridis neovascular glaucoma. In addition to these lesions the engorged tortous retinal veins leakage from these veins macular retinal edema shunt vessels hypoxic areas microaneurysms (fig. 5) can be seen more easily with fluorescein angiography.

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.

Retinal arteriovenous shunt at the arteriovenous crossing

Objective The purpose of the study was to demonstrate that the arteriovenous shunt at the arteriovenous crossing could occur in major retinal vascular diseases other than Takayasu disease. Design Clinical review of consecutive case series. Participants The authors studied 1885 eyes with retinal vascular diseases such as diabetic retinopathy, branch retinal vein occlusion, central retinal vein occlusion, central retinal artery occlusion, Leber’s miliary aneurysms, Eales disease, Behçet disease, and systemic lupus erythematosus retinopathy. Intervention Fluorescein fundus angiography using a wide-field fundus camera (60 degrees) was performed. Main outcome measures Dye transit from artery to vein through sequential angiography. Results The arteriovenous shunt at the arteriovenous crossing was found in 8 eyes with proliferative diabetic retinopathy, 27 eyes with branch retinal vein occlusion in the chronic stage, 2 eyes with central retinal vein occlusion, 2 eyes with central retinal artery occlusion, and 2 eyes with miliary aneurysms. The arteriovenous shunt was formed by a direct inflow from artery to vein, showing vasodilatation and hyperpermeability, followed by obliteration peripheral to the shunts. The pattern of initial inflow was classified into axial flow and laminar flow, and the inflow became wider and more rapid in the advanced stage. Conclusions These findings indicate that the arteriovenous shunt at the arteriovenous crossing is not a unique phenomenon in Takayasu disease but rather is a basic pattern of retinal vascular reaction pathologic states.

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.

Neuro-Ophthalmologic Manifestations of Behcet's Disease

Three patients with retinal vasculitis are reported who were found to be seroreactive for Lyme borreliosis. Careful investigation revealed no other apparent etiology for the angiitis, and improvement of the retinal vasculitis on tetracycline therapy was documented by fluorescein angiography in one of them. Two cases of retinal vasculitis were presented at the International Conference on Lyme Borreliosis in Stockholm 18-21 June 1990, and two cases of cerebral vasculitis due to Borrelia burgdorferi have been published. To our knowledge, this is the first published report of retinal vasculitis occurring in patients seroreactive for Lyme borreliosis. Although further investigation will be necessary to prove a cause-and-effect relationship, ophthalmologists encountering patients with otherwise unexplained cases of retinal vasculitis, or Eales disease, are encouraged to study these patients carefully for the possibility of Borrelia burgdorferi infection.

Rheologic findings in patients with Eales disease

In a retrospective analysis of findings in 12 patients with Eales' disease significant changes in blood fluidity were established. The six female and six male patients, aged between 15 and 59, were examined in the acute and subclinical stages and when a recurrence occurred. The rheologic parameters plasma viscosity, erythrocyte rigidity, and erythrocyte aggregation were significantly increased in the acute stage and when there was a recurrence, while in the subclinical stage the rheologic values improved to normal. No correlation could be found between the severity of the clinical picture in the various phases and the rheologic values. None of the other biochemical, microbiologic, and immunologic parameters were pathologic in any stage of the disease. In particular, virus serology, protein, immune, and hemoglobin electrophoresis were normal in all patients. While the etiology of Eales' disease remains unknown, deteroration in erythrocyte rigidity appears to play a part in the pathophysiology of the disease.

Oxygen dissociation curve in Eales's disease.

The oxyhaemoglobin dissociation curve (ODC) was investigated in 15 patients with Eales's disease and 11 controls to test the hypothesis that Eales's disease is caused by retinal hypoxia secondary to impaired oxygen release from the blood. Patients with the peripheral form of Eales's disease did not have any significant difference in the P50 values when compared with the controls. However, the P50 values were significantly lower (P < 0.005) for the patients with mixed retinopathy. This degree of increased oxygen affinity is not physiologically significant but may reflect an intrinsic abnormality of the red cells in these cases.

東海大学眼科におけるアルゴンレーザー光凝固について

Ocular photocoagulation is now indispensable for treatment of many kinds of retino-choroidal diseases. We adopted this therapeutic method with an argon laser photocoagulator(Coherent System 900) at Tokai University in May,1979. In the following 13 months, 74 eyes(66 cases) were treated with this method. The authors reported here statistical studies of these cases. They included diabetic retinopathy 34 eyes(27 cases), occlusion of branch of central retinal vein 14 eyes(14 cases), occlusion of central retinal vein 2 eyes (2 cases), retinal detachment 16 eyes (16 cases), central serous choroidopathy 4 eyes (3 cases), Eales disease one eye, Coats disease one eye and others 2 eyes (2 cases). Good results were obtained in 35 eyes (34 cases). We did not experienced immediate complications, but experienced 3 late complications(increased macular edema 2, enlarging of retinal hole 1).

30-Year Observation of Patients with Eales's Disease

Of 135 patients with Eale's disease, two thirds of the patients were men around 20 years of age at the onset, while the women were older. The disease continued from six months to 51 years. Several patients were followed for 40 years. The prognosis for useful vision was good as only one patient became blind in both eyes.

Etiology of vitreous hemorrhage in a tertiary eye care center in Nepal

Vitreous hemorrhage is one of the most common differential diagnoses of sudden painless decrease in vision. To find out the etiology of vitreous hemorrhage in cases of vitreous hemorrhage at a tertiary eye centre in Nepal. This was a hospital-based cross-sectional study done over a period of one-and-a-half years. One hundred and one subjects with vitreous hemorrhage were evaluated in detail to establish the etiology. The mean value and standard deviation were calculated. The data were analyzed using microsoft excel and SPSS 11.5 program. A total of 122 eyes of 101 patients were evaluated. The mean age was 41.90 (± 21.50) years with a range of 2 months to 84 years. Male were 73 %. Bilateral involvement was found in 20.8 %. Proliferative diabetic retinopathy, retinal vasculitis, branch retinal vein occlusion, rhegmatogenous retinal detachment together with ocular trauma constituted the etilogoy of vitreous hemorrhage in more than 75 % of patients. Proliferative diabetic retinopathy, retinal vasculitis and branch retinal vein occlusion are the most common causes of vitreous hemorrhage in adults whereas in children trauma is the commonest cause.