Eales Disease 

Updated: Sep 28, 2018
Author: Jonathan C Tsui, MD; Chief Editor: Hampton Roy, Sr, MD 

Overview

Background

Eales disease is an idiopathic obliterative vasculopathy that usually involves the peripheral retina of young adults. In 1880, Henry Eales first described it in healthy young men with abnormal retinal veins and recurrent vitreal hemorrhages.

Clinical findings in Eales disease are characterized by avascular areas in the retina periphery, followed posteriorly by microaneurysms, dilatation of capillary channels, tortuosity of neighboring vessels, and spontaneous chorioretinal scars. It is a diagnosis of exclusion, as many other retinal disorders can mimic Eales disease, especially conditions of retinal inflammation or neovascularization. Note the clinical image below:

Eales disease. Fundus photo of the peripheral reti Eales disease. Fundus photo of the peripheral retina, revealing vascular tortuosity and peripheral retinal neovascularization.

Pathophysiology

The pathophysiology of Eales disease is mostly unknown. Eales disease is believed to be a primary, noninflammatory disorder of the walls of peripheral retinal vessels, namely the shunt vessels. This often leads to vascular occlusions, peripheral neovascularization, and vitreous hemorrhage. The microvascular abnormalities are seen at the junction of perfused and nonperfused zones of the retina. Although associations with tuberculosis and multiple sclerosis have been suggested, these findings have not been substantiated in other studies. It is possible that the association of Eales disease with both ocular inflammation and sensitivity to tuberculin protein suggests that this disease may be associated with immunologic phenomena whose mechanisms remain unknown.[1]

Epidemiology

Frequency

United States

Eales disease is uncommon, with most reports based upon a series of cases.

International

Eales disease is most commonly seen in India and portions of the Middle East.

Mortality/Morbidity

No known mortality is associated with Eales disease. Visual compromise is seen in patients with recurrent vitreous hemorrhage; however, the visual acuity resolves to better than 20/200 in greater than 70% of patients. If retinal nonperfusion extends into the macula, the visual acuity usually is worse than 20/400.

Race

No racial predilection is known in Eales disease; however, the disease is more prevalent in India and portions of the Middle East.

Sex

Young adult males have been reported to have an increased prevalence of Eales disease; however, a study of 55 patients by Gieser and Murphy found that men and women are affected equally.[2]

Age

Peak age of onset for Eales disease is 20-35 years, with a reported range of 13-63 years.

Prognosis

More than 90% of Eales disease patients can be brought to a morphological standstill with unchanging visual acuity.

Gieser and Murphy reported that 67% of patients had a final visual acuity in the better eye of 20/40 or better, 24% ranged from 20/50 to 20/200, and 9% were worse than 20/250.[2]

In another study from India, 72% of eyes that underwent vitrectomy for complications of Eales disease maintained a vision of 20/200 or better over 5 years of follow-up care.[3]

Patient Education

Patients with Eales disease should be educated to report visual symptoms of floaters or decreased vision to their ophthalmologist as soon as possible, in order to implement effective treatment and to prevent the need of vitrectomy surgery for vitreous hemorrhage or retinal detachment.

 

Presentation

History

Most Eales disease patients present with symptoms of floaters, specks, cobwebs, blurring, or decreased vision associated with vitreous hemorrhage. Other Eales disease patients have blurring associated with retinal vasculitis or uveitis, but without hemorrhage. Often, patients report uniocular symptoms, but ophthalmic examination reveals early changes of Eales disease in the other eye. Bilateral involvement is evident in 80-90% of patients.

Physical

The physical findings in Eales disease mostly involve the retina and vitreous. Vascular sheathing with adjacent nerve fiber layer hemorrhages is seen in most patients. The sheathing can manifest as thin white lines, limiting the blood column on both sides of the sheathed vessel to heavy exudative sheathing that can cause vascular occlusion. Although believed to affect primarily the retinal veins, others have reported the same prevalence of both venules and arterioles. Areas of vascular sheathing often leak dye on fluorescein angiography (FA).

The anterior chamber may exhibit cell and flare with keratic precipitates. Vitreous debris and cells often are seen, even in the absence of vitreous hemorrhage. Macular edema can occur in eyes with vascular sheathing, and it often is cystoid in nature. Epiretinal membranes with or without macular edema can compromise visual acuity. The etiology of the macular edema is thought to be associated with low-grade inflammation.

Peripheral nonperfusion is a typical feature of Eales disease. The temporal retina is affected most commonly, often in a confluent area. The surrounding vasculature is tortuous with microvascular abnormalities, which include the following: microaneurysms, arteriovenous shunts, venous beading, hard exudates, and cotton-wool spots. Fine solid white lines occasionally can be seen, representing obliterated larger vessels.

Branch retinal vein occlusion (BRVO) can be seen in patients with Eales disease and may be limited to one area or may be multifocal. BRVO alone can be differentiated from BRVO in the presence of Eales disease by the more extensive peripheral retinal involvement in Eales disease. BRVO alone usually is confined to a single affected quadrant. BRVO alone also respects the anatomical distribution of the horizontal raphe, unlike Eales disease.

Neovascularization of the disc (NVD) or neovascularization elsewhere (NVE) in the retina is observed in up to 80% of patients with Eales disease. The NVE usually is located peripherally, at the junction of perfused and nonperfused retina. The neovascularization often is the source of vitreous hemorrhage in these eyes, compromising vision. Rubeosis iridis or neovascularization of the iris can develop and may lead to neovascular glaucoma. Fibrovascular proliferation on the surface of the retina may accompany retinal neovascularization. These eyes have associated anteroposterior traction that could lead to retinal detachment.

Cystoid macular edema can occur in patients with Eales disease due to increased capillary permeability. This can often be associated with significant vision loss.

A posterior vitreous separation has been reported in 27% of patients with Eales disease, and several patients have been found to have concomitant macular holes. Macular hole surgery may effectively repair this abnormality and lead to significant visual improvement similar to that seen in patients with idiopathic macular holes.

Systemic abnormalities have been reported in association with Eales disease, mostly neurologic findings. Myelopathy,[4, 5] ischemic stroke,[6] hemiplegia,[7] and multifocal white matter abnormalities have been reported.[8, 9] A higher incidence of vestibuloauditory dysfunction is seen in patients with Eales disease when compared to the general population of the same age. It is presumed that a similar mechanism of vascular occlusion and hypoxia leads to these systemic findings.

Causes

The cause of Eales disease is unknown. Eales disease is a diagnosis of exclusion and is thought to be idiopathic. No causative drugs, environmental factors, or infectious agents for Eales disease have been identified. Although a hypersensitivity to tuberculin protein has been reported, no clear relationship to tuberculosis has been found. Nonetheless, limited data have shown that elevated erythrocyte sedimentation rate (ESR), high tuberculin skin test (TST) result, and vitreous polymerase chain reaction (PCR) positive for Mycobacterium tuberculosis indicated a more likely diagnosis of Eales disease.[10]

An 88-kd acute phase reactant protein has been found in patients with Eales disease that is immunologically identical to that found in patients with posterior uveitis, tuberculosis, leprosy, and rheumatoid arthritis. This protein complex consists of haptoglobin, complement C3, and galectin-1, although its exact role is yet to be determined.[11]

Increasing data implicate interleukin (IL)–1 and tumor necrosis factor-alpha (TNFα) in the inflammatory stage of Eales disease.[12] In addition, inflammatory cytokines IL-6, IL-8, MCP-1, and VEGF have been found in Eales disease and proliferative diabetic retinopathy (PDR), suggesting similar pathophysiology.[13] Genetic polymorphism studies suggest low IL-10 expression and high TNFα may increase the occurrence and severity of Eales.[14] Furthermore, copper is known to have pro-oxidant characteristics when body copper levels are excessive. A study of copper transporter 1 (CTR1) protein levels in Eales disease found elevated expression in the retina and peripheral blood mononuclear cells (PBMCs) involved in inflammation.[15]

Complications

Complications of retinal neovascularization can lead to severe visual loss due to persistent vitreous hemorrhage and retinal detachment.

Anterior segment neovascularization can cause neovascular glaucoma with resultant visual loss and, occasionally, even loss of the eye.

Peripheral retinal nonperfusion can limit a patient's visual field, and, if the area of nonperfusion extends into the macula, severe visual loss may result. No effective treatment exists to prevent capillary nonperfusion.

Macular puckering has been reported to occur in 3% of eyes after scatter laser photocoagulation treatment of Eales disease.

 

DDx

 

Workup

Laboratory Studies

No clinical laboratory studies are available to confirm the diagnosis of Eales disease, as it is a diagnosis of exclusion. However, laboratory studies are necessary to exclude other similar entities. See the following:

  • Blood glucose or fasting blood glucose to rule out diabetes mellitus

  • Complete blood count to rule out hemoglobinopathies

  • Sickle cell preparation and serum protein electrophoresis to rule out sickle cell disease

  • Angiotensin converting enzyme and lysozyme to rule out sarcoidosis

  • Antinuclear antibody, rheumatoid factor, and erythrocyte sedimentation rate to rule out collagen vascular disease

  • Tuberculin skin testing may be useful, as patients with Eales disease have a higher incidence of tuberculin hypersensitivity, despite the absence of a history of tuberculosis.

Imaging Studies

Fluorescein angiography (FA) can be useful to determine the nature of the microvascular abnormalities associated with Eales disease. Neovascularization and exudative sheathing of vessels will leak fluorescein dye. The area and degree of nonperfusion can be determined on FA and help delineate where to apply laser photocoagulation, when indicated. Note the image below.

Eales disease. Fluorescein angiogram of late leaka Eales disease. Fluorescein angiogram of late leakage from peripheral retinal neovascularization.

Echographic evaluation often is useful to evaluate the retina in the setting of vitreous hemorrhage. When the details of the fundus are obscured, ultrasound can determine the presence or absence of a retinal detachment or vitreoretinal traction.

Chest radiography may be considered to rule out sarcoidosis or a history of tuberculosis, in the setting of a positive tuberculin skin test. In specific cases, high-resolution computed tomography of the chest may be helpful for further delineating pathology seen on equivocal chest radiographs.[16]

Magnetic resonance imaging (MRI) of the brain may reveal multifocal white matter abnormalities, but this study probably is not warranted in the absence of neurologic symptoms.

Optical coherence tomography (OCT) is a useful modality to image the macular morphology and architecture. Changes in the macula contributing to visual loss may be detected with OCT, including macular edema and epiretinal membrane. In some cases, spectral-domain OCT has been able to detect changes that have not been evident on fluorescein angiography.[17]

Other Tests

Studies have found an increased level of oxidation and peroxidation products in vitreous samples from patients with Eales disease (ie, an increased amount of thiobarbituric acid reacting substances). A decreased level of antioxidant enzymes also has been found in vitreous samples from patients with Eales disease (ie, a decreased amount of reduced glutathione, superoxide dismutase, and glutathione peroxidase).[18, 19]

Hearing and balance should be tested formally, as patients with Eales disease may have associated vestibuloauditory dysfunction.

 

Treatment

Medical Care

Several treatments have been proposed for Eales disease; however, none of these treatments is of proven benefit. Treatments include thyroid extract, osteogenic hormones, androgenic hormones, and systemic steroids. The antioxidant vitamins A, C, and E have been suggested as a possible therapy because antioxidizing enzymes are deficient in the vitreous samples of patients with Eales disease.

In cases complicated by cystoid macular edema, intravitreal triamcinolone acetonide has been effectively used in reversing the edema and in leading to visual improvement.[19] Doses of 1-25 mg of triamcinolone have been reported; however, doses of 2-4 mg of triamcinolone are more commonly used in clinical practice.[20]

Intravitreal injections of bevacizumab have been reported to induce regression of the neovascularization associated with Eales disease. Bevacizumab also reduces cystoid macular edema in Eales disease by inhibiting vascular endothelial growth factor (VEGF)–mediated capillary hyperpermeability.[21, 22, 23, 24]

A randomized, prospective trial with intravitreal bevacizumab was performed in eyes with vitreous hemorrhage secondary to Eales disease. The small study demonstrated bevacizumab did not hasten resolution of vitreous hemorrhage and had a trend toward increased risk of progression to tractional retinal detachment.[25]

A completed clinical trial is Lucentis (Ranibizumab) for Eales' Disease.

Surgical Care

Moderately light, full-scatter laser photocoagulation to areas of nonperfused retina has become the treatment of choice in patients with Eales disease.[26, 27] The junctional area between perfused and nonperfused retina is to be treated. This treatment results in resolution of neovascularization of the disc, elsewhere in the retina, or the iris, and lowers the incidence of vitreous hemorrhage.

A major cause of visual loss in patients with Eales disease results from recurrent vitreous hemorrhage. Although the hemorrhage often settles in the inferior portion of the vitreous and reabsorbs within several weeks, surgical intervention occasionally is indicated. Pars plana vitrectomy is effective in removing nonclearing vitreous hemorrhage and enabling adequate scatter laser photocoagulation. In cases of tractional retinal detachment, vitrectomy in combination with membrane dissection is necessary.

Consultations

Consultation with a neurologist is appropriate in the setting of concomitant neurologic symptoms.

Diet

No dietary modification has been proven to be of benefit in Eales disease. However, studies suggest that vitamin A, C, and E supplementation may have a beneficial effect.

Activity

No limitations in activity exist for patients with Eales disease. However, in the setting of vitreous hemorrhage, a sitting position may expedite the clearing of the central visual axis, as the blood is reabsorbed.

Long-Term Monitoring

After scatter laser photocoagulation, monitor the Eales disease patients for regression or progression of neovascularization. Instruct the patient to contact an ophthalmologist if a decrease or change in vision is noted.

 

Medication

Medication Summary

No drugs have been found to be effective in the treatment of the underlying mechanism of Eales disease. Medications used in different studies are mentioned above, but they have not been proven to be beneficial. Cystoid macular edema can complicate Eales disease and has responded to periocular and intravitreal triamcinolone.

Corticosteroids

Class Summary

Have anti-inflammatory properties and cause profound and varied metabolic effects. Modify the body's immune response to diverse stimuli. Used to stabilize the blood-retinal barrier and to induce resolution of macular edema.

Triamcinolone (Amcort, Kenalog)

For inflammatory dermatosis responsive to steroids; decreases inflammation by suppressing migration of polymorphonuclear leukocytes and reversing capillary permeability. Posterior sub-Tenon injection of steroid to reduce cystoid macular edema. Depending on etiology of edema, it is often DOC.

Antineoplastic Agent, Monoclonal Antibody

Class Summary

Bevacizumab (Avastin) is a monoclonal antibody that binds to VEGF or vascular endothelial growth factor. It was approved originally in the treatment of colorectal carcinoma. It is now used commonly via intravitreal injection to treat disorders such as exudative macular edema and retinal vein occlusion. Its use has been reported as useful to induce regression of neovascularization in proliferative diabetic retinopathy and would have a similar effect against the neovascularization of Eales disease.

Bevacizumab (Avastin)

Inhibitor of VEGF, a potent mediator of angiogenesis and capillary permeability.