Eales Disease

From EyeWiki
Original article contributed by: Andreas K. Lauer, M.D.
All contributors: Andreas K. Lauer, M.D. and Vinay A. Shah M.D.
Assigned editor: Jennifer I Lim MD
Review: Assigned status Up to Date by Andreas K. Lauer, M.D. on August 16, 2015.



Eales Disease
Classification and external resources
DiseasesDB 4028


Disease Entity

Eales Disease

Authors

Kristen Ann Mendoza, MD; Andreas Lauer, MD

Disease

Eales disease is an idiopathic peripheral retinal vasculopathy characterized by inflammation, ischemia, retinal neovascularization and is hallmarked by recurrent vitreous hemorrhages.

Etiology

No definite cause for Eales disease has been found to date and it is considered idiopathic.

Risk Factors

Eales disease has been reported predominantly in India, although it has been found in North America and Europe (rare in the modern era). The incidence in India is 1/200. Eales disease tends to occur in males in their second decade and has been related to tuberculosis exposure and hypersensitivity to tuberculoprotein. Less commonly, it has been linked to CNS pathology (stroke, demyelination, intranuclear ophthalmoplegia), hematological abnormalities (abnormal red blood cell morphology), vestibuloauditory dysfunction, and focal sepsis.

General Pathology

Eales disease was originally described as a combination of recurrent intraocular hemorrhages in young men with constipation, epistaxis, and headache. More recently, it has been found to be a process that progresses through retinal periphlebitis, ischemia, and neovascularization. Specifically, peripheral retinal vessels first become inflamed and sheathed, then become occluded. The loss of perfusion leads to retinal neovascularization that causes recurrent vitreous hemorrhages. Eales is considered a bilateral disease in up to 90% of patients, although symptoms often present unilaterally.

Pathophysiology

The exact pathological mechanisms in Eales disease are largely unclear despite several basic science and clinical studies. Immunologic mechanisms have been proposed. T-cell lymphocytic infiltration has been found in the epiretinal and subretinal membranes associated with Eales. There have also been associations made with the retinal S-antigen and HLA B5, DR1, DR4 and patients with autoimmune disease. Support has been found for oxidative stress, as increased accumulation of lipid peroxide, increased carboxy methyl lysine, decreased glutathione, and decreased vitamins C and E has been found. Similarly, increased vascular endothelial growth factor (VEGF) results in retinal neovascularization.

Primary prevention

There are no preventative measures for Eales disease.

Diagnosis

Eales disease is a clinical diagnosis of exclusion.

History

Those with Eales disease typically present as young males living in India. Patients may have other associated risk factors as mentioned above. A history of a systemic disorder can point away from the diagnosis of Eales.

Physical examination

  • Visual acuity: Two-thirds of patients have vision 20/40 or better as the disease tends to spare the macula and predominantly affects the peripheral retina. In patients with vitreous hemorrhage or more severe disease, the vision may be very poor and as bad as no light perception (NLP).
  • Anterior segment: cell and flare, rubeosis irides (late finding), neovascular glaucoma (late finding), nongranulomatous uveitis (rare finding).
  • Vitreous: cells and debris (early finding), hemorrhage (late finding); dense vitritis is uncommon.
  • Optic nerve: edema, neovascularization.
  • Retina: perivascular sheathing and exudate, vessel tortuosity, venous obstruction, capillary non-perfusion, neovascularization, retinal detachment, epiretinal membrane, macular edema.

Signs

  • Eales is initially asymptomatic, but then progresses through general stages of the disease. While there is no standardized classification of Eales due to clinical overlap of early and late signs of the disease, three phases are typically recognized:
  • Early (inflammatory) Stage: periphlebitis is hallmark and may be found in various stages and in various quadrants concurrently; venous dilation and perivascular exudates can be found as well.
  • Middle (ischemic) Stage: characterized by capillary ischemia; demarcation between perfused and nonperfused zones is marked by veno-venous shunts, venous beadings, and micro-aneurysms.
  • Late (proliferative) Stage: neovascularization occurs at the junction between perfused and non-perfused retina that leads to recurrent vitreous hemorrhages with or without retinal detachment.
  • Eales disease tends to occur peripherally, but macular edema and disc neovascularization may occur.

Symptoms

Patients may present with decreased vision, photopsia, and floaters unilaterally or bilaterally.

Clinical diagnosis

Eales disease is a diagnosis of exclusion. Peripheral retinal inflammation and recurrent vitreous hemorrhages in the absence of other systemic conditions are important defining features.

Diagnostic procedures

  • Fluorescein angiography (FA): leakage of sheathed vessels, retinal vascular tortuosity and telangiectasias, shunt vessels, venous stasis, capillary non-perfusion and sharply demarcated areas of non-perfusion, retinal neovascularization
  • Inflammation correlates to venous insufficiency. In the inflammatory stage, extravasation of dye indicates active inflammation. Venous staining without leakage indicates sclerosed vessels or resolved inflammation.
  • Ultrasonography: useful for detecting retinal detachment when vitreous hemorrhage obscures view of the fundus.

Laboratory test

Laboratory tests are neither sensitive nor specific for Eales disease, but may be helpful in detecting systemic causes of retinal vasculitis or peripheral retinal non-perfusion. As Mycobacterium tuberculosis DNA has been found in the vitreous of patients with Eales disease, the Mantoux test and a chest x-ray may be helpful. Hemoglobin electrophoresis can assess for sickle cell retinopathy, serum angiotensin converting enzyme and a chest x-ray can point to sarcoidosis, the Veneral Disease Research Laboratory test (VDRL) is useful for syphilis, and anti nuclear antibody (ANA) can indicate systemic lupus erythematosus (SLE).

A distinct protein with an isoelectric point of 5.9 and a weight of 23 kDa has been associated with Eales disease, as have increased alpha globulins, increased alpha-1 acid glycoproteins, decreased serum albumin, and increased matrix metalloproteinase 9 (MMP-9).

Differential diagnosis

  • Vasculitides and retinopathies comprise the differential for Eales disease.
  • Vascular: retinopathy of prematurity, branch retinal vein occlusion, Bechet’s syndrome, radiation retinopathy, coagulopathy, granulomatosis with polyangiitis (formerly Wegener's).
  • Infectious: lyme disease, syphilis.
  • Autoimmune: frosted branch angiitis, ulcerative colitis, multiple sclerosis, sarcoidosis, Birdshot retinochoroidopathy.
  • Idiopathic: serpiginous choroiditis, central serous retinopathy, idiopathic hypereosinophilia, Coat’s disease, idiopathic retinal vasculitis aneurysms and neuretinitis, Susac disease.
  • Neoplastic: leukemia.
  • Congenital: sickle cell retinopathy, incontinenti pigmenti, familial exudative vitreoretinopathy.
  • Endocrine: diabetic retinopathy
  • Choroiditis or hypopyon are not present in Eales disease.

General treatment & Management

Observation is warranted in patients with inactive vasculitis or new vitreous hemorrhage in the setting of an attached retina for 6 months and 6 weeks, respectively.

Medical therapy

In the early or inflammatory stage, oral prednisone (1-1.5 mg/kg tapered over 6-8 weeks) is recommended in patients with involvement of two quadrants, with maintenance dose (15-20 mg per day for up to 2 months) if needed. However, in patients with macular edema or involvement of three quadrants, intravitreal triamcinolone acetonide has shown improvement in visual acuity from counting fingers to 20/40. Non-steroidal immunosuppressive agents are reserved for those in whom steroids are ineffective or contraindicated. With vascular non-perfusion and retinal neovascularization, intravitreal anti-VEGF therapy may be successful, however its effects may cause vitreoretinal contraction. In patients with exposure to tuberculosis, anti-tubercular therapy can be given for 9 months, but this is reserved for patients with massive infiltration, nodule formation, and venous obliteration.

Medical follow up

Ultransonographic surveillance of the retina when allowing vitreous hemorrhage to clear spontaneously is useful. Use of supplemental antioxidants such as vitamins C and E to help fight oxidative stress on the retina has been advocated in the past but is less commonly recommended in recent times.

Surgery

For patients with later stage disease where retinal neovascularization is present, laser scatter photocoagulation (peripheral pan retinal photocoagulation) in the areas of retinal non-perfusion induces regression of neovascularization. Moderately strong, 200-500 micrometer, overlapping laser spots are applied to the areas of retinal non-perfusion and direct photocoagulation of new and underlying feeder vessels is suggested. When optic disc neovascularization is present, panretinal photocoagulation laser is recommended. For nonresolving vitreous hemorrhage and/or retinal detachment (whether tractional, rhegmatogenous, or combined), pars plana vitrectomy is necessary, with or without other vitreoretinal surgical procedures. Endolaser treatment may be applied at the time of surgery. Vitrectomy for nonresolving vitreous hemorrhage should be performed no later than 6 months following onset of hemorrhage.

When access to vitrectomy is not possible and the view to the peripheral retina is compromised by vitreous hemorrhage, trans-scleral anterior retinal cryoablation may be use alone or in conjunction with photocoagulation of ophthalmoscopically visible non-perfused retina.


Surgical follow up

Since subsequent ischemia develops often, further photocoagulation is typically required.

Complications

Post-operative complications include choroidal neovascularization, retinal, choroidal or vitreous hemorrhage, retinal detachment, epiretinal membrane, glaucoma and cataract.

Prognosis

With proper treatment, the overall prognosis of Eales disease is good. The major cause of visual loss is recurrent vitreous hemorrhages. Complications of neovascularization, such as retinal detachment and neovascular glaucoma, may contribute to significant vision loss, however, blindness is rare, and vision less than 20/200 occurs in less than 1% of patients.


References

1. Das T, Pathengay A, Hussain N, Biswas J. Eales’ disease: diagnosis and management. Eye (Lond). 2010;24(3):472-82.

2. Agrawal S, Agrawal J, Agrawal TK. Intravitreal triamcinolone acetonide in Eales disease. Retina. 2006;26(2):227-9.

3. Biswas J, Sharma T, Gopal L, Madhavan HN, Ramakrishnan S. Eales disease – an update. Surv. Ophthalmol. 2002;47(3):197-214.

4. Fraunfelder FT, Roy FH. Current Ocular Therapy. 5th edition. Philadelphia: W.B. Saunders Company; 2000. 609-11.

5. Roy FH, Fraunfelder FW, Fraunfelder FT. Current Ocular Therapy. 6th edition. Elsevier; 2008. 624-5.

6. Gupta SR, Flaxel CJ. The use of a vascular endothelial growth factor inhibitor (ranibizumab) in macular edema due to eales disease. Retin. Cases Brief Rep. 2012;6(1):122-4.

7. Patwardhan SD, Azad R, Shah BM, Sharma Y. Role of intravitreal bevacizumab in Eales disease with dense vitreous hemorrhage: a prospective randomized control study. Retina. 2011;31(5):866-70.

8. Sen A, Paine SK, Chowdhury IH, Mukherjee A, Choudhury S, Mandal LK, Bhattacharya B. Assessment of gelatinase and tumor necrosis factor-alpha level in the vitreous and serum of patients with Eales disease: role of inflammation-mediated angiogenesis in the pathogenesis of Eales disease. Retina. 2011;31(7):1412-20.