Eales Disease

Published on 08/03/2015 by admin

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Last modified 08/03/2015

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Chapter 83 Eales Disease

Introduction

Eales disease is an idiopathic, occlusive perivasculitis affecting peripheral retina in young men, leading to retinal nonperfusion, new vessel formation, and recurrent vitreous hemorrhages. Eales disease was reported from the UK, USA, and Canada in the latter half of the 19th century and early 20th century.1,2 The eponym originated from the first description of a syndrome of recurrent vitreous hemorrhage in young men with epistaxis and constipation by Henry Eales.3 Most cases in the last decade have been reported from the Indian subcontinent, with a few reports from Turkey, Saudi Arabia, and Iran.413 However, the incidence of Eales disease appears to have declined globally, due probably to improved general health and living standards and reduced incidence of tuberculosis (TB),1,2,10 as well as to improved etiologic diagnosis in a heterogeneous group of allegedly primary vasculitides, previously amalgamated as presumed Eales disease.14 Most patients are healthy young men, aged 20–40 years; the mean age of onset is generally earlier in Asians than in Caucasians.2,1517

Clinical features and natural history

Three sequential vascular responses which determine the natural course of Eales disease are inflammation, occlusion, and neovascularization.1,2,10,15 Most patients are asymptomatic at the stages of inflammation and occlusion. The disease starts quietly as multiple, peripheral inflammatory branch retinal vein occlusions: fine, solid white lines representing venous sheathing are the commonest clinical presentation (Fig. 83.1).1,2 As active vasculitis slowly resolves, the fuzzy vascular sheathing, with indistinct margins, becomes well defined and distinct. Retinal arteries may be involved later, but their involvement is not central to the disease presentation,1 and is generally suggestive of other conditions like systemic vasculitides.11,18 Other clinical features which suggest alternative inflammatory etiologies are exudative or focal vasculitis, cotton-wool spots,11,18 and central retinal involvement including macular and optic disc edema, choroiditis, anterior uveitis, and vitritis.2,14

As the occlusions are primarily venous, they occur gradually, allowing development of compensatory phenomena like collaterals, microaneurysms, capillary telangiectasia, corkscrew vessels, and venous beading; some of these changes may be observed by careful examination of the apparently uninvolved fellow eye of a patient with unilateral involvement. Prolonged and extensive retinal nonperfusion eventually leads to peripheral neovascularization in up to 80% of eyes; disc neovascularization is rare.2,4,15 New vessels bleed into vitreous, resulting in the classic presentation of Eales disease: a sudden, unilateral blurring of vision or floaters15,17 (Fig. 83.2). Vision often improves, but recurrences are common. The second eye is ultimately affected in 50–90% of cases, after a gap of 3–10 years.2,4,14,15 Isolated episodes of vitreous hemorrhage usually settle down without visual deficit; recurrent bleeds lead to progressive contraction of vitreous cortex, resulting in tractional retinal detachments, secondary retinal tears, and epimacular membranes.1 Though anterior-segment neovascularization occurs in a small fraction of eyes, the prognosis is better than what is typically associated with iris neovascularization.4

Charamis graded the evolution of Eales disease into four stages. Stage I was characterized by mild peripheral perivasculitis; stage II by extensive inflammation involving larger vessels; neovascularization and vitreous hemorrhage heralded stage III; and tractional complications marked stage IV.19 A system for grading Eales disease on the basis of the degree and extent of retinal vasculopathy, neovascular proliferations, and vitreous hemorrhage has also been proposed.20 However, the course of the disease is variable, and a fixed sequence of stages may not be followed consistently.1,2

Pathology and pathogenesis

The classic histopathological connotation of the term “vasculitis” is a type III hypersensitivity reaction with deposition of immune complexes in the vessel wall.21 This definition is not applicable to retinal vasculitis in general, and Eales disease in particular, which represents perivascular cuffing with inflammatory cells, graded by clinical appearance rather than vascular caliber or type of immune response.11,21 Most authors have therefore used the terms “vasculitis” and “perivasculitis” interchangeably in the context of Eales disease.

Central to the visually debilitating complications of Eales disease is retinal hypoxia. Inflammation causes hypoxia by an increase in the metabolic demands of cells and a reduction in metabolic substrates caused by inflammatory vascular occlusion. Hypoxia in turn triggers further inflammation, setting up a vicious cycle.22 This sequence suggest a pathogenetic role for both angiogenic factors and inflammatory cytokines in Eales disease, in a manner similar to noninflammatory vascular diseases like diabetic retinopathy. A simultaneous upregulation of vascular endothelial growth factor (VEGF), and interleukins (IL-6 and IL-9) has indeed been observed during the proliferative phases of both diabetic retinopathy and Eales disease.7 Other biochemical analyses have also implicated retinal autoimmunity, angiogenic growth factors, and oxidative stress in causing inflammation and neovascularization in Eales disease.2 Recent serologic and genetic studies have reinforced the role of cell-mediated immunity in Eales disease, particularly interleukins and tumor necrosis factor-alpha.9,12

The pathogenesis of inflammatory vascular occlusions in Eales disease remains unclear. Systemic association with neurological, vestibuloauditory, hematological, and parasitic diseases and infections have been proposed but never proven.2,15 The most frequently reported association is with systemic TB. While viable organisms have not been demonstrated from the eyes with Eales disease, polymerase chain reaction-based studies have identified mycobacterial DNA in vitreous and epiretinal tissue.23,24 These findings make the case for hypersensitivity to tuberculoprotein; the case is reinforced by the presence of Mantoux tuberculin skin test positivity in the majority of patients.2 This concept continues to be popular among current researchers.11 Several other studies have however disputed this notion by demonstrating Mantoux positivity in healthy controls, as well as Mantoux negativity among Eales patients.2,15,25

Differential diagnosis

Eales disease is a diagnosis of exclusion (see Fig. 83.3). Several ocular and systemic inflammatory and noninflammatory diseases cause retinal vascular sheathing or occlusion, which may closely resemble Eales disease. However, a battery of investigations is not necessary for every patient. A detailed history and a thorough systemic examination rule out most of the mimicking diseases; only a few tailored investigations are required to clinch the diagnosis.

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