Eales’ Disease: Current Concepts in Etiopathogenesis and Management
Sandeep Saxena. MS., MAMS.
Professor, Department of Ophthalmology, CSM Medical University,(Erstwhile King George’s Medical University), Lucknow, India. e-mail: sandeepsaxena2020@yahoo.com
Introduction
Eales’ disease is an idiopathic retinal periphlebitis that primarily affects the peripheral retina in young adults. Eales’ disease was first described by Henry Eales, a British ophthalmologist, in 1880 and 1882.1,2 He found it in seven young, male patients ranging in age from 14 to 29 years with recurrent vitreous hemorrhage. In addition, these patients had history of headache, variation in peripheral circulation, chronic constipation and epistaxis. In the next century, the disease was redefined by several investigators. 3-6 Elliot first recognized the inflammation of retinal vein and described it as periphlebitis retinae.4 Subsequently several investigators documented both venular and arteriolar inflammation.5,7
Eales’ disease most commonly affects healthy young adult males and is an important cause of preventable blindness in young adults. The predominant age of onset of symptoms is 20-30 years. The disease is more commonly seen in the Indian subcontinent. However, it has been reported from United Kingdom, U.S.A., Canada, Germany, Greece and Turkey.
Eales’ disease is characterized by retinal periphlebitis (Fig. 1), peripheral retinal ischemia (Fig. 2), and neovascularization (Fig.3). Visual loss is characteristically caused by recurrent vitreous haemorrhage.8 Vascular involvement in Eales’ disease may be peripheral or central. Central Eales’ disease is markedly uncommon (Fig. 4). 9-11
Fig. 1. Color fundus photograph shows retinal periphelbitis along with superficial retinal hemorrhages.
Fig. 2. Fundus fluorescein angiography shows capillary non perfusion, microaneurysms and leakage of fluorescein dye from retinal neovascularization.
Fig. 3. Color fundus photographs shows neovascularization elsewhere, sheathing of retinal vessels and hard exudates at macula.
Fig. 4. Color fundus photographs shows Central Eales’ disease.
Etiopathogenesis
Eales’ disease appears to be an immunologic reaction that may be triggered by an exogenous exposure. Retinal S-antigen and Interphotoreceptor Retinoid Binding Protein play a role in the etiopathogenesis of this condition. An extraneous agent results in the exposure of normally sequestered uveitopathogenic antigens of the immune system, leading to an immune response in the eye that initiates the disease process. 12
Oxidative stress has been found to play an important role in the etiopathogenesis. 13-20 Lowered levels of antioxidant vitamins E and C and consequent accumulation of oxygen and lipid free radicals, or vice versa, could explain the inflammation, neovascularization and retinal pathology in patients with Eales' disease. Also, vitamin A deficiency could aggravate retinal illness. Elevated lipid peroxides have been found in the proliferative stage, which induce synthesis of cytokines and growth factors in retina during neovascularization.15
Eales’ disease is distinctively characterized both by stage of inflammation as well as stage of proliferation.7 Cytokines play an important role in intraocular inflammation.8,9 The cascade of multiple angiogenic cytokines induced by oxidative damage, associated with tissue hypoxia, may interact to promote sustained retinal neovascularization.10 During the inflammatory and proliferative stages of the disease statistically significant increase in IL-1b, IL-6, IL-10 and TNF-a expression was observed as compared to controls, highlighting the role of pro- and anti-inflammatory cytokines in the pathogenesis.21
Markedly raised levels of IL-1b and TNF-a have been observed in the inflammatory stage which persisted in the proliferative stage. Raised levels of IL-1b, in the inflammatory stage, decreased significantly in the proliferative stage. Elevated TNF-a levels, observed in the inflammatory stage, increased significantly in the proliferative stage where clinically, inflammation (periphlebitis) had subsided but retinal neovascularization and vitreous hemorrhage had developed with the occurrence of retina hypoxia and ischemia. This data suggests that despite clinical absence of periphlebitis in the proliferative stage of the disease, IL-1b and TNF-a levels remain raised significantly as compared to controls. The synergism of IL-1 and TNF is a commonly reported phenomenon. IL-1 and TNF initiate the cascade of inflammatory mediators by targeting the endothelium. Although the receptors for TNF and IL-1 are clearly different, the post receptor events are similar. IL-1 often synergizes with TNF for NO induction which mediates cell death.11 Nitrosoactive stress has been found to promote retinal vasculitis in Eales’ disease.12 Significant TNF-a expression was observed during the proliferative stage. These findings indicate that angiogenesis during the proliferative stage is induced by TNF-a. Angiogenesis induced by TNF-a, during post-ischemic inflammation, may be modulated through induction of potent angiogenic factors.14 Hypoxia-induced expression of vascular endothelial growth factor is only one aspect of the complicated processes in intraocular neovascularization.15 Chemokines have also been found to be involved in the recruitment of neutrophils and monocytes into the vitreous and play a role in the intraocular neovascularization.16 Thus, the IL-1 system represents a novel target for controlling inflammatory activity and/or the associated long-term sequelae related to angiogenesis in Eales’ disease. Role of TNF-a in the inflammatory as well as proliferative stage of the disease has implications for anti-TNF-a therapy in Eales’ disease. Reducing the biological activities of IL-1 and TNF may be accomplished by several different, but highly specific strategies, which involve neutralizing antibodies, soluble receptors, receptor antagonist, and inhibitors of proteases that convert inactive precursors to active, mature molecules. Anti-cytokine therapeutic agents such as TNF-neutralizing antibodies, soluble TNF receptors, and IL-1 receptor antagonist may prove beneficial. Infliximab (anti-TNF-a) may prove to be beneficial in patients of Eales’ disease.21
