Coats disease is an idiopathic exudative retinopathy characterized by abnormal retinal vascular development (telangiectasia) that results in massive intraretinal and subretinal lipid accumulation. This disease entity was first described by a Scottish ophthalmologist, George Coats, in 1908.1 Coats disease is classically a unilateral process (80% of cases) affecting young males with a peak age of diagnosis at 6 to 8 years of age, without racial predominance. Males are affected three times as often as females. An adult variant of the disease is less commonly seen and is frequently associated with hypercholesterolemia.
PATHOPHYSIOLOGY OF COATS DISEASE
The clinical picture of Coats disease is that of localized, lipid-rich, subretinal exudation and abnormal vasculature, including aneurysmal dilitations, telangiectasias, areas of capillary nonperfusion, and neovascularization. Shields et al2 defined the stages of Coats disease as following Stage 1 is limited to retinal telangiectasia. Stage 2 includes telangiectasia with exudation (2A is extrafoveal and 2B is foveal exudation). Stage 3 occurs with development of an exudative retinal detachment (3A subtotal and 3B total retinal detachment). Stage 4 has total retinal detachment with glaucoma, and Stage 5 is advanced, end-stage disease. The natural history of Coats disease is generally progressive, but in a variably relapsing-remitting fashion. Spontaneous remissions have rarely been reported.3
In 1971, Tripathi and Ashton4 described in detail the pathologic features of Coats disease, comprised of a host of retinal abnormalities, in particular the absence of endothelium and pericytes in aberrant retinal blood vessels. They proposed presciently that abnormal endothelial permeability, ie, breakdown of the inner blood-retinal barrier, was the primary pathology. Whether this breakdown was structural or functional, it would secondarily result in telangiectasis and leakage. Three decades later, Black et al,5 through genetic analysis, proposed that a somatic mutation in the NDP gene, which results in a deficiency of the protein norrin, is a causal factor in Coats disease. The NDP gene is responsible for Norrie disease, and researchers believe that norrin is important in normal retinal vasculogenesis.
TREATMENT OF COATS DISEASE
Early therapeutic intervention is necessary to halt the progression of Coats disease. Laser photocoagulation or which compromise the visual outcome. Recently, antivascular endothelial growth factor (anti-VEGF) agents (bevacizumab [Avastin, Genentech, Inc.], ranibizumab [Lucentis, Genentech, Inc.], and pegaptanib sodium [Macugen, Eyetech]) have been used adjunctively. Intraocular corticosteroids have also been employed.
Multiple case reports and case series document beneficial responses to anti-VEGF agents in Coats' disease.6-13 Intraocular VEGF is noted to be elevated in Coats disease. 13 Typically, anti-VEGF agents are used to stabilize the blood-retina barrier and reduce the amount of subretinal exudation prior to laser photocoagulation. These reports often document substantial improvement of visual acuity, rather than mere stabilization of the disease process or preservation of the globe, as is expected with more traditional approaches.
One exemplary case from our institution is that of a 15 year-old boy who presented with bilateral Coats disease. The patient presented with decreased visual acuity (20/50) in his right eye secondary to subretinal exudation extending into the fovea (Figure 1) and peripheral visual field changes in his left eye (visual acuity 20/20) secondary to subretinal exudation inferior to the macula (Figure 2). Fluorescein angiography of the right eye (Figure 3) revealed abnormal inferotemporal vessels with aneurysmal dilatation and telangiectasia, which leaked profusely. Peripheral to the abnormal vasculature was an area of capillary nonperfusion. Fluorescein angiography of the left eye (Figure 4) demonstrated similar vascular changes, but of less severity. The patient was treated with intravitreal bevacizumab and laser photocoagulation, followed by vitrectomy with fluid-air exchange in his right eye. His left eye was treated with laser photocoagulation photocoagulation only, as the amount of subretinal exudation did not necessitate treatment with intravitreal bevacizumab.
Seven months after treatment, the patient regained vision to 20/20 in both eyes (Figures 5 and 6). Fluorescein angiography 5 months after treatment demonstrated obliteration of abnormal vessels with cessation of peripheral leakage in both eyes (Figures 7 and 8). The peripheral retina completely flattened in both eyes and now has an epiretinal membrane that developed over the course of treatment in the right eye.
Given the rarity of Coats disease and its variable course, therapeutic strategies have to be tailored to each individual patient. As with other diseases, a search for approaches that improve outcomes with fewer side effects is warranted. A promising new addition to our retinal tool kit is perioperative intravitreal anti-VEGF agents. With reduction of vascular permeability, there have been reports of reduction in subretinal lipid exudation, exudative retinal detachment, and macular edema in patients with Coats. This enables more effective laser photocoagulation, as the retina is better apposed to the retinal pigment epithelium following anti-VEGF treatment. In our case, we believe that the use of intravitreal bevacizumab obviated the need for subretinal fluid drainage, and we support its use as an adjunct prior to laser photocoagulation. The promising efficacy signals observed with anti-VEGF agents suggest that VEGF plays a role in the pathophysiology of Coats disease. Areas of retinal ischemia are present in the disease, and anti-VEGF therapies presumably act by reducing vascular permeability secondary to VEGF blockade.
In summary, a multimodality and stepwise approach to the treatment of Coats disease, including the use of tools that target the pathophysiology of the disease, appears to provide encouraging results.
Karl Waite, MD, is a vitreoretinal fellow at the Retina Institute of Hawaii in Honolulu.
Eugene Ng, MD, MBA, is a vitreoretinal surgeon at the Retina Institute of Hawaii.
Michael D. Bennett, MD, is a vitreoretinal surgeon at the Retina Institute of Hawaii and an Associate Professor in the Department of Surgery at the University of Hawaii, John A. Burns School of Medicine. He states that he is a paid consultant to Alcon Laboratories, Inc., Allergan, Inc., Genentech, Inc., Optimedica, Optos, Optovue, (OSI) Eyetech, Heidelberg Engineering, and Neovista. Dr. Bennett is a Retina Today Editorial Board member. He can be reached at +1 808 955 0255.