Coats disease is a condition characterized by idiopathic retinal telangiectasia and aneurysmal vessels, often with intraretinal and subretinal exudation.1 Described in 1908, the exact etiology of Coats disease remains unknown; however, mutations in retinal proteins encoded by CRB1 and NDP may be shedding light on possible causes.1

Coats disease usually presents in childhood; it has a 3:1 male predominance and is unilateral in 95% of cases.2,3 Patients present with poor vision, strabismus, or leukocoria. 3 Fundus evaluation often reveals peripheral retinal telangiectasia, aneurysms (light bulbs), and subretinal fluid and exudation, often tracking back to the macula.1 As the disease further progresses, complications include secondary glaucoma, anterior chamber cholesterolosis, corneal edema, cataract, lens dislocation, macular fibrosis, and amblyopia.3,4 In some cases, enucleation is necessary for intractable pain from secondary neovascular glaucoma. We hereby report a case of Coats disease with dramatic resolution of exudation following treatment.

CASE

A 24-month old Hispanic male was noticed by his parents to have a white pupil and lazy eye. On examination, the visual acuity of the right eye was fix and follow, but the left eye showed no fix or follow. There was left esotropia of 35 prism diopters. Intraocular pressure was 16 mm Hg in both eyes.

On evaluation, the right eye was unremarkable and findings were limited to the left eye. The OS displayed xanthocoria from a shallow total retinal detachment (RD) and subretinal exudates around the optic disc inferiorly and extending temporally, emanating from a mass of telangiectasia in the nasal retina (Figure 1 A). Flourescein angiography (FA) showed peripheral retinal nonperfusion for 360° immediately anterior to leaking telangiectasia and aneurysms. (Figure 1 B-D). The clinical findings and FA suggested the diagnosis of Coats disease stage 3B.2 Treatment involved closure of all leaking telangiectasia with three sessions of cryotherapy and one session of laser photocoagulation delivered over 2 to 3 months. The exudation and RD resolved completely by 19 months; however, subfoveal gliosis resulted along the superotemporal arcade. At 24 months, the eye remained stable and the reduced visual acuity was attributed to chronic scarring from the RD and Coats disease compounded by amblyopia (Figure 2). The child was advised to undergo amblyopia occlusion therapy.

DISCUSSION

Coats first described unilateral exudative retinopathy in young males and divided it into three groups depending on the presence of exudation and abnormal retinal vasculature. In 2001, Shields and associates proposed a classification of Coats disease based on disease course and prognosis (Table 1).5 A simplified classification has been extracted (Table 2). Stage 1 is characterized by telangiectasia only.2,5 Stage 2 demonstrates telangiectasias and exudation and is further subcategorized depending on involvement of the fovea.2,5 Stage 3 demonstrates subtotal retinal detachment, also subcategorized based on foveal involvement, while stage 4 exhibits total RD with glaucoma.2,5 Stage 5 is endstage disease with a blind, painless eye and total RD, often with cataract and eventual phthisis bulbi.2,5

Current management aims to preserve patient comfort and vision. Treatment options include cryotherapy applied transconjuctivally to the telangiectatic areas and/or photocoagulation. 1 Schefler and associates used repeated diode laser treatment in 17 patients with advanced Coats disease.6 The telangiectasia and exudates resolved in 14 cases (82%), with globe salvage in 16 (94%) and poor visual acuity in 7 (47%).6 In more advanced cases with RD, subretinal fluid drainage and pars plana vitrectomy combined with scleral buckling have been successful.7 Jumper and associates used multiple sessions of laser treatment in 47

patients and detected dense macular fibrosis in 11 (23%) patients.4 Various treatment modalites were used, including laser photocoagulation, cryotherapy, and vitrectomy.4 Macular fibrosis resulted in 23% of patients, all of whom had temporal retinal telangiectasias.4 The authors proposed that the etiology for macular fibrosis was neovascularization secondary to lipid exudation, concluding that the macular fibrosis contributed to poor vision.4

Shields and coworkers reported on management of 158 eyes based on Coats disease staging (Table 1).2 Stage 1 patients were managed generally with observation as there was no leakage from the telangiectasia.2 Stages 2 and 3 eyes were treated with cryotherapy or laser photocoagulation to reverse retinal leakage. Stage 4 eyes usually require enucleation for intractable ocular pain from secondary neovascular glaucoma.2 Stage 5 eyes were observed, as these end-stage eyes had very poor visual acuity with no hope for return of vision.2 The authors concluded that earlier diagnosis and treatment could preserve vision and prevent complications such as secondary glaucoma.2

Studies of gene mutations are shedding some light on the possible pathogenesis of Coats disease. In 1999, Norrie disease pseudoglioma (NDP) gene was shown to carry a somatic missense mutation in nine enucleated eyes in male children with Coats disease.8 The authors of this report concluded that the somatic mutations in the NDP gene during the development of the retina led to formation of telangiectasia in Coats disease.8 In animal studies, den Hollander and associates have implicated Crumbs homologue 1 (CRB1) gene as being abnormal in exudative retinopathies including Coats disease, and they proposed that heterozygous CRB1 mutations may be a risk factor for development of classic Coats disease.9

The use of bevacizumab (Avastin, Genentech) in the treatment of Coats disease is currently an area of research. It has been shown that vascular endothelial growth factor (VEGF) levels in Coats disease eyes are considerably elevated in stages 2 and 3.10 Several case reports have been published with bevacizumab as a treatment modality. In a recent case study by Cakir and associates, a 14-year-old boy with stage 3A Coats disease was treated with intravitreal bevacizumab and intravitreal triamcinolone acetonide after being unresponsive to laser treatment.11 Following treatment, there was resolution of the superior bullous exudative retinal detachment and subfoveal serous fluid. Visual acuity improved from 20/400 to 20/125 and remained stable at 6 months.11

In summary, we present a case of stage 3B Coats disease treated with cryotherapy and laser photocoagulation, which resulted in complete resolution of subretinal fluid with residual chronic subretinal exudation and gliosis. Coats disease responds to destructive procedures, but the future role of less invasive therapy has yet to be defined.

Support provided by the Retina Research Foundation of the Retina Society in Capetown, South Africa (CLS), and the Eye Tumor Research Foundation, Philadelphia, PA (CLS).

Rishav Kansal, BS, is a medical student at Temple University in Philadelphia.

Kiran Turaka, MD, is an Ocular Oncology Fellow at Wills Eye Institute, Thomas Jefferson University in Philadelphia.

Carol L. Shields, MD, is the Co-Director of the Ocular Oncology Service, Wills Eye Institute, Thomas Jefferson University. She is a Retina Today Editorial Board member. Dr. Shields can be reached at +1 215 928 3105; fax: +1 215 928 1140; or via e-mail at carol.shields@shieldsoncology.com.

The authors have no financial interest in the devices or medications in this document.