Causes of Severe Visual Loss in the Early Treatment Diabetic Retinopathy Study: ETDRS Report No. 24 DONALD S. FONG, MD, MPH, FREDERICK L. FERRIS III, MD, MATTHEW D. DAVIS, MD, AND EMILY Y. CHEW, MD, FOR THE EARLY TREATMENT DIABETIC RETINOPATHY STUDY RESEARCH GROUP ● PURPOSE: To describe the causes of and risk factors for persistent severe visual loss occurring in the Early Treat- ment Diabetic Retinopathy Study (ETDRS). ● METHODS: The ETDRS was a randomized clinical trial investigating photocoagulation and aspirin in 3,711 per- sons with mild to severe nonproliferative or early prolif- erative diabetic retinopathy. Severe visual loss, defined as best-corrected visual acuity of less than 5/200 on at least two consecutive 4-month follow-up visits, developed in 257 eyes (219 persons). Of these 257 eyes, 149 (127 persons) did not recover to 5/200 or better at any visit (persistent severe visual loss). Ocular characteristics of these eyes were compared with those of eyes with severe visual loss that improved to 5/200 or better at any subsequent visit. Characteristics of patients with severe visual loss that did and did not improve and those without severe visual loss were also compared. ● RESULTS: Severe visual loss that persisted developed in 149 eyes of 127 persons. In order of decreasing frequency, reasons recorded for persistent visual loss included vitreous or preretinal hemorrhage, macular edema or macular pig- mentary changes related to macular edema, macular or retinal detachment, and neovascular glaucoma. Compared with all patients without persistent severe visual loss, patients with persistent severe visual loss had higher mean levels of hemoglobin A 1c (10.4% vs 9.7%; P  .001) and higher levels of cholesterol (244.1 vs 228.5 mg/dl; P  .0081) at baseline. Otherwise, patients with persistent severe visual loss were similar to patients with severe visual loss that improved and to those without severe visual loss. ● CONCLUSIONS: Persistent severe visual loss was an infrequent occurrence in the ETDRS. Its leading cause was vitreous or preretinal hemorrhage, followed by mac- ular edema or macular pigmentary changes related to macular edema and retinal detachment. The low fre- quency of persistent severe visual loss in the ETDRS is most likely related to the nearly universal intervention with scatter photocoagulation (either before or soon after high-risk proliferative diabetic retinopathy developed) and the intervention with vitreous surgery when clini- cally indicated. (Am J Ophthalmol 1999;127: 137–141. © 1999 by Elsevier Science Inc. All rights reserved.) D IABETES IS A LEADING CAUSE OF BLINDNESS IN THE United States. 1 Clinical trials have demonstrated that photocoagulation and vitrectomy surgery are effective in reducing the risk of blindness. 2 However, despite the use of these treatments, 219 of 3,711 persons enrolled in the Early Treatment Diabetic Retinopathy Study (ETDRS), a multicenter clinical trial, experienced a decrease in visual acuity to less than 5/200 at two consec- utive follow-up visits (severe visual loss). In some eyes, severe visual loss persisted at all subsequent follow-up visits. We assessed the cause of and risk factors for persistent severe visual loss in these eyes. PATIENTS AND METHODS FROM APRIL 1980 TO JULY 1985, THE ETDRS ENROLLED 3,711 patients with diabetes whose eyes met the following criteria: (1) no macular edema, visual acuity of 20/40 or better, and moderate or severe nonproliferative diabetic retinopathy or early proliferative diabetic retinopathy, or (2) macular edema, visual acuity of 20/200 or better, and mild, moderate, or severe nonproliferative or early proliferative diabetic retinop- athy. Patients with favorable prognosis for survival and follow-up for at least 5 years were enrolled in the ETDRS and Accepted for publication Aug 7, 1998. From the Clinical Trials Branch, Division of Biometry and Epidemi- ology, National Eye Institute, National Institutes of Health, Bethesda, Maryland (Drs Fong, Ferris, and Chew); Department of Ophthalmology, UCLA School of Medicine, Los Angeles, California (Dr Fong); and Fundus Photograph Reading Center, University of Wisconsin, Madison, Wisconsin (Dr Davis). Reprint requests to Donald S. Fong, MD, MPH, Department of Ophthalmology, Kaiser Pemanente Medical Center, 1011 Baldwin Park Ave, Baldwin Park, CA 91706; e-mail: donald.s.fong@kp.org © 1999 BY ELSEVIER SCIENCE INC.ALL RIGHTS RESERVED. 0002-9394/99/$20.00 137 PII S0002-9394(98)00309-2