The Ischemic Optic Neuropathy Decompression Trial

Abstract

N ONARTERITIC ANTERIOR ISCHEMIC OPTIC neuropathy (NAION) is the most common cause of acute optic nerve disease in the elderly and often results in severe visual loss. The average annual incidence has been estimated at 2.3 to 10.2 per 100 000 persons aged 50 years and older with about 1500 to 6000 new cases seen each year in the United States. Although the visual acuity in patients with NAION remains better than 20/60 in approximately 50% of affected patients, the visual field is invariably abnormal, and more than one-third of patients have vision worse than 20/200 in the affected eye. Second eye involvement occurs in approximately 15% to 20% of patients with NAION within 5 years and often results in a dramatic reduction in patient independence and quality of life. No therapy for acute NAION or prevention of fellow eye involvement has yet proved to be effective. In 1989, it was first suggested that optic nerve decompression surgery (ONDS) might improve vision, particularly in patients with a progressive form of NAION. The surgery involves making 2 or more slits or a window in the optic nerve sheath, allowing cerebrospinal fluid to escape, purportedly reducing the pressure surrounding the optic nerve. Subsequent publications reported a beneficial effect of ONDS, even in the nonprogressive form of NAION, while others were in disagreement about the efficacy. None of these reports were based on a randomized controlled trial, sample sizes were small, uniform visual testing procedures were not used, and progressive disease was not well defined. As surgery was being performed more frequently, it became imperative to test the procedure in a randomized clinical trial before use of the procedure became even more widespread. The Ischemic Optic Neuropathy Decompression Trial (IONDT) was a randomized, single-masked, controlled trial conducted at 25 US clinical centers, sponsored by the National Eye Institute. The objective of the IONDT was to assess the safety and efficacy of ONDS compared with observation alone in patients with NAION. Secondary objectives were to describe the demographic and clinical characteristics and the natural history of a large prospectively followed-up cohort of patients with NAION seen within 2 weeks of onset. Eligibility criteria for randomization to either ONDS or observation included a diagnosis of acute unilateral NAION in a patient aged 50 years or older and a visual acuity of 20/64 or worse and better than no light perception. Patients who were eligible except for having a visual acuity better than 20/64 were followed weekly and subsequently randomized only if their visual acuity fell to 20/64 or worse within 30 days (“late-entry group”). Standardized histories and examinations were obtained at 3, 6, 12, 18, and 24 months and annually thereafter by certified study personnel, and masked personnel performed outcome measures. Surgery was performed by experienced, certified study surgeons according to an explicit study protocol. A surgical quality-assurance committee developed and implemented a quality-assurance program, which included administration of surgical technique questionnaires, masked review of operative notes, and approval of a masked videotape of an ONDS performed by each study surgeon. Recruitment for the IONDT began in October 1992. On the recommendation of its data and safety monitoring committee, recruitment was stopped in October 1994. The preliminary results bearing on the primary outcome measure were reported in 1995 in the Journal of the American Medical Association and were based on data from 244 patients with NAION and visual acuity of 20/64 or worse, representing 125 patients randomized to observation and 119 to surgery. As regards visual improvement at 6 months (defined as an improvement of 3 lines or more), patients assigned to surgery did no better than patients who were observed without intervention; 32.6% of the surgery group improved compared with 42.7% of the observed group. Furthermore, patients who underwent surgery had a significantly greater risk of losing 3 or more lines of vision at 6 months; 23.9% in the surgery group worsened compared with 12.4% in the cohort who did not have surgery. No difference in treatment effect was observed between patients with progressive NAION and all others. The conclusion of this first publication from the IONDT was that ONDS for NAION is not effective, may be harmful, and should be abandoned. This caveat was reinforced by a January 3, 1995, flier from the National Eye Institute. The articles that follow are part of an ongoing series that aims to review collaborative prospective studies supported by the National Eye Institute. The first article, written by investigators, will remind readers of the rationale, goals, methods, findings, and recommendations. The second article, written by an expert who did not participate in the investigations, will offer a constructive critique and attempt to estimate the impact of the study on the practice of ophthalmology.