NEI Clinical Studies
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Ischemic Optic Neuropathy Decompression Trial (IONDT)
Also see Ischemic Optic Neuropathy Decompression Trial Followup.
To assess the safety and efficacy of optic nerve sheath decompression surgery for non-arteritic ischemic optic neuropathy (NAION).
Non-arteritic ischemic optic neuropathy (NAION), the most common cause of acute optic nerve disease in older persons, causes permanent and severe visual loss. Visual function can be impaired through decreased central visual acuity or peripheral field loss, or both. NAION strikes both eyes in up to 40 percent of affected patients. The incidence of NAION has been estimated at 2.3 per 100,000 persons over the age of 50 years and 0.54 per 100,000 for all ages. Estimates of the number of new cases seen each year in the United States range from a low of approximately 1,500 to a high of 6,000.
NAION has been hypothesized to be caused by vascular insufficiency leading to optic nerve head ischemia. There is general agreement that NAION results from transient non-perfusion of nutrient vessels. The wide range of visual field defects and visual loss with NAION can be explained by the extent and number of the blood vessels involved.
Anatomical factors appear to contribute to the vascular event initiating NAION. Clinically, the number of discs congenitally lacking a physiological cup in eyes with NAION is higher than expected. Presumably, in eyes with NAION, these discs have small scleral openings that crowd the nerve fibers as they pass through the restricted space in the optic disc and lamina cribrosa, thereby predisposing to an ischemic spiral.
One current theory holds that NAION begins as a minor ischemic event that later progresses to a major infarction due to congenitally anomalous optic nerves. The inciting ischemic event leads to local anterior nerve edema, and this causes further ischemia.
Optic nerve sheath decompression surgery was reported in 1989 to be of benefit to patients with NAION. The presumed mechanism of action in optic nerve decompression surgery revolved around restoration of impaired blood flow to the optic nerve through reduction of the pressure around the nerve.
The Ischemic Optic Neuropathy Decompression Trial (IONDT) was a randomized clinical trial designed to compare the improvements in visual acuity at 6 months in patients assigned to receive surgery with optic nerve sheath decompression with those assigned to careful followup. A cohort of patients, with a baseline visual acuity of better than 20/64 are also being followed to better understand the natural history of the disease, including second eye involvement.
Enrollment began in October 1992. Randomization was stratified by clinic, and patients had an equal probability of assignment to surgery or careful followup. All patients are being followed for a minimum of 2 years.
The primary outcome is a change of three lines or more in visual acuity at the 6-month followup visit compared with visual acuity measured at the randomization visit. Secondary outcomes include a change in visual acuity beyond 6 months, change in peripheral visual function as measured by automated Humphrey perimetry, local and systemic side effects from treatment, change in quality of life, and other associated morbidity and mortality.
Men and women age 50 years or older, with acute NAION and visual symptoms for 14 days or less since the onset of symptoms, and visual acuity worse than or equal to 20/64 were eligible for randomization.
Patient Recruitment Status
Recruitment began in October 1992 and ceased in October 1994, when it was determined that the surgery was ineffective and possibly harmful. A total of 258 patients were randomized to surgery or careful followup, while 162 patients are being followed in the natural history study.
Current Status of Study
The results of the Ischemic Optic Neuropathy Decompression Trial indicate that optic nerve sheath decompression surgery for NAION is not effective, may be harmful, and should be abandoned. A clinical alert to this effect was issued on January 3, 1995, by the National Eye Institute and the Ischemic Optic Neuropathy Decompression Trial to all ophthalmologists, neuro-ophthalmologists, and neurologists.
Patients assigned to surgery did no better when compared with patients assigned to careful followup: 32.6 percent of the surgery group improved by three or more lines of visual acuity at 6 months, compared with 42.7 percent of the careful followup. The odds ratio (OR) for three or more lines better, adjusted for baseline visual acuity and diabetes, was 0.74 (95 percent confidence interval [CI], 0.39 to 1.38). Patients receiving surgery had a significantly greater risk of losing three or more lines of vision at 6 months: 23.9 percent in the surgery group worsened compared with 12.4 percent in the careful followup group. The 6-month adjusted OR for three or more lines worse was 1.96 (95 percent CI, 0.87 to 4.41). No difference in treatment effect was observed between patients with progressive NAION and all others.
These results from the IONDT indicate that optic nerve decompression surgery for NAION is not effective, may be harmful, and should be abandoned. The spontaneous improvement rate was found to be better than previously reported.
All randomized and natural history patients are being followed for the purpose of learning more about the natural history of NAION and the incidence of NAION in the second eye.
Ischemic Optic Neuropathy decompression Trial Research Group: The Ischemic Optic Neuropathy Decompression Trial (IONDT): design and methods. Controlled Clinical Trials 3: 276-296, 1998.
Ischemic Optic Neuropathy Decompression Trial Study Group: Characteristics of patients with nonarteritic anterior ischemic optic neuropathy eligible for the Ischemic Optic Neuropathy Decompression Trial. Arch Ophthalmol 114: 1366-1374, 1996.
Optic Neuropathy Decompression Trial: Sex, race, and age. Submitted to Ophthalmic Epidemiology) 114: 1366-1374, 1996.
Ischemic Optic Neuropathy Decompression Trial Research Group: Optic nerve decompression surgery for nonarteritic anterior ischemic optic neuropathy (NAION) is not effective and may be harmful. JAMA 273: 625-632, 1995.
Kaufman D, Ischemic Optic Neuropathy Decompression Trial Study Group: Optic nerve decompression surgery for nonarteritic ischemic optic neuropathy (NAION is not effective and could be harmful: Results of the Ischemic Optic Neuropathy Decompression Trial (IONDT). [Abstract]. Invest Ophthalmol Vis Sci 36: S196, 1995.
Kelman SE: The Ischemic Optic Neuropathy Decompression Trial, in reply (letter). [Editorial]. JAMA 274: 612, 1995.
Crawley B, Scherer RW: Ischemic Optic Neuropathy Decompression Trial (IONDT): Participation in the IONDT. Race, gender and age. [Abstract]. Controlled Clinical Trials 15: 102S, 1994.
Crawley B, Waring MT, Scherer RW: Coordinating Center for the Ischemic Optic Neuropathy Decompression Trial (IONDT): IONDT tracking system: Where is form 2034 for patient ICMORE and who is responsible? [Abstract]. Controlled Clinical Trials 15: 93S, 1994.
Kelman SE: The Ischemic Optic Neuropathy Decompression Trial, in reply. [Editorial]. Arch Ophthalmol 112: 1275-76, 1994.
Scherer RW, Crawley B, Abstracts for the Ischemic Optic Neuropathy Study Group: Responses to ethical and other questions on a knowledge assessment form for a multicenter trial. [Abstract]. Controlled Clinical Trials 14: 442S, 1993.
Kelman SE: The Ischemic Optic Neuropathy Decompression Trial. [Editorial]. Arch Ophthalmol 111: 1616-1818, 1993.
Kelman SE: The Ischemic Optic Neuropathy Decompression Trial. [Editorial]. Arch Ophthalmol 111: 1616-18, 1993.
Kelman SE: The Ischemic Optic Neuropathy Decompression Trial, in reply (letter). [Editorial]. Ophthalmol/World News (in press).
Shalom E. Kelman, M.D.
University of Maryland
419 West Redwood Street, Suite 460
Baltimore, MD 21201
Telephone: (410) 328-3858
Kay Dickersin, Ph.D.
University of Maryland
Department of Epidemiology and Preventive Medicine
Century Building, First Floor
506 West Fayette Street
Baltimore, MD 21201
Telephone: (410) 328-8159
Donald F. Everett, M.A.
National Eye Institute
National Institutes of Health
Executive Plaza South, Suite 350
6120 Executive Boulevard, MSC 7164
Bethesda, MD 20892-7164
Telephone: (301) 496-5983
Fax: (301) 402-0528
Last Updated: 10/21/99