Commentary.

Except for the Ischemic Optic Neuropathy Decompression Trial (IONDT), recent attempts at developing prospective controlled treatment trials in acute nonarteritic anterior ischemic optic neuropathy (NAION) have failed because of the extreme difficulty in recruiting NAION patients within a few hours of visual loss.[1] Recent reviews have emphasized that many proposed therapies for NAION have been inadequately studied. In addition, most published studies have used treatment windows much too long to demonstrate any major benefit of any treatment in acute NAION.[12]

As discussed in this controversy, the only potential treatment that may be considered in acute NAION is oral prednisone. The rationale for the use of steroids in NAION is based on a study from the late 1960's, which postulated that treatment of NAION with steroids would reduce capillary permeability, thereby inducing faster resolution of disc edema.[3] This, in turn, presumably reduces compression of capillaries in the optic nerve head and improves blood flow, restoring the function of surviving, but nonfunctioning, ischemic axons. However, there is no evidence that decreasing the duration of disc edema directly improves visual outcome of patients with NAION.[2]

The study published by Hayreh and Zimmerman in 2008[4] on the treatment of a large cohort of NAION patients with oral prednisone has generated a vivid debate regarding the treatment of acute NAION. In the Hayreh and Zimmerman study,[4] 312 patients voluntarily opted for oral prednisone and 301 patients elected not to be treated. The authors suggested that early treatment of NAION with prednisone 80 mg improved visual acuity and visual field more than in the untreated group.[4] However, because the patients were not randomized, the untreated group had more vascular risk factors, including diabetes, suggesting possible bias from unmeasured health factors related to self-selection for treatment, making it difficult to interpret the results of this study. A subsequent small nonrandomized controlled case series comparing 27 control NAION patients with 10 acute NAION patients treated with 80 mg of daily prenisolone for 2 weeks, showed opposite results.[5] No significant change was found in visual acuity, visual fields, and retinal nerve fiber layer thickness measured with optical coherence tomography at 6 months. More importantly, the study was halted early due to the higher rate of complications in the group treated with oral steroids.

Given the paucity of data regarding the exact pathophysiology of NAION and its treatment, the maxim “first, do no harm” describes the first tenet in the management of this devastating optic neuropathy. I believe that we should not systematically recommend oral steroids to patients with acute NAION; oral prednisone should only be considered in selected patients without vascular risk factors, who have persistent disc edema, or unusual progressive worsening of vision over more than 2-3 weeks, or those with bilateral NAION or sequential NAION with poor outcome in the first eye.