Progression of Nonarteritic Anterior Ischemic Optic Neuropathy (NAION) Occurs Early and Is Unassociated With Modifiable Risk Factors

Abstract

OBJECTIVE: To report the true frequency and risk factors for acute nonarteritic anterior ischemic optic neuropathy (NAION) progression and identify modifiable features to reduce vision worsening. DESIGN: Secondary case-control analysis of the QRK207 multicenter, double-masked, sham-controlled, randomized clinical trial. SUBJECTS: We analyzed 599 study eyes with acute NAION (of 729 individuals prospectively enrolled in the QRK207 trial) with separate screening and Day 1 (mean 2.5-day interval) evaluations for progression. No participants included in this analysis received treatment. The Month 2 analysis included only the 167 sham-injected study eyes. METHODS: Visual outcomes were assessed using best-corrected visual acuity (BCVA) using early treatment diabetic retinopathy study (ETDRS) charts and standardized automated perimetry. MAIN OUTCOME MEASURES: We defined progression as ≥10 ETDRS letter loss (also analyzed ≥15 ETDRS letter loss) or worsening of censored corrected average total deviation (avgTD) using quantile regression to define progression and recovery thresholds. We evaluated systemic and ophthalmic features associated with progression. RESULTS: From screening to Day 1, 7.3% (43/583) of eyes had ≥ 10 ETDRS letter loss, and 4.1% eyes had ≥ 15 ETDRS letter loss. Diabetes mellitus, hypertension, hyperlipidemia (HLD), and cardiovascular risk factors did not increase the risk of progression. Previous fellow-eye (FE) NAION and obstructive sleep apnea (OSA) were significantly associated with ≥10 ETDRS letter loss. Only FE NAION remained a risk factor ≥15 ETDRS letter loss. Of the 167 sham-injected eyes with screening to Month 2 evaluation, 21.6% (36/167) had ≥10 ETDRS letter loss, and 14.4% (24/167) had ≥15 ETDRS letter loss. About 91.6% of eyes (33/36) progressed within 22 days of symptom onset (by Day 8). Of the 139 sham-injected eyes with Day 1 to Month 2 evaluation, 18.7% had ≥10 ETDRS letter loss, and 13.7% had ≥15 ETDRS letter loss. TD progression from screening to Day 1 occurred in 32.1% (192/599) eyes, 66.1% remained stable, and 1.8% improved. FE NAION and HLD were associated with TD progression. CONCLUSIONS: Worsening of vision in NAION occurs acutely. The results do not support cardiovascular risk factors as important hazard features for NAION progression. The only consistent factor associated with progression for both BCVA and VF loss was previous FE NAION.