Following our earlier observation of clinically evident optic tract neuropathy in patients receiving low-dose interferon (IFN) therapy, we prospectively evaluated 53 consecutive patients treated for chronic hepatitis B or C with a median dose of 3 MU of IFN-a 2b thrice weekly. Measurements included routine ophthalmologic evaluation and recordings of visual evoked responses (VER), electroretinograms (ERG), visual acuity, and visual fields, before, at the end of IFN treatment, and at follow-up visits. Baseline P100 latencies of VERs (base-VER) were abnormally prolonged in 24 patients (32 of 106 eyes, 30.2%); age was the only significant covariate associated with increased risk for an abnormal base-VER by multiple logistic regression (relative risk [RR] 5.3 per each 5-year increase in age). In 45 patients (74 eyes) with normal baseline P100 latencies, the end-of-treatment VERs (end-VER) were significantly prolonged compared with baseline, becoming abnormal in 11 (15 of 74 eyes, 20.3%) (138.8 Ψ 8.7 vs. 117.7 Ψ 5.2 ms, P F .001). This subgroup had older age (59.1 Ψ 11.0 vs. 47.5 Ψ 15.3, P β«Ψβ¬ .007) and reduced visual sensitivity compared with their own pretreatment measurements (24.5 Ψ 1.6 vs. 23.0 Ψ 1.2db, P β«Ψβ¬ .019). Changes of end-VERs by age had a sigmoid distribution with a steep increase of values beyond the 5 th decade (R 2 β«Ψβ¬ .326, P F .001). In a logistic regression model, significant predictors of abnormal end-VERs were, patients' age (RR 5.6 per each 5-year increase), presence of hepatitis B virus (HBV) infection (RR 15.1 compared with hepatitis C virus [HCV] infection) and serum cholesterol levels above 240 mg% (RR 7.1 compared with values F240 mg%). Subconjunctival hemorrhages were seen in 2 cases and funduscopic examination revealed cotton wool spots in one other. ERG recordings and the P100 amplitude remained unchanged. After stopping IFN, the treatment-associated neurovisual abnormalities re-versed to normal in 7 patients (10 of 15 eyes) and persisted in 5 (5 of 15 eyes, 33.3%) for up to 37 (median 7.3) months observation, all patients remaining clinically asymptomatic. In conclusion, subclinical neurovisual impairment is a frequent, largely unrecognized complication of low-dose IFN therapy, and patients with chronic hepatitis B and older age appear to be most susceptible. This apparently innocuous complication is long lasting, possibly irreversible in some patients, with yet undetermined consequences on visual function. (HEPATOLOGY 1998;27:1421-1427.)
Ocular side effects are infrequently reported during β£interferon (IFN) therapy, including among else, cases of transient blurred vision, 1 increased intraocular pressure, 2 neovascular glaucoma, 3 anterior ischemic optic neuropathy, 4 retinal detachment, 5 papilloedema, 6 and eyeball rupture. 2,7 A better documented and apparently more frequent complication, especially in Japan, is IFN retinopathy, characterized by cotton wool spots, retinal hemorrhages, and microaneurysms occurring in an appreciable proportion of patients receiving high-dose IFN. [8][9][10][11][12] Following the recent description of symptomatic optic tract neuropathy in 3 of our patients treated with low-dose IFN for chronic viral hepatitis, 13 we subjected all patients with viral hepatitis entering IFN treatment to ophthalmologic evaluation, including visual neurophysiologic measurements before, at the end of treatment, and at follow-up visits. We herein report our findings.