The Roche European American Cataract Trial (REACT): a randomized clinical trial to investigate the efficacy of an oral antioxidant micronutrient mixture to slow progression of age-related cataract

Abstract

Context: Funding surgery worldwide for age-related cataract (ARC), a leading cause of blindness, is a huge economic burden. Non-surgical means of slowing ARC progression could benefit patients and reduce this burden.

Objective: To determine if a mixture of oral antioxidant micronutrients [mg/day] (beta-carotene [18], vitamin C [750], and vitamin E [600]) would modify progression of ARC.

Design: REACT was a multi-centered, prospective, double-masked, randomized, placebo-controlled, 3-year trial.

Setting: Consecutive adult American and English outpatients with early ARC were recruited.

Patients: Four-hundred-and-forty-five patients were eligible; 297 were randomized; 231 (78%) were followed for two years; 158 (53%) were followed for three years; 36 (12%) were followed for four years. Twelve patients died during the trial (9 on vitamins; 3 on placebo (p = 0.07)). There were no serious safety issues.

Intervention: After a three-month placebo run-in, patients were randomized by clinical center to the vitamin or placebo groups and followed every four months.

Main outcome measure: Cataract severity was documented with serial digital retroillumination imagery of the lens; progression was quantified by image analysis assessing increased area of opacity. This measure of area, 'increase % pixels opaque' (IPO), was the main outcome measure.

Results: There were no statistically significant differences between the treatment groups at baseline. The characteristics of dropouts and the mean follow-up times by treatment group were the same. After two years of treatment, there was a small positive treatment effect in U.S. patients (p = 0.0001); after three years a positive effect was apparent (p = 0.048) in both the U.S. and the U.K. groups. The positive effect in the U.S. group was even greater after three years: (IPO = 0.389 (vitamin) vs. IPO = 2.517 (placebo); p = 0.0001). There was no statistically significant benefit of treatment in the U.K. group. In spite of nearly perfect randomization into treatment groups, the U.S. and U.K. cohorts differed significantly.

Conclusion: Daily use of the afore-mentioned micronutrients for three years produced a small deceleration in progression of ARC.