The HIT Study-The Hydroxychloroquine Effect in the Treatment of Patients with Age-Related Macular Degeneration: A Randomized Controlled Trial.

Background and Objectives: Decreased age-related macular degeneration (AMD) has been reported in individuals with rheumatoid arthritis treated with hydroxychloroquine (HCQ, plaquenil). Materials and Methods: In a randomized controlled trial with a parallel study design, we assessed visual acuity, central macular thickness measured with macular optical coherence tomography (OCT), and the number and size of drusen, following treatment with HCQ or a placebo in individuals with AMD. The patients received a daily dosage of 400 mg hydroxychloroquine (study group) or placebo (control group) during 12 months, and underwent complete ophthalmic examinations at 3, 6, 9, 12 and 24 months after initiation of treatment. Results: Of the 110 patients who were randomized to the treatment groups, 46 (29 females) in the study group and 50 (29 females) in the control group completed the study. The study group showed less visual acuity deterioration at two-year follow-up than did the control group (-0.03 ± 0.07 vs. -0.07 ± 0.07, p = 0.027). At two years after treatment initiation, the mean number of drusen per eye was lower for ARDS2 (8.1 vs. 12.3, p = 0.045) in the study group, compared to the control group. Compared to the control group, the proportion of eyes with increased drusen growth was smaller for both ARDS2 and ARDS3 drusen in the study group, and the proportion of the total drusen with growth was smaller for the study group as well: 32/46 eyes (70%) vs. 40/50 eyes (80%). Drusen volume growth, as calculated by the area and height measured with macular OCT, was also more reduced in the study than the control group (0.20 ± 0.15 vs. 0.23 ± 0.16 mm4 , p = 0.05). None of the participants showed HCQ toxicity or adverse effects. Conclusion: Among patients with AMD, visual deterioration, the growth and the amount of drusen formation at two years after treatment initiation was less among those treated with HCQ than with a placebo. In this study, there was a negative association between HCQ treatment and wet AMD development.