Rapid Macular Thinning Is an Early Indicator of Hydroxychloroquine Retinal Toxicity

Purpose: To demonstrate rapid macular thinning as an early and objective sign of hydroxychloroquine retinopathy.

Design: Retrospective case cohort.

Participants: Cohort of 301 patients receiving long-term hydroxychloroquine therapy at Kaiser Permanente Northern California who underwent a minimum of 4 OCT studies that included Early Treatment Diabetic Retinopathy Study (ETDRS) retinal thickness values over a minimum of 4 years.

Methods: Creation of sequential retinal thickness plots to show the rate of change in macular thickness within ETDRS regions.

Main outcome measures: Identification of rapid macular thinning, comparison of patients with rapid thinning to those with stable macular thickness, and comparison of rapid thinning patients with and without conventional OCT or 10-2 visual field signs of hydroxychloroquine toxicity.

Results: Retina thinning in 219 stable patients receiving long-term hydroxychloroquine therapy averaged (mean ± standard deviation) 0.62 ± 0.45 μm/year, whereas 82 patients showed a period of relatively linear rapid thinning with a loss of 3.75 ± 1.34 μm/year. Of the patients with rapid thinning, 38 eventually demonstrated conventional OCT or 10-2 visual field signs of hydroxychloroquine retinal toxicity. The cumulative retinal thinning in these patients was 25.1 ± 6.2 μm compared with 15.7 ± 4.0 μm in those without conventional toxicity (P < 0.01).

Conclusions: Retinal thickness remains stable for many years in most patients receiving long-term hydroxychloroquine therapy, but after a critical point, the retina may begin to thin rapidly. Sequential plots of inner and outer ETDRS ring macular thickness provide objective evidence of this early structural change several years before conventional signs appear. This approach can alert patients and prescribing physicians to potential retinal damage and uses readily available OCT measurements that could be automated by manufacturers for use in comprehensive eye care settings.