Loss of external limiting membrane integrity predicts progression of hydroxychloroquine retinal toxicity after drug discontinuation

Purpose: To quantify external limiting membrane (ELM) disruption and photoreceptor volume over time, using spectral domain optical coherence tomography in eyes with hydroxychloroquine (HCQ) toxic effects after discontinuation. Methods: We performed a retrospective chart review of patients who were screened for toxic effects of HCQ between January 1, 2009 and August 31, 2014, and identified 10 patients diagnosed as having HCQ retinal toxic effects. Intact ELM and the Bruch membrane were manually traced using ImageJ software and their lengths from each scan of the spectral domain optical coherence tomography macular volume were summed. The ratio of intact ELM length/Bruch membrane length was calculated. We measured the two-dimensional photoreceptor area between the intact ELM and Bruch membrane in every cross-sectional B-scan. We calculated the total volume of photoreceptors in a volumetric OCT by multiplying photoreceptor area by the distance between B-scans. Results: Of the 10 patients (120 eyes), 1 eye was excluded because of the presence of vitreomacular traction. The mean cumulative dose of HCQ was 1,951 g (range, 584-3,650 g). The mean follow-up duration was 34.1 months (range, 11-64 months). Based on the extent of ELM integrity at diagnosis of HCQ toxicity, we classified eyes into 2 groups: 1) 12 eyes showed severe ELM disruption and 2) 7 eyes had intact ELM. All 19 eyes showed characteristic signs of HCQ toxicity on the visual field examination at the baseline. Seven of 12 eyes with ELM disruption showed progressive ELM changes, including 7 eyes that additionally developed progressive photoreceptor volume decline, whereas 5 eyes remained stable. All 7 eyes with intact ELM remained stable over time. Conclusion: Intact ELM status at the time of HCQ discontinuation is a good prognostic sign, and ELM status may allow clinicians to predict patients at risk for progression of retinopathy. Quantitative measurements of ELM disruption and photoreceptors volume may provide an objective tool to monitor outer retinal changes due to HCQ.