Hydroxychloroquine Toxicity Screening Using Semi-Automated Ellipsoid Zone Mapping Program

Abstract

Purpose : Loss of ellipsoid zone (EZ) integrity is an important imaging feature of hydroxychloroquine (HCQ) toxicity. Early identification of toxicity is critical to enable drug cessation and limit progressive retinal damage. Alterations to the outer retinal structures can be subtle and difficult to identify. The purpose of this study was to evaluate a semi-automated EZ mapping program to identify quantitative alterations and thresholds for potential early toxicity due to HCQ.

Methods : A retrospective, IRB-approved, case series of patients currently taking HCQ without clinical evidence of macular pathology was performed. Eyes with concurrent macular disease were excluded. Spectral domain Optical Coherence Tomography (OCT) was performed on all eyes. The macular cube scan was exported and analyzed in our proprietary EZ mapping platform. Based on previous studies evaluating HCQ toxicity, 7 outer retinal parameters were utilized to assess for potential underlying toxicity: mean parafoveal (central 2-mm) ONL-EZ thickness/volume, parafoveal EZ-RPE thickness/volume, en face percentage of EZ total attenuation (EZ thickness = 0μm), and en face EZ attenuation (EZ thickness < 20 μm). The results were compared to a previously-described, normative, age matched, control data set to establish thresholds for toxicity.

Results : Outer retinal quantitative metrics was performed on 401 eyes of 401 subjects. The mean age was 58 years, dose of HCQ was 367 mg per day, and duration of HCQ use was 5.6 years. Subnormal quantitative outer retinal parameters were found in 135-199 eyes (26.9-49.6%). In addition, 4-48 eyes (1.0-12%) had outer retinal metrics measurements consistent with moderate HCQ toxicity. Outer retinal parameters reflective of severe retinal toxicity were identified in 2-8 eyes (0.5-2.0%). En face attenuation and total attenuation metrics appeared to be most sensitive and mean parafoveal thickness/volume measurements were the most specific for HCQ toxicity.

Conclusions : Outer retinal mapping with a semi-automated EZ mapping technology may facilitate identification of eyes at risk for HCQ toxicity. Additional research is needed to further validate this program as a potential screening tool and to identify the optimal metrics for screening purposes.

This abstract was presented at the 2019 ARVO Annual Meeting, held in Vancouver, Canada, April 28 - May 2, 2019.