Purpose To determine the diagnostic validity of quantitative measures derived from optical coherence tomography (OCT) images in their ability to discriminate between cohorts of eyes unaffected by hydroxychloroquine (HCQ) and those with a range of toxicity severities, including mild toxicity.

Methods Prospective, single-centre, case–control study conducted between August 2010 and May 2017. Participants were exposed to HCQ for at least 5 years (mean±SD =14±7.2 years) and classified into affected and unaffected cohorts based on the American Academy of Ophthalmology’s 2016 recommendations. For affected eyes, severity (groups 1–4) was assigned based on the extent of ellipsoid zone loss. For all eyes, spectral domain-OCT scans were analysed quantitatively to compute inner retinal thickness (IRT), outer retinal thickness (ORT), and minimum signal intensity (MI) and compared across toxicity groups.

Results Of the 85 participants (mean age 59±12 years, 93% female), 30 had retinal toxicity. Significant differences in ORT and MI were observed between each affected severity group and unaffected eyes. Significant differences in IRT were observed for groups 3–4 but not groups 1–2. ORT and MI were each able to discriminate between unaffected and group 1 eyes with the highest discrimination at the inner subfields (areas under the curve, AUC=0.96 for ORT and AUC=0.93 for MI).

Conclusions Quantitative analysis of OCT scans revealed significant differences between eyes with and without toxicity in two different measures. Each individual metric could discriminate between the unaffected and the lowest severity category, suggesting their potential utility in screening for HCQ toxicity in patients at risk.