Ellipsoid Zone Hyporeflectivity as an Early Sign of Non-Reversible Hydroxychloroquine Retinopathy: A Case Series

The purpose of this study was to evaluate the progression of hydroxychloroquine (HCQ) retinopathy following parafoveal loss of the ellipsoid zone (EZ) without retinal pigment epithelium damage (RPE).

This was a single-center retrospective case series of patients with hydroxychloroquine retinopathy who presented between 2012 and 2023 and in whom the drug was stopped prior to damage of the RPE. Patient imaging from the time of HCQ discontinuation to the most recent follow up appointment was reviewed to assess for retinopathy progression, and spectral domain optical coherence tomography (SD-OCT) images were analyzed using ImageJ2 to quantify ellipsoid zone damage.

Five patients met the criteria for inclusion in this study. All patients were female, with a mean age of 69.5 ± 12.2 years. Patients had been taking HCQ for 18.2 years on average (range: 5-32 years). 40% of patients were overdosed according to real weight guidelines and 60% by ideal weight guidelines. All patients demonstrated worsening of retinopathy following drug discontinuation. The length of parafoveal zones of EZ hyporeflectivity on SD-OCT increased by an average of 26.8 ± 8.6% in right eyes and 22.5 ± 15.0% in left eyes over an average follow-up period of 31.4 months (range 8-71 months).

Progression of HCQ retinopathy can occur even when HCQ is discontinued before RPE damage. Ophthalmologists should be aware of the risks associated with HCQ use following damage to the EZ. The acknowledged threshold at which irreversible progression of retinopathy is predicted despite cessation of the drug may need to be reconsidered and shifted earlier than RPE loss.