Retinal toxicity in a multinational inception cohort of patients with systemic lupus on hydroxychloroquine
Almeida-Brasil CC., Hanly JG., Urowitz M., Clarke AE., Ruiz-Irastorza G., Gordon C., Ramsey-Goldman R., Petri MA., Ginzler EM., Wallace DJ., Bae SC., Romero-Diaz J., Dooley MA., Peschken C., Isenberg D., Rahman A., Manzi S., Jacobsen S., Sam Lim S., Van Vollenhoven R., Nived O., Jönsen A., Kamen DL., Aranow C., Sánchez-Guerrero J., Gladman DD., Fortin PR., Alarcon GS., Merrill JT., Kalunian K., Ramos-Casals M., Steinsson K., Zoma A., Askanase AD., Khamashta M., Bruce IN., Inanc M., Lukusa L., Bernatsky S.
Objective To evaluate hydroxychloroquine (HCQ)-related retinal toxicity in the Systemic Lupus International Collaborating Clinics (SLICC) inception cohort. Methods Data were collected at annual study visits between 1999 and 2019. We followed patients with incident SLE from first visit on HCQ (time zero) up to time of retinal toxicity (outcome), death, loss-to-follow-up or end of study. Potential retinal toxicity was identified from SLICC Damage Index scores; cases were confirmed with chart review. Using cumulative HCQ duration as the time axis, we constructed univariate Cox regression models to assess if covariates (ie, HCQ daily dose/kg, sex, race/ethnicity, age at SLE onset, education, body mass index, renal damage, chloroquine use) were associated with HCQ-related retinal toxicity. Results We studied 1460 patients (89% female, 52% white). Retinal toxicity was confirmed in 11 patients (incidence 1.0 per 1000 person-years, 0.8% overall). Average cumulative time on HCQ in those with retinal toxicity was 7.4 (SD 3.2) years; the first case was detected 4 years after HCQ initiation. Risk of retinal toxicity was numerically higher in older patients at SLE diagnosis (univariate HR 1.05, 95% CI 1.01 to 1.09). Conclusions This is the first assessment of HCQ and retinal disease in incident SLE. We did not see any cases of retinopathy within the first 4 years of HCQ. Cumulative HCQ may be associated with increased risk. Ophthalmology monitoring (and formal assessment of cases of potential toxicity, by a retinal specialist) remains important, especially in patients on HCQ for 10+ years, those needing higher doses and those of older age at SLE diagnosis.