Cushing's syndrome related to higher rates and earlier onset of cataract: A nationwide retrospective cohort study.

Purpose: To investigate the risk of cataract in patients with Cushing's syndrome (CS) and evaluate whether disease onset occurs at an earlier age compared to general population.

Methods: A nationwide retrospective matched-cohort study including individuals diagnosed with endogenous CS from 2000 to 2023. Patients with CS were matched in a 1:5 ratio with a control group individually matched for age, sex, socioeconomic status, and body mass index. The primary outcome was the incidence of cataract and cataract surgery. The Cox proportional hazards model, accounting for death without cataract as a competing risk, was employed to estimate hazard ratio.

Results: The study cohort included 609 patients with CS, 65% women and 35% men, and 3018 controls. The average age at CS diagnosis was 48.1 ± 17 years. Follow-up duration was 14.6 years (IQR 9.8-20.2). The source of hypercortisolism was Cushing's disease (CD) in 259 (42.6%) and adrenal CS (aCS) in 206 patients (33.8%). After CS diagnosis, cataract was observed in 171 patients (28.1%), and 771 controls (25.5%). Patients with CS had a 34% higher risk of developing cataract compared to their matched controls (HR = 1.34, 95% CI 1.03-1.75, p = 0.03). Cataract developed earlier in patients with CS compared to controls, with a mean age of onset at 64.7 ± 9.7 versus 67.6 ± 8.4 years, respectively (p = 0.01). A total of 49 (8.05%) patients had undergone cataract surgery after a diagnosis of CS compared to 177 (5.86%) in the control group (p = 0.07).

Conclusion: Patients with endogenous CS have an increased likelihood of developing cataracts and they experienced onset at a younger age. Guidelines should include annual cataract monitoring for CS patients, beginning 3-5 years earlier than the current general recommendations.