Association of Fenofibrate Add-on Therapy with Postoperative Diabetic Retinal Outcomes After Cataract Surgery in Patients with Type 2 Diabetes Mellitus

Purpose: To examine whether preoperative fenofibrate-plus-statin exposure was associated with postoperative diabetic macular edema (DME)-related and proliferative diabetic retinopathy (PDR)-related composites compared with statin exposure alone. Methods: This retrospective cohort study used the TriNetX Global Collaborative Network. Adults with type 2 diabetes undergoing cataract surgery who received fenofibrate plus statin therapy were matched 1:1 with those receiving statin therapy alone. The co-primary outcomes were a DME-related composite, defined by a DME diagnosis or intravitreal injection, and a PDR-related composite comprising PDR, panretinal photocoagulation, or vitreous hemorrhage. Cox models estimated hazard ratios (HRs) over cumulative 1- to 5-year horizons. Sensitivity analyses evaluated 6-month outcomes, recent preoperative fenofibrate exposure, a laboratory-complete cohort, and Nd:YAG capsulotomy. Results: Matching yielded 2,521 pairs. After outcome-specific exclusions, the DME-related composite analysis included 2,292 exposed and 2,327 comparator patients. Fenofibrate-plus-statin exposure was associated with a lower hazard of the DME-related composite at every horizon, including 1 year (HR, 0.486 [95% confidence interval [CI], 0.324-0.728], P < 0.001) and 5 years (HR, 0.678 [95% CI, 0.515-0.892], P = 0.005). For the PDR-related composite, the 95% CI excluded 1.0 only at 2 years (HR, 0.605 [95% CI, 0.397-0.922], P = 0.018). Sensitivity analyses using a recent-exposure definition and a laboratory-complete cohort generally supported the DME-related composite finding, whereas Nd:YAG capsulotomy hazards were similar between groups. Conclusion: Preoperative fenofibrate-plus-statin exposure was associated with a lower hazard of the postoperative DME-related composite, while findings for the PDR-related composite were inconclusive. Prospective validation is needed