Objective: To investigate the association between tetracycline use and the development of short-term vision threatening complications (VTC) among patients with diabetic retinopathy (DR).

Methods: Using a deidentified database, 4 596 patients with severe nonproliferative diabetic retinopathy (NPDR) or proliferative diabetic retinopathy (PDR) associated with tetracycline use versus 87,974 patients with NPDR or PDR but no tetracycline use, respectively, were included before propensity score matching (PSM). After PSM, 4 576 patients in each cohort were analyzed. Incidence of developing VTC, including diabetic macular edema (DME), vitreous hemorrhage (VH), tractional retinal detachment (TRD), neovascular glaucoma (NVG), and subsequent need for ocular interventions including intravitreal anti-vascular endothelial growth factor (VEGF) injections, panretinal photocoagulation (PRP), or pars plana vitrectomy (PPV).

Results: Patients with DR and repeated tetracycline use had a reduced risk of developing DME (RR: 0.45, 95% CI: 0.28-0.72; p = 0.009) and VH (RR: 0.37, 95% CI: 0.20-0.69; p = 0.001) compared to the tetracycline-naive cohort at 6 months and 1 year. Further, there was a reduced risk of subsequent need for anti-VEGF (RR: 0.25, 95% CI: 0.13-0.47; p = 0.003) and PRP (RR: 0.40, 95% CI: 0.19-0.84; p = 0.012) in the tetracycline cohort compared to the tetracycline-naive group at 6 months and 1 year. There were no significant differences in the development of NVG, TRD, or the requirement for PPV between both cohorts.

Conclusions: Repeated tetracycline use was associated with a potentially reduced short-term risk of developing DME, VH, and needing subsequent anti-VEGF or PRP therapy versus tetracycline naive patients.