Objective: To evaluate practice patterns and long-term complications of proliferative diabetic retinopathy (PDR) treatment outside DRCR's Protocol S.

Methods: A retrospective cohort study using Vestrum Health Retina Database included 26,632 treatment-naive eyes receiving anti-VEGF injections for PDR between 2016-2021. Primary outcomes were concordance with Protocol S, defined as four anti-VEGF injections within 14 weeks of baseline, and 6-month gaps in care, assessed via multivariable logistic regressions.

Results: Among eyes with DME, those concordant with Protocol S had mean VA gain of +3.0 letters compared to -0.6 letters among those not concordant with Protocol S at two years. Over 40% of patients became loss to follow up within one year. Those experiencing 6-month gaps in care within the first year had higher rates of vitrectomy, retinal detachment, and neovascular glaucoma at two years. Patients with DME were more likely to be concordant while those with ETDRS letter score >70 were less likely to be concordant with Protocol S regimen relative to those without DME and ETDRS letter score between 24-40, respectively.

Conclusions: The frequent follow-up appointments and repeat treatments necessary for anti-VEGF monotherapy in PDR can pose challenges to maintaining the required schedule and can result in worse visual acuity outcomes and increased ocular complications.