Simulation of long-term impact of intravitreal anti-VEGF therapy on patients with severe non-proliferative diabetic retinopathy

OBJECTIVE: A simulation model was constructed to assess long-term outcomes of proactively treating severe non-proliferative diabetic retinopathy (NPDR) with anti-vascular endothelial growth factor (anti-VEGF) therapy versus delaying treatment until PDR develops. METHODS AND ANALYSIS: Simulated patients were generated using a retrospective real-world cohort of treatment-naive patients identified in an electronic medical records database (IBM Explorys) between 2011 and 2017. Impact of anti-VEGF treatment was derived from clinical trial data for intravitreal aflibercept (PANORAMA) and ranibizumab (RISE/RIDE), averaged by weighted US market share. Real-world risk of PDR progression was modelled using Cox multivariable regression. The Monte Carlo simulation model examined rates of progression to PDR and sustained blindness (visual acuity <20/200) for 2 million patients scaled to US NPDR disease prevalence. Simulated progression rates from severe NPDR to PDR over 5 years and blindness rates over 10 years were compared for delayed versus early-treatment patients. RESULTS: Real-world data from 77 454 patients with mild-to-severe NPDR simulated 2 million NPDR patients, of which 86 680 had severe NPDR. Early treatment of severe NPDR with anti-VEGF therapy led to a 51.7% relative risk reduction in PDR events over 5 years (15 704 early vs 32 488 delayed), with a 19.4% absolute risk reduction (18.1% vs 37.5%). Sustained blindness rates at 10 years were 4.4% for delayed and 1.9% for early treatment of severe NPDR. CONCLUSION: The model suggests treating severe NPDR early with anti-VEGF therapy, rather than delaying treatment until PDR develops, could significantly reduce PDR incidence over 5 years and sustained blindness over 10 years.