Neovascular Age-Related Macular Degeneration: A Visual Acuity Model of Natural Disease Progression and Ranibizumab Treatment Effect.

Intravitreal ranibizumab is a first-line therapy for neovascular age-related macular degeneration (nAMD), but there is a need to optimize patient outcomes while minimizing treatment burden. Here, we developed an indirect response, nonlinear, mixed effects model of disease progression and drug effect in anti-vascular endothelial growth factor (VEGF) treatment-naïve patients. A total of 1,524 treatment-naïve patients and 29,754 visual acuity observations from the ANCHOR, MARINA, PIER, and EXCITE clinical trials informed the model. The model accurately described natural nAMD disease progression and predicted mean visual acuity gains in the HARBOR study, notably with a 2.0 mg ranibizumab dose not used for model development. Furthermore, individualized treatment regimens were shown by simulation to be a viable alternative to the commonly used pro re nata or fixed monthly dosing regimen approaches. Therefore, this model could be a useful tool to predict the outcomes of different, more patient-tailored treatment regimens in nAMD.