Individual-Eye Pharmacokinetics of Intravitreal Ranibizumab: Linking Ocular Geometry to Drug Retention Using MRI and Modeling.

Purpose: The purpose of this study was to quantify the influence of ocular geometry on intravitreal (IVT) ranibizumab pharmacokinetics (PKs) in rabbits by integrating magnetic resonance imaging (MRI)-derived geometries, diffusion-based modeling, and PK measurements. Methods: MRI was performed to obtain detailed ocular geometries in 39 New Zealand White (NZW) rabbits. Ranibizumab PKs were assessed in the same animals by serial aqueous humour (AH) sampling following single or three 0.5 mg doses. Individual eye parameters were estimated using profile likelihood analysis. A mean first passage time model was developed to predict ocular half-life as a function of eye size and injection location. Simplified ocular models parameterized by axial length (AL) were constructed to assess whether reduced anatomic representations capture population-level trends. Results: MRI-derived vitreous geometries enabled quantification of inter-eye anatomic variability. The study cohort of adult rabbits exhibited a limited range of AL and vitreous volume compared to human variability. Modeling predicted increased ocular half-life with eye size, a trend reproduced by simplified AL-based models. Experimentally estimated half-lives ranged between 2.8 and 4.9 days and showed weak correlation to AL and vitreous volume. The population mean half-life was 3.67 days, consistent with previous results. Conclusions: This study provides a quantitative framework for analyzing IVT PKs at the level of individual eyes. Modeling predicts that ocular geometry influences drug elimination, and this relationship was also detected experimentally in rabbits, albeit over a limited anatomic range. Greater variability in human eye size may therefore contribute to interindividual PK differences and warrants further investigation, as it may inform personalized dosing strategies.