Individual-Eye Pharmacokinetics of Intravitreal Ranibizumab: Linking Ocular Geometry to Drug Retention Using MRI and Modeling.
7 affiliations
- 1Wolfson Centre for Mathematical Biology, Mathematical Institute, Andrew Wiles Building, University of Oxford, Oxford, United Kingdom.
- 2Department of Mathematics and Statistics and Sainte-Justine University Hospital Azrieli Research Centre, Université de Montréal, Montréal, Quebec, Canada.
- 3Pharmaceutical Sciences, Roche Innovation Center Basel, Roche Pharma Research and Early Development, Basel, Switzerland.
- 4Neuroscience and Rare Diseases, Roche Innovation Center Basel, Roche Pharma Research and Early Development, Basel, Switzerland.
- 5School of Mathematical Sciences, Queensland University of Technology, Brisbane, Australia.
- 6Pharmaceutical Sciences, Roche Innovation Center Munich, Roche Pharma Research and Early Development, Penzberg, Germany.
- 7Ophthalmology Section, Vetsuisse Faculty, University of Zurich, Zurich, Switzerland.
Abstract
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.
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BibTeX
@article{lamirande2026individualeye,
title = {{Individual-Eye Pharmacokinetics of Intravitreal Ranibizumab: Linking Ocular Geometry to Drug Retention Using MRI and Modeling.}},
author = {Patricia Lamirande and Eamonn A Gaffney and Michael Gertz and Basil Künnecke and Thomas Bielser and Andreas Bruns and Jessica R Crawshaw and Uwe Wessels and Antonella Rampazzo and Philip K Maini and Antonello Caruso},
journal = {Investigative ophthalmology \& visual science},
year = {2026},
month = oct,
doi = {10.1167/iovs.67.12.31},
url = {https://europepmc.org/article/MED/42885992},
note = {CC BY},
}
RIS
TY - JOUR
TI - Individual-Eye Pharmacokinetics of Intravitreal Ranibizumab: Linking Ocular Geometry to Drug Retention Using MRI and Modeling.
AU - Patricia Lamirande
AU - Eamonn A Gaffney
AU - Michael Gertz
AU - Basil Künnecke
AU - Thomas Bielser
AU - Andreas Bruns
AU - Jessica R Crawshaw
AU - Uwe Wessels
AU - Antonella Rampazzo
AU - Philip K Maini
AU - Antonello Caruso
PY - 2026
DA - 2026/10/01
JO - Investigative ophthalmology & visual science
DO - 10.1167/iovs.67.12.31
UR - https://europepmc.org/article/MED/42885992
AB - 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.
SN - 0146-0404
SN - 1552-5783
ER -