Simulating intravitreal injections in anatomically accurate models for rabbit, monkey, and human eyes

Area of Science:

• Ophthalmology
• Pharmacokinetics
• Biomedical Engineering

Background:

• Predicting drug clearance after intravitreal injections is crucial for ocular drug development.
• Species-specific differences in ocular anatomy can significantly impact drug pharmacokinetics.
• Existing models often simplify ocular anatomy, potentially limiting predictive accuracy.

Purpose of the Study:

• To develop and validate anatomically accurate computational models for predicting intravitreal drug clearance in rabbits, monkeys, and humans.
• To assess the impact of specific anatomical features, such as the space of Petit, on drug clearance.
• To enable cross-species extrapolation of intravitreal injection experimental data.

Main Methods:

• Construction of anatomically accurate geometric models for rabbit, monkey, and human eyes.
• Utilizing computational fluid dynamics (CFD) to simulate the clearance of intravitreal injected substances.
• Incorporating and excluding the retrozonular space of Petit in model variations.
• Validating rabbit model predictions against literature data for substances up to 157 kDa.

Main Results:

• The space of Petit significantly enhances clearance of slowly diffusing substances via the anterior pathway.
• Models excluding the space of Petit failed to accurately predict clearance, especially for substances cleared by pressure-driven convection.
• Accurate reconstruction of ocular anatomy is essential for reliable clearance predictions.

Conclusions:

• Detailed ocular anatomical modeling is critical for accurate prediction of intravitreal drug clearance.
• The developed CFD modeling approach provides a robust method for cross-species scaling of pharmacokinetic data.
• This approach offers a more refined alternative to traditional methods relying solely on volume and flow rate scaling.