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

PURPOSE

To develop models for rabbit, monkey, and human that enable prediction of the clearance after intravitreal (IVT) injections in one species from experimental results obtained in another species.

METHODS

Anatomically accurate geometric models were constructed for rabbit, monkey, and human that enabled computational fluid dynamic simulation of clearance of an IVT injected bolus. Models were constructed with and without the retrozonular space of Petit. Literature data on clearance after IVT injection of substances spanning a range of molecular weight up to 157 kDa were used to validate the rabbit model.

RESULTS

The space of Petit had a significant increase on the clearance of slowly diffusing substances cleared by the anterior pathway by reducing the bottleneck for drug efflux. Models that did not include this zone could not accurately predict the clearance of slowly diffusing substances whose clearance was accelerated by intraocular pressure-driven convection.

CONCLUSIONS

The ocular anatomy must be carefully reconstructed in the model to enable accurate predictions of clearance. This method offers an alternative means for scaling experimental data from one species to another that may be more appropriate than other simple approaches based entirely upon scaling of compartment volumes and flow rates.