<p>Sustained release of drugs by devices such as dexamethasone implant placed in vitreous humor can reduce the frequency of intravitreal injections. The duration over which the device provides therapeutic drug exposure is a critical parameter and so models for predicting ocular pharmacokinetics after placing the device in vitreous humor are valuable. This study developed a model using parameters from literature to predict concentrations in aqueous humor, vitreous humor, retina and sclera-choroid after placing Ozurdex in vitreous humor and validated the model using data reported in literature for rabbits and Cynomolgus monkeys. The model is based on ordinary differential equations representing mass balances in vitreous humor, retina, aqueous humor and sclera-choroid. Additionally, a partial differential equation representing mass balance in the lens is included. The model can be simplified to yield explicit expressions for concentration in all tissues. The results are in reasonable agreement with concentrations reported in literature, particularly considering the in vivo data variability and lack of dependence on fitting parameters in the model. The simulation results suggest that the duration of therapeutic concentration in the retina is longer than the drug release duration from the implant because drug diffuses into the lens, creating a depot. The drug depot in the lens eventually releases the drug back into vitreous humor, which increases the total duration over which the concentrations are efficacious. The model can be applied to other sustained release devices placed in vitreous humor or elsewhere in the eye.</p> Graphical abstract <p></p>