Simulations of delivery of IgG1 Fab, an anti vascular epithelial growth factor (VEGF) macromolecular drug for the treatment of age related macular degeneration (AMD), from an episcleral thermally responsive-poly(N-isopolyacrylamide) (NIPAM)-gel implant, arc made to evaluate the effectiveness of sustained delivery. The model of the human eye used in the above simulations is validated as far as its anatomical and physiological features by the agreement observed in comparing results of simulations of intravitreal fluorescein delivery with relevant experimental data. Simulations of IgG1 Fab delivery from an episcleral NIPAM-gel implant to the posterior eye, with the previously validated anatomically and physiologically correct model of the human eye, show that drug therapeutic levels in the posterior eye are sustained for 8 weeks similarly to those associated with intravitreal injection of IgG1 Fab. Thus, delivery of the macromolecular anti-VEGF drug IgG1 Fab from an episcleral NIPAM-gel implant seems to be a viable alternative to more invasive, risk-related delivery by intravitreal injection, as effective and sustainable as the latter. (C) 2014 Elsevier Ltd. All rights reserved