The global population continues to age leading to a higher incidence of age-related ophthalmic diseases, notably those affecting the back-of-the-eye, i.e. the posterior segment or more specifically the retina. Dysfunction within the neuroretina or the adjacent retinal pigment epithelium (RPE) or choroid, can result in significant or substantial decline of vision and potentially blindness. While there have been remarkable and even breakthrough advances in the form of anti-VEGF biologics for neovascular AMD, and more recently, anti-complement therapy for dry AMD/geographic atrophy, as well as gene therapies to address inherited retinal disease/dystrophies, these therapies require direct injection into the eye (e.g. intravitreal or subretinal). While generally highly effective, these in-office or surgical procedures are associated with logistical, financial and risk burdens on the patient and medical community. Topical ocular drug treatment, via eye drop administration, has long been considered an ideal non-invasive route for its convenience to the patient, generally lower cost, and lower burden on the health care provider. However, the evidence for topical drug reaching the back-of-the-eye and clinical evidence for efficacy have been mixed and debatable, with noteworthy drug development failures along the way. Lack of clinical efficacy has often been attributed to insufficient drug reaching the site of action, i.e. retina or RPE/choroid targets, presumably due to the formidable ocular barriers to drug penetration and distribution from front to the back of the eye, and the task of crossing substantial blood-retinal barriers on the way to reaching the light-sensing neuroretina.

This presentation will review the ocular barriers that make topical ocular delivery to the back-of-the-eye so challenging, discuss the pharmacokinetic/pharmacodynamic and clinical efficacy science and explore drug design and formulation development strategies for optimizing delivery to the back-of-the-eye.

James Chastain, Ph.D.

James Chastain, Ph.D. is an independent consultant with over three decades experience in PK/PD and clinical pharmacology and specializes in ocular pharmacokinetics/pharmacodynamics and drug delivery. He has published journal articles and book chapters and presented at key scientific meetings. Dr. Chastain has held various pharma company positions, most recently as Executive Director and PK Sciences (PKS) Ophthalmology Unit Head at Novartis Institutes for BioMedical Research in Cambridge, MA. Prior to this, he was Head of the Ocular Pharmacokinetics and Disposition department at Alcon Research, Ltd. in Fort Worth, TX, where he oversaw the characterization of small and large molecule preclinical and clinical DMPK/PD supporting development of ophthalmic pharmaceuticals. He received his BA in Chemistry and MS in Physical Sciences from the University of Missouri and his PhD in Pharmacology from Dept. of Pharmacology, Toxicology and Therapeutics at the University of Kansas Medical Center, followed by post-doctoral studies and research in the Dept. of Pharmaceutical Sciences at the University of Kansas. He is a member of American Association of Pharmaceutical Scientists and founding member and former chair of the AAPS Ocular Drug Delivery and Biodisposition Community.