Quantitative systems pharmacology of the eye: Tools and data for ocular QSP

Good eyesight belongs to the most-valued attributes of health, and diseases of the eye are a significant healthcare burden. Case numbers are expected to further increase in the next decades due to an aging society. The development of drugs in ophthalmology, however, is difficult due to limited accessibility of the eye, in terms of drug administration and in terms of sampling of tissues for drug pharmacokinetics (PKs) and pharmacodynamics (PDs). Ocular quantitative systems pharmacology models provide the opportunity to describe the distribution of drugs in the eye as well as the resulting drug-response in specific segments of the eye. In particular, ocular physiologically-based PK (PBPK) models are necessary to describe drug concentration levels in different regions of the eye. Further, ocular effect models using molecular data from specific cellular systems are needed to develop dose-response correlations. We here describe the current status of PK/PBPK as well as PD models for the eyes and discuss cellular systems, data repositories, as well as animal models in ophthalmology. The application of the various concepts is highlighted for the development of new treatments for postoperative fibrosis after glaucoma surgery.

Automated summary

Good eyesight is highly valued for overall health, but eye diseases pose a significant healthcare burden. With an aging population, the number of cases is expected to rise. However, developing drugs for eye diseases is challenging due to limited access and sampling of eye tissues. Ocular quantitative systems pharmacology models offer a chance to understand drug distribution and response in specific parts of the eye. Physiologically-based pharmacokinetic models are crucial for understanding drug concentration levels in different eye regions, and molecular data from cellular systems are needed to establish dose-response correlations. This article discusses the current status of PK/PBPK and PD models for the eyes, as well as the use of cellular systems, data repositories, and animal models in ophthalmology. The concepts are illustrated by exploring new treatments for postoperative fibrosis after glaucoma surgery.