Development of Anterior Segment Focused Biologic Therapies to Regenerate Corneal Tissue for the Treatment of Disease: Drug Development Experience.

On February 24-27, 2021, the Association for Ocular Pharmacology and Therapeutics (AOPT) held its 15th biennial scientific meeting online. The meeting was organized by Dr. Sanjoy Bhattacharya of the University of Miami in conjunction with the board of trustees of the AOPT.

Ophthalmic Drug Discovery and Development: Regulatory Aspects of Patient Focused Drug Development in Ophthalmology.

In 2009, members of the ophthalmic research community held a joint meeting with members of the Food and Drug Administration (FDA) and the National Eye Institute (NEI) to define and describe the types of patient-focused drug development (PFDD) tools used in ophthalmology. Since then numerous reports have been published which indicate that many of the questionnaires used for patient-reported outcomes (PROs) in ophthalmic clinical development lack rigor and reliability according to modern methods. In 2017, the FDA began development of a series of four methodological guidances for sponsors of clinical trials on the significance of PFDD.

Making Basic Science Studies in Glaucoma More Clinically Relevant: The Need for a Consensus.

Glaucoma is a chronic, progressive, and debilitating optic neuropathy that causes retinal damage and visual defects. The pathophysiologic mechanisms of glaucoma remain ill-defined, and there is an indisputable need for contributions from basic science researchers in defining pathways for translational research. However, glaucoma researchers today face significant challenges due to the lack of a map of integrated pathways from bench to bedside and the lack of consensus statements to guide in choosing the right research questions, techniques, and model systems.

Ocular Hypotensive Effect of ONO-9054, an EP3/FP Receptor Agonist: Results of a Randomized, Placebo-controlled, Dose Escalation Study.

Purpose: To assess pharmacodynamic and safety profiles of ONO-9054 following single and multiple day dosing in subjects with ocular hypertension or open-angle glaucoma.

Materials And Methods: This was a phase I, single-center, randomized, double-masked, placebo-controlled dose-escalation study. Nine subjects were randomized to each of ONO-9054 3, 10, 20, 30 μg/mL and 12 to placebo.

A Novel Dual Agonist of EP3 and FP Receptors for OAG and OHT: Safety, Pharmacokinetics, and Pharmacodynamics of ONO-9054 in Healthy Volunteers.

Purpose: The use of a dual prostaglandin E3 (EP3) and prostaglandin F (FP) receptor agonist is a novel approach for the reduction of intraocular pressure (IOP) in open angle glaucoma and ocular hypertension and, as such, ONO-9054 may have benefits over existing therapies. The objectives of this phase I study were to assess the safety, tolerability, systemic pharmacokinetics (PK), and pharmacodynamics (PD) profiles of ONO-9054 (Sepetoprost), the prodrug of ONO-AG-367, in healthy, normotensive adults.

Methods: In this randomized, double-masked, placebo-controlled, single-dose escalating study, 48 male and female healthy volunteers each received a single drop of ONO-9054 0.

EP3/FP dual receptor agonist ONO-9054 administered morning or evening to patients with open-angle glaucoma or ocular hypertension: results of a randomised crossover study.

Background/aims: The novel prostaglandin E (EP) 3 and prostaglandin F (FP) receptor agonist ONO-9054 is effective in lowering intraocular pressure (IOP) in patients with ocular hypertension and open-angle glaucoma when administered once daily. This study compares the effects of morning (AM) versus evening (PM) dosing of ONO-9054 on tolerability and IOP lowering.

Methods: This was a single-centre, randomised, double-masked, two-sequence, placebo-controlled crossover study in 12 subjects with bilateral primary open-angle glaucoma or ocular hypertension.

Validation of molecular and genomic biomarkers of retinal drug efficacy: use of ocular fluid sampling to evaluate VEGF.

The use of tissue- and cell-based methods in developing drugs for retinal diseases is inefficient. Consequently, many aspects of ocular drug therapy for retinal diseases are poorly understood. Biomarkers as prognostic indicators of change are needed to optimize the use of drugs.

Possible therapy for age-related macular degeneration using human telomerase.

Age-related macular degeneration (AMD) is the leading cause of irreversible blindness in people over 60 years of age in the US and many other developed countries. Increasingly sophisticated methods for the diagnosis and treatment of macular degeneration are not effective for the majority of patients in whom late stage disease is present at the time of diagnosis. Research to elucidate the changes in RPE cell biology during aging has stimulated interest in preventive and prophylactic therapies for earlier intervention in the degenerative process.

In vitro differentiation capacity of telomerase immortalized human RPE cells.

Purpose: To investigate conditions promoting the differentiation of cultured human retinal pigment epithelial (RPE) cells and assess the differentiation potential of telomerase-immortalized RPE cells.

Methods: Serially passaged RPE 340 (parental) cells have limited replicative ability and senesce after 50 to 60 population doublings (PD)s. RPE 340 cells transfected with the catalytic component of human telomerase (hTERT) have an extended lifespan.