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A decade has passed since the first topical prostaglandin analog was prescribed to reduce intraocular pressure (IOP) for the treatment of glaucoma. Now four prostaglandin analogs are available for clinical use around the world and more are in development. The three most efficacious of these drugs are latanoprost, travoprost, and bimatoprost, and their effects on IOP and aqueous humor dynamics are similar. A consistent finding is a substantial increase in uveoscleral outflow and a less consistent finding is an increase in trabecular outflow facility. Aqueous flow appears to be slightly stimulated as well. Prostaglandin receptors and their associated mRNAs have been located in the trabecular meshwork, ciliary muscle, and sclera providing evidence that endogenous prostaglandins have a functional role in aqueous humor drainage. Earlier evidence found that topical PG analogs release endogenous prostaglandins. One well-studied mechanism for the enhancement of outflow by prostaglandins is the regulation of matrix metalloproteinases and remodeling of extracellular matrix. Other proposed mechanisms include widening of the connective tissue-filled spaces and changes in the shape of cells. All of these mechanisms alter the permeability of tissues of the outflow pathways leading to changes in outflow resistance and/or outflow rates. This review summarizes recent (since 2000) animal and clinical studies of the effects of topical prostaglandin analogs on aqueous humor dynamics and recent cellular and molecular studies designed to clarify the outflow effects.

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Cultured trabecular meshwork (TM) cells are a valuable model system to study the cellular mechanisms involved in the regulation of conventional outflow resistance and thus intraocular pressure; and their dysfunction resulting in ocular hypertension. In this review, we describe the standard procedures used for the isolation of TM cells from several animal species including humans, and the methods used to validate their identity. Having a set of standard practices for TM cells will increase the scientific rigor when used as a model, and enable other researchers to replicate and build upon previous findings.

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AimTo assess the efficacy and safety of latanoprostene bunod (LBN) compared with latanoprost 0.005%, and to determine the optimum drug concentration(s) of LBN in reducing intraocular pressure (IOP) in subjects with open angle glaucoma or ocular hypertension.MethodsRandomised, investigator-masked, parallel-group, dose-ranging study. Subjects instilled one drop of study medication in the study eye once daily each evening for 28 days and completed five study visits. The primary efficacy endpoint was the reduction in mean diurnal IOP at Day 28.ResultsOf the 413 subjects randomised (LBN 0.006%, n=82; LBN 0.012%, n=85; LBN 0.024%, n=83; LBN 0.040%, n=81; latanoprost, n=82), 396 subjects completed the study. Efficacy for LBN was dose-dependent reaching a plateau at 0.024%–0.040%. LBN 0.024% led to significantly greater reductions in diurnal IOP compared with latanoprost at the primary endpoint, Day 28 (p=0.005), as well as Days 7 (p=0.033) and 14 (p=0.015). The incidence of adverse events, mostly mild and transient, was numerically higher in the LBN treatment groups compared with the latanoprost group. Hyperaemia was similar across treatments.ConclusionsLBN 0.024% dosed once daily was the lower of the two most effective concentrations evaluated, with significantly greater IOP lowering and comparable side effects relative to latanoprost 0.005%. LBN dosed once daily for 28 days was well tolerated.Clinical trial numberNCT01223378.