New and Emerging Drug Therapy in Primary Open-Angle and Normal-Tension Glaucoma: Pharmacology, Neuroprotection and the Endpoint Problem

Glaucoma is a group of progressive optic neuropathies characterized by retinal ganglion cell (RGC) loss, optic nerve head damage and corresponding visual-field loss. Intraocular pressure (IOP) is the principal modifiable risk factor, and lowering IOP remains the only treatment approach that has been shown in randomized clinical trials to slow glaucomatous progression, including in normal-tension glaucoma (NTG). However, IOP reduction does not eliminate progression in all patients, indicating that susceptibility to pressure-related damage is heterogeneous and that additional biological mechanisms are relevant. This review examines current and emerging pharmacological strategies for IOP lowering, approaches intended to protect RGCs independently of IOP, and the methodological problem of demonstrating neuroprotection in clinical trials.