Glaucomatous optic neuropathy treatment options: the promise of novel therapeutics, techniques and tools to help preserve vision

Peripheral vision loss followed by “tunnel vision” and eventual irreversible blindness is the fate of patients afflicted by various forms of glaucoma including primary open-angle glaucoma (POAG) and normotensive glaucoma (NTG). These complex and heterogeneous diseases are characterized by extensive death of retinal ganglion cells (RGCs) accompanied by retraction and severance of their axonal connections to the brain and thus damage to and thinning of the optic nerve. Since patients suffering from this glaucomatous optic neuropathy (GON) first notice visual impairment when they have lost > 40% of their RGCs, early diagnosis is the key to retard the progression of glaucoma. Elevated intraocular pressure (IOP), low cerebrospinal and/or low intracranial fluid pressure, advancing age, and ethnicity are major risk factors associated with POAG. However, retinal vascular abnormalities and a high sensitivity of RGCs and optic nerve head components to neurotoxic, inflammatory, oxidative and mechanical insults also contribute to vision loss in POAG/GON. Current treatment modalities for POAG and NTG involve lowering IOP using topical ocular drugs, combination drug products, and surgical interventions. Two recently approved multi-pharmacophoric drugs (e.g., rho kinase inhibitor, Netarsudil; a drug conjugate, Latanoprostene Bunod) and novel aqueous humor drainage devices (iStent and CyPass) are also gaining acceptance for treating POAG/ NTG. Neuroprotective and regenerative agents, coupled with electroceutical, mechanical support systems, stem cell transplantation and gene therapy are emerging therapeutics on the horizon to help combat GON. The latter techniques and approaches hope to rejuvenate RGCs and repair the optic nerve structures, thereby providing a gain of function of the visual system for the glaucoma patients.