Beyond IOP: Neuroprotection and neuroregeneration as important therapeutic strategies for glaucoma

Glaucoma is the leading cause of irreversible blindness characterized by the progressive death of retinal ganglion cells (RGCs) and damage to the optic nerve. Although the main goal of current treatment approaches is to reduce intraocular pressure (IOP), many patients' disease progression persists even after IOP returns to normal, highlighting the urgent need for effective neuroprotective strategies . The pathogenesis of glaucomatous neurodegeneration is thoroughly reviewed in this study, with special attention given to the roles of inflammation, excitotoxicity, mitochondrial dysfunction, oxidative stress, and compromised neurotrophic support. This study examines both pharmaceutical and nonpharmacological neuroprotective strategies while discussing the complex pathophysiology of glaucomatous neurodegeneration. Glutamate modulators, antioxidants, mitochondrial protectants, and anti-inflammatory drugs are examples of pharmacological tactics. Moreover, novel nonpharmacological approaches such as stem cell transplantation, gene therapy, and drug delivery systems based on nanotechnology show promise as long-term neuroprotective strategies. These strategies could increase the number of therapeutic options available for glaucoma by targeting mechanisms other than IOP. However, most of them are still in the preclinical or early clinical stages and need well-designed randomized controlled trials and long-term safety data before they can change standard clinical practice. We conclude by describing potential future paths, such as the need for integrated, patient-centered therapy paradigms, AI-driven prognostic tools, and precision medicine. Overall, this review highlights how crucial neuroprotection is as a developing element in the comprehensive treatment of glaucoma. • The review paper highlights a change in treatment for glaucoma from lowering intraocular pressure (IOP) to promoting neuroprotection and neuro-regeneration. • It covers the complex processes of glaucomatous neurodegeneration, such as neuroinflammation, mitochondrial dysfunction, and oxidative stress. • A comprehensive assessment is conducted of recently discovered neuroprotective treatments, including neurotrophic factors, antioxidants, and mitochondrial stabilizers. • For possible translational use, cutting-edge techniques including gene therapy, nanotechnology, and stem-cell therapies are highlighted.