At a glaucoma follow-up visit, a lower intraocular pressure (IOP) is reassuring

Glaucoma is a multifaceted optic neuropathy, characterized by the progressive loss of retinal ganglion cells. This damage frequently continues even after intraocular pressure (IOP) has been effectively lowered. This resistance to conventional IOP-lowering therapy underscores the critical role of interacting IOP-independent mechanisms; specifically metabolic failure and systemic mitochondrial dysfunction have emerged as key parallel drivers. This review analyzes the paradigm shift from a pressure-centric model to a bioenergetic one, focusing on mitochondrial function, peripheral blood mononuclear cell (PBMC) biomarkers, and oxygen consumption dynamics. We synthesize evidence demonstrating that glaucoma patients exhibit a metabolic vulnerability, characterized by lower PBMC oxygen consumption rates and depleted systemic nicotinamide adenine dinucleotide levels relative to healthy individuals. Furthermore, compromised systemic respiratory performance correlates with more rapid worsening of visual fields and structural thinning, independent of IOP status. Moreover, we delineate the role of Complex I defects, SARM1-mediated axonal degeneration, and proteomic alterations, which indicate defective mitophagy. These findings establish systemic metabolic profiling as a valuable supplementary tool for assessing patient risk and support the clinical translation of neuroprotective therapies targeting mitochondrial bioenergetics, specifically nicotinamide, pyruvate, coenzyme Q₁₀, and metformin.

Primary glaucoma is a leading global cause of irreversible visual impairment, necessitating management strategies to preserve visual function over a lifetime. This narrative review synthesizes contemporary evidence on risk stratification, target intraocular pressure (IOP), and interventional decision-making for primary open-angle glaucoma (POAG) and the primary angle-closure disease (PACD) spectrum. A risk-stratified approach integrates baseline risk factors, gonioscopic anatomy, structural optical coherence tomography (OCT), standard automated perimetry, rate of progression, life expectancy, ocular surface status, medication adherence, patient preference, and resource setting. Early laser or surgical intervention can reduce medication burden and improve IOP control in selected patients. However, conservative medical management and observation remain appropriate when progression risk is low or procedural risk is disproportionate. Landmark trials support first-line selective laser trabeculoplasty in suitable POAG. Additionally, evidence supports primary trabeculectomy as an option for advanced disease and early lens extraction for selected older patients with primary angle closure or primary angle-closure glaucoma. Artificial intelligence, polygenic risk scores, and sustained-release platforms serve as promising adjuncts. Nevertheless, these technologies require external validation, equitable implementation, and clearly defined clinical action thresholds before routine adoption. Overall, glaucoma care should transition from a uniform sequence prioritizing topical medications toward an individualized, evidence-based escalation strategy. This approach optimally balances visual prognosis, procedural risk, and patient-centered outcomes.