Glaucoma is a chronic optic neuropathy and a leading cause of irreversible blindness worldwide. Varma et al. projected a global prevalence above 79 million by 2020, and annual costs reach USD 3 billion in the USA. The only clinically modifiable risk factor is intraocular pressure (IOP), managed via topical drops, laser, and surgery. However, glaucoma is not solely a pressure disease, and there is growing interest in IOP-independent, neuroprotective strategies. Nutrients, antioxidants, vitamins, and micronutrients—so-called "nutraceuticals"—have been proposed as adjunctive options to slow retinal ganglion cell (RGC) degeneration and benefit other ophthalmologic conditions.
This was a narrative minireview. A PubMed search using the query on dietary supplements AND eye was conducted in February 2023, following PRISMA guidance. Inclusion criteria covered PubMed full-text articles from 2012–2023 in English focused on selected nutrients in ophthalmology. Two or more reviewers (M.M., G.A., E.E., E.T., M.Z.) independently assessed each study, with consensus on inclusion. A total of 374 references were included. Nutrients reviewed include glutathione, minocycline, spermidine, fisetin, omega-3 fatty acids, rapamycin, metformin, alpha-ketoglutarate, vitamins B3, D, A, B1, B2, B9, B12, C, E, citicoline, quercetin, resveratrol, pyruvate, lutein, zeaxanthin, and eyebright (Euphrasia officinalis).
GLUTATHIONE
Takeshi et al. found significantly elevated glutathione disulfide and smaller redox indices in glaucoma patients, suggesting mitochondrial dysfunction; Gherghel et al. reported significantly lower reduced glutathione in POAG and NTG patients versus controls. Minocycline: In a rat model, 13.5 mg/kg minocycline inhibited microglia and protected optic nerve neurofilaments after S100B-induced degeneration. Spermidine: Buisset et al. reported reduced spermine in open-angle glaucoma eyes; Lillo et al. found elevated spermidine in aqueous humor of open-angle glaucoma patients; Wang et al. linked reduced spermidine to glaucomatous damage. Fisetin: Downregulates VEGF in diabetic retinopathy and protected retinal function in murine glaucoma; Kan et al. showed fisetin-treated mice had statistically lower cataract levels than alpha-lipoic acid or placebo groups. Omega-3: Topical DHA inhibited bleb fibrosis comparably to mitomycin C in murine filtration surgery; DHA and EPA with timolol showed retinal neuroprotection in murine hereditary glaucoma; lutein/zeaxanthin supplementation reduced progression to advanced AMD by 25% in early-stage disease. Rapamycin: Topical RAPA decreased IOP via Rho-kinase inhibition in murine aqueous humor and provided RGC neuroprotection; systemic RAPA suppressed VEGF and oxidative stress in hyperglycemic murine retina. Metformin: Reduced steroid-induced ocular hypertension in mice via integrin/ROCK pathway; a possible association between metformin and lower open-angle glaucoma risk in NIDDM patients has been suggested. Alpha-ketoglutarate: Antioxidant effects reduced cataractogenesis in animal models. Vitamin B3 (niacin): Gaynon et al. report functional and anatomical improvements in CRVO patients on niacin. Vitamin D: Deficiency is linked with myopia, glaucoma, AMD, diabetic retinopathy, and dry eye; keratoconus patients show lower serum vitamin D than controls. Zeaxanthin/lutein: Improved foveal pigment response in glaucoma patients; lutein/zeaxanthin reduced oxidized LDL in metabolic syndrome. Resveratrol: Decreased oxidative stress and inflammatory markers in trabecular meshwork; neuroprotection of RGCs in rat glaucoma models. Pyruvate: Phase II trial of nicotinamide and pyruvate showed significant momentary improvement in visual function in glaucoma; oral pyruvate provided neuroprotection in rodent glaucoma models. Vitamin A: Sato et al. demonstrated neuroprotection by all-trans retinol in mice. Vitamin B1 (thiamine): Lee et al. linked thiamine intake to reduced progression in normal tension glaucoma. Vitamin B12 deficiency is associated with pseudoexfoliation glaucoma and other open-angle glaucomas; high deficiency rates occur in Leber's hereditary optic neuropathy. Vitamin C: Zanon-Moreno et al. (391 POAG vs 383 controls) found genetic risk scores inversely correlated with plasma vitamin C, though Han and Fu's systematic review did not support an association with reduced glaucoma prevalence. Vitamin E-enriched diets reduced RGC death in murine models. Citicoline is currently used as a supplement in glaucoma management with reported improvements in visual function. Quercetin induced neuroprotection in rat glaucoma models and reduced apoptotic RGC death. Eyebright eyedrops ameliorated conjunctivitis indices in humans. Combination therapy (Focus Forte) improved retinal function in POAG, and a forskolin/homotaurine/spearmint/B-vitamin mixture reduced RGC loss in elevated-IOP mouse models.
**Clinical Implications**
Nutrients are inexpensive, generally well tolerated, and easily absorbed, making them attractive adjuncts. They cannot replace IOP-lowering drops, laser, or surgery but may provide synergistic neuroprotective, antioxidant, and anti-inflammatory effects that stabilize RGCs and ocular tissues. The authors emphasize the need for large multicenter clinical trials with long-term functional and morphologic endpoints to validate these integrative IOP-independent strategies in glaucoma and other ophthalmologic pathologies.