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Pressure-independent risk factors in glaucoma are receiving steadily increasing attention. Nocturnal hypotension, atrial fibrillation, Raynaud's phenomenon, low intracranial pressure, and sleep apnea may lead to decreased optic nerve head perfusion. Hemorheologic abnormalities, autoimmune phenomena, and low-grade inflammation may also play a role. Glial activation, mitochondrial dysfunction, and oxidative stress appear to be important in glaucomarelated neurodegeneration. Oxidative stress results from an imbalance between factors causing buildup of reactive oxygen species and natural antioxidant funciton within the eye. Evidence for a beneficial effect of antioxidant therapy is accumulating for a variety disorders in which this imbalance occurs. This comprehensive review by Mozaffarieh et al. (1675) focuses on the potential beneficiality of dietary antioxidants in slowing the progression of glaucomatous damage. There is a very useful refresher on the chemistry of redox reactions and the generation of reactive oxygen and nitrogen species. The antioxidant defense system is typified by superoxide dismutase, catalase, and glutathione peroxidase. A section reviewing our current knowledge regarding the role of oxidative stress in the pathophysiology of glaucoma, both in the trabecular meshwork and optic nerve head, leads into the concept of reperfusion injury and primary vascular dysregulation, the central focus of these authors' research.
Many compounds with powerful antioxidant activity exist in nature. Some of these are regarded as food and others are plant extracts which form the basis of many traditional medical systems, such as Chinese traditional medicine and Ayurvedic medicine. The polyphenolic flavonoids, such as the catechins in tea and resveratrol in red wine, have received much attention, while coffee, dark chocolate, and soy sauce have more recently been suggested as beneficial. The most important plant extract currently known is that of Ginkgo biloba, which has both vasoprotective and neuroprotective properties. It increases ocular, cerebral and peripheral blood flow, improves symptoms of Raynaud's and intermittent claudication, reduces ischemia-reperfusion injury, inhibits apoptosis, and stabilizes mitochondrial function. Melatonin, ubiquinone, cobalamin, alpha-lipoic acid and bilberry are also mentioned. This review is less a pharmacopoiea of interventional modalities, which are only briefly covered, than an overview of the biochemistry of oxidative processes. Proof of the clinical efficacy of these compounds in glaucoma is lacking for the most part, but also very difficult to achieve. For the forseeable future, evidence will remain inferential and extrapolative, but there is certainly little to lose and potentially much to gain in advocating them.