Prior to the initiation of treatment, a comprehensive ocular examination is required. This includes a complete ophthalmic history, with an emphasis on previous glaucoma diagnosis and therapy. The time of initial diagnosis, maximum IOP, recent IOP measurements, and corneal thickness should be noted. All previous glaucoma medications used, as well as their efficacy and side effects, must be recorded. Secondary causes of glaucoma (e.g., pigmentary, exfoliation, corticosteroid use, trauma, uveitis, or previous ocular surgery) should also be noted. Where available, copies of prior visual fields, optic nerve photographs, and nerve fiber layer measurements should be obtained. Systemic medical conditions and drug allergies must be noted. A family history of ocular diseases, including glaucoma and visual impairment, is important.
Several risk factors have been closely associated with the development and progression of POAG. These include IOP, age, race, family history, thinner central corneal thickness, and increased cup-to-disk ratio.6-9 Of these risk factors, IOP is the only one that is amenable to treatment.
Experimental studies have shown that raising IOP in animals produces typical glaucomatous optic nerve cupping.10,11 Clinical examples of patients with asymmetric glaucoma, with worse damage occurring in the eye with higher IOP, have been documented.12,13 The Collaborative Glaucoma Study found that the relative risk for developing glaucoma was 10.5 times greater in persons who had baseline IOPs of 24 mm Hg or greater compared with those who had IOPs less than 16 mm Hg.6 The study also found that the relative risk of developing glaucoma rises in a dose-response fashion with baseline IOP. Several randomized, prospective clinical trials have shown that lowering IOP can delay the development and progression of glaucoma.14-16 Improvement in optic nerve cupping with significant lowering of IOP has also been reported.17
However, even though recent clinical trials have shown the benefits of lowering IOP in managing glaucoma, some patients continue to lose visual function from glaucoma despite what may appear to be adequately controlled IOP. Of course, IOP-related factors such as nonadherence with medical therapy and IOP fluctuation may contribute to this phenomenon. Other factors, however, may play a role. Research continues to look for IOP independent treatment modalities.18,19 Current areas of research include ocular blood flow, calcium metabolism, blockage of glutamate excitotoxicity, inhibition of nitric oxide production, prevention of tumor necrosis factor activation, modulation of heat-shock protein expression, free radicals, neurotrophins, alpha-2-adrenergic receptor agonists, and other approaches to inhibit apoptosis. The results from a large randomized clinical trial investigating the use of memantine, an N-methyl-D-aspartate receptor antagonist, as a potential neuroprotectant are expected in the near future. Until more definitive data are available, IOP reduction remains the only proven glaucoma treatment.
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