Diabetes mellitus as a risk factor for glaucomatous optic neuropathy

Open-angle glaucoma (OAG) is an optic neuropathy characterized by progressive retinal ganglion cell (RGC) death and optic disk excavation. Evidence is accumulating that RGC apoptosis is the fundamental pathology of OAG. Among several risk factors for development and progression of OAG, inclusion of comorbid diabetes has been controversial. Some large population-based prevalence and incidence studies found a positive association between diabetes and OAG, whereas others did not. This inconsistency is derived from selection-, recall-, or survival-bias or misclassification due to low incidence of the two diseases. On the other hand, recent basic studies have shown that diabetes not only affects vascular tissues but also compromises neuronal and glial functions and metabolism in the retina, which ultimately gives rise to apoptotic death of retinal neurons including RGCs. The impaired metabolism of neurons and glia by diabetes may render RGCs susceptible to additional stresses related to OAG such as elevated intraocular pressure. In fact, our latest data demonstrate that retinas taken from rats with streptozotocin-induced diabetes, which underwent cauterization of three episcleral veins to become a chronic glaucoma model, had significantly more apoptotic cells than those from rats with diabetes alone or with chronic glaucoma alone. In this regard, diabetes is a 'risk factor' for glaucomatous optic neuropathy. Additionally, prospective studies are needed to determine if OAG patients with diabetes have a more aggressive course than those without diabetes.