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Editors Selection IGR 21-4

Prevention: Estrogens and glaucoma

Comment by Louis Pasquale on:

50578 Is low dose of Estrogen beneficial for prevention of glaucoma?, Wei X; Cai SP; Zhang X et al., Medical Hypotheses, 2012; 79: 377-380

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In a forum where provocative hypotheses are entertained, the authors propose that low dose estrogen be considered as a treatment for glaucoma. Many studies show that postmenopausal hormone use lowers intraocular pressure. Furthermore exogenous estrogen prevents retinal ganglion cell loss in animal models of glaucoma. Wei and colleagues state that estrogen enhances collagen synthesis, which improves optic nerve resiliency and allows retinal ganglion cells to maintain themselves in a state of active quiescence. The paper does not reconcile this hypothesis with several key issues. How does up-regulated collagen synthesis impact trabecular meshwork function? The uniform thinning and disorganization of the lamina cribrosa seen in advanced glaucoma and the normal aging process categorized by a thickening of the lamina cribrosa can both hamper optic nerve compliance. The authors do not explain how increased collagen synthesis induced by estrogen leads to improved optic nerve compliance. The authors do not consider that estrogen modifies the expression of hundreds of genes and that changes other than altered extracellular matrix composition occurs when estrogen interacts with ocular estrogen receptors. The estrogen hypothesis proposed by the authors does not resonate with some because there is not a preponderance of evidence that gender is a risk factor for primary open-angle glaucoma. However, this does not preclude the possibility that normal and glaucomatous optic nerve change proceed in an estrogen-dependent manner. There are many lines of evidence for this the authors do not cite, including the effect of the menstrual cycle on optic-nerve head structure.¹ Furthermore, at least one analysis of incident open-angle glaucoma showed a trend where pre- and peri-menopausal women had a lower burden of disease compared to men of comparable age.² More research is needed to understand the effects of estrogen on ocular structures relevant to the glaucomatous process.

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