EyeWorld Asia-Pacific September 2015 Issue

49 EWAP GLAUCOMA September 2015 How will glaucoma treatment change into the future? by Tony Realini, MD, MPH EyeWorld Contributing Writer Will IOP reduction remain our primary approach? P rimary open-angle glaucoma is considered to be a primary optic neuropathy with a multifactorial pathogenesis. Of the many factors associated with the glaucoma disease process, IOP gets most of the attention. IOP is the only modifiable risk factor for glaucoma, and IOP reduction is the only therapy proven to reduce the risk of both the development and progression of glaucoma at all levels of IOP. Even in normal tension glaucoma, where elevated IOP is absent, evidence still supports the role of IOP in the disease process. “Elevated IOP is a known risk factor for diagnosis and progression of optic nerve damage and visual field loss even in the normal range of IOP,” said Martin Wax, MD , Far Hills, NJ. “But glaucoma is multifactorial and IOP is only one of the factors. Some patients have an IOP-independent component.” “In eyes with low IOP,” said Robert N. Weinreb, MD, University of California, San Diego, “the IOP-independent factors may play a relatively larger role.” What are some of these non- IOP factors, and how close are we to developing new strategies for glaucoma therapy? Vascular factors The relative roles of mechanical and ischemic damage to the optic nerve have been discussed by proponents on both sides for decades. Does cupping arise from the mechanical forces attributable to elevated IOP or to ischemia related to impairment of the relevant ocular vascular beds? Both are likely to contribute to the glaucomatous process. “There are many aspects of endothelial cell function that are abnormal in both normal tension and high tension glaucoma,” said Louis Pasquale, MD, Harvard University, Boston. “Vascular and autoregulatory dysfunction are common both inside and outside the eye in glaucoma.” Many patients with vascular risk factors are already receiving systemic therapies to treat or prevent cardiac and/ or cerebrovascular events. These systemic therapies—such as lipid-lowering agents and blood pressure medications—may play a role in reducing glaucoma risk, Dr. Wax said. “In addition, we have known for years that our glaucoma patients with peripheral vasospasm can benefit from treatment with oral calcium channel blockers.” Inflammatory factors “The exact mechanism of retinal ganglion cell death in glaucoma is unclear,” said Stuart McKinnon, MD, Duke University, Durham, NC. One of the many processes likely to be involved is neuroinflammation. The retina is an immune-privileged site, he explained, and inflammation should not occur in the retina or elsewhere in the CNS. However, in animal models and in human glaucoma, evidence is mounting that neuroinflammation may play a role in the process. Key mediators of inflammation—including complement, heat shock protein, and tumor necrosis factor, among others—are activated or upregulated in human eyes with glaucoma. “The potential triggers for these responses may be age- related or attributable to disease- related stress or injury,” he said. When better understood, these process may represent novel One hypothesis is that POAG is categorized by impaired signaling between: a) the inner wall of Schlemm’s canal endothelial cells as well as endothelial cells located in the ciliary body and the posterior longitudinal muscle that helps to set out ow resistance, and b) the ocular vascular endothelial cell and underlying luminal smooth muscle for vessels that supply the retinal ganglion cells. This hypothesis could explain why POAG can occur across the spectrum of IOP. Source: Louis Pasquale, MD continued on page 50