EyeWorld Asia-Pacific September 2015 Issue

50 EWAP GLAUCOMA September 2015 How will glaucoma - from page 49 therapeutic targets for glaucoma therapy, he added. Fortifying the optic nerve “Glaucoma is a frustrating disease from the standpoint of designing interventional clinical trials,” said Harry Quigley, MD, Johns Hopkins University, Baltimore. “The slow rate of glaucoma progression necessitates long, expensive trials when the endpoint is a reduction in the rate of disease progression.” Considered a holy grail of glaucoma therapy, neuroprotection—treatment given prophylactically to render the optic nerve impervious to damage from a variety of insults—has remained elusive in clinical research. IOP reduction can be considered a form of neuroprotection, but its protective effects are limited. “We don’t know the ideal target IOP for patients. Some get worse despite IOP reduction. Adherence also limits the therapeutic benefits,” Dr. Quigley said. Ideally, we could develop a neuroprotective agent that works independently of IOP reduction. Unfortunately, failure to demonstrate a neuroprotective effect of the oral Alzheimer’s drug memantine in a pair of long and expensive glaucoma clinical trials dampened enthusiasm and support for neuroprotection research. Despite this, Dr. Quigley remains optimistic about neuroprotection. Neuroenhancement A more realistic shorter-term goal might be neuroenhancement, said Jeffrey Goldberg, MD, PhD , Stanford University, Palo Alto, Calif. “Neuroenhancement is the concept of supporting injured RGCs and enhancing their function before they die,” he explained. Neuroenhancement therapies are currently in early-phase human trials, he said. One promising potential therapy is an implant that provides sustained delivery of ciliary neurotrophic factor (CNTF), a growth factor known to promote the growth and survival of nerve cells. In one phase 1 trial, 11 patients with bilateral POAG received the implant in one eye and continued their IOP- lowering therapy in both eyes. While both implanted and control eyes maintained comparable IOP control, the implanted eye manifested improvements in visual field status, nerve fiber layer thickness on OCT, and contrast sensitivity compared to untreated fellow eyes. “Results of these early phase studies are suggestive of biological activity with corresponding changes in structure and function,” Dr. Goldberg said. Clinical implications In addition to the innovative discoveries described above, there are some current IOP-independent interventions that can be offered for some of our patients with glaucoma. “We know from various studies that obstructive sleep apnea (OSA) is a risk factor for glaucoma,” Dr. Wax said. Patients with OSA can greatly benefit from weight loss— either through diet and exercise or bariatric surgery—and in some cases from supplemental oxygen Evolving views - from page 47 delivered via continuous positive airway pressure (CPAP). Likewise, nocturnal hypotension is a known risk factor for glaucoma. Ambulatory 24- hour blood pressure monitoring is routine in clinical practice and can identify patients in whom nocturnal dips in blood pressure may be contributory to their glaucoma, Dr. Wax said. “In these patients, a reduction in the nighttime dose of blood pressure medication may be helpful,” Dr. Wax said. If the patient’s primary care provider deems this inappropriate, ingestion of a salty snack such as a small bag of potato chips before bed may help prevent the nocturnal dip in blood pressure. IOP is and always will be an important strategy for glaucoma therapy. However, novel therapeutic target are being explored, and preliminary studies suggest that we may soon have entirely new treatments for glaucoma that will complement IOP reduction. EWAP Editors’ note: Dr. Pasquale has financial interests with Allergan (Irvine, Calif.), Bausch + Lomb (Bridgewater, NJ), the National Eye Institute (Bethesda, Md.), and Novartis (Basel, Switzerland). Drs. Goldberg, McKinnon, Quigley, Wax, and Weinreb have no financial interests related to their comments. Contact information Goldberg: jeffrey.goldberg@stanford.edu McKinnon : stuart.mckinnon@duke.edu Pasquale : louis_pasquale@meei.harvard.edu Quigley : hquigley@jhmi.edu Wax : mbw817@y ahoo.com Weinreb : rweinreb@ucsd.edu believe that pressure on one side of the lamina cribrosa—IOP—matters, then why wouldn’t pressure on the other side of the lamina cribrosa matter? One theory for the relevance of both IOP and ICP is that of laminar deformation caused by the translaminar pressure difference of IOP and ICP, which can squeeze the axons of retinal ganglion cells as they travel through the nerve. Disruption of axonal transport can lead to retinal ganglion cell death—a hallmark of glaucoma. Intriguingly, ICP has been shown to be lower in people with both normal-tension and high- tension glaucoma compared to normal subjects, Dr. Allingham said. “Cerebrospinal fluid pressure starts dropping after age 40–50, the same time in life when the prevalence of glaucoma begins to increase,” he added. Clinical implications IOP still matters and likely always will for patients with glaucoma. In some patients, IOP may matter less than in others. The absolute level of IOP may matter less than its value relative to other biologic parameters, such as blood pressure or intracranial pressure. As we develop home and continuous tonometry tools, we will likely learn more about the complex relationship between IOP, glaucoma, and the whole body. EWAP Editors’ note: Dr. Liebmann has financial interests with Reichert (Depew, NY). Drs. Allingham, Harris, Kaufman, Quigley, Weinreb, and Wilson have no financial interests related to this article. Contact information Allingham : allin002@mc.duke.edu Harris : alharris@indiana.edu Kaufman : kaufmanp@mhub.ophth.wisc.edu Liebmann : jml18@earthlink.net Quigley : hquigley@jhmi.edu Weinreb : rweinreb@ucsd.edu Wilson : president@wayne.edu