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EW GLAUCOMA 92 October 2015 by Tony Realini, MD, MPH, EyeWorld Contributing Writer of retinal ganglion cells." This is supportive of a primary disease of retinal ganglion cells that is poten- tially independent of IOP. Intracranial pressure (ICP) may also play a role. There has been great interest recently in the concept of a pressure differential across the lamina cribrosa determined by the difference between IOP and ICP. When ICP is low relative to IOP, the lamina can be deformed posteriorly, potentially injuring the axons. Animal studies have suggest- ed that lowering ICP can lead to glaucoma. In humans, said Timothy McCulley, MD, Johns Hopkins Uni- versity, Baltimore, some studies have reported lower ICP in glaucoma pa- tients compared to control subjects and, importantly, lower in people with NTG compared to POAG. "Low intracranial pressure may help explain normal tension glauco- ma," Dr. McCulley said. The case against NTG In the opposite camp are those who believe NTG dos not exist as a sepa- rate clinical entity. "Normal tension glaucoma is not a clinical entity. It is a statistical entity," said Robert N. Weinreb, MD, University of California-San Diego. He pointed out that the range the two entities are, in fact, the same disease. But as Nancy Newman, MD, Emory University, Atlanta, ob- served, "The optic nerve may have a limited number of ways to express damage, and cupping may be the final phenotypic appearance of a plethora of optic neuropathies." NTG may also have more distinct risk factors and genetic factors than POAG. "Both epidemi- ologic and genetic studies suggest that patients with normal tension glaucoma have a different set of pre- disposing risk factors compared to high tension glaucoma," said Janey Wiggs, MD, PhD, Massachusetts Eye and Ear, Boston. Vascular factors such as disc hemorrhage and vasospasm have been associated with NTG more so than POAG. NTG also differentially affects some populations more than others. "In Japan, 92% of open angle glaucoma is normal tension glau- coma," Dr. Wiggs said. This is likely a genetic phenomenon and not an environmental one because Japanese Americans also have a high risk of NTG, she added. "In genetics studies," she said, "the genes associated with normal tension glaucoma seem to influence processes likely to impact the health IOP consistently fell within this range. The case for NTG Those who believe that NTG is a distinct entity from POAG point to several apparent differences between these two conditions. Jonathan Myers, MD, Wills Eye Hospital, Philadelphia, described several phenotypic differences between these two conditions. "Disc size may be larger in normal ten- sion glaucoma," he said. This would mean a larger lamina cribrosa span- ning a larger opening in the poste- rior sclera. "This may provide less support for axons," he explained, as the larger lamina may be at greater risk for posterior deformation by IOP even in the normal range. Likewise, he pointed out that while disc hemorrhages are seen infrequently in both conditions, they are more commonly seen in NTG compared to POAG. Also, the visual field defects in NTG tend to be denser, more sharply demarcated, more focal, and closer to fixation than in POAG. Cupping of the optic nerve is considered the pathognomonic sign of glaucoma, and the similarity of cupping between NTG and POAG could be considered evidence that T he more we learn about the relationship between IOP and glaucoma, the less strong the relationship appears. "One hundred years ago," said Robert Ritch, MD, New York Eye and Ear Infirmary of Mount Sinai, New York, "elevated IOP was the definition of glaucoma. Now IOP is considered the most important risk factor for the disease, but it's only a risk factor and is not the disease." As a risk factor, elevated IOP is neither necessary nor sufficient to account for the presence of glau- coma. Glaucoma often occurs in eyes with elevated IOP. However, eyes can have elevated IOP without developing glaucoma, and eyes can develop glaucoma with IOP in the normal range. We have developed a language for discussing these scenar- ios: primary open-angle glaucoma (POAG) for glaucoma with elevated IOP, ocular hypertension for ele- vated IOP without glaucoma, and normal tension glaucoma (NTG) for glaucoma with normal IOP. The distinction between POAG and NTG has given rise to a number of important clinical trials that have led us to believe that the clinical ap- pearance, risk factors, and treatment of these two entities may differ. More recently, some experts have begun to question whether this is strictly true. Is NTG a distinct enti- ty or is it simply POAG occurring in the normal range of IOP? This issue was discussed by glaucoma special- ists and neuro-ophthalmologists at a joint session of the American Glau- coma Society and the North Amer- ican Neuro-Ophthalmology Society in February in San Diego. The history of NTG The concept of normal tension glaucoma dates back 50 years or more and has its roots in popula- tion studies designed to define the normal range of IOP as measured by Goldmann tonometry. These studies revealed a non-Gaussian distribution of Goldmann IOP with a mean in the mid-teens and skewed toward higher values. Overall, 95% of all the values fell within the range of 10 mm Hg to 21 mm Hg. Soon after, the term normal tension (or pressure) glaucoma was coined to describe people with the classic findings of POAG but whose Does normal tension glaucoma exist? Normal tension glaucoma with notch and nerve fiber layer defect, as also seen in many primary open-angle glaucoma eyes Source: Jonathan Myers, MD

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