OCT 2013

EyeWorld is the official news magazine of the American Society of Cataract & Refractive Surgery.

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October 2013 February 2011 EW GLAUCOMA 67 Which glaucoma suspects should we worry about most? G laucoma suspects are common in most comprehensive clinical practices. These are the patients who have some of the features of glaucoma, but not enough to justify the official diagnosis. They may have elevated intraocular pressure (IOP) but healthy optic nerves and normal visual fields—an entity we call ocular hypertension. Others may have suspicious optic nerves with normal IOP and visual fields— so-called normal tension glaucoma suspects. Our typical approach to these patients is to watch them over time to see if they develop fullblown glaucoma. These two groups—the suspects by IOP and the suspects by nerve appearance—are different in important ways. Thanks to the Ocular Hypertension Treatment Study (OHTS), we know more about the former than the latter. For instance, we know that among ocular hypertensives, approximately 10% will progress to glaucoma every five years, and the risk factors that predict this progression are higher IOP, greater age, lower central corneal thickness values, bigger cup-disc ratio, and higher visual field mean deviation values. We have not had the benefit of a comparable study for patients who are glaucoma suspects by nerve appearance. At the 2013 meeting of the Association for Research in Vision and Ophthalmology (ARVO) in Seattle, several research teams presented new data to help us better determine which of our glaucoma suspects are at highest risk for developing glaucoma. New lessons from OHTS The OHTS continues to be a goldmine of useful information regarding ocular hypertensive patients. Mae Gordon, PhD, a methodologist at Washington University, St. Louis, and one of the architects of OHTS, presented a new analysis aimed at addressing a hot topic in glaucoma: Is IOP variability a risk factor for developing glaucoma? IOP variability can be measured in a number of ways. Historically, we have looked at the range of IOP: the highest value minus the lowest value. But this approach relies on outlying values and does not take full advantage of all the data in be- by Tony Realini, MD tween these extreme values. More recently, researchers have recognized that the standard deviation of all IOP values (the average difference of each value from the mean) is likely a more robust measure of IOP variability. Dr. Gordon and colleagues determined the long-term IOP variability across study visits (using the standard deviation) for each OHTS participant in both the observation and treatment groups. Patients were then grouped into high and low IOP variability groups, with the cutoff being a standard deviation of IOP above or below 2.5 mm Hg. "In the observation group, there was no difference in progression rates among those whose standard deviation of IOP was above versus below 2.5 mm Hg in any of the three mean IOP subgroups," she said. "In the medication group, however, a higher standard deviation of IOP did increase the risk of developing glaucoma in all three of the mean IOP subgroups." One possible explanation for this involves adherence to therapy. In theory, treatment should lower IOP at all times. But if patients aren't completely adherent to therapy, then there will be times when IOP is very low due to medication and also times when IOP approaches untreated baseline due to missed doses of medication. This has the effect of increasing IOP variability. "In fact, we found that IOP variability correlated with attendance of OHTS study visits," said Dr. Gordon. "People who missed visits had higher IOP variability." It isn't much of a stretch to assume that people who are noncompliant with followup are also noncompliant with medication adherence. This would explain why IOP variability predicted progression only in the medication group. Inconsistent use of medication increases IOP variability in excess of that seen in the observation group, which in turn leads to higher risk of progression. Insight from ADAGES The African Descent and Glaucoma Evaluation Study (ADAGES) is an ongoing National Eye Institutefunded multicenter effort coordinated through the University of California, San Diego under the leadership of Linda Zangwill, PhD. Its overarching goal is to characterize the importance of ancestry and other risk factors for the development and progression of glaucoma. Naira Khachatryan, MD, of the University of California, San Diego, presented an analysis of ADAGES that sheds some additional light on progression from glaucoma suspect to glaucoma. Overall, 722 eyes from 492 glaucoma suspects of both African and European ancestry were analyzed. These represented both suspects by IOP and suspects by nerve appearance who have now been followed with regularly scheduled visual field assessment for several years. "In the ADAGES cohort, glaucoma suspects of African descent were four times more likely to develop repeatable visual field damage than those of European descent, even after adjusting for other relevant risk factors," said Dr. Khachatryan. "Older age, worse baseline visual field, higher mean IOP, and larger disc area each contributed to an increased risk of future visual field damage." Interestingly, this analysis confirmed a finding that has been seen in other studies but not yet explained: Statin therapy for hypercholesterolemia tended to reduce the risk of visual field loss in glaucoma suspects. Take-home points From OHTS and ADAGES, we can surmise that the glaucoma suspects most likely to develop glaucoma over time are those with higher IOP, thinner corneas, older age, with higher IOP variation (which may be due to therapeutic non-adherence), and those of African ancestry. Intriguingly, we may be less concerned about patients on statin therapy for cholesterol issues. To help better understand the potential role of statins in glaucoma management, investigators at the University of Michigan are designing a prospective study to more fully explore this. Stay tuned. EW Contact information Gordon: mae@vrcc.wustl.edu Khachatryan: nairakhachatryan@gmail.com

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