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American Glaucoma Society presenters highlight new developments
One of the premier glaucoma meetings of the year is the annual meeting of the American Glaucoma Society (AGS), which was held this year in San Francisco. According to the AGS, “The goal of this meeting is to provide members and guests of the American Glaucoma Society with a professionally stimulating forum in which they can exchange information and ideas regarding the diagnosis and treatment of glaucoma and present new developments in glaucoma research.” For this column, I would like to present information from several of the posters and presentations at the meeting.
Epidemiology
Regarding the epidemiology of glaucoma, David S. Friedman, MD, and colleagues estimated the prevalence and distribution of open-angle glaucoma (OAG) in the United States by age, race/ethnicity and gender. The overall prevalence of OAG in the U.S. population 40 years of age and older is estimated to be 1.86%, with 1.57 million whites and 398,000 blacks affected. As our population gets older, it is estimated that the number of U.S. citizens with OAG will increase by 50%, from 2.2 million to 3.36 million, by 2020. Regarding race, African Americans had almost three times the age-adjusted prevalence of glaucoma as whites.
Nathan Congdon, MD, delivered a paper evaluating the number of individuals who are blind from glaucoma. He found that an estimated 87,800 Americans older than 40 years were blind from primary open-angle glaucoma (POAG) in 2000. Included in this group were 49,500 whites, 29,400 blacks and 6,300 Hispanics. POAG was the leading cause of blindness among Hispanics (28.6%), the second leading cause among blacks (26.0%) and the third leading cause among whites (6.4% of blindness). The number of blind people in the United States is projected to increase by more than 70% by 2020, with a similar increase expected in the cases related to glaucoma as the American population ages.
Work was presented from the Beaver Dam Eye Study, which investigated whether there is a similarity among family members related to the size of the optic disc, optic cup, cup/disc ratios and intraocular pressure. Vertical optic disc size and optic cup measurements were compared between parents and their children. Correlations were found and were greater between mother-child than between father-child. Correlations were similar between sibling pairs for optic disc parameters and IOPs as compared to parent-child correlations. Similarly, correlations of IOPs tended to be greater for mother-child than for father-child. These data provide ammunition in the argument that genetic determinants related to glaucoma may be more significant than environmental factors.
Pseudoexfoliation and glaucoma
Good and colleagues from the Mayo Clinic examined the question of how often pseudoexfoliation syndrome converts to pseudoexfoliative glaucoma. The Rochester Epidemiology Project database was used to identify newly diagnosed patients with pseudoexfoliation syndrome and pseudoexfoliative glaucoma in Olmsted County, Minn., between 1976 and 1991.
Two hundred ninety patients, with a mean age of 73 years, were diagnosed with pseudoexfoliation syndrome. Of these, 221 (76%) were women. Thirty-five patients were excluded because they had a diagnosis of pseudoexfoliative glaucoma. Of the remaining 255, 113 (44%) were diagnosed with pseudoexfoliative glaucoma during the study period. These patients had a mean age of 76, and 84 (74%) were women. The cumulative probability for treatment of ocular hypertension or conversion to pseudoexfoliative glaucoma was 20% at 5 years, 40% at 10 years and 44% at 15 years.
H. pylori and glaucoma
A series of papers from Greece have proposed that Helicobacter pylori may be involved in the development of glaucoma, probably due to an immunologic mechanism. The studies were controversial for several reasons, including lack of a proper control group.
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Fred Mikelberg, MD, and colleagues looked at this issue in a prospective case-control study. Ninety-seven consecutive patients attending a glaucoma clinic had blood samples drawn, including 38 patients with POAG, 19 with normal pressure glaucoma, 16 with pseudoexfoliation glaucoma and 24 with ocular hypertension. Ninety-four age-matched subjects without glaucoma served as a control population. Serum was analyzed for the presence of H. pylori-specific IgG antibodies by enzyme-linked immunosorbent assay (ELISA). Seropositivity for H. pylori was higher in patients with glaucoma (26.0%) than in controls (20.2%), but it did not achieve statistical significance. The following patients were seropositive: 26.3% of POAG patients, 26.3% of normal pressure glaucoma patients, 25.0% of the patients with pseudoexfoliation syndrome and 25.0% of patients with ocular hypertension. This work suggests that exposure to H. pylori infection is not associated with the development of OAG and illustrates the importance of using a control group.
SLT vs. ALT
Selective laser trabeculoplasty (SLT) is a new procedure and is a modification of argon laser trabeculoplasty (ALT). It uses a different laser and may be less traumatic to the trabecular meshwork. This could have benefits if treatments can be repeated with comparable efficacy.
A study done by Mark Juzych, MD, and associates compared the reduction in IOP with SLT to ALT. The study evaluated 201 eyes of 201 patients with uncontrolled chronic OAG. Forty-two eyes underwent SLT, and 159 eyes underwent ALT. Success was defined as no additional need for glaucoma surgery and an IOP of 20 mm Hg with no additional medications. The success rate was similar using Kaplan-Meier survival analysis with log-rank test.
At 1 year, success was 36% for ALT and 30% for SLT. At 2 years, success was 28% compared to 22%; and at 3 years, success was 25% compared with 19%. Both ALT and SLT groups showed significant IOP reductions. No differences were observed between the two groups during the 3-year follow-up period. In this study, SLT was found to be as effective as ALT in lowering IOP. Still, future studies are needed to understand whether the ability to lower IOP is repeatable when done over time.
Latanoprost and heat
One concern in regard to latanoprost is the medication’s stability and whether or not it will degrade when exposed to either heat or UV light, leading to a degradation in the active ingredient and loss of efficacy. Rohit Varma, MD, MPH, and colleagues investigated this issue. Bottles were either dispensed from a pharmacy or the clinic. All returned bottles were masked, and the residual content was analyzed for latanoprost concentration using a reverse-phase high-performance liquid chromatography (HPLC) technique. To ensure validation, an additional nine bottles filled with various quantities of drug or sterile water were included in the analysis.
Of the 110 patients enrolled in the study, 89 patients returned their bottles. All patients stored the bottles in a non-refrigerated environment. Of the 89 patient bottles that were sent for HPLC analyses, 69 contained sufficient volume for analysis. The mean concentration of all samples (excluding controls) was 48.31 g/mL. Low concentrations of latanoprost could be due to loss of stability, error in the HPLC method or error in handling of the bottle.
The study was conducted in the Palm Springs area where the average high temperature during the study was 81°F. In this community setting, the concentration of latanoprost 0.005% was maintained within the required limit (90% of labeled concentration) for the majority of patients. Still, one concern not addressed in this study is how the drug would hold up when patients receive it from mail-order pharmacies. In this situation, there are greater opportunities for the drug to be exposed to elevated temperatures while in transit. Still, it appears that latanoprost is a hardy molecule that does not degrade easily when exposed to heat.
Prostaglandins: missing a dose
Prostaglandins enjoy several advantages over other glaucoma medications, including the ability to reduce the IOP when used just once per day. Another advantage is that they are a forgiving medication, with IOP reduction occurring over a long period of time.
Harvey DuBiner, MD, evaluated IOP elevation when a patient forgets a daily dose. In this study, 35 patients with elevated IOPs (24 to 36 mm Hg at 8 a.m.) were washed out from their prior medications. Baseline IOP measurements were taken every 4 hours for 24 hours. Patients then received either Travatan (travoprost ophthalmic solution 0.004%, Alcon) or Xalatan (latanoprost ophthalmic solution 0.005%, Pharmacia), every day at 8 p.m. After 14 days of therapy, IOP was measured prior to the final dose at 8 p.m. and then every 4 hours for 44 hours.
Diurnal baseline IOPs ranged from 21.4 to 25.1 mm Hg for Travatan and 22.2 to 25.4 mm Hg for Xalatan. Just prior to the 8 p.m. dose on day 14, mean IOP was 16.3 ± 3.96 for Xalatan and 14.3 ± 3.38 mm Hg for Travatan. During the 44-hour washout, the diurnally adjusted ocular hypotensive effect of Travatan was greater than that of Xalatan at eight of 12 measurements. The largest differences between treatments (up to 3.3 mm Hg) were observed late in the day (4 p.m. and 10 p.m.). At 44 hours after the last dose, mean reductions were –7.7 mm Hg for Travatan and –6.0 mm Hg for Xalatan. This indicates that when patients miss a dose, they may continue to experience an ocular hypotensive effect, though less than at peak.
Ocugene Test
Jon Polansky, MD, PhD, and colleagues evaluated a new genetic test, the Ocugene Test (InSite Vision, Alameda, Calif.) and studied whether there is a relationship between a promoter genetic defect (myocilin mt.1+) and severity of glaucoma. The Ocugene test looks for defects related to the myocilin gene. Myocilin is one of the few genes identified that is related to the development of OAG.
The study used blood samples and obtained a genetic analysis for 147 POAG patients, all of whom were older than 35 years of age, who had a minimum follow-up time of 8 years (average of about 15 years). Optic disc and visual field damage were graded separately in a masked fashion using eight-point graded scales previously reported by George Spaeth, MD. The mt.1(+) genotype (promoter) was found in approximately 15% of the patients examined. Analysis was performed, evaluating changes in disc and field scores over time, watching for progression.
Time-to-event analyses using the Cox proportional hazards model showed progression using separate analyses of optic disc and visual field measures. Statistical significance was demonstrated, taking into account the effects of other baseline risk factors (age, family history, initial drug treatment, initial surgical treatment, diabetes, gender, myopia and initial disease severity). The finding that the mt.1(+) genotype showed progression for both optic disc and visual field measures, not related to other baseline clinical factors, appears to support the use of the Ocugene test in selected POAG patients.
Home tonometer
A new instrument, the Proview Home Pressure Monitor (Bausch & Lomb, Rochester, N.Y.), has been developed to allow patients to monitor their IOPs at home. Ramesh Ayyala, and colleagues evaluated the accuracy of the Proview Home Pressure Monitor as compared to the Goldmann tonometer. Forty patients were trained in the use of the Proview Home Pressure Monitor. IOP measurements were obtained using Goldmann and Proview tonometers and were highly correlated for the right and left eyes. Agreement between the Goldmann and Proview methods within 2 mm Hg was 88% for the right eye and 95% for the left eye. Although IOP agreement between the two methods was excellent, values with the Proview method were, on average, 1 mm Hg higher than those obtained by the Goldmann method.
Glaucoma is an evolving subspecialty, with new medications, surgical procedures, monitoring devices and diagnostic instruments. While each of these changes is small, it is obvious that the diagnosis and management of glaucoma is evolving with increasing precision.