Many important clinical outcomes a product of OHTS

The long-running Ocular Hypertension Treatment Study has produced many important clinical findings. Among them is the conclusion that African-American and white patients have similar responses to treatment with topical beta-blockers and prostaglandin analogs. The study also found that optic disk hemorrhages are a risk factor for progression from ocular hypertension to primary open-angle glaucoma.

Key Points

St. Louis-The long-term Ocular Hypertension Treatment Study (OHTS) has produced substantial information over the years about progression from ocular hypertension to glaucoma. Two of the most important findings concern the response of individuals in different racial groups to pressure-lowering drugs and the importance of detecting optic disk hemorrhages, which are a risk factor for development of disease, said Michael A. Kass, MD, professor and chairman, Department of Ophthalmology and Visual Sciences, Washington University School of Medicine, St. Louis.

Dr. Kass is the study chairman for OHTS, sponsored by the National Eye Institute and the National Center for Minority Health and Health Disparities. The study compared the IOP response of African Americans and whites to topical glaucoma medication. The study began in January 1993; enrollment ended in 1996 with more than 1,500 participants who were followed for at least 5 years. More than 30 U.S. centers participated.

The study of potential racial disparities in response to treatment used initial one-eyed medication trials from OHTS. Investigators assigned 538 participants in a medication group to receive topical beta-blockers for 4 ± 2 weeks. Later, 191 patients who had been in an observation group and were moving on to treatment received one of the prostaglandin analogs in one eye for 4 ± 2 weeks.

Patient response

To assess patient response to the study medications, investigators performed multiple linear regression analysis with dependent variable IOP at 4 to 6 weeks and independent variables: race, baseline IOP, corneal thickness, hypertension, diabetes, gender, and age.

Results indicated that African Americans and whites appear to respond similarly to short-term treatment with fixed doses of topical beta-blockers and prostaglandin analogs. The response to beta-blockers among whites was a 24 ± 12% reduction in IOP; among African Americans the reduction was 23.6 ± 11.9%. In response to treatment with topical prostaglandins, whites had an IOP reduction of 24.8 ± 14.5%, while African Americans had a reduction of 30.3 ± 14.1%.

"The measured IOP reduction was associated with baseline IOP and corneal thickness," Dr. Kass said. "That is, the higher the baseline IOP, the greater the IOP reduction, and the thinner the cornea, the greater the apparent IOP reduction. Race was not significant in the multivariate model."

Optic disk hemorrhages

OHTS also evaluated the detection and prognostic significance of optic disk hemorrhages. This was done by comparing the detection rate by twice-yearly clinical examination versus annual review of disk photos at an Optic Disk Reading Center (ODRC). Investigators also sought to determine whether a disk hemorrhage was associated with an elevated risk of developing primary open-angle glaucoma (POAG) and to identify factors associated with the occurrence of disk hemorrhage.

A prospective observation study was conducted from February 1994 through November 2003. For this study, a glaucomatous disk hemorrhage was defined as flame- or splinter-shaped with radial orientation perpendicular to the disk margin. Disk hemorrhage caused by a disease other than glaucoma, such as vascular occlusive disease, diabetic retinopathy, or ischemic optic neuropathy, was excluded.

Results showed that the ODRC was more sensitive at detecting disk hemorrhages despite the fact that clinical exams were performed twice as often as the review of photographs, Dr. Kass said. The ODRC detected 128 hemorrhages, while 33 were found through clinical examinations. Clinicians detected only 21 of the 128 hemorrhages (16%) by reviewing photos.

Analysis further revealed that 17 (13.2%) of the eyes with a disk hemorrhage developed POAG and 111 (86.7%) did not during a median follow-up of 30.7 months.

"Disk hemorrhage is a risk factor for developing glaucoma. In a multivariate model the hazard ratio is 3.7," Dr. Kass said. "The majority of people who had a disk hemorrhage did not go on to develop glaucoma over a period of 30 months. The median time from a disk hemorrhage to developing glaucoma by our study criteria was 13 months."

Several reasons explain the greater sensitivity of the review of photographs, Dr. Kass said. First, technicians at the ODRC spent a long time reviewing the photos, probably more time than the clinicians spent on patient examinations. Secondly, it's likely that the physicains came to depend on the reading center over time for photo review. Lastly, it's easier to look at photos than at patients, he explained.

Not all ophthalmologists use optic disk photography, and other forms of technology for studying the optic disk will not always detect a disk hemorrhage, Dr. Kass added. Therefore, given the prognostic value of hemorrhages, it is still important for clinicians to look closely at the optic disk during patient exams.