June 2010

 

OPHTHALMOLOGY NEWS

 

When should we treat ocular hypertension?


by Tony Realini, M.D.

   

Phase II of the Ocular Hypertension Treatment Study offers new insights

Occlusion of macular branch of upper temporal arcade Source: Anand Sudhalkar, M.D.

The management of ocular hypertension has always been a clinical challenge. Some patients with high IOP will go on to develop glaucoma, while others will not. Can we reduce the risk of developing glaucoma by lowering IOP? If so, who should we treat? The Ocular Hypertension Treatment Study (OHTS) answered many of these questions. With the initial OHTS reports in the summer of 2001, we learned that a modest 20% reduction in IOP can cut the risk of developing glaucoma in half. OHTS also defined the risk factors that predispose one to the progression of glaucoma, facilitating the development of a calculator to determine our patients’ risk of converting to glaucoma.

“OHTS provided proof of concept that medications reduce the incidence of primary open-angle glaucoma,” said Michael Kass, M.D., professor and chair, Department of Ophthalmology and Visual Sciences, Washington University, St. Louis, and principal investigator of the OHTS.

But, as with all good research, the OHTS findings raised as many questions as they answered. “OHTS did not tell us, however, when we should begin medical treatment or if all ocular hypertensives should be treated,” he said. “Is there a penalty for delaying treatment for ocular hypertension?”

Phase II of the OHTS sheds some light on this question. Dr. Kass presented the results of OHTS Phase II for the first time in March at the 2010 American Glaucoma Society (AGS) meeting in Naples, Fla., where he delivered the annual AGS Lecture.

The goal of OHTS Phase II

“At the completion of OHTS Phase I,” Dr. Kass explained, “the subjects initially randomized to medication remained on medication, and the subjects initially randomized to observation were offered medication. Thus, OHTS Phase II had two groups: the early-treatment group and the delayed-treatment group who initiated therapy an average of 7.5 years later.”

The goal of therapy in OHTS Phase II was similar to that in Phase I, a 20% IOP reduction. Over the next 5.5 years (a total of 13 years for OHTS Phases I and II), IOP reduction in both the early-treatment and delayed-treatment groups was equivalent. Interestingly, said Dr. Kass, even in the era of prostaglandin analogues, 40%-45% of subjects required two or more medications to achieve the 20% IOP reduction.

“Does delaying therapy in ocular hypertension matter? Yes, but the effect for the delayed-treatment group is small,” Dr. Kass said.

In OHTS Phase I, the benefit of treatment in preventing glaucoma was clear. After five years, the incidence of glaucoma in the treated and observation groups was 4.4% and 9.5%, respectively. So at the end of five years, the two groups differed by about 5% and the two incidence curves were diverging. During Phase II, when everyone was on therapy, the two lines stopped diverging, indicating an equivalent incidence of glaucoma between groups during this phase of the study. After a total of 13 years of follow-up, the incidence of glaucoma in the early-treatment and delayed-treatment groups was 16% and 22%, respectively.

The delayed-treatment group did pay some price, however. Bilateral glaucoma was more common in this group compared to the early-treatment group. Similarly, more eyes in the delayed-treatment group experienced joint visual field and optic nerve endpoints than in the early-treatment group.

In the OHTS Phase I, African-Americans developed glaucoma more often than subjects of other races. This was also true in Phase II. “By the end of Phase II, the cumulative incidence of glaucoma was 28% in African-Americans and only 16% in non-African-Americans,” Dr. Kass said. In both Phases I and II, he said, the effect of race disappeared when adjusted for central corneal thickness and baseline cup-disc ratio.

Putting OHTS Phase II into practice

Dr. Kass pointed out that the data from both the OHTS and the European Glaucoma Prevention Study were pooled to develop a risk calculator, available online at ohts.wustl.edu/risk/calculator.html. He suggested that this calculator can help guide clinical management decisions for ocular hypertensive patients. “For low-risk patients—those with a five-year risk for glaucoma below 6%—OHTS Phase II demonstrated no benefit to early treatment versus delayed treatment,” he said. “These patients can be safely monitored without treatment. In contrast, those with five-year risk above 13% had a significantly lower risk of developing glaucoma with early treatment versus delayed treatment.” These patients may be better off with early treatment, he said.

“The risk calculator available online has been quite useful to illustrate to my patients the basis for my recommendation for treatment or observation,” said Robert Fechtner, M.D., professor, Institute of Ophthalmology and Visual Science, New Jersey Medical School, Newark, N.J., and a former OHTS Phase I investigator. “We had to make some guesses as to what represented low, moderate, and high risk. OHTS Phase II better establishes those thresholds.”

All clinical tools have limitations, and the risk calculator is no exception. “We should remember the calculator is only validated for patients who match the OHTS study subjects and have been tested similarly,” said Dr. Fechtner. For the rest of our patients it is an approximation. I recommend observation for patients at relatively low risk but will suggest treatment as a means of risk reduction for those at high risk of converting to glaucoma.” Some experts have suggested that all patients with ocular hypertension can be followed without treatment until the development of glaucoma. “I have no problem with that,” Dr. Kass said. “Starting treatment at the time of glaucoma diagnosis did not have a major impact on prognosis over five years.” But he cautioned that structural and functional surveillance must continue on these patients so as not to miss the development of glaucoma.

Editors’ note: Drs. Kass and Fechtner did not indicate any financial interests related to their comments.

Contact information

Fechtner: fechtner@umdnj.edu
Kass: kass@vision.wustl.edu

When should we treat ocular hypertension? When should we treat ocular hypertension?
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