New phase of OHTS about to begin for glaucoma care

The Ocular Hypertension Treatment Study (OHTS) provided evidence supporting early treatment of selected patients with OHT, especially in high-risk individuals identified by a glaucoma risk prediction model. A new phase designed to gather data to guide even more personalized care is about to begin.

TAKE HOME MESSAGE: The Ocular Hypertension Treatment Study (OHTS) provided evidence supporting early treatment of selected patients with OHT, especially in high-risk individuals identified by a glaucoma risk prediction model. A new phase designed to gather data to guide even more personalized care is about to begin.



By Cheryl Guttman Krader; Reviewed by Michael A. Kass, MD 

St. Louis, MO-Findings from the Ocular Hypertension Treatment Study (OHTS) based on median of 13 years of follow-up have had an important impact on clinical care. The story, however, is not yet complete as a new phase of OHTS is about to begin.

Michael A. Kass, MD, summarized the lessons learned from OHTS phases I and II and the motivation for and objectives of OHTS phase III.

“OHTS phases I and II provided us with level-1 evidence to support early treatment of selected patients with OHT and by inference that it is positive to treat glaucoma by lowering IOP,” said Dr. Kass, professor of ophthalmology, Washington University School of Medicine, St. Louis, MO.

In addition, the OHTS model for predicting 5-year glaucoma risk is now widely used and included in many preferred practice plans, there is a new CPT code for measuring central corneal thickness (CCT) because of OHTS, and research on CCT has increased, especially in terms of understanding its relationship to glaucoma, he noted.

“Now, in OHTS phase III, we will reexamine patients after 20+ years of follow-up with the hope of developing more informed, evidence-based guidelines about the optimal frequency of examinations and the potential benefits of early treatment,” Dr. Kass said.

About the study

OHTS, sponsored by the National Eye Institute and other organizations, was initially undertaken to address existing uncertainty over whether reducing IOP in patients with OHT delayed or prevented the development of primary open-angle glaucoma (POAG).

The study randomly assigned patients ages 40 to 80 years with untreated IOP of 24 to 32 mm Hg in one eye and 21 to 32 mm Hg in the fellow eye, normal visual field, and normal optic disc to observation or treatment with any commercially available topical ocular hypotensive medication with the goal of lowering IOP by 20% to ≤24 mm Hg.

After 5 years of follow-up and the end of phase I, medical treatment was found to reduce the incidence of POAG by 60%. Moreover, the benefit was achieved with little evidence of any safety concerns. Data from the study also led to creation of a prediction model for 5-year POAG risk that takes into account age, IOP, CCT, vertical cup/disc ratio, and visual field pattern standard deviation.

“While OHTS phase I provided proof of concept that lowering IOP with medication reduces the incidence of POAG, it did not address the question of when treatment should begin or indicate if all patients with OHT should receive early intervention,” Dr. Kass said.

“The answer to the latter question depends in large part on whether there is a penalty for delaying treatment,” he said. “In other words, if treatment for OHT is withheld and a patient goes on to develop glaucoma, has the train already left the station?”

In OHTS phase II, patients originally assigned to medication remained on treatment and patients in the original observation group became a delayed treatment group as they were started on medication after about 7.5 years medication group.

Early medical treatment did reduce the cumulative risk of POAG, and the absolute effect of treatment was greatest in the highest risk group but minimal in those at low-risk for developing POAG.

In addition, longitudinal visual field data from OHTS phase II indicated that starting treatment of glaucoma at diagnosis did not have a major negative impact on the subsequent course of disease.

OHTS phase II also showed that the risk of developing POAG continues over at least 15 years.

Why phase III?

The rationale for OHTS phase III derives from the growing emphasis on increasing the value and appropriateness of health care and reducing wasteful care-so-called personalized medicine, precision medicine, patient-centered care, or evidence-based care.

“While developing POAG is an important clinical landmark, the true goal of managing patients with OHT is to prevent the development of visual limitations from POAG during their lifetime while conserving medical resources. This means reducing unnecessary tests and visits and avoiding treatment that is unlikely to benefit the patient,” Dr. Kass said.

In 2013, statements from the US Preventatives Service Task Force (USPSTF) identified gaps in knowledge pertaining to a personalized medicine approach for POAG. The USPSTF noted there was inadequate evidence that treatment of increased IOP or early asymptomatic POAG reduces the number of persons who will develop impaired vision or quality of life.

Further, the group said that treatments that are effective in reducing IOP have potential harms and their effectiveness in reducing patient perceived impairments in vision related function is uncertain.

Finally, the USPSTF stated more evidence is needed on the link between the intermediate glaucoma outcomes of optic nerve damage and visual field loss and the final health outcomes of visual disability and patient reported outcomes.

OHTS phase III has multiple aims with one being to determine the 20-year incidence and severity of glaucoma in the OHTS cohort.

“Twenty years of follow-up approaches life expectancy for people diagnosed in their 60s and 70s and reaches about half of life expectancy for people diagnosed in their 40s and 50s. We will find out if the incidence of glaucoma increases, decreases, or stays the same over 20 years and how many people develop substantive visual field loss as opposed to just preperimetric glaucoma,” Dr. Kass said.

A second goal is to see if it is possible to develop a 20-year prediction model for stratifying OHT patients by their risk of developing POAG.

“Perhaps we will find out that it is better to take the 5-year model and repeat it periodically or whenever something changes,” Dr. Kass said.

Third, OHTS phase III aims to develop a model for predicting which OHT and early POAG patients will progress rapidly versus slowly. That information could be used to personalize evaluation and management strategies.

As a final specific aim, OHTS phase III will determine the frequency and severity of self-reported limitations associated with POAG and see if the limitations correlate with clinical findings.

“We are interested in knowing, for example, if there is a level of visual field loss where patients begin to have functional limitations or if it varies from patient to patient. We don’t think we know the answer now,” Dr. Kass said.



Michael A. Kass, MD


This article was adapted from Dr. Kass’ 2015 American Glaucoma Society Subspecialty Day Lecture. Dr. Kass has no personal financial interest to disclose.

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