The OHTS trial: Topical ocular hypotensive medication reduces risk of open-angle glaucoma [Classics Series]

1. At 5 years, the probability of developing open-angle glaucoma was significantly lower in the group that received topical ocular hypotensive medication compared to the observed group.

2. Older age, male gender, African-American ethnicity, larger cup-to-disc ratios, higher IOP, greater visual field deficits, heart disease, and reduced cornea thickness were predictors of the development of glaucoma.

Original Date of Publication: June 2002

Study Rundown: Glaucoma is the leading cause of irreversible blindness worldwide, and is thought to result from increased intraocular pressure (IOP). Prior to the Ocular Hypertension Treatment Study (OHTS), the efficacy of topical ocular hypotensive medications was unclear. In this study, over 1,500 patients were randomized to receive treatment or simply be observed. After 5 years, the probability of developing glaucoma was 60% lower in the group that received ocular hypotensive medication compared to the observed group. Treatment was not associated with an increase in side effects compared to the observation arm. Older age, male gender, African-American ethnicity, larger cup-to-disc ratios, higher IOP, greater visual field deficits, heart disease, and thinner corneas were found to be predictive of open-angle glaucoma. Limitations to the study include the fact that neither patients nor physicians were blinded to the randomization, although the endpoint evaluators were masked. The OHTS trial demonstrates that ocular anti-hypertensive treatment significantly reduces the incidence of primary open-angle glaucoma, and that patients identified as high-risk could benefit from earlier treatment.

Click to read Part 1 in Archives of Ophthalmology

Click to read Part 2 in Archives of Ophthalmology

In-Depth [randomized controlled study]: Approximately 1,636 patients who had no prior glaucomatous damage but elevated IOP in both eyes were randomized into treatment or observation arms. The treatment arm involved reducing IOP by 20% to at least 24 mm Hg using various topical hypotensive medications. Patients were evaluated semi-annually, including visual field testing and optic disc imaging. Masked reviewers assessed for signs of glaucomatous damage from these studies. After 5 years, the probability of developing primary open-angle glaucoma (POAG) was 4.4% and 9.5% in the treatment and observation groups, respectively (HR 0.40; 95%CI 0.27-0.59). In univariate analysis, age, sex, ethnicity, cup-to-disc ratios, elevated IOP, and thinner central corneal thickness (CCT) were found to increase the risk of developing glaucoma. Patients with significantly thin corneas (<555 µm) were found to have a hazard ratio of 3.4, reflecting how CCT can be an essential metric in risk assessment. Ultimately, the OHTS trial demonstrated that topical ocular antihypertensive therapy is essential to reducing progression to glaucoma, and identifying criteria to risk stratify patients.

Image: PD

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