Ocular Hypertension Treatment Study (OHTS)

Purpose

  • To determine whether medical reduction of intraocular pressure prevents or delays the onset of glaucomatous visual field loss and/or optic disc damage in ocular hypertensive subjects judged to be at moderate risk for developing open-angle glaucoma. 
  • To produce natural history data to assist in identifying patients at most risk for developing open-angle glaucoma and those most likely to benefit from early medical treatment. 

  • To quantify risk factors for developing open-angle glaucoma among ocular hypertensive subjects.

Description

The Ocular Hypertension Treatment Study (OHTS) is a long-term, randomized, controlled multicenter clinical trial. Ocular hypertensive subjects judged to be at moderate risk of developing primary open-angle glaucoma are randomly assigned to either close observation only or a stepped medical regimen. Medical treatment consists of all commercially available topical antiglaucoma agents.

After completion of baseline measures (IOP, visual fields, disc photos) and randomization, the subjects are followed for a minimum of 5 years with automated threshold central static perimetry (Humphrey program 30-2) twice yearly and stereoscopic optic disc photographs once yearly. Study end points are reproducible visual field loss and/or progressive optic disc damage in either eye of a patient. All visual fields and optic disc photographs are read in a masked fashion in Reading Centers.

In the 1991 Baltimore Eye Survey, African Americans were shown to have a prevalence of open-angle glaucoma four to five times higher than whites. Given this high prevalence of glaucoma in the African American population, it is important to recruit and follow an adequate sample of African American subjects in the trial (approximately 25 percent of the total patient sample).

At the conclusion of this study, practitioners should be able to make reasonable estimates of risk for individual ocular hypertensive patients and to determine which ocular hypertensive individuals are most likely to benefit from early prophylactic medical treatment.
 

Patient Eligibility

Men and nonpregnant women between the ages of 40 and 80 with IOP greater than or equal to 24 mm Hg but less than or equal to 32 mm Hg in at least one eye and IOP greater than or equal to 21 but less than or equal to 32 mm Hg in the fellow eye, as well as normal visual fields and optic discs are eligible for the trial. Patients presenting with best-corrected visual acuity worse than 20/40 in either eye, previous intraocular surgery, a life-threatening or debilitating disease, secondary causes of elevated IOP, angle-closure glaucoma or anatomically narrow angles, other diseases that can cause visual field loss, background diabetic retinopathy, optic disc abnormalities that can produce visual field loss or obscure the interpretation of the optic disc, or unwillingness to undergo random assignment are excluded from the trial.
 

Results

In univariate analyses, baseline factors that predicted the development of primary open-angle glaucoma (POAG) included older age, race (African American), sex (male), larger vertical cup-disc ratio, larger hoizontal cup-disc ratio, higher intraocular pressure, greater Humphrey visual field pattern standard deviation, heart disease, and thinner central corneal measurement. In multivariate analyses, baseline factors that predicted POAG included older age, larger vertical or hotrizontal cup-disc ratio, higher intraocular pressure, greater pattern standard deviation, and thinner central corneal meaturement.

During the course of the study, the mean ±SD reduction in IOP in the medication group was 22.5 percent ±9.9 percent. The IOP declined by 4.0 percent ± 11.6 percent in the observation group. At 60 months, the cumulative probability of developing POAG was 4.4 percent in the medication group and 9.5 percent in the observation group. There was little evidence of increased systemic or ocular risk associated with ocular hypotensive medication.

Topical ocular hypotensive medication was effective in delaying or preventing onset of POAG in individuals with elevated IOP. Although this does not imply that all patients with borderline or elevated IOP should receive medication, clinicians should consider initiating treatment for individuals with ocular hypertension who are at moderate or high risk for developing POAG.
 

Publications:
 

  • Kass MA, Heuer DK, Higginbotham EJ, Johnson CA, Keltner JL, Miler JP, Parrish II RK, Wilson MR, Gordon MO, for the Ocular Hypertension Treatment Study Group: The Ocular Hypertension Treatment Study: A Randomized Trial Determines that Topical Ocular Hypotensive Medication Delays or Prevents the Onset of Primary Open-Angle Glaucoma. Arch Ophthalmol 120: 701-713, 2002.
  • Gordon MO, Beiser JA, Brandt JD, Heuer DK, Higginbotham EJ, Johnson CA, Keltner JL, Miller JP, Parrish II RK, Wilson MR, Kass MA, for the Ocular Hypertension Treatment Study Group: The Ocular Hypertension Treatment Study: Baseline Factors that Predict the Onset of Primary Open-Angle Glaucoma. Arch Ophthalmol 120: 714-720, 2002.
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