Ocular Hypertension Treatment Study

Ocular Hypertension Treatment Study
Name	Ocular Hypertension Treatment Study
Acronym	OHTS
Phase	N/A
Status	Completed
Sponsor	National Eye Institute
Locations	United States, multiple centers
Start date	1994
Completion date	2002

Ocular Hypertension Treatment Study The Ocular Hypertension Treatment Study was a multicenter, randomized clinical trial assessing whether topical intraocular pressure lowering could delay or prevent the onset of primary open-angle glaucoma in eyes with elevated intraocular pressure. The trial involved collaboration among academic centers, funding agencies, and professional societies, enrolling participants who were followed with standardized clinical examinations and visual field testing. Results influenced clinical guidelines, regulatory decisions, and subsequent research on glaucoma prevention and risk stratification.

Background

The trial was initiated amid rising interest from the National Eye Institute, academic institutions such as Johns Hopkins University, Massachusetts Eye and Ear, and Mayo Clinic, and professional organizations including the American Academy of Ophthalmology and the Association for Research in Vision and Ophthalmology. Contemporary debates involved clinicians from Harvard Medical School, University of California, San Francisco, and University of Miami concerning management strategies favored by authors publishing in journals like the New England Journal of Medicine and JAMA. Influences included prior observational cohorts from Blue Mountains Eye Study, randomized trials such as those coordinated by the World Health Organization, and epidemiologic reports from the Framingham Heart Study and Beaver Dam Eye Study that highlighted risk factors for optic neuropathies. Funding and ethical oversight invoked standards from the Department of Health and Human Services and institutional review boards at centers like Duke University and Columbia University.

Study Design and Methods

OHTS was designed as a randomized, controlled trial enrolling participants from clinical centers including University of Wisconsin, University of Illinois at Chicago, and Bascom Palmer Eye Institute. Eligibility criteria were informed by diagnostic methods taught at Wilmer Eye Institute and testing protocols from the American Academy of Ophthalmology. Participants underwent standardized pachymetry from devices validated in studies at Stanford University, perimetry using technology developed at Horton Research Laboratory, and optic disc assessment protocols aligned with methodology used at Scheie Eye Institute. Randomization assigned subjects to either topical intraocular pressure lowering therapy using medications approved after review by the Food and Drug Administration or to observation, with outcomes adjudicated by masked committees modeled on endpoints committees from trials at Oxford University and Vanderbilt University. Statistical analysis plans referenced methods from investigators affiliated with University of Michigan and University of Pennsylvania and employed data coordinating operations similar to those at the Clinical and Translational Science Awards network.

Results

Primary outcomes reported that treatment reduced the 5-year incidence of primary open-angle glaucoma compared with observation, a finding presented at meetings of the Association for Research in Vision and Ophthalmology and published in venues read by clinicians at Moorfields Eye Hospital and researchers at Basel University Hospital. Results included stratified risk information associated with central corneal thickness measurements, age strata familiar to clinicians at Mount Sinai Hospital, and baseline intraocular pressure ranges described in meta-analyses involving groups at University College London. Data analyses were conducted by statisticians with affiliations to Johns Hopkins Bloomberg School of Public Health and Harvard T.H. Chan School of Public Health, and were interpreted in the context of concurrent epidemiologic findings from cohorts such as Rotterdam Study and Blue Mountains Eye Study.

Interpretation and Impact

Investigators and guideline panels at organizations like the American Academy of Ophthalmology and the American Glaucoma Society used OHTS findings to refine recommendations for monitoring and treating patients with elevated intraocular pressure. The trial influenced regulatory and reimbursement discussions involving the Food and Drug Administration and national health authorities, and shaped academic curricula at institutions including Columbia University Vagelos College of Physicians and Surgeons and University of California, Los Angeles. Clinical practice patterns cited in surveys by groups such as the American Medical Association and clinical outcomes research at Kaiser Permanente reflected changes attributable to OHTS. The study also informed device and pharmaceutical research programs at companies collaborating with academic centers like Stanford University School of Medicine.

Criticisms and Limitations

Critiques from investigators at centers such as Yale School of Medicine, University of Toronto, and Imperial College London highlighted issues including the generalizability of trial populations, the applicability of trial endpoints to community settings, and the interpretation of subgroup analyses. Methodological discussions referenced standards from the CONSORT initiative and statistical perspectives voiced by scholars at University of Oxford and London School of Hygiene & Tropical Medicine. Debates published in journals read by researchers at University of Edinburgh and University of Melbourne questioned long-term cost-effectiveness and the translation of trial protocols into routine care in systems like the National Health Service and private networks like Mayo Clinic Health System.

Subsequent Research and Legacy

Following OHTS, follow-up studies and secondary analyses were conducted by investigators affiliated with Duke University School of Medicine, University of Alabama at Birmingham, and Johns Hopkins University School of Medicine, addressing long-term outcomes and risk prediction models incorporating factors studied at Massachusetts General Hospital and Cleveland Clinic. The study’s influence is evident in contemporary trials funded by agencies including the National Institutes of Health and in guideline updates by professional societies such as the American Academy of Ophthalmology and European Glaucoma Society. OHTS data remain a reference point for systematic reviews produced by groups at Cochrane and for clinical decision tools developed at Mayo Clinic and University of California, San Diego.

Category:Clinical trials in ophthalmology