Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2021 Apr 15;139(5):1-9.
doi: 10.1001/jamaophthalmol.2021.0341. Online ahead of print.

Assessment of Cumulative Incidence and Severity of Primary Open-Angle Glaucoma Among Participants in the Ocular Hypertension Treatment Study After 20 Years of Follow-up

Michael A Kass  1 , Dale K Heuer  2 , Eve J Higginbotham  3 , Richard K Parrish  4 , Cheryl L Khanna  5 , James D Brandt  6 , Joern B Soltau  7 , Chris A Johnson  8 , John L Keltner  9 , Julia B Huecker  1 , Bradley S Wilson  1 , Lei Liu  1 , J Phillip Miller  1 , Harry A Quigley  10 , Mae O Gordon  11 ; Ocular Hypertension Study Group
Collaborators, Affiliations

Assessment of Cumulative Incidence and Severity of Primary Open-Angle Glaucoma Among Participants in the Ocular Hypertension Treatment Study After 20 Years of Follow-up

Michael A Kass et al. JAMA Ophthalmol. .

Erratum in

  • Labeling Errors in Figure.
    [No authors listed] [No authors listed] JAMA Ophthalmol. 2021 Sep 1;139(9):1042. doi: 10.1001/jamaophthalmol.2021.2850. JAMA Ophthalmol. 2021. PMID: 34292316 Free PMC article. No abstract available.

Abstract

Importance: Ocular hypertension is an important risk factor for the development of primary open-angle glaucoma (POAG). Data from long-term follow-up can be used to inform the management of patients with ocular hypertension.

Objective: To determine the cumulative incidence and severity of POAG after 20 years of follow-up among participants in the Ocular Hypertension Treatment Study.

Design, setting, and participants: Participants in the Ocular Hypertension Treatment Study were followed up from February 1994 to December 2008 in 22 clinics. Data were collected after 20 years of follow-up (from January 2016 to April 2019) or within 2 years of death. Analyses were performed from July 2019 to December 2020.

Interventions: From February 28, 1994, to June 2, 2002 (phase 1), participants were randomized to receive either topical ocular hypotensive medication (medication group) or close observation (observation group). From June 3, 2002, to December 30, 2008 (phase 2), both randomization groups received medication. Beginning in 2009, treatment was no longer determined by study protocol. From January 7, 2016, to April 15, 2019 (phase 3), participants received ophthalmic examinations and visual function assessments.

Main outcomes and measures: Twenty-year cumulative incidence and severity of POAG in 1 or both eyes after adjustment for exposure time.

Results: A total of 1636 individuals (mean [SD] age, 55.4 [9.6] years; 931 women [56.9%]; 1138 White participants [69.6%]; 407 Black/African American participants [24.9%]) were randomized in phase 1 of the clinical trial. Of those, 483 participants (29.5%) developed POAG in 1 or both eyes (unadjusted incidence). After adjusting for exposure time, the 20-year cumulative incidence of POAG in 1 or both eyes was 45.6% (95% CI, 42.3%-48.8%) among all participants, 49.3% (95% CI, 44.5%-53.8%) among participants in the observation group, and 41.9% (95% CI, 37.2%-46.3%) among participants in the medication group. The 20-year cumulative incidence of POAG was 55.2% (95% CI, 47.9%-61.5%) among Black/African American participants and 42.7% (95% CI, 38.9%-46.3%) among participants of other races. The 20-year cumulative incidence for visual field loss was 25.2% (95% CI, 22.5%-27.8%). Using a 5-factor baseline model, the cumulative incidence of POAG among participants in the low-, medium-, and high-risk tertiles was 31.7% (95% CI, 26.4%-36.6%), 47.6% (95% CI, 41.6%-53.0%), and 59.8% (95% CI, 53.1%-65.5%), respectively.

Conclusions and relevance: In this study, only one-fourth of participants in the Ocular Hypertension Treatment Study developed visual field loss in either eye over long-term follow-up. This information, together with a prediction model, may help clinicians and patients make informed personalized decisions about the management of ocular hypertension.

Trial registration: ClinicalTrials.gov Identifier: NCT00000125.

PubMed Disclaimer

Conflict of interest statement

Conflict of Interest Disclosures: Dr Kass reported receiving grants from Merck, the National Institutes of Health, Pfizer, and Research to Prevent Blindness during the conduct of the study and owning stock options in Smartlens outside the submitted work. Dr Heuer reported receiving personal fees from Washington University as a subcontractor for the National Eye Institute and the National Institutes of Health during the conduct of the study and receiving personal fees from Advanced Clinical (for serving as consultant to Google) and InnFocus outside the submitted work. Dr Higginbotham reported receiving grants from the National Eye Institute and being a subcontractor for Washington University during the conduct of the study. Ms Huecker reported receiving grants from the National Eye Institute during the conduct of the study and outside the submitted work. Mr Wilson reported receiving grants from the National Eye Institute during the conduct of the study. Dr Liu reported receiving grants from the National Institutes of Health during the conduct of the study and receiving consulting fees from Mesoblast outside the submitted work. Mr Miller reported receiving grants from the National Institutes of Health during the conduct of the study and receiving grants from the National Institutes of Health and the Patient-Centered Outcomes Research Institute and personal fees from General Dynamics (US Department of Defense) and the National Institutes of Health outside the submitted work. Dr Brandt reported receiving grants from the National Eye Institute during the conduct of the study and receiving consulting fees from Aerie Pharmaceuticals and Graybug Vision outside the submitted work. Dr Soltau reported receiving grants from the National Institutes of Health during the conduct of the study. Dr Gordon reported receiving grants from the National Eye Institute during the conduct of the study. No other disclosures were reported.

Figures

Figure 1.
Figure 1.. Participant Flowchart for Ocular Hypertension Treatment Study (OHTS) Phases 1, 2, and 3
POAG indicates primary open-angle glaucoma. aData collection period. bAssessment of visual function required an OHTS examination or ocular and medical history after January 1, 2013, or within 2 years of death. cThe cumulative number of deaths from February 1994 to April 2019 was 515, which includes 225 participants with OHTS 1 and OHTS 2 visits or medical history within 2 years of death, 19 participants who died after completing an OHTS 3 visit, and 9 participants who died but provided medical history after January 2013.
Figure 2.
Figure 2.. Kaplan-Meier Curves of Cumulative Incidence of Primary Open-Angle Glaucoma (POAG) at 5, 10, 15, and 20 Years
A, Cumulative incidence of POAG by treatment group. B, Cumulative incidence of POAG by race. C, Cumulative incidence of POAG by risk tertile. The whiskers indicate 95% CIs.
See this image and copyright information in PMC

Comment in

References

    1. Kass MA, Heuer DK, Higginbotham EJ, et al. . 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. 2002;120(6):701-713. doi:10.1001/archopht.120.6.701 - DOI - PubMed
    1. Gordon MO, Beiser JA, Brandt JD, et al. . The Ocular Hypertension Treatment Study: baseline factors that predict the onset of primary open-angle glaucoma. Arch Ophthalmol. 2002;120(6):714-720. doi:10.1001/archopht.120.6.714 - DOI - PubMed
    1. Gordon MO, Torri V, Miglior S, et al. ; Ocular Hypertension Treatment Study Group; European Glaucoma Prevention Study Group . Validated prediction model for the development of primary open-angle glaucoma in individuals with ocular hypertension. Ophthalmology. 2007;114(1):10-19. doi:10.1016/j.ophtha.2006.08.031 - DOI - PMC - PubMed
    1. Medeiros FA, Weinreb RN, Sample PA, et al. . Validation of a predictive model to estimate the risk of conversion from ocular hypertension to glaucoma. Arch Ophthalmol. 2005;123(10):1351-1360. doi:10.1001/archopht.123.10.1351 - DOI - PubMed
    1. Kass MA, Gordon MO, Gao F, et al. ; Ocular Hypertension Treatment Study Group . Delaying treatment of ocular hypertension: the ocular hypertension treatment study. Arch Ophthalmol. 2010;128(3):276-287. doi:10.1001/archophthalmol.2010.20 - DOI - PMC - PubMed

Associated data