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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

Educational Objective
To determine the cumulative incidence and severity of primary open-angle glaucoma (POAG) after 20 years of follow-up among participants in the Ocular Hypertension Treatment Study (OHTS).
1 Credit CME
Key Points

Question  Do 20-year follow-up data from the Ocular Hypertension Treatment Study inform the management of patients with ocular hypertension?

Findings  In this cohort study of 1636 participants with ocular hypertension who participated in the Ocular Hypertension Treatment Study, the 20-year cumulative incidence of primary open-angle glaucoma was 46% in 1 or both eyes, and the cumulative incidence of visual field loss was 25% after adjusting for exposure time.

Meaning  This study’s findings, together with a predictive model, may help clinicians and patients make informed personalized decisions about the management of ocular hypertension.

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.

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CME Disclosure Statement: Unless noted, all individuals in control of content reported no relevant financial relationships. If applicable, all relevant financial relationships have been mitigated.

Article Information

Accepted for Publication: January 26, 2021.

Published Online: April 15, 2021. doi:10.1001/jamaophthalmol.2021.0341

Correction: This article was corrected on July 22, 2021, to fix labeling errors in Figure 2A.

Corresponding Author: Mae O. Gordon, PhD, Department of Ophthalmology and Visual Sciences, Washington University School of Medicine in St Louis, 660 S Euclid, CB 8096, St Louis, MO 63122 (gordon.mae@wustl.edu).

Author Contributions: Drs Gordon and Kass had full access to all of the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis.

Concept and design: Kass, Heuer, Higginbotham, Parrish, Johnson, Miller, Brandt, Khanna, Quigley, Gordon.

Acquisition, analysis, or interpretation of data: Heuer, Johnson, Keltner, Huecker, Wilson, Liu, Miller, Brandt, Khanna, Soltau, Gordon.

Drafting of the manuscript: Kass, Parrish, Wilson, Liu, Khanna, Quigley, Gordon.

Critical revision of the manuscript for important intellectual content: Kass, Heuer, Higginbotham, Johnson, Keltner, Huecker, Miller, Brandt, Khanna, Soltau, Gordon.

Statistical analysis: Wilson, Liu, Miller, Gordon.

Obtained funding: Kass, Brandt, Gordon.

Administrative, technical, or material support: Kass, Heuer, Higginbotham, Johnson, Keltner, Huecker, Brandt, Khanna, Gordon.

Supervision: Kass, Parrish, Soltau, Gordon.

Other—Served on study Executive Committee: Brandt.

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.

Funding/Support: This study was supported by grant UL1 TR002345 (Drs Liu and Gordon and Mr Miller) from the Institute of Clinical and Translational Sciences; grants U10 EY09341 (Dr Gordon), U10 EY09370 (Dr Kass), UG1 EY025180 (Dr Kass, chairman), UG1 EY025181 (Dr Gordon, clinical center), UG1 EY025182 (Dr Gordon, coordinating center), and UG1 EY025183 (Dr Kass, resource centers) from the National Eye Institute; grant P30 EY002687 (Dr Gordon, Ms Huecker, and Mr Wilson) from the National Institutes of Health; and an unrestricted grant from Research to Prevent Blindness.

Role of the Funder/Sponsor: The funding organizations had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; and decision to submit the manuscript for publication.

Group Information: The Ocular Hypertension Study Group Investigators, Coordinators, and Executive Committee are listed in Supplement 2.

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 PubMedGoogle ScholarCrossref
2.
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 PubMedGoogle ScholarCrossref
3.
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 PubMedGoogle Scholar
4.
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 PubMedGoogle ScholarCrossref
5.
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 PubMedGoogle Scholar
6.
Gordon  MO , Kass  MA .  The Ocular Hypertension Treatment Study: design and baseline description of the participants.   Arch Ophthalmol. 1999;117(5):573-583. doi:10.1001/archopht.117.5.573 PubMedGoogle ScholarCrossref
7.
Gordon  MO , Higginbotham  EJ , Heuer  DK ,  et al; Ocular Hypertension Treatment Study.  Assessment of the impact of an endpoint committee in the Ocular Hypertension Treatment Study.   Am J Ophthalmol. 2019;199:193-199. doi:10.1016/j.ajo.2018.11.006 PubMedGoogle ScholarCrossref
8.
Bengtsson  B , Heijl  A .  Inter-subject variability and normal limits of the SITA standard, SITA fast, and the Humphrey full threshold computerized perimetry strategies, SITA STATPAC.   Acta Ophthalmol Scand. 1999;77(2):125-129. doi:10.1034/j.1600-0420.1999.770201.x PubMedGoogle ScholarCrossref
9.
Sharma  AK , Goldberg  I , Graham  SL , Mohsin  M .  Comparison of the Humphrey Swedish interactive thresholding algorithm (SITA) and full threshold strategies.   J Glaucoma. 2000;9(1):20-27. doi:10.1097/00061198-200002000-00005 PubMedGoogle ScholarCrossref
10.
Sun J. The Statistical Analysis of Interval-Censored Failure Time Data. Springer; 2006.
11.
Hodapp  E , Parrish  RK  II , Anderson  DR .  Clinical Decisions in Glaucoma. 1st ed. Mosby; 1993.
12.
Lundberg  L , Wettrell  K , Linner  E .  Ocular hypertension. a prospective twenty-year follow-up study.   Acta Ophthalmol (Copenh). 1987;65(6):705-708. doi:10.1111/j.1755-3768.1987.tb07067.x PubMedGoogle ScholarCrossref
13.
Hovding  G , Aasved  H .  Prognostic factors in the development of manifest open angle glaucoma. a long-term follow-up study of hypertensive and normotensive eyes.   Acta Ophthalmol (Copenh). 1986;64(6):601-608. doi:10.1111/j.1755-3768.1986.tb00675.x PubMedGoogle ScholarCrossref
14.
Oskarsdottir  SE , Heijl  A , Midlov  P , Bengtsson  B .  Lifetime risk of visual impairment resulting from glaucoma in patients initially followed up for elevated intraocular pressure.   Ophthalmol Glaucoma. 2020;3(1):60-65. doi:10.1016/j.ogla.2019.09.002 PubMedGoogle ScholarCrossref
15.
Gordon  MO , Gao  F , Beiser  JA , Miller  JP , Kass  MA .  The 10-year incidence of glaucoma among patients with treated and untreated ocular hypertension.   Arch Ophthalmol. 2011;129(12):1630-1631. doi:10.1001/archophthalmol.2011.337 PubMedGoogle ScholarCrossref
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