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Original Investigation
June 10, 2021

Estimated Utility of the Short-term Assessment of Glaucoma Progression Model in Clinical Practice

Author Affiliations
  • 1Hamilton Glaucoma Center, Shiley Eye Institute, Viterbi Family Department of Ophthalmology, University of California, San Diego, La Jolla
  • 2Duke Eye Center, Department of Ophthalmology, Duke University, Durham, North Carolina
JAMA Ophthalmol. 2021;139(8):839-846. doi:10.1001/jamaophthalmol.2021.1812
Key Points

Question  Can a study design that evaluates current clinical practice assess glaucomatous change in a shorter than usual study period in patients with glaucoma?

Findings  In this cohort study of 178 eyes from 97 patients with glaucoma, with testing every 3 months, clinically relevant rates of retinal nerve fiber layer and visual field mean deviation change were detected in 18 months. Assuming moderate differences in the rates of change and testing every 3 months, sufficient power was demonstrated for glaucoma therapy trials with 18 months follow-up.

Meaning  In this study using frequent testing and the rate of change in retinal nerve fiber layer thickness or visual field mean deviation as the end point, the results suggest that clinical trials of glaucoma therapy can be completed within a relatively short time frame.

Abstract

Importance  Clinical trials of glaucoma therapies focused on protecting the optic nerve have required large sample sizes and lengthy follow-up to detect clinically relevant change due to its slow rate of progression. Whether shorter trials may be possible with more frequent testing and use of rate of change as the end point warrants further investigation.

Objective  To describe the design for the Short-term Assessment of Glaucoma Progression (STAGE) model and provide guidance on sample size and power calculations for shorter clinical trials.

Design, Setting, and Participants  A cohort study of patients with mild, moderate, or advanced open-angle glaucoma recruited from the Diagnostic Innovations in Glaucoma Study at the University of California, San Diego. Enrollment began in May 2012 with follow-up for every 3 months for 2 years after baseline examination. Follow-up was concluded in September 2016. Data were analyzed from July 2019 to January 2021. Visual fields (VF) and optic coherence tomography (OCT) scans were obtained at baseline and for 2 years with visits every 3 months.

Exposures  Glaucoma was defined as glaucomatous appearing optic discs classified by disc photographs in at least 1 eye and/or repeatable VF damage at baseline.

Main Outcomes and Measures  Longitudinal rates of change in retinal nerve fiber layer (RNFL) thickness and VF mean deviation (MD) are estimated in study designs of varying length and observation frequency. Power calculations as functions of study length, observation frequency, and sample size were performed.

Results  In a total referred sample of 97 patients with mild, moderate, or advanced glaucoma (mean [SD] age, 69 [11.4] years; 50 [51.5%] were female; 19 [19.6%]), over the 2-year follow-up, the mean VF 24-2 MD slope was −0.32 dB/y (95% CI, −0.43 to −0.21 dB/y) and the mean RNFL thickness slope was −0.54 μm/y (95% CI, −0.75 to −0.32 μm/y). Sufficient power (80%) to detect similar group differences in the rate of change in both outcomes was attained with total follow-up between 18 months and 2 years and fewer than 300 total participants.

Conclusions and Relevance  In this cohort study, results from the STAGE model with reduction of the rate of progression as the end point, frequent testing, and a moderate effect size, suggest that clinical trials to test efficacy of glaucoma therapy can be completed within 18 months of follow-up and with fewer than 300 participants.

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