City Research Online

Abstract

Purpose
to compare the statistical power of structural and visual field (VF) outcomes for randomised clinical trials (RCTs) in glaucoma.

Design
analysis of retrospectively collected data.

Participants
Eighty-two glaucoma patients were recruited to a test–retest study, during which up to ten 24-2 SITA Standard VF and circumpapillary retinal nerve fibre layer (cpRNFL) Spectralis OCT scans were collected in separate sessions over 3 months.

Methods
Eyes with at least three sessions with a reliable VF (false positives < 15%) and cpRNFL scan (quality index ≥ 25 dB) were selected (127 eyes, 68 patients) to model the test-retest variability and the structural floor effect. These estimates were combined with a published realistic structure-function progression model from the United Kingdom Glaucoma Treatment Study to simulate longitudinal RCTs (30% neuroprotective effect). Simulations only included data from eyes with early to moderate VF loss (Mean Deviation, MD, ≥-10 dB, 107 eyes, 65 patients). Simulations were repeated 5000 times to estimate sample size requirements to detect a significant difference (p < 0.05) in the rate of change of MD and average cpRNFL thickness, estimated with a linear mixed effect model. We also tested the power of a significant outcome with either metric (p < 0.025). A supplementary analysis was performed including eyes with early VF loss only (MD ≥-6 dB). Main outcome measures sample size at 80% power for the linear rate of MD, cpRNFL and their combination.

Results
at 80% power, the required sample size (patients [95%-Confidence Interval]) was 38% smaller for the MD rate (292 [300, 283]) than the cpRNFL rate (470 [481, 459]). The sample size for the combined outcome was only marginally smaller than the MD alone (275 [283, 268]). The supplementary analysis on eyes with early VF loss showed similar results.

Conclusions
Using realistic modelling of structure-function progression and test-retest data, MD progression showed higher statistical power cpRFNL as an outcome measure for clinical trials.

Publication Type:	Article
Additional Information:	© 2026 Published by Elsevier Inc. on behalf of the American Academy of Ophthalmology. This is an open access article distributed under the terms of the Creative Commons CC-BY license, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
Publisher Keywords:	OCT, RNFL, clinical trials, glaucoma, neuroprotection, outcome measures, visual field
Subjects:	R Medicine > RE Ophthalmology
Departments:	School of Health & Medical Sciences School of Health & Medical Sciences > Department of Optometry & Visual Science
SWORD Depositor:	Symplectic Administrator

Export

Downloads