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Evaluating Time in Range for Visual Acuity and Macular Thickness as Outcome Measures for Randomized Clinical Trials

In brief

Time-in-range visual acuity yields the biggest effect size (0.66) in eyes with poor baseline vision

In diabetic macular edema trials, the proportion of follow-up time with visual acuity above 69 letters produced an effect size of 0.66, larger than both change-from-baseline and area-under-curve metrics for patients starting with low vision. Similar or superior performance was seen for macular thickness outcomes across all baseline groups, suggesting TIR could serve as a complementary endpoint in future studies, though its advantage varies with initial visual acuity.

Journal
Translational vision science & technology (Q1)
Published
3 August 2026
Study design
Randomized controlled trial
Evidence level
Level 1, High (CEBM 1b)
Authors
Igor Kozak, Meet Panjwani, Robert Wu, Jonathan M Holmes
PMID
42610596
DOI
10.1167/tvst.15.8.12

Why clinicians should know about it

  • Picked for Ophthalmology (paper of the day, 20 August 2026): Time‑in‑range outcome measure for diabetic macular edema trials

Abstract

PURPOSE: To compare performance of time in range (TIR) with other traditional longitudinal outcome measures (change from baseline and area under the curve [AUC] for change). METHODS: We used data from DRCR.net Randomized Clinical Trials (Protocol T, I and AC) for diabetic macular edema, with outcomes of visual acuity (VA) and optical coherence tomography (OCT) central subfield thickness (CST). Outcomes were calculated at one year, stratified by baseline VA (0-39, 40-59, 60-69, and ≥70 letters score). TIR-VA was defined as proportion of time with VA above threshold (64, 69, 74, 79, and 84), and TIR-CST as proportion of time with CST equal or less than threshold (250, 300, 350, and 400 µm). Performance was assessed based on effect size. RESULTS: In Protocol T, TIR-VA had largest effect size when baseline VA was poor: TIR-VA 69 (0.655), AUC-VA (0.607), and change VA (0.557). When baseline VA was moderate and good, TIR-VA effect sizes were similar to AUC-VA and change-VA. When baseline VA was excellent, effect size was largest for TIR-VA 74 versus AUC-VA or change-VA (0.199 vs. 0.179 vs. 0.083). For CST outcomes, TIR-CST was similar to or better than AUC-CST and change-CST across most baseline VA strata. In Protocols I and AC, TIR outcomes also had similar or larger effect size than AUC and change. CONCLUSIONS: TIR-VA and TIR-CST performed well across baseline VA strata and across RCTs. TRANSLATIONAL RELEVANCE: TIR-VA and TIR-CST may be complementary outcome measures for future RCTs.

Abstract as published, via PubMed.

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For healthcare professionals. The summary is generated by AI from the published abstract, and the evidence level is assigned automatically from the study design on the Oxford CEBM hierarchy. Neither is medical advice. Read the full paper before changing practice.