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Multicenter Study
. 2022 Aug 1;140(8):780-789.
doi: 10.1001/jamaophthalmol.2022.2113.

Repeatability and Discriminatory Power of Chart-Based Visual Function Tests in Individuals With Age-Related Macular Degeneration: A MACUSTAR Study Report

Hannah M P Dunbar  1   2 , Charlotte Behning  3 , Amina Abdirahman  1 , Bethany E Higgins  4 , Alison M Binns  4 , Jan H Terheyden  5 , Nadia Zakaria  6 , Stephen Poor  7 , Robert P Finger  5 , Sergio Leal  8 , Frank G Holz  5 , Matthias Schmid  3 , David P Crabb  4 , Gary S Rubin  1   2 , Ulrich F O Luhmann  9 ; MACUSTAR Consortium
Collaborators, Affiliations
Multicenter Study

Repeatability and Discriminatory Power of Chart-Based Visual Function Tests in Individuals With Age-Related Macular Degeneration: A MACUSTAR Study Report

Hannah M P Dunbar et al. JAMA Ophthalmol. .

Abstract

Importance: There is a need for validated clinical end points that are reliably able to quantify potential therapeutic effects of future treatments targeting age-related macular degeneration (AMD) before the onset of serious visual impairment.

Objective: To assess the reliability and discriminatory power of 5 simple chart-based visual function (VF) tests as potential measures for clinical trial end points with regulatory and patient-access intention in intermediate AMD (iAMD).

Design, setting, and participants: This international noninterventional study took place at 18 tertiary ophthalmology departments across Europe. Participants were recruited between April 2018 and March 2020 and were identified during routine clinical review. Participants with no AMD and early AMD were recruited from hospital staff, friends, and family of participants with AMD and via referrals from community ophthalmologists and optometrists. The repeatability and discriminatory power of 5 simple chart-based assessments of VF (best-corrected visual acuity [BCVA], low-luminance visual acuity [LLVA], Moorfields Acuity Test [MAT], Pelli-Robson Contrast Sensitivity [CS], and International Reading Speed Test [IReST]) were assessed in a repeated-measures design. VF assessments were performed on day 0 and day 14. Participants with early AMD, iAMD, late AMD, and no AMD were recruited.

Main outcomes and measures: Intraclass correlation coefficients (ICCs) and Bland-Altman 95% limits of agreement (LoA) were computed to assess repeatability. Area under the receiver operating characteristic curves (AUCs) determined the discriminatory ability of all measures to classify individuals as having no AMD or iAMD and to differentiate iAMD from its neighboring disease states.

Results: A total of 301 participants (mean [SD] age, 71 [7] years; 187 female participants [62.1%]) were included in the study. Thirty-four participants (11.3%) had early AMD, 168 (55.8%) had iAMD, 43 (14.3%) had late AMD, and 56 (18.6%) had no AMD. ICCs for all VF measures ranged between 0.88 and 0.96 when all participants were considered, indicating good to excellent repeatability. All measures displayed excellent discrimination between iAMD and late AMD (AUC, 0.92-0.99). Early AMD was indistinguishable from iAMD on all measures (AUC, 0.54-0.64). CS afforded the best discrimination between no AMD and iAMD (AUC, 0.77). Under the same conditions, BCVA, LLVA, and MAT were fair discriminators (AUC, 0.69-0.71), and IReST had poor discrimination (AUC, 0.57-0.61).

Conclusions and relevance: BCVA, LLVA, MAT, CS, and IReST had adequate repeatability in this multicenter, multiexaminer setting but limited power to discriminate between no AMD and iAMD. The prognostic power of these variables to predict conversion from iAMD to late AMD is being examined in the ongoing longitudinal part of the MACUSTAR study.

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Conflict of interest statement

Conflict of Interest Disclosures: Dr Dunbar reported grants from the Innovative Medicines Initiative 2 Joint Undertaking during the conduct of the study and personal fees from Boehringer Ingelheim outside the submitted work. Dr Binns reported grants from Innovative Medicines Initiative, which funded the MACUSTAR project that was the basis of this article, during the conduct of the study; in addition, Dr Binns had a patent for apparatus and method for retinal measurement (US 9,492,081 B2) issued by the Science and Technology Facilities Council. Dr Terheyden reported grants from Innovative Medicines Initiative Horizon 2020 during the conduct of the study; nonfinancial support from Heidelberg Engineering, Optos, Zeiss Meditec, Centervue; and personal fees from Novartis and Okko outside the submitted work. Dr Zakaria reported being an employee of Novartis during the conduct of the study. Dr Finger reported personal fees from Novartis, Bayer, Apellis, Alimera, Boehringer -Ingelheim, Roche/Genentech, Chiesi, ODOS, Opthea, Oxford Innovation Ltd., and ProQR as well as grants from Biogen outside the submitted work. Dr Leal reported being an employee of Bayer Consumer Care. Dr Holz reported grants from Innovative Medicines Initiative during the conduct of the study and nonfinancial support from Heidelberg Engineering, Centervue, and Optos outside the submitted work. Dr Schmid reported grants from Innovative Medicines Initiative during the conduct of the study. Dr Crabb reported personal fees from Santen, Allergan/AbbVie, Bayer, and THEA and grants from Santen, Allergan/AbbVie, Apellis, and Roche outside the submitted work. Dr Luhmann reported being an employee of F. Hoffmann-La Roche outside the submitted work. No other disclosures were reported.

Figures

Figure 1.
Figure 1.. Intraclass Correlation Coefficients (ICCs) for the Full Cohort and Each Disease Group
ICC values for the full cohort, no age-related macular degeneration (AMD), early AMD, intermediate AMD (iAMD), and late AMD groups. BCVA indicates best-corrected visual acuity; CS, contrast sensitivity; LLVA, low-luminance visual acuity; LPS, large-print standardized reading speed; MAT, Moorfields Acuity Test; SPS, small-print standardized reading speed.
Figure 2.
Figure 2.. Receiver Operating Characteristic Curves Comparing No Age-Related Macular Degeneration (AMD) With Intermediate AMD for the 4 Best-Performing Chart-Based Visual Function Tests.
Area under the curve (AUC) and 95% CIs (shading) for each curve are provided. BCVA indicates best-corrected visual acuity; CS, contrast sensitivity; LLVA, low-luminance visual acuity; MAT, Moorfields Acuity Test.
See this image and copyright information in PMC

Comment in

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