Diagnostic Accuracy of Monitoring Tests of Fellow Eyes in Patients with Unilateral Neovascular Age-Related Macular Degeneration: Early Detection of Neovascular Age-Related Macular Degeneration Study

Abstract

Purpose: To evaluate the diagnostic accuracy of routinely used tests of visual function and retinal morphology compared with fundus fluorescein angiography (FFA) to detect onset of active macular neovascularization in unaffected fellow eyes of patients with unilateral neovascular age-related macular degeneration (nAMD).

Design: Prospective diagnostic accuracy cohort study conducted in 24 eye clinics in the United Kingdom over 3 years.

Participants: Older adults (>50 years) with recently diagnosed unilateral nAMD with a fellow (study) eye free of nAMD.

Methods: Self-reported vision, Amsler, clinic-measured visual acuity (VA), fundus assessment, and spectral domain OCT. The reference standard is FFA.

Main outcome measures: Sensitivity and specificity of the 5 index tests.

Results: Of 552 participants monitored for up to 3 years, 145 (26.3%) developed active nAMD in the study eye, of whom 120 had an FFA at detection and constituted the primary analysis cohort. Index test positives at nAMD detection in those confirmed by FFA were self-reported vision much worse (5), distortion on Amsler (33), 10-letter decrease in acuity from baseline (36), fundus examination (64), and OCT (110). Percentage index test sensitivities were: self-reported vision 4.2 (95% confidence interval [CI], 1.6-9.8); Amsler 33.7 (95% CI, 25.1-43.5); VA 30.0 (95% CI, 22.5-38.7); fundus examination 53.8 (95% CI, 44.8-62.5); and OCT 91.7 (95% CI, 85.2-95.6). All 5 index test specificities were high at 97.0 (95% CI, 94.6-98.5), 81.4 (95% CI, 76.4-85.5), 66.3 (95% CI, 61.0-71.1), 97.6 (95% CI, 95.3-98.9), and 87.8 (95% CI, 83.8-90.9), respectively. The combination of OCT with one other index test that was a secondary outcome measure increased sensitivity marginally and decreased specificity for all combinations except fundus examination.

Conclusions: Tests of self-reported change in vision, unmasking of new distortion, measurements of acuity, and fundus checks to diagnose active nAMD performed poorly in contrast to OCT. Our findings support a change to guidelines in clinical practice to monitor for onset of nAMD.

Keywords: Amsler; Diagnostic accuracy; Fluorescein angiography; Neovascular age-related macular degeneration; OCT; Sensitivity and specificity; Visual acuity.

Figure 1

Flowchart of participants included in the main and enhanced reference standards. EDNA = Early Detection of Neovascular Age-Related Macular Degeneration; FFA = fundus fluorescein angiography; nAMD = neovascular age-related macular degeneration.

Figure 2

Sensitivity of index tests (A) using the primary reference standard (clinician determination based on FFA) and (B) using the enhanced reference standard (reading center determination based on FFA). Test performance is shown in the 3 panels separated by dotted lines. The time periods are all visits, last 6 months of follow-up, and final visit. Index test performance remained similar regardless of the time period, with sensitivities that are lowest for self-reported vision moderate and similar for Amsler test and visual acuity (VA), good for fundus examination, and best for OCT. Specificity of index tests (C) using the primary reference standard (clinician determination based on FFA) and (D) enhanced reference standard (reading center determination based on FFA). The time periods are all visits, last 6 months of follow-up, and final visit. Index test performance. Specificities were clustered at the high end and the performance of the index tests were not altered by changing the time period. EDNA = Early Detection of Neovascular Age-Related Macular Degeneration; FFA = fundus fluorescein angiography; nAMD = neovascular age-related macular degeneration.