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.
The author(s) have made the following disclosure(s): R.G.: Personal fees ? Heidelberg Engineering.S.S.: Grants and personal fees ? Bayer, during the conduct of the study; Grants and personal fees ? Novartis, Boehringer Ingleheim; Grants ? Allergan, Roche; Personal fees ? Apellis, Oxurion, Heidelberg Engineering, Optos, outside the submitted work; Funded by the Moorfields Biomedical Research Centre and Clinical Research Facility.The project was funded by the National Institute for Health Research Health Technology Assessment Programme (Project Number: 12/142/07) and will be published in full in Health Technology Assessment. The Health Services Research Unit and the Health Economics Research Unit are core funded by the Chief Scientist Office of the Scottish Government Health and Social Care Directorate. F.G.: Grants ? NIHR, during the conduct of the study; Grants and personal fees ? Novartis, Roche, Bayer; Personal fees ? Allergan, Alimera; Grants ? Chengdu Pharma; Grants and nonfinancial support ? NIHR, outside the submitted work. J.A.C.: Study grant ? NIHR. K.B.: Grants ? NIHR HTA Programme, during the conduct of the study. Obtained funding: Chakravarthy, Ramsay, Sivaprasad, Scotland, Azuara-Blanco, Heiman and Cook
- Diagnostic accuracy
- Fluorescein angiography
- Neovascular age-related macular degeneration
- Sensitivity and specificity
- Visual acuity