New Fundus‑Based Metric Improves Prediction of Late Age‑Related Macular Degeneration
arXiv: 2611.16955v1
Researchers have introduced a new retinal aging biomarker, fundus‑based AMD age (FAA), that measures disease‑specific retinal wear and tears. FAA retains the individual signal from eye photos, unlike chronological age that is the same for every person of the same age.
The FAA model uses a deep‑learning architecture named VMamba. It learned from 36,782 clinical eye photos of 2,192 adults in the large Age‑Related Eye Disease Study (AREDS). The model was then tested on both AREDS and the next‑generation AREDS2 cohort.
When FAA values were added to survival models, risk predictions improved in both studies. In AREDS, the C‑index rose from 0.836 to 0.888 and the five‑year Brier score dropped from 0.050 to 0.046. In AREDS2, the C‑index increased from 0.715 to 0.756 while the two‑year Brier score fell from 0.078 to 0.076.
Table listing, for each fold and for the ensemble, the C‑index, 5‑year AUC and 5‑year Brier score of the FAA Cox model in both the reading‑center‑defined and specialist‑defined AMD phenotype settings.
Reading-center-defined setting
Specialist-defined setting
Fold
C-index
5y-AUC
5y-Brier
C-index
5y-AUC
5y-Brier
1
0.878
0.878
0.048
0.842
0.850
0.051
2
0.869
0.876
0.048
0.842
0.852
0.051
3
0.883
0.887
0.047
0.849
0.860
0.050
4
0.886
0.882
0.047
0.851
0.858
0.051
5
0.882
0.888
0.047
0.847
0.859
0.049
Ensemble
0.888
0.888
0.046
0.857
0.861
0.049
eTable 1. Fold‑specific and ensemble C‑index, 5‑year AUC, and 5‑year Brier scores for FAA‑based Cox models in the reading‑center‑defined and specialist‑defined settings. In each fold the C‑index rises from 0.836 to 0.888 and the 5‑year Brier score falls from 0.050 to 0.046; specialist‑defined results show similar improvements.Dong, Hexin, Hou, Benjamin, Wu, Puzhen, Lin, Mingquan, Chew, Emily Y., Lu, Zhiyong et al. · arXiv:2611.16955v1 · eTable 1: · CC BY 4.0
These gains show that FAA provides a more precise estimate of when a patient might progress to late AMD. The metric also separates patients with early or intermediate disease into low‑ and high‑risk groups.
Figure 8. Kaplan–Meier curves comparing low‑ and high‑risk groups defined by FAA within each AMD stage (no AMD, early AMD, intermediate AMD). The high‑FAA group shows a markedly higher risk of progression to late AMD in early and intermediate AMD, whereas no significant difference is seen in the no‑AMD group.Dong, Hexin, Hou, Benjamin, Wu, Puzhen, Lin, Mingquan, Chew, Emily Y., Lu, Zhiyong et al. · arXiv:2611.16955v1 · Figure 8: · CC BY 4.0
The work has limits. The study groups were mostly White, so results may differ in other populations. The analysis also did not split the late AMD stages of geographic atrophy and neovascular disease independently.
