Prolonged Photostress Recovery Time Significantly Associated with AMD

Caroline Brandl

A recent systematic evaluation investigated photostress recovery time (PRT) as a potential predictive biomarker for age-related macular degeneration (AMD) using three independent data sets from a population-based cohort of older adults.¹

The study's results show a highly significant association of prolonged PRT with early as well as late AMD in cross-sectional data involving approximately 1200 individuals, with investigators confirming the association in independent replication data.

“Our observation of a prolonged PRT among initially AMD-free individuals who showed signs of early or late AMD on color fundus photography 3 years later suggests PRT as a predictive biomarker for early and late AMD, independent of age and VA,” investigators wrote.¹

Led by Caroline Brandl, Department of Ophthalmology, Department of Genetic Epidemiology, University of Regensburg, investigators evaluated PRT as a concurrent or predictive marker of AMD in a cohort 70 years and older from Germany’s population-based AugUR study. The age of the target population allowed investigators to observe incident AMD within a short follow-up period.

The present analysis of approximately 1800 participants investigated the association of PRT with AMD status cross-sectionally in two independent surveys, to enable replication. In addition, the analysis evaluated the association of the AMD genetic risk score (GRS) with PRT to prove the PRT association with AMD and not with age. Finally, the analysis investigated the capability of PRT to predict late and early AMD, using longitudinal analyses in an independent subset of AugUR participants with 3-year follow-up.

On color fundus images from baseline and at 3-year follow-up, the presence of AMD was graded manually using the Three Continent AMD Consortium Severity Scale into no AMD, mild/moderate/severe early AMD, or late AMD. Investigators first assessed visual acuity and after a 30-second bleaching of the macular region via direct ophthalmoscope, they measured PRT as the seconds to regain VA

The primary cross-sectional study analyzed 1208 AugUR participants, including 288 individuals with early AMD and 78 with late AMD. In this cohort, PRT increased by higher age and by severity of AMD (P <.0001).

Upon analysis, the findings indicated a statistically significant association of prolonged PRT with any, early, and late AMD compared to no AMD. The odds ratios (OR) per 10 seconds of PRT were 1.109 (95% confidence interval [CI], 1.085 – 1.132), 1.095 (95% CI, 1.070 - 1.121), and 1.165 (95% CI, 1.122 to 1.210), respectively (P <.0001). Sensitivity analyses with alternative models or restricting to individuals after cataract surgery reported similar ORs, according to investigators.

Then, to replicate these findings, investigators analyzed the second cross-sectional sample of 486 participants who had a valid PRT value for the eye with the worse AMD status. Characteristics of the sample were noted as comparable to the primary analysis and investigators confirmed the significant association of prolonged PRT with any, early, and late AMD with similar OR estimates.

After observing the association in two independent data sets, the team aimed to uncover if PRT was predictive for AMD development in the follow-up 3 years later. Data show the median PRT was 129.0 seconds for the 37 individuals with incident early or late AMD 3 years later and 87.0 seconds for the 196 individuals who remained AMD free. In longitudinal analysis, with a mean follow-up time of 3.2 years, investigators found prolonged PRT was significantly associated with incident AMD (OR, 1.112 – 1.162 per 10 seconds; P <.05).

They noted that sensitivity analyses without adjustment or only adjusted for sex and age yielded similar results.

“Despite the limited sample size of individuals with incident AMD, these statistically significant results suggest prolonged PRT as a predictive biomarker for the development of late and early AMD,” they wrote.¹

References

1. Caroline Brandl, Martina E. Zimmermann, Janina M. Herold, Horst Helbig, Klaus J. Stark, Iris M. Heid; Photostress Recovery Time as a Potential Predictive Biomarker for Age-Related Macular Degeneration. Trans. Vis. Sci. Tech. 2023;12(2):15. doi: https://doi.org/10.1167/tvst.12.2.15.