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Association of Reticular Pseudodrusen Burden and Dark Adaptation in Nonadvanced Age-Related Macular Degeneration: A
Ariel Yuhan Ong1, Robbert R Struvyen2, David A Merle3
1Institute of Ophthalmology, University College London, London, United Kingdom; Moorfields Eye Hospital NHS Foundation Trust, London, United Kingdom; NIHR Moorfields Biomedical Research Centre, London, United Kingdom; Oxford Eye Hospital, Oxford University Hospital NHS Foundation Trust, Oxford, United Kingdom.
Purpose:
Dark adaptation (DA) is an emerging functional outcome in age-related macular degeneration (AMD). Although reticular pseudodrusen (RPD) have been linked to poorer DA, previous studies have largely assessed RPD presence/absence or comprised small cross-sectional cohorts. We investigated whether automated quantification of RPD area and volume is associated with rod-mediated DA and its longitudinal decline in nonadvanced AMD.
Design:
Prospective cross-sectional and longitudinal study.
Participants:
Patients with nonadvanced AMD and controls aged >50 years.
Methods:
Participants underwent multimodal retinal imaging and extended protocol DA testing (20-minutes; AdaptDx, MacuLogix), yielding rod intercept time (RIT) and area under the DA curve (AUDAC). A deep learning algorithm quantified RPD en face area (mm2, square-root transformed) and volume (mm3, cube-root transformed), including within the DA testing locus. Linear mixed-effects models were used, accounting for age, sex, smoking, classic drusen volume, and inter-eye correlation.
Main Outcome Measures:
Cross-sectional and longitudinal associations of RPD burden with RIT and AUDAC.
Results:
We included 545 eyes (52 early AMD, 285 intermediate AMD, 208 controls) from 310 patients (mean age, 69.6 ± 7.4 years); 128 (23.5%) had RPD. Greater RPD area and volume were associated with prolonged RIT (β = 1.59, P = 0.002; β = 9.29, P = 9.78 × 10-5, respectively) and higher AUDAC (β = 0.032, P = 2.15 × 10-4; β = 0.166, P = 5.88 × 10-5, respectively). Overall macular RPD burden, rather than local burden at the testing locus, was independently associated with worse AUDAC (β = 0.005, P = 0.001). Longitudinally (n = 204 eyes; mean age, 2.8 ± 1.8 years), RPD presence (β = 0.011, P = 0.0067), area (β = 0.012, P = 4.48 × 10-4), and volume (β = 0.054, P = 2.11 × 10-4) were associated with faster AUDAC decline, and predictive of subsequent AUDAC (β = 0.048, P = 6.72 × 10-5 and β = 0.198, P = 2.02 × 10-4).
Conclusions:
Quantitative RPD burden is independently associated with impaired rod-mediated DA and subsequent functional decline, supporting its value as a prognostic structural biomarker for risk stratification and monitoring in nonadvanced AMD.
Financial Disclosure(S):
Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.
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