Ophthalmology. Retina · 2026
Association of reticular pseudodrusen burden and dark adaptation in non-advanced age-related macular degeneration: a cross-sectional and longitudinal study.
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Ong Ariel Yuhan, Struvyen Robbert R, Merle David A, Mendez Kevin, Ashourizadeh Helia, Mukherjee Souvick, Lima-Cabrita Afonso, Chang Jooyoung, Wu Dylan, Pundlik Shrinivas, Vavvas Demetrios G, Kim Ivana K, Miller Joan W, Wu Zhichao, Keane Pearse A, Miller John B, Husain Deeba, Lains Ines
Аннотация
PURPOSE: Dark adaptation (DA) has emerged as a potential functional outcome for assessing age-related macular degeneration (AMD). While reticular pseudodrusen (RPD) have been linked to poorer DA, most studies to date have focused on qualitative RPD presence/absence or comprised small cross-sectional cohorts. This work aimed to assess how automated quantification of RPD area and volume relates to rod-mediated DA and its longitudinal decline in non-advanced AMD.
DESIGN: Prospective cross-sectional and longitudinal study.
PARTICIPANTS: Patients with non-advanced AMD and controls, all aged above 50, from the Massachusetts Eye and Ear AMD Biomarkers Study.
METHODS: All subjects underwent baseline multimodal retinal imaging and DA testing with a 20-minute extended protocol (AdaptDx, MacuLogix). Rod intercept time (RIT) and area under the dark adaptation curve (AUDAC) were calculated. A deep learning algorithm was employed to quantify RPD en face area (mm2) and volume (mm3), which were square- and cube-root transformed respectively for analysis. RPD extent within the DA testing locus was also measured. Linear mixed-effect models evaluated the relationship of RPD burden with DA metrics, accounting for age, sex, smoking, classic drusen volume and inter-eye correlation.
MAIN OUTCOME MEASURES: Association between RPD burden and dark adaptation (RIT and AUDAC) on a cross-sectional and longitudinal basis RESULTS: We included 545 eyes (52 early AMD, 285 intermediate AMD, 208 controls) from 310 patients (mean 69.6±7.4 years). 128 (23.5%) had RPD. Greater RPD en-face area and volume were associated with prolonged RIT (β 1.59, p=0.002 and β 9.29, p=9.78 x 10-5 respectively) and higher AUDAC (β 0.032, p=2.15 x 10-4 and β 0.166, p=5.88x10-5 respectively). Overall macular RPD burden, rather than local density at the DA testing locus, was independently associated with worse AUDAC (β 0.005, p=0.001). In longitudinal analyses (n=204 eyes, mean 2.8±1.8 years), RPD presence (β 0.011, p=0.0067), en face area (β 0.012, p=4.48 x 10-4), and volume (β 0.054, p=2.11 x 10-4) were all significantly associated with a faster rate of AUDAC decline over time, and were predictive of AUDAC at any subsequent visit (β 0.048, p=6.72 x 10-5 and β 0.198, p=2.02 x 10-4).
CONCLUSIONS: Quantitative RPD burden is independently associated with impaired rod-mediated DA and with subsequent functional decline, supporting its value as a prognostic structural biomarker for risk stratification and progression monitoring in non-advanced AMD.
DESIGN: Prospective cross-sectional and longitudinal study.
PARTICIPANTS: Patients with non-advanced AMD and controls, all aged above 50, from the Massachusetts Eye and Ear AMD Biomarkers Study.
METHODS: All subjects underwent baseline multimodal retinal imaging and DA testing with a 20-minute extended protocol (AdaptDx, MacuLogix). Rod intercept time (RIT) and area under the dark adaptation curve (AUDAC) were calculated. A deep learning algorithm was employed to quantify RPD en face area (mm2) and volume (mm3), which were square- and cube-root transformed respectively for analysis. RPD extent within the DA testing locus was also measured. Linear mixed-effect models evaluated the relationship of RPD burden with DA metrics, accounting for age, sex, smoking, classic drusen volume and inter-eye correlation.
MAIN OUTCOME MEASURES: Association between RPD burden and dark adaptation (RIT and AUDAC) on a cross-sectional and longitudinal basis RESULTS: We included 545 eyes (52 early AMD, 285 intermediate AMD, 208 controls) from 310 patients (mean 69.6±7.4 years). 128 (23.5%) had RPD. Greater RPD en-face area and volume were associated with prolonged RIT (β 1.59, p=0.002 and β 9.29, p=9.78 x 10-5 respectively) and higher AUDAC (β 0.032, p=2.15 x 10-4 and β 0.166, p=5.88x10-5 respectively). Overall macular RPD burden, rather than local density at the DA testing locus, was independently associated with worse AUDAC (β 0.005, p=0.001). In longitudinal analyses (n=204 eyes, mean 2.8±1.8 years), RPD presence (β 0.011, p=0.0067), en face area (β 0.012, p=4.48 x 10-4), and volume (β 0.054, p=2.11 x 10-4) were all significantly associated with a faster rate of AUDAC decline over time, and were predictive of AUDAC at any subsequent visit (β 0.048, p=6.72 x 10-5 and β 0.198, p=2.02 x 10-4).
CONCLUSIONS: Quantitative RPD burden is independently associated with impaired rod-mediated DA and with subsequent functional decline, supporting its value as a prognostic structural biomarker for risk stratification and progression monitoring in non-advanced AMD.