UNASSIGNED: We evaluate the impact of test target location in assessing rod-mediated dark adaptation (RMDA) along the transition from normal aging to intermediate age-related macular degeneration (AMD). We consider whether RMDA slows because the test locations are near mechanisms leading to or resulting from high-risk extracellular deposits. Soft drusen cluster under the fovea and extend to the inner ring of the ETDRS grid where rods are sparse. Subretinal drusenoid deposits (SDDs) appear first in the outer superior subfield of the ETDRS grid where rod photoreceptors are maximal and spread toward the fovea without covering it.
UNASSIGNED: Cross-sectional.
UNASSIGNED: Adults ≥ 60 years with normal older maculas, early AMD, or intermediate AMD as defined by the Age-Related Eye Disease Study (AREDS) 9-step and Beckman grading systems.
UNASSIGNED: In 1 eye per participant, RMDA was assessed at 5° and at 12° in the superior retina. Subretinal drusenoid deposit presence was identified with multi-modal imaging.
UNASSIGNED: Rod intercept time (RIT) as a measure of RMDA rate at 5° and 12°.
UNASSIGNED: In 438 eyes of 438 persons, RIT was significantly longer (i.e., RMDA is slower) at 5° than at 12° for each AMD severity group. Differences among groups were bigger at 5° than at 12°. At 5°, SDD presence was associated with longer RIT as compared to SDD absence at early and intermediate AMD but not in normal eyes. At 12°, SDD presence was associated with longer RIT in intermediate AMD only, and not in normal or early AMD eyes. Findings were similar in eyes stratified by AREDS 9-step and Beckman systems.
UNASSIGNED: We probed RMDA in relation to current models of deposit-driven AMD progression organized around photoreceptor topography. In eyes with SDD, slowed RMDA occurs at 5° where these deposits typically do not appear until later in AMD. Even in eyes lacking detectable SDD, RMDA at 5° is slower than at 12°. The effect at 5° may be attributed to mechanisms associated with the accumulation of soft drusen and precursors under the macula lutea throughout adulthood. These data will facilitate the design of efficient clinical trials for interventions that aim to delay AMD progression.

UNASSIGNED: Quantification of retinal xanthophyll carotenoids in eyes with and without age-related macular degeneration (AMD) via macular pigment optical volume (MPOV), a metric for xanthophyll abundance from dual wavelength autofluorescence, plus correlations to plasma levels, could clarify the role of lutein (L) and zeaxanthin (Z) in health, AMD progression, and supplementation strategies.
UNASSIGNED: Cross-sectional observational study (NCT04112667).
UNASSIGNED: Adults ≥ 60 years from a comprehensive ophthalmology clinic, with healthy maculas or maculas meeting fundus criteria for early or intermediate AMD.
UNASSIGNED: Macular health and supplement use was assessed by the Age-related Eye Disease Study (AREDS) 9-step scale and self-report, respectively. Macular pigment optical volume was measured from dual wavelength autofluorescence emissions (Spectralis, Heidelberg Engineering). Non-fasting blood draws were assayed for L and Z using high-performance liquid chromatography. Associations among plasma xanthophylls and MPOV were assessed adjusting for age.
UNASSIGNED: Age-related macular degeneration presence and severity, MPOV in fovea-centered regions of radius 2.0° and 9.0°; plasma L and Z (μM/ml).
UNASSIGNED: Of 809 eyes from 434 persons (89% aged 60-79, 61% female), 53.3% eyes were normal, 28.2% early AMD, and 18.5% intermediate AMD. Macular pigment optical volume 2° and 9° were similar in phakic and pseudophakic eyes, which were combined for analysis. Macular pigment optical volume 2° and 9° and plasma L and Z were higher in early AMD than normal and higher still in intermediate AMD (P < 0.0001). For all participants, higher plasma L was correlated with higher MPOV 2° (Spearman correlation coefficient [Rs] = 0.49; P < 0.0001). These correlations were significant (P < 0.0001) but lower in normal (Rs = 0.37) than early and intermediate AMD (Rs = 0.52 and 0.51, respectively). Results were similar for MPOV 9°. Plasma Z, MPOV 2°, and MPOV 9° followed this same pattern of associations. Associations were not affected by supplement use or smoking status.
UNASSIGNED: A moderate positive correlation of MPOV with plasma L and Z comports with regulated xanthophyll bioavailability and a hypothesized role for xanthophyll transfer in soft drusen biology. An assumption that xanthophylls are low in AMD retina underlies supplementation strategies to reduce progression risk, which our data do not support. Whether higher xanthophyll levels in AMD are due to supplement use cannot be determined in this study.