Dataset Information

How Vision Is Impaired From Aging to Early and Intermediate Age-Related Macular Degeneration: Insights From ALSTAR2 Baseline.

ABSTRACT:

Purpose

We hypothesize the first visual dysfunction in transitioning to early and intermediate age-related macular degeneration (AMD) is delayed rod-mediated dark adaptation (RMDA), owing to impaired photoreceptor sustenance from the circulation. This analysis from the Alabama Study on Early Age-related Macular Degeneration 2 provides insight on our framework's validity, comparing RMDA and other visual tests among older normal, early, and intermediate AMD eyes.

Methods

AMD disease severity was determined via fundus photos using the Age-Related Eye Disease Study nine-step system. Visual functions evaluated were RMDA 5°, acuity, contrast sensitivity (photopic, mesopic), and light sensitivity for a macular grid (scotopic, mesopic, photopic). Presence versus absence of subretinal drusenoid deposits (SDD) was identified through multimodal imaging.

Results

One eye from each of 481 persons (mean age, 72 years) was evaluated. All visual functions were significantly worse with increasing AMD disease severity. Using z-scores to standardize visual function measures across groups, the greatest difference in probability density functions between older normal and intermediate AMD was for RMDA. Early and intermediate AMD eyes with SDD present had longer rod intercept times than eyes with SDD absent. SDD absent eyes also exhibited delayed RMDA and wide probability density functions relative to normal eyes.

Conclusions

Among the visual functions evaluated, RMDA best discriminates among normal, early AMD, and intermediate AMD eyes. The Alabama Study on Early Age-related Macular Degeneration 2 will evaluate whether AMD's natural history confirms our hypothesis at the 3-year follow-up.

Translational relevance

Results support a sequence of visual function impairments in aging and AMD, suggesting RMDA as a promising outcome for evaluating interventions in early disease.

SUBMITTER: Owsley C

PROVIDER: S-EPMC9315068 | biostudies-literature |

REPOSITORIES: biostudies-literature

ACCESS DATA

Similar Datasets

Project description:PurposeQuantification 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.DesignCross-sectional observational study (NCT04112667).ParticipantsAdults ≥ 60 years from a comprehensive ophthalmology clinic, with healthy maculas or maculas meeting fundus criteria for early or intermediate AMD.MethodsMacular 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.Main outcome measuresAge-related macular degeneration presence and severity, MPOV in fovea-centered regions of radius 2.0° and 9.0°; plasma L and Z (μM/ml).ResultsOf 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.ConclusionsA 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.

Project description:PurposeUltrahigh resolution spectral domain-OCT (UHR SD-OCT) enables in vivo visualization of micrometric structural markers which differentially associate with normal aging versus age-related macular degeneration (AMD). This study explores the hypothesis that UHR SD-OCT can detect and quantify sub-retinal pigment epithelium (RPE) deposits in early AMD, separating AMD pathology from normal aging.DesignProspective cross-sectional study.ParticipantsA total of 53 nonexudative (dry) AMD eyes from 39 patients, and 63 normal eyes from 39 subjects.MethodsClinical UHR SD-OCT scans were performed using a high-density protocol. Exemplary high-resolution histology and transmission electron microscopy images were obtained from archive donor eyes. Three trained readers evaluated and labeled outer retina morphological features, including the appearance of a hyporeflective split within the RPE-RPE basal lamina (RPE-BL)-Bruch's membrane (BrM) complex on UHR brightness (B)-scans. A semi-automatic segmentation algorithm measured the thickness of the RPE-BL-BrM split/hyporeflective band.Main outcome measuresQualitative description of outer retinal morphological changes on UHR SD-OCT B-scans; the proportion of the RPE-BL-BrM complex with visible split (%) and the thickness of the resulting hyporeflective band (μm).ResultsIn young normal eyes, UHR SD-OCT consistently revealed an RPE-BL-BrM split/hyporeflective band. Its visibility and thickness were less in eyes of advanced age. However, the split/hyporeflective band was again visible in early AMD eyes. Both qualitative reading and quantitative thickness measurements showed significantly elevated visibility and thickness of the RPE-BL-BrM split/hyporeflective in early AMD eyes compared to age-matched controls.ConclusionsOur imaging results strongly support the hypothesis that appearance of the RPE-BL-BrM split/hyporeflective band in older subjects is dominated by the BL deposit, an indicator of early AMD well known from histology. Ultrahigh resolution SD-OCT can be used to investigate physiological aging as well as early AMD pathology in clinical imaging studies. Developing quantifiable markers associated with disease pathogenesis and progression can facilitate drug discovery, as well as reduce clinical trial times.Financial disclosuresProprietary or commercial disclosure may be found after the references.

Project description:To describe baseline night vision symptoms and their association with >/=3-lines loss in visual acuity (VA), choroidal neovascularization (CNV), and geographic atrophy (GA).Cohort study within a multicenter randomized clinical trial.A total of 1052 participants with >/=10 large (>125 mu) drusen and VA >/=20/40 in each eye.At baseline, participants self-administered a 10-item Night Vision Questionnaire (NVQ-10). VA testing was performed at baseline, 6 months, and annually. One eye of each participant was randomly assigned to laser treatment, and the contralateral eye was assigned to observation. During follow-up, trained readers identified CNV on the basis of fluorescein angiograms and end point GA, defined as >1 disc area of new GA, based on color photographs. Evaluation was performed by repeated-measures logistic regression for NVQ-10 score as a risk factor for >/=3-lines loss in VA and by survival analysis for CNV and GA, with and without adjustment for participant and ocular characteristics. Evaluations were based on observed eyes and treated eyes, considered separately and combined.A >/=3-lines loss in VA, development of CNV and end point GA.At baseline, NVQ-10 scores ranged from 3 to 100 with a mean of 70 (100 corresponds to no night vision symptoms). Compared with participants with the best night vision (fourth quartile of scores), participants with the worst night vision (first quartile of scores) were at increased risk of >/=3-lines loss in VA in both observed and treated eyes; odds ratios (95% confidence interval) were 2.85 (1.85-4.39) and 2.00 (1.27-3.14), respectively. The relative risk for the first quartile versus the fourth quartile for development of GA was 4.18 (1.80-9.68) in observed eyes and 2.59 (1.13-5.95) in treated eyes. The relative risk for CNV incidence was 1.99 (1.12-3.54) in observed eyes and 1.33 (0.81-2.19) in treated eyes. These relationships were maintained after adjustment for baseline participant and ocular characteristics.Participants who perceived the most problems in their night vision at baseline had an increased risk of >/=3-lines loss in VA, CNV, and GA. These associations are independent of established risk factors.