Hypertransmission and vision in aging and age-related macular degeneration: longitudinal data from ALSTAR2.

Purpose: To investigate the presence of hypertransmission (HT) in normal aging, early (e)AMD, and intermediate (i)AMD, changes over 3 years, and the impact of HTs ≥ 250 µm (LHyperTD) on seven tests of scotopic, mesopic, and photopic vision.

Design: Prospective cohort study.

Subjects: Participants of the Alabama Study on Early Age-Related Macular Degeneration 2.

Genetic Associations of Rod- and Cone-Mediated Vision in Aging and Age-Related Macular Degeneration.

Purpose: To compare genetic associations of rod- and cone-driven vision with those previously defined for delayed rod-mediated dark adaptation (RMDA), a functional risk indicator for incident age-related macular degeneration (AMD).

Methods: In adults aged ≥60 years with two normal eyes (per the Age-Related Eye Disease Study 9-step scale) or with AMD in one or both eyes, we measured RMDA at 5° superior retina, photopic vision (acuity, contrast sensitivity, light sensitivity), and mesopic vision (low luminance acuity and deficit). Vision associations of risk-conferring single-nucleotide polymorphisms in CFH and ARMS2 genes were adjusted for age and smoking and stratified for the presence of subretinal drusenoid deposit (SDD).

Topographic Analysis of Two-Wavelength Autofluorescence Supports Higher Macular Xanthophyll Pigment in AMD Than Aging: ALSTAR2 Baseline.

Purpose: To advance metabolic imaging of the high-risk macula lutea by quantifying the topography of macular pigment optical density (MPOD), measured with two-wavelength autofluorescence (2WAF), and quantitative (short-wavelength) autofluorescence (qAF) intensity, which share the same signal source and cross-retinal light path, in aging, early (e), and intermediate (i) age-related macular degeneration (AMD).

Methods: 2WAF and qAF images of 384 pseudophakic eyes of 230 persons (mean age, 74.2 ± 5.

Band Visibility in High-Resolution Optical Coherence Tomography Assessed With a Custom Review Tool and Updated, Histology-Derived Nomenclature.

Purpose: For structure-function research at the transition of aging to age-related macular degeneration, we refined the current consensus optical coherence tomography (OCT) nomenclature and evaluated a novel review software for investigational high-resolution OCT imaging (HR-OCT; <3 µm axial resolution).

Method: Volume electron microscopy, immunolocalizations, histology, and investigational devices informed a refined OCT nomenclature for a custom ImageJ-based review tool to assess retinal band visibility. We examined effects on retinal band visibility of automated real-time averaging (ART) 9 and 100 (11 eyes of 10 healthy young adults), aging (10 young vs 22 healthy aged), and age-related macular degeneration (AMD; 22 healthy aged, 17 early (e)AMD, 15 intermediate (i)AMD).

Extent and Topography of Subretinal Drusenoid Deposits Associate With Rod-Mediated Vision in Aging and AMD: ALSTAR2 Baseline.

Purpose: In AMD, rod-mediated dark adaptation (RMDA) at 5° eccentricity is slower in eyes with subretinal drusenoid deposits (SDDs) than in eyes without. Here we quantified SDD burden using supervised deep learning for comparison to vision and photoreceptor topography.

Methods: In persons ≥60 years from the Alabama Study on Early Age-Related Macular Degeneration 2, normal, early AMD, and intermediate AMD eyes were classified by the AREDS nine-step system.

Choriocapillaris Impairment, Visual Function, and Distance to Fovea in Aging and Age-Related Macular Degeneration: ALSTAR2 Baseline.

Purpose: In aging and early-intermediate age-related macular degeneration (AMD), rod-mediated dark adaptation (RMDA) slows more at 5° superior than at 12°. Using optical coherence tomography angiography (OCTA), we asked whether choriocapillaris flow deficits are related to distance from the fovea.

Methods: Persons ≥60 years stratified for AMD via the Age-Related Eye Disease Study's nine-step system underwent RMDA testing.

Unusual morphology of foveal Müller glia in an adult human born pre-term.

The fovea of the human retina, a specialization for acute and color vision, features a high concentration of cone photoreceptors. A pit on the inner retinal aspect is created by the centrifugal migration of post-receptoral neurons. Foveal cells are specified early in fetal life, but the fovea reaches its final configuration postnatally.

Quantitative Autofluorescence at AMD's Beginnings Highlights Retinal Topography and Grading System Differences: ALSTAR2 Baseline.

Introduction: The aims of the study were to describe baseline quantitative (short-wavelength) autofluorescence (qAF) findings in a large pseudophakic cohort at age-related macular degeneration (AMD)'s beginnings and to assess qAF8 as an outcome measure and evaluate Age-Related Eye Disease Study (AREDS) and Beckman grading systems.

Methods: In the ALSTAR2 baseline cohort (NCT04112667), 346 pseudophakic eyes of 188 persons (74.0 ± 5.

Age-Related Macular Degeneration, a Mathematically Tractable Disease.

A progression sequence for age-related macular degeneration onset may be determinable with consensus neuroanatomical nomenclature augmented by drusen biology and eye-tracked clinical imaging. This narrative review proposes to supplement the Early Treatment of Diabetic Retinopathy Study (sETDRS) grid with a ring to capture high rod densities. Published photoreceptor and retinal pigment epithelium (RPE) densities in flat mounted aged-normal donor eyes were recomputed for sETDRS rings including near-periphery rich in rods and cumulatively for circular fovea-centered regions.

Volumetric Reconstruction of a Human Retinal Pigment Epithelial Cell Reveals Specialized Membranes and Polarized Distribution of Organelles.

Purpose: Despite the centrality of the retinal pigment epithelium (RPE) in vision and retinopathy our picture of RPE morphology is incomplete. With a volumetric reconstruction of human RPE ultrastructure, we aim to characterize major membranous features including apical processes and their interactions with photoreceptor outer segments, basolateral infoldings, and the distribution of intracellular organelles.

Methods: A parafoveal retinal sample was acquired from a 21-year-old male organ donor.

Volume electron microscopy reveals human retinal mitochondria that align with reflective bands in optical coherence tomography [Invited].

Mitochondria are candidate reflectivity signal sources in optical coherence tomography (OCT) retinal imaging. Here, we use deep-learning-assisted volume electron microscopy of human retina and imaging to map mitochondria networks in the outer plexiform layer (OPL), where photoreceptors synapse with second-order interneurons. We observed alternating layers of high and low mitochondrial abundance in the anatomical OPL and adjacent inner nuclear layer (INL).

Choriocapillaris Impairment Is Associated With Delayed Rod-Mediated Dark Adaptation in Age-Related Macular Degeneration.

Purpose: Progress toward treatment and prevention of age-related macular degeneration (AMD) requires imaging end points that relate to vision. We investigated choriocapillaris flow signal deficits (FD%) and visual function in eyes of individuals aged ≥60 years, with and without AMD.

Methods: One eye of each participant in the baseline visit of the Alabama Study on Early Age-Related Macular Degeneration 2 (ALSTAR2; NCT04112667) was studied.

Ultrahigh Resolution OCT Markers of Normal Aging and Early Age-related Macular Degeneration.

Purpose: Ultrahigh 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.

Design: Prospective cross-sectional study.

Biologically Guided Optimization of Test Target Location for Rod-mediated Dark Adaptation in Age-related Macular Degeneration: Alabama Study on Early Age-related Macular Degeneration 2 Baseline.

Purpose: 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.

Macular and Plasma Xanthophylls Are Higher in Age-related Macular Degeneration than in Normal Aging: Alabama Study on Early Age-related Macular Degeneration 2 Baseline.

Purpose: 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.

Design: Cross-sectional observational study (NCT04112667).

Participants: Adults ≥ 60 years from a comprehensive ophthalmology clinic, with healthy maculas or maculas meeting fundus criteria for early or intermediate AMD.

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

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.

Histology and Clinical Lifecycle of Acquired Vitelliform Lesion, a Pathway to Advanced Age-Related Macular Degeneration.

Purpose: To evaluate hypotheses about the role of acquired vitelliform lesion (AVL) in age-related macular degeneration pathophysiology.

Design: Laboratory histology study; retrospective, observational case series.

Methods: Two donor eyes in a research archive with AVL and age-related macular degeneration were analyzed with light and electron microscopy for AVL content at locations matched to ex vivo B-scans.

Hyperreflective Foci, Optical Coherence Tomography Progression Indicators in Age-Related Macular Degeneration, Include Transdifferentiated Retinal Pigment Epithelium.

Purpose: By optical coherence tomography (OCT) imaging, hyperreflective foci (HRF) indicate progression risk for advanced age-related macular degeneration (AMD) and are in part attributable to ectopic retinal pigment epithelium (RPE). We hypothesized that ectopic RPE are molecularly distinct from in-layer cells and that their cross-retinal course follows Müller glia.

Methods: In clinical OCT (61 eyes, 44 patients with AMD, 79.

Biometrics, Impact, and Significance of Basal Linear Deposit and Subretinal Drusenoid Deposit in Age-Related Macular Degeneration.

Purpose: Basal linear deposit (BLinD) is a thin layer of soft drusen material. To elucidate the biology of extracellular deposits conferring age-related macular degeneration (AMD) progression risk and inform multimodal clinical imaging based on optical coherence tomography (OCT), we examined lipid content and regional prevalence of BLinD, soft drusen, pre-BLinD, and subretinal drusenoid deposit (SDD) in AMD and non-AMD aged eyes. We estimated BLinD volume and illustrated its relation to type 1 macular neovascularization (MNV).

Local Abundance of Macular Xanthophyll Pigment Is Associated with Rod- and Cone-Mediated Vision in Aging and Age-Related Macular Degeneration.

Purpose: We assessed the association between the abundance of macular xanthophyll carotenoid pigment using dual-wavelength autofluorescence and multimodal vision testing including rod-mediated dark adaptation (RMDA), a measure of retinoid re-supply, in adults ≥60 years old with and without age-related macular degeneration (AMD).

Methods: AMD severity was determined using the nine-step Age-Related Eye Disease Study grading. Tests probed cones (best-corrected visual acuity, contrast sensitivity), cones and rods (low-luminance visual acuity, low-luminance deficit, mesopic light sensitivity), or rods only (scotopic light sensitivity, RMDA).

Hyperreflective Foci and Specks Are Associated with Delayed Rod-Mediated Dark Adaptation in Nonneovascular Age-Related Macular Degeneration.

Purpose: Hyperreflective foci (HRF) are OCT biomarkers for the progression of nonneovascular age-related macular degeneration (AMD) attributed to anteriorly migrated retinal pigment epithelial cells. We examined associations between rod- and cone-mediated vision and HRF plus smaller hyperreflective specks (HRS); we identified a histologic candidate for HRS.

Design: Cross-sectional study and histologic survey.