Dataset Information

Relating Retinal Morphology and Function in Aging and Early to Intermediate Age-related Macular Degeneration Subjects.

ABSTRACT: To evaluate relationships between age-related macular degeneration (AMD) morphology on spectral-domain optical coherence tomography (SDOCT) and visual function.Cross-sectional, observational.From the Alabama Study on Early AMD baseline visit, visual acuity, cone-mediated sensitivity, rod-mediated dark adaptation, and SDOCT were obtained in 1 eye per subject with no apparent retinal aging (n = 15), normal aging (n = 15), early AMD (n = 15), and intermediate AMD (n = 46). The volumes of retinal pigment epithelium (RPE)-drusen complex, RPE-drusen complex abnormal thinning, RPE-drusen complex abnormal thickening, and inner and outer retina were calculated in specified regions using semi-automated SDOCT segmentation.Better cone-mediated sensitivity was associated with greater RPE-drusen complex volume (r = 0.34, P < .001) and less RPE-drusen complex abnormal thinning volume (r = -0.31, P = .003). Longer rod-mediated dark adaptation time, the duration for rod-mediated sensitivity to recover from photo-bleach exposure, correlated with lower RPE-drusen complex volume (r = -0.34, P = .005) and greater RPE-drusen complex abnormal thinning volume (r = 0.280, P = .023). In 19 eyes with subretinal drusenoid deposits (SDD) vs 47 eyes without SDD, rod-mediated dark adaptation time was longer (mean ± SD 13.5 ± 7.0 vs 10.2 ± 3.1 minutes, P = .004), RPE-drusen complex abnormal thinning volume was greater (P < .0001), and visual acuity and cone sensitivity did not differ.Decreased function relates to structural markers on SDOCT in AMD. Because the RPE-drusen complex includes the interdigitation of outer segments and RPE apical processes and SDD in eyes with AMD, slower dark adaptation might be related to structural abnormalities of the RPE, the RPE-photoreceptor interface, or both.

SUBMITTER: Sevilla MB

PROVIDER: S-EPMC5567819 | biostudies-literature | 2016 May

REPOSITORIES: biostudies-literature

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Relating Retinal Morphology and Function in Aging and Early to Intermediate Age-related Macular Degeneration Subjects.

Sevilla Monica B MB McGwin Gerald G Lad Eleonora M EM Clark Mark M Yuan Eric L EL Farsiu Sina S Curcio Christine A CA Owsley Cynthia C Toth Cynthia A CA

American journal of ophthalmology 20160303

<h4>Purpose</h4>To evaluate relationships between age-related macular degeneration (AMD) morphology on spectral-domain optical coherence tomography (SDOCT) and visual function.<h4>Design</h4>Cross-sectional, observational.<h4>Methods</h4>From the Alabama Study on Early AMD baseline visit, visual acuity, cone-mediated sensitivity, rod-mediated dark adaptation, and SDOCT were obtained in 1 eye per subject with no apparent retinal aging (n = 15), normal aging (n = 15), early AMD (n = 15), and inter ...[more]

PMID: 26940163

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Project description:PurposeThe purpose of this study was to analyze spatially resolved structural changes at retinal locations in presence (+) or absence (-) of hyper-reflective foci (HRF) in eyes with subretinal pigment epithelium (RPE) drusen in intermediate age-related macular degeneration (iAMD).MethodsPatients with IAMD (n = 40; mean age = 69.7 ± 9.2 [SD] years) and healthy controls (n = 27; 64.2 ± 9.0) underwent spectral-domain optical-coherence-tomography imaging and fundus-controlled perimetry testing. After reviewing retinal layer segmentation, presence of HRF was annotated and retinal layer thicknesses (RLTs) extracted using ImageJ. Localized RLTs were compared between +HRF and -HRF positions. Univariate mixed linear models were used to investigate associations among RLT, HRF presence, and HRF size.ResultsIn iAMD eyes, a mean of 11.1 ± 12.5 HRF were detected with a peak abundance at 0.5 to 1.5 mm eccentricity to the fovea. At +HRF positions, outer nuclear layer (ONL; P = 0.0013, average difference = -12.4 µm) and retinal pigment epithelium drusen complex (RPEDC; P < 0.0001, +45.6 µm) thicknesses differed significantly compared to -HRF positions, even after correcting for accompanying drusen-related RPEDC layer thickening (P = 0.01). Mixed linear models revealed a significant association between increasing HRF area and decreasing ONL (association score = -0.17, P < 0.0001; 95% confidence interval [CI] = -0.22 to -0.11), and inner photoreceptor segments (IS) layer thicknesses (-0.08, P = 0.005; 95% CI = -0.14 to -0.03). Spearman rank correlation analysis yielded a significant correlation between total HRF area and mesopic (P = 0.015), but not scotopic (P = 0.305) retinal sensitivity losses.ConclusionsDescriptive analysis of this study demonstrated a predominant distribution of HRF at a foveal eccentricity of 0.5 to 1.5 mm, whereas further refined topographic analysis revealed a significant ONL layer thinning in presence of HRF even after correction for sub-RPE drusen presence compared to lesions in absence of HRF. Longitudinal studies are further needed to analyze the prognostic impact as well as the role of HRF presence in the context of iAMD.

Project description:Age-related macular degeneration (AMD), the leading cause of blindness in elderly populations, involves the loss of central vision due to progressive dysfunction of the retinal pigment epithelium (RPE) and subsequent loss of light-sensing photoreceptors. While age is a key risk factor, not every aged individual develops AMD. Thus, the critical question is what specific cellular changes tip the balance from healthy aging to disease. To distinguish between changes associated with aging and AMD, we compared the RPE proteome in human eye bank tissue from nondiseased donors during aging (n = 50, 29-91 years) and in donors with AMD (n = 36) compared to age-matched donors without disease (n = 28). Proteins from RPE cells were separated on two-dimensional gels, analyzed for content, and identified using mass spectrometry. A total of 58 proteins displayed significantly altered content with either aging or AMD. Proteins involved in metabolism, protein turnover, stress response, and cell death were altered with both aging and AMD. However, the direction of change was predominantly opposite. With aging, we detected an overall decrease in metabolism and reductions in stress-associated proteins, proteases, and chaperones. With AMD, we observed upregulation of metabolic proteins involved in glycolysis, TCA, and fatty acid metabolism, with a concurrent decline in oxidative phosphorylation, suggesting a reprogramming of energy utilization. Additionally, we detected upregulation of proteins involved in the stress response and protein turnover. Predicted upstream regulators also showed divergent results, with inhibition of inflammation and immune response with aging and activation of these processes with AMD. Our results support the idea that AMD is not simply advanced aging but rather the culmination of perturbed protein homeostasis, defective bioenergetics, and increased oxidative stress within the aging RPE, exacerbated by environmental factors and the genetic background of an individual.

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:PurposeDrusen and migrating retinal pigment epithelium have been associated with hyperreflective foci (HF) detected by spectral-domain optical coherence tomography (SD-OCT). This study sought to quantify the change in intraretinal HF distribution and its correlation with age-related macular degeneration (AMD) disease progression.DesignProspective observational study from the multicenter Age-Related Eye Disease Study 2 (AREDS2) Ancillary SD-OCT Study.ParticipantsPatients (n=299) with 1 enrolled eye with intermediate AMD and baseline SD-OCT, followed by SD-OCT imaging at 1-year and 2-year visits.MethodsThe number and location of HF were scored in SD-OCT scans of all 299 eyes. The change in transverse (horizontal) and axial (vertical) distribution of HF in the macula were evaluated with pairwise signed-rank tests. Two-year inner retinal HF migration was determined by the change in HF-weighted axial distribution (AxD) score calculated for each eye. The correlation of HF with SD-OCT features of AMD progression was evaluated with logistic regression analysis.Main outcome measuresThe mean change in number of HF, transverse and axial distribution of HF in the macula, and AxD per eye.ResultsIn 299 study eyes, the 2-year increase in the number of HF (P<0.001) and the AxD (P<0.001) per eye represented longitudinal proliferation and shift to inner retinal layers, respectively. Eyes with geographic atrophy (GA) at 2 years were correlated with the presence of baseline HF (P<0.001; odds ratio [OR], 4.72; 95% confidence interval [CI], 2.43-9.80), greater number of baseline HF (P<0.001; OR, 1.61 per HF; 95% CI, 1.32-2.00), and greater baseline AxD (P<0.001; OR, 1.58 per AxD point; 95% CI, 1.29-1.95).ConclusionsProliferation and inner retinal migration of SD-OCT HF occurred during follow-up in eyes with intermediate AMD. These characteristics were associated with greater incidence of GA at year 2; therefore, SD-OCT HF proliferation and migration may serve as biomarkers for AMD progression.Financial disclosure(s)Proprietary or commercial disclosure may be found after the references.

Dataset Information

Relating Retinal Morphology and Function in Aging and Early to Intermediate Age-related Macular Degeneration Subjects.

Publications

Relating Retinal Morphology and Function in Aging and Early to Intermediate Age-related Macular Degeneration Subjects.

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