Dataset Information

Topographic Variation of the Growth Rate of Geographic Atrophy in Nonexudative Age-Related Macular Degeneration: A Systematic Review and Meta-analysis.

ABSTRACT: Purpose:To determine the impact of topographic locations on the progression rate of geographic atrophy (GA). Methods:We searched in five literature databases up to May 3, 2019, for studies that evaluated the growth rates of GA lesions at different retinal regions. We performed random-effects meta-analyses to determine and compare the GA effective radius growth rates in four location groups defined by two separate classification schemes: (1) macular center point involved (CPI) or spared (CPS) in classification 1, and (2) foveal zone involved (FZI) or spared (FZS) in classification 2. We then estimated the GA growth rate in eight topographic zones and used the data to model the GA expansion. Results:We included 11 studies with 3254 unique eyes. In studies that used classification 1, the effective radius growth rate was 30.1% higher in the CPS group (0.203 ± 0.013 mm/year) than in the CPI group (0.156 ± 0.011 mm/year) (P < 0.001). This trend became significantly more prominent in classification 2, where the growth rate was 61.7% higher in the FZS group (0.215 ± 0.012 mm/year) than in the FZI group (0.133 ± 0.009 mm/year) (P < 0.001). The estimated GA effective radius growth rates in eight retinal zones fit a Gaussian function, and the modeling of GA expansion gave rise to various GA configurations comparable to clinical observations. Conclusions:This study indicates that the GA progression rate varies significantly across different retinal locations. Our analysis may shed light on the natural history and underlying mechanism of GA progression.

SUBMITTER: Shen LL

PROVIDER: S-EPMC7205189 | biostudies-literature | 2020 Jan

REPOSITORIES: biostudies-literature

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Topographic Variation of the Growth Rate of Geographic Atrophy in Nonexudative Age-Related Macular Degeneration: A Systematic Review and Meta-analysis.

Shen Liangbo L LL Sun Mengyuan M Khetpal Sumun S Grossetta Nardini Holly K HK Del Priore Lucian V LV

Investigative ophthalmology & visual science 20200101 1

<h4>Purpose</h4>To determine the impact of topographic locations on the progression rate of geographic atrophy (GA).<h4>Methods</h4>We searched in five literature databases up to May 3, 2019, for studies that evaluated the growth rates of GA lesions at different retinal regions. We performed random-effects meta-analyses to determine and compare the GA effective radius growth rates in four location groups defined by two separate classification schemes: (1) macular center point involved (CPI) or s ...[more]

PMID: 31995152

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Project description:BACKGROUND:There is growing evidence of the importance of nutrition in age-related macular degeneration (AMD), but few studies have explored associations with folate and B vitamins. No effective therapeutic strategy for geographic atrophy (GA) is available, and prevention could be of great value. OBJECTIVE:We investigated associations between dietary folate, B vitamins, and progression to GA and whether these associations might be modified by genetic susceptibility. DESIGN:Among 2525 subjects (4663 eyes) in the Age-Related Eye Disease Study, 405 subjects (528 eyes) progressed to GA over 13 y. Folate and B vitamins were log transformed and calorie adjusted separately for men and women. Ten loci in 7 AMD genes [complement factor H, age-related maculopathy susceptibility 2/high-temperature requirement A serine peptidase 1, complement component 2, complement component 3, complement factor B, collagen type VIII ? 1, and RAD51 paralog B] were examined. Survival analysis was used to assess associations between incident GA and dietary intake of folate and B vitamins. Interaction effects between these nutrients and genetic variation on AMD risk were also evaluated. Subjects with at least one eye free of advanced AMD at baseline were included in these analyses. RESULTS:There was a reduced risk of progression to GA with increasing intake of thiamin, riboflavin, and folate after adjusting for age, sex, and total energy intake (P-trend = 0.01, 0.03, and 0.001, respectively). After adjustment for demographic, behavioral, ocular, and genetic covariates, trends remained statistically significant for folate (P-trend = 0.007) and were borderline for thiamin (P-trend = 0.05). Riboflavin did not retain statistical significance (P-trend = 0.20). Folate was significantly associated with lower risk of incident GA among subjects homozygous for the complement component 3 (C3) R102G rs2230199 nonrisk genotype (CC) (HR = 0.43; 95% CI: 0.27, 0.70; P = 0.0005) but not subjects carrying the risk allele (G) (P = 0.76). Neither folate nor any B vitamin was significantly associated with neovascular AMD. CONCLUSIONS:High folate intake was associated with a reduced risk of progression to GA. This relation could be modified by genetic susceptibility, particularly related to the C3 genotype. This trial was registered at clinicaltrials.gov as NCT00594672.

Project description:To evaluate the growth of geographic atrophy (GA) during anti-vascular endothelial growth factor (VEGF) therapy.Cohort within a clinical trial.Patients included in the Comparison of Age-related Macular Degeneration Treatments Trials (CATT).Participants were randomly assigned to injections of ranibizumab or bevacizumab and to a 2-year dosing regimen of monthly or pro re nata (PRN) or to monthly for 1 year and PRN the following year. Digital color photographs and fluorescein angiograms at baseline and 1 and 2 years were evaluated for GA, and the total area of GA was measured by 2 graders masked to treatment; differences were adjudicated. Multivariate linear mixed models of the annual change in the square root of the area included baseline demographic, treatment, and ocular characteristics on imaging as candidate risk factors.Geographic atrophy growth rate.Among 1185 participants, 86 (7.3%) had GA at baseline, 120 (10.1%) developed GA during year 1, and 36 (3.0%) developed GA during year 2. Among 194 eyes evaluable for growth, the rate was 0.43 mm/yr (standard error [SE], ±0.03 mm/year). In multivariate analysis, the growth rate was 0.37 mm/year in eyes receiving bevacizumab and 0.49 mm/year in eyes receiving ranibizumab (difference, 0.11 mm/yr; 95% confidence interval [CI], 0.01-0.22; P = 0.03). Growth rate did not differ between eyes treated monthly and PRN (P = 0.85). Eyes with subfoveal choroidal neovascularization (CNV) lesions had a lower growth rate than eyes with nonsubfoveal CNV lesions (difference, 0.12; 95% CI, 0.01-0.22; P = 0.03). Eyes with GA farther from the fovea had higher growth rates by 0.14 (95% CI, 0.01-27) mm/year for every millimeter farther from the fovea. The growth rate was 0.58 mm/year for eyes with predominantly classic lesions, 0.41 mm/year for eyes with minimally classic lesions, and 0.30 mm/year for eyes with occult only lesions (P < 0.01). The growth rate in eyes having a fellow eye with GA was higher by 0.13 mm/year (95% CI, 0.01-0.24; P = 0.03) than in eyes without GA in the fellow eye. Eyes with epiretinal membrane had a higher growth rate than eyes without epiretinal membrane (difference, 0.16; 95% CI, 0.03-0.30; P = 0.02).Geographic atrophy growth depends on several ocular factors. Ranibizumab may accelerate GA growth.

Project description:ImportanceSensitive outcome measures for disease progression are needed for treatment trials in geographic atrophy (GA) secondary to age-related macular degeneration (AMD).ObjectiveTo quantify photoreceptor degeneration outside regions of GA in eyes with nonexudative AMD, to evaluate its association with future GA progression, and to characterize its spatio-temporal progression.Design, setting, and participantsMonocenter cohort study (Directional Spread in Geographic Atrophy [NCT02051998]) and analysis of data from a normative data study at a tertiary referral center. One hundred fifty-eight eyes of 89 patients with a mean (SD) age of 77.7 (7.1) years, median area of GA of 8.87 mm2 (IQR, 4.09-15.60), and median follow-up of 1.1 years (IQR, 0.52-1.7 years), as well as 93 normal eyes from 93 participants.ExposuresLongitudinal spectral-domain optical coherence tomography (SD-OCT) volume scans (121 B-scans across 30° × 25°) were segmented with a deep-learning pipeline and standardized in a pointwise manner with age-adjusted normal data (z scores). Outer nuclear layer (ONL), photoreceptor inner segment (IS), and outer segment (OS) thickness were quantified along evenly spaced contour lines surrounding GA lesions. Linear mixed models were applied to assess the association between photoreceptor-related imaging features and GA progression rates and characterize the pattern of photoreceptor degeneration over time.Main outcomes and measuresAssociation of ONL thinning with follow-up time (after adjusting for age, retinal topography [z score], and distance to the GA boundary).ResultsThe study included 158 eyes of 89 patients (51 women and 38 men) with a mean (SD) age of 77.7 (7.1) years. The fully automated B-scan segmentation was accurate (dice coefficient, 0.82; 95% CI, 0.80-0.85; compared with manual markings) and revealed a marked interpatient variability in photoreceptor degeneration. The ellipsoid zone (EZ) loss-to-GA boundary distance and OS thickness were prognostic for future progression rates. Outer nuclear layer and IS thinning over time was significant even when adjusting for age and proximity to the GA boundary (estimates of -0.16 μm/y; 95% CI, -0.30 to -0.02; and -0.17 μm/y; 95% CI, -0.26 to -0.09).Conclusions and relevanceDistinct and progressive alterations of photoreceptor laminae (exceeding GA spatially) were detectable and quantifiable. The degree of photoreceptor degeneration outside of regions of retinal pigment epithelium atrophy varied markedly between eyes and was associated with future GA progression. Macula-wide photoreceptor laminae thinning represents a potential candidate end point to monitor treatment effects beyond mere GA lesion size progression.

Project description:PurposeWe sought to determine whether genotype is associated with rate of growth of geographic atrophy (GA) in eyes with age-related macular degeneration (AMD).DesignProspective analysis of participants in a randomized controlled clinical trial.ParticipantsWe included 114 eyes of 114 participants in the Age-Related Eye Disease Study (AREDS).MethodsFundus photographs from AREDS participants with GA from whom a DNA specimen had been obtained and serial photographs had been taken over a minimum of 2 years were evaluated for progression as determined by change in cumulative area of GA. All fundus photographs were scanned, digitized, and centrally graded longitudinally for area of GA. The relationship of GA progression with previously identified genetic variants associated with AMD was assessed.Main outcome measuresGenotype frequencies and change in cumulative area of GA.ResultsThe mean growth rate of GA for the 114 eyes was 1.79 mm(2)/year (range, 0.17-4.76). No association between growth rate and genotype was present for variants in the CFH, C2, C3, APOE, and TLR3 genes. For the single nucleotide polymorphism rs10490924 in LOC387715/ARMS2, there was a significant association of GA growth rate, both adjusted and unadjusted for initial lesion size, with the homozygous risk genotype as compared with the homozygous nonrisk genotype (unadjusted P = 0.002; Bonferroni-corrected P = 0.014) and for allelic association (Bonferroni-corrected P value = 0.011). Analyses of other measures of GA progression (progression to central GA from extrafoveal GA and development of bilateral GA in those initially with unilateral GA) showed no statistically significant association between progression and the LOC387715/ARMS2/HTRA1 genotype.ConclusionsGrowth rates of GA calculated from digitized serial fundus photographs showed no association with variants in the CFH, C2, C3, APOE, or TLR3 genes. There was a nominally significant association with the LOC387715/ARMS2/HTRA1 genotype, although this finding was not supported by analyses of secondary measures of GA progression. Replication in other populations is needed to establish the existence of an association.

Project description:PURPOSE:In an eye with geographic atrophy (GA) secondary to age-related macular degeneration, we correlated ex vivo histologic features with findings recorded in vivo using optical coherence tomography (OCT), near-infrared reflectance imaging, and fundus autofluorescence. METHODS:In the left eye of an 86-year-old white woman, in vivo near-infrared reflectance and eye-tracked OCT B-scans at each of 6 clinic visits and a baseline fundus autofluorescence image were correlated with high-resolution histologic images of the preserved donor eye. RESULTS:Clinical imaging showed a small parafoveal multilobular area of GA, subfoveal soft drusen, refractile drusen, hyperreflective lines near the Bruch membrane, subretinal drusenoid deposit (reticular pseudodrusen), and absence of hyperautofluorescent foci at the GA margin. By histology, soft drusen end-stages included avascular fibrosis with highly reflective cholesterol crystals. These accounted for hyperreflective lines near the Bruch membrane in OCT and plaques in near-infrared reflectance imaging. Subretinal drusenoid deposit was thick, continuous, extracellular, extensive outside the fovea, and associated with distinctive retinal pigment epithelium dysmorphia and photoreceptor degeneration. A hyporeflective wedge corresponded to ordered Henle fibers without cellular infiltration. The external limiting membrane descent, which delimits GA, was best visualized in high-quality OCT B-scans. Retinal pigment epithelium and photoreceptor changes at the external limiting membrane descent were consistent with our recent histologic survey of donor eyes. CONCLUSION:This case informs on the extent, topography, and lifecycle of extracellular deposits. High-quality OCT scans are required to reveal all tissue features relevant to age-related macular degeneration progression to GA, especially the external limiting membrane descent. Histologically validated signatures of structural OCT B-scans can serve as references for other imaging modalities.

Dataset Information

Topographic Variation of the Growth Rate of Geographic Atrophy in Nonexudative Age-Related Macular Degeneration: A Systematic Review and Meta-analysis.

Publications

Topographic Variation of the Growth Rate of Geographic Atrophy in Nonexudative Age-Related Macular Degeneration: A Systematic Review and Meta-analysis.

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