Dataset Information

{omega}-3 Long-chain polyunsaturated fatty acid intake and 12-y incidence of neovascular age-related macular degeneration and central geographic atrophy: AREDS report 30, a prospective cohort study from the Age-Related Eye Disease Study.

ABSTRACT:

Background

omega-3 (n-3) Long-chain polyunsaturated fatty acids (LCPUFAs) affect processes implicated in vascular and neural retinal pathogenesis and thus may influence the risk of developing age-related macular degeneration (AMD).

Objective

We investigated whether omega-3 LCPUFA intake was associated with a reduced likelihood of developing central geographic atrophy (CGA) and neovascular (NV) AMD.

Design

We undertook a nested cohort study within a multicenter phase 3 clinical trial, the Age-Related Eye Disease Study (AREDS), to study progression to advanced AMD in 1837 persons at moderate-to-high risk of this condition. The AREDS was designed to assess the clinical course, prognosis, risk factors, and nutrient-based treatments of AMD and ran from November 1992 to December 2005. We obtained baseline data on omega-3 LCPUFA intake with a validated food-frequency questionnaire. Trained fundus graders ascertained AMD status from annual stereoscopic color photographs by using standardized methods at a single reading center across a 12-y period. We applied multivariable repeated-measures logistic regression with the incorporation of generalized estimating equation methods, because this permitted determination of progression to outcome at each visit.

Results

Participants who reported the highest omega-3 LCPUFA intake (median: 0.11% of total energy intake) were 30% less likely than their peers to develop CGA and NV AMD. The respective odds ratios were 0.65 (95% CI: 0.45, 0.92; P ConclusionsThe 12-y incidence of CGA and NV AMD in participants at moderate-to-high risk of these outcomes was lowest for those reporting the highest consumption of omega-3 LCPUFAs. If these results are generalizable, they may guide the development of low-cost and easily implemented preventive interventions for progression to advanced AMD. This trial was registered at clinicaltrials.gov as NCT00594672.

SUBMITTER: Sangiovanni JP

PROVIDER: S-EPMC2777471 | biostudies-literature | 2009 Dec

REPOSITORIES: biostudies-literature

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Publications

{omega}-3 Long-chain polyunsaturated fatty acid intake and 12-y incidence of neovascular age-related macular degeneration and central geographic atrophy: AREDS report 30, a prospective cohort study from the Age-Related Eye Disease Study.

Sangiovanni John Paul JP Agrón Elvira E Meleth A Dhananjayan AD Reed George F GF Sperduto Robert D RD Clemons Traci E TE Chew Emily Y EY

The American journal of clinical nutrition 20091007 6

<h4>Background</h4>omega-3 (n-3) Long-chain polyunsaturated fatty acids (LCPUFAs) affect processes implicated in vascular and neural retinal pathogenesis and thus may influence the risk of developing age-related macular degeneration (AMD).<h4>Objective</h4>We investigated whether omega-3 LCPUFA intake was associated with a reduced likelihood of developing central geographic atrophy (CGA) and neovascular (NV) AMD.<h4>Design</h4>We undertook a nested cohort study within a multicenter phase 3 clini ...[more]

PMID: 19812176

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Project description:PurposeTo evaluate the risk factors, incidence, and rate of progression of geographic atrophy (GA) in eyes with neovascular age-related macular degeneration (nAMD) treated with ranibizumab.DesignPost-hoc analysis of a prospective clinical study.Participants69 participants with nAMD in at least one eye.MethodsParticipants were prospectively treated in the study eye with 0.5 mg intravitreal ranibizumab. Study eyes received 4 monthly injections followed by pro re nata injections until a fluid-free macula was achieved on optical coherence tomography. Risk factors assessed included baseline demographics, treatment, and ocular characteristics on imaging. Eyes were evaluated on fundus autofluorescence (FAF) for GA. The rate of GA area growth in study and fellow eyes was analyzed by linear regression of square-root transformed areas.Main outcome measuresDevelopment of new-onset GA and rate of GA area growth measured on ocular imaging, including FAF images of the study eyes.ResultsSixty-nine participants (mean age 78.8±7.8 years) with an average of 40.0±13.6 months of follow-up were analyzed. Twenty-two of 69 study eyes (32%) were treatment naïve. During their first year of the study, participants received an average of 9.2±3.3 injections in the study eye. Of 63 study eyes with quality baseline images, 22 (35%) had pre-existing GA. Of the remaining 41 eyes, 7 (17%) developed new-onset GA during study follow-up. Those who developed new GA were older (all ≥79 years old) and had received fewer study injections on average (6.9 vs. 10.4 injections at 1 year) compared to those who did not develop new GA. Of the 12 treatment naïve study eyes without GA at baseline, 1 (8.3%) developed new GA during the study. In 21 study eyes with quantifiable GA area, eyes with GA present at baseline (16/21) enlarged by 0.34±0.26 mm/year, compared to 0.19±0.12 mm/year in eyes developing new-onset GA (5/21).ConclusionsWhile 17% of study eyes without GA present at baseline receiving ranibizumab developed new GA, the role of ranibizumab in the development of GA is unclear. Further prospective longitudinal studies are required to determine the eyes most at risk of developing GA in the setting of anti-VEGF treatment.

Project description:PurposeTo examine whether the rate of geographic atrophy (GA) enlargement is influenced by subsequent exudative neovascular age-related macular degeneration (nAMD) and hence, to explore indirectly whether nonexudative nAMD may slow GA enlargement.DesignPost hoc analysis of a controlled clinical trial cohort.ParticipantsAge-Related Eye Disease Study 2 participants 50 to 85 years of age.MethodsBaseline and annual stereoscopic color fundus photographs were evaluated for (1) GA presence and area and (2) exudative nAMD presence. Two cohorts were constructed: eyes with GA at study baseline (prevalent cohort) and eyes in which GA developed during follow-up (incident cohort). Mixed-model regression of the square root of GA area was performed according to the presence or absence of subsequent exudative nAMD.Main outcome measuresChange over time in square root of GA area.ResultsOf the 757 eyes in the incident GA cohort, over a mean follow-up of 2.3 years (standard deviation [SD], 1.2 years), 73 eyes (9.6%) demonstrated subsequent exudative nAMD. Geographic atrophy enlargement in these eyes was significantly slower (0.20 mm/year; 95% confidence interval [CI], 0.12-0.28 mm/year) compared with the other 684 eyes in which subsequent exudative nAMD did not develop (0.29 mm/year; 95% CI, 0.27-0.30 mm/year; P = 0.037). Of the 456 eyes in the prevalent GA cohort, over a mean follow-up of 4.1 years (SD, 1.4 years), 63 eyes (13.8%) demonstrated subsequent exudative nAMD. Geographic atrophy enlargement in these eyes was similar (0.31 mm/year; 95% CI, 0.24-0.37 mm/year) compared with the other 393 eyes in which subsequent exudative nAMD did not develop (0.28 mm/year; 95% CI, 0.26-0.29 mm/year; P = 0.37).ConclusionsIn eyes with recent GA, GA enlargement before the development of exudative nAMD seems slowed. This association was not observed in eyes with more long-standing GA, which have larger lesion sizes. Hence, perilesional nonexudative choroidal neovascular tissue (presumably present before the development of clinically apparent exudation) may slow enlargement of smaller GA lesions through improved perfusion. This hypothesis warrants further evaluation in prospective studies.

Project description:PurposeTo report the natural history of untreated neovascular age-related macular degeneration (nAMD) regarding subsequent macular atrophy.DesignProspective cohort within a randomized, controlled trial of oral micronutrient supplements.ParticipantsAge-Related Eye Disease Study (AREDS) participants (55-80 years) who demonstrated nAMD during follow-up (1992-2005), prior to anti-vascular endothelial growth factor (VEGF) therapy.MethodsColor fundus photographs were collected at annual study visits and graded centrally for late age-related macular degeneration (AMD). Incident macular atrophy after nAMD was examined by Kaplan-Meier analysis and proportional hazards regression.Main outcome measuresIncident macular atrophy after nAMD.ResultsOf the 4757 AREDS participants, 708 eyes (627 participants) demonstrated nAMD during follow-up and were eligible. The cumulative risks of incident macular atrophy after untreated nAMD were 9.6% (standard error, 1.2%), 31.4% (standard error, 2.2%), 43.1% (standard error, 2.6%), and 61.5% (standard error, 4.3%) at 2, 5, 7, and 10 years, respectively. This corresponded to a linear risk of 6.5% per year. The cumulative risk of central involvement was 30.4% (standard error, 3.2%), 43.4% (standard error, 3.8%), and 57.0% (standard error, 4.8%) at first appearance of atrophy, 2 years, and 5 years, respectively. Geographic atrophy (GA) in the fellow eye was associated with increased risk of macular atrophy (hazard ratio [HR], 1.70; 95% confidence interval [CI], 1.17-2.49; P = 0.006). However, higher 52-single nucleotide polymorphism AMD genetic risk score was not associated with increased risk of macular atrophy (HR, 1.03; 95% CI, 0.90-1.17; P = 0.67). Similarly, no significant differences were observed according to SNPs at CFH, ARMS2, or C3.ConclusionsThe rate of incident macular atrophy after untreated nAMD is relatively high, increasing linearly over time and affecting half of eyes by 8 years. Hence, factors other than anti-VEGF therapy are involved in atrophy development, including natural progression to GA. Comparison with studies of treated nAMD suggests it may not be necessary to invoke a large effect of anti-VEGF therapy on inciting macular atrophy, although a contribution remains possible. Central involvement is present in one third of eyes at the outset (similar to pure GA) and increases linearly to half at 3 years.

Project description:PurposeMacular atrophy (MA) of retinal pigment epithelium (RPE) and photoreceptors leads to vision loss in neovascular age-related macular degeneration (nAMD) despite successful treatment with antiangiogenic agents. To enhance understanding of MA, fortify the cellular basis of fundus autofluorescence (FAF) imaging, and inform management of nAMD, we performed histologic analysis of an eye with multimodal clinical imaging and apparent prior exudation due to nAMD.DesignCase study and clinicopathologic correlation.ParticipantA White woman in whom age-related macular degeneration (AMD) findings of inactive subretinal fibrosis (right eye) were followed for 9 years using FAF and OCT, with no detectable subretinal fluid or other recurrent exudation and no intravitreal injections before her death at age 90 years.MethodsThe right eye was preserved 6.25 hours after death, postfixed in osmium tannic acid paraphenylenediamine, and prepared for submicrometer epoxy resin sections (n = 115), with 19 matched to clinical OCT B-scans.Main outcome measuresLight microscopic morphology of a hyperautofluorescent (hyperFAF) area due to prior exudation ("floodplain" hyperFAF), hypoautofluorescent (hypoFAF) spots of MA, and areas of unremarkable FAF.ResultsFloodplain hyperFAF was visible throughout the 9 years of follow-up, with several hypoFAF atrophic spots expanding within it over time. The hyperFAF pattern corresponded to outer retinal atrophy (ORA) on OCT and photoreceptor loss over dysmorphic yet continuous RPE in histology. The hypoFAF spots inside the floodplain corresponded to complete RPE and outer retinal atrophy (cRORA) on OCT and loss of both photoreceptors and RPE in histology. In contrast, areas of unremarkable FAF showed continuous RPE accompanied by full-length photoreceptors and a thick outer nuclear layer.ConclusionsThis direct clinicopathologic correlation for FAF imaging is the first for nAMD. Fundus autofluorescence is a projection image that involves optical signal modulation by photoreceptors as well as emission signal sources in RPE. Hyperautofluorescence due to an exudative floodplain signifies loss of photoreceptors over continuous RPE. Hypoautofluorescence in MA signifies loss of both cell layers. For maximal value, fundus autofluorescence imaging should be interpreted with the multilayer perspective provided by OCT. Prevention of exudation in nAMD may preserve photoreceptors.

Project description:PurposeTo identify the development and progression of macular retinal pigment epithelial atrophy in eyes with neovascular (CNV) age-related macular degeneration (AMD) and to correlate with visual acuity (VA).DesignCohort study.ParticipantsAge-Related Eye Disease Study 2 (AREDS2) participants with intermediate AMD enrolled in a randomized controlled clinical trial of oral supplements. Analyses were conducted in the subset of AREDS2 participants who were also enrolled in the fundus autofluorescence ancillary (FAF) ancillary study.MethodsColor photographs and FAF images were evaluated in eyes that developed CNV. Presence of geographic atrophy (GA) prior to the incidence of CNV and the development of macular atrophy following incident CNV were assessed. Areas of hypoautofluorescence representing atrophy were measured for area and macular involvement. Enlargement rate of atrophy and change in visual acuity over time were analyzed.Main outcome measuresincidence and enlargement rate of atrophy and VA changes in eyes with incident CNV.ResultsIncident CNV developed in 334 (9.2%) of eyes evaluated in the AREDS2 FAF substudy. Of these, 40% had macular atrophy at incidence of CNV with half of these attributable to pre-existing GA. Atrophy developed in 14.7 % of eyes over 4 years of follow-up. Mean area of atrophy was largest in eyes with pre-existing GA and CNV (5.17 mm2, p<0.001), and atrophy involved the center of the macula in > 65% of eyes. Mean VA letter score at the annual visit in which CNV was documented was similar in the three groups with atrophy; eyes with CNV and pre-existing GA, incident atrophy at the first visit with CNV, and atrophy during follow up (60 letters). Enlargement rate of atrophy was also similar in eyes in the three groups (1.23 - 1.86 mm2, p = 0.47). Eyes with macular atrophy lost more visual acuity compared to eyes without atrophy, particularly after 2 years of follow-up (-10.9 vs. - 3.6 letters, p = 0.07).ConclusionAtrophy is commonly seen in neovascular AMD and often can be attributed to pre-existing GA. Macular atrophy and GA appear to be a continuum of the same disease process and are both associated with poor vision.

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.

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.

Dataset Information

{omega}-3 Long-chain polyunsaturated fatty acid intake and 12-y incidence of neovascular age-related macular degeneration and central geographic atrophy: AREDS report 30, a prospective cohort study from the Age-Related Eye Disease Study.

Background

Objective

Design

Results

Publications

{omega}-3 Long-chain polyunsaturated fatty acid intake and 12-y incidence of neovascular age-related macular degeneration and central geographic atrophy: AREDS report 30, a prospective cohort study from the Age-Related Eye Disease Study.

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