Dataset Information

Association Between the Cilioretinal Artery and Choroidal Neovascularization in Age-Related Macular Degeneration: A Secondary Analysis From the Age-Related Eye Disease Study.

ABSTRACT: Importance:A hemodynamic role in the pathogenesis of age-related macular degeneration (AMD) has been proposed, but to our knowledge, an association between retinal vasculature and late AMD has not been investigated. Objective:To determine whether the presence and location of a cilioretinal artery may be associated with the risk of late AMD in the Age-Related Eye Disease Study (AREDS). Design, Setting, and Participants:Retrospective analysis of prospective, randomized clinical trial data from 3647 AREDS participants. Fundus photographs of AREDS participants were reviewed by 2 masked graders for the presence or absence of a cilioretinal artery and whether any branch extended within 500 ?m of the central macula. Multivariate regressions were used to determine the association of the cilioretinal artery and vessel location, adjusted for age, sex, and smoking status, with the prevalence of choroidal neovascularization (CNV) or central geographic atrophy (CGA) and AMD severity score for eyes at randomization and progression at 5 years. Main Outcomes and Measures:Association of cilioretinal artery with prevalence and 5-year incidence of CNV or CGA. Results:Among AREDS participants analyzed, mean (SD) age was 69.0 (5.0) years, with 56.3% female, 46.6% former smokers, and 6.9% current smokers. A total of 26.9% of patients had a cilioretinal artery in 1 eye, and 8.4% had the vessel bilaterally. At randomization, eyes with a cilioretinal artery had a lower prevalence of CNV (5.0% vs 7.6%; OR, 0.66; 95% CI, 0.51-0.85; P?=?.001) but no difference in CGA (1.1% vs 0.8%; OR, 1.33; 95% CI, 0.76-2.32; P?=?.31). In eyes without late AMD, those with a cilioretinal artery also had a lower mean (SD) AMD severity score (3.00 [2.35] vs 3.19 [2.40]; P?=?.02). At 5 years, eyes at risk with a cilioretinal artery had lower rates of progression to CNV (4.1% vs 5.5%; OR, 0.75; 95% CI, 0.56-1.00; P?=?.05) but no difference in developing CGA (2.2% vs 2.7%; OR, 0.83; 95% CI, 0.56-1.23; P?=?.35) or change in AMD severity score (0.65 [1.55] vs 0.73 [1.70]; P?=?.11). In patients with a unilateral cilioretinal artery, eyes with the vessel showed a lower prevalence of CNV than fellow eyes (4.7% vs 7.2%; P?=?.01). Conclusions and Relevance:The presence of a cilioretinal artery is associated with a lower risk of developing CNV, but not CGA, suggesting a possible retinal hemodynamic contribution to the pathogenesis of neovascular AMD. Trial Registration:ClinicalTrials.gov Identifier: NCT00000145.

SUBMITTER: Snyder K

PROVIDER: S-EPMC6142983 | biostudies-literature | 2018 Sep

REPOSITORIES: biostudies-literature

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Association Between the Cilioretinal Artery and Choroidal Neovascularization in Age-Related Macular Degeneration: A Secondary Analysis From the Age-Related Eye Disease Study.

Snyder Kiersten K Yazdanyar Amirfarbod A Mahajan Aditi A Yiu Glenn G

JAMA ophthalmology 20180901 9

<h4>Importance</h4>A hemodynamic role in the pathogenesis of age-related macular degeneration (AMD) has been proposed, but to our knowledge, an association between retinal vasculature and late AMD has not been investigated.<h4>Objective</h4>To determine whether the presence and location of a cilioretinal artery may be associated with the risk of late AMD in the Age-Related Eye Disease Study (AREDS).<h4>Design, setting, and participants</h4>Retrospective analysis of prospective, randomized clinic ...[more]

PMID: 29978186

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Project description:ObjectiveTo assess the influence of drug; dosing regimen; and traditional, nontraditional, and genetic risk factors on the incidence of choroidal neovascularization (CNV) in the fellow eye of patients treated for CNV with ranibizumab or bevacizumab.DesignCohort study of patients enrolled in a multicenter, randomized clinical trial.ParticipantsPatients with no CNV in the fellow eye at the time of enrollment in the Comparison of Age-Related Macular Degeneration Treatments Trials (CATT).MethodsEligibility criteria for the clinical trial required that study eyes have evidence on fluorescein angiography and optical coherence tomography of CNV secondary to age-related macular degeneration (AMD) and visual acuity between 20/25 and 20/320. Treatment for the study eye was assigned randomly to either ranibizumab or bevacizumab and to 3 different regimens for dosing over a 2-year period. The genotypes for 4 single nucleotide polymorphisms (SNPs) associated with risk of AMD were determined. Only patients without CNV in the fellow eye at baseline were considered at risk. The CATT ophthalmologists examined patients every 4 weeks through 2 years and recorded treatment for CNV in the fellow eye.Main outcome measuresDevelopment of CNV in the fellow eye.ResultsAmong 1185 CATT participants, 727 (61%) had no CNV in the fellow eye at enrollment. At 2 years, CNV had developed in 75 (20.6%) of 365 patients treated with ranibizumab and in 60 (16.6%) of 362 patients treated with bevacizumab (absolute difference, 4.0%; 95% confidence interval [CI], -1.7% to 9.6%; P = 0.17). The risk ratio for pro re nata dosing relative to monthly dosing was 1.1 (95% CI, 0.8-1.6). Greater elevation of the retinal pigment epithelium and fluid in the foveal center of the study eye were associated with increased incidence of CNV in the fellow eye. Incidence was not associated with genotype on rs1061170 (CFH), rs10490924 (ARMS2), rs11200638 (HTRA1), and rs2230199 (C3; P>0.35).ConclusionsThrough 2 years, there was no statistically significant difference between ranibizumab and bevacizumab in incidence of CNV in the fellow eye. Genotype on 4 SNPs previously found to be associated with AMD did not affect the risk of CNV in the fellow eye among CATT patients.Financial disclosure(s)Proprietary or commercial disclosure may be found after the references.

Project description:ImportanceRecent reports suggest that cilioretinal arteries (CRAs) confer protection against developing advanced age-related macular degeneration (AMD).ObjectiveTo further characterize the association between the presence of a CRA and incidence of geographic atrophy (GA) or choroidal neovascularization (CNV).DesignThis cohort study constituted an ad hoc secondary analysis of data from the Comparison of Age-Related Macular Degeneration Treatments Trials (CATT) and was performed at 44 clinical centers in the United States among participants in CATT with CNV in the study eye and without advanced AMD in the fellow eye at baseline. The presence of a CRA was determined by 2 graders, masked to clinical data, using color fundus photographs, red-free fundus photographs, and fluorescein angiography. The proportion with CRAs at baseline between the study eye with CNV and fellow eye without CNV was first compared. The association of a CRA with incidence of CNV or GA at 5 years among fellow eyes and with incidence of GA among study (treated) eyes was then assessed. In addition, the association of CRAs with the Age-Related Eye Disease Study severity scale among the fellow eyes at baseline was assessed. Data were collected from February 1, 2008, through April 30, 2015, and analyzed from July 1, 2018, through April 30, 2019.ExposuresPresence of a CRA.Main outcomes and measuresThe association between the presence of a CRA and incidence of CNV or GA at 5 years of follow-up.ResultsA total of 350 patients (700 eyes) (230 [65.7% women; mean [SD] age, 77 [7.2] years) were included in the analysis. Cilioretinal arteries were present in 67 of 345 (19.4%) fellow eyes without baseline CNV and 73 of 349 (20.9%) study eyes with baseline CNV (P = .60). Cilioretinal arteries in fellow eyes were not associated with incidence of CNV at 5 years (125 of 278 [45.0%] among eyes without CRAs and 30 of 67 [44.8%] among eyes with CRAs; P = .99) or with incidence of GA at 5 years (110 of 278 [39.6%] among eyes without CRAs and 25 of 67 [37.3%] among eyes with CRAs; P = .89). Cilioretinal arteries in study eyes were not associated with incidence of GA at 5 years (105 of 276 [38.0%] study eyes without CRAs and 26 of 73 [35.6%] study eyes with CRAs; P = .72).Conclusions and relevanceThe analysis did not find a protective association between CRAs and incidence of CNV or GA among CATT participants who had unilateral exudative AMD. Why these findings were different from those of previous publications is unclear but may be partially explained by the different techniques used to detect CRAs or by the baseline advanced disease in CATT participants.Trial registrationClinicalTrials.gov identifier: NCT00593450.

Project description:PurposeTo detect and quantify choroidal neovascularization (CNV) in patients with age-related macular degeneration (AMD) using optical coherence tomography (OCT) angiography.DesignObservational, cross-sectional study.ParticipantsA total of 5 normal subjects and 5 subjects with neovascular AMD were included.MethodsA total of 5 eyes with neovascular AMD and 5 normal age-matched controls were scanned by a high-speed (100 000 A-scans/seconds) 1050-nm wavelength swept-source OCT. The macular angiography scan covered a 3 × 3-mm area and comprised 200 × 200 × 8 A-scans acquired in 3.5 seconds. Flow was detected using the split-spectrum amplitude-decorrelation angiography (SSADA) algorithm. Motion artifacts were removed by 3-dimensional (3D) orthogonal registration and merging of 4 scans. The 3D angiography was segmented into 3 layers: inner retina (to show retinal vasculature), outer retina (to identify CNV), and choroid. En face maximum projection was used to obtain 2-dimensional angiograms from the 3 layers. The CNV area and flow index were computed from the en face OCT angiogram of the outer retinal layer. Flow (decorrelation) and structural data were combined in composite color angiograms for both en face and cross-sectional views.Main outcome measuresThe CNV angiogram, CNV area, and CNV flow index.ResultsEn face OCT angiograms of CNV showed sizes and locations that were confirmed by fluorescein angiography (FA). Optical coherence tomography angiography provided more distinct vascular network patterns that were less obscured by subretinal hemorrhage. The en face angiograms also showed areas of reduced choroidal flow adjacent to the CNV in all cases and significantly reduced retinal flow in 1 case. Cross-sectional angiograms were used to visualize CNV location relative to the retinal pigment epithelium and Bruch's layer and classify type I and type II CNV. A feeder vessel could be identified in 1 case. Higher flow indexes were associated with larger CNV and type II CNV.ConclusionsOptical coherence tomography angiography provides depth-resolved information and detailed images of CNV in neovascular AMD. Quantitative information regarding CNV flow and area can be obtained. Further studies are needed to assess the role of quantitative OCT angiography in the evaluation and treatment of neovascular AMD.

Project description:PurposeTo evaluate the first association specific to exudative age-related macular degeneration (AMD) located near the matrix metalloproteinase 9 (MMP9) gene.DesignGenetic association study.ParticipantsOne thousand seven hundred twelve patients with AMD (672 nonexudative, 1040 exudative) of predominantly northern European descent seeking treatment at the University of Iowa Hospitals and Clinics.MethodsWe reanalyzed the International AMD Genetics Consortium (IAMDGC) data to validate the association of polymorphisms near MMP9 with exudative AMD and to identify additional associated single nucleotide polymorphisms (SNPs), especially MMP9 coding sequence SNPs. We genotyped a cohort of 1712 AMD patients from Iowa with 3 SNPs identified with our analysis of the IAMDGC cohort using commercially available real-time quantitative polymerase chain reaction (PCR) assays. Firth regression was used to measure the association between MMP9 SNP genotypes and exudative AMD in our cohort of patients from Iowa. In addition, we developed a PCR-based assay to genotype the Iowa cohort at a short tandem repeat polymorphism (STRP) at the MMP9 locus.Main outcome measuresOdds ratios and P values for exudative compared with nonexudative AMD patients in the Iowa cohort for MMP9 SNPs (rs4810482, rs17576, and rs17577) and STRP.ResultsWe identified 3 SNPs in the MMP9 locus (rs4810482, rs17576, and rs17577) that are highly associated with exudative AMD in patient cohorts of the IAMDGC. These MMP9 SNPs also are associated with exudative AMD in the cohort of 1712 AMD patients from Iowa (rs4810482: odds ratio [OR], 0.82; P = 0.010; rs17576: OR, 0.86; P = 0.046; and rs17577: OR, 0.80; P = 0.041). We also genotyped the cohort of AMD patients from Iowa at rs142450006, another MMP9 polymorphism that previously was associated with exudative AMD. We detected a 4bp STRP, (TTTC)n, at the rs142450006 locus that is highly polymorphic and associated significantly with exudative AMD (OR, 0.78; P = 0.016).ConclusionsThis study independently confirms and expands an association between the MMP9 locus and exudative AMD, further implicating a role for extracellular matrix abnormalities in choroidal neovascularization.

Dataset Information

Association Between the Cilioretinal Artery and Choroidal Neovascularization in Age-Related Macular Degeneration: A Secondary Analysis From the Age-Related Eye Disease Study.

Publications

Association Between the Cilioretinal Artery and Choroidal Neovascularization in Age-Related Macular Degeneration: A Secondary Analysis From the Age-Related Eye Disease Study.

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