Dataset Information

Genetic variants linked to myopic macular degeneration in persons with high myopia: CREAM Consortium.

ABSTRACT: PURPOSE:To evaluate the roles of known myopia-associated genetic variants for development of myopic macular degeneration (MMD) in individuals with high myopia (HM), using case-control studies from the Consortium of Refractive Error and Myopia (CREAM). METHODS:A candidate gene approach tested 50 myopia-associated loci for association with HM and MMD, using meta-analyses of case-control studies comprising subjects of European and Asian ancestry aged 30 to 80 years from 10 studies. Fifty loci with the strongest associations with myopia were chosen from a previous published GWAS study. Highly myopic (spherical equivalent [SE] ? -5.0 diopters [D]) cases with MMD (N = 348), and two sets of controls were enrolled: (1) the first set included 16,275 emmetropes (SE ? -0.5 D); and (2) second set included 898 highly myopic subjects (SE ? -5.0 D) without MMD. MMD was classified based on the International photographic classification for pathologic myopia (META-PM). RESULTS:In the first analysis, comprising highly myopic cases with MMD (N = 348) versus emmetropic controls without MMD (N = 16,275), two SNPs were significantly associated with high myopia in adults with HM and MMD: (1) rs10824518 (P = 6.20E-07) in KCNMA1, which is highly expressed in human retinal and scleral tissues; and (2) rs524952 (P = 2.32E-16) near GJD2. In the second analysis, comprising highly myopic cases with MMD (N = 348) versus highly myopic controls without MMD (N = 898), none of the SNPs studied reached Bonferroni-corrected significance. CONCLUSIONS:Of the 50 myopia-associated loci, we did not find any variant specifically associated with MMD, but the KCNMA1 and GJD2 loci were significantly associated with HM in highly myopic subjects with MMD, compared to emmetropes.

SUBMITTER: Wong YL

PROVIDER: S-EPMC6695159 | biostudies-literature | 2019

REPOSITORIES: biostudies-literature

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Genetic variants linked to myopic macular degeneration in persons with high myopia: CREAM Consortium.

Wong Yee-Ling YL Hysi Pirro P Cheung Gemmy G Tedja Milly M Hoang Quan V QV Tompson Stuart W J SWJ Whisenhunt Kristina N KN Verhoeven Virginie V Zhao Wanting W Hess Moritz M Wong Chee-Wai CW Kifley Annette A Hosoda Yoshikatsu Y Haarman Annechien E G AEG Hopf Susanne S Laspas Panagiotis P Sensaki Sonoko S Sim Xueling X Miyake Masahiro M Tsujikawa Akitaka A Lamoureux Ecosse E Ohno-Matsui Kyoko K Nickels Stefan S Mitchell Paul P Wong Tien-Yin TY Wang Jie Jin JJ Hammond Christopher J CJ Barathi Veluchamy A VA Cheng Ching-Yu CY Yamashiro Kenji K Young Terri L TL Klaver Caroline C W CCW Saw Seang-Mei SM

PloS one 20190815 8

<h4>Purpose</h4>To evaluate the roles of known myopia-associated genetic variants for development of myopic macular degeneration (MMD) in individuals with high myopia (HM), using case-control studies from the Consortium of Refractive Error and Myopia (CREAM).<h4>Methods</h4>A candidate gene approach tested 50 myopia-associated loci for association with HM and MMD, using meta-analyses of case-control studies comprising subjects of European and Asian ancestry aged 30 to 80 years from 10 studies. F ...[more]

PMID: 31415580

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Project description:BackgroundMyopic macular degeneration (MMD) is a primary cause of blindness and visual impairment in many parts of the world. A review of clinical practice guidelines (CPGs) for intervention selection are required with the increasing demand for MMD management in clinical practice as well as in national health services. Therefore, we aim to systematically review CPGs for MMD and assist the recommendations development of the Package of Eye Care Interventions (PECI) program of the World Health Organization.MethodsA systematic review of CPGs published on MMD between 2010 and April 2020 was conducted. Guidelines were evaluated using the Appraisal of Guidelines for Research and Evaluation II (AGREE II) tool. Cochrane systematic reviews were also included when the evidence from included CPGs were inadequate or contradict.ResultsAfter applying exclusion criteria and conducting the quality appraisal, two CPGs were finally included. The average of the AGREE II ratings for the identified Guidelines were 56 and 63 respectively (7 for each item). To provide further information on interventions for MMD, one Cochrane review on MMD was additionally identified and included in the study. Intravitreal anti-vascular endothelial growth factor (anti-VEGF) drugs were recommended for patients with myopic choroidal neovascularization (mCNV) as first-line therapy to improve vision and reduce central macular thickness, and ranibizumab showed significant effectiveness compared to photodynamic therapy (PDT). PDT was recommended to be performed in those resistant to the treatment by one CPG but lacked of adequate description and support. Data extracted from the Cochrane systematic reviews indicated that anti-VEGF therapy for mCNV had significant effectiveness in improving visual acuity and reducing CMT compared to PDT with moderate to low certainty of evidence. Ranibizumab and bevacizumab were considered as equally effective with moderate certainty.ConclusionsThe outcomes of this review suggest that high quality clinical practice guidelines for MMD management are limited. Intravitreal injection of anti-VEGF agents was recommended as an effective intervention to treat myopic CNV as the first-line treatment, while there was inadequate guidance for the application of PDT in myopic CNV management. The use of other interventions for MMD were not recommended at this time and additional evidence is called for.

Project description:ImportanceHigh myopia incidence and prevalence is increasing worldwide, and the visual burden caused by myopia is expected to rise accordingly. Studies investigating the occurrence of myopic complications in individuals of European ancestry with high myopia are scarce, hampering insights into the frequency of myopic retinal complications in European individuals and their visual burden.ObjectiveTo assess the frequency of myopic macular features in individuals of European ancestry with high myopia.Design, setting, and participantsThis cross-sectional analysis of the Dutch Myopia Study (MYST) and individuals with high myopia from the Rotterdam Study (RS) included 626 patients with high myopia (spherical equivalent of refractive error [SER] ≤-6 diopters [D] or axial length [AL] ≥26 mm) who underwent an extensive ophthalmic examination including multimodal retinal imaging. In addition to this combination of a population-based cohort study and mix-based high myopia study, a systematic literature review was also performed to compare findings with studies of individuals of Asian ancestry.ExposuresHigh myopia, age, and AL.Main outcomes and measuresFrequency of myopic macular and optic disc features: tessellated fundus, myopic macular degeneration (MMD), staphyloma, peripapillary intrachoroidal cavitation, peripapillary atrophy (PPA), and "plus" lesions (choroidal neovascularization, Fuchs spot, and lacquer cracks).ResultsThe mean (SD) SER of the combined study population (MYST and RS) was -9.9 (3.2) D; the mean (SD) age was 51.4 (15.1) years, and 387 (61.8%) were women. The prevalence of MMD was 25.9% and increased with older age (P for trend <.001), lower SER (odds ratio [OR], 0.70; 95% CI, 0.65-0.76; P < .001), and higher AL (OR, 2.53; 95% CI, 2.13-3.06; P < .001). Choroidal neovascularization or Fuchs spot was present in 2.7% (n = 17), both lesions in 0.3% (n = 2), and lacquer cracks in 1.4% (n = 9). Staphyloma, PPA, and MMD were highly prevalent in visual impaired and blind eyes (frequency was 73.9% [20 of 27], 90.5% [19 of 21], and 63.0% [17 of 27] of unilateral blind eyes for MMD, staphyloma, and PPA, respectively). Seven previous studies in Asian populations reported a variable MMD frequency ranging from 8.3% to 64%, but frequencies were similar for comparable risk profiles based on age and SER.Conclusions and relevanceIn this cross-sectional study of a highly myopic Dutch population of European ancestry, myopic retinal features were frequent; were associated with age, SER, and AL; and occurred in all visually severely impaired eyes. The absence of treatment options for most of these retinal complications emphasizes the need for effective strategies to prevent high myopia.

Project description:BackgroundRecent evidence indicates that gene variants related to carotenoid metabolism play a role in the uptake of macular pigments lutein (L) and zeaxanthin (Z). Moreover, these pigments are proposed to reduce the risk for advanced age-related macular degeneration (AMD). This study provides the initial examination of the relationship between the gene variants related to carotenoid metabolism, macular pigment optical density (MPOD) and their combined expression in healthy humans and patients with AMD.Participants and methodsForty-four participants were enrolled from a general population and a private practice including 20 healthy participants and 24 patients with advanced (neovascular) AMD. Participants were genotyped for the three single nucleotide polymorphisms (SNPs) upstream from BCMO1, rs11645428, rs6420424 and rs6564851 that have been shown to either up or down regulate beta-carotene conversion efficiency in the plasma. MPOD was determined by heterochromatic flicker photometry.ResultsHealthy participants with the rs11645428 GG genotype, rs6420424 AA genotype and rs6564851 GG genotype all had on average significantly lower MPOD compared to those with the other genotypes (p<0.01 for all three comparisons). When combining BCMO1 genotypes reported to have "high" (rs11645428 AA/rs6420424 GG/rs6564851 TT) and "low" (rs11645428 GG/rs6420424 AA/rs6564851 GG) beta-carotene conversion efficiency, we demonstrate clear differences in MPOD values (p<0.01). In patients with AMD there were no significant differences in MPOD for any of the three BCMO1 gene variants.ConclusionIn healthy participants MPOD levels can be related to high and low beta-carotene conversion BCMO1 genotypes. Such relationships were not found in patients with advanced neovascular AMD, indicative of additional processes influencing carotenoid uptake, possibly related to other AMD susceptibility genes. Our findings indicate that specific BCMO1 SNPs should be determined when assessing the effects of carotenoid supplementation on macular pigment and that their expression may be influenced by retinal disease.

Dataset Information

Genetic variants linked to myopic macular degeneration in persons with high myopia: CREAM Consortium.

Publications

Genetic variants linked to myopic macular degeneration in persons with high myopia: CREAM Consortium.

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