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      Diabetes Mellitus and Risk of Age-Related Macular Degeneration: A Systematic Review and Meta-Analysis

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          Abstract

          Age-related macular degeneration (AMD) is a major cause of severe vision loss in elderly people. Diabetes mellitus is a common endocrine disorder with serious consequences, and diabetic retinopathy (DR) is the main ophthalmic complication. DR and AMD are different diseases and we seek to explore the relationship between diabetes and AMD. MEDLINE, EMBASE, and the Cochrane Library were searched for potentially eligible studies. Studies based on longitudinal cohort, cross-sectional, and case-control associations, reporting evaluation data of diabetes as an independent factor for AMD were included. Reports of relative risks (RRs), hazard ratios (HRs), odds ratio (ORs), or evaluation data of diabetes as an independent factor for AMD were included. Review Manager and STATA were used for the meta-analysis. Twenty four articles involving 27 study populations were included for meta-analysis. In 7 cohort studies, diabetes was shown to be a risk factor for AMD (OR, 1.05; 95% CI, 1.00–1.14). Results of 9 cross-sectional studies revealed consistent association of diabetes with AMD (OR, 1.21; 95% CI, 1.00–1.45), especially for late AMD (OR, 1.48; 95% CI, 1.44–1.51). Similar association was also detected for AMD (OR, 1.29; 95% CI, 1.13–1.49) and late AMD (OR, 1.16; 95% CI, 1.11–1.21) in 11 case-control studies. The pooled ORs for risk of neovascular AMD (nAMD) were 1.10 (95% CI, 0.96–1.26), 1.48 (95% CI, 1.44–1.51), and 1.15 (95% CI, 1.11–1.21) from cohort, cross-sectional and case-control studies, respectively. No obvious divergence existed among different ethnic groups. Therefore, we find diabetes a risk factor for AMD, stronger for late AMD than earlier stages. However, most of the included studies only adjusted for age and sex; we thus cannot rule out confounding as a potential explanation for the association. More well-designed prospective cohort studies are still warranted to further examine the association.

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          Most cited references59

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          A simplified severity scale for age-related macular degeneration: AREDS Report No. 18.

          To develop a simplified clinical scale defining risk categories for development of advanced age-related macular degeneration (AMD). Following development of a detailed scale for individual eyes based on gradings of fundus photographs in the Age-Related Eye Disease Study, rates of progression to advanced AMD were assessed in cross-tabulations of presence or absence in each eye of 2 easily identified retinal abnormalities, drusen and pigment abnormalities. Large drusen and any pigment changes were particularly predictive of developing advanced AMD. The scoring system developed for patients assigns to each eye 1 risk factor for the presence of 1 or more large (> or = 125 microm, width of a large vein at disc margin) drusen and 1 risk factor for the presence of any pigment abnormality. Risk factors are summed across both eyes, yielding a 5-step scale (0-4) on which the approximate 5-year risk of developing advanced AMD in at least one eye increases in this easily remembered sequence: 0 factors, 0.5%; 1 factor, 3%; 2 factors, 12%; 3 factors, 25%; and 4 factors, 50%. For persons with no large drusen, presence of intermediate drusen in both eyes is counted as 1 risk factor. This simplified scale provides convenient risk categories for development of advanced AMD that can be determined by clinical examination or by less demanding photographic procedures than used in the Age-Related Eye Disease Study.
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            An international classification and grading system for age-related maculopathy and age-related macular degeneration. The International ARM Epidemiological Study Group.

            A common detection and classification system is needed for epidemiologic studies of age-related maculopathy (ARM). Such a grading scheme for ARM is described in this paper. ARM is defined as a degenerative disorder in persons > or = 50 years of age characterized on grading of color fundus transparencies by the presence of the following abnormalities in the macular area: soft drusen > or = 63 microns, hyperpigmentation and/or hypopigmentation of the retinal pigment epithelium (RPE), RPE and associated neurosensory detachment, (peri)retinal hemorrhages, geographic atrophy of the RPE, or (peri)retinal fibrous scarring in the absence of other retinal (vascular) disorders. Visual acuity is not used to define the presence of ARM. Early ARM is defined as the presence of drusen and RPE pigmentary abnormalities described above; late ARM is similar to age-related macular degeneration (AMD) and includes dry AMD (geographic atrophy of the RPE in the absence of neovascular AMD) or neovascular AMD (RPE detachment, hemorrhages, and/or scars as described above). Methods to take and grade fundus transparencies are described.
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              Age-related macular degeneration is the leading cause of blindness...

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                Author and article information

                Contributors
                Role: Editor
                Journal
                PLoS One
                PLoS ONE
                plos
                plosone
                PLoS ONE
                Public Library of Science (San Francisco, USA )
                1932-6203
                2014
                19 September 2014
                : 9
                : 9
                : e108196
                Affiliations
                [1 ]Department of Ophthalmology, The First Affiliated Hospital of Nanjing Medical University and State Key Laboratory of Reproductive Medicine, Nanjing Medical University, Nanjing, China
                [2 ]Department of Ophthalmology & Visual Sciences, The Chinese University of Hong Kong, Hong Kong, China
                [3 ]Department of Ophthalmology, The Affiliated Jiangyin Hospital of Southeast University Medical College, Jiangyin, China
                [4 ]Department of Ophthalmology, Ningbo Medical Treatment Center Lihuili Hospital, Ningbo, China
                Purdue University, United States of America
                Author notes

                Competing Interests: The authors have declared that no competing interests exist.

                Conceived and designed the experiments: CP CZ. Performed the experiments: XC SR. Analyzed the data: XC SR QX FT YL HG. Contributed reagents/materials/analysis tools: PT LC MB. Wrote the paper: XC SR CP CZ.

                Article
                PONE-D-14-18055
                10.1371/journal.pone.0108196
                4169602
                25238063
                e6b941e2-35fa-4a77-867d-13bf045a13b6
                Copyright @ 2014

                This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

                History
                : 22 April 2014
                : 18 August 2014
                Page count
                Pages: 12
                Funding
                This work was supported by National Key Basic Research Program of China (2013CB967500); National Natural Science Foundation of China (No. 81222009 and 81170856); Thousand Youth Talents Program of China (to C.Z.); Jiangsu Outstanding Young Investigator Program (BK2012046); Jiangsu Province's Key Provincial Talents Program (RC201149); Jiangsu Province's Scientific Research Innovation Program for Postgraduates (CXZZ13_0590 to X.C.); an Endowment Fund for the Lim Por-Yen Eye Genetics Research Centre; the General Research Fund from the Research Grants Council of Hong Kong (No. 473410); and A Project Funded by the Priority Academic Program Development of Jiangsu Higher Education Institutions (PAPD). The sponsor or funding organization had no role in the design or conduct of this research.
                Categories
                Research Article
                Medicine and Health Sciences
                Metabolic Disorders
                Diabetes Mellitus
                Ophthalmology
                Retinal Disorders
                Retinal Degeneration
                Macular Degeneration
                Custom metadata
                The authors confirm that all data underlying the findings are fully available without restriction. All relevant data are within the paper and its Supporting Information files.

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