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      Risk factors for early-onset exfoliation syndrome

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      Scientific Reports
      Nature Publishing Group UK
      Glaucoma, Optic nerve diseases

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          Abstract

          Although exfoliation syndrome (XFS) is an age-related, late-onset disease, early-onset XFS has been reported, and its associated factors remain unknown. In this study, we investigated the clinical features and risk factors of early-onset XFS. The participants were divided into two groups according to age at the time of XFS diagnosis: early-onset (< 60 years) or late-onset (≥ 70 years) group. Among the 302 eyes of 240 patients with XFS, the early-onset group included 41 eyes (14%) of 33 patients, and the late-onset group included 163 eyes (54%) of 126 patients; the mean age was 54.8 ± 5.0 and 76.6 ± 4.9 years, respectively ( p < 0.001). All eight cases diagnosed with XFS at the earliest age, ranging from 36 to 52 years, underwent trabeculectomy before the diagnosis of XFS. Multivariable logistic regression analysis showed that a history of trabeculectomy (odds ratio [OR] = 11.435, p < 0.001), presence of iridectomy (OR = 11.113, p < 0.001), and longer axial length (OR = 2.311, p = 0.003) were significantly associated with the development of early-onset XFS. Collectively, patients with early-onset XFS were more likely to have undergone trabeculectomy and have more axial myopia compared with those with late-onset XFS. These findings suggest that surgical trauma compromising the blood-aqueous barrier may trigger early manifestation of XFS.

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          Common sequence variants in the LOXL1 gene confer susceptibility to exfoliation glaucoma.

          Glaucoma is a leading cause of irreversible blindness. A genome-wide search yielded multiple single-nucleotide polymorphisms (SNPs) in the 15q24.1 region associated with glaucoma. Further investigation revealed that the association is confined to exfoliation glaucoma (XFG). Two nonsynonymous SNPs in exon 1 of the gene LOXL1 explain the association, and the data suggest that they confer risk of XFG mainly through exfoliation syndrome (XFS). About 25% of the general population is homozygous for the highest-risk haplotype, and their risk of suffering from XFG is more than 100 times that of individuals carrying only low-risk haplotypes. The population-attributable risk is more than 99%. The product of LOXL1 catalyzes the formation of elastin fibers found to be a major component of the lesions in XFG.
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            Exfoliation Syndrome

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              Role of transforming growth factor-beta1 and its latent form binding protein in pseudoexfoliation syndrome.

              Pseudoexfoliation (PEX) syndrome is a common and clinically important systemic condition characterized by the pathologic production and accumulation of an abnormal fibrillar extracellular material in many intra- and extraocular tissues. Recent evidence suggests that it is a type of elastosis associated with the excess synthesis of elastic microfibrillar components such as fibrillin-1. Since transforming growth factor (TGF)-beta is a major modulator of extracellular matrix formation, the potential involvement of TGF-beta and its latent form binding protein (LTBP) in this aberrant matrix process was investigated. The expression of various isoforms of TGF-beta and LTBP was investigated in the anterior segment tissues of PEX and control eyes on the protein and mRNA level by light and electron microscopic immunohistochemistry, in situ hybridization, and semiquantitative RT-PCR. TGF-beta1 and TGF-beta2 levels were measured in aqueous humor and serum of PEX and control patients by ELISA. Cultures of Tenon's capsule fibroblasts were established to study the effect of TGF-beta1 on fibrillin-1 mRNA expression by Northern blot analysis. Significantly increased concentrations of both total and active TGF-beta1 were measured in the aqueous humor of PEX eyes without and with glaucoma as compared to control eyes, whereas levels of TGF-beta2 were not significantly different. The expression of TGF-beta1, LTBP-1, and LTBP-2, but not TGF-beta2, was markedly increased in anterior segment tissues of PEX eyes, particularly in the non-pigmented epithelium of the ciliary body, on both the mRNA and the protein level. Latent TGF-beta1 staining was consistently associated with PEX material deposits and could be released by proteolytic processing. Double immunolabeling revealed clear co-localization of LTBP-1 and -2 with latent TGF-beta1 and with fibrillin-1 on PEX fibrils. The expression of mRNA coding for fibrillin-1 was up-regulated in vitro by TGF-beta1. This study provides evidence for a significant role of TGF-beta1 and the LTBPs 1 and 2 in PEX syndrome. The results suggest that increased levels of latent and active TGF-beta1 in the aqueous humor of PEX patients, derived from enhanced local synthesis and activation, promote the buildup of the abnormal extracellular elastic material characteristic of PEX syndrome. They further support a dual role for LTBPs, both as integral structural components of PEX fibers and as a means of matrix anchorage of latent TGF-beta1, representing one possible mechanism for the regulation of TGF-beta1 activity in PEX eyes. Future therapeutic strategies might focus on TGF-beta1 antagonistic approaches. Copyright 2001 Academic Press.
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                Author and article information

                Contributors
                sccha@yumail.ac.kr
                Journal
                Sci Rep
                Sci Rep
                Scientific Reports
                Nature Publishing Group UK (London )
                2045-2322
                30 August 2022
                30 August 2022
                2022
                : 12
                : 14728
                Affiliations
                GRID grid.413040.2, ISNI 0000 0004 0570 1914, Department of Ophthalmology, , Yeungnam University College of Medicine, Yeungnam University Hospital, ; Daegu, 42415 Korea
                Article
                18738
                10.1038/s41598-022-18738-z
                9427841
                db19bb8f-4ff2-4ce3-9d79-6e2fdc9880ed
                © The Author(s) 2022

                Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/.

                History
                : 15 June 2022
                : 18 August 2022
                Funding
                Funded by: FundRef http://dx.doi.org/10.13039/501100003725, National Research Foundation of Korea;
                Award ID: 2022R1C1C1008365
                Award Recipient :
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                © The Author(s) 2022

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                glaucoma,optic nerve diseases
                Uncategorized
                glaucoma, optic nerve diseases

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