Association of pseudoexfoliation syndrome with cardiovascular and cerebrovascular disease: a systematic review and meta-analysis

Chung, Helen; Arora, Sourabh; Damji, Karim F.; Weis, Ezekiel

doi:10.1016/j.jcjo.2017.10.039

Cited by 30 publications

(26 citation statements)

References 43 publications

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“…; Chung et al. ). It has been suggested that higher rates of cataract development in XFS patients could be a result of more frequent apoptosis in lens epithelial cells (Oltulu & Oltulu ).…”

Section: Introductionmentioning

confidence: 96%

“…Thus, XFG patients are likely to have earlier and more frequent filtering surgery (Vesti & Kivela 2000;. In addition to the risk of developing glaucoma, XFS has been suggested as a risk factor for many intraocular complications, including complicated cataract surgery, dispersion of melanin granules, inadequate mydriasis, circular posterior synechiae, blood-aqueous barrier dysfunction, anterior segment hypoxia, corneal decompensation, accelerated cataracts, retinal vascular diseases, cerebrovascular and cardiovascular complications, zonular instability and lens subluxation (Conway et al 2004;Desai & Lee 2008;Ritch 2014;Aboobakar et al 2017;Chung et al 2018). It has been suggested that higher rates of cataract development in XFS patients could be a result of more frequent apoptosis in lens epithelial cells (Oltulu & Oltulu 2018).…”

Section: Introductionmentioning

confidence: 99%

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Recent advances in risk factors associated with ocular exfoliation syndrome

Sharaf

Damji

Unsworth

2019

Acta Ophthalmologica

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Exfoliation syndrome is generally considered a progressive age‐related systemic disorder of the extracellular matrix, which is clinically characterized through the observation of flaky white aggregates on ocular tissues. Exfoliation syndrome is directly linked to exfoliative glaucoma in elderly patients, where it is known as the most common identifiable cause of open‐angle glaucoma. Despite the identification of various risk factors associated with exfoliation syndrome, the exact pathogenesis of this syndrome has not been fully elucidated. There is a growing number of genome‐wide association studies in different populations around the world to identify genetic factors underlying exfoliation syndrome. Besides variants in LOXL1 and CACNA1A genes, new loci have been recently identified which are believed to be associated with exfoliation syndrome. Among different genetic factors, functional variants might help to better understand mechanisms underlying this systemic disorder. Besides genetic factors, epigenetic regulation of different gene expression patterns has been thought to play a role in its pathogenesis. Other factors have been also considered to be involved in the development of exfoliation syndrome at cellular organelles level where mitochondrial impairment and autophagy dysfunction have been suggested in relation to exfoliation syndrome. This review addresses the most recent findings on genetic factors as well as cellular and molecular mechanisms involved in both the development and progression of exfoliation syndrome.

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“…; Chung et al. ). It has been suggested that higher rates of cataract development in XFS patients could be a result of more frequent apoptosis in lens epithelial cells (Oltulu & Oltulu ).…”

Section: Introductionmentioning

confidence: 96%

Section: Introductionmentioning

confidence: 99%

Recent advances in risk factors associated with ocular exfoliation syndrome

Sharaf

Damji

Unsworth

2019

Acta Ophthalmologica

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“…2,4 In addition to elastic tissue disorders, XFS has also been associated with increased risk of vascular diseases. [5][6][7] Associations of XFS to several systemic biomarkers of inflammation, including complement components and homocysteine, have also been reported. 3,8,9 Genetic mechanisms have substantial influence on XFS etiology as evidenced in family and twin studies.…”

Section: Introductionmentioning

confidence: 92%

Analysis of Genetically Determined Gene Expression Suggests Role of Inflammatory Processes in Etiology of Exfoliation Syndrome

Hirbo

Pasutto

Gamazon

et al. 2020

Preprint

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Exfoliation syndrome (XFS) is an age-related systemic disorder characterized by excessive production and progressive accumulation of abnormal extracellular material, with pathognomonic ocular manifestations. It is the most common cause of secondary glaucoma, resulting in widespread global blindness. We performed Transcriptomic Wide Association Studies using PrediXcan models trained in 48 GTEx tissues to identify genetically-determined gene expression changes associated with XFS risk, leveraging on results from a global GWAS that included 123,457 individuals from 24 countries. Twenty-eight genes in the chr15q22-25 region showed statistically significant associations in both single-tissue and multi-tissue analysis. Reduced models for these genes that excluded variants in LD with the known LOXL1 signal showed genome-wide significant association signals in nine genes, independently of LOXL1. Out of these ten genes, mRNA transcript levels for ARID3B, CD276, LOXL1, NEO1, SCAMP2, and UBL7 were significantly decreased in iris tissues from XFS patients compared to control samples. Genes with genetically determined expression changes in XFS were significantly enriched for genes associated with inflammatory conditions. We further explored the health consequences of high susceptibility to XFS using a large electronic health record and observed a higher incidence of XFS comorbidity with inflammatory and connective tissue diseases. Our results implicate a role for connective tissues and inflammation in the etiology of XFS. Targeting the inflammatory pathway may be a potential therapeutic option to reduce progression in XFS.

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“…In contrast to patients with POAG, people with PEG (and PES) show morphological changes in vascular and connective tissues throughout the body [12,13,14,15]. Some studies claim that patients with PES have increased vascular morbidity [16,17,18] or that there is a linkage to cardiovascular and cerebrovascular disease [19,20]. A recent meta-analysis concluded that the overall literature suggests that pseudoexfoliation is associated with an increased risk of cardiovascular disease [21].…”

Section: Introductionmentioning

confidence: 99%

Significant lifespan difference between primary open-angle glaucoma and pseudoexfoliation glaucoma

Slettedal

Sandvik

Ringvold

2021

Heliyon

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Open-angle glaucoma (OAG) is a collective term for various subgroups of glaucoma of which primary open-angle glaucoma (POAG) and pseudoexfoliation glaucoma (PEG) are the most common. There is increasing evidence that both conditions have systemic ramifications. We wanted to examine to what extent lifespan and cause of death are influenced by POAG, pseudoexfoliation syndrome (PES), and PEG. Materials and methods: Of 1864 people who underwent an eye examination in 1985-86, the presence of PES and/ or glaucoma, along with date and cause of death were recorded. Based on information from the National Death Registry, the individuals were classified into the following groups of systemic diseases regarded as causing death: Cardiovascular disease (with two subgroups), cerebrovascular disease and neoplasms. Results: All 1864 persons were followed to death, up to 30 years after examination. No difference in lifespan was observed when comparing OAG (i.e. POAG and PEG together) with the rest of the population. When adjusting for gender and age at inclusion, patients with POAG showed a reduced lifespan in the cardiovascular death group (2.44 years, p ¼ 0.043). When comparing lifespan in the neoplastic group in the glaucoma patients, POAG and PEG, directly against each other, a mean age difference of 6.87 years (p ¼ 0.017) was found. Conclusions: POAG patients showed reduced lifespan due to neoplasia and cardiovascular disease. Persons with PES and PEG did not show these lifespan reductions. Our main conclusion is that POAG and PEG, the two main OAG subgroups, are very different disease entities both from an ocular and a systemic point of view.

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Association of pseudoexfoliation syndrome with cardiovascular and cerebrovascular disease: a systematic review and meta-analysis

Cited by 30 publications

References 43 publications

Recent advances in risk factors associated with ocular exfoliation syndrome

Recent advances in risk factors associated with ocular exfoliation syndrome

Analysis of Genetically Determined Gene Expression Suggests Role of Inflammatory Processes in Etiology of Exfoliation Syndrome

Significant lifespan difference between primary open-angle glaucoma and pseudoexfoliation glaucoma

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