Association of Exfoliation Syndrome With Risk of Indirect Inguinal Hernia

Besch, Brian M.; Curtin, Karen; Ritch, Robert; Allingham, R. Rand; Wirostko, Barbara

doi:10.1001/jamaophthalmol.2018.4157

Cited by 21 publications

(18 citation statements)

References 53 publications

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“…Interestingly, STRA6 mutations constitute the only demonstrated cases of human mutations that affect a gene from the retinoid pathway and lead to a complex spectrum of developmental abnormalities including micro/anophthalmia, heart defects, pulmonary dysplasia and diaphragmatic hernia (41,42). A similar disease spectrum, including relative anterior microphthalmos, atrial fibrillation, obstructive pulmonary disease and inguinal hernias, has been reported to occur in PEX patients (9,43,44). Silencing of STRA6 can also cause tissue fibrosis via suppression of STRA6 cascades through upregulation and activation of TGF-ß1 and collagen type I (45).…”

Section: Discussionmentioning

confidence: 59%

The protective variant rs7173049 at LOXL1 locus impacts on retinoic acid signaling pathway in pseudoexfoliation syndrome

Berner

Hoja

Zenkel

et al. 2019

Human Molecular Genetics

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LOXL1 (lysyl oxidase-like 1) has been identified as the major effect locus in pseudoexfoliation (PEX) syndrome, a fibrotic disorder of the extracellular matrix and frequent cause of chronic open-angle glaucoma. However, all known PEX-associated common variants show allele effect reversal in populations of different ancestry, casting doubt on their biological significance. Based on extensive LOXL1 deep sequencing, we report here the identification of a common non-coding sequence variant, rs7173049A>G, located downstream of LOXL1, consistently associated with a decrease in PEX risk (odds ratio, OR = 0.63; P = 6.33 × 10−31) in nine different ethnic populations. We provide experimental evidence for a functional enhancer-like regulatory activity of the genomic region surrounding rs7173049 influencing expression levels of ISLR2 (immunoglobulin superfamily containing leucine-rich repeat protein 2) and STRA6 [stimulated by retinoic acid (RA) receptor 6], apparently mediated by allele-specific binding of the transcription factor thyroid hormone receptor beta. We further show that the protective rs7173049-G allele correlates with increased tissue expression levels of ISLR2 and STRA6 and that both genes are significantly downregulated in tissues of PEX patients together with other key components of the STRA6 receptor-driven RA signaling pathway. siRNA-mediated downregulation of RA signaling induces upregulation of LOXL1 and PEX-associated matrix genes in PEX-relevant cell types. These data indicate that dysregulation of STRA6 and impaired retinoid metabolism are involved in the pathophysiology of PEX syndrome and that the variant rs7173049-G, which represents the first common variant at the broad LOXL1 locus without allele effect reversal, mediates a protective effect through upregulation of STRA6 in ocular tissues.

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Section: Discussionmentioning

confidence: 59%

The protective variant rs7173049 at LOXL1 locus impacts on retinoic acid signaling pathway in pseudoexfoliation syndrome

Berner

Hoja

Zenkel

et al. 2019

Human Molecular Genetics

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“…It is associated with other ocular conditions such as cataract, angle closure, retinal vein occlusion, and zonular fragility. It is also associated with multiple systemic vascular conditions, such as renal artery stenosis and aortic aneurysm, as well as cerebrovascular and cardiovascular disease, hearing loss, and elastic tissue disorders, such as pelvic organ prolapse, inguinal hernia, and chronic obstructive pulmonary disease 5–10…”

mentioning

confidence: 99%

Macula Vessel Density and Foveal Avascular Zone Parameters in Exfoliation Glaucoma Compared to Primary Open-Angle Glaucoma

Philip

Najafi

Tantraworasin

et al. 2019

Invest. Ophthalmol. Vis. Sci.

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Purpose The purpose of this study was to explore macula vessel density and foveal avascular zone (FAZ) parameters in exfoliation glaucoma (XFG) compared to primary open-angle glaucoma (POAG) using optical coherence tomography angiography (OCTA). Methods This was a cross-sectional observational study. Twenty-six XFG and 28 POAG patients with comparable visual field defects on Humphrey 24-2 and 10-2 perimetries were recruited. OCTA scans (3 × 3 mm) centered on the fovea were obtained. Built-in software was used to measure superficial capillary plexus (SCP) vessel density at different quadrants of the macula. Custom software was then used to create a full-thickness image. The FAZ was manually delineated, and large vessels were removed. Vessel density in eight concentric rings with increments of 200-μm diameters from the delineated FAZ was measured. FAZ parameters were calculated using the custom software. Results SCP density was significantly lower in the superior (mean difference [MD] = −4.32, 95% confidence interval [CI] = −7.02, −1.61, P = 0.003) and nasal (MD = −3.00, 95% CI = 05.22, −0.77, P = 0.010) quadrants in XFG versus POAG. SCP vessel density using the concentric ring approach revealed significantly decreased values at all eight rings in XFG versus POAG. In the full-thickness analysis, density was significantly less in the XFG group in all rings except the initial 200 μm. No significant differences existed in FAZ parameters between the groups. Conclusions Despite the presence of comparable central visual field defects, the macula vessel density was predominately lower in XFG compared with POAG in our sample of patients. Further studies are warranted to investigate the consistency of our results.

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“…Literature review of positive risk factors for XFS in general [Tables 5 - 7 ][ 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60 61 62 63 64 65 66 67 68 69 70 71 72 73 74 75 76 77 78 79 80 81 ] and XFS in young subjects [ Table 8 ][ 82 83 84 85 86 87 88 89 90 91 …”

Section: Resultsmentioning

confidence: 99%

“…In the Lebanese cohort under investigation, XFS was associated with advanced age, glaucoma, habitual ocular rubbing, and longer time for cataract surgery. While advanced age [ Table 6 ],[ 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60 61 62 63 64 65 66 67 68 69 70 ] glaucoma [ Table 5 ],[ 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 ] and longer surgery duration[ 100 ] are well established risk factors for XFS [ Table 5 ],[ 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 <...>…”

Section: Discussionmentioning

confidence: 99%

A Case–Cohort Study of Exfoliation Risk Factors and Literature Review

Mansour

Konstas

Mansour

et al. 2021

Middle East African Journal of Ophthalmology

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The purpose of the study is to evaluate the risk factors associated with exfoliation in a case-cohort setting and literature review. This single-center, prospective, case-cohort study was carried out from January 2010 to April 2020 on patients operated for cataract surgery by a single surgeon in Lebanon. Forty-nine consecutive patients with exfoliation syndrome (XFS) and 62 consecutive control patients were identified and further investigated for selected systemic (diabetes mellitus, systemic hypertension, asthma, or atopy) and ocular variables (baseline vision, severity of nuclear sclerosis, glaucoma, eye rubbing, history of dry eye, or allergic eye disease). The mean baseline Snellen visual acuity was 20/283 in XFS versus 20/145 in control cases ( P = 0.012). XFS also demonstrated significantly denser nuclear sclerosis than controls ( P = 0.00958). By univariate analysis, allergic conjunctivitis (15 [30.6%] vs. 2 [3.2%]; P < 0.001), dry eye (20 [40.8%] vs. 13 [21.0%]; P = 0.0133), and habitual rubbing of the eyes (33 [67.3%] vs. 19 [30.6%]; P < 0.001) were associated with the presence of XFS. Habitual ocular rubbing was closely associated with allergic conjunctivitis (odds ratio [OR] = 13.0; 95% confidence interval [CI]: 2.8–58.8; P = 0.032). After multivariable analysis, the following variables showed significant results: glaucoma (OR = 34.5; 95% CI: 4.4–250; P = 0.010), duration of surgery (OR = 5.6; 95% CI 2.43–12.9; P < 0.001), and habitual ocular rubbing (OR = 4.42; 95% CI: 1.97–9.90; P = 0.029). This study shows a novel potential correlation between eye rubbing and XFS in a Lebanese cohort. Chronic eye rubbing induces or may exacerbate preexistent zonular damage in subjects with XFS, hence the need to better manage concurrent ocular surface disorder in these patients.

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Association of Exfoliation Syndrome With Risk of Indirect Inguinal Hernia

Cited by 21 publications

References 53 publications

The protective variant rs7173049 at LOXL1 locus impacts on retinoic acid signaling pathway in pseudoexfoliation syndrome

The protective variant rs7173049 at LOXL1 locus impacts on retinoic acid signaling pathway in pseudoexfoliation syndrome

Macula Vessel Density and Foveal Avascular Zone Parameters in Exfoliation Glaucoma Compared to Primary Open-Angle Glaucoma

A Case–Cohort Study of Exfoliation Risk Factors and Literature Review

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