Evaluation of Lamina Cribrosa and Peripapillary Sclera Stiffness in Pseudoexfoliation and Normal Eyes by Atomic Force Microscopy

Braunsmann, Christoph; Hammer, Christian; Rheinlaender, Johannes; Kruse, Friedrich E.; Schäffer, Tilman E.; Schlötzer‐Schrehardt, Ursula

doi:10.1167/iovs.11-8409

Cited by 104 publications

(71 citation statements)

References 52 publications

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“…Follow up biological experiments suggests that the protective effect may be a consequence of stabilization of the ECM due to increased elastin and fibrillin-1 deposition. This notion is supported by histopathological observations demonstrating decreased elastic fiber formation and tissue stiffness as well as impaired cell adhesion in ocular tissues of patients with XFS 60,61 . We speculate that carrying the rare protective p.407Tyr variant could maintain cellular integrity and render cells more resistant to environmental stressors which destabilize or disrupt the ECM.…”

Section: Discussionmentioning

confidence: 54%

Genetic association study of exfoliation syndrome identifies a protective rare variant at LOXL1 and five new susceptibility loci

et al. 2017

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Exfoliation syndrome (XFS) is the commonest known risk factor for secondary glaucoma and a significant cause of blindness worldwide. Variants in two genes, LOXL1 and CACNA1A have been previously associated with XFS. To further elucidate the genetic basis of XFS, we collected a global sample of XFS cases to refine the association at LOXL1, which previously showed inconsistent results between populations, and to identify new variants associated with XFS. We identified a rare, protective allele at LOXL1 (p.407Phe, OR = 25, P =2.9 × 10−14) through deep resequencing of XFS cases and controls from 9 countries. This variant results in increased cellular adhesion strength compared to the wild-type (p.407Tyr) allele. A genome-wide association study (GWAS) of XFS cases and controls from 24 countries followed by replication in 18 countries identified seven genome-wide significant loci (P < 5 × 10−8). Index variants at the new loci map to chromosomes 13q12 (POMP), 11q23.3 (TMEM136), 6p21 (AGPAT1), 3p24 (RBMS3) and 5q23 (near SEMA6A). These findings provide biological insights into the pathology of XFS, and highlight a potential role for naturally occurring rare LOXL1 variants in disease biology.

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Section: Discussionmentioning

confidence: 54%

Genetic association study of exfoliation syndrome identifies a protective rare variant at LOXL1 and five new susceptibility loci

et al. 2017

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“…For older PXS patients, OCT measurements of peripapillary retinal thickness should be performed frequently in order to monitor RNFL loss and to ensure timely intervention for early treatment of visual function damage. The decreased stiffness of the lamina cribrosa and peripapillary scleral tissues caused by PXS may reflect an inherent tissue weakness, especially in older patients [37,38] . This may in turn render these eyes more vulnerable to IOP fluctuations and optic nerve damage.…”

Section: Discussionmentioning

confidence: 99%

Retinal Nerve Fiber Layer Thickness Changes in the Pseudoexfoliation Syndrome: A Meta-Analysis of Case-Control Studies

et al. 2017

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Purpose: To evaluate and compare changes in retinal nerve fiber layer (RNFL) thickness in patients with the pseudoexfoliation syndrome (PXS) and healthy controls. Methods: Case-control studies were selected through an electronic search of the Cochrane Controlled Trials Register, PubMed, and Embase. Results were reviewed to ensure that the included studies met prespecified inclusion/exclusion criteria, and the quality of each study was assessed using the Newcastle-Ottawa Scale. All included studies measured average and 4-quadrant (temporal, superior, nasal, and inferior) RNFL thickness using optical coherence tomography (OCT). For the continuous outcomes, we calculated the weighted mean difference (WMD) and 95% confidence intervals (CIs). Results: Eight case-control studies were included in this meta-analysis involving 225 eyes of PXS patients and 208 eyes of healthy controls in total. Statistical analysis revealed that the average RNFL thickness in PXS patients was significantly reduced compared to healthy controls (WMD = −6.91, 95% CI: −9.99 to −3.82, p < 0.0001). Additionally, differences in RNFL thickness in the superior quadrant (WMD = −10.68, 95% CI: −16.40 to −4.95, p = 0.0003), inferior quadrant (WMD = −8.20, 95% CI: −10.85 to −5.55, p < 0.00001), nasal quadrant (WMD = −3.05, 95% CI: −5.21 to −0.90, p = 0.005), and temporal quadrant (WMD = −6.39, 95% CI: −9.98 to −2.80, p = 0.0005) were all significant between the two groups. Conclusions: These results suggest that it is important to evaluate RNFL thickness and the optic nerve head through OCT in patients with PXS in order to determine early glaucomatous damage and start timely intervention prior to visual field loss.

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“…It has been postulated that a marked decrease in stiffness of the LC in PXS eyes would result in increased deformability of the ONH in these patients. 11 Peripheral deformation in the LC structure, either in PXS or in NTG patients, may lead to increased susceptibility of retinal ganglion cell (RGC) axons to pressure-induced damage, thus making it a potential risk factor of glaucoma development and progression.…”

Section: Discussionmentioning

confidence: 99%

“…It has been shown that in PXS, a primary disturbance of the elastic fiber homeostasis in this structure may lead to decreased stiffness and increased deformability of the ONH, rendering PEX eyes more vulnerable to pressure-induced optic nerve damage and glaucoma development and progression. [9][10][11] The nutrition of the choroid could be another possible source of vulnerability of PXS eyes to develop glaucoma. As an analogy, some histologic studies have demonstrated decreased density of capillaries and large choroidal vessels as well as choroidal thinning in advanced primary angle closure glaucoma.…”

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Evaluation of Lamina Cribrosa and Choroid in Nonglaucomatous Patients With Pseudoexfoliation Syndrome Using Spectral-Domain Optical Coherence Tomography

Moghimi

Mazloumi

Johari

et al. 2016

Invest. Ophthalmol. Vis. Sci.

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Citation: Moghimi S, Mazloumi M, Johari MK, et al. Evaluation of lamina cribrosa and choroid in nonglaucomatous patients with pseudoexfoliation syndrome using spectral-domain optical coherence tomography. Invest Ophthalmol Vis Sci. 2016;57:129357: -130057: . DOI:10.1167 PURPOSE. To evaluate the lamina cribrosa (LC) and peripapillary choroid in patients with pseudoexfoliation syndrome (PXS). METHODS.In this cross-sectional study, one eye each of 32 nonglaucomatous PXS cases and 29 healthy volunteers were enrolled. The optic discs were scanned using enhanced depth imaging spectral-domain optical coherence tomography, and measurements were obtained using HEYEX software 6.0. LC and other related variables at three areas (mid-superior, center, and mid-inferior) and peripapillary choroidal thickness were determined. Linear mixed modeling was used to adjust the variables. RESULTS.After adjustment for age, sex, and axial length, there was no significant difference between the two groups in peripapillary choroidal thickness or in retinal nerve fiber layer thickness. The LC was significantly thinner in all three areas in the PXS group when compared with the control group, even after adjustment. Although no significant difference in central laminar depth was observed between the two groups (P ¼ 0.74), the superior and inferior laminar depth were significantly deeper in the PXS group when compared with the control group (P ¼ 0.04 and P ¼ 0.006, respectively). Although there was a significant negative association between age and central choroidal thickness in the control group (b ¼ À2.820, P ¼ 0.02), this correlation was not significant in the PXS group.CONCLUSIONS. We found that LC is significantly thinner in all three areas of the optic nerve head in nonglaucomatous PXS patients than in controls. Although no significant difference in peripapillary choroidal thickness was observed between the two groups, peripheral posterior displacement of LC in nonglaucomatous PXS eyes was noted.

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Evaluation of Lamina Cribrosa and Peripapillary Sclera Stiffness in Pseudoexfoliation and Normal Eyes by Atomic Force Microscopy

Cited by 104 publications

References 52 publications

Genetic association study of exfoliation syndrome identifies a protective rare variant at LOXL1 and five new susceptibility loci

Genetic association study of exfoliation syndrome identifies a protective rare variant at LOXL1 and five new susceptibility loci

Retinal Nerve Fiber Layer Thickness Changes in the Pseudoexfoliation Syndrome: A Meta-Analysis of Case-Control Studies

Evaluation of Lamina Cribrosa and Choroid in Nonglaucomatous Patients With Pseudoexfoliation Syndrome Using Spectral-Domain Optical Coherence Tomography

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