A Reflectivity Measure to Quantify Bruch's Membrane Calcification in Patients with Pseudoxanthoma Elasticum Using Optical Coherence Tomography

Risseeuw, Sara; Bennink, Edwin; Poirot, Maarten G.; Jong, Pim A. de; Spiering, Wilko; Imhof, Saskia M.; Leeuwen, Redmer van; Norel, Jeannette Ossewaarde–van

doi:10.1167/tvst.9.8.34

Cited by 11 publications

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References 48 publications

(63 reference statements)

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“…The categorical classification of the length of angioid streaks leads to loss of information when compared to a continuous measure. Other approaches, including quantification of Bruch's membrane reflectivity on macular OCT-scan [36] and measurement of the border of peau d'orange on 30 • NIR imaging are under development. However, these measurements are only possible in the early stage of disease when there is no macular degeneration yet [36,37].…”

Section: Discussionmentioning

confidence: 99%

“…Other approaches, including quantification of Bruch's membrane reflectivity on macular OCT-scan [36] and measurement of the border of peau d'orange on 30 • NIR imaging are under development. However, these measurements are only possible in the early stage of disease when there is no macular degeneration yet [36,37]. The length of angioid streaks is the first measure that allows for semi-quantitative measurements in nearly all PXE patients, including those with end-stage disease.…”

Section: Discussionmentioning

confidence: 99%

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Genotype-phenotype correlation in pseudoxanthoma elasticum

et al. 2021

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Background and aims: Pseudoxanthoma elasticum (PXE) is caused by variants in the ABCC6 gene. It results in calcification in the skin, peripheral arteries and the eyes, but has considerable phenotypic variability. We investigated the association between the ABCC6 genotype and calcification and clinical phenotypes in these different organs. Methods: ABCC6 sequencing was performed in 289 PXE patients. Genotypes were grouped as two truncating, mixed, or two non-truncating variants. Arterial calcification mass was quantified on whole body, low dose CT scans; and peripheral arterial disease was measured with the ankle brachial index after treadmill test. The presence of pseudoxanthoma in the skin was systematically scored. Ophthalmological phenotypes were the length of angioid streaks as a measure of Bruchs membrane calcification, the presence of choroidal neovascularizations, severity of macular atrophy and visual acuity. Regression models were built to test the age and sex adjusted genotype-phenotype association. Results: 158 patients (median age 51 years) had two truncating variants, 96 (median age 54 years) a mixed genotype, 18 (median age 47 years) had two non-truncating variants. The mixed genotype was associated with lower peripheral (β: 0.39, 95%CI:-0.62;-0.17) and total (β: 0.28, 95%CI:-0.47;-0.10) arterial calcification mass scores, and lower prevalence of choroidal neovascularizations (OR: 0.41 95%CI:0.20; 0.83) compared to two truncating variants. No association with pseudoxanthomas was found. Conclusions: PXE patients with a mixed genotype have less severe arterial and ophthalmological phenotypes than patients with two truncating variants in the ABCC6 gene. Research into environmental and genetic modifiers might provide further insights into the unexplained phenotypic variability.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Genotype-phenotype correlation in pseudoxanthoma elasticum

et al. 2021

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“…Recently, an OCT-based quantification for BM calcification in patients with PXE was proposed. 32 However, further research and external validation is warranted before this is suitable as a biomarker in normal subjects.…”

Section: In This Study We Developed a Measure For The Extentmentioning

confidence: 99%

The Extent of Angioid Streaks Correlates With Macular Degeneration in Pseudoxanthoma Elasticum

Risseeuw

Norel

Buchem

et al. 2020

American Journal of Ophthalmology

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PURPOSE: To investigate whether the extent of Bruch's membrane calcification is associated with choroidal neovascularization (CNV) and macular atrophy in patients with pseudoxanthoma elasticum (PXE) by using the extent of angioid streaks as a surrogate marker for the degree of Bruch's membrane calcification.DESIGN: Retrospective cross-sectional study. METHODS: We investigated 301 patients with PXE (median age, 52 years; range, 9-79 years) in a tertiary referral center. For both eyes, we graded the extent of angioid streaks, that is, their distance from the optic disc, into 5 groups. Imaging was systematically assessed for signs of CNV and macular atrophy. Associations between the extent of angioid streaks and CNV or macular atrophy were investigated using regression analysis.RESULTS: CNV was present in 148 patients (49%) and retinal atrophy in 71 patients (24%). The extent of angioid streaks was associated with older age (P for trend ¼ 1.92 3 10 L15 ) and a higher prevalence of CNV and/or macular atrophy (P for trend [ 4.22 3 10 L10 and P for trend [ 5.17 3 10 L6 , respectively). In addition, the extent of angioid streaks was associated with the presence of CNV when adjusted for age and sex (odds ratio, 1.9; 95% confidence interval, 1.3-2.9) and with more severe macular atrophy (proportional odds ratio, 2.3; 95% confidence interval, 1.5-3.6).CONCLUSIONS: In patients with PXE, longer angioid streaks are associated with an increased risk of CNV and macular atrophy, even after adjustment for age. These findings are relevant when counseling PXE patients on their visual prognosis.

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“…Ideally, such a biomarker should be able to detect change over time in pre-atrophic stages of the disease. Risseeuw et al 15 have recently shown that BrM calcification can be measured in vivo based on the increased reflectivity of the RPE–BrM retinal band on optical coherence tomography (OCT). However, with current imaging and image analysis techniques, the reproducibility of reflectivity metrics is limited.…”

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confidence: 99%

“…However, with current imaging and image analysis techniques, the reproducibility of reflectivity metrics is limited. 15 …”

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confidence: 99%

Choriocapillaris Flow Signal Impairment in Patients With Pseudoxanthoma Elasticum

Loewinger

Pfau

Herrmann

et al. 2023

Invest. Ophthalmol. Vis. Sci.

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Purpose To quantify choriocapillaris flow alterations in patients with pseudoxanthoma elasticum (PXE) in pre-atrophic stages and its association with structural changes of the choroid and outer retina. Methods Thirty-two eyes of 21 patients with PXE and 35 healthy eyes of 35 controls were included. The density of choriocapillaris flow signal deficits (FDs) was quantified on 6 × 6-mm optical coherence tomography angiography (OCTA) images. Spectral-domain optical coherence tomography (SD-OCT) images were analyzed for thicknesses of the choroid and outer retinal microstructure and correlated with choriocapillaris FDs in the respective Early Treatment Diabetic Retinopathy Study subfield. Results The multivariable mixed model analysis for choriocapillaris FDs revealed significantly higher FDs associated with the group (PXE patients vs. controls +13.6; 95% confidence interval [CI] 9.87–17.3; P < 0.001), with increasing age (+0.22% per year; 95% CI 0.12–0.33; P < 0.001), and with retinal location (significantly higher FDs in nasal compared to temporal subfields). Choroidal thickness (CT) did not differ significantly between both groups ( P = 0.078). The CT and choriocapillaris FDs were inversely correlated (−1.92 µm per %FDs; interquartile range −2.81 to −1.03; P < 0.001). Larger values of the choriocapillaris FDs were associated with significant thinning of the overlying photoreceptor layers (outer segments: −0.21 µm per %FDs, P < 0.001; inner segments: −0.12 µm per %FDs, P = 0.001; outer nuclear layer: −0.72 µm per %FDs; P < 0.001). Conclusions Patients with PXE display significant alterations of the choriocapillaris on OCTA even in pre-atrophic stages and in the absence of significant choroidal thinning. The analysis favors choriocapillaris FDs over choroidal thickness as a potential early outcome measure for future interventional trials in PXE. Further, increased FDs in nasal compared to temporal locations mirror the centrifugal spread of Bruch's membrane calcification in PXE.

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A Reflectivity Measure to Quantify Bruch's Membrane Calcification in Patients with Pseudoxanthoma Elasticum Using Optical Coherence Tomography

Cited by 11 publications

References 48 publications

Genotype-phenotype correlation in pseudoxanthoma elasticum

Genotype-phenotype correlation in pseudoxanthoma elasticum

The Extent of Angioid Streaks Correlates With Macular Degeneration in Pseudoxanthoma Elasticum

Choriocapillaris Flow Signal Impairment in Patients With Pseudoxanthoma Elasticum

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