Background: Retinal vasculopathy with cerebral leukoencephalopathy and systemic manifestations (RVCL-S) is a monogenic small vessel disease caused by mutations in TREX1. Several organs, including... Show moreBackground: Retinal vasculopathy with cerebral leukoencephalopathy and systemic manifestations (RVCL-S) is a monogenic small vessel disease caused by mutations in TREX1. Several organs, including retina and brain, are affected. Analyzing retinal anatomy is increasingly used as a biomarker for ophthalmological and neurological disorders (due to the shared embryological origin of retina and brain). Optical coherence tomography (OCT) provides a noninvasive cross-sectional visualization of optic disc and macula. We aimed to use OCT to investigate retinal layer thickness in RVCL-S. Methods: Cross-sectional, 17 TREX1 mutation carriers (34 eyes) and 9 controls (18 eyes) underwent comprehensive ophthalmologic assessment followed by spectral domain OCT for measuring peripapillary retinal nerve fiber layer (pRNFL) thickness and total macular volume (TMV). Secondary outcomes included measuring thickness of individual macular retinal layers and peripapillary sectors. Findings were analyzed using generalized estimating equations to account for intereye correlation. Results: TREX1 mutation carriers had decreased pRNFL thickness (median [interquartile range] 76 [60-99] vs 99 [87-108] mu m, P < 0.001) and TMV (8.1 [7.4-8.5] vs 8.7 [8.4-8.8] mm(3), P = 0.006) compared with controls. With the exception of the temporal sector, the thickness of all peripapillary sectors was decreased in TREX1 mutation carriers. Ganglion cell layer (30 [22-37] vs 39 [36-41] mu m, P < 0.001) and inner plexiform layer (27 [24-34] vs 34 [31-35], P = 0.001) were thinner in TREX1 mutation carriers. Notably, in 9 of 12 eyes with normal funduscopic examination, retinal thinning was already detected. Conclusions: RVCL-S, which may serve as a vascular retinopathy model, is associated with retinal thinning in the peripapillary and macular area. OCT findings can potentially serve as early biomarkers for RVCL-S and other vascular retinopathies. Show less
Boer, I. de; Steenmeijer, S.R.; Pelzer, N.; Al-Nofal, M.; Dijkman, G.; Notting, I.C.; Terwindt, G.M. 2022
Background: Retinal vasculopathy with cerebral leukoencephalopathy and systemic manifestations (RVCL-S) is a monogenic small vessel disease caused by mutations in TREX1. Several organs, including... Show moreBackground: Retinal vasculopathy with cerebral leukoencephalopathy and systemic manifestations (RVCL-S) is a monogenic small vessel disease caused by mutations in TREX1. Several organs, including retina and brain, are affected. Analyzing retinal anatomy is increasingly used as a biomarker for ophthalmological and neurological disorders (due to the shared embryological origin of retina and brain). Optical coherence tomography (OCT) provides a noninvasive cross-sectional visualization of optic disc and macula. We aimed to use OCT to investigate retinal layer thickness in RVCL-S.Methods: Cross-sectional, 17 TREX1 mutation carriers (34 eyes) and 9 controls (18 eyes) underwent comprehensive ophthalmologic assessment followed by spectral domain OCT for measuring peripapillary retinal nerve fiber layer (pRNFL) thickness and total macular volume (TMV). Secondary outcomes included measuring thickness of individual macular retinal layers and peripapillary sectors. Findings were analyzed using generalized estimating equations to account for intereye correlation.Results: TREX1 mutation carriers had decreased pRNFL thickness (median [interquartile range] 76 [60–99] vs 99 [87–108] µm, P < 0.001) and TMV (8.1 [7.4–8.5] vs 8.7 [8.4–8.8] mm3, P = 0.006) compared with controls. With the exception of the temporal sector, the thickness of all peripapillary sectors was decreased in TREX1 mutation carriers. Ganglion cell layer (30 [22–37] vs 39 [36–41] µm, P < 0.001) and inner plexiform layer (27 [24–34] vs 34 [31–35], P = 0.001) were thinner in TREX1 mutation carriers. Notably, in 9 of 12 eyes with normal funduscopic examination, retinal thinning was already detected.Conclusions: RVCL-S, which may serve as a vascular retinopathy model, is associated with retinal thinning in the peripapillary and macular area. OCT findings can potentially serve as early biomarkers for RVCL-S and other vascular retinopathies. Show less
Gagaouzova, B.S.; Datema, M.; Thijs, R.D.; Tannemaat, M.R.; Steenmeijer, S.R.; Notting, I.C.; Dijk, J.G. van 2021
Background: Pure autonomic failure (PAF) and multiple system atrophy (MSA) are rare disorders causing severe autonomic failure. Their initially similar clinical presentation may lead to years of... Show moreBackground: Pure autonomic failure (PAF) and multiple system atrophy (MSA) are rare disorders causing severe autonomic failure. Their initially similar clinical presentation may lead to years of diagnostic difficulties. Improving the differentiation would have an important impact on patients and families in view of better prediction of disease progression. Objective: To investigate whether several new non-invasive autonomic tests are beneficial in discriminating between PAF and MSA. Methods: Patients and controls underwent two tests examining the autonomic innervation of the skin (Sudoscan and water-induced skin wrinkling) and one test measuring retinal nerve fiber layer thickness in the eye. Results: The skin vasomotor tests yielded differences between the disease and control groups, but did not discriminate between PAF and MSA. No differences in retinal nerve fiber layer thickness were found between the groups. Conclusion: The tests applied in this study may help to confirm autonomic failure but did not support the differential diagnosis between PAF and MSA. Show less
Etten, E.S. van; Boer, I. de; Steenmeijer, S.R.; Al-Nofal, M.; Wermer, M.J.H.; Notting, I.C.; Terwindt, G.M. 2020
Background and purpose Investigating mutation carriers with Dutch-type hereditary (D-) cerebral amyloid angiopathy (CAA), offers the possibility to identify markers in pre- and symptomatic stages... Show moreBackground and purpose Investigating mutation carriers with Dutch-type hereditary (D-) cerebral amyloid angiopathy (CAA), offers the possibility to identify markers in pre- and symptomatic stages of CAA. Optical coherence tomography (OCT) has shown potential to detect retinal changes in several neurodegenerative diseases. The aim of the present exploratory study was to investigate thinning of retinal layers as a possible (early) biomarker in D-CAA mutation carriers. Methods Twenty-one D-CAA mutation carriers (n = 8 presymptomatic,n = 13 symptomatic, median age 50 years) and nine controls (median age 53 years) were scanned using spectral-domain OCT. Symptomatic mutation carriers were defined as having a history of >= 1 symptomatic intracerebral hemorrhage. D-CAA mutation carriers and controls were recruited from our D-CAA cohort and a healthy control cohort. Total peripapillary retinal nerve fiber layer (pRNFL) thickness, six regions of pRNFL, total macular volume (TMV), and individual macular region thickness were measured and analysed, adjusted for age. Results The overall median (interquartile range) thickness of pRNFL was lower in symptomatic, but not presymptomatic D-CAA mutation carriers compared with controls [91 (86-95) mu m vs. 99 (87-108) mu m;P = 0.006]. Both presymptomatic [111 (93-122) mu m vs. 131 (123-143) mu m;P < 0.001] and symptomatic carriers [119 (95-128) mu m vs. 131 (123-143) mu m;P = 0.034] had a thinner temporal-superior quadrant of the pRNFL versus controls. TMV or individual macular layer thickness did not differ between carriers and controls. Conclusions Thinning of the retinal nerve fiber layer may be a candidate marker of disease in hereditary CAA. Further studies are needed to determine whether retinal thinning is present in sporadic CAA and estimate its value as a marker for disease progression. Show less
