scholarly journals Serum ceramide levels are altered in multiple sclerosis

2020 ◽  
pp. 135245852097181
Author(s):  
Angeliki G Filippatou ◽  
Mohammed Moniruzzaman ◽  
Elias S Sotirchos ◽  
Kathryn C Fitzgerald ◽  
Grigorios Kalaitzidis ◽  
...  

Background: Sphingolipids are myelin components and inflammatory signaling intermediates. Sphingolipid metabolism may be altered in people with multiple sclerosis (PwMS), but existing studies are limited by small sample sizes. Objectives: To compare the levels of serum ceramides between PwMS and healthy controls (HCs) and to determine whether ceramide levels correlate with disability status, as well as optical coherence tomography (OCT)-derived rates of retinal layer atrophy. Methods: We performed targeted lipidomics analyses for 45 ceramides in PwMS ( n = 251) and HCs ( n = 68). For a subset of PwMS, baseline and 5-year Expanded Disability Status Scale (EDSS) assessments ( n = 185), or baseline and serial spectral-domain OCT ( n = 180) were assessed. Results: Several ceramides, including hexosylceramides, lactosylceramides, and dihydroceramides, were altered in PwMS compared with HCs. Higher levels of Cer16:0 were associated with higher odds of EDSS worsening at 5 years in univariable (odds ratio (OR) = 3.84, 95% confidence interval (CI) = 1.41–10.43) and multivariable analyses accounting for age, sex, and race (OR = 2.97, 95% CI = 1.03–8.59). Each 1 ng/mL higher concentration of Hex-Cer22:0 and DH-HexCer22:0 was associated with accelerated rates (μm/year) of ganglion cell + inner plexiform layer (–0.138 ± 0.053, p = 0.01; –0.158 ± 0.053, p = 0.003, respectively) and peripapillary retinal nerve fiber layer thinning (–0.305 ± 0.107, p = 0.004; –0.358 ± 0.106, p = 0.001, respectively). Conclusion: Ceramide levels are altered in PwMS and may be associated with retinal neurodegeneration and physical disability.

2017 ◽  
Vol 24 (2) ◽  
pp. 158-166 ◽  
Author(s):  
Danko Coric ◽  
Lisanne J Balk ◽  
Merike Verrijp ◽  
Anand Eijlers ◽  
Menno M Schoonheim ◽  
...  

Background: Inner retinal layer (IRL) atrophy is a potential biomarker for neurodegeneration in multiple sclerosis (MS). Objective: To investigate the relationship between cognitive impairment and IRL atrophy in MS. Methods: Cross-sectional study design, including 217 patients and 59 healthy controls. Subjects were investigated clinically, underwent retinal optical coherence tomography (OCT) and comprehensive cognitive assessments. The association between these modalities was evaluated by regression analyses. Results: Of the patients, 44.2% were cognitively impaired. In the absence of multiple sclerosis–associated optic neuritis (MSON), cognitively impaired patients had a significantly lower mean peripapillary retinal nerve fiber layer (pRNFL, Δ: 8.13 µm, p < 0.001) and mean macular ganglion cell–inner plexiform layer (mGCIPL, Δ: 11.50 µm, p < 0.001) thickness compared to cognitively preserved patients. There was a significant association between the presence of cognitive impairment and pRNFL (odds ratio (OR): 1.11, 95% confidence interval (CI): 1.04–1.18, p = 0.001) and mGCIPL (OR = 1.11, 95% CI = 1.05–1.18, p < 0.001) atrophy. This association was masked by the severe IRL atrophy seen following MSON. Conclusion: The strong relationship between cognitive impairment across multiple cognitive domains and atrophy of the pRNFL and mGCIPL in patients who never suffered from MSON suggests that OCT is useful in assessing central nervous system neurodegeneration in MS.


2020 ◽  
Vol 6 (4) ◽  
pp. 205521732096634
Author(s):  
Gabriel Bsteh ◽  
Harald Hegen ◽  
Patrick Altmann ◽  
Michael Auer ◽  
Klaus Berek ◽  
...  

Background PIRA (progression independent of relapse) has emerged as a term to quantify the proportion of disability worsening due to non-inflammatory neurodegenerative processes in multiple sclerosis (MS). Objective To determine the impact of PIRA on retinal thinning, a biomarker of neuroaxonal degeneration in MS, in comparison to traditional disability worsening and relapse. Methods In a 4-year, prospective observational study including 171 relapsing MS (RMS) patients, retinal thinning was determined by annual spectral-domain optical coherence tomography measuring macular ganglion-cell-and-inner-plexiform-layer (GCIPL) and peripapillary-retinal-nerve-fibre-layer (pRNFL). PIRA was defined as an expanded disability status scale (EDSS) or symbol digit modalities test (SDMT) worsening confirmed after 24 weeks with no relapse in the 30 days before or after the disability worsening. Results Each PIRA event was associated with a mean additional loss of GCIPL (1.8 µm) and pRNFL (1.9 µm), similar to the impact of EDSS and SDMT worsening. Overall relapse and relapse without subsequent EDSS worsening did not influence retinal thinning, while a relapse with EDSS worsening was associated with an additional loss of GCIPL (1.3 µm) and pRNFL (1.4 µm). Conclusions PIRA is associated with retinal thinning, likely reflecting neurodegenerative processes, not directly associated with focal inflammation. It might be a clinical measure to identify MS patients with ongoing MS-associated neurodegeneration.


2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Ga-In Lee ◽  
Kyung-Ah Park ◽  
Sei Yeul Oh ◽  
Doo-Sik Kong ◽  
Sang Duk Hong

AbstractWe evaluated postoperative retinal thickness in pediatric and juvenile craniopharyngioma (CP) patients with chiasmal compression using optical coherence tomography (OCT) auto-segmentation. We included 18 eyes of 18 pediatric or juvenile patients with CP and 20 healthy controls. Each thickness of the macular retinal nerve fiber layer (RNFL), ganglion cell layer (GCL), inner plexiform layer (IPL), inner nuclear layer, outer plexiform layer, outer nuclear layer, and photoreceptor layer was compared between the CP patients and healthy controls. There was significant thinning in the macular RNFL (estimates [μm], superior, − 10.68; inferior, − 7.24; nasal, − 14.22), all quadrants of GCL (superior, − 16.53; inferior, − 14.37; nasal, − 24.34; temporal, − 9.91) and IPL (superior, − 11.45; inferior, − 9.76; nasal, − 15.25; temporal, − 4.97) in pediatric and juvenile CP patients postoperatively compared to healthy control eyes after adjusting for age and refractive errors. Thickness reduction in the average and nasal quadrant of RNFL, GCL, and IPL was associated with peripapillary RNFL thickness, and reduced nasal quadrant GCL and IPL thicknesses were associated with postoperative visual field defects. In pediatric and juvenile patients with CP, decreased inner retinal layer thickness following chiasmal compression was observed. The changes in retinal structures were closely related to peripapillary RNFL thinning and functional outcomes.


2019 ◽  
Vol 2019 ◽  
pp. 1-7 ◽  
Author(s):  
Jingfei Chen ◽  
Qihui Luo ◽  
Chao Huang ◽  
Wen Zeng ◽  
Ping Chen ◽  
...  

Purpose. To investigate the changes of thickness in each layer, the morphology and density of inner neurons in rhesus monkeys’ retina at various growth stages, thus contribute useful data for further biological studies. Methods. The thickness of nerve fiber layer (NFL), the whole retina, inner plexiform layer (IPL), and outer plexiform layer (OPL) of rhesus monkeys at different ages were observed with hematoxylin and eosin (H&E) staining. The morphology and the density of inner neurons of rhesus monkey retina were detected by immunofluorescence. Results. The retina showed the well-known ten layers, the thickness of each retinal layer in rhesus monkeys at various ages increased rapidly after infant, and the retina was the thickest in adulthood, but the retinal thickness stop growing in senescent. Quantitative analysis showed that the maximum density of inner neurons was reached in adolescent, and then, the density of inner neurons decreased in adults and senescent retinas. And some changes in the morphology of rod bipolar cells have occurred in senescent. Conclusions. The structure of retina in rhesus monkeys is relatively immature at infant, and the inner retina of rhesus monkeys is mature in adolescent, while the thickness of each retinal layer was the most developed in the adult group. There was no significant change in senescence for the thickness of each retinal layer, but the number of the neurons in our study has a decreasing trend and the morphological structure has changed.


2020 ◽  
Vol 26 (7) ◽  
pp. 843-854
Author(s):  
Angeliki G Filippatou ◽  
Jeffrey Lambe ◽  
Elias S Sotirchos ◽  
Kathryn C Fitzgerald ◽  
Andrew Aston ◽  
...  

Background: Studies evaluating associations between body mass index (BMI) and optical coherence tomography (OCT) measures in multiple sclerosis (MS) are lacking. Objective: To assess whether elevated BMI is associated with accelerated retinal atrophy. Methods: In this observational study, 513 MS patients were followed with serial spectral-domain OCT for a median of 4.4 years. Participants were categorized as normal weight (BMI: 18.5–24.9 kg/m2), overweight (BMI: 25–29.9 kg/m2), and obese (BMI: ⩾30 kg/m2). Participants with diabetes mellitus or uncontrolled hypertension and eyes with optic neuritis (ON) ⩽6 months prior to baseline OCT or during follow-up were excluded. Statistical analyses were performed with mixed-effects linear regression. Results: Obese patients ( n = 146) exhibited accelerated rates of ganglion cell + inner plexiform layer (GCIPL) atrophy relative to normal weight patients ( n = 214; –0.57%/year (95% confidence interval (CI): –0.65% to –0.48%) versus –0.42%/year (95% CI: –0.49% to –0.35%); p = 0.012). GCIPL atrophy rate did not differ between overweight ( n = 153) and normal weight patients (–0.47%/year vs –0.42%/year; p = 0.41). Each 1 kg/m2 higher BMI was associated with accelerated GCIPL (–0.011%/year; 95% CI: –0.019% to –0.004%; p = 0.003) atrophy. Multivariable analyses accounting for age, sex, race, MS subtype, and ON history did not alter the above findings. Conclusions: Elevated BMI, in the absence of overt metabolic comorbidities, may be associated with accelerated GCIPL atrophy. Obesity, a modifiable risk factor, may be associated with accelerated neurodegeneration in MS.


2018 ◽  
Vol 5 (3) ◽  
pp. e449 ◽  
Author(s):  
Timm Oberwahrenbrock ◽  
Ghislaine L. Traber ◽  
Sebastian Lukas ◽  
Iñigo Gabilondo ◽  
Rachel Nolan ◽  
...  

ObjectiveTo evaluate the inter-rater reliability of semiautomated segmentation of spectral domain optical coherence tomography (OCT) macular volume scans.MethodsMacular OCT volume scans of left eyes from 17 subjects (8 patients with MS and 9 healthy controls) were automatically segmented by Heidelberg Eye Explorer (v1.9.3.0) beta-software (Spectralis Viewing Module v6.0.0.7), followed by manual correction by 5 experienced operators from 5 different academic centers. The mean thicknesses within a 6-mm area around the fovea were computed for the retinal nerve fiber layer, ganglion cell layer (GCL), inner plexiform layer (IPL), inner nuclear layer, outer plexiform layer (OPL), and outer nuclear layer (ONL). Intraclass correlation coefficients (ICCs) were calculated for mean layer thickness values. Spatial distribution of ICC values for the segmented volume scans was investigated using heat maps.ResultsAgreement between raters was good (ICC > 0.84) for all retinal layers, particularly inner retinal layers showed excellent agreement across raters (ICC > 0.96). Spatial distribution of ICC showed highest values in the perimacular area, whereas the ICCs were poorer for the foveola and the more peripheral macular area. The automated segmentation of the OPL and ONL required the most correction and showed the least agreement, whereas differences were less prominent for the remaining layers.ConclusionsAutomated segmentation with manual correction of macular OCT scans is highly reliable when performed by experienced raters and can thus be applied in multicenter settings. Reliability can be improved by restricting analysis to the perimacular area and compound segmentation of GCL and IPL.


2018 ◽  
Vol 25 (14) ◽  
pp. 1878-1887 ◽  
Author(s):  
Angeliki Filippatou ◽  
Thomas Shoemaker ◽  
Megan Esch ◽  
Madiha Qutab ◽  
Natalia Gonzalez-Caldito ◽  
...  

Background: The role of retinal imaging with optical coherence tomography (OCT) in assessing individuals with radiologically isolated syndrome (RIS) remains largely unexplored. Objective: To assess retinal layer thicknesses in RIS and examine their associations with clinical features suggestive of increased risk for conversion to multiple sclerosis (MS). Methods: A total of 30 RIS subjects and 60 age- and sex-matched healthy controls (HC) underwent retinal imaging with spectral-domain OCT, followed by automated segmentation of retinal layers. Results: Overall, retinal layer thicknesses did not differ between RIS and HC. However, RIS subjects with spinal cord (SC) lesions had lower ganglion cell + inner plexiform layer (GCIP) thickness compared to HC (−4.41 μm; p = 0.007) and RIS without SC lesions (–3.53 μm; p = 0.041). Similarly, RIS subjects with infratentorial (IT) brain lesions had lower GCIP thickness compared to HC (–4.07 μm; p < 0.001) and RIS without IT lesions (–3.49 μm; p = 0.029). Multivariate analyses revealed that the presence of SC or IT lesions were independently associated with lower GCIP thickness in RIS ( p = 0.04 and p = 0.03, respectively). Other patient characteristics, including sex, abnormal cerebrospinal fluid, and presence of gadolinium-enhancing or juxtacortical lesions, were not associated with retinal layer thicknesses. Conclusion: The presence of SC or IT lesions in RIS may be associated with retinal neuro-axonal loss, supporting the presence of more disseminated disease.


2018 ◽  
Vol 2018 ◽  
pp. 1-8
Author(s):  
Chul Hee Lee ◽  
Min Woo Lee ◽  
Eun Young Choi ◽  
Suk Ho Byeon ◽  
Sung Soo Kim ◽  
...  

Purpose. To compare changes in the retinal layer thickness and visual outcomes in patients undergoing epiretinal membrane (ERM) surgery with or without internal limiting membrane (ILM) peeling. Methods. Seventy-six eyes of 76 patients who underwent ERM surgery from January 2013 to March 2015 at the Department of Ophthalmology, Yonsei University College of Medicine, Seoul, South Korea, were analyzed. While ERM removal with ILM peeling was performed in ILM peeling (P) group (n=39), ILM peeling was not performed in non-ILM peeling (NP) group (n=37). Retinal layer segmentation was performed using optical coherence tomography images. Individual retinal layer thicknesses before and at 6 months after ERM surgery were compared. The postoperative best-corrected visual acuity (BCVA) was also compared. Results. In the P group, the thicknesses of retinal nerve fiber layer (RNFL), ganglion cell layer (GCL), and inner plexiform layer (IPL) were significantly reduced. In the NP group, significant decreases in the RNFL, GCL, IPL, inner nuclear layer, and outer plexiform layer were observed. The P group manifested a greater mean postoperative GCL (35.56 ± 1.53 µm vs 29.86 ± 2.16 µm; p=0.033) and less loss of GCL (−10.26 ± 1.91 µm vs −19.86 ± 2.74 µm; p=0.004) compared to the NP group. No statistically significant differences were observed when comparing the changes in BCVA. Conclusions. This study demonstrates that ILM peeling for ERM surgery may result in better preservation of GCL compared to no ILM peeling.


2017 ◽  
Vol 25 (1) ◽  
pp. 31-38 ◽  
Author(s):  
Anna M Pietroboni ◽  
Laura Dell’Arti ◽  
Michela Caprioli ◽  
Marta Scarioni ◽  
Tiziana Carandini ◽  
...  

Background: The importance of neurodegeneration in multiple sclerosis (MS) is increasingly well recognized. Objectives: To evaluate retinal pathology using optical coherence tomography (OCT) and to investigate possible associations between retinal layers’ thickness and specific patterns of gray matter volume in patients with a new diagnosis of MS. Methods: A total of 31 patients underwent OCT scans and brain magnetic resonance imaging. In total, 30 controls underwent the same OCT procedure. The association between focal cortical volume and OCT measurements was investigated with voxel-based morphometry (VBM). Results: Compared to controls, patients’ macular retinal nerve fiber layer (mRNFL), macular ganglion cell layer (mGCL), macular inner plexiform layer (mIPL), and macular ganglion cell-inner plexiform layer (mGCIPL) thickness were significantly reduced ( p = 0.0009, p = 0.0003, p = 0.0049, and p = 0.0007, respectively). Peripapillary RNFL (pRNFL) and temporal sector pRNFL (T-pRNFL) did not show any significant changes, although there was a trend toward T-pRNFL thinning ( p = 0.0254). VBM analysis showed that mGCIPL and pRNFL were significantly correlated with the volume reduction of occipital-parietal cortex ( p < 0.005). Conclusion: mRNFL, mGCL, and mIPL are significantly reduced in MS patients without concomitant pRNFL thinning. These retinal changes show a significant association with cortical regions that are known to be important for visuospatial performance.


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