Macular ganglion cell–inner plexiform layer thinning as a biomarker of disability progression in relapsing multiple sclerosis

Bsteh, Gabriel; Berek, Klaus; Hegen, Harald; Altmann, Patrick; Wurth, Sebastian; Auer, Michael; Zinganell, Anne; Pauli, Franziska Di; Rommer, Paulus; Leutmezer, Fritz; Deisenhammer, Florian; Berger, Thomas

doi:10.1177/1352458520935724

Cited by 43 publications

(55 citation statements)

References 32 publications

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“…Retinal thinning in absence of optic neuritis is a robust and established marker of MS-associated neuroaxonal damage correlated with disability worsening and faster rates of whole brain, thalamic, and grey matter atrophy, but independent of relapse activity. 7 , 8 , 10 , 23 , 24 Our results clearly show that PIRA events are reflected by retinal thinning adding an important component of evidence to the concept of PIRA. However, the very important question of which comes first or who is driving whom, retinal thinning or disability worsening, remains to be elucidated.…”

Section: Discussionsupporting

confidence: 55%

“…We included 171 patients diagnosed with RMS according to the 2010 McDonald criteria aged between 18 and 65 years from a prospective, observational study on OCT in RMS. 8 – 10 …”

Section: Methodsmentioning

confidence: 99%

“…DMT was grouped as following: 1) “no DMT” (N-DMT) defined as patients receiving no DMT at least 6 months prior to baseline visit and during the whole observation period, 2) “moderate efficacious DMT” (M-DMT) defined as patients receiving one or more DMT of either interferon beta preparations, glatiramer acetate, dimethylfumarate, or teriflunomide during the whole observation period, 3) “highly efficacious DMT” (H-DMT) defined as patients receiving one or more DMT of either natalizumab, fingolimod, alemtuzumab, ocrelizumab or cladribine during the whole observation period, and 4) “ESC-DMT” defined as patients in whom DMT was escalated either from no DMT to moderate or from moderate to highly efficacious DMT during the observation period. 9 , 10 …”

Section: Methodsmentioning

confidence: 99%

“…In MS, atrophy of the macular ganglion cell layer plus the adjacent inner plexiform layer (GCIPL) and the peripapillary retinal nerve fibre layer (pRNFL) are established markers of neurodegeneration in MS. GCIPL and pRNFL thickness correlate with and also predict physical and cognitive disability progression. 7 – 10 …”

Section: Introductionmentioning

confidence: 99%

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Retinal layer thinning is reflecting disability progression independent of relapse activity in multiple sclerosis

Bsteh

Hegen

Altmann

et al. 2020

Multiple Sclerosis Journal - Experimental, Translational and Cl

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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.

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Section: Discussionsupporting

confidence: 55%

“…We included 171 patients diagnosed with RMS according to the 2010 McDonald criteria aged between 18 and 65 years from a prospective, observational study on OCT in RMS. 8 – 10 …”

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Retinal layer thinning is reflecting disability progression independent of relapse activity in multiple sclerosis

Bsteh

Hegen

Altmann

et al. 2020

Multiple Sclerosis Journal - Experimental, Translational and Cl

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“…4 Peripapillary retinal nerve fiber layer (pRNFL) and macular ganglion-cell-and-inner-plexiformlayer (GCIPL) thinning have been established as markers of neuroaxonal degeneration in MS. 4 Cross-sectionally determined pRNFL thickness ≤88μm and GCIPL thickness <70-77µm are associated with an increased risk of disability worsening within subsequent years. [5][6][7][8][9] Measured longitudinally, pRNFL and GCIPL were shown to thin in absence of acute optic neuritis (ON) correlating strongly with global brain atrophy. 10,11 Loss of GCIPL and pRNFL exceeding −1.0µm and −1.5μm per year, respectively, were reported to be associated with physical and cognitive disability worsening.…”

Section: Introductionmentioning

confidence: 99%

Evaluation of Retinal Layer Thickness Parameters as Biomarkers in a Real-World Multiple Sclerosis Cohort

Schurz

Sariaslani

Altmann

et al. 2021

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Retinal layer thickness parameters measured by optical coherence tomography (OCT) are emerging biomarkers of neuroaxonal degeneration and inflammation in multiple sclerosis (MS). We aimed to evaluate the value of retinal layer thickness for prediction of disability worsening and relapse in a real-world MS cohort. Patients and Methods: For this longitudinal observational study, we included MS patients with spectral-domain OCT scans available and ≥1 year of clinical follow-up. The value of peripapillary retinal nerve fiber layer (pRNFL), macular ganglion-cell-and-inner-plexiformlayer (GCIPL) and inner nuclear layer (INL) thickness for prediction of disability worsening and relapse during the observation period was tested by multivariate models. Results: We analyzed 60 MS patients during a mean observation period of 2.9 years (SD 1.8). Lower baseline thickness of GCIPL (cut-off <77µm; HR 4.1, p=0.001) and pRNFL (cut-off ≤88µm; HR 3.1, p=0.019) were associated with an increased risk of disability worsening. Longitudinally, mean thinning rates were −0.8µm/year (SD 1.6) for GCIPL, −0.6µm/year (SD 3.5) for pRNFL. GCIPL thinning ≥1.0µm/year and pRNFL >1.5µm/year is associated with higher likelihood of disability worsening (HR 5.7, p=0.009 and HR 6.8, p=0.003, respectively). INL thickened in patients with relapse by a mean 0.9µm while thinning by 0.3µm in patients without relapse (p=0.04). In multivariate analyses, INL thickening was associated with an increased probability of relapse (OR 17.8, p=0.023). Conclusion: Cross-sectional and longitudinal measurement of GCIPL and pRNFL thinning is reliable as a biomarker of disability worsening in a real-world setting. Change of INL thickness is a promising marker of relapse, i.e. inflammatory activity.

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The thickness of the retinal nerve fiber layer, macula, and ganglion cell‐inner plexiform layer in people with drug‐resistant epilepsy

Chen,

Xiong,

et al. 2024

Epilepsia Open

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ObjectiveUsing Optical coherence tomography (OCT), we evaluated the association between peripapillary retinal nerve fiber, macular thickness, macular ganglion cell‐inner plexiform layer, and drug resistance.MethodsIn this cross‐sectional study, we recruited people diagnosed with epilepsy and healthy controls. People with epilepsy were further stratified as drug‐resistant or non‐drug‐resistant based on their response to anti‐seizure medications. OCT measurements were conducted, and findings in right eye were analyzed.ResultsFifty‐one drug‐resistant participants, 37 non‐drug‐resistant, and 45 controls were enrolled. The average peripapillary retinal nerve fiber layer, ganglion cell‐inner plexiform layer, and macular thickness were thinner in the epilepsy groups than in controls. The drug‐resistant group had significantly lower average ganglion cell‐inner plexiform layer thickness (p = 0.004) and a higher proportion of abnormal/borderline GC/IPL thickness (p = 5.40E‐04) than the non‐drug‐resistant group. Nevertheless, no significant differences were seen between the average thickness of peripapillary retinal nerve fiber and macular thickness. The temporal sectors of these three parameters were also significantly thinner in the drug‐resistant group than in the non‐drug‐resistant. In a multivariate regression model, drug resistance was an independent predictor of reduced ganglion cell‐inner plexiform thickness (Odds ratios OR = 10.25, 95% CI 2.82 to 37.28). Increased seizure frequency (r = −0.23, p = 0.039) and a higher number of anti‐seizure medications ever used (r = −0.27, p = 0.013) were negatively associated with ganglion cell‐inner plexiform layer thickness.SignificanceIndividuals with drug‐resistant epilepsy had a consistent reduction in average ganglion cell‐inner plexiform layer thickness and the temporal sector of peripapillary retinal nerve fiber layer and macular thickness. This suggests that ganglion cell‐inner plexiform layer thickness could potentially serve as an indicator of the burden of drug resistance, as it correlated with reduced thickness in individuals having more frequent seizures and greater exposure to ASMs.Plain Language SummaryIn our study, we used a special tool called OCT to measure how thick the retina is in people with epilepsy and in healthy control. We found that the retina was consistently thinner in all areas for those with epilepsy compared to healthy control. Particularly, a specific layer called the ganglion cell‐inner plexiform layer was a lot thinner in the group that didn't respond to medications, and this thinning was related to how often seizures occurred and how much medications were taken. Also, certain parts of the retina were thinner in the drug‐resistant group.

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Macular ganglion cell–inner plexiform layer thinning as a biomarker of disability progression in relapsing multiple sclerosis

Cited by 43 publications

References 32 publications

Retinal layer thinning is reflecting disability progression independent of relapse activity in multiple sclerosis

Retinal layer thinning is reflecting disability progression independent of relapse activity in multiple sclerosis

Evaluation of Retinal Layer Thickness Parameters as Biomarkers in a Real-World Multiple Sclerosis Cohort

The thickness of the retinal nerve fiber layer, macula, and ganglion cell‐inner plexiform layer in people with drug‐resistant epilepsy

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