A multi-regression approach to improve optical coherence tomography diagnostic accuracy in multiple sclerosis patients without previous optic neuritis

Chua, Jacqueline; Bostan, Mihai; Li, Chi; Sim, Yin Ci; Bujor, Inna; Wong, Damon Wing Kee; Tan, Bingyao; Yao, Xinwen; Schwarzhans, Florian; Garhöfer, Gerhard; Fischer, Georg; Vass, Clemens; Tiu, Cristina; Pîrvulescu, Ruxandra; Popa-Cherecheanu, Alina; Schmetterer, Leopold

doi:10.1016/j.nicl.2022.103010

Cited by 8 publications

(17 citation statements)

References 45 publications

(71 reference statements)

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“…This could be implemented in clinical practice in order to understand and manage MS-related vision complaints. As shown in our present study, there was comparable diagnostic performance of both functional and structural indices in MS with AUCs ranging between 70 and 80%, which is in accordance with previous reports ( Chua et al, 2022 ; Piedrabuena and Bittar, 2022 ). Based on these findings and our results, ERG, and OCT appeared to be complementary and each appeared to provide a different and integral dimension of MS damage.…”

Section: Discussionsupporting

confidence: 93%

Functional and structural readouts for early detection of retinal involvement in multiple sclerosis

Al-Nosairy

Duscha

Buhr

et al. 2023

Front. Integr. Neurosci.

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IntroductionThe retina, a window into the brain, allows for the investigation of many disease-associated inflammatory and neurodegenerative changes affecting the central nervous system (CNS). Multiple sclerosis (MS), an autoimmune disease targeting the CNS, typically impacts on the visual system including the retina. Hence, we aimed to establish innovative functional retinal measures of MS-related damage, e.g., spatially resolved non-invasive retinal electrophysiology, backed by established morphological retinal imaging markers, i.e., optical coherence tomography (OCT).Methods20 healthy controls (HC) and 37 people with MS [17 without history of optic neuritis (NON) and 20 with (HON) history of optic neuritis] were included. In this work, we differentially assessed photoreceptor/bipolar cells (distal retina) and retinal ganglion cell (RGC, proximal retina) function besides structural assessment (OCT). We compared two multifocal electroretinography-based approaches, i.e., the multifocal pattern electroretinogram (mfPERG) and the multifocal electroretinogram to record photopic negative response (mfERGPhNR). Structural assessment utilized peripapillary retinal nerve fiber layer thickness (pRNFL) and macular scans to calculate outer nuclear thickness (ONL) and macular ganglion cell inner plexiform layer thickness (GCIPL). One eye was randomly selected per subject.ResultsIn NON, photoreceptor/bipolar cell layer had dysfunctional responses evidenced by reduced mfERGPhNR-N1 peak time of the summed response, but preserved structural integrity. Further, both NON and HON demonstrated abnormal RGC responses as evidenced by the photopic negative response of mfERGPhNR (mfPhNR) and mfPERG indices (P < 0.05). Structurally, only HON had thinned retina at the level of RGCs in the macula (GCIPL, P < 0.01) and the peripapillary area (pRNFL, P < 0.01). All three modalities showed good performance to differentiate MS-related damage from HC, 71–81% area under curve.ConclusionIn conclusion, while structural damage was evident mainly for HON, functional measures were the only retinal read-outs of MS-related retinal damage that were independent of optic neuritis, observed for NON. These results indicate retinal MS-related inflammatory processes in the retina prior to optic neuritis. They highlight the importance of retinal electrophysiology in MS diagnostics and its potential as a sensitive biomarker for follow-up in innovative interventions.

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Section: Discussionsupporting

confidence: 93%

Functional and structural readouts for early detection of retinal involvement in multiple sclerosis

Al-Nosairy

Duscha

Buhr

et al. 2023

Front. Integr. Neurosci.

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“…27 Lower temporal quadrant RNFL values were also confirmed in both optic neuritis and non-optic neuritis MS eyes in comparison to controls. 3,28 Furthermore, a previous study evaluating the utility of OCT in predicting MS using standard statistical methods showed that combined macular ganglion cell complex thickness and peripapillary retinal nerve fiber layer thickness measures differentiated MS from controls with an area under the receiver operating characteristics curve (AUC) of 0.85 and a sensitivity of 72% at 80% specificity, 29 suggesting a similar yield to our ML analysis.…”

Section: Discussionsupporting

confidence: 71%

Machine learning classification of multiple sclerosis in children using optical coherence tomography

et al. 2022

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Background: In children, multiple sclerosis (MS) is the ultimate diagnosis in only 1/5 to 1/3 of cases after a first episode of central nervous system (CNS) demyelination. As the visual pathway is frequently affected in MS and other CNS demyelinating disorders (DDs), structural retinal imaging such as optical coherence tomography (OCT) can be used to differentiate MS. Objective: This study aimed to investigate the utility of machine learning (ML) based on OCT features to identify distinct structural retinal features in children with DDs. Methods: This study included 512 eyes from 187 ( neyes = 374) children with demyelinating diseases and 69 ( neyes = 138) controls. Input features of the analysis comprised of 24 auto-segmented OCT features. Results: Random Forest classifier with recursive feature elimination yielded the highest predictive values and identified DDs with 75% and MS with 80% accuracy, while multiclass distinction between MS and monophasic DD was performed with 64% accuracy. A set of eight retinal features were identified as the most important features in this classification. Conclusion: This study demonstrates that ML based on OCT features can be used to support a diagnosis of MS in children.

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“…This also holds true for other OCTA derived parameters such as DCP, where the increased 13 and decreased values 11 , 27 have been observed, with retinal thinning association 11 , 13 . In our recent OCT paper on the same cohort of patients, we demonstrated thinning of the peripapillary RNFL and inner macular ganglion cell complex 29 . Importantly, the paper highlighted that the capability of OCT in MS differentiation is made more robust by accounting OCT scans for individual anatomical differences and incorporating information from both optic disc and macular regions, representing markers of axonal damage and neuronal injury, respectively.…”

Section: Discussionmentioning

confidence: 52%

Microvascular changes in the macular and parafoveal areas of multiple sclerosis patients without optic neuritis

Bostan

Chua

Sim

et al. 2022

Sci Rep

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Retinal imaging has been proposed as a biomarker for neurological diseases such as multiple sclerosis (MS). Recently, a technique for non-invasive assessment of the retinal microvasculature called optical coherence tomography angiography (OCTA) was introduced. We investigated retinal microvasculature alterations in participants with relapsing–remitting MS (RRMS) without history of optic neuritis (ON) and compared them to a healthy control group. The study was performed in a prospective, case–control design, including 58 participants (n = 100 eyes) with RRMS without ON and 78 age- and sex-matched control participants (n = 136 eyes). OCTA images of the superficial capillary plexus (SCP), deep capillary plexus (DCP) and choriocapillaris (CC) were obtained using a commercial OCTA system (Zeiss Cirrus HD-5000 Spectral-Domain OCT with AngioPlex OCTA, Carl Zeiss Meditec, Dublin, CA). The outcome variables were perfusion density (PD) and foveal avascular zone (FAZ) features (area and circularity) in both the SCP and DCP, and flow deficit in the CC. MS group had on average higher intraocular pressure (IOP) than controls (P < 0.001). After adjusting for confounders, MS participants showed significantly increased PD in SCP (P = 0.003) and decreased PD in DCP (P < 0.001) as compared to controls. A significant difference was still noted when large vessels (LV) in the SCP were removed from the PD calculation (P = 0.004). Deep FAZ was significantly larger (P = 0.005) and less circular (P < 0.001) in the eyes of MS participants compared to the control ones. Neither LV, PD or FAZ features in the SCP, nor flow deficits in the CC showed any statistically significant differences between the MS group and control group (P > 0.186). Our study indicates that there are microvascular changes in the macular parafoveal retina of RRMS patients without ON, showing increased PD in SCP and decreased PD in DCP. Further studies with a larger cohort of MS patients and MRI correlations are necessary to validate retinal microvascular changes as imaging biomarkers for diagnosis and screening of MS.

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A multi-regression approach to improve optical coherence tomography diagnostic accuracy in multiple sclerosis patients without previous optic neuritis

Cited by 8 publications

References 45 publications

Functional and structural readouts for early detection of retinal involvement in multiple sclerosis

Functional and structural readouts for early detection of retinal involvement in multiple sclerosis

Machine learning classification of multiple sclerosis in children using optical coherence tomography

Microvascular changes in the macular and parafoveal areas of multiple sclerosis patients without optic neuritis

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