Diagnostic Performance of Adding the Optic Nerve Region Assessed by Optical Coherence Tomography to the Diagnostic Criteria for Multiple Sclerosis

Abstract

Background:The optic nerve has been recommended as an additional region for demonstrating dissemination in space (DIS) in diagnostic criteria for multiple sclerosis (MS).Objective:To investigate whether adding the optic nerve region as determined by optical coherence tomography (OCT) as part of the DIS criteria improves the 2017 diagnostic criteria.Methods:From a prospective observational study, we included patients with a first demyelinating event who had complete information to assess DIS and a spectral-domain OCT scan obtained within 180 days. Modified DIS criteria (DIS+OCT) were constructed by adding the optic nerve to the current DIS regions based on validated thresholds for OCT inter-eye differences. Time to second clinical attack was the primary endpoint.Results:We analyzed 267 MS patients (mean age 31.3 years [SD 8.1], 69% female) during a median observation period of 59 months (range: 13 - 98).Adding the optic nerve as a fifth region improved the diagnostic performance by increasing accuracy (DIS+OCT 81.2% vs. DIS 65.6%,) and sensitivity (DIS+OCT 84.2% vs. DIS 77.9%) without lowering specificity (DIS+OCT 52.2% vs. DIS 52.2%).Fulfilling DIS+OCT criteria (≥2 of 5 DIS+OCT regions involved) indicated a similar risk of a second clinical attack (HR 3.6, CI 1.4 – 14.5) compared to a 2.5-fold increased risk when fulfilling DIS criteria (HR 2.5, CI 1.2 – 11.8).When the analysis was conducted according to topography of the first demyelinating event, DIS+OCT criteria performed similarly in both optic neuritis and non–optic neuritis.Conclusions:Addition of the optic nerve, assessed by OCT, as a fifth region in the current DIS criteria improves diagnostic performance by increasing sensitivity without lowering specificity.Classification of Evidence:This study provides Class II evidence that adding the optic nerve as determined by optical coherence tomography (OCT) as a fifth dissemination in space (DIS) criterion to the 2017 McDonald criteria improves diagnostic accuracy.

Optic nerve topography in multiple sclerosis diagnostic criteria: Existing knowledge and future directions

“…As with the other tests, non-ON CIS patients exhibited lower frequencies of optic nerve involvement, ranging from 17.8% to 48.3% for pRNFL IEA cut-off and 3.5% to 25% for mGCIPL IEA cut-off (Table 1). 18,19,28,39 Two studies have evaluated modifications of the DIS criteria by incorporating OCT findings to demonstrate optic nerve involvement (Table 2). 18,19 Although these studies evaluated different outcomes, the modified DIS criteria improved the accuracy of the current 2017 DIS criteria by increasing sensitivity, with no impact on specificity observed in the study with longer follow-up, 18 and with a slight decrease in specificity in the prospective cohort with shorter followup period.…”

“…35,36 Notably, recent studies have used OCT to assess the frequency of optic nerve involvement in CIS cohorts. 18,19,28,39 In patients presenting with ON as the initial manifestation, OCT detected optic nerve involvement in 70.3% to 75% when using pRFNL IEA cut-off, and in 64.3% to 68% using mGCIPL IEA cut-off. As with the other tests, non-ON CIS patients exhibited lower frequencies of optic nerve involvement, ranging from 17.8% to 48.3% for pRNFL IEA cut-off and 3.5% to 25% for mGCIPL IEA cut-off (Table 1).…”

“…More recently, research efforts have focused on evaluating the potential benefits of incorporating the optic nerve into the current McDonald criteria, comparing its diagnostic performance to the existing criteria. [16][17][18][19] These studies employ a design involving a typical CIS cohort, evaluated either retrospectively or prospectively, to compare the diagnostic performance of modified DIS criteria, which include the optic nerve as a fifth region, to the current 2017 DIS criteria. Retrospective studies with longer follow-up periods often utilize the occurrence of a second relapse as the gold standard for MS diagnosis, while prospective studies with shorter follow-up times tend to use McDonald MS diagnosis (Table 2).…”

“…26 MS patients with no ON history, n = 95 (disease duration : 8.9 years); control group with other diseases, n = 503D sagittal DIR with coronal reconstruction (3.0 T) Asymptomatic ON lesion detection: 72% in MS patients; 0% in control group Riederer et al 24 CIS/RRMS/SPMS patients, n = 39 (53.8% with ON; might be acute); control group, n = 17 3D-DIR sequence Whole cohort: 58.9% Patients with ON history: 100% Patients without ON history: 9.5% London et al 25 CIS patients, n = 66 (33.3% with ON; 92.4% DIS fulfilment) Multiplanar 3D DIR reconstruction (3.0 T) T2 lesion in ON-CIS: 100% T2 lesion in non-ON-CIS: 22.7% Davion et al 27 MS patients, n = 98 (median disease duration: 11.6 years); analysis conducted at an eye level 35 MS patients, n = 1898 (33% prior ON history, median disease duration: 6 years) Spectral-domain OCT (Spectralis, Heidelberg or Cirrus, Carl Zeiss) Optic nerve lesions in prior ON Hx: IEA pRNFL ⩾5 µm: 71% Optic nerve lesions in non-ON Hx: IEA pRNFL ⩾5 µm: 18% Bsteh et al 36 MS patients, n = 340 (20.9% prior ON history, median disease duration: 3.5 years) Spectral-domain OCT (Spectralis, Heidelberg) Optic nerve lesions in prior ON Hx: IEA pRNFL ⩾5 µm: 69% Optic nerve lesions in non-ON Hx: not reported Bsteh et al18 CIS patients, n = 267 (30.3% ON-CIS)…”

Is the Optic Nerve Overdue as a Criterion to Support the Diagnosis of Multiple Sclerosis?

“…In this issue of Neurology ®, Bsteh et al 9 make significant contributions to this debate by publishing a study that uses, for the first time, optical coherence tomography (OCT) to distinguish optic nerve involvement. The authors used data from 267 patients with MS, enrolled at 2 centers (30% presenting with ON), and determined the effect on conversion to CDMS, of adding optic nerve as a fifth region to the current 2017 McDonald criteria.…”