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

Abstract

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.

Combining retinal structural and vascular measurements improves discriminative power for multiple sclerosis patients

“…The reason for these conflicting results may be partially due to the failure to account for important biological confounding factors, that is, age, 14 systemic vascular risks (diabetes 15 and systemic hypertension 16 ), signal strength of scans, 17 and/or axial length measurements 18,19 . After accounting for these factors, we found a higher capillary density in the SCP and lower capillary density in the DCP in MSNON subjects as compared to controls 4,20 …”

“…Pupils were not dilated prior to imaging; instead, room lighting was dimmed to achieve maximal pupil dilation. Each participant received two OCT scans, one centered on the macula (512 A‐scans x 128 B‐scans; 6×6 mm) and the other centered on the optic disc (200 A‐scans x 200 B‐scans; 6×6 mm), and one 3×3 mm macula‐centered OCTA scan, with each scan consisting of an isotropic sampling (245×245 pixels) and four consecutive B‐scans obtained at each raster location to compute the angiographic information using an optical microangiography protocol 4,20 . The quality of scans was reviewed by a single trained grader masked to the participant's characteristics according to APOSTEL recommendations and the OSCAR‐IB protocol 24–26 .…”

“…Each participant received two OCT scans, one centered on the macula (512 A-scans x 128 B-scans; 6×6 mm) and the other centered on the optic disc (200 A-scans x 200 B-scans; 6×6 mm), and one 3×3 mm macula-centered OCTA scan, with each scan consisting of an isotropic sampling (245×245 pixels) and four consecutive B-scans obtained at each raster location to compute the angiographic information using an optical microangiography protocol. 4,20 The quality of scans was reviewed by a single trained grader masked to the participant's characteristics according to APOSTEL recommendations and the OSCAR-IB protocol. [24][25][26] Briefly, eyes with poor quality images (signal strength score below 6, movement artifacts causing offcentration, breakages, the weak local signal caused by artifacts, such as floaters, algorithm failures resulting in segmentation errors), and/or eyes with ocular pathology and missing variables were excluded from analysis.…”

“…18,19 After accounting for these factors, we found a higher capillary density in the SCP and lower capillary density in the DCP in MSNON subjects as compared to controls. 4,20 To date, studies on the use of OCT/OCTA for the detection of MSNON subjects have not addressed whether the combination of OCT and OCTA measurements improves the performance of detection models compared to separate indices. Given the high classification accuracy of anatomically compensated OCT 4 and OCTA 20 in the discrimination of healthy and MSNON patients, the study aimed to investigate the diagnostic performance of combining OCT with OCTA in detecting the presence of MSNON from controls.…”

Retinal Vascular Density Using Optical Coherence Tomography-Angiography in Optic Neuritis

“…However, these authors did not find any vascular density damage in MS patients without ON [ 10 , 11 ]. More recently, Bostan et al found an impairment of perifoveolar vascular density in MS patients without ON [ 12 ].…”