Optical coherence tomography angiography measurements in multiple sclerosis: a systematic review and meta-analysis

Abstract

Background and objectives: Recent literature on multiple sclerosis (MS) demonstrates the growing implementation of optical coherence tomography-angiography (OCT-A) to discover potential qualitative and quantitative changes in the retina and optic nerve. In this review, we analyze OCT-A studies in patients with MS and examine its utility as a surrogate or precursor to changes in central nervous system tissue.

Methods: PubMed and EMBASE were systematically searched to identify articles that applied OCT-A to evaluate the retinal microvasculature measurements in patients with MS. Quantitative data synthesis was performed on all measurements which were evaluated in at least two unique studies with the same OCT-A devices, software, and study population compared to controls. A fixed-effects or random-effects model was applied for the meta-analysis based on the heterogeneity level.

Results: The study selection process yielded the inclusion of 18 studies with a total of 1552 evaluated eyes in 673 MS-associated optic neuritis (MSON) eyes, 741 MS without optic neuritis (MSNON eyes), and 138 eyes without specification for the presence of optic neuritis (ON) in addition to 1107 healthy control (HC) eyes. Results indicated that MS cases had significantly decreased whole image superficial capillary plexus (SCP) vessel density when compared to healthy control subjects in the analyses conducted on Optovue and Topcon studies (both P < 0.0001). Likewise, the whole image vessel densities of deep capillary plexus (DCP) and radial peripapillary capillary (RPC) were significantly lower in MS cases compared to HC (all P < 0.05). Regarding optic disc area quadrants, MSON eyes had significantly decreased mean RPC vessel density compared to MSNON eyes in all quadrants except for the inferior (all P < 0.05). Results of the analysis of studies that used prototype Axsun machine revealed that MSON and MSNON eyes both had significantly lower ONH flow index compared to HC (both P < 0.0001).

Conclusions: This systematic review and meta-analysis of the studies reporting OCT-A measurements of people with MS confirmed the tendency of MS eyes to exhibit reduced vessel density in the macular and optic disc areas, mainly in SCP, DCP, and RPC vessel densities.

Keywords: MS; Meta-analysis; Multiple sclerosis; OCT; OCT-A; Optical coherence tomography; Optical coherence tomography angiography; Perfusion density; Retina; Vascular density.

Fig. 1

Macula and optic disc regions of each included study which were measured for vascular, perfusion, and flow density. A Illustration of retinal fundus and location of the macula and optic disc segments. Foveal avascular zone (FAZ) parts are also displayed in the left circle. B Fields analyzed in each study. Blue shows sections of macula and green shows sections of the optic disc. * indicates studies using an Optovue machine, ** Indicates studies using a Zeiss machine. *** indicates studies using a prototype Axsun SS-OCT machine, **** indicates studies using a Nidek machine, ***** indicates studies using a Heidelberg machine, and ****** indicates studies using a Topcon machine. Note: Parts of the figure were drawn using pictures from Servier Medical Art. Servier Medical Art by Servier is licensed under a Creative Commons Attribution 3.0 Unported License (https://creativecommons.org/licenses/by/3.0/)

Fig. 2

Flow diagram of study selection process

Fig. 3

Forrest plot of the meta-analysis for the mean average RPC% between MS cases and healthy controls using Optovue machine. The meta-analysis was conducted with a random-effects model. The size of the square for each article demonstrates the attributed weight, and the horizontal line indicates the 95% confidence interval (CI). The diamonds show the standardized mean difference, and their width represents the 95% CI. N, number of subjects; SD, standard deviation; RPC: radial peripapillary capillary; MS: multiple sclerosis

Fig. 4

Forrest plot of the meta-analysis for the mean SCP vascular density between MS cases and healthy controls. The meta-analysis was conducted with a fixed-effects model. The size of the square for each article demonstrates the attributed weight, and the horizontal line indicates the 95% confidence interval (CI). The diamonds show the standardized mean difference, and their width represents the 95% CI. N, number of subjects; SD, standard deviation; SCP: superficial capillary plexus; MS: multiple sclerosis