Retinal neuroaxonal degeneration in NMOSD vs. MS and unaffected controls: A systematic review and meta-analysis of...

Neuromyelitis optica spectrum disorder (NMOSD) is an autoimmune disease characterized by optic neuritis and myelitis, often misdiagnosed as multiple sclerosis (MS). Optical coherence tomography (OCT) provides noninvasive quantification of retinal layer damage, offering potential for NMOSD diagnosis and differentiation from MS.

Fifty-five articles were included in this meta-analysis. All patients underwent OCT examination, with at least one measurement recorded for retinal assessment. This review is reported according to the Meta-analysis of Observational Studies in Epidemiology guidelines and assessed the risk of bias of the included studies. Subgroup analysis assessed the clinical utility of OCT biomarkers across predefined subgroups. Sensitivity analysis was used to evaluate stability of results. Begg's and Egger's test and funnel plot were applied to assess publication bias.

The results showed that the thickness of peripapillary retinal nerve fiber layer (pRNFL) (WMD = -17.73, p < 0.001), macular RNFL (WMD = -5.35, p < 0.001), superior RNFL (RNFL-S) (WMD = -32.91, p < 0.001), inferior RNFL (RNFL-I) (WMD = -39.21, p < 0.001), temporal RNFL (RNFL-T) (WMD = -17.74, p < 0.001), nasal RNFL (RNFL-N) (WMD = -13.59, p < 0.001), superotemporal RNFL (WMD = -25.60, p < 0.001), inferotemporal RNFL (WMD = -26.97, p = 0.001), superonasal RNFL (WMD = -19.84, p < 0.001), inferonasal RNFL (WMD = -23.31, p < 0.001), ganglion cell and inner plexiform layer (GCIPL) (WMD = -14.03, p < 0.001), ganglion cell layer (WMD = -9.34, p < 0.001), inner plexiform layer (WMD = -6.02, p < 0.001), outer nuclear layer (WMD = -2.03, p < 0.001), foveal (WMD = -12.95, p < 0.001) and GCIPL volume (WMD = -0.11, p < 0.001) in NMOSD were significantly thinner than those in the normal population, but no significant changes were found in the outer plexiform layer and photorreceptor layer. On the other hand, compared with MS, NMOSD had significantly thinner pRNFL (WMD = -11.68, p < 0.001), RNFL-S (WMD = -18.09, p = 0.017) /RNFL-I (WMD = -21.25, p = 0.008)/ RNFL-T (WMD = -6.47, p < 0.001)/RNFL-N (WMD = -2.38, p = 0.048) and GCIPL (WMD = -4.22, p < 0.001). Similarly, NMOSD patients had reduced macular volume compared with NC and MS (WMD = -0.32, p < 0.001), with no difference in inner nuclear layer thickness.

OCT serves as a validated imaging biomarker for detecting NMOSD-specific intraretinal neurodegeneration, delineating pathological mechanisms and enhancing differential diagnosis, prognostication, and therapeutic monitoring.