Retinal nerve fiber layer thinning in multiple sclerosis: clinical implications, cognitive associations, and effects...

Peripapillary retinal nerve fiber layer (pRNFL) thinning, detected by optical coherence tomography (OCT), is an early marker of neuroaxonal injury in multiple sclerosis (MS). Its prognostic value for long-term outcomes and responsiveness to disease-modifying therapies (DMTs) remains insufficiently explored, particularly in Asian populations. This study aimed to identify clinical and radiological correlates of pRNFL thickness, evaluate whether pRNFL thinning predicts disability and cognitive decline, and examine the effects of DMTs on retinal neurodegeneration in Chinese MS patients.

We analyzed 354 Chinese MS patients who underwent OCT, neurological assessments, and brain MRI. Multivariate regression identified determinants of baseline pRNFL thickness. Among 159 patients with follow-up longer than 12 months, logistic regression was used to assess whether baseline pRNFL thickness and annualized pRNFL thinning predicted disability or cognitive decline. Linear mixed-effects models were applied to evaluate longitudinal effects of DMT classes on pRNFL thinning.

Median pRNFL thickness was 105.0 μm (range: 65.0-136.5). Thinner pRNFL was associated with longer disease duration (p < 0.001), optic neuritis (p = 0.019), longer 9-Hole Peg Test completion time (p = 0.025), and increased paramagnetic rim lesions (p = 0.002). Baseline pRNFL thickness did not predict EDSS progression or Symbol Digit Modalities Test (SDMT) decline. In contrast, faster annualized pRNFL thinning predicted SDMT worsening (OR = 1.29, p = 0.018), alongside fewer years of education (OR = 0.84, p = 0.033) and a secondary progressive MS phenotype (OR = 7.67, p = 0.006). No significant differences in pRNFL preservation were observed among DMT classes.

pRNFL thinning reflects disease severity and predicts cognitive decline in MS. Current DMTs provide limited retinal neuroprotection. These findings support the routine OCT-derived pRNFL monitoring and highlight the need for neuroprotective strategies in MS.