Optical coherence tomography (OCT) is a non-invasive imaging technique (Huang et al., 1991) that enables the quantification of retinal layer thickness and volume, providing insights into underlying neuroaxonal degeneration (Saidha et al., 2015). Additionally, its rapid execution and low cost make it a practical option for repeated, longitudinal use in clinical settings. Consequently, in recent years, numerous studies have employed OCT primarily to assess retinal damage following optic neuritis (ON) (Petzold et al., 2022), predict disability progression (Martinez-Lapiscina et al., 2016; Cordano et al., 2018), and monitor retinal markers of axonal and neuronal degeneration and inflammation in multiple sclerosis (MS) (Petzold et al., 2017; Nguyen et al., 2019; Cordano et al., 2022; Cordano et al., 2024; Olbert and Struhal, 2022; Knier et al., 2016; Cordano et al., 2021). Notably, OCT-measured retinal thinning in eyes without a history of ON has emerged as a reliable marker for MS-associated neuroaxonal damage, correlating with disability progression independently of relapse activity in MS (Bsteh et al., 2020).

Traditionally, brain atrophy measured via magnetic resonance imaging (MRI) has been used to evaluate the effectiveness of disease-modifying therapies (DMTs) in preventing MS-associated neuroaxonal damage. However, growing evidence suggests that OCT may also serve as a valuable clinical outcome measure for assessing DMT efficacy in relation to neurodegeneration (Saidha et al., 2015; Abalo-Lojo et al., 2014). Several high-efficacy DMTs (HE-DMTs) have demonstrated positive effects on reducing retinal atrophy in people with MS. For instance, natalizumab (NTZ), one of the most effective treatments for MS, has been shown to significantly reduce thinning of the peripapillary retinal nerve fiber layer (pRNFL)—a key marker of axonal loss—compared to moderate-efficacy DMTs (ME-DMTs) (Jakimovski et al., 2021). Alemtuzumab (ATZ) has demonstrated stabilization not only of the pRNFL but also of the ganglion cell and inner plexiform layer (GCIPL), a retinal marker of neuronal loss (Chan et al., 2020). Additionally, after the first year of treatment with rituximab (RTX), GCIPL atrophy rates were comparable to those observed with NTZ treatment (Lambe et al., 2021). Conversely, fingolimod has been associated with macular edema, which can mildly increase total macular volume and thus complicate the assessment of retinal atrophy (Nørgaard et al., 2020; D'Ambrosio et al., 2021).

Given the growing number of available DMTs, further prospective studies are needed to systematically compare the effects of various DMT categories on OCT-derived retinal atrophy.

In this monocentric study, we prospectively collected data from two groups of individuals with MS undergoing treatment with either HE-DMTs or ME-DMTs. Longitudinal OCT scans were acquired to assess the atrophy rate of the GCIPL.