Autologous haematopoietic stem cell transplantation stabilizes retinal atrophy in multiple sclerosis

Autologous haematopoietic stem cell transplantation is an effective treatment for aggressive multiple sclerosis refractory to disease-modifying therapies. Yet, its impact on neurodegeneration remains underexplored, and few predictive biomarkers for clinical outcomes after autologous haematopoietic stem cell transplantation exist. We investigated whether autologous haematopoietic stem cell transplantation attenuates retinal neurodegeneration and whether optical coherence tomography-derived retinal measures predict disability progression after transplantation. In this single-centre longitudinal cohort study, optical coherence tomography was performed in people with multiple sclerosis treated with autologous haematopoietic stem cell transplantation and non-transplanted controls with relapsing-remitting multiple sclerosis. Retinal layer atrophy rates pre-transplantation and up to 36 months post-transplantation were estimated using linear mixed-effects models, and post-transplantation rates were compared with those of non-transplanted controls. Cumulative link mixed models were used to assess whether baseline retinal layer thickness predicted clinical progression after transplantation. The autologous haematopoietic stem cell transplantation cohort included 39 participants [23/39 (59%) female], comprising 23 with relapsing-remitting [15/23 (65%) female], 8 with secondary progressive [5/8 (62.5%) female] and 8 with primary progressive multiple sclerosis [3/8 (37.5%) female]. The relapsing-remitting multiple sclerosis control cohort on disease-modifying treatment included 48 participants [31/48 (65%) female]. In relapsing-remitting multiple sclerosis, autologous haematopoietic stem cell transplantation reduced thinning of the ganglion cell/inner plexiform layer by 0.65 µm/year (95% CI 0.16 to 1.15, P = 0.010), temporal-quadrant peripapillary retinal-nerve-fibre layer by 1.22 µm/year (95% CI 0.63 to 1.81, P < 0.001) and papillomacular bundle peripapillary retinal-nerve-fibre layer by 1.59 µm/year (95% CI 0.89 to 2.29, P < 0.001). Post-transplantation atrophy rates of the global, temporal and papillomacular-bundle peripapillary retinal nerve fibre layer were lower in the autologous haematopoietic stem cell transplantation cohort than in the control cohort by 0.275 µm/year (95% CI 0.048 to 0.502, P = 0.014), 0.294 µm/year (95% CI 0.118 to 0.470, P = 0.001) and 0.200 µm/year (95% CI 0.043 to 0.357, P = 0.015), respectively. Higher baseline inner nuclear layer thickness predicted better disability outcomes after transplantation in both relapsing and progressive multiple sclerosis in exploratory statistical models (P < 0.001). In conclusion, retinal optical coherence tomography demonstrated reduced retinal atrophy rates in relapsing-remitting multiple sclerosis after autologous haematopoietic stem cell transplantation. Higher inner nuclear layer thickness before transplantation predicted more favourable neurological outcomes, indicating that the inner nuclear layer, a retinal layer linked to inflammatory multiple sclerosis activity, may help identify patients most likely to benefit from autologous haematopoietic stem cell transplantation.