Predictive value of retinal atrophy for cognitive decline across disease duration in multiple sclerosis.

BACKGROUND

We investigated the association between changes in retinal thickness and cognition in people with MS (PwMS), exploring the predictive value of optical coherence tomography (OCT) markers of neuroaxonal damage for global cognitive decline at different periods of disease.

METHOD

We quantified the peripapillary retinal nerve fibre (pRFNL) and ganglion cell-inner plexiform (GCIPL) layers thicknesses of 207 PwMS and performed neuropsychological evaluations. The cohort was divided based on disease duration (≤5 years or >5 years). We studied associations between changes in OCT and cognition over time, and assessed the risk of cognitive decline of a pRFNL≤88 µm or GCIPL≤77 µm and its predictive value.

RESULTS

Changes in pRFNL and GCIPL thickness over 3.2 years were associated with evolution of cognitive scores, in the entire cohort and in patients with more than 5 years of disease (p<0.01). Changes in cognition were related to less use of disease-modifying drugs, but not OCT metrics in PwMS within 5 years of onset. A pRFNL≤88 µm was associated with earlier cognitive disability (3.7 vs 9.9 years) and higher risk of cognitive deterioration (HR=1.64, p=0.022). A GCIPL≤77 µm was not associated with a higher risk of cognitive decline, but a trend was observed at ≤91.5 µm in PwMS with longer disease (HR=1.81, p=0.061).

CONCLUSIONS

The progressive retinal thinning is related to cognitive decline, indicating that cognitive dysfunction is a late manifestation of accumulated neuroaxonal damage. Quantifying the pRFNL aids in identifying individuals at risk of cognitive dysfunction.

Informations de copyright

© Author(s) (or their employer(s)) 2023. No commercial re-use. See rights and permissions. Published by BMJ.

Déclaration de conflit d'intérêts

Competing interests: ES received travel reimbursement from Sanofi, Merck and ECTRIMS. EL-S holds a predoctoral grant from the University of Barcelona (APIF) and she received travel support from Sanofi, IP-V received travel reimbursement from Roche and Genzyme, and she holds stock options in Aura Innovative Robotics. Currently, she is an employee at UCB Pharma, her contribution to this work is associated with her previous work at IDIBAPS; MA holds equity shares of Bionure, S.L. and Goodgut S.L. and stock options of Attune Neurosciences. He is currently an employee of Roche, although his contribution to this work is associated with his previous work at IDIBAPS; MS received speaker honoraria from Genzyme, Novartis and Biogen; JMC received speaker honoraria from Sanfi; EF received funding for an ECTRIMS Clinical Training Fellowship Programme; AC is supported by the ECTRIMS post-doc fellowship (2022), previously received a UK MS Society PhD studentship (2020), a Guarantors of Brain “Entry” clinical fellowship (2019), and an ECTRIMS-MAGNIMS fellowship (2018). He received travel reimbursement from UK MS society, ECTRIMS, NAIMS. AS received compensation for consulting services and speaker honoraria from Bayer-Schering, Merck-Serono, Biogen-Idec, Sanofi-Aventis, TEVA, Novartis and Roche; EHML received travel support for international and national meetings from Roche and Sanofi-Genzyme, and honoraria for consultancies from Novartis, Roche and Sanofi before 16 April 2019. She is currently employed by the European Medicines Agency (Human Medicines) since 16 April 2019. This article is related to her activity under Hospital Clinic of Barcelona/IDIBAPS affiliation and consequently, as external activity, it does not represent the views of the Agency or its Committees. She is a member of the International Multiple Sclerosis Visual System (IMSVISUAL) Consortium; PV is a shareholder and has received consultancy fees from Accure Therapeutics SL, Attune Neurosciences, QMenta, Spiral Therapeutix, CLight and NeuroPrex, as well as having held grants from the Instituto de Salud Carlos III and the European Commissions; YB received speaking honoraria from Biogen, Novartis and Genzyme; BS-D received compensation for consulting services and speaker honoraria from Chiesi and Sanofi-Genzyme and holds equity shares of Accure Therapeutics S.L. SL received compensation for consulting services and speaker honoraria from Biogen Idec, Novartis, TEVA, Genzyme, Sanofi, Merck and Bristol-Myers Squibb, and holds grants from the Instituto de Salud Carlos III.