Corneal axonal loss as an imaging biomarker of neurodegeneration in multiple sclerosis: a longitudinal study.

Background: Resourceful endpoints of axonal loss are needed to predict the course of multiple sclerosis (MS). Corneal confocal microscopy (CCM) can detect axonal loss in patients with clinically isolated syndrome and established MS, which relates to neurological disability.
Objective: To assess corneal axonal loss over time in relation to retinal atrophy, and neurological and radiological abnormalities in MS.
Methods: Patients with relapsing-remitting (RRMS) ( n  = 68) or secondary progressive MS (SPMS) ( n  = 15) underwent CCM and optical coherence tomography. Corneal nerve fibre density (CNFD-fibres/mm ² ), corneal nerve branch density (CNBD-branches/mm ² ), corneal nerve fibre length (CNFL-mm/mm ² ) and retinal nerve fibre layer (RNFL-μm) thickness were quantified along with neurological and radiological assessments at baseline and after 2 years of follow-up. Age-matched, healthy controls ( n  = 20) were also assessed.
Results: In patients with RRMS compared with controls at baseline, CNFD ( p  = 0.004) and RNFL thickness ( p  < 0.001) were lower, and CNBD ( p  = 0.003) was higher. In patients with SPMS compared with controls, CNFD ( p  < 0.001), CNFL ( p  = 0.04) and RNFL thickness ( p  < 0.001) were lower. For identifying RRMS, CNBD had the highest area under the receiver operating characteristic (AUROC) curve (0.99); and for SPMS, CNFD had the highest AUROC (0.95). At follow-up, there was a further significant decrease in CNFD ( p  = 0.04), CNBD ( p  = 0.001), CNFL ( p  = 0.008) and RNFL ( p  = 0.002) in RRMS; in CNFD ( p  = 0.04) and CNBD ( p  = 0.002) in SPMS; and in CNBD ( p  = 0.01) in SPMS compared with RRMS. Follow-up corneal nerve loss was greater in patients with new enhancing lesions and optic neuritis history.
Conclusion: Progressive corneal and retinal axonal loss was identified in patients with MS, especially those with more active disease. CCM may serve as an imaging biomarker of axonal loss in MS.
Competing Interests: The authors declared the following potential conflicts of interest with respect to the research, authorship and/or publication of this article: Drs Ioannis N. Petropoulos, Fatima Al-Shibani, Gulfidan Bitirgen, Georgios Ponirakis, Adnan Khan, Hoda Gad, Ziyad R. Mahfoud, Heba Altarawneh, Muhammad Hassan Rehman, Karen John, Dhabia Al-Merekhi, Pooja George, Ali Ulvi Uca, Ahmet Ozkagnici, Faiza Ibrahim, Reny Francis, Beatriz Canibano, Dirk Deleu, Ahmed El-Sotouhy, Surjith Vattoth, Ahmed Own, Ashfaq Shuaib, Naveed Akhtar and Saadat Kamran declare no conflict of interest. Dr. Rayaz A. Malik is a principal investigator on grants from Proctor and Gamble and Pfizer and has received consulting honoraria for serving on advisory boards for Novo Nordisk, Aventis Pharma, and Proctor and Gamble.
(© The Author(s), 2023.)