Associations between retinal nerve fiber layer and ganglion cell-inner plexiform layer thickness and MRI/clinical outcomes in MS showed consistent directionality across both age-matched and age-heterogeneous cohorts, and were largely independent of age.
Key Findings
Results
RNFL and GCIPL thickness were significantly associated with EDSS in both the birth-year cohort and the age-heterogeneous cohort.
In the birth-year cohort (N=378): RNFL β = -0.020, p < 0.001; GCIPL β = -0.017, p = 0.005
In the age-heterogeneous cohort (N=206): RNFL β = -0.024, p = 0.010; GCIPL β = -0.033, p < 0.001
Direction of associations remained consistent across both cohorts
Models were adjusted for sex, history of optic neuritis, and disease duration; age was an additional covariate in the heterogeneous cohort
Results
RNFL and GCIPL thickness were significantly associated with several MRI measures including whole brain volume, white matter volume, lesion volume, and thalamus volume in both cohorts.
Associations were observed in both the birth-year cohort (N=378) and the age-heterogeneous cohort (N=206)
Direction of associations with MRI-derived brain volumes was consistent across cohorts
Effect sizes varied between cohorts but directionality remained consistent
Multilevel linear regression models were used to assess cross-sectional associations
Results
RNFL and GCIPL thickness were significantly associated with the Symbol Digit Modality Test (SDMT) in both cohorts.
Significant associations were observed in both the birth-year cohort and the age-heterogeneous cohort
Direction of associations remained consistent across cohorts
SDMT was one of the clinical outcome measures assessed alongside EDSS
Results
Including age as a covariate did not substantially change the associations between retinal measures and MRI or clinical outcomes.
Adding age as an additional covariate in the age-heterogeneous cohort did not substantially alter the observed associations
Findings were described as 'largely independent of age'
The study compared a birth-year-selected cohort (Project Y, N=378) with an age-heterogeneous cohort (PrograMS, N=206) to assess the influence of age
This suggests standard statistical correction for age successfully addresses age-related confounding in these associations
Methods
The study used two MS cohorts with different age structures to investigate how age influences cross-sectional associations between retinal measures and MS outcomes.
Cohort 1 (Project Y): N=378, selected on birth year (age-homogeneous)
Cohort 2 (PrograMS): N=206, age-heterogeneous MS cohort
Multilevel linear regression models were used for cross-sectional associations
Models were adjusted for sex, history of optic neuritis, and disease duration; age was an additional covariate only in the heterogeneous cohort
Kaçar S, Jelgerhuis J, Killestein J, Barkhof F, Schoonheim M, Uitdehaag B, et al.. (2026). Aging does not affect the relationship between OCT and clinical or MRI outcome measures.. Multiple sclerosis and related disorders. https://doi.org/10.1016/j.msard.2026.107046