Patients with optic neuritis (ON) undergo cortical and subcortical neuroplasticity as revealed by functional magnetic resonance imaging (fMRI). However, the effect of the heterogeneity of scotomas his not been adequately addressed previously. We introduce a new method of modelling scotomas in fMRI, to reveal a clearer pattern of neuroplasticity, across a mixed patient population. A longitudinal fMRI-study of visual function in 19 ON patients examined at four timepoints between presentation and 6 months was performed. Four different models were compared. The first model included the four different examination timepoints as separate explanatory variables without adjustment for Visual held defects. The second model also included covariates reflecting subject-specific deviations in Visual field defect from the average group value of the Humphrey mean deviation (HMD) at each examination timepoint. in the third and fourth models the four examination timepoints were not modelled explicitly, but entered vicariously through the associated changes in the HMD for each subject that marked their individual recovery. The results show that the third and fourth models were more sensitive to geniculate and Visual Cortical neuroplasticity during recovery. Moreover, inferences from the fourth model can be extended to the general Population of patients recovering from ON. In Conclusion, we present a method of accommodating subject-specific differences between patients with acute ON by inclusion of an HMD-index. This method is sensitive to the processes of neuroplasticity whilst the generalisation of inferences makes the method suitable for future studies of treatment.