The Role Of Vitamin D In Optic Neuritis

Background: Optic neuritis (ON) is a common manifestation of demyelinating disease and cause of vision loss.  The optic nerve can serve as a model of the central nervous system, thus allowing for evaluation of both inflammatory and degenerative activity as well as testing of posited therapies using optical coherence tomography (OCT).  Optical coherence tomography allows for the measurement of retinal nerve fiber layer (RNFL) thickness as well as other markers of the afferent visual pathway.  We plan to make use of OCT markers in ON to study vitamin D in demyelinating disease.  Vitamin D insufficiency is a known risk factor in multiple sclerosis (MS) development, and sufficiency ameliorates inflammatory activity with some in-vitro evidence of neuroprotection.  Assessment of vitamin D status on ON parameters may provide evidence for neuroprotection and a potential role for vitamin D therapy in demyelinating disease.

Objectives: Our objective is to study the relationship between vitamin D status and ON recovery by RNFL measures at 6 months using OCT.  The hypothesis is that vitamin D sufficiency will be associated with better RNFL outcomes and axonal preservation.  Primary outcomes include affected eye RNFL and inter-eye RNFL difference (IED, a measure of RNFL difference between the unaffected and ON eye) at 6 months between vitamin D sufficient and insufficient groups.  We will also examine the relationship between vitamin D status and ON features at onset.

Methods: In this prospective cohort study, patients with acute ON undergo OCT to assess mean RNFL thickness, macular volume (MV) and IED, visual acuity and evoked potentials, and vitamin D (serum 25(OH)D) status testing at baseline, months 3 and 6.  Vitamin D insufficiency is defined as 25(OH)D < 80 nmol/L.

Results: Forty-two of 50 patients have been enrolled (32 women, 10 men), 30 having completed the study. Thus far, 62% of patients were vitamin D insufficient at baseline, which was associated with greater baseline edema seen in mean RNFL (132.4 vs 95.5 µm, p=0.0219) and MV (10.25 vs 9.83 mm3, p=0.0134).  At month 6, edema is still subtly present, but IED is significantly greater in vitamin D insufficient vs sufficient patients (11.6 vs 3.7 µm, p=0.16) as is the proportion of vitamin D insufficient patients with a 6 month IED > 10 µm (58% vs 25% of sufficient patients).

Conclusions: Our results suggest that vitamin D insufficiency at ON onset is associated with greater edema with greater baseline RNFL and MV in ON eyes.  At 6 months, ON eye RNFL thickness in vitamin D insufficient patients, as evaluated by IED, drops below the RNFL value of the unaffected eye, while this does not appear to occur in sufficient patients.  Vitamin D insufficient patients also make up a greater proportion of those with an IED > 10 µm.  As we near the end of this study, it appears that vitamin D sufficiency may protect against both the acute inflammatory and late degenerative/axonal loss associated with optic nerve demyelination.