Promising recovery biomarkers after first event acute demyelinating optic neuritis

Background: Acute demyelinating optic neuritis is often a first episode of subsequent CNS demyelinating disease, most frequently multiple sclerosis (MS). The majority of the patients have substantial recovery of the high contrast visual acuity (HCVA) and 30-2 perimetry, but reduced contrast sensitivity persists in 56% of eyes after an episode of optic neuritis. Cross sectional studies of MS patients show low contrast visual acuity (LCVA) correlates modestly with RNFL thickness and macula ganglion cell +IPL layer (GCL) thickness. Considering the potential severity of the vision deficits at onset, and GCL thinning at outcome, we hypothesized 10-2 perimetry and LCVA deficits would be frequent following an episode of optic neuritis. Methods: We prospectively studied 32 eyes of 32 patients (9 men, 23 women, age 34 years ± 10) with first time acute optic neuritis. We measured LCVA 2.5% (# letters seen), GCL thickness and loss, and 10-2 mean deviation (MD in decibels, dB) within 15 days from symptoms onset and at six months. The 10-2 threshold perimetry, a novel assessment in the MS research field, included to further characterize central vision function. We used correlation analysis to assess associations between GCL thickness and thinning and 10-2 perimetry as well as LCVA 2.5% at six months. Results: Compared to fellow eyes we found significant residual LCVA deficits in 28/32 study eyes at 6 months with 12.6 ± 15.8 letters seen, p=0.001). Similarly, 10-2 MD threshold perimetry in the study eyes at 6 months showed significant difference relative to the fellow eyes, p=0.01. In regards to GCL changes at 6 months, we found statistically significant reduction of the GCL thickness in the study eyes relative to the fellow eyes (study eyes 69.6 ± 9.6 µm, fellow eyes 82.7 ± 4.7 µm, p=0.001), with thinning present in 29/32 eyes. The mean GCL thinning at 6 months in the study eyes was 12.4 ± 8.4 µm. Correlation analysis of associations between primary outcome measures at 6 months showed significant relationship between GCL thickness and 10-2 MD threshold perimetry (0.43, p = 0.015) but not with LCVA. At six months, the mean GCL thinning strongly correlated with the 10-2 MD (-0.60, p=0.01) and moderately with LCVA (-0.46, p=0.008). Conclusions: GCL thickness is the best structural and LCVA and 10-2 MD are sensitive functional measures for determining residual deficits due to optic neuritis. The 10-2 MD correlates best with the outcome GCL thickness and loss. Our findings also suggest that 10-2 threshold perimetry and macular GCL can provide functional and structural promising biomarker signals to explore neuro-protective research.