Following an episode of
optic neuritis, thinning of the
retinal nerve fibre layer, which indicates axonal loss, is observed using optical coherence tomography. The longitudinal course of the
retinal changes has not been well characterized. We performed a serial optical coherence tomography study in patients presenting with
optic neuritis in order to define the temporal evolution of
retinal nerve fibre layer changes and to estimate sample sizes for proof-of-concept trials of neuroprotection using
retinal nerve fibre layer loss as the outcome measure. Twenty-three patients (7 male, 16 female, mean age 31 years) with acute clinically isolated unilateral
optic neuritis were recruited to undergo optical coherence tomography, visual assessments and visual evoked potentials at presentation (median 16 days from onset of visual loss) and after 3, 6, 12 and 18 months. Compared with the clinically unaffected fellow eye, the
retinal nerve fibre layer thickness of the affected eye was significantly increased at presentation and significantly reduced at all later time points. The evolution of
retinal nerve fibre layer changes in the affected eye fitted well with an exponential model, with thinning appearing a mean of 1.6 months from symptom onset and the rate of ongoing
retinal nerve fibre layer loss decreasing thereafter. At presentation, increased
retinal nerve fibre layer thickness was associated with impaired visual acuity and prolonged visual evoked potential latency. Visual function after 12 months was not related to the extent of acute
retinal nerve fibre layer swelling but was significantly associated with the extent of concurrent
retinal nerve fibre layer loss. Sample size calculations for placebo-controlled trials of acute neuroprotection indicated that the numbers needed after 6 months of follow up are smaller than those after 3 months and similar to those after 12 months of follow-up. Study power was greater when investigating differences between clinically unaffected and affected eyes rather than
retinal nerve fibre layer thickness of the affected eye alone.
Inflammation in the optic nerve and impaired axonal transport (implied by
retinal nerve fibre layer swelling) are associated with visual dysfunction and
demyelination (long visual evoked potential latency) during acute
optic neuritis.
Retinal nerve fibre layer thinning is usually evident within 3 months. Optical coherence tomography-measured
retinal nerve fibre layer loss after 6 months is a suitable outcome measure for proof-of-concept trials of acute neuroprotection in
optic neuritis.