Abstract
Objective to investigate whether optical coherence tomography (OCT) could demonstrate axonal loss through thinning of the retinal nerve fiber layer (RNFL) in multiple sclerosis (MS) patients. Furthermore, the degree of RNFL loss was compared in the different MS subgroups (with or without optic neuritis, affected or fellow eye, single episode or recurrent optic neuritis, relapsing remitting or progressive MS). RNFL thinning was also determined in MS patients who had serial OCT without any intervening clinical optic neuritis. Design: Retrospective chart review. Setting: Academic tertiary care MS centers. Participants: 177 patients (334 eyes) with multiple sclerosis, with or without optic neuritis, and 159 healthy controls that underwent OCT RNFL measurements. Main Outcome: Retinal nerve fiber layer measurements by OCT. Results: Average RNFL measurements were thinner in MS patients (90 μm) compared to controls (105 μm), p <0.0001. RNFL was significantly reduced in MS patients with optic neuritis (87 μm) versus those without optic neuritis (94 μm), p <0.0001. Among the different quadrants, the degree of RNFL loss was greatest in the temporal quadrant of MS patients (22%). Progressive (primary and secondary progressive) MS patients had thinner RNFL (82 μm) compared to all relapsing remitting MS patients (90 μm), p <0.0001. Greater RNFL loss was seen in SPMS patients (77 μm) versus PPMS (88 μm), p = 0.004. In the 45 MS patients without any intervening clinical optic neuritis, serial OCT (mean of 2 OCT scans per patients, averaging 11 months apart) showed that RNFL decreased by 3.7 μm per year. Conclusion: Retinal nerve fiber layer is significantly reduced in patients with multiple sclerosis. Progressive MS subtypes showed more marked RNFL thinning than relapsing remitting MS. This study reflects the role of OCT in MS patient monitoring and its potential as a surrogate marker in MS therapeutic trials.
Highlights
Optic neuritis-mediated visual loss is the initial symptom in 20% of patients with multiple sclerosis (MS)[1,2] and occurs at some stage in the course of MS in approximately 75% of patients.[3,4]
Our aim was to investigate whether optical coherence tomography could demonstrate axonal loss through thinning of the retinal nerve fiber layer of patients with multiple sclerosis
Eyes affected with clinical optic neuritis were scanned at least nine months after the attack to allow for resolution of acute inflammation and evolution of atrophy; further recovery of the optic nerve is less likely after this time period.[30]
Summary
Optic neuritis-mediated visual loss is the initial symptom in 20% of patients with multiple sclerosis (MS)[1,2] and occurs at some stage in the course of MS in approximately 75% of patients.[3,4] In the Optic Neuritis Treatment Trial (ONTT), the entrance visual acuity (VA) varied considerably, with VA worse than 20/50 in 65% of patients,[5] VA spontaneously improved to 20/40 or better in 64% of patients at 6 months.[6] At 6 months, 63% of patients perceived their vision to be somewhat or much worse that it was before the onset of optic neuritis.[7] Clinical post-mortem data,[8] animal models[9,10] and magnetic resonance imaging (MRI)[11,12] have demonstrated optic nerve atrophy after optic neuritis and MS. A non-invasive in-vivo biological marker that could and accurately quantify axon loss secondary to the disease process is needed to follow the course and monitor treatment effects
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