Optic Nerve Atrophy And Retinal Nerve Fiber Layer Thinning Following Optic Neuritis: Evidence That Axonal Loss Is A Substrate Of MRI-Detected Atrophy
Trip SA, Schlottmann PG, Jones SJ, Li WY, Garway-Heath DF, Thompson AJ, Plant GT, Miller DH
NeuroImage 2006 Jan 26
Institute of Neurology, University College London, NMR Research Unit, Department of NeuroInflammation, UK; Moorfields Eye Hospital, Department of Neuro-Ophthalmology, City Road, London, UK
Magnetic Resonance Imaging (MRI) measures of Brain Atrophy are often considered to be a marker of Axonal Loss in Multiple Sclerosis (MS) but evidence is limited. Optic Neuritis is a common manifestation of MS and results in Optic Nerve Atrophy.
Retinal Nerve Fiber Layer (RNFL) imaging is a non-invasive way of detecting axonal loss following Optic Neuritis.
We hypothesise that if the Optic Nerve Atrophy that develops following Optic Neuritis is contributed to by Axonal Loss, it will correlate with thinning of the RNFL.
Twenty-five patients were studied at least 1 year after a single unilateral attack of Optic Neuritis without recurrence, with a selection bias towards incomplete recovery.
They had MR quantification of Optic Nerve cross-sectional area and optic nerve lesion length, as well as Optical Coherence Tomography (OCT) measurement of mean RNFL thickness and Macular volume, quantitative visual testing, and Visual Evoked Potentials (VEPs). Fifteen controls were also studied.
Significant Optic Nerve Atrophy (mean decrease 30% versus controls), RNFL thinning (mean decrease 33% versus controls), and Macular volume loss occurred in patients' affected eyes when compared with patients' unaffected eyes and healthy controls.
The Optic Nerve Atrophy was correlated with the RNFL thinning, Macular volume loss, Visual Acuity, Visual Field mean deviation, and whole field VEP amplitude but not latency.
These findings suggest that Axonal loss contributes to Optic Nerve Atrophy following a single attack of Optic Neuritis.
By inference, Axonal Loss due to other post-inflammatory Brain lesions is likely to contribute to the global MRI measure of Brain Atrophy in Multiple Sclerosis.
Retinal Nerve Fiber Layer Axonal Loss And Visual Dysfunction In Optic Neuritis
Trip SA, Schlottmann PG, Jones SJ, Altmann DR, Garway-Heath DF, Thompson AJ, Plant GT, Miller DH
Ann Neurol 2005 Sep;58(3):383-91
Institute of Neurology, University College London, NMR Research Unit, Department of NeuroInflammation, Brain Injury and Rehabilitation, London, United Kingdom
Axonal Loss is thought to be a likely cause of persistent disability after a Multiple Sclerosis relapse; therefore, noninvasive in vivo markers specific for Axonal Loss are needed.
We used Optic Neuritis as a model of Multiple Sclerosis relapse to quantify Axonal Loss of the Retinal Nerve Fiber Layer (RNFL) and secondary Retinal Ganglion Cell loss in the Macula with Optical Coherence Tomography.
We studied 25 patients who had a previous single episode of Optic Neuritis with a recruitment bias to those with incomplete recovery and 15 control subjects.
Optical Coherence Tomography measurement of RNFL thickness and Macular volume, quantitative visual testing, and electrophysiological examination were performed.
There were highly significant reductions (p < 0.001) of RNFL thickness and Macular volume in affected patient eyes compared with control eyes and clinically unaffected fellow eyes.
There were significant relationships among RNFL thickness and Visual Acuity, Visual Field, Color Vision, and Visual-Evoked Potential amplitude.
This study has demonstrated functionally relevant changes indicative of Axonal Loss and Retinal Ganglion Cell loss in the RNFL and Macula, respectively, after Optic Neuritis.
This noninvasive RNFL imaging technique could be used in trials of experimental treatments that aim to protect Optic Nerves from Axonal Loss.
A Double-Blind, Randomized Trial Of IV ImmunoGlobulin Treatment In Acute Optic Neuritis
Roed HG, Langkilde A, Sellebjerg F, Lauritzen M, Bang P, Morup A, Frederiksen JL
Neurology 2005 Mar 8;64(5):804-10
University of Copenhagen, MS Clinic, Department of Neurology, Glostrup Hospital, Glostrup, Denmark
To investigate if IV ImmunoGlobulin (IVIG) treatment in the acute phase of Optic Neuritis (ON) could improve visual outcome and reduce MRI disease activity 6 months after onset of ON.
Sixty-eight patients with ON were randomized within 4 weeks from onset of symptoms. Thirty-four patients were randomized to IVIG 0.4 g/kg body wt, and 34 patients were randomized to placebo.
Infusions were given at days 0, 1, 2, 30, and 60. Contrast sensitivity, visual acuity, and color vision were measured at baseline and after 1 week, 1 month, and 6 months.
Pattern reversal Visual Evoked Potential studies and Gadolinium-enhanced MRI were performed at baseline and after 1 and 6 months. Clinical relapses during follow-up were recorded.
There was no difference in the primary outcome, contrast sensitivity after 6 months, between patients randomized to treatment with IVIG or placebo.
In addition, there was no significant difference in the secondary outcome measures, improvement in the visual function measures and MRI, at any time during follow-up.
At baseline, a significantly higher number of patients in the IVIG group had one or more enhancing lesions on MRI and IVIG-treated patients had a significantly higher number of enhancing lesions on MRI than patients treated with placebo.
No difference was found in number of patients with one or more enhancing lesions or number of enhancing lesions in subsequent scans between treatment groups. Number of relapses was equal in the two treatment groups during follow-up.
There was no effect of IV ImmunoGlobulin (IVIG) on long-term visual function following acute Optic Neuritis, nor was there an effect of IVIG treatment in reducing latency on Visual Evoked Potentials and thus preserving function of Axons of the Optic Nerve.
A Serial MRI Study Following Optic Nerve Mean Area In Acute Optic Neuritis
Hickman SJ, Toosy AT, Jones SJ, Altmann DR, Miszkiel KA, MacManus DG, Barker GJ, Plant GT, Thompson AJ, Miller DH
Brain 2004 Nov;127(Pt 11):2498-505
Institute of Neurology, University College London, NMR Research Unit, Department of NeuroInflammation, Queen Square, London WC1N 3BG, UK
This study assessed Optic Nerve mean area on serial MRI in a cohort of patients with a first episode of acute unilateral Optic Neuritis to assess the effects of a single acute inflammatory DeMyelinating lesion.
Twenty-nine patients with a median delay from onset of visual symptoms of 13 days (range 7-24 days) were recruited.
After a clinical examination and Visual Evoked Potential (VEP) measurement, each patient had their Optic Nerves imaged with a coronal fat-saturated short echo fast Fluid-Attenuated Inversion Recovery sequence.
Twenty-one patients had serial examinations after 2, 4, 8, 12, 26 and 52 weeks.
In addition, 32 control subjects had their Optic Nerves imaged up to three times. The mean cross-sectional area of the Intra-Orbital portion of each Optic Nerve was calculated by a blinded observer using a computer-assisted contouring technique.
At baseline, the mean area of diseased Optic Nerves was 16.1 mm2 compared with 13.4 mm2 for healthy contralateral Optic Nerves (20.1% higher, P < 0.0001) and 13.6 mm2 for controls (18.4% higher, P = 0.0003).
The diseased Optic Nerve mean area declined over time, from initial swelling to later atrophy. The mean decline at 52 weeks was -0.0018 mm2/day (95% confidence interval -0.0038 to -0.00051).
At 52 weeks, the mean area of diseased Optic Nerves was 11.3 mm2 compared with 12.8 mm2 for healthy contralateral Optic Nerves (11.7% lower, P = 0.032) and 13.1 mm2 for controls (13.7% lower, P = 0.008).
The 52 week diseased Optic Nerve mean area was not significantly affected by the baseline mean area.
There was an association between baseline Optic Nerve mean area and logMAR Visual Acuity (rS = 0.46, P = 0.012) and visual field mean deviation (rS = -0.55, P = 0.002), but there was no evidence of an association between 1 year mean area and visual outcome.
There was no evidence of association between baseline, rates of decline or 1 year diseased Optic Nerve mean areas and any of the baseline, 1 year or time-averaged VEP variables.
The present study shows a consistent pattern of changes associated with individual inflammatory DeMyelinating lesions in the Optic Nerve.
Acutely, there was swelling, consistent with the presence of acute inflammation, which was related to visual impairment.
Over the longer term, there was loss of tissue. The lack of association between 1 year Optic Nerve mean area and visual outcome may reflect a mild loss of tissue, redundancy or remodelling of function.