Multiple Sclerosis
Figure 1: High-resolution Images of the Internal Retinal Structure Taken with Optical Coherence Tomography
Detector
Semi-transparent mirror splits light beam
Infrared light (800nm
wavelength) Mirror #2 A: Transmitted light
Retina same distance as mirror #2
Detector C
have a lower risk of developing MS, particularly when their baseline MRI scan is normal.19
Approximately 50–80% of patients with ON
have periventricular white-matter abnormalities consistent with demyelination on an initial MRI scan.26
In the ONTT, 10 years after acute ON the presence or absence of MRI lesions was the main factor in determining the risk of MS:19
56% of
Infrared light (800nm
wavelength) Mirror #2
A: Low-coherence infrared light is transmitted into the eye through use of an interoferometer. B: The infrared light is transmitted through the pupil and then penetrates through the nine transparent layers of the retina. C: A fundus image from the optical coherence tomography (OCT) device showing the optic disc appropriately centred and surrounded by the target image circumference marker for analysis of the retinal nerve fibre layer. Source: Frohman et al., 2008.34
specifically nerve damage itself. Furthermore, extensive lesions and brain shrinking occur relatively late in the progression of the disease and this can be confounded by inflammation in MS that may increase overall volume. MRI is therefore not a good tool for the detection of MS in its early stages. There is an urgent need for tools able to detect axonal loss early. In addition, MRI facilities are expensive and require expertise and considerable resources to operate, and are mostly confined to specialist centres. MRI investigation is thus not readily available to patients with MS in many locations, and for some people scanning can be an unpleasant procedure.
Although there is a broad age range at onset, most patients with acute demyelinating ON are young (20–45 years of age).22,23
as men to develop ON.22
usually experiences a decline in vision over a seven- to 10-day period, often characterised by a decline in contrast sensitivity.24
Optic Neuritis in Multiple Sclerosis The visual system is often affected in MS and, as the retina is an integral part of the central nervous system (CNS), examination of the eye enables unmyelinated axons of the CNS to be visualised directly. ON is inflammation with accompanying demyelination in the optic nerve that may cause complete or partial loss of vision. It is frequently the initial clinical manifestation of MS and is reported in 94–96% of MS autopsy cases.21
There is a gender difference: women are three times as likely A patient with typical demyelinating ON
The
progression of visual loss beyond two weeks is distinctly unusual and visual acuity usually recovers well.
In the Optic Neuritis Treatment Trial (ONTT),25 which investigated the
use of corticosteroids to treat a population of 448 patients with ON, the majority (92%) of patients had pain, particularly with eye movements. In a patient with typical ON, some recovery of vision should occur within 30 days of onset. Clinical features that suggest non-typical ON include the presence of retinal haemorrhages, a markedly swollen nerve, retinal exudates, the absence of pain and the presence of no light-perception vision at onset. These patients
74 B: Reflected light
patients with one or more white-matter lesion on their baseline brain MRI scan developed MS, whereas 22% of patients with a normal baseline MRI developed MS at 10 years. The presence of oligoclonal bands in the CSF is also an independent risk factor for MS.27 Subclinical or chronic forms of demyelinating ON in which the patient notices a gradual decline in vision instead of acute vision loss followed by improvement may also develop in MS. These patients may show abnormalities on neuro-ophthalmological examination, including field loss, pupillary abnormalities and disc pallor.28 Subclinical ON can be sensitively detected using lower-contrast letter acuity testing.29
ON and other visual defects contribute significantly to the reduction in quality of life of MS patients.30
The use of oral corticosteroids was associated with an increased risk of recurrent ON five years after an initial bout of ON; patients who received oral prednisone (1mg/kg) had the highest rate of recurrence (41%) compared with those who received methyl- prednisolone or placebo (25% for both groups). However, there was no significant difference in the long-term risk of MS.
Optical Coherence Tomography
One of the most exciting developments in ophthalmic imaging is arguably OCT, which was introduced in 199132 clinical practice since 1995.33
and has been a part of OCT is widely used to obtain high-
resolution images of the retina and the anterior segment of the eye. Figure 1 provides a summary of the operation of OCT. OCT creates images by reflecting laser light on the retina to generate a cross- sectional image. The extent of the reflectivity differs between cell types in retinal layers. OCT measures retinal nerve fibre layer (RNFL) thickness utilising interferometry – the technique of determining the properties of two waves by analysing the pattern of interference created by their superposition.34
In patients with acute ON, treatment with a three-day course of high- dose (1g/day) intravenous corticosteroids is usually recommended. The ONTT used three treatment groups: intravenous methylprednisolone for three days followed by an oral prednisone taper; oral prednisone; and oral placebo.31
The light source is a super-luminescent diode. OCT captures cross-sectional images from a series of lateral adjacent depth- scans. OCT therefore determines overall thickness and quadrant thicknesses in different pathological conditions including ON or MS and compared with normative values (see Figure 2). OCT has the advantages of being non-invasive, easy to use and quantitative. Its sensitivity allows direct visualisation and measurement of RNFL thickness and macular volume with micron-scale resolution (see Figure 3).35,36
The latest
technical improvements, such as higher resolution (between 2 and 3µm) and dual laser beams to overcome eye movements, have enabled these instruments to gain a high clinical utility in predicting MS disease course and determining treatment response.33,37
Optical Coherence Tomography Studies in Optic Neuritis and Multiple Sclerosis Among patients with ON, optic nerve atrophy has often been detected by MRI.38–40
In a study in the UK including 10 patients with a history of ON, a correlation was found between the mean loss of
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