Research: Eye Problems in MS

EpubGelfand et al. Microcystic macular oedema in multiple sclerosis is associated with disease severity. Brain. 2012 Apr 25.

Macular (centre of retina) oedema (swelling) typically results from blood-retinal barrier disruption. It has recently been reported that MSers treated with fingolimod may exhibit macular oedema. MS is not otherwise thought to be associated with macular oedema except in the context of comorbid clinical uveitis.

Despite a lack of myelin, the retina is a site of inflammation and microglial activation in MS and demonstrates significant neuronal and axonal loss. These investigators unexpectedly observed microcystic (small cysts) macular oedema using spectral domain optical coherence tomography (OCT) in MSers who did not have another reason for macular oedema. They therefore evaluated spectral domain optical coherence tomography images in consecutive MSers for microcystic macular oedema and examined correlations between macular oedema and visual and ambulatory disability in a cross-sectional analysis. Participants were excluded if there was a comorbidity that could account for the presence of macular oedema, such as uveitis (inflammation in the eye), diabetes or other retinal disease. A microcystic pattern of macular oedema was observed on optical coherence tomography in 15 of 318 (4.7%) MSers. No macular oedema was identified in 52 healthy controls assessed over the same period.

The microcystic oedema predominantly involved the inner nuclear layer of the retina and tended to occur in small, discrete patches. MSers with microcystic macular oedema had significantly worse disability [median Expanded Disability Score Scale 4 (interquartile range 3-6)] than MSers without macular oedema [median Expanded Disability Score Scale 2 (interquartile range 1.5-3.5)], Pā€‰=ā€‰0.0002. MSers with microcystic macular oedema also had higher Multiple Sclerosis Severity Scores, a measure of disease progression, than those without oedema [median of 6.47 (interquartile range 4.96-7.98) versus 3.65 (interquartile range 1.92-5.87), Pā€‰=ā€‰0.0009].

Microcystic macular oedema occurred more commonly in eyes with prior optic neuritis than eyes without prior optic neuritis (50 versus 27%) and was associated with lower visual acuity (median logMAR acuity of 0.17 versus -0.1) and a thinner retinal nerve fibre layer. The presence of microcystic macular oedema in MS suggests that there may be breakdown of the blood-retinal barrier and tight junction integrity in a part of the nervous system that lacks myelin. Microcystic macular oedema may also contribute to visual dysfunction beyond that explained by nerve fibre layer loss. Microcystic changes need to be assessed, and potentially adjusted for, in clinical trials that evaluate macular volume as a marker of retinal ganglion cell survival. These findings also have implications for clinical monitoring in MSers on sphingosine 1-phosphate receptor modulating agents, i.e. fingolimod and follow-on compounds.



"Macular oedema has been reported in MSers on fingolimod (Gilenya); this study shows that this can occur spontaneously in a small number of MSers. This was worse in MSers with more advanced disease and occurred more in people that have had optic nerve disease in the past. Visual disturbances can occur result from macular swelling in addition to that which may also relate to influences on the nerve fibre layer (ganglion cells), which are damaged as nerves in the optic nerve are damaged. Therefore it will be important to be assessed before starting fingolimod (Gilenya) and whilst on the drug to make sure it is not a side-effect of the drug."

"The observation that inflammation occurs in the retinae of MSers, where there is no myelin questions the dogma that the autoimmune target in MS is myelin. There must be something else in the retina that the immune system is targeting. Could it be a virus?"


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