Microcystic macular oedema in multiple sclerosis is associated with disease severity

Multiple Sclerosis Centre, University of California, San Francisco, Department of Neurology, 400 Parnassus Ave, San Francisco, CA 94143-0114, USA.
Brain (Impact Factor: 9.2). 04/2012; 135(Pt 6):1786-93. DOI: 10.1093/brain/aws098
Source: PubMed


Macular oedema typically results from blood-retinal barrier disruption. It has recently been reported that patients with multiple sclerosis treated with FTY-720 (fingolimod) may exhibit macular oedema. Multiple sclerosis 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 multiple sclerosis and demonstrates significant neuronal and axonal loss. We unexpectedly observed microcystic macular oedema using spectral domain optical coherence tomography in patients with multiple sclerosis who did not have another reason for macular oedema. We therefore evaluated spectral domain optical coherence tomography images in consecutive patients with multiple sclerosis 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, diabetes or other retinal disease. A microcystic pattern of macular oedema was observed on optical coherence tomography in 15 of 318 (4.7%) patients with multiple sclerosis. 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. Patients with multiple sclerosis with microcystic macular oedema had significantly worse disability [median Expanded Disability Score Scale 4 (interquartile range 3-6)] than patients without macular oedema [median Expanded Disability Score Scale 2 (interquartile range 1.5-3.5)], P = 0.0002. Patients with multiple sclerosis 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), P = 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 multiple sclerosis 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 patients with multiple sclerosis on sphingosine 1-phosphate receptor modulating agents.

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    • "This prospective study of a large population of patients with OA shows that microcystic changes in the RINL observed in OA are not specific of an etiology as previously thought in multiple sclerosis [5–8] but are found in many diseases of various etiologies, mostly genetic. Effectively, microcysts were found in 75% of eyes presenting mitochondrial OA or ADOA, 50% of eyes presenting ischemic optic neuritis, 50% of eyes having drusen of the ON, 44.4% of eyes presenting a compressive OA, 32% of eyes presenting MS, 18.5% of eyes presenting OA from undetermined origin, and 17.6% of eyes having POAG. "
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    • "Ocular manifestations such as retrobulbar neuritis (RBN), retinal vasculitis (RV), and anterior granulomatous uveitis occur as part of MS. According to some authors, RV (periphlebitis) is a primary inflammation subsequent to vitreal inflammation and snow bank formation [3] [11]. Sarcoidosis is a multisystemic, granulomatous disease of unknown etiology. "
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    • "The INL is predominantly made up of the nuclei of the horizontal, bipolar, and amacrine cells. MME was originally identified in patients with multiple sclerosis (MS) by Gelfand et al., and it was characterized by cystic lacunar areas of hyporeflectivity with clear boundaries in the spectral domain optical coherence tomographic (SD- OCT) images [23]. They suggested that MME represented a breakdown of the blood-retina barrier caused by subclinical uveitis or retinitis. "
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