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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    ABSTRACT: Purpose . This study aimed at assessing the prevalence of pathologies presenting retinal inner nuclear layer (RINL) microcystic perimacular changes associated with optic nerve atrophy (OA). The charts of patients presenting a significant defect of the Retinal Nerve Fiber Layer (RNFL) were included prospectively in this study. Patients were classified according to the etiology of the RNFL defect. Two hundred and one eyes of 138 patients were enrolled in this analysis. Retinal images obtained showed the typical hyporeflective perifoveal crescent-shaped lesion composed of small round hyporeflective microcysts confined to the RINL in 35.3% of the eyes. Those findings were found in 75% of eyes presenting hereditary OA, 50% of eyes presenting ischemic optic neuritis, 50% of eyes with drusen of the optic nerve (ON), 44.4% of eyes presenting a compressive OA, 32% of eyes presenting inflammatory optic neuropathy from multiple sclerosis, 18.5% of eyes presenting OA from undetermined origin, and 17.6% of eyes having primary open-angle glaucoma. This study demonstrates that microcystic changes in RINL are not specific to a disease but are found in OA of various etiologies. Moreover, their incidence was found to be dependent upon the cause of OA, with the highest incidence occurring in genetic OA.
    Journal of Ophthalmology 02/2014; 2014(5):395189. DOI:10.1155/2014/395189 · 1.43 Impact Factor
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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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    ABSTRACT: Patient was followed up over the course of 30 years. In 1978, after severe systemic infection followed by fever, pulmonary edema, and numerous neurological manifestations, patient was differentially diagnosed with apoplectic form of multiple sclerosis (MS), which was confirmed a year later via neurological and MRI findings. Approximately 20 years following the initial attack, sarcoidosis was diagnosed during the regular preoperative procedures required for cataract surgery. As consequence of lower immune system, infectious granulomatosis in form of pulmonary tuberculosis developed. Ophthalmological findings revealed bilateral retrobulbar neuritis (RBN) approximately six years after initial attack. This developed into total uveitis with retinal periphlebitis and anterior granulomatous uveitis-all of which are clinically similar in both MS and sarcoidosis.
    02/2014; 2014:876525. DOI:10.1155/2014/876525
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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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    ABSTRACT: The purpose of this study was to investigate the characteristics of microcystic macular edema (MME) determined from the en face images obtained by an adaptive optics (AO) fundus camera in patients with autosomal dominant optic atrophy (ADOA) and to try to determine the mechanisms underlying the degeneration of the inner retinal cells and RNFL by using the advantage of AO. Six patients from 4 families with ADOA underwent detailed ophthalmic examinations including spectral domain optical coherence tomography (SD-OCT). Mutational screening of all coding and flanking intron sequences of the OPA1 gene was performed by DNA sequencing. SD-OCT showed a severe reduction in the retinal nerve fiber layer (RNFL) thickness in all patients. A new splicing defect and two new frameshift mutations with premature termination of the Opa1 protein were identified in three families. A reported nonsense mutation was identified in one family. SD-OCT of one patient showed MME in the inner nuclear layer (INL) of the retina. AO images showed microcysts in the en face images of the INL. Our data indicate that AO is a useful method to identify MME in neurodegenerative diseases and may also help determine the mechanisms underlying the degeneration of the inner retinal cells and RNFL.
    11/2013; 2013(6):676803. DOI:10.1155/2013/676803
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