Microcystic macular oedema (MMO) of the retinal inner nuclear layer (INL) has been identified in patients with multiple sclerosis (MS) by use of optical coherence tomography (OCT). We aimed to determine whether MMO of the INL, and increased thickness of the INL are associated with disease activity or disability progression.
This retrospective study was done at the Johns Hopkins Hospital (Baltimore, MD, USA), between September, 2008, and March, 2012. Patients with MS and healthy controls underwent serial OCT scans and clinical assessments including visual function. OCT scanning, including automated intraretinal layer segmentation, yielded thicknesses of the retinal nerve fibre layer, the ganglion cell layer plus inner plexiform layer, the INL plus outer plexiform layer (the combined thickness of these layers was used as a surrogate measure of INL thickness), and the outer nuclear layer. Patients with MS also underwent annual brain MRI scans. Disability scores were compared with the Wilcoxon rank-sum test. Mixed-effects linear regression was used to compare OCT measures and letter-acuity scores. Logistic regression was used to examine the relations of baseline OCT thicknesses with clinical and radiological parameters.
164 patients with MS and 60 healthy controls were assessed. Mean follow-up was 25·8 months (SD 9·1) for patients with MS and 22·4 months (11·4) for healthy controls. Ten (6%) patients with MS had MMO during at least one study visit; MMO was visible at baseline in four of these patients. Healthy controls did not have MMO. Patients with MS and MMO had higher baseline MS severity scores (median 5·93 [range 2·44-8·91]) than those who did not have MMO at any time during the study (151 patients; 3·81 [0·13-9·47]; p=0·032), although expanded disability status scale (EDSS) scores were not significantly different (5·2 [1·0-6·5] for patients with MS and MMO vs 2·5 [0·0-8·0] for those without MMO; p=0·097). The eyes of patients with MS and MMO (12 eyes) versus those without MMO (302 eyes) had lower letter-acuity scores (100% contrast, p=0·017; 2·5% contrast, p=0·031; 1·25% contrast, p=0·014), and increased INL thicknesses (p=0·003) at baseline. Increased baseline INL thickness in patients with MS was associated with the development of contrast-enhancing lesions (p=0·007), new T2 lesions (p=0·015), EDSS progression (p=0·034), and relapses in patients with relapsing-remitting MS (p=0·008) during the study. MMO was not associated with disease activity during follow-up.
Increased INL thickness on OCT is associated with disease activity in MS. If this finding is confirmed, INL thickness could be a useful predictor of disease progression in patients with MS.
National Multiple Sclerosis Society, National Eye Institute, Braxton Debbie Angela Dillon and Skip Donor Advisor Fund.
"This has enabled imaging in patients with infantile and acquired forms of nystagmus. Recent OCT studies in multiple sclerosis have suggested that this imaging modality has an important role in monitoring disease activity (19) and the retinal changes reflect global CNS processes (20). Similarly, OCT studies in infantile nystagmus have highlighted the spectrum of abnormal retinal phenotypes and its role in predicting visual acuity (7). "
[Show abstract][Hide abstract] ABSTRACT: Idiopathic infantile nystagmus (IIN) is a genetically heterogeneous disorder, often associated with FRMD7 mutations. As the appearance of the retina is reported to be normal based on conventional fundus photography, IIN is postulated
to arise from abnormal cortical development. To determine whether the afferent visual system is involved in FRMD7 mutations, we performed in situ hybridization studies in human embryonic and fetal stages (35 days post-ovulation to 9 weeks post-conception). We show a
dynamic retinal expression pattern of FRMD7 during development. We observe expression within the outer neuroblastic layer, then in the inner neuroblastic layer and at
9 weeks post-conception a bilaminar expression pattern. Expression was also noted within the developing optic stalk and optic
disk. We identified a large cohort of IIN patients (n = 100), and performed sequence analysis which revealed 45 patients with FRMD7 mutations. Patients with FRMD7 mutations underwent detailed retinal imaging studies using ultrahigh-resolution optical coherence tomography. The tomograms
were compared with a control cohort (n = 60). The foveal pit was significantly shallower in FRMD7 patients (P < 0.0001). The optic nerve head morphology was abnormal with significantly decreased optic disk area, retinal nerve fiber
layer thickness, cup area and cup depth in FRMD7 patients (P < 0.0001). This study shows for the first time that abnormal afferent system development is associated with FRMD7 mutations and could be an important etiological factor in the development of nystagmus.
Human Molecular Genetics 03/2014; 23(15). DOI:10.1093/hmg/ddu122 · 6.39 Impact Factor
"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. "
[Show abstract][Hide abstract] 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
"Segmentation of intra-retinal layers is very important not only in ophthalmology but also in neurology. Except for the RNFL, the thicknesses of the deeper retinal layers are reported to change in multiple sclerosis, Parkinsonian syndromes, and less frequently in disorders such as neuromyelitis optica and Wilson’s disease , , , , . "
[Show abstract][Hide abstract] ABSTRACT: To evaluate the repeatability, reproducibility, and agreement of thickness profile measurements of eight intra-retinal layers determined by an automated algorithm applied to optical coherence tomography (OCT) images from two different instruments.
Twenty normal subjects (12 males, 8 females; 24 to 32 years old) were enrolled. Imaging was performed with a custom built ultra-high resolution OCT instrument (UHR-OCT, ∼3 µm resolution) and a commercial RTVue100 OCT (∼5 µm resolution) instrument. An automated algorithm was developed to segment the macular retina into eight layers and quantitate the thickness of each layer. The right eye of each subject was imaged two times by the first examiner using each instrument to assess intra-observer repeatability and once by the second examiner to assess inter-observer reproducibility. The intraclass correlation coefficient (ICC) and coefficients of repeatability and reproducibility (COR) were analyzed to evaluate the reliability.
The ICCs for the intra-observer repeatability and inter-observer reproducibility of both SD-OCT instruments were greater than 0.945 for the total retina and all intra-retinal layers, except the photoreceptor inner segments, which ranged from 0.051 to 0.643, and the outer segments, which ranged from 0.709 to 0.959. The CORs were less than 6.73% for the total retina and all intra-retinal layers. The total retinal thickness measured by the UHR-OCT was significantly thinner than that measured by the RTVue100. However, the ICC for agreement of the thickness profiles between UHR-OCT and RTVue OCT were greater than 0.80 except for the inner segment and outer segment layers.
Thickness measurements of the intra-retinal layers determined by the automated algorithm are reliable when applied to images acquired by the UHR-OCT and RTVue100 instruments.
PLoS ONE 02/2014; 9(2):e87996. DOI:10.1371/journal.pone.0087996 · 3.23 Impact Factor
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