Jose R. Ara

Retinal layer segmentation in patients with multiple sclerosis using spectral domain optical coherence tomography.

PURPOSE To evaluate the thickness of the 10 retinal layers in the paramacular area of patients with multiple sclerosis (MS) compared with healthy subjects using the new segmentation technology of spectral domain optical coherence tomography (OCT). To examine which layer has better sensitivity for detecting neurodegeneration in patients with MS. DESIGN Observational, cross-sectional study. PARTICIPANTS Patients with MS (n = 204) and age-matched healthy subjects (n = 138). METHODS The Spectralis OCT system (Heidelberg Engineering, Inc., Heidelberg, Germany) was used to obtain automated segmentation of all retinal layers in a parafoveal scan in 1 randomly selected eye of each participant, using the new segmentation application prototype. MAIN OUTCOME MEASURES The thicknesses of 512 parafoveal points in the 10 retinal layers were obtained in each eye, and the mean thickness of each layer was calculated and compared between patients with MS and healthy subjects. The analysis was repeated, comparing patients with MS with and without previous optic neuritis. Correlation analysis was performed to evaluate the association between each retinal layer mean thickness, duration of disease, and functional disability in patients with MS. A logistic regression analysis was performed to determine which layer provided better sensitivity for detecting neurodegeneration in patients with MS. RESULTS All retinal layers, except the inner limiting membrane, were thinner in patients with MS compared with healthy subjects (P < 0.05). Greater effects were observed in the inner retinal layers (nerve fiber, ganglion cells, inner plexiform, and inner nuclear layers) of eyes with previous optic neuritis (P < 0.05). The retinal nerve fiber layer and ganglion cell layer thicknesses were inversely correlated with the functional disability score in patients with MS. The ganglion cell layer and inner plexiform layer thicknesses could predict axonal damage in patients with MS. CONCLUSIONS Analysis based on the segmentation technology of the Spectralis OCT revealed retinal layer atrophy in patients with MS, especially of the inner layers. Reduction of the ganglion cell and inner plexiform layers predicted greater axonal damage in patients with MS.

Increased serum interleukin-17 levels in patients with myasthenia gravis.

It has been suggested that interleukin‐17 (IL‐17) plays a crucial role in the development of several autoimmune diseases. However, there are no data about the relationship between myasthenia gravis and IL‐17. The aim of this study was to measure the concentration of IL‐17 and determine whether levels depend on the severity of MG. Serum IL‐17 concentrations were measured in 25 patients. IL‐17 concentrations were higher in generalized MG compared with controls and correlated with anti‐acetylcholinesterase receptor antibody titers. Muscle Nerve, 2011

Sub‐clinical atrophy of the retinal nerve fibre layer in multiple sclerosis

Acta Ophthalmol. 2010: 88: 748–752

Risk factors for progressive axonal degeneration of the retinal nerve fibre layer in multiple sclerosis patients

Aim To quantify structural and functional degeneration in the retinal nerve fibre layer (RNFL) of patients with multiple sclerosis (MS) over a 2-year time period, and to analyse the effect of prior optic neuritis (ON) as well as the duration and incidence of MS relapses. Methods 166 MS patients and 120 healthy controls underwent assessment of visual acuity and colour vision, visual field examination, optical coherence tomography, scanning laser polarimetry and visual evoked potentials (VEPs). All subjects were re-evaluated after a period of 12 and 24 months. Results Changes in the optic nerve were detected by structural measurements but not by functional assessments. Changes registered in MS patients were greater than changes in healthy controls (p<0.05). Eyes with previous ON showed a greater reduction of parameters in the baseline evaluation, but RNFL atrophy was not significantly greater in the longitudinal study. Patients with MS relapses showed a greater reduction of RNFL thickness and VEP amplitude compared with non-relapsing cases. Patients with and without treatment showed similar measurement reduction, but the non-treated group had a significantly higher increase in Expanded Disability Status Scale (p=0.029). Conclusions MS causes progressive axonal loss in the optic nerve, regardless of a history of ON. This ganglion cell atrophy occurs in all eyes but is more marked in MS eyes than in healthy eyes.

Neuro-ophthalmologic evaluation, quality of life, and functional disability in patients with MS

Objective: To evaluate correlations between longitudinal changes in neuro-ophthalmologic measures and quality of life (QOL) and disability in patients with multiple sclerosis (MS), using optical coherence tomography (OCT), visual evoked potentials (VEP), and visual field examination. Methods: Fifty-four patients with relapsing-remitting MS were enrolled in this study and underwent Multiple Sclerosis Quality of Life questionnaire (54 items) (MSQOL-54) and Expanded Disability Status Scale (EDSS) evaluation, as well as complete neuro-ophthalmologic examination including visual field testing and retinal nerve fiber layer (RNFL) measurements using Cirrus and Spectralis OCT and VEP. All patients were re-evaluated at 12, 24, and 36 months. Logistical regression was performed to analyze which measures, if any, could predict QOL. Results: Overall, RNFL thickness results at the baseline evaluation were significantly different from those at 3 years (p ≤ 0.05), but there were no differences in functional measures (visual acuity, contrast sensitivity, color vision, visual field, and VEP). A reduced MSQOL-54 score was associated with an increase in EDSS score and a decrease in both functional and structural parameters. Patients with longer MS duration presented with a lower MSQOL-54 score (reduction in QOL). Conclusions: Patients with progressive axonal loss as seen in RNFL results had a lower QOL and more functional disability.

Progressive Degeneration of the Retinal Nerve Fiber Layer in Patients with Multiple Sclerosis

PURPOSE To quantify changes in the retinal nerve fiber layer (RNFL) of patients with multiple sclerosis (MS) over 3 years and to evaluate whether treatment protects against RNFL degeneration. METHODS Ninety-four MS patients and 50 healthy subjects were followed-up over 3 years. All subjects underwent a complete ophthalmic examination, which included assessment of visual acuity (Snellen chart), color vision (Ishihara pseudoisochromatic plates), visual field examination, optical coherence tomography (OCT), and visual evoked potentials (VEPs). All patients were reevaluated at 12, 24, and 36 months to quantify changes in the RNFL. RESULTS Changes were detected in RNFL thickness at the 36-month follow-up. Significant decreases (P < 0.05, t-test) were observed in the mean, superior, inferior, and temporal RNFL thicknesses, and macular volume provided by OCT, and in the P100 latency of VEP of the MS group, but only in the mean and inferior RNFL thicknesses of the healthy control group. Greater changes in the superior and inferior RNFL thicknesses during follow-up were detected in the MS group. Differences between treatments were not detected, but untreated patients had higher degeneration in the mean and superior RNFL thicknesses during the follow-up (P = 0.040 and P = 0.19, respectively). CONCLUSIONS Progressive axonal loss can be detected in the optic nerve fiber layer of MS patients. Analysis of the RNFL by OCT can be useful for evaluating MS progression and efficacy of treatment as a neuroprotective factor against axonal degeneration.

POSTERIOR REVERSIBLE ENCEPHALOPATHY SYNDROME AFTER RITUXIMAB INFUSION IN NEUROMYELITIS OPTICA

The first complete description of the posterior reversible encephalopathy syndrome (PRES) was made in 1996.1 Its initial description has been amplified by several atypical or additional clinical and radiologic findings. Throughout the last few years, this syndrome has been presented as a neurologic complication associated with various medical diseases in the context of rapid-onset hypertension or immunosuppressive treatments; its association with neuromyelitis optica (NMO) spectrum disorders has recently been suggested, with series of PRES in NMO cases recently published, implicating a possible role for aquaporin-4 channelopathy in the pathogenesis of some cases of PRES.2 We present a case of PRES in a patient with an established NMO diagnosis happening after rituximab infusion (anti-CD20 monoclonal antibody), a treatment that has just recently been introduced for severe forms of the disease.3 We underline the fact that PRES secondary to rituximab may be responsible for neurologic worsening that can simulate a demyelinating relapse. ### Case report. We report a 35-year-old woman who exhibited mild myelitis in 2006 and right optic neuritis (ON) in 2007. New ON and C3-C6 posterior cord myelitis was noted in February 2008. Cerebral MRI was normal. NMO diagnosis was made on the basis of the …

Optical Coherence Tomography as a Biomarker for Diagnosis, Progression, and Prognosis of Neurodegenerative Diseases

Neurodegenerative diseases present a current challenge for accurate diagnosis and for providing precise prognostic information. Developing imaging biomarkers for multiple sclerosis (MS), Parkinson disease (PD), and Alzheimers disease (AD) will improve the clinical management of these patients and may be useful for monitoring treatment effectiveness. Recent research using optical coherence tomography (OCT) has demonstrated that parameters provided by this technology may be used as potential biomarkers for MS, PD, and AD. Retinal thinning has been observed in these patients and new segmentation software for the analysis of the different retinal layers may provide accurate information on disease progression and prognosis. In this review we analyze the application of retinal evaluation using OCT technology to provide better understanding of the possible role of the retinal layers thickness as biomarker for the detection of these neurodegenerative pathologies. Current OCT analysis of the retinal nerve fiber layer and, specially, the ganglion cell layer thickness may be considered as a good biomarker for disease diagnosis, severity, and progression.

Diagnostic ability of a new method for measuring haemoglobin levels in the optic nerve head in multiple sclerosis patients

Aims To evaluate a new method for measuring haemoglobin (Hb) levels and quantifying the colour changes in the optic nerve head of multiple sclerosis (MS) patients to detect axonal loss and consequently optic disc atrophy. Material and methods 40 MS patients and 40 age and sex-matched healthy subjects were included in this prospective cross-sectional study and underwent a full ophthalmological examination, including three photographs of the optic disc. The Laguna ONhE (‘optic nerve hemoglobin’; Insoft SL, Tenerife, Spain) software was used to obtain the Hb analysis in each of the 24 sectors and average Hb of optic disc photographs acquired. Reproducibility of measurements provided by Laguna ONhE program was analysed. Results MS patients showed significant reduction of optic disc Hb percentages in average Hb (58.99% in MS, 65.39% in healthy subjects; p<0.001) and in almost all analysed sectors with the largest differences in temporal sectors. Laguna ONhE program showed good reproducibility measuring Hb percentages in MS patients and healthy subjects. Conclusions Measurements of optic disc Hb levels obtained with Laguna ONhE software had good ability detecting optic atrophy and axonal loss in MS patients. This method had good reliability and is easy to implement in routine clinical practice.

Retinal and Optic Nerve Degeneration in Patients with Multiple Sclerosis Followed up for 5 Years

PURPOSE To quantify retinal nerve fiber layer (RNFL) changes in patients with multiple sclerosis (MS) and healthy controls with a 5-year follow-up and to analyze correlations between disability progression and RNFL degeneration. DESIGN Observational and longitudinal study. PARTICIPANTS One hundred patients with relapsing-remitting MS and 50 healthy controls. METHODS All participants underwent a complete ophthalmic and electrophysiologic exploration and were re-evaluated annually for 5 years. MAIN OUTCOME MEASURES Visual acuity (Snellen chart), color vision (Ishihara pseudoisochromatic plates), visual field examination, optical coherence tomography (OCT), scanning laser polarimetry (SLP), and visual evoked potentials. Expanded Disability Status Scale (EDSS) scores, disease duration, treatments, prior optic neuritis episodes, and quality of life (QOL; based on the 54-item Multiple Sclerosis Quality of Life Scale score). RESULTS Optical coherence tomography (OCT) revealed changes in all RNFL thicknesses in both groups. In the MS group, changes were detected in average thickness and in the mean deviation using the GDx-VCC nerve fiber analyzer (Laser Diagnostic Technologies, San Diego, CA) and in the P100 latency of visual evoked potentials; no changes were detected in visual acuity, color vision, or visual fields. Optical coherence tomography showed greater differences in the inferior and temporal RNFL thicknesses in both groups. In MS patients only, OCT revealed a moderate correlation between the increase in EDSS and temporal and superior RNFL thinning. Temporal RNFL thinning based on OCT results was correlated moderately with decreased QOL. CONCLUSIONS Multiple sclerosis patients exhibit a progressive axonal loss in the optic nerve fiber layer. Retinal nerve fiber layer thinning based on OCT results is a useful marker for assessing MS progression and correlates with increased disability and reduced QOL.