Carmen Almarcegui

Axonal loss in the retinal nerve fiber layer in patients with multiple sclerosis

Objective To quantify axonal loss in the retinal nerve fiber layer (RNFL) in patients with multiple sclerosis (MS), with and without a history of optic neuritis, by means of ocular imaging technologies. Methods This cross-sectional study enrolled 50 patients with MS and 25 age- and sex-matched healthy controls. All patients underwent neurologic assessment and a complete ophthalmic examination that included visual acuity, visual field examination, optical coherence tomography (OCT), scanning laser polarimetry (GDx) and visual evoked potentials (VEPs). Visual parameters and RNFL measurements were evaluated in MS eyes with a prior optic neuritis episode (MS-ON), with no prior episode (MS-NON) and control subjects. Results There were significant differences (p < 0.05, analysis of variance) between MS-ON (n = 25 eyes) and healthy eyes (n = 25 eyes) for all RNFL parameters measured by OCT and GDx. Significant differences between MS-NON (n = 75 eyes) and healthy eyes were also found for most of these parameters. RNFL thickness in the temporal quadrant was the parameter with the greatest differences between groups (71.79 μm in healthy eyes, 60.29 μm in MS-NON and 53.92 μm in MS-ON, p < 0.0005). Although there was a highly significant but moderate correlation between RNFL thickness and duration of the disease, no correlation was observed between RNFL thickness and neurologic impairment (Expanded Disability Status Scale). Conclusions Axonal loss was detected not only in MS eyes with a previous acute optic neuritis, but also in MS eyes with no known optic neuritis episode. Structural abnormalities correlate with functional assessments of the optic nerve.

Progressive changes in 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 a 1-year time period and to compare the ability of noninvasive diagnostic imaging devices and visual evoked potentials (VEP) to detect axonal loss in these patients. Methods Eighty-one patients with MS underwent a complete ophthalmic examination that included assessment of visual acuity and color vision, refractive evaluation, visual field examination, optical coherence tomography (OCT), scanning laser polarimetry (GDx), and measurement of VEP. All the patients were re-evaluated after a period of 12 months in order to quantify any change in the RNFL. Only one randomly chosen eye from each patient was included in the study. Results Statistically significant differences between the 2 examinations were recorded for the overall mean and inferior RNFL thickness and the macular volume, as assessed by OCT, as well as for the temporal-superior-nasal-inferior-temporal average standard deviation provided by GDx. The greatest differences were obtained for the mean RNFL thickness (90.46 μm vs 85.96 μm). Changes in the optic nerve were detected by structural measurements but not by functional assessments. Conclusions Axonal loss in the optic nerve of patients with MS is greater than that expected in healthy subjects, regardless of the presence of a previous optic neuritis.

Electrophysiology and Optical Coherence Tomography to Evaluate Parkinson Disease Severity

PURPOSE To evaluate correlations between visual evoked potentials (VEP), pattern electroretinogram (PERG), and macular and retinal nerve fiber layer (RNFL) thickness measured by optical coherence tomography (OCT) and the severity of Parkinson disease (PD). METHODS Forty-six PD patients and 33 age and sex-matched healthy controls were enrolled, and underwent VEP, PERG, and OCT measurements of macular and RNFL thicknesses, and evaluation of PD severity using the Hoehn and Yahr scale to measure PD symptom progression, the Schwab and England Activities of Daily Living Scale (SE-ADL) to evaluate patient quality of life (QOL), and disease duration. Logistical regression was performed to analyze which measures, if any, could predict PD symptom progression or effect on QOL. RESULTS Visual functional parameters (best corrected visual acuity, mean deviation of visual field, PERG positive (P) component at 50 ms -P50- and negative (N) component at 95 ms -N95- component amplitude, and PERG P50 component latency) and structural parameters (OCT measurements of RNFL and retinal thickness) were decreased in PD patients compared with healthy controls. OCT measurements were significantly negatively correlated with the Hoehn and Yahr scale, and significantly positively correlated with the SE-ADL scale. Based on logistical regression analysis, fovea thickness provided by OCT equipment predicted PD severity, and QOL and amplitude of the PERG N95 component predicted a lower SE-ADL score. CONCLUSIONS Patients with greater damage in the RNFL tend to have lower QOL and more severe PD symptoms. Foveal thicknesses and the PERG N95 component provide good biomarkers for predicting QOL and disease severity.

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

Acta Ophthalmol. 2010: 88: 748–752

Effect of optic neuritis on progressive axonal damage in multiple sclerosis patients

Objective: The objective of this research was to study the effect of optic neuritis (ON) on axonal damage in multiple sclerosis (MS) patients. Specifically, we compared changes over 2 years in the retinal nerve fibre layer (RNFL) between affected and contralateral eyes in MS patients with a prior history of ON. Methods: Thirty-four patients with one unilateral definitive episode of ON were included and underwent a complete ophthalmic examination, optical coherence tomography (OCT), scanning laser polarimetry, visual evoked potentials (VEP) and pattern electroretinogram (pERG). All patients were re-evaluated at 12 and 24 months. Parameters were compared between ON-affected and contralateral eyes in an initial exploration and over the course of the follow-up. Correlations between parameter changes were analysed. Results: RNFL thickness and functional parameters showed more affection in ON eyes (p ≤ 0.05), but changes in measurements during the study were similar between both groups of eyes. Conclusions: Progressive axonal loss can be detected in the optic nerve, but ON is not a risk factor for increased chronic damage in MS patients without ophthalmic relapses. Loss of the RNFL is caused by progressive degeneration associated with the disease.

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.

Electropysiologic evaluation of the visual pathway in patients with multiple sclerosis.

Purpose: To evaluate the ability of visual evoked potentials and pattern electroretinograms (PERG) to detect subclinical axonal damage in patients during the early diagnostic stage of multiple sclerosis (MS). The authors also compared the ability of optical coherence tomography (OCT), PERG, and visual evoked potentials to detect axonal loss in MS patients and correlated the functional and structural properties of the retinal nerve fiber layer. Methods: Two hundred twenty-eight eyes of 114 subjects (57 MS patients and 57 age- and sex-matched healthy controls) were included. The visual pathway was evaluated based on functional and structural assessments. All patients underwent a complete ophthalmic examination that included assessment of visual acuity, ocular motility, intraocular pressure, visual field, papillary morphology, OCT, visual evoked potentials, and PERG. Results: Visual evoked potentials (P100 latency and amplitude), PERG (N95 amplitude and N95/P50 ratio), and OCT parameters differed significantly between MS patients and healthy subjects. Moderate significant correlations were found between visual evoked potentials or PERG parameters and OCT measurements. Conclusions: Axonal damage in ganglion cells of the visual pathway can be detected based on structural measures provided by OCT in MS patients and by the N95 component and N95/P50 index of PERG, thus providing good correlation between function and structure.

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.