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1.  Optic Nerve Diffusion Tensor Imaging after Acute Optic Neuritis Predicts Axonal and Visual Outcomes 
PLoS ONE  2013;8(12):e83825.
Background
Early markers of axonal and clinical outcomes are required for early phase testing of putative neuroprotective therapies for multiple sclerosis (MS).
Objectives
To assess whether early measurement of diffusion tensor imaging (DTI) parameters (axial and radial diffusivity) within the optic nerve during and after acute demyelinating optic neuritis (ON) could predict axonal (retinal nerve fibre layer thinning and multi-focal visual evoked potential amplitude reduction) or clinical (visual acuity and visual field loss) outcomes at 6 or 12 months.
Methods
Thirty-seven patients presenting with acute, unilateral ON were studied at baseline, one, three, six and 12 months using optic nerve DTI, clinical and paraclinical markers of axonal injury and clinical visual dysfunction.
Results
Affected nerve axial diffusivity (AD) was reduced at baseline, 1 and 3 months. Reduced 1-month AD correlated with retinal nerve fibre layer (RNFL) thinning at 6 (R=0.38, p=0.04) and 12 months (R=0.437, p=0.008) and VEP amplitude loss at 6 (R=0.414, p=0.019) and 12 months (R=0.484, p=0.003). AD reduction at three months correlated with high contrast visual acuity at 6 (ρ = -0.519, p = 0.001) and 12 months (ρ = -0.414, p=0.011). The time-course for AD reduction for each patient was modelled using a quadratic regression. AD normalised after a median of 18 weeks and longer normalisation times were associated with more pronounced RNFL thinning and mfVEP amplitude loss at 12 months. Affected nerve radial diffusivity (RD) was unchanged until three months, after which time it remained elevated.
Conclusions
These results demonstrate that AD reduces during acute ON. One month AD reduction correlates with the extent of axonal loss and persistent AD reduction at 3 months predicts poorer visual outcomes. This suggests that acute ON therapies that normalise optic nerve AD by 3 months could also promote axon survival and improve visual outcomes.
doi:10.1371/journal.pone.0083825
PMCID: PMC3873392  PMID: 24386285
2.  Optical coherence tomography is less sensitive than visual evoked potentials in optic neuritis 
Neurology  2009;73(1):46-52.
Objectives:
Determine the utility of optical coherence tomography (OCT) to detect clinical and subclinical remote optic neuritis (ON), its relationship to clinical characteristics of ON and visual function, and whether the retinal nerve fiber layer (RNFL) thickness functions as a surrogate marker of global disease severity.
Methods:
Cross-sectional study of 65 subjects with at least 1 clinical ON episode at least 6 months prior. Measures included clinical characteristics, visual acuity (VA), contrast sensitivity (CS), OCT, and visual evoked potentials (VEP).
Results:
Ninety-six clinically affected optic nerves were studied. The sensitivity of OCT RNFL after ON was 60%, decreasing further with mild onset and good recovery. VEP sensitivity was superior at 81% (p = 0.002). Subclinical ON in the unaffected eye was present in 32%. VEP identified 75% of all subclinically affected eyes, and OCT identified <20%. RNFL thickness demonstrated linear correlations with VA (r = 0.65) and CS (r = 0.72) but was unable to distinguish visual categories <20/50. RNFL was thinner with severe onset and disease recurrence but was unaffected by IV glucocorticoids. OCT measurements were not related to overall disability, ethnicity, sex, or age at onset. The greatest predictor for RNFL in the unaffected eye was the RNFL in the fellow affected eye.
Conclusions:
Visual evoked potentials (VEP) remains the preferred test for detecting clinical and subclinical optic neuritis. Optical coherence tomography (OCT) measures were unrelated to disability and demographic features predicting a worse prognosis in multiple sclerosis. OCT may provide complementary information to VEP in select cases, and remains a valuable research tool for studying optic nerve disease in populations.
GLOSSARY
= analysis of variance;
= clinically isolated syndrome;
= contrast sensitivity;
= Expanded Disability Status Score;
= logarithm of the minimum angle of resolution;
= multiple sclerosis;
= Multiple Sclerosis Severity Score;
= National Center for Research Resources;
= neuromyelitis optica;
= not significant;
= optical coherence tomography;
= optic neuritis;
= retinal nerve fiber layer;
= visual acuity;
= visual evoked potentials.
doi:10.1212/WNL.0b013e3181aaea32
PMCID: PMC2707110  PMID: 19564583
3.  Radial diffusivity in remote optic neuritis discriminates visual outcomes 
Neurology  2010;74(21):1702-1710.
Objective:
Diffusion tensor imaging (DTI) quantifies Brownian motion of water within tissue. The goal of this study was to test whether, following a remote episode of optic neuritis (ON), breakdown of myelin and axons within the optic nerve could be detected by alterations in DTI parameters, and whether these alterations would correlate with visual loss.
Methods:
Seventy subjects with a history of ON ≥6 months prior underwent DTI of the optic nerves, assessment of visual acuities (VA) and contrast sensitivities (CS), and laboratory measures of visual evoked potentials (VEP) and optical coherence tomography (OCT).
Results:
Radial diffusivity (RD) correlated with visual acuity (r = −0.61), Pelli-Robson CS (r = −0.60), 5%CS (r = 0.61), OCT (r = −0.78), VEP latency (r = 0.61), and VEP amplitude (r = −0.46). RD differentiated the unaffected fellow nerves from affected nerves in all visual outcome categories. RD also discriminated nerves with recovery to normal from mild visual impairment, and those with mild impairment from profound visual loss. RD differentiated healthy controls from both clinically affected nerves and unaffected fellow nerves after ON. RD differentiated all categories of 5%CS outcomes, and all categories of Pelli-Robson CS with the exception of normal recovery from mildly affected.
Conclusions:
Increased optic nerve radial diffusivity (RD) detected by diffusion tensor imaging (DTI) was associated with a proportional decline in vision after optic neuritis. RD can differentiate healthy control nerves from both affected and unaffected fellow nerves. RD can discriminate among categories of visual recovery within affected eyes. Optic nerve injury as assessed by DTI was corroborated by both optical coherence tomography and visual evoked potentials.
GLOSSARY
= 5% contrast sensitivity;
= confidence interval;
= clinically isolated syndrome;
= contrast sensitivity;
= diffusion tensor imaging;
= fractional anisotropy;
= magnetic resonance;
= multiple sclerosis;
= neuromyelitis optica;
= optical coherence tomography;
= optic neuritis;
= Pelli-Robson contrast sensitivity;
= radial diffusivity;
= retinal nerve fiber layer;
= region of interest;
= visual acuity;
= visual evoked potential.
doi:10.1212/WNL.0b013e3181e0434d
PMCID: PMC2882214  PMID: 20498438
4.  Disability in optic neuritis correlates with diffusion tensor-derived directional diffusivities 
Neurology  2009;72(7):589-594.
Objective:
To determine the potential of directional diffusivities from diffusion tensor imaging (DTI) to predict clinical outcome of optic neuritis (ON), and correlate with vision, optical coherence tomography (OCT), and visual evoked potentials (VEP).
Methods:
Twelve cases of acute and isolated ON were imaged within 30 days of onset and followed prospectively. Twenty-eight subjects with a remote clinical history of ON were studied cross-sectionally. Twelve healthy controls were imaged for comparison. DTI data were acquired at 3T with a surface coil and 1.3 × 1.3 × 1.3 mm3 isotropic voxels.
Results:
Normal DTI parameters (mean ± SD, μm2/ms) were axial diffusivity = 1.66 ± 0.18, radial diffusivity = 0.81 ± 0.26, apparent diffusion coefficient (ADC) = 1.09 ± 0.21, and fractional anisotropy (FA) = 0.43 ± 0.15. Axial diffusivity decreased up to 2.5 SD in acute ON. The decrease in axial diffusivity at onset correlated with visual contrast sensitivity 1 month (r = 0.59) and 3 months later (r = 0.65). In three subjects followed from the acute through the remote stage, radial diffusivity subsequently increased to >2.5 SD above normal, as did axial diffusivity and ADC. In remote ON, radial diffusivity correlated with OCT (r = 0.81), contrast sensitivity (r = 0.68), visual acuity (r = 0.56), and VEP (r = 0.54).
Conclusion:
In acute and isolated demyelination, axial diffusivity merits further investigation as a predictor of future clinical outcome. Diffusion parameters are dynamic in acute and isolated optic neuritis, with an initial acute decrease in axial diffusivity. In remote disease, radial diffusivity correlates with functional, structural, and physiologic tests of vision.
GLOSSARY
= apparent diffusion coefficient;
= confidence interval;
= contrast sensitivity;
= diffusion tensor imaging;
= experimental autoimmune encephalitis;
= fractional anisotropy;
= mean diffusivity;
= multiple sclerosis;
= normal-appearing white matter;
= optical coherence tomography;
= optic neuritis;
= relative anisotropy;
= reduced field of view;
= retinal nerve fiber layer;
= region of interest;
= standard deviation;
= signal-to-noise ratio;
= visual acuity;
= visual evoked potentials.
doi:10.1212/01.wnl.0000335766.22758.cd
PMCID: PMC2672917  PMID: 19073948
5.  MRI texture heterogeneity in the optic nerve predicts visual recovery after acute optic neuritis☆ 
NeuroImage : Clinical  2014;4:302-307.
Purpose
To test the feasibility of using multi-scale MRI texture analysis to assess optic nerve pathology and to investigate how visual recovery relates to the severity of acute tissue damage in the optic nerve in patients after optic neuritis (ON).
Materials and Methods
We recruited 25 patients with acute ON. Retinal nerve fiber layer (RNFL) thickness; MRI lesion length and enhancement; optic nerve area ratio; and multi-scale MRI texture analysis, a measure of structural integrity, were used to assess tissue damage at baseline, and at 6 and 12 months. The recovery in vision was defined as the functional outcome. Eight healthy subjects were imaged for control.
Results
We identified 25 lesions in the affected eyes (9 enhanced) and 5 in the clinically non-affected eyes (none enhanced). At baseline, we found that RNFL values were 20% thicker and lesion texture 14% more heterogeneous in the affected eyes than in the non-affected eyes, and lesion texture ratio of affected to non-affected eyes was greater in patients than in controls. In the affected eyes, visual acuity recovered significantly over 6 (18/23 patients) and 12 months (18/21 patients) when RNFL thickness and optic nerve area ratio decreased over time. Texture heterogeneity in the standard MRI of acute optic nerve lesions was the only measure that predicted functional recovery after ON.
Conclusions
Tissue heterogeneity may be a potential measure of functional outcome in ON patients and advanced analysis of the texture in standard MRI could provide insights into mechanisms of injury and recovery in patients with similar disorders.
Highlights
•We studied structure–function relationships in patients after acute optic neuritis.•Besides standard MRI and OCT, we used MRI texture analysis to assess tissue damage.•Vision recovered significantly at 6 and 12 months, but not tissue injury.•Only MRI texture heterogeneity in the optic nerve predicted visual recovery.•Novel texture analysis may help advance patient care in diagnostic MRI.
doi:10.1016/j.nicl.2014.01.003
PMCID: PMC4107369  PMID: 25061567
Acute tissue damage; MRI; Texture heterogeneity; Visual recovery; Prediction; Optic neuritis
6.  Optic Nerve Magnetisation Transfer Ratio after Acute Optic Neuritis Predicts Axonal and Visual Outcomes 
PLoS ONE  2012;7(12):e52291.
Magnetisation transfer ratio (MTR) can reveal the degree of proton exchange between free water and macromolecules and was suggested to be pathological informative. We aimed to investigate changes in optic nerve MTR over 12 months following acute optic neuritis (ON) and to determine whether MTR measurements can predict clinical and paraclinical outcomes at 6 and 12 months. Thirty-seven patients with acute ON were studied within 2 weeks of presentation and at 1, 3, 6 and 12 months. Assessments included optic nerve MTR, retinal nerve fibre layer (RNFL) thickness, multifocal visual evoked potential (mfVEP) amplitude and latency and high (100%) and low (2.5%) contrast letter acuity. Eleven healthy controls were scanned twice four weeks apart for comparison with patients. Patient unaffected optic nerve MTR did not significantly differ from controls at any time-point. Compared to the unaffected nerve, affected optic nerve MTR was significantly reduced at 3 months (mean percentage interocular difference = −9.24%, p = 0.01), 6 months (mean = −12.48%, p<0.0001) and 12 months (mean = −7.61%, p = 0.003). Greater reduction in MTR at 3 months in patients was associated with subsequent loss of high contrast letter acuity at 6 (ρ = 0.60, p = 0.0003) and 12 (ρ = 0.44, p = 0.009) months, low contrast letter acuity at 6 (ρ = 0.35, p = 0.047) months, and RNFL thinning at 12 (ρ = 0.35, p = 0.044) months. Stratification of individual patient MTR time courses based on flux over 12 months (stable, putative remyelination and putative degeneration) predicted RNFL thinning at 12 months (F2,32 = 3.59, p = 0.02). In conclusion, these findings indicate that MTR flux after acute ON is predictive of axonal degeneration and visual disability outcomes.
doi:10.1371/journal.pone.0052291
PMCID: PMC3525585  PMID: 23272235
7.  Disability in optic neuritis correlates with diffusion tensor-derived directional diffusivities 
Neurology  2008;72(7):589-594.
Objective
To determine the potential of directional diffusivities from diffusion tensor imaging (DTI) to predict clinical outcome of optic neuritis (ON), and correlate with vision, optical coherence tomography (OCT), and visual evoked potentials (VEP).
Methods
Twelve cases of acute and isolated ON were imaged within 30 days of onset and followed prospectively. Twenty-eight subjects with a remote clinical history of ON were studied cross-sectionally. Twelve healthy controls were imaged for comparison. DTI data were acquired at 3T with a surface coil and 1.3 × 1.3 × 1.3 mm3 isotropic voxels.
Results
Normal DTI parameters (mean ± SD, μm2/ms) were axial diffusivity = 1.66 ± 0.18, radial diffusivity = 0.81 ± 0.26, apparent diffusion coefficient (ADC) = 1.09 ± 0.21, and fractional anisotropy (FA) = 0.43 ± 0.15. Axial diffusivity decreased up to 2.5 SD in acute ON. The decrease in axial diffusivity at onset correlated with visual contrast sensitivity 1 month (r = 0.59) and 3 months later (r = 0.65). In three subjects followed from the acute through the remote stage, radial diffusivity subsequently increased to >2.5 SD above normal, as did axial diffusivity and ADC. In remote ON, radial diffusivity correlated with OCT (r = 0.81), contrast sensitivity (r = 0.68), visual acuity (r = 0.56), and VEP (r = 0.54).
Conclusion
In acute and isolated demyelination, axial diffusivity merits further investigation as a predictor of future clinical outcome. Diffusion parameters are dynamic in acute and isolated optic neuritis, with an initial acute decrease in axial diffusivity. In remote disease, radial diffusivity correlates with functional, structural, and physiologic tests of vision.
doi:10.1212/01.wnl.0000335766.22758.cd
PMCID: PMC2672917  PMID: 19073948
8.  Retinal Nerve Fibre Layer Thinning in Patients with Clinically Isolated Optic Neuritis and Early Treatment with Interferon-Beta 
PLoS ONE  2012;7(12):e51645.
Background
Optic neuritis is associated with neurodegeneration leading to chronic impairment of visual functions.
Objective
This study investigated whether early treatment with interferon beta (IFN-β) slows retinal nerve fibre layer (RNFL) thinning in clinically isolated optic neuritis.
Methods
Twenty patients with optic neuritis and visual acuity decreased to ≤0.5 (decimal system) were included into this prospective, open-label, parallel group 4-month observation. After methylprednisolone pulse therapy, 10 patients received IFN-β from week 2 onwards. This group was compared to 10 patients free of any disease modifying treatment (DMT). The parameter of interest was change in RNFL thickness assessed at baseline and at weeks 4, 8, and 16. Changes in visual acuity, visual field, and visual evoked potentials (VEPs) served as additional outcome parameters.
Results
RNFL thinning did not differ between the groups with a mean reduction of 9.80±2.80 µm in IFN-β-treated patients (±SD) vs. 12.44±5.79 µm in patients who did not receive DMT (baseline non-affected eye minus affected eye at week 16; p = 0.67, t-test, 95% confidence interval: −15.77 to 10.48). Parameters of visual function did not show any differences between the groups either.
Conclusions
In isolated optic neuritis, early IFN-β treatment did not influence RNFL thinning nor had it any effect on recovery of visual functions.
doi:10.1371/journal.pone.0051645
PMCID: PMC3521715  PMID: 23272128
9.  Relationship between Optical Coherence Tomography and Electrophysiology of the Visual Pathway in Non-Optic Neuritis Eyes of Multiple Sclerosis Patients 
PLoS ONE  2014;9(8):e102546.
Purpose
Loss of retinal ganglion cells in in non-optic neuritis eyes of Multiple Sclerosis patients (MS-NON) has recently been demonstrated. However, the pathological basis of this loss at present is not clear. Therefore, the aim of the current study was to investigate associations of clinical (high and low contrast visual acuity) and electrophysiological (electroretinogram and multifocal Visual Evoked Potentials) measures of the visual pathway with neuronal and axonal loss of RGC in order to better understand the nature of this loss.
Methods
Sixty-two patients with relapsing remitting multiple sclerosis with no previous history of optic neuritis in at least one eye were enrolled. All patients underwent a detailed ophthalmological examination in addition to low contrast visual acuity, Optical Coherence Tomography, full field electroretinogram (ERG) and multifocal visual evoked potentials (mfVEP).
Results
There was significant reduction of ganglion cell layer thickness, and total and temporal retinal nerve fibre layer (RNFL) thickness (p<0.0001, 0.002 and 0.0002 respectively). Multifocal VEP also demonstrated significant amplitude reduction and latency delay (p<0.0001 for both). Ganglion cell layer thickness, total and temporal RNFL thickness inversely correlated with mfVEP latency (r = −0.48, p<0.0001 respectively; r = −0.53, p<0.0001 and r = −0.59, p<0.0001 respectively). Ganglion cell layer thickness, total and temporal RNFL thickness also inversely correlated with the photopic b-wave latency (r = −0.35, p = 0.01; r = −0.33, p = 0.025; r = −0.36, p = 0.008 respectively). Multivariate linear regression model demonstrated that while both factors were significantly associated with RGC axonal and neuronal loss, the estimated predictive power of the posterior visual pathway damage was considerably larger compare to retinal dysfunction.
Conclusion
The results of our study demonstrated significant association of RGC axonal and neuronal loss in NON-eyes of MS patients with both retinal dysfunction and post-chiasmal damage of the visual pathway.
doi:10.1371/journal.pone.0102546
PMCID: PMC4148263  PMID: 25166273
10.  Monocular and binocular low-contrast visual acuity and optical coherence tomography in pediatric multiple sclerosis 
Background
Low-contrast letter acuity and optical coherence tomography (OCT) capture visual dysfunction and axonal loss in adult-onset multiple sclerosis (MS), and have been proposed as secondary outcome metrics for therapeutic trials. Clinical trials will soon be launched in pediatric MS, but such outcome metrics have not been well-validated in this population.
Objectives
To determine whether MS onset during childhood and adolescence is associated with measurable loss of visual acuity and thinning of the retinal nerve fiber layer (RNFL), whether such features are noted only in the context of clinical optic nerve inflammation (optic neuritis, ON) or are a feature of MS even in the absence of optic nerve relapses, and to define the optimal methods for such detection.
Study design
Cross-sectional study
Methods
Monocular and binocular high- and low-contrast letter acuity and contrast sensitivity were assessed in a cross-sectional cohort of children (ages 5 to 17 years) with MS (N=22 patients, 44 eyes; 8 patients with a history of ON) and disease-free controls (N=29 patients; 58 eyes) from three academic centers. Binocular summation was determined by calculating the number of letters correctly identified using the binocular score minus the better eye score for each visual test. RNFL thickness was measured using OCT (Stratus OCT-3). Results were analyzed in terms of “eyes” as: MS ON+, MS ON−, and control eyes. Generalized estimating equation (GEE) regression models were used to compare patients to controls.
Results
Traditional high-contrast visual acuity scores did not differ between MS ON+, MS ON−, and controls eyes. MS ON+ eyes had decreased monocular (p<0.001) and decreased binocular (p=0.007) low-contrast letter acuity (Sloan 1.25% contrast charts) scores. Monocular visual acuity did not differ when comparing MS ON− and control eyes. The magnitude of binocular summation using low-contrast charts was similar for pediatric MS participants and controls and was not diminished in children with a history of ON. While the mean RNFL thickness for all MS eyes (103±17 μm) trended lower when compared to corresponding measures in control eyes (109±9 μm, p=0.085), we confirmed a highly significant reduction in mean RNFL thickness in MS eyes with a history of ON (86±22 μm, p<0.001). RNFL thickness of MS ON− eyes in pediatric MS patients (109±11 μm) did not differ from controls (p=0.994).
Conclusions
Low-contrast letter acuity detects subtle visual loss in MS patients with prior ON, consistent with incomplete recovery, a finding further supported by RNFL loss in ON affected eyes. In MS patients with prior unilateral ON, binocular acuity is decreased; however, the magnitude of binocular summation is preserved, unlike adult-onset MS who exhibit a reduced capacity for visual compensation in the context of unilateral injury. Also unlike findings in adult-onset MS, we did not demonstrate RNFL thinning in ON− eyes of children and adolescents with MS. Further validation is required to confirm whether neurodegeneration of visual pathways occurs in the absence of relapse, and thus whether OCT will serve as a sensitive metric for such pathology in the pediatric and adolescent MS context.
doi:10.1016/j.msard.2013.10.008
PMCID: PMC3964624  PMID: 24683535
multiple sclerosis; optic neuritis; pediatric; demyelinating disease
11.  Prospective Study on Retinal Nerve Fibre Layer Thickness Changes in Isolated Unilateral Retrobulbar Optic Neuritis 
The Scientific World Journal  2013;2013:694613.
Purpose. To investigate the retinal nerve fibre layer (RNFL) thickness after unilateral acute optic neuritis using optical coherence tomography (OCT). Patients and Methods. This prospective cohort study recruited consecutive patients with a first episode of isolated, unilateral acute optic neuritis. RNFL thickness and visual acuity (VA) of the attack and normal fellow eye were measured at presentation and 3 months in both the treatment and nontreatment groups. Results. 11 subjects received systemic steroids and 9 were treated conservatively. The baseline RNFL thickness was similar in the attack and fellow eye (P ≥ 0.4). At 3 months, the attack eye had a thinner temporal (P = 0.02) and average (P = 0.05) RNFL compared to the fellow eye. At 3 months, the attack eye had significant RNFL thinning in the 4 quadrants and average thickness (P ≤ 0.0002) compared to baseline. The RNFL thickness between the treatment and nontreatment groups was similar at baseline and 3 months (P ≥ 0.1). Treatment offered better VA at 3 months (0.1 ± 0.2 versus 0.3 ± 0.2 LogMAR, P = 0.04). Conclusion. Generalized RNFL thinning occurred at 3 months after a first episode of acute optic neuritis most significantly in the temporal quadrant and average thickness. Visual improvement with treatment was independent of RNFL thickness.
doi:10.1155/2013/694613
PMCID: PMC3886364  PMID: 24459442
12.  Measurement of the retinal nerve fibre layer with scanning laser polarimetry in patients with previous demyelinating optic neuritis 
OBJECTIVES—Subjective visual deficits are common after demyelinating optic neuritis despite the frequent return of normal visual acuity. Visual and electrodiagnostic tests have demonstrated evidence of these persisting functional abnormalities, which are thought to be secondary to demyelination and variable axonal loss in the optic nerve. Scanning laser polarimetry (SLP) is a new image analysis technique which uses the polarising properties of the retinal nerve fibre layer (RNFL) to produce a quantitative measure of its thickness. This study was carried out to assess the prevalence, extent, and pattern of RNFL loss after demyelinating optic neuritis using SLP.
METHODS—Twenty four patients with a history of previous demyelinating optic neuritis were re-examined. Examination included measurement of logmar visual acuity, Pelli-Robson contrast sensitivity, and the presence of a relative afferent pupil defect and optic atrophy. SLP was performed and a mean RNFL profile from a series of three images from each eye was constructed. This was compared with normative data from 20 age matched normal subjects. The lower 99.9% confidence limit of the normal data was calculated and used as the cut off criterion for abnormality.
RESULTS—There were a total of 31 eyes with a history of demyelinating optic neuritis and SLP disclosed an abnormality in 29 (94%) of these. Twenty three eyes recovered an acuity of 0.0 or better, 21 of which had evidence of RNFL loss on polarimetry. Scanning laser polarimetry was the only abnormality found in nine of the 31 eyes (29%). The pattern and extent of RNFL loss was very variable and there was no significant difference in these indices between patients with multiple sclerosis compared with those with isolated demyelinating optic neuritis.
CONCLUSION—Scanning laser polarimetry can provide a quantitative measure of RNFL loss after demyelinating optic neuritis, demonstrating its occurrence in a high percentage of patients recovering normal visual acuity.


PMCID: PMC2170052  PMID: 9576544
13.  Sex-specific differences in retinal nerve fiber layer thinning after acute optic neuritis 
Neurology  2012;79(18):1866-1872.
Objective:
The primary objective of this study was to explore the potential influence of gender on recovery from optic neuritis (ON) by determining whether differences in retinal nerve fiber layer (RNFL) thickness can be detected between men and women 6 months after an ON event.
Methods:
In this prospective cohort study, 39 men and 105 women with acute ON underwent repeat visual and optical coherence tomography (OCT) testing. The main outcome measures were change in RNFL measurements for male and female patients 6 months after ON.
Results:
Men were older (mean age = 39 years) than women (35 years) (p = 0.05) in this study, and more men (62%) than women (41%) had a diagnosis of relapsing-remitting multiple sclerosis (MS) (p = 0.02). Because age and MS subtype were 2 significant covariates, both variables were controlled for in multiple regression analyses. Other covariates controlled for in the multivariate regression included disease duration (years), use of disease-modifying therapy (yes/no), and use of high-dose corticosteroids for acute ON (yes/no). After 6 months, mean RNFL values were lower in men (74 μm) than women (91 μm) (p < 0.001). Men showed more apparent change in RNFL thickness in their ON eyes from baseline to 6 months after ON than women (p = 0.003).
Conclusions:
There may be differences in recovery between men and women after ON, which can be difficult to detect with conventional visual testing. Our findings raise interesting questions about the potential influence of gender in MS, which may be explored in future studies.
doi:10.1212/WNL.0b013e318271f755
PMCID: PMC3525310  PMID: 23077012
14.  Efficacy of vision restoration therapy after optic neuritis (VISION study): study protocol for a randomized controlled trial 
Trials  2012;13:94.
Background
Optic neuritis is a frequent manifestation of multiple sclerosis. Visual deficits range from a minor impairment of visual functions through to complete loss of vision. Although many patients recover almost completely, roughly 35% of patients remain visually impaired for years, and therapeutic options for those patients hardly exist. Vision restoration therapy is a software-based visual training program that has been shown to improve visual deficits after pre- and postchiasmatic injury. The aim of this pilot study is to evaluate whether residual visual deficits after past or recent optic neuritis can be reduced by means of vision restoration therapy.
Methods/design
A randomized, controlled, patient- and observer-blinded clinical pilot study (VISION study) was designed to evaluate the efficacy of vision restoration therapy in optic neuritis patients. Eighty patients with a residual visual deficit after optic neuritis (visual acuity ≤0.7 and/or scotoma) will be stratified according to the time of optic neuritis onset (manifestation more than 12 months ago (40 patients, fixed deficit) versus manifestation 2 to 6 months ago (40 patients, recent optic neuritis)), and randomized into vision restoration therapy arm or saccadic training arm (control intervention). Patients will be instructed to complete a computer-based visual training for approximately 30 minutes each day for a period of 6 months. Patients and evaluators remain blinded to the treatment allocation throughout the study. All endpoints will be analyzed and P-values < 0.05 will be considered statistically significant. The primary outcome parameter will be the expansion of the visual field after 3 and 6 months of treatment as determined by static visual field perimetry and high resolution perimetry. Secondary outcome variables will include visual acuity at both low and high contrast, glare contrast sensitivity, visually evoked potentials, optical coherence tomography and other functional tests of the visual system, alertness, health-related quality of life, fatigue, and depression.
Discussion
If vision restoration therapy is shown to improve visual function after optic neuritis, this method might be a first therapeutic option for patients with incomplete recovery from optic neuritis.
Trial registration
NCT01274702
doi:10.1186/1745-6215-13-94
PMCID: PMC3408329  PMID: 22742888
Multiple sclerosis; Neuroplasticity; Optic neuritis; Treatment; Vision restoration therapy; Visual function
15.  Evaluation of changes in retinal nerve fiber layer thickness and visual functions in cases of optic neuritis and multiple sclerosis 
Indian Journal of Ophthalmology  2013;61(10):562-566.
Context:
Retinal nerve fiber layer (RNFL) thinning has been demonstrated in cases of optic neuritis (ON) and multiple sclerosis (MS) in Caucasian eyes, but no definite RNFL loss pattern or association with visual functions is known in Indian eyes.
Aim:
To evaluate RNFL thickness in cases of ON and MS, and to correlate it with visual function changes in Indian patients.
Settings and Design:
Cross-sectional case-control study at a tertiary level institution.
Materials and Methods:
Cases consisted of patients of (i) typical ON without a recent episode (n = 30:39 ON eyes and 21 fellow eyes), (ii) MS without ON (n = 15;30 eyes) while the controls were age-matched (n = 15; 30 eyes). RNFL thickness was measured using the Stratus 3°CT. The visual functions tested included the best-corrected visual acuity (BCVA), contrast sensitivity, stereopsis, visual evoked responses, and visual fields.
Statistical analysis used:
Intergroup analysis was done using ANOVA and Pearson's correlation coefficient used for associations.
Results:
RNFL thickness was reduced significantly in the ON and MS patients compared to the controls (P-0.001). Maximum loss is in the temporal quadrant. Lower visual function scores are associated with reduced average overall RNFL thickness. In ON group, RNFL thinning is associated with severe visual field defects while contrast sensitivity has strongest correlation with RNFL in the MS group.
Conclusions:
RNFL thickness is reduced in ON and MS cases in a pattern similar to Caucasians and is associated with the magnitude of impairment of other visual parameters. Contrast sensitivity and stereoacuity are useful tests to identify subclinical optic nerve involvement in multiple sclerosis.
doi:10.4103/0301-4738.121071
PMCID: PMC3853452  PMID: 24212307
Multiple sclerosis; optic neuritis; optical coherence tomography; retinal nerve fiber layer; visual functions
16.  Optical coherence tomography segmentation reveals ganglion cell layer pathology after optic neuritis 
Brain  2011;135(2):521-533.
Post-mortem ganglion cell dropout has been observed in multiple sclerosis; however, longitudinal in vivo assessment of retinal neuronal layers following acute optic neuritis remains largely unexplored. Peripapillary retinal nerve fibre layer thickness, measured by optical coherence tomography, has been proposed as an outcome measure in studies of neuroprotective agents in multiple sclerosis, yet potential swelling during the acute stages of optic neuritis may confound baseline measurements. The objective of this study was to ascertain whether patients with multiple sclerosis or neuromyelitis optica develop retinal neuronal layer pathology following acute optic neuritis, and to systematically characterize such changes in vivo over time. Spectral domain optical coherence tomography imaging, including automated retinal layer segmentation, was performed serially in 20 participants during the acute phase of optic neuritis, and again 3 and 6 months later. Imaging was performed cross-sectionally in 98 multiple sclerosis participants, 22 neuromyelitis optica participants and 72 healthy controls. Neuronal thinning was observed in the ganglion cell layer of eyes affected by acute optic neuritis 3 and 6 months after onset (P < 0.001). Baseline ganglion cell layer thicknesses did not demonstrate swelling when compared with contralateral unaffected eyes, whereas peripapillary retinal nerve fibre layer oedema was observed in affected eyes (P = 0.008) and subsequently thinned over the course of this study. Ganglion cell layer thickness was lower in both participants with multiple sclerosis and participants with neuromyelitis optica, with and without a history of optic neuritis, when compared with healthy controls (P < 0.001) and correlated with visual function. Of all patient groups investigated, those with neuromyelitis optica and a history of optic neuritis exhibited the greatest reduction in ganglion cell layer thickness. Results from our in vivo longitudinal study demonstrate retinal neuronal layer thinning following acute optic neuritis, corroborating the hypothesis that axonal injury may cause neuronal pathology in multiple sclerosis. Further, these data provide evidence of subclinical disease activity, in both participants with multiple sclerosis and with neuromyelitis optica without a history of optic neuritis, a disease in which subclinical disease activity has not been widely appreciated. No pathology was seen in the inner or outer nuclear layers of eyes with optic neuritis, suggesting that retrograde degeneration after optic neuritis may not extend into the deeper retinal layers. The subsequent thinning of the ganglion cell layer following acute optic neuritis, in the absence of evidence of baseline swelling, suggests the potential utility of quantitative optical coherence tomography retinal layer segmentation to monitor neuroprotective effects of novel agents in therapeutic trials.
doi:10.1093/brain/awr264
PMCID: PMC3281477  PMID: 22006982
optical coherence tomography; retinal segmentation; optic neuritis; multiple sclerosis; demyelinating disease; neuro-ophthalmology
17.  Baseline Magnetic Resonance Imaging of the Optic Nerve Provides Limited Predictive Information on Short-Term Recovery after Acute Optic Neuritis 
PLoS ONE  2015;10(1):e0113961.
Background
In acute optic neuritis, magnetic resonance imaging (MRI) may help to confirm the diagnosis as well as to exclude alternative diagnoses. Yet, little is known on the value of optic nerve imaging for predicting clinical symptoms or therapeutic outcome.
Purpose
To evaluate the benefit of optic nerve MRI for predicting response to appropriate therapy and recovery of visual acuity.
Methods
Clinical data as well as visual evoked potentials (VEP) and MRI results of 104 patients, who were treated at the Department of Neurology with clinically definite optic neuritis between December 2010 and September 2012 were retrospectively reviewed including a follow up within 14 days.
Results
Both length of the Gd enhancing lesion (r = -0.38; p = 0.001) and the T2 lesion (r = -0.25; p = 0.03) of the optic nerve in acute optic neuritis showed a medium correlation with visual acuity after treatment. Although visual acuity pre-treatment was little but nonsignificantly lower if Gd enhancement of the optic nerve was detected via orbital MRI, improvement of visual acuity after adequate therapy was significantly better (0.40 vs. 0.24; p = 0.04). Intraorbitally located Gd enhancing lesions were associated with worse visual improvement compared to canalicular, intracranial and chiasmal lesions (0.35 vs. 0.54; p = 0.02).
Conclusion
Orbital MRI is a broadly available, valuable tool for predicting the improvement of visual function. While the accurate individual prediction of long-term outcomes after appropriate therapy still remains difficult, lesion length of Gd enhancement and T2 lesion contribute to its prediction and a better short-term visual outcome may be associated with detection and localization of Gd enhancement along the optic nerve.
doi:10.1371/journal.pone.0113961
PMCID: PMC4312052  PMID: 25635863
18.  Clinical profile of simultaneous bilateral optic neuritis in adults 
Aim
To establish the clinical profile of simultaneous bilateral optic neuritis in adults, the efficacy of steroid therapy, extent of visual recovery, and neurological outcome.
Methods
The authors performed a retrospective review of records of patients referred to a neuro‐ophthalmology service with acute bilateral optic neuritis from 2000–4. Exclusion criteria included previous multiple sclerosis or myelopathy, known systemic disorders or medications associated with optic neuropathy, uveitis, or neoplasm. Patients received intravenous methylprednisolone followed by oral prednisone. Visual acuity (logMAR conversion), mean deviation (dB) for visual fields, percentage of Ishihara plates seen, ophthalmoscopy, and neurological evaluation were recorded at baseline and at 6 months or 12 months. Owing to strong correlation for visual loss between eyes, the results for the worse eye in each patient were analysed.
Results
11 men and four women, with an age range of 18–64 years, had bilateral decreased vision, 12 with pain on eye movement. Except for one patient, no aetiology was found. All patients had normal neurological evaluations, average visual acuity 1.71 (SD 0.55), colour vision 2.7% (SD 9.9%), and mean deviation −25.35 dB (SD −7.95 dB). Both optic nerves showed abnormal signal on magnetic resonance imaging. 14 patients improved and their last average visual acuity, colour vision, and mean deviation were 0.36 (SD 0.54), 69% (SD 46%), and −7.05 dB (SD 8.40 dB), respectively. No patient developed a neurological problem during the follow up with a mean of 11 months.
Conclusion
Idiopathic acute bilateral optic neuritis without myelopathy occasionally occurs in adults. Vision recovers with corticosteroid therapy and during the first year neurological dysfunction will frequently not occur.
doi:10.1136/bjo.2005.085399
PMCID: PMC1857074  PMID: 16622084
bilateral optic neuritis; corticosteroid therapy; neuromyelitis optica
19.  Heterogeneous Pattern of Retinal Nerve Fiber Layer in Multiple Sclerosis. High Resolution Optical Coherence Tomography: Potential and Limitations 
PLoS ONE  2010;5(11):e13877.
Background
Recently the reduction of the retinal nerve fibre layer (RNFL) was suggested to be associated with diffuse axonal damage in the whole CNS of multiple sclerosis (MS) patients. However, several points are still under discussion. (1) Is high resolution optical coherence tomography (OCT) required to detect the partly very subtle RNFL changes seen in MS patients? (2) Can a reduction of RNFL be detected in all MS patients, even in early disease courses and in all MS subtypes? (3) Does an optic neuritis (ON) or focal lesions along the visual pathways, which are both very common in MS, limit the predication of diffuse axonal degeneration in the whole CNS? The purpose of our study was to determine the baseline characteristics of clinical definite relapsing-remitting (RRMS) and secondary progressive (SPMS) MS patients with high resolution OCT technique.
Methodology
Forty-two RRMS and 17 SPMS patients with and without history of uni- or bilateral ON, and 59 age- and sex-matched healthy controls were analysed prospectively with the high resolution spectral-domain OCT device (SD-OCT) using the Spectralis 3.5mm circle scan protocol with locked reference images and eye tracking mode. Furthermore we performed tests for visual and contrast acuity and sensitivity (ETDRS, Sloan and Pelli-Robson-charts), for color vision (Lanthony D-15), the Humphrey visual field and visual evoked potential testing (VEP).
Principal Findings
All 4 groups (RRMS and SPMS with or without ON) showed significantly reduced RNFL globally, or at least in one of the peripapillary sectors compared to age-/sex-matched healthy controls. In patients with previous ON additional RNFL reduction was found. However, in many RRMS patients the RNFL was found within normal range. We found no correlation between RNFL reduction and disease duration (range 9–540 months).
Conclusions
RNFL baseline characteristics of RRMS and SPMS are heterogeneous (range from normal to markedly reduced levels).
doi:10.1371/journal.pone.0013877
PMCID: PMC2975633  PMID: 21079732
20.  Corticosteroids for treating optic neuritis 
Background
Optic neuritis is an inflammatory disease of the optic nerve. It occurs more commonly in women than in men. Usually presenting with an abrupt loss of vision, recovery of vision is almost never complete. Closely linked in pathogenesis to multiple sclerosis, it may be the initial manifestation for this condition. In certain patients, no underlying cause can be found.
Objectives
To assess the effects of corticosteroids on visual recovery of patients with acute optic neuritis.
Search methods
We searched CENTRAL (which contains the Cochrane Eyes and Vision Group Trials Register) (The Cochrane Library 2012, Issue 1), MEDLINE (January 1950 to February 2012), EMBASE (January 1980 to February 2012), Latin American and Caribbean Literature on Health Sciences (LILACS) (January 1982 to February 2012), the metaRegister of Controlled Trials (mRCT) (www.controlled-trials.com), ClinicalTrials.gov (www.clinicaltrials.gov) and the WHO International Clinical Trials Registry Platform (ICTRP) (www.who.int/ictrp/search/en). There were no date or language restrictions in the electronic searches for trials. The electronic databases were last searched on 21 February 2012. We also searched reference lists of identified trial reports to find additional trials.
Selection criteria
We included randomized trials that evaluated corticosteroids, in any form, dose or route of administration, in people with acute optic neuritis.
Data collection and analysis
Two authors independently extracted the data on methodological quality and outcomes for analysis.
Main results
We included six randomized trials which included a total of 750 participants. Two trials evaluated low dose oral corticosteroids while one trial evaluated low dose intravenous corticosteroids across two treatment arms and two trials evaluated a higher dose of intravenous corticosteroids. One three-arm trial evaluated low-dose oral corticosteroids and high-dose intravenous corticosteroids against placebo. Trials evaluating oral corticosteroids compared varying doses of corticosteroids with placebo. Hence, we did not conduct a meta-analysis of such trials. In a meta-analysis of trials evaluating corticosteroids with total dose greater than 3000 mg administered intravenously, the relative risk of normal visual acuity with intravenous corticosteroids compared with placebo was 1.06 (95% confidence interval (CI) 0.89 to 1.27) at six months and 1.06 (95% CI 0.92 to 1.22) at one year. The risk ratio of normal contrast sensitivity for the same comparison was 1.10 (95% CI 0.92 to 1.32) at six months follow up. We did not conduct a meta-analysis for this outcome at one year follow up since there was substantial statistical heterogeneity. The risk ratio of normal visual field for this comparison was 1.08 (95% CI 0.96 to 1.22) at six months and 1.02 (95% CI 0.86 to 1.20) at one year. Quality of life was assessed and reported in one trial.
Authors' conclusions
There is no conclusive evidence of benefit in terms of recovery to normal visual acuity, visual field or contrast sensitivity with either intravenous or oral corticosteroids at the doses evaluated in trials included in this review.
doi:10.1002/14651858.CD001430.pub3
PMCID: PMC4269246  PMID: 22513900
Adrenal Cortex Hormones [*therapeutic use]; Contrast Sensitivity [drug effects]; Optic Neuritis [*drug therapy]; Randomized Controlled Trials as Topic; Visual Acuity [drug effects]; Humans
21.  Optical coherence tomography versus visual evoked potential in multiple sclerosis patients 
Iranian Journal of Neurology  2012;11(1):12-15.
Background
Optical coherence tomography (OCT) is a non-invasive instrument, which can be used to estimate the thickness of the retinal nerve fibre layer (RNFL) and provides an indirect measurement of axonal destruction in multiple sclerosis (MS). The main aim of this study was to find out any correlations between P100 latency in visual evoked potential (VEP) and RNFL thickness.
Methods
The patients with the definite history of optic neuritis regardless of the diagnosis of MS were included. The eyes with the history of blurred vision and increased VEP latency (> 115 milliseconds) were considered as cases and the eyes with normal latency were regarded as controls. RNFL thickness was compared between two groups of cases and controls. In addition, the correlation between VEP P100 latency and RNFL thickness in four quadrants of superior, nasal, inferior and temporal fields was estimated by spearman correlation coefficient. RNFL thickness between the patients with history of clinically isolated syndrome (CIS) was also compared to other two subgroups of RRMS and SPMS.
Results
There was significant negative correlation between VEP P100 latency and RNFL. In all four quadrants, with increasing VEP latency, RNFL thickness decreased. Furthermore, there was significant correlation between P100 latencies and mean RNFL thickness [Pearson correlation coefficient = -0.527, P < 0.001; RNFL (mean) = (-0.44 ± 0.087) × P100 + (153.6 ± 10.94)]. Comparing RNFL thickness between three groups of CIS, RRMS, and SPSM, no significant difference was detected in RNFL thickness (P > 0.05). Power analysis demonstrated that RNFL average had the highest area under curve.
Conclusion
OCT does have good correlations with P100 latency, indicating retinal non-myelinated axonal involvement in early stages in addition to the myelinated axonal involvement. However, it cannot be used as the sole test in evaluating visual pathway in optic neuritis and complementary tests as VEPs are recommended.
PMCID: PMC3829235  PMID: 24250852
Optical Coherence Tomography; Multiple Sclerosis; Clinically Isolates Syndrome; Visual Evoked Potential
22.  The role of Magnetic Resonance Imaging and Visual Evoked Potential in management of optic neuritis 
Introduction
To report our experience in management of patients with optic neuritis. The effects of brain magnetic resonance imaging and visual evoked potential on management were investigated
Methods
This is a four years clinical trial that included patients presenting with first attack of optic neuritis older than 16 years with visual acuity of less than 6/60 and presentation within first week of illness. Brain magnetic resonance imaging and visual evoked potentials were done for all patients. Patients were classified into three groups. First group received placebo, second received oral steroids and third received intravenous and oral steroids. Primary outcome measure was improvement in visual acuity.
Results
A total number of 150 patients were enrolled in the study. Ocular pain was seen 127 patients Relative afferent pupillary defect in 142 patients and color vision impairment in 131 patients. Abnormal MRI findings were seen in 84 patients. Pattern reversal VEP was abnormal in all patients. Using oral or intravenous steroid resulted in faster recovery but did not affect the final visual outcome. Recurrence rate was higher in patients with multiple MRI lesions and diminished VEP amplitude. Using intravenous steroids decreased recurrence rate in patients with three and more MRI lesions and non recordable VEP response.
Conclusion
MRI and pattern reversal VEP are recommended to be done in all patients presenting with optic neuritis. We advise to give intravenous methyl prednisolone in patients with multiple MRI white matter lesions and non recordable VEP at presentation.
doi:10.11604/pamj.2014.17.54.2462
PMCID: PMC4085977  PMID: 25018804
Optic neuritis; steroids; recurrence; visual evoked potential
23.  Vision in Multiple Sclerosis (MS): The Story, Structure-Function Correlations, and Models for Neuroprotection 
Visual dysfunction is one of the most common clinical manifestations of multiple sclerosis (MS). Just over a decade ago, MS clincial trials did not include visual outcomes but experts recognized the need for more senstive measures of visual function. Low-contrast letter acuity emerged as the leading candidate to measure visual disability in MS and subsequent studies found low-contrast acuity testing to correlate well with brain MRI lesion burden, visual-evoked potentials (VEPs), quality of life (QOL), and retinal nerve fiber layer (RNFL) loss as measured by optical coherence tomography (OCT). OCT in MS has allowed for assessment of structure-funciton correlations that make the anterior visual pathway and acute optic neuritis (ON) ideal models for testing novel agents for neuroprotection and repair. New therapies that reduce axonal loss by neuroprotective or myelin repair mechanisms can now be assessed non-invasively by OCT and coupled with visual function data. Based on OCT studies in MS, RNFL thickness is reduced significantly among patients (92 µm) versus controls (105 µm), and is particularly reduced in MS eyes with a history of ON (85 µm). Worsening of visual function by a clinically significant ≥7 letters or ~1.5 lines for low-contrast acuity is associated with approximately 4.5 µm reductions in RNFL thickness in MS eyes. Longitudinal studies of OCT have also shown RNFL axonal loss over time that occurs even in the absence of acute ON, and that correlates with clincially meaningful worsening of vision and QOL, even in patients with benign MS. The latest OCT investigations involve high-resolution spectral-domain (SD) OCT with segmentation and measurement of specific retinal layers using computerized algorithms. These methods allow quantitation of ganglion cell (neuronal) layer loss as well as axonal degeneration in MS in vivo. In this review, we examine the data from these studies and ongoing trials that highlight the entity of ON as a model to investigate neuroprotection and neurorepair. In doing so, we also present representative group data from studies that have examined visual function, OCT measures, and QOL scales in patients with MS, ON, and disease-free controls. These data, as well as those from recent meta-analyses, may be used to provide reference values for the development of clinical trial protocols.
doi:10.1097/WNO.0b013e318238937f
PMCID: PMC3427931  PMID: 22089500
multiple sclerosis (MS); visual pathway; low-contrast letter acuity; optical coherence tomography (OCT); neuroprotection
24.  Directional diffusivity changes in the optic nerve and optic radiation in optic neuritis 
Li, M | Li, J | He, H | Wang, Z | Lv, B | Li, W | Hailla, N | Yan, F | Xian, J | Ai, L
The British Journal of Radiology  2011;84(1000):304-314.
Objective
Optic neuritis (ON) is defined as an inflammation of the optic nerve and provides a useful model for studying the effects of inflammatory demyelination of white matter. The aim of this study was to assess the diffusion changes in both the optic nerve and optic radiation in patients with acute and chronic ON using diffusion tensor (DT) MRI.
Methods
33 patients with idiopathic demyelinating optic neuritis (IDON) and 33 gender- and age-matched healthy controls were examined with DT-MRI and with T1 and T2 weighted MRI.
Results
Compared with controls, both first-episode and recurrent patients with IDON in the acute stage showed significantly increased radial diffusivity (λ⊥) and decreased mean fractional anisotropy (FA) in the affected nerves. Reduced FA, increased λ⊥, mean diffusivity (MD) and axial diffusivity (λ∥) were determined in patients with subacute IDON. We found no significant difference in the directional diffusivity of optic radiation in patients whose disease had lasted less than 1 year compared with healthy controls. However, significant changes in the FA and λ⊥ of the optic radiation were detected in patients with disease duration of more than 1 year.
Conclusion
These results show the great potential and capacity of DT-MRI measures as useful biomarkers and indicators for the evaluation of myelin injury in the visual pathway.
doi:10.1259/bjr/93494520
PMCID: PMC3473480  PMID: 21415301
25.  Multifocal VEP and OCT findings in patients with primary open angle glaucoma: A cross-sectional study 
BMC Ophthalmology  2012;12:34.
Bakground
To evaluate objectively the anatomical and functional changes of optic nerve in eyes with primary open angle glaucoma (POAG) by the joint use of optical coherence tomography (OCT) and multifocal visual evoked potentials (mfVEP).
Methods
29 eyes with open angle glaucoma and visual field defects, as well as 20 eyes of 10 age-matched control normal subjects were tested. All participants underwent a complete ophthalmological examination. Moreover, Humphrey visual field test, OCT examination and recording of mfVEP were performed. Amplitude and implicit time of mfVEP, as well as RNFL thickness were measured. Differences in density components of mfVEP and in RNFL thickness among POAG eyes and control eyes were examined using Student’s t-test.
Results
In glaucomatous eyes the mean Retinal Response Density (RRD) was lower than normal in ring 1, 2 and 3 of mfVEP (p < 0.0001). Specifically the mean amplitude of mfVEP in POAG eyes was estimated at 34.2 ± 17.6 nV/deg2, 6.9 ± 4.8 nV/deg2 and 2.6 ± 1.6 nV/deg2 in rings 1, 2 and 3 respectively. In contrast the mean implicit time was similar to control eyes. In addition, the mean RNFL thickness in POAG eyes was estimated at 76.8 ± 26.6 μm in the superior area, 52.1 ± 16.3 μm in the temporal area, 75.9 ± 32.5 μm in the inferior area and 58.6 ± 19.4 μm in the nasal area. There was a statistically significant difference in RNFL thickness in all peripapillary areas (p < 0.0001) between POAG eyes and controls, with superior and inferior area to present the highest decrease.
Conclusions
Our study shows that, although Standard Automatic Perimetry is the gold standard to evaluate glaucomatous neuropathy, the joint use of mfVEP and OCT could be useful in better monitoring glaucoma progression.
doi:10.1186/1471-2415-12-34
PMCID: PMC3549724  PMID: 22856337

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