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1.  Predictive value of visual evoked potentials, relative afferent pupillary defect, and orbital fractures in patients with traumatic optic neuropathy 
The purpose of this study was to determine the predictive value of flash visual-evoked potentials (VEP), relative afferent pupillary defect, and presence of orbital fractures in patients with traumatic optic neuropathy.
A prospective study was conducted in 15 patients with indirect traumatic optic neuropathy. All patients underwent a thorough ophthalmic examination. Initial visual acuity, final visual acuity, and relative afferent pupillary defect were determined, and visual acuity was converted into logMAR units. We performed flash VEP and an orbital computed tomography scan in all patients.
There was a good correlation between relative afferent pupillary defect and final visual acuity (r = −0.83), and better initial visual acuity could predict better final visual acuity (r = 0.92). According to findings from flash VEP parameters, there was a relationship between final visual acuity and amplitude ratio of the wave (r = 0.59) and latency ratio of the wave (r = −0.61). Neither primary visual acuity nor final visual acuity was related to the presence of orbital fractures in the orbital CT scan.
Patients with traumatic optic neuropathy often present with severe vision loss. Flash VEP, poor initial visual acuity, and higher grade of relative afferent pupillary defect could predict final visual acuity in these patients. Presence of orbital fracture was not a predictive factor for primary visual acuity or final visual acuity.
PMCID: PMC3151564  PMID: 21845028
visual acuity; flash VEP; RAPD; orbital fracture; CT scan
2.  Early Visual Evoked Potential Acuity and Future Behavioral Acuity in Cortical Visual Impairment 
Cortical Visual Impairment (CVI) is bilateral visual impairment caused by damage to the posterior visual pathway. Both preferential looking (PL) and sweep visual evoked potential (VEP) can be used to measure visual acuity. The purpose of this study was to determine if an early VEP measure of acuity is related to a young patient’s future behavioral acuity.
The visual acuity of 33 patients with CVI was assessed using the sweep VEP and a behavioral measure on two occasions. The median age of the patients at the initial visit was 4.8 years (range: 1.3–19.2 years), and they were followed for an average of 6.9 years (SD: 3.5 years).
The mean initial VEP acuity was 20/135 (0.735 logMAR), and the mean initial behavioral acuity was 20/475 (1.242 logMAR). The average difference between the two initial measures of acuity was 0.55 log unit, with the behavioral measure reporting a poorer visual acuity in all patients. However, the mean final behavioral acuity was 20/150 (0.741 logMAR), and the average difference between the initial VEP acuity and the final behavioral acuity was only 0.01 log unit. Therefore, the initial VEP measure was not statistically different from the final behavioral measure (t=0.11; df=32; p=0.45).
Even though the initial VEP measure was much better than the initial behavioral measure, the initial VEP measure was similar to the behavioral visual acuity measured approximately 7 years later. Sweep VEP testing can be used as a predictive tool for at least the lower limit of future behavioral acuity in young patients with CVI.
PMCID: PMC3910439  PMID: 20016393
cortical visual impairment; cerebral visual impairment; sweep vep acuity; behavioral acuity; visual acuity
3.  Visual acuity in unilateral cataract. 
BACKGROUND: Patching the fellow eye in infancy is a well recognised therapy to encourage visual development in the lensectomised eye in cases of unilateral congenital cataract. The possibility of iatrogenic deficits of the fellow eye was investigated by comparing the vision of these patients with untreated unilateral patients and binocularly normal controls. METHODS: Sweep visual evoked potentials (VEPs) offer a rapid and objective method for estimating grating acuity. Sweep VEPs were used to estimate acuity in 12 children aged between 4 and 16 years who had had a congenital cataract removed in the first 13 weeks of life. The acuities of aphakic and fellow phakic eye were compared with the monocular acuities of similarly aged children who have good binocular vision, and with children with severe untreated uniocular visual impairment. Recognition linear acuities were measured with a linear Bailey-Lovie logMAR chart and compared with the sweep VEP estimates. RESULTS: A significant difference was found between Bailey-Lovie acuity of the fellow eye of the patient group and the right eye of binocular controls, and the good eye of uniocular impaired patients (one way ANOVA, p < 0.01). However, this was not evident for a similar comparison with sweep VEP estimates. There was no significant difference between the right and left eye acuities in binocular controls measured by the two techniques (paired t test). CONCLUSION: A loss of recognition acuity in the fellow phakic eye of patients treated for unilateral congenital cataract has been demonstrated with a logMAR chart. This loss was not apparent in children who have severe untreated uniocular visual impairment and may therefore be an iatrogenic effect of occlusion. An acuity loss was not apparent in the patient group using the sweep VEP method. Sweep VEP techniques have a place for objectively studying acuity in infants and in those whose communication difficulties preclude other forms of behavioural test. The mean sweep VEP acuity for the control groups is 20 cpd--that is, about 6/9. When acuities higher than this are under investigation--for example, in older children, slower transient VEP recording may be more appropriate, because higher spatial frequency patterns are not as visible at higher temporal rates (for example, 8 Hz used in sweep VEP recordings).
PMCID: PMC505614  PMID: 8942375
4.  Metrics of Retinal Image Quality Predict Visual Performance in Eyes With 20/17 or Better Visual Acuity 
The purpose of this study is to determine the ability of single-value metrics of retinal image quality of the eye to predict visual performance as measured by high (HC) and low (LC) -contrast acuity at photopic (P) and mesopic (M) light levels in eyes with 20/17 and better visual acuity.
Forty-nine normal subjects in good health ranging in age from 21.8 to 62.6 with 20/17 or better monocular high-contrast logarithm of the minimum angle of resolution (logMAR) acuity served as subjects. Wavefront error through the 10th Zernike radial order over a 7-mm pupil was measured on each test eye using a custom-built Shack/Hartmann wavefront sensor. For each eye, 31 different single-value retinal image quality metrics were calculated. Visual acuity was measured using HC (95%) and LC (11%) logMAR at photopic (270 cd/m2) and mesopic (0.75 cd/m2) light levels. To determine the ability of each metric of retinal image quality to predict each type of logMAR acuity (P HC, P LC, M HC, and M LC), each acuity measure was regressed against each optical quality metric.
The ability of the metrics of retinal image quality to predict logMAR acuity improved as luminance and/or contrast is lowered. The best retinal image quality metric (logPFSc) accounted for 2.6%, 15.1%, 27.6%, and 40.0% of the variance in P HC, P LC, M HC, and M LC logMAR acuity, respectively.
In eyes with 20/17 and better P HC acuity, P HC logMAR acuity is insensitive to variations in retinal image quality compared with M LC logMAR acuity. Retinal image quality becomes increasingly predictive of logMAR acuity as contrast and/or luminance is decreased. Everyday life requires individuals to function over a large range of contrast and luminance levels. Clinically, the impact of retinal image quality as a function of luminance and contrast is readily measurable in a time-efficient manner with M LC logMAR acuity charts.
PMCID: PMC1764494  PMID: 16971841
aberration; wavefront error; optical quality metrics; visual performance; visual acuity
5.  Optical coherence tomography is less sensitive than visual evoked potentials in optic neuritis 
Neurology  2009;73(1):46-52.
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.
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).
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.
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.
= 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.
PMCID: PMC2707110  PMID: 19564583
6.  Measuring colour rivalry suppression in amblyopia 
The British Journal of Ophthalmology  1999;83(11):1283-1286.
AIMS—To determine if the colour rivalry suppression is an index of the visual impairment in amblyopia and if the stereopsis and fusion evaluator (SAFE) instrument is a reliable indicator of the difference in visual input from the two eyes.
METHODS—To test the accuracy of the SAFE instrument for measuring the visual input from the two eyes, colour rivalry suppression was measured in six normal subjects. A test neutral density filter (NDF) was placed before one eye to induce a temporary relative afferent defect and the subject selected the NDF before the fellow eye to neutralise the test NDF. In a non-paediatric private practice, 24 consecutive patients diagnosed with unilateral amblyopia were tested with the SAFE. Of the 24 amblyopes, 14 qualified for the study because they were able to fuse images and had no comorbid disease. The relation between depth of colour rivalry suppression, stereoacuity, and interocular difference in logMAR acuity was analysed.
RESULTS—In normal subjects, the SAFE instrument reversed temporary defects of 0.3 to 1.8 log units to within 0.6 log units. In amblyopes, the NDF to reverse colour rivalry suppression was positively related to interocular difference in logMAR acuity (β=1.21, p<0.0001), and negatively related to stereoacuity (β=−0.16, p=0.019). The interocular difference in logMAR acuity was negatively related to stereoacuity (β=−0.13, p=0.009).
CONCLUSIONS—Colour rivalry suppression as measured with the SAFE was found to agree closely with the degree of visual acuity impairment in non-paediatric patients with amblyopia.

PMCID: PMC1722877  PMID: 10535858
7.  Detection of tumor progression in optic pathway glioma with and without neurofibromatosis type 1 
Neuro-Oncology  2013;15(11):1560-1567.
We wanted to determine the sensitivity and specificity of serial changes in visual acuity and visual evoked potentials (VEPs) to detect radiological progression of tumor volume in children with optic pathway gliomas.
From a retrospective review of a cohort of 69 patients, 54 patients met inclusion criteria (31 with primary chemotherapy, 4 with primary radiotherapy, and 19 with stable tumor volume and no treatment). Age at presentation ranged from 0.3 to 13 years. Patients were serially followed by MRI, age-corrected visual acuity in log minimum angle of resolution (logMAR), and pattern VEP. Longitudinal data averaged 7.9 years (range 0.5–16 y). Visual assessments were aligned with MRI data within 6-month intervals. Tumor progression was defined by 25% or greater increase in volume.
Visual acuity in the better eye had poor sensitivity and specificity for detecting tumor volume progression (0.5 and 0.5, respectively). Visual acuity in the worse eye showed worse sensitivity and specificity because false positives (visual decline without tumor progression) were more frequent than true positives (visual decline with tumor progression). VEPs showed slightly better sensitivity and specificity (0.69 and 0.58, respectively). In patients with stable tumors, visual acuity fluctuated ±0.55 logMAR (SD = 0.15) between examinations. VEP amplitude fluctuated −0.74 to 0.48 log units (SD = 0.19) between examinations.
Serial changes in visual function do not reliably detect tumor progression. Conversely, tumor progression does not reliably indicate decreased visual function. Objective visual function and serial MRIs are complementary in management of optic pathway gliomas.
PMCID: PMC3813420  PMID: 24101736
optic pathway glioma; tumor progression; visual acuity
8.  Radial diffusivity in remote optic neuritis discriminates visual outcomes 
Neurology  2010;74(21):1702-1710.
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.
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).
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.
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.
= 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.
PMCID: PMC2882214  PMID: 20498438
9.  Optic Nerve Diffusion Tensor Imaging after Acute Optic Neuritis Predicts Axonal and Visual Outcomes 
PLoS ONE  2013;8(12):e83825.
Early markers of axonal and clinical outcomes are required for early phase testing of putative neuroprotective therapies for multiple sclerosis (MS).
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.
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.
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.
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.
PMCID: PMC3873392  PMID: 24386285
10.  Efficacy of perceptual vision therapy in enhancing visual acuity and contrast sensitivity function in adult hypermetropic anisometropic amblyopia 
The purpose of this study was to evaluate the efficacy of neural vision therapy, also termed perceptual vision therapy, in enhancing best corrected visual acuity (BCVA) and contrast sensitivity function in amblyopic patients.
This prospective study enrolled 99 subjects previously diagnosed with unilateral hypermetropic amblyopia aged 9–50 years. The subjects were divided into two groups, with 53 subjects (53 eyes) in the perceptual vision therapy group and 46 subjects (46 eyes) in the control group. Because the nature of the treatment demands hard work and strict compliance, we enrolled the minimal number of subjects required to achieve statistically significant results. Informed consent was obtained from all subjects. Study phases included a baseline screening, a series of 45 training sessions with perceptual vision therapy, and an end-of-treatment examination. BCVA and contrast sensitivity function at 1.5, 3, 6, 12, and 18 cycles per degree spatial frequencies were obtained for statistical analysis in both groups. All subjects had follow-up examinations within 4–8 months. With the exception of one subject from the study group and two subjects from the control group, all subjects had occlusion during childhood. The study was not masked.
The results for the study group demonstrated a mean improvement of 2.6 logarithm of the minimum angle of resolution (logMAR) lines in visual acuity (from 0.42 to 0.16 logMAR). Contrast sensitivity function improved at 1.5, 3, 6, 12, and 18 cycles per degree spatial frequencies. The control group did not show any significant change in visual acuity or contrast sensitivity function. None of the treated eyes showed a drop in visual acuity. Manifest refractions remained unchanged during the study.
The results of our study demonstrate the efficacy of perceptual vision therapy in improving visual acuity. The 2.6 logMAR lines improvement in visual acuity is encouraging, and is consistent with the results of previous studies. However, long-term follow-up and further studies are needed.
PMCID: PMC3864996  PMID: 24376340
perceptual learning; visual acuity; contrast sensitivity function; amblyopia
11.  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.
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.
To evaluate the benefit of optic nerve MRI for predicting response to appropriate therapy and recovery of visual acuity.
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.
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).
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.
PMCID: PMC4312052  PMID: 25635863
12.  Comparison of spherical aberration and small pupil profiles in improving depth of focus for presbyopic corrections 
To compare the validity and effectiveness of 2 methods for expanding depth of focus to correct for presbyopia; that is, induction of spherical aberration and small pupil apertures.
University of California, Berkeley, California, USA.
Comparative case series.
A random 4-alternative forced-choice acuity task was performed. Visual performance and depth of focus was compared using adaptive optics–corrected distance visual acuity (CDVA) values and mean visual acuity over a 3.0 diopter (D) range of defocus using the following 3 adaptive optics–corrected profiles: 2.0 mm pupil, 5.0 mm pupil, and 5.0 mm pupil with −0.274 µm of spherical aberration.
The study enrolled 13 subjects. The 5.0 mm pupil profile had a CDVA of −0.218 logMAR and a mean visual acuity through focus of 0.156 logMAR. The 2.0 mm pupil profile had a worse CDVA (0.012 logMAR) but an improved mean visual acuity (0.061 logMAR). The 5.0 mm pupil profile with −0.274 µm of spherical aberration measured a CDVA of −0.082 logMAR and a mean visual acuity 0.103 logMAR.
The spherical aberration and small-pupil profiles improved the mean visual acuity across a 3.0 D range of defocus but resulted in decreased CDVA at the plane of best focus in comparison to an adaptive optics–corrected 5.0 mm pupil. Small-pupil profiles are a better choice than spherical aberration profiles for presbyopic corrections due to expected accuracy, predictability, and patient satisfaction.
PMCID: PMC3511607  PMID: 23031641
13.  The Teller Acuity Cards Are Effective in Detecting Amblyopia 
Detection of amblyopia in infants and toddlers is difficult because the current clinical standard for this age group, fixation preference, is inaccurate. Although grating acuity represents an alternative, studies of preschoolers and schoolchildren report that it is not equivalent to the gold standard optotype acuity. Here, we examine whether the Teller Acuity Cards (TAC) can detect amblyopia effectively by testing children old enough (7.8 ± 3.6 years) to complete optotype acuity testing.
Grating acuity was assessed monocularly in 45 patients with unilateral amblyopia, 44 patients at risk for amblyopia, and 37 children with no known vision disorders. Each child’s grating acuity was classified as normal/abnormal based on age-appropriate norms. These classifications were compared with formal amblyopia diagnoses.
Grating acuity was finer than optotype acuity among amblyopic eyes (medians: 0.28 vs. 0.40 logMAR, respectively, p < 0.0001) but not among fellow eyes (medians: 0.03 vs. 0.10 logMAR, respectively, p = 0.36). The optotype acuity-grating acuity discrepancy among amblyopic eyes was larger for cases of severe amblyopia than for moderate amblyopia (means: 0.64 vs. 0.18 logMAR, respectively, p = 0.0001). Nevertheless, most cases of amblyopia were detected successfully by the TAC, yielding a sensitivity of 80%. Furthermore, grating acuity was relatively sensitive to all amblyopia subtypes (69 to 89%) and levels of severity (79 to 83%).
Although grating acuity is finer than optotype acuity in amblyopic eyes, most children with amblyopia were identified correctly suggesting that grating acuity is an effective clinical alternative for detecting amblyopia.
PMCID: PMC2869287  PMID: 19390474
infant; vision; amblyopia; visual acuity; grating acuity
14.  The Farnsworth-Munsell 100 hue test in the first episode of demyelinating optic neuritis. 
The Farnsworth-Munsell 100 hue test (F-M 100) was used to examine 30 patients with their first episode of unilateral demyelinating optic neuritis (DON) at presentation, after 6 weeks and after 6 months. Twelve patients satisfactorily completed the test with the affected eye at presentation. This number had increased to 23 by 6 weeks and to 27 by 6 months. No patient with a visual acuity of LogMAR 0.86 (Snellen equivalent approx 6/43) or worse, could complete the test. The mean total error score of affected eyes showed significant improvement at each subsequent examination but was always worse than the non-affected eyes. There was a significant correlation between total error scores and visual acuities of affected eyes at presentation and after 6 months. Fourteen patients recovered a visual acuity of LogMAR 0.0 (Snellen equivalent 6/6) or better but the total error scores of the affected eyes were significantly worse than the non-affected eyes (p = 0.017), indicating that defective colour vision is an indicator of a previous episode of DON despite the recovery of normal visual acuity. DON is reported to produce a red-green (Type II) axis of colour defect but individual F-M 100 polar diagrams were usually generally abnormal and did not show any predominance of recognisable axis of colour defect at any examination. Group averaging of the F-M 100 data from such a well-defined group of patients with acute DON revealed a significant bipolar abnormality in the tritan (blue-yellow) axis at presentation which was not demonstrated at the subsequent examinations or at any examination of the non-affected eyes.
PMCID: PMC504432  PMID: 8435421
15.  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.
PMCID: PMC3525585  PMID: 23272235
16.  Recovery from optic neuritis is associated with a change in the distribution of cerebral response to visual stimulation: a functional magnetic resonance imaging study 
OBJECTIVES—Recovery to normal or near normal visual acuity is usual after acute demyelinating optic neuritis, despite the frequent persistence of conduction abnormalities as evidenced by the visual evoked potential (VEP). This raises the possibility that cortical adaptation to a persistently abnormal input contributes to the recovery process. The objective of this study was to investigate the pattern of cerebral response to a simple visual stimulus in recovered patients in comparison to normal subjects.
METHODS—Functional magnetic resonance imaging (fMRI) was used to study the brain activation pattern induced by a periodic monocular 8Hz photic stimulus in seven patients who had recovered from a single episode of acute unilateral optic neuritis, and in seven normal controls. VEPs and structural optic nerve MRI were performed on patients.
RESULTS—Stimulation of either eye in controls activated only the occipital visual cortex. However, in patients, stimulation of the recovered eye also induced extensive activation in other areas including the insula-claustrum, lateral temporal and posterior parietal cortices, and thalamus; stimulation of the clinically unaffected eye activated visual cortex and right insula-claustrum only. The volume of extraoccipital activation in patients was strongly correlated with VEP latency (r=0.71, p=0.005).
CONCLUSIONS—The extraoccipital areas that were activated in patients all have extensive visual connections, and some have been proposed as sites of multimodal sensory integration. The results indicate a functional reorganisation of the cerebral response to simple visual stimuli after optic neuritis that may represent an adaptive response to a persistently abnormal input. Whether this is a necessary part of the recovery process remains to be determined.

PMCID: PMC1736877  PMID: 10727479
17.  Long term visual outcome in amblyopia treatment 
The British Journal of Ophthalmology  2002;86(10):1148-1151.
Aim: To evaluate long term visual outcome of treatment for amblyopia.
Methods: In a previous study, 44 children with unilateral amblyopia caused by strabismus or anisometropia were enrolled in a prospective study investigating the results of treatment. All children were regularly examined up to at least 8 years of age and outcome was evaluated. All subjects were invited to a re-examination and in total 26 subjects attended. Two of these were excluded because of insufficient records. The final sample consists of 24 subjects. Mean follow up time was 10.4 (SD 1.9) years.
Results: For the amblyopic eyes, 17% deteriorated in visual acuity, 50% were stable, and 33% gained in visual acuity. For the non-amblyopic eyes, 8% lost one line in visual acuity, 38% were stable, and 54% gained in visual acuity. No eye in any subject shifted more than 0.2 logMAR units. The increase in visual acuity for the non-amblyopic eyes was significant, while the increase for the amblyopic eyes was not. All straight eyed anisometropic amblyopes showed a distinct decrease in magnitude of anisometropia.
Conclusions: Visual acuity was essentially stable in the amblyopic eyes 10 years after cessation of treatment in the studied population.
PMCID: PMC1771300  PMID: 12234897
amblyopia; treatment outcome; visual acuity
18.  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.
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.
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).
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.
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.
PMCID: PMC4148263  PMID: 25166273
19.  Validation of printed and computerised crowded Kay picture logMAR tests against gold standard ETDRS acuity test chart measurements in adult and amblyopic paediatric subjects 
Eye  2011;26(4):593-600.
The impression exists that picture acuity scores may overestimate function when subjects are switched to letter charts. This has not been systematically investigated. The aims of this study were to validate both printed crowded Kay picture (pCKP) and computerised CKP (cCKP) logMAR test acuity measurements against gold standard ETDRS letter chart scores.
A total of 30 adult subjects with various ophthalmic disease and 40 amblyopic children underwent test and re-test visual acuity measurements using the ETDRS chart, the pCKP logMAR test, and the cCKP acuity scores taken, using the COMPlog visual acuity measurement system. Bland and Altman methods were employed.
Computerised and printed Kay picture acuity scores agreed well. Both Kay picture test measurements were systematically biased when compared with ETDRS chart measurements. No significant proportional bias was found. The test retest variability (TRV) of all three tests was found to be similar between ±0.14 and 0.16 logMAR in both groups.
All three tests were similarly replicable and computerised Kay pictures appear to be a valid alternative to hard copy Kay pictures. Kay picture acuity measurements were systematically biased when compared with the gold standard ETDRS. Measurement error means that differences of up to 0.16 logMAR may be observed in clinically stable patients when re-measured using the same technique. A combination of TRV and systematic bias can however lead to differences of up to 0.40 logMAR in stable amblyopic patients when switched from CKPs to ETDRS chart acuity measurements.
PMCID: PMC3325559  PMID: 22193878
visual acuity; Kay picture test; COMPlog; logMAR
20.  Monocular and binocular reading performance in children with microstrabismic amblyopia 
The British Journal of Ophthalmology  2005;89(10):1324-1329.
Aim: To evaluate if functionally relevant deficits in reading performance exist in children with essential microstrabismic amblyopia by comparing the monocular and binocular reading performance with the reading performance of normal sighted children with full visual acuity in both eyes.
Methods: The reading performance of 40 children (mean age 11.6 (SD 1.4) years) was evaluated monocularly and binocularly in randomised order, using standardised reading charts for the simultaneous determination of reading acuity and speed. 20 of the tested children were under treatment for unilateral microstrabismic amblyopia (visual acuity in the amblyopic eyes: logMAR 0.19 (0.15); fellow eyes −0.1 (0.07)); the others were normal sighted controls (visual acuity in the right eyes −0.04 (0.15); left eyes −0.08 (0.07)).
Results: In respect of the binocular maximum reading speed (MRS), significant differences were found between the children with microstrabismic amblyopia and the normal controls (p = 0.03): whereas the controls achieved a binocular MRS of 200.4 (11) wpm (words per minute), the children with unilateral amblyopia achieved only a binocular MRS of 172.9 (43.9) wpm. No significant differences between the two groups were found in respect of the binocular logMAR visual acuity and reading acuity (p>0.05). For the monocular reading performance, significant impairment was found in the amblyopic eyes, whereas no significant differences were found between the sound fellow eyes of the amblyopic children and the control group.
Conclusion: In binocular MRS, significant differences could be found between children with microstrabismic amblyopia and normal controls. This result indicates the presence of a functionally relevant reading impairment, even though the binocular visual acuity and reading acuity were both comparable with the control group.
PMCID: PMC1772895  PMID: 16170125
amblyopia; microstrabismus; reading performance; reading speed
21.  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.
PMCID: PMC3886364  PMID: 24459442
22.  Visual evoked potential importance in the complex mechanism of amblyopia 
International Ophthalmology  2013;33(5):515-519.
To compare the visual evoked potential (VEP) responses of amblyopic eyes with VEP responses of sound eyes in amblyopic children. A study of 65 amblyopic children with pattern-reversal VEPs elicited by checkerboard stimuli with large, medium and small checks. The children were classified into three groups: Group A, 22 children with anisometropic amblyopia; Group B, 16 children with exotropic strabismic amblyopia; and Group C, 27 children with esotropic strabismic amblyopia. Visual acuity (VA) was significantly worse in the amblyopic eye as compared to the sound eye. However, no statistically significant difference was found between the amblyopic and sound eye of amblyopic children in the three groups for VEP P1 amplitude and latencies for any check sizes. VEP is a very important tool in understanding the complex amblyopic mechanism. Although the sound eye has superior VA, the absence of differences in VEP P1 amplitudes and latencies demonstrate the functional abnormality of the eye considered ‘good’. More studies are necessary to explain why the sound eye in amblyopic children cannot be considered completely normal. Special attention should therefore be paid to amblyopic treatment, as patching can have a negative effect on the sound eye.
PMCID: PMC3782652  PMID: 23417145
Amblyopia; Anisometropia; Strabismus; Visual evoked potential (VEP)
23.  Comparative evaluation of megadose methylprednisolone with dexamethasone for treatment of primary typical optic neuritis 
Indian Journal of Ophthalmology  2007;55(5):355-359.
To compare the efficacy of intravenous methylprednisolone and intravenous dexamethasone on visual recovery and evaluate their side-effects for the treatment of optic neuritis.
Materials and Methods:
Prospective, randomized case-controlled study including 21 patients of acute optic neuritis presenting within eight days of onset and with visual acuity less then 20/60 in the affected eye who were randomly divided into two groups. Group I received intravenous dexamethasone 200 mg once daily for three days and Group II received intravenous methylprednisolone 250 mg/six-hourly for three days followed by oral prednisolone for 11 days. Parameters tested were pupillary reactions, visual acuity, fundus findings, color vision, contrast sensitivity, Goldmann visual fields and biochemical investigations for all patients at presentation and follow-up.
Both groups were age and sex-matched. LOGMAR visual acuity at presentation was 1.10 ± 0.52 in Group I and 1.52 ± 0.43 in Group II. On day 90 of steroid therapy, visual acuity improved to 0.28 ± 0.33 in Group I and 0.36 ± 0.41 in Group II ( P =0.59). At three months there was no statistically significant difference in the color vision, contrast sensitivity, stereoacuity, Goldman fields and the amplitude and latency of visually evoked response between the two groups. The concentration of vitamin C, glucose, sodium, potassium, urea and creatinine were within the reported normal limits.
Intravenous dexamethasone is an effective treatment for optic neuritis. However, larger studies are required to establish it as a safe, inexpensive and effective modality for the treatment of optic neuritis.
PMCID: PMC2636008  PMID: 17699944
Dexamethasone; methylprednisolone; optic neuritis.
24.  VEP Vernier, VEP Grating and Behavioral Grating Acuity in Patients with Cortical Visual Impairment 
Cortical visual impairment (CVI) is a leading cause of bilateral vision impairment. Since many patients with CVI cannot perform an optotype test, their acuity is often measured with a grating stimulus using a preferential looking (PL) test or the visual evoked potential (VEP) recording. The purpose of this study is to determine the relationship between VEP vernier acuity, VEP grating acuity and behavioral grating acuity in patients with CVI.
Sweep VEP vernier acuity, sweep VEP grating acuity, and behavioral grating acuity (measured with PL cards) were measured in 29 patients with CVI. The patients ranged in age from 3.2 to 22.7 years (mean: 12.3; SD: 5.3). Because the measures of vernier acuity and grating acuity have different units, the results were expressed as the log deficit (with normal being 30 c/deg and 0.5 arc min respectively).
VEP grating acuity loss and VEP vernier acuity loss were significantly related (r=0.70) with a slope of 1.31, indicating that indicating that on average, vernier acuity showed a 0.2 log unit deficit compared to VEP grating acuity. Behavioral grating acuity loss and VEP grating acuity loss were also significantly related (r=0.64) with a slope of 1.55, indicating that behavioral acuity was more reduced (by approximately 0.3 log unit). VEP vernier acuity loss and behavioral grating acuity loss were significantly related (r=0.66) with a slope of 0.85, indicating that behavioral acuity and VEP vernier acuity showed a similar magnitude of reduction. A Bland-Altman comparison between the VEP vernier acuity method and the behavioral acuity method showed a flat slope (0.30), indicating that the two measures produce similar visual acuity measures across the range of acuity levels.
In patients with CVI, VEP vernier acuity showed greater deficits than VEP grating acuity and was more similar to the behavioral measures of grating acuity.
PMCID: PMC3862531  PMID: 19390471
cortical visual impairment; cerebral visual impairment; vernier visual acuity; visual evoked potential; low vision
25.  Disability in optic neuritis correlates with diffusion tensor-derived directional diffusivities 
Neurology  2009;72(7):589-594.
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).
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.
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).
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.
= 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.
PMCID: PMC2672917  PMID: 19073948

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