Reproducibility of multifocal VEP latency using different stimulus presentations.

The aims of the article were to study the reproducibility of latency of multifocal visual evoked potential (mfVEP) recorded using different stimulus presentations and to identify the peak with least variability. Ten normal subjects, aged between 22 and 52 years (mean age 32 ± 8.37 years), participated in the study. All subjects underwent mfVEP testing with pattern reversal and pattern pulse stimulus presentations. The stimulus subtends 26° from fixation and includes 24 segments. Only the vertical channel was recorded on all subjects. Testing was repeated after 1-2 weeks. Only the right eye of all subjects was analysed. Segments with low signal-to-noise ratios (SNR < 1.5) were excluded from analysis. The latencies were analysed to confirm values from the same peak for the two tests. The latency values were then analysed for the start of the response, the first peak and the second peak. The waveforms were reproducible throughout the field. Reproducibility of latency at the "start of the response" was significantly lesser than the first and the second peaks studied, while the reproducibility of latency at the first peak was not statistically different from the second peak for either pattern reversal or pattern pulse stimulation. The latency values were not different between the first and the second sessions for either pattern reversal or pattern pulse stimulation for any of the peaks. The pattern reversal stimulus presentation produced less variability in latency. The first peak is the most reproducible among the three measures in both the stimulus presentation.

A comparison of participants and non-participants in the Chennai Glaucoma Study-rural population.

PURPOSE: To study whether the difference in the demographic characteristics of participants and non participants could result in biased prevalence estimates and associations. AIM: To compare the non-participant and participant characteristics, and to ascertain if non-response bias is present in the rural population of the Chennai Glaucoma Study (CGS). METHODS: Rural participants and non-participants were compared with regard to socio-demographic variables (age, gender, religion, mother tongue, literacy and employment). RESULTS: 4800 subjects aged 40 years or over were enumerated, 82% (3934: 45% male and 55% female) responded. Gender did not influence participation (adjusted OR-1.11, CI: .91-1.36). Subjects in the 70-79 year age group were more likely to respond (OR-1.76; CI-1.31-2.38). Hindus had a higher participation rate than Christians or Muslims (adjusted OR-2.63, CI: 1.80-3.84). The other predictors of participation were illiteracy (adjusted OR-1.44, CI: 1.22-1.70), unemployment (OR-1.28, CI: 1.04-1.58), place of residence (main villages) (OR-6.66, 95% CI: 4.6-9.64). CONCLUSION: Based on our study findings, it does not seem likely that participation bias will affect the study results.

Optimizing the Detection of Preperimetric Glaucoma by Combining Structural and Functional Tests.

PURPOSE: We evaluated the performance of low contrast achromatic (LLA) multifocal visual evoked potentials (mfVEP) in preperimetric glaucoma and compared its diagnostic performance to other early diagnostic tests. We identified the clinically most useful tests and combinations in preperimetric glaucoma. METHODS: We studied 59 patients with at least one glaucomatous disc, with normal, reliable visual fields in that eye, and 17 normal controls. All participants underwent complete ophthalmic examination including Humphrey visual fields (HVF), short wavelength automated perimetry (SWAP), frequency doubling perimetry (FDT Matrix), Spectralis optical coherence tomography (OCT), Heidelberg retinal tomography (HRT 3), and color stereoscopic optic disc photographs. We recorded mfVEPs using LLA stimulation. RESULTS: We studied 85 eyes of 59 patients (64.89 ± 8.15 years) and 34 eyes of 17 controls (64.28 ± 13.06 years; P = 0.64). Heidelberg retinal tomography and LLA mfVEP demonstrated the best sensitivities (50.6% and 51.8%, respectively) in identifying preperimetric glaucoma, and were not significantly different from each other. Both tests had significantly better sensitivity than all other tests (P < 0.0001). Of the eyes, 76.5% were identified by the combination of (any one of) LLA mfVEP and HRT. Sensitivity of the combination was significantly better than any of the individual tests (P < 0.05 for all pairs), or any other combinations of tests, with better negative than positive predictive value. CONCLUSIONS: The LLA mfVEP test identified approximately 50.6% eyes with preperimetric glaucoma, which was significantly higher than other perimetric methods, and similar to HRT. The combination of LLA mfVEP and HRT had exceptionally high sensitivity of 76.5% for preperimetric glaucoma.

Relationship between optical coherence tomography and electrophysiology of the visual pathway in non-optic neuritis eyes of multiple sclerosis patients.

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.

Axonal loss in non-optic neuritis eyes of patients with multiple sclerosis linked to delayed visual evoked potential.

OBJECTIVE: Recent studies demonstrate significant thinning of the retinal nerve fiber layer (RNFL) in multiple sclerosis (MS) non-optic neuritis (MS-NON) eyes. However, the pathologic basis of this reduction is not clear. The aim of the current study was to investigate the relationship of the RNFL thickness in MS-NON eyes with latency delay of the multifocal visual evoked potential (mfVEP), a surrogate marker of the visual pathway demyelination. METHODS: Total and temporal RNFL thickness and latency of the mfVEP in 45 MS-NON eyes of 45 patients with relapsing-remitting MS and 25 eyes of age- and gender-matched controls were measured and analyzed. RESULTS: There was significant reduction of total and temporal RNFL thickness (p = 0.015 and p = 0.006, respectively) and significant latency delay (p < 0.0001) in MS-NON eyes. Both total and temporal RNFL thickness were associated with latency of the mfVEP (r2 = 0.43, p < 0.0001 and r2 = 0.36, p = 0.001, respectively). MS-NON eyes with normal latency (n = 26) showed no significant reduction of RNFL thickness compared with controls (p = 0.44 and p = 0.1 for total and temporal RNFL, respectively), whereas eyes with delayed latency (n = 19) demonstrated significantly thinner RNFL (p = 0.001 and p = 0.0005). MS-NON eyes with delayed latency also had significantly thinner RNFL compared with those with normal latencies (p = 0.013 and p = 0.02). In patients with no previous optic neuritis in either eye, delayed latency and reduced RNFL were bilateral whenever present. CONCLUSIONS: The study demonstrated significant association between RNFL loss and a latency delay of the mfVEP in MS-NON eyes.

Inner nuclear layer thickening is inversley proportional to retinal ganglion cell loss in optic neuritis.

AIM: To examine the relationship between retinal ganglion cell loss and changes in the inner nuclear layer (INL) in optic neuritis (ON). METHODS: 36 multiple sclerosis (MS) patients with a history of ON and 36 age and sex-matched controls underwent Optical Coherence Tomography. The paramacular retinal nerve fiber layer (RNFL), combined ganglion cell and inner plexiform layers (GCL/IPL) and inner nuclear layer (INL) thickness were measured at 36 points around the fovea. To remove inter-subject variability, the difference in thickness of each layer between the ON and fellow eye of each patient was calculated. A topographic analysis was conducted. RESULTS: The INL of the ON patients was thicker than the controls (42.9µm versus 39.6µm, p=0.002). ON patients also had a thinner RNFL (27.8µm versus 32.2µm, p<0.001) and GCL/IPL (69.3µm versus 98.1µm, p<0.001). Among the controls, there was no correlation between RNFL and GCL/IPL as well as RNFL and INL, but a positive correlation was seen between GCL/IPL and INL (r=0.65, p<0.001). In the ON group, there was a positive correlation between RNFL and GCL/IPL (r=0.80, p<0.001) but a negative correlation between RNFL and INL (r=-0.61, p<0.001) as well as GCL/IPL and INL (r=-0.44, p=0.007). The negative correlation between GCL/IPL and INL strengthened in the ON group when inter-subject variability was removed (r=-0.75, p<0.001). Microcysts within the INL were present in 5 ON patients, mainly in the superior and infero-nasal paramacular regions. While patients with microcysts lay at the far end of the correlation curve between GCL/IPL and INL (i.e. larger INL and smaller GCL/IPL compared to other patients), their exclusion did not affect the correlation (r= -0.76, p<0.001). CONCLUSIONS: INL enlargement in MS-related ON is associated with the severity of GCL loss. This is a continuous relationship and patients with INL microcysts may represent the extreme end of the scale.

Gaussian wavelet transform and classifier to reliably estimate latency of multifocal visual evoked potentials (mfVEP).

This paper describes a method to reliably estimate latency of multifocal visual evoked potential (mfVEP) and a classifier to automatically separate reliable mfVEP traces from noisy traces. We also investigated which mfVEP peaks have reproducible latency across recording sessions. The proposed method performs cross-correlation between mfVEP traces and second order Gaussian wavelet kernels and measures the timing of the resulting peaks. These peak times offset by the wavelet kernel's peak time represents the mfVEP latency. The classifier algorithm performs an exhaustive series of leave-one-out classifications to find the champion mfVEP features which are most frequently selected to infer reliable traces from noisy traces. Monopolar mfVEP recording was performed on 10 subjects using the Accumap1™ system. Pattern-reversal protocol was used with 24 sectors and eccentricity upto 33°. A bipolar channel was recorded at midline with electrodes placed above and below the inion. The largest mfVEP peak and the immediate peak prior had the smallest latency variability across recording sessions, about ±2ms. The optimal classifier selected three champion features, namely, signal-to-noise ratio, the signal's peak magnitude response from 5 to 15Hz and the peak-to-peak amplitude of the trace between 70 and 250 ms. The classifier algorithm can separate reliable and noisy traces with a high success rate, typically 93%.

Transsynaptic retinal degeneration in optic neuropathies: optical coherence tomography study.

PURPOSE: Recently demonstrated neuronal loss in the inner nuclear layer of the retina in multiple sclerosis (MS) and glaucoma raises the question of a primary (possibly immune-mediated) or secondary (transsynaptic) mechanism of retinal damage in these diseases. In the present study we used optical coherence tomography to investigate retrograde retinal transsynaptic degeneration in patients with long-standing and severe loss of ganglion cells due to optic neuropathy. METHODS: Fifteen eyes of glaucoma patients with visual field defect limited to upper hemifield and 15 eyes of MS patients with previous episode of optic neuritis (ON) and extensive loss of ganglion cells were imaged using spectral-domain optical coherence tomography and compared with two groups of age-matched controls. Combined retinal ganglion cell layer/inner plexiform layer (GCL/IPL) thickness and inner nuclear layer (INL) thickness were analyzed. RESULTS: In the glaucoma group there was a significant (P = 0.0005) reduction of GCL/IPL thickness in the lower (affected) retina compared with normal controls; however INL thickness was not statistically reduced (P = 0.49). In the MS group reduction of GCL/IPL thickness in both hemifields of ON eyes was also significant (P = 0.0001 and P < 0.0001 for inferior and superior retina respectively). However, similar to the glaucomatous eyes, there was no significant reduction of INL thickness in both hemifields (P = 0.25 and P = 0.45). CONCLUSIONS: This study demonstrates no significant loss of INL thickness in parts of the retina with long-standing and severe loss of retinal ganglion cells.