Investigation of the temporal properties of the retina using the m-sequence.

The mfERG provides a topographic map of function of the retina and has been used in numerous studies to identify macular, paramacular and peripheral retinal dysfunction. This study investigates the changes in response due to the presentation rate of the stimulus. Twenty subjects gave informed consent to take part in the study, which had local regional ethical committee approval. Only a single hexagon of 8° diameter was presented to reduce ambiguity when identifying the higher-order kernels (HOK). Six rates were tested using a 60-Hz CRT monitor by introducing blank (black ~0 cd/m2) filler frames (FF). The rates tested were 0FF; 1FF; 2FF; 4FF; 7FF; and 14FF. The first-order kernel had largest responses to the slower stimuli (4FF and above). HOK had largest amplitudes at faster rates with the second-order kernel peaking at 1FF. At rates with 4FF and slower, the higher-order kernels were indiscernible above the noise.

Early multifocal electroretinogram findings during intravitreal ranibizumab treatment for neovascular age-related macular degeneration.

PURPOSE: To evaluate changes in the multifocal electroretinogram (mfERG) in patients with neovascular age-related macular degeneration (nAMD) undergoing ranibizumab treatment. METHODS: This was an observational, longitudinal, prospective study. Treatment-naive patients with nAMD who met the inclusion and exclusion criteria underwent a course of monthly injections of ranibizumab over 3 months. At baseline and month 3, each subject was evaluated with best corrected visual acuity (BCVA), contrast sensitivity (CS), fluorescein and indocyanine green angiography, optical coherence tomography (OCT), and mfERG. Additional mfERGs were performed at weeks 1 and 4 and BCVA and OCT at weeks 4 and 8. RESULTS: Eighteen patients were enrolled. Between baseline and week 12, median BCVA improved from 59 to 69 ETDRS letters (P = 0.001), median CS improved from 29 to 30 letters (P = 0.05), mean OCT central foveal subfield thickness (CFT) decreased from 294 to 199 µm (P = 0.005), mean P1 amplitude density of the mfERG central zone increased from 35.85 to 51.55 nV/deg(2) (P = 0.009). The mfERG response correlated positively with BCVA (F = 22; P < 0.0001) and negatively with CFT (F = 12.73; P = 0.00078). CONCLUSIONS: Intravitreal ranibizumab therapy appears to induce an increase in mfERGs centrally in patients with nAMD at least in the short term. Longer term studies to investigate the prognostic value of mfERG responses to predict changes in visual acuity in nAMD and other diseases are warranted. (ClinicalTrials.gov number, NCT01023971.).

Multifocal electroretinography as a predictor of maintenance of vision after photodynamic therapy for neovascular age-related macular degeneration.

PURPOSE: To investigate the role of multifocal electroretinography (mfERG) in predicting the outcome of photodynamic therapy (PDT) for neovascular age-related macular degeneration (AMD). METHODS: Participants underwent refraction protocol VA assessment using the ETDRS logMAR chart at 1 m, Contrast Sensitivity (CS) using the Pelli-Robson chart at 1 m, fundus fluorescein angiography (FA) and mfERGs in response to 19 segments. Response to PDT was binary (1 = the loss of less than 15 letters at 12 months, 0 = the loss of 15 letters or more) and was used as the dependent variable for logistic regression analysis. RESULTS: Logistic regression modelling identified mfERG central segment amplitude, lesion size on FA, VA and CS as predictors of outcome (P = 0.05, 0.02, 0.01, 0.03). The model is stable and has excellent discriminability. CONCLUSION: The outcomes of this study are particularly relevant to patients in the UK who are sometimes treated with PDT alone. A larger prospective study would facilitate development of an index to predict outcome of future treatments for AMD.

Automatic positioning of cursors in the transient pattern electroretinogram (PERG) with very poor SNR using an Expert System.

An expert system is described which automatically cursors PERG waveforms of very poor signal-to-noise ratio. The training data-set is derived from shape-perturbated PERG waveforms based on the ISCEV Standard and a series of clinically-normal waveforms. In validation trials, the Expert System is clearly shown to out-perform the Human Expert in the presence of noise. All software was written in MatLab((R)). It is proposed that this system is generic and similarly applicable to other transient recordings. A comprehensive Internet demonstration (SPoC: Smart Positioning of Cursors) is maintained at www.liverpooleye.org.

Deficits in the electroretinogram in neovascular age-related macular degeneration and changes during photodynamic therapy.

PURPOSE: To describe the deficits in four electroretinography (ERG) modalities in patients with neovascular age-related macular degeneration (AMD). To describe the changes in these parameters during a course of verteporfin photodynamic therapy (PDT). METHODS: Pattern (PERG), multifocal (mfERG) (19 segment simplified test protocol), flash ERG and flicker ERG were performed in patients with active neovascular AMD before PDT and compared to fellow eye controls using paired t-tests. Changes in ERG parameters during the 12 month treatment course were visualised using 95% confidence intervals of the median difference. The statistical significance of any changes was quantified using Wilcoxon signed ranks tests. RESULTS: Fifty patients were recruited and followed. At presentation all ERG amplitudes were reduced with greater reductions in focal as opposed to global test protocols (P < 0.05). Over the 12 month course of PDT, PERG P50 amplitude showed a general downward trend and latency remained unchanged. mfERG p1 amplitude density showed an upward trend at six months before returning to baseline by 12 months. mfERG ring 2 amplitude density was significantly increased at 12 months compared to baseline (P = 0.010). Flicker ERG latency was significantly increased at six months compared to baseline (P = 0.015). DISCUSSION: The simplified mfERG protocol was tolerated by this patient group, however, they found the full test protocol demanding. Large deficits in the retinal ERG function occur in neovascular AMD and involve retinal locations adjacent to as well as overlying choroidal neovascularisation (CNV). After PDT there is an improvement in electro-retinal function in retinal locations overlying the CNV.

Examination of short binary sequences for mfERG recording.

The mfERG, when first introduced by Erich Sutter used long sequences with short periods (approximately 15 ms) between steps (flashes). Since then a number of studies have introduced slower or modified sequences to emphasise Oscillatory Potentials (OPs), Optic Nerve Head Components (ONHC) or the s-wave. With this reduction in the rate of presentation many of the investigators have reduced the length of the sequence to allow a shorter recording period. This is also desirable for patient comfort and co-operation in diagnostic investigations. When reducing the length of the sequence there is a risk that it will be too short to ensure orthogonality of the first order component and all significant higher order components, particularly when a large number of areas (hexagons) are stimulated. This paper aims to verify that a short sequence (using the sequence used by the Roland Retiscan stimulating 19 hexagons) is capable of keeping responses of both first and higher orders separate for each stimulating area. The sequence was investigated by placing photodiodes connected to a Diagnosys Espion and then exported to Excel and MATLAB for analysis. It was determined that the sequences used were m-sequences length n = 9. The photodiode only responded to flashes of light so was unable to detect a correcting 0 at the end of sequence. The sequences driving each hexagon were then determined and found to be shifted 26 steps from each other. The correlation coefficients between all sequences was found to be -1/(2n -1). The sequences to decode the second order kernels were determined and the correlation coefficients between each of these sequences, and between these and the original sequences, were also -1/(2n -1). This work provides a mathematical validation of the use of short sequences for slow mfERG, and describes an empirical test method.

Automated post hoc removal of power-line and CRT frame pulse contamination from retinal and cortical evoked potentials (EPs).

Recordings of the ERG, PERG, VEP and their multi-focal variants are occasionally contaminated with harmonic noise arising from the mains supply and CRT monitors. These noise contributions can be modelled as distorted sinusoids and identified by means of non-linear multiple regression and removed: no a priori estimates of number or frequency of noise sources are required. This approach is termed noise cancellation and does not constitute any form of notch filter: the fidelity of the underlying waveform is preserved. Here the simple theory is illustrated in artificial datasets and then applied to clinical examples of PERG and VEP. The programming language used throughout is MatLab R13SP3 (Mathworks UK Ltd.).

Congenital absence of optic chiasm: demonstration of an uncrossed visual pathway using monocular flash visual evoked potentials.

A 35 month old child was referred for electrophysiology testing with pendular nystagmus, corresponding head oscillations and reduced vision. Flash visual evoked potential (VEP) revealed large responses at the right occiput (but not the left occiput) from the right eye and similar large responses at only the left occiput from the left eye, indicating absent/deficient crossover at the chiasm. A magnetic resonance imaging (MRI) scan subsequently confirmed absence of the optic chiasm. There was no other evidence of midline brain defects. Her subsequent development to age 11 has been followed. The nystagmus has remained mainly horizontal but a torsional component was noted from age 5 years and described as see-saw at age 6 years. A small right esotropia was noted at 6 years and spectacles prescribed for low hypermetropic refractive error. Bilateral superior rectus recessions at age 7 years produced an improved head posture. Her visual acuity has remained stable at around 6/24 from age 4 years. No binocularity nor stereopsis has been demonstrated over subsequent visits.