Malcolm C. Brown

ISCEV Standard for Clinical Electro-oculography (EOG) 2006

The Clinical Electro-oculogram (EOG) is an electrophysiological test of function of the outer retina and retinal pigment epithelium (RPE) in which the change in the electrical potential between the cornea and the ocular fundus is recorded during successive periods of dark and light adaptation. This document sets out a Standard Method for performance of the test, and also gives detailed guidance on technical and practical issues, and on reporting test results. The main object of the Standard is to promote consistent quality of testing and reporting within and between centres. This 2006 Standard, from the International Society for Clinical Electrophysiology of Vision (ISCEV: www.iscev.org ), is a revision of the previous Standard published in 1993, and reviewed and re-issued in 1998.

Modification of the tear function index and its use in the diagnosis of Sjögren's syndrome.

BACKGROUND The tear function index (TFI) has been shown to be of value in the diagnosis of patients suffering from Sjögrens syndrome. It is dependent, however, on introducing into the conjunctival fornix the correct concentration of fluorescein in at least one and a half times the normal tear volume. The stimulus and effect of this added volume on the tear dynamics is likely to vary between individuals. These factors, together with the method of performing the test, limit its general applicability. AIM To devise a method of performing the TFI with less variability and more general applicability. To present a theoretical and in vitro assessment of the dynamics of the TFI. METHOD The study was divided into three parts. The first part was to compare the results obtained using a prepared strip containing 1.3 μl of 0.5% fluorescein with the introduction of the same amount of fluorescein as a drop. The second part was to compare the results obtained with prepared strips with the standard method of performing the TFI, both with and without topical anaesthetic. The third part was an in vitro study of the rate of flow of graded volumes on a filter paper strip. 42 subjects with a diagnosis of Sjögrens syndrome according to the European criteria and 126 without Sjögrens syndrome were included. RESULTS There was no significant difference between the results obtained with a prepared strip and the introduction of 1.3 μl into the eye before performing the Schirmers test and TFI (0.1<p<0.93). There was, likewise, no significant difference between using the prepared strips and the standard method of performing the TFI (0.36<p<0.93). There was, however, less interocular difference (p=0.01) and variability (p=0.001) using the prepared strips than using a drop of fluorescein. Patients with Sjögrens syndrome had mean TFIs of 11.7 and 8.61 with upper 95% confidence values of 15 and 12 without and with topical anaesthetic, respectively. The theoretical calculation of the TFI was similar to the observed values. The in vitro results allow the filter paper to be removed from the eye at any interval and to estimate the volume of tears that the filter paper was in contact with. CONCLUSION The proposed method of performing the TFI is easy to perform, reliable, and therefore has general applicability for primary care and general practitioners. It allows the rapid identification of subjects who may be suffering from Sjögrens syndrome.

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.).

Removal of eye movement artefacts from single channel recordings of retinal evoked potentials using synchronous dynamical embedding and independent component analysis.

A system is described for the removal of eye movement and blink artefacts from single channel pattern reversal electroretinogram recordings of very poor signal-to-noise ratios. Artefacts are detected and removed by using a blind source separation technique based on the jadeR independent component analysis algorithm. The single channel data are arranged as a series of overlapping time-delayed vectors forming a dynamical embedding matrix. The structure of this matrix is constrained to the phase of the stimulation epoch: the term synchronous dynamical embedding is coined. A novel method using a marker channel with a non-independent synchronous feature is employed to identify the single most relevant source estimation for reconstruction and signal recovery. This method is non-lossy, all underlying signal being recovered. In synthetic datasets of defined noise content and in standardised real data recordings, the performance of this technique is compared to conventional fixed-threshold hard-limit rejection. The most significant relative improvements are achieved when movement and blink artefacts are greatest: no improvement is demonstrable for the random noise only situation.

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®. 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

Relatively spared central multifocal electroretinogram responses in acute quinine toxicity.

A 71-year-old man was investigated with electrodiagnostic testing 4 months after a deliberate quinine overdose. Initially he was admitted to intensive care unit with visual acuity (VA) of perception of light in both eyes. VA recovered to 6/6 right eye and 6/12 left eye, though severely constricted fields were noted. Slow stimulus (base period of 83 ms) multifocal electroretinogram (ERG) showed electronegative responses outside the inner 5 degrees, with a reduced but electropositive response seen in this central area. It appears that in this case of bilaterally negative ERGs that the macula/fovea (which has a vascular supply through the choroid) is relatively spared as is seen in bilateral vascular electronegative ERGs. This may indicate that quinine toxicity to the retina may be secondary to effects similar to vascular occlusion or severe ischemia during the acute phase of quinine poisoning.

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.).

Keratoconus associated with CSNB1.

A 35-year-old man with best corrected visual acuities of −18.00/+10.00×180 (6/60) OD and −10.00/+8.00×5 (6/36) OS. Bilateral steep central corneal thinning, paracentral ectasia and Vogts striae were present; normal fundi. Corneal topography disclosed 7.4 dioptres of irregular astigmatism in the central 3 mm with thinning (335 &mgr;m). Electroretinography (ERG) showed no response. There were no medical or environmental influences for his keratoconus. Occurrence of keratoconus and CSNB in the patient may represent a chance association, but keratoconus has not been previously linked with CSNB1 either as a chance or true association though both show genetic predisposition.

Keratoconus associated with congenital stationary night blindness type 1.

A 35-year-old man presented with keratoconus; his best corrected visual acuities were −18.00/+10.00 ×180 (6/60) oculus dexter and −10.00/+8.00 ×5 (6/36) oculus sinister. Bilateral steep central corneal thinning, paracentral ectasia and Vogts striae were present. Normal fundi. Corneal topography disclosed 7.4 dioptres of irregular astigmatism in the central 3 mm with thinning (335 &mgr;m). Electroretinography (ERG) showed no response. There were no medical or environmental influences for his keratoconus. Occurrence of keratoconus and congenital stationary night blindness (CSNB) in the patient may represent a chance association, but keratoconus has not been previously linked with CSNB1 either as a chance or true association though both show genetic predisposition.

Keratoconus associated with CSNB1

A 35-year-old man was referred with progressive impairment of vision. He was previously diagnosed with anisometropic amblyobia and registered partially sighted. He had lifelong problems of night vision and described a family pedigree suggestive of X-linked inheritance, with two generations of male members affected with nyctalopia and high myopia. No male-to-male transmission occurred and female relatives were unaffected. Family members could not be contacted. Refraction showed distorted retinsocopy reflexes, with best corrected visual acuities of −18.00/+10.00 ×180 (6/60) OD and −10.00/+8.00 ×5 (6/36) OS. …