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Vaegan

Publications and source records attributed to Vaegan.

At least 19 recordsLinked to original sources

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.

Adaptation, Ocular↗

Assessment of structure and function over a 3-year period after gene transfer in RPE65-/- dogs.

AIM: To assess retinal structure and function over a 3-year period in a group of five RPE65-/- dogs treated by unilateral rAAV- mediated subretinal gene transfer. METHODS: Post-operative functional follow-ups were performed using simultaneous, bilateral, full-field ERGs. Structure was evaluated by SLO using FL and ICG angiography and by EM. RESULTS: Significant improvement of retinal function was observed through ERGs approximately 4 weeks following surgery. Scotopic b-wave amplitudes peaked 3 months after surgery. Then there was a successive reduction, although greater amplitudes than base-line values were observed at all post-operative time points. A-wave amplitudes increased at a later time than b-wave amplitudes and were sustained throughout the follow-up period. The increased cone function was preserved longer than the rod function. Angiography showed structural changes at the site of injection, corroborated by photoreceptor destruction observed ultrastructurally. Immediately adjacent to the subretinal injection area photoreceptor outer segments appeared normal. CONCLUSION: Despite local structural alterations at the subretinal injection site, subretinal gene transfer in the RPE65 null mutation dog effectively increases retinal function for at least 3 years after surgery.

Animals↗

A(max) is the best a-wave measure for classifying Abyssinian cat rod/cone dystrophy.

AIM: To see if any a-wave measure segregated normal cats from those affected by a recessively inherited Abyssinian rod/cone dystrophy more efficiently than a(max) to scotopic I(max). METHOD: A-waves to electroretinograms (ERGs) evoked by a 4 cd x s/m(2) scotopic flash were extracted from 241 ERG sessions using 108 cats. They were either wild type or from an affected Abyssinian stock. Fourty four were bred by back-crossing to have a 50% probability of being affected. Most were diagnosed by retinal appearance or by the pattern of loss in a long protocol ERG. Eight were still unclassified. The diagnostic efficiency of amplitudes at 7, 8, 9, and 10 ms and a(max), of a(max) peak time, age at testing, and the main components of principal components factor analysis were compared by scaling their ability to segregate affected and normal cats. RESULTS: Variance and overlap between the groups both decreased as time along the a-wave increased. The loading of each animal on the largest factor also gave considerable overlap. There was a small absolute separation between groups when a(max) itself was used. Age and peak time were uncorrelated with disease. The light intensity used could be calculated to be equivalent to one sufficient for about 75% of full saturation in man. CONCLUSION: A(max) is a simple measure that is already in routine clinical use. When the flash is very bright and the animal fully dark adapted, this single measure is the most efficient sign of this rod/cone degeneration and possibly of all degenerations involving rods.

Animals↗

Visual-evoked response, pattern electroretinogram, and psychophysical magnocellular thresholds in glaucoma, optic atrophy, and dyslexia.

PURPOSE: The purpose of this study is to compare visual-evoked response (VEP) pattern electroretinogram (PERG) and psychophysical thresholds to the same stimulus, designed to be optimal for the magnocellular system, in suspects and patients with early glaucoma, patients with optic nerve disease, dyslexic children, and age-matched controls. METHODS: Stimuli were low spatial frequency sinusoidal luminance profile gratings abruptly phase reversing at 7.14 Hz. Electrophysiological recordings were made at 50%, 30%, 20%, 10%, and 5% contrast. Threshold was the lowest contrast evoking a clear response at the stimulus frequency. Three independent judges scored the traces. Psychophysical thresholds were obtained by ascending and descending method of limits. VEPs and PERGs to International Society for Clinical Electrophysiology of Vision (ISCEV) standards and to increasing spatial frequencies were obtained as parvocellular specific controls. Patients were diagnosed independently by the referring professionals. RESULTS: Parvocellular-specific responses were normal, except in cases with explicable visual acuity loss. The judges scores correlated highly (> 0.9). VEPs and PERGs correlated highly and each correlated less well with psychophysics in normals, glaucoma, and dyslexia but the opposite occurred in optic nerve disease. VEPs had the lowest normal values and least variance (all adults < 5%, children < 10%, PERGs < 20%). In glaucoma, VEP magnocellular deficits occurred in 85% of recently diagnosed positive cases, 48% of high-risk suspects, 39% of low-risk suspects, and ocular hypertensives. Approximately 28% of dyslexics had VEP magnocellular deficits. PERG losses were less frequent. There was a clear dichotomy and low correlations between psychophysics and electrophysiology both within and between groups. Psychophysical threshold elevations were absent in all glaucoma groups, often large in optic atrophy and small (2.5%) but highly significant in dyslexia. CONCLUSION: Contrast thresholds to magnocellular-specific stimuli are consistent in cortex and retina. VEPs are more reliable. Psychophysics seems to tap different mechanisms. VEPs are very sensitive to early glaucoma. The lack of VEP loss in dyslexia suggests the other losses are artifactual. Further research is needed to see if stimuli even more like the frequency-doubling technology are more useful clinically.

Adult↗

Electrophysiologic differentiation of homozygous and heterozygous Abyssinian-crossbred cats with late-onset hereditary retinal degeneration.

OBJECTIVE: To develop a method to electrophysiologically differentiate heterozygous-carrier Abyssinian-crossbred cats from homozygous-affected Abyssinian-crossbred cats before clinical onset of inherited rod-cone retinal degeneration. ANIMALS: 14 back-crossed Abyssinian-crossbred cats of unknown genotype (homozygous or heterozygous) for inherited rod-cone retinal degeneration, 24 age-matched mixed-breed control cats, 6 age-matched heterozygous Abyssinian-crossbred cats, and 6 homozygous Abyssinian cats. PROCEDURE: Electroretinography (ERG) of heterozygous and homozygous cats revealed differences, especially for scotopic recordings. Frequent ophthalmoscopy and ERG (2 to 5 times; at intervals of 3 to 6 months) of back-crossed cats were performed. Amplitudes and implicit times were analyzed by use of a graphic representation of results. Ratios for amplitudes of the b-waves to amplitudes of the a-waves (b-wave:a-wave) were compared. RESULTS: 8 back-crossed cats had decreased a-wave amplitudes, increased b-wave implicit times, and abnormal ERG waveforms. Values for the b-wave:a-wave for the highest scotopic light intensity were significantly higher for those same 8 cats. CONCLUSIONS AND CLINICAL RELEVANCE: The 8 back-crossed Abyssinian-crossbred cats with abnormal results developed fundus changes over time consistent with disease. A graphic representation of ERG results can be used to differentiate between genotypes prior to funduscopic changes. Values for the b-wave:a-wave ratio provide confirmation. These ERG analyses may be applied clinically in the diagnosis of retinal degenerations in various species. IMPACT FOR HUMAN MEDICINE: Cats with hereditary rod-cone degeneration may be a useful model for comparative studies in relation to retinitis pigmentosa in humans. Similar evaluations of ERG results could possibly be used for humans with suspected generalized retinal degeneration.

Animals↗

Optimal discrimination of an Abyssinian cat recessive retinal degeneration: a short electroretinogram protocol is more efficient than a long one.

AIM: To determine the diagnostic efficiency of scores in a long protocol ectroretinogram (ERG) for Abyssinian cat slow recessive rod/cone dystrophy. METHODS: Kittens (n = 22) were bred from homozygous,affected and heterozygous normals. Ophthalmoscopy was regularly performed and disease signs noted. Cats (age > or = 8 months, 40 sessions, 1-3 repeats) were dark-adapted overnight, anaesthetized and simultaneous binocular ERG recorded using a long protocol. Conventional a- and b-amplitudes and peak implicit times were measured and b/a ratios calculated, initially only for ERG to the maximum photopic and scotopic stimulus. Principal components factor analysis was applied to various subsets of these scores plus age at testing. RESULTS: Six cats with ophthalmoscopic change were classed as affected. Three cats, one tested three times, were suspect. The rest were considered normal. The first analysis, of 80 eyes and 37 parameters, showed that the first factor was the only effective one. Using it, the groups overlapped 5%, scotopic amplitudes and b/a ratios loaded higher than peak times, the eyes were very similar, and age and photopic b/a ratios loaded poorly. The groups were discriminable with all the data. A second analysis, with eyes averaged and the 20 measures loading over 0.5 on the first factor, showed better group separation on factor I alone. An iterative search with varying data sets found that factor I was optimal, with eight ERG measures to the three brightest scotopic and one brightest photopic response. It produced a large absolute separation and classified the suspects consistently. With b/a ratios on these four ERG also included, 12 parameters gave better separation. CONCLUSION: Twelve scores on four ERG separate affected from normal cats with a wide gap and consistently classify suspects. It may work for earlier ages. Additional data probably adds noise. This combination of optimal scores needs confirmation in new data.

Animals↗

Light rise of the human electroretinogram is normal in retinitis pigmentosa.

AIM: To determine if the electroretinogram (ERG) light rise is reduced below normal in patients with retinitis pigmentosa (RP) and whether it is greater in patients with smaller ERG. METHODS: Both eyes of 31 normal subjects and 59 subjects with RP had photopic ERGs on ISCEV standard and brighter backgrounds, before and after dark adaptation. Recordings <2.5 micro V were excluded. RESULTS: Ratios of amplitudes before and after dark adaptation varied little. The b-wave averaged 1.88 (SD 0.41) in normal subjects and 1.66 (SD 0.62) in RP subjects, and a-waves averaged 1.44 (SD 0.42) and 1.31 (SD 0.73), respectively. None of eight t-tests were significant (<2.4). There was a positive (not negative) correlation between RP subjects' initial b-wave amplitude and light rise but not for a-waves. A-wave light rises were smaller. CONCLUSION: Retinitis pigmentosa does not reduce the light rise of recordable ERG. The light rise of the ERG is larger in those RP subjects with larger initial b-waves. This confirms previous findings. The difference between a- and b-waves in RP suggests post-receptoral processes are involved.

Case-Control Studies↗

Transient and steady state focal and pattern electroretinogram nerve section losses in cats with unilateral optic.

This study shows the ketamine/xylazine anaesthetised cat is a useful model for the effect of unilateral optic nerve section on pattern electroretinograms (PERGs), especially if stimuli extending to previously untested low spatial frequencies and preferably down to the focal ERG (FERG) are included. The transient reversal rate, seldom used in animals,has advantages over steady state recording. Transient PERGs had signs of true spatial tuning, a higher amplitude and signal noise ratio and showed the effect of optic atrophy at low spatial frequencies more rapidly.

Animals↗

Swelling and loss of photoreceptors in chronic human and experimental glaucomas.

OBJECTIVE: To determine whether outer retinal changes occur in chronic, presumed primary open-angle glaucoma (POAG). METHODS: The outer retinas from 128 human eyes with a diagnosis of chronic glaucoma (presumably POAG in most cases) and 90 control eyes were examined histologically by 3 masked observers for photoreceptor swelling and loss. Retinas from 9 rhesus monkeys with glaucoma induced experimentally by laser trabecular destruction were compared with 7 fellow (control) eyes. The mean pressure elevations in the eyes with laser trabecular destruction ranged from 26.6 to 53.6 mm Hg with durations varying from 7 to 33 weeks. RESULTS: Swelling of the red- and green-sensitive cones was observed in a statistically significantly greater proportion of human eyes with presumed POAG compared with the control eyes. Patchy loss of red/green cones and rods was also found in some of the glaucomatous retinas. In a subset of the human eyes with end-stage disease, cone swelling was a variable finding. Although no photoreceptor loss was found in the 9 monkey eyes with experimental glaucoma, 8 had swelling of their red/green cones that was remarkably similar to that seen in the human eyes. Swelling was not present in any of the control monkey eyes. CONCLUSIONS: The photoreceptors are affected by chronically elevated intraocular pressure. CLINICAL RELEVANCE: These findings may explain some of the abnormalities of color vision and the electrophysiological effects that have been observed in patients with POAG.

Aged↗

Standard for pattern electroretinography. International Society for Clinical Electrophysiology of Vision.

The pattern electroretinogram (PERG) is a retinal response evoked by viewing an alternating checkerboard or grating. It receives clinical and research attention because it can provide information about inner retinal cells and the macula. However, clinicians may have trouble choosing between different techniques for recording the PERG that have been described in the literature. The International Society for Clinical Electrophysiology of Vision has prepared a standard for a basic PERG recording procedure to aid new users in obtaining reliable responses and to encourage more uniformity among existing users.

Clinical Protocols↗

Multifocal, pattern and full field electroretinograms in cats with unilateral optic nerve section.

AIM: To look for a subcomponent of the mFERG generated at the optic nerve head and increasing in latency with distance from it. To compare multifocal electroretinogram (mFERG, mPERG) changes to those in full field ERGs and transient and steady state pattern and focal ERGs (PERGs, FERGs) in cats with total unilateral optic nerve section. METHOD: We recorded multifocal flash ERGs (mFERGs) at three levels of intensity and multifocal pattern ERGs (mPERGs) within 61 equal areas after total unilateral optic nerve section in five long term (> 18 month) survival cats, as part of a long term serial study of full field flash and pattern ERG changes to many stimuli, in a larger population. Cats were anaesthetised with Ketamine/Xylazine and wore Henkes electrodes with 6mm artificial pupils. Intact retinal circulation was verified by fluorescein angiography and optic nerve section by retinal photography and histology. We compared the mean and mean summed multifocal responses, from the normal and denervated eyes. We also compared the mean interocular difference around the area centralis and as a function of distance from the optic nerve head, across the horizontal meridian for the mFERG to the most intense stimulus. The degree of change was compared to that in other types of ERG, in the larger set of cats. RESULTS: mFERGs were similar across cats. Response density was flat with no prominence at the area centralis. Average summed mFERGs were similar in the normal and denervated eye. In the interocular differences a component near OP2 was reduced in the first kernel to the most intense stimulus, near OP1 and OP3 in the second kernel and locally, there was a hint of a component near OP2, which varied in latency in a ring around the disk and at the area centralis. Nevertheless, no component could be seen, varying in latency with distance from the optic nerve head, across the horizontal meridian. No mPERG was recordable in these conditions. Full field PERGs and FERGs were very reduced. Full field flash ERG amplitude changes were small (4-20%) and slower to appear than PERG changes. Degree of ERG reduction and correlation with PERG losses was greatest for the mesopic OPs, low for the scotopic tests (STR, ERG and OPs) and near zero for the mesopic ERG. The mFERG and mesopic ERG both lost OPs without overall amplitudes. CONCLUSIONS: The cat mFERG does not have a component, varying in latency with distance from the optic nerve head. The only change was qualitiatively similar to that in the light adapted ERG. With intense stimuli there were local changes around the time of OP2 near the area centralis which might be explained by local variations in ganglion cell density.

Animals↗

Reproducibility of ERG responses obtained with the DTL electrode.

Previous investigators have suggested that the DTL fibre electrode might not be suitable for the recording of replicable electroretinograms. We present experimental evidence that when used adequately, this electrode does permit the recording of highly reproducible retinal potentials.

Electrodes↗

Etoposide as a virocidal anticytomegalovirus therapy: intravitreal toxicology and pharmacology in rabbits.

BACKGROUND: Although Cytomegalovirus (CMV) retinitis is now a common intraocular infection, current therapy is only virostatic so ongoing treatment is required. Etoposide was found to be virocidal for CMV in laboratory experiments and it might prove to be beneficial clinically. We investigated the toxicity and intraocular concentration of etoposide (VP16) and its new analogue etoposide-phosphate (VP16P) following intravitreal injections in rabbit eyes. METHODS: First a sequential dose-response was assessed with flash electroretinogram for both eyes of light- and dark-adapted rabbits (n = 7; one rabbit for each dose) over a range of light intensities before and after intravitreal injection of VP16 or VP16P to one eye; the other eye was injected with normal saline as a control. A multidose study was then performed on four rabbits. A non-toxic dose of VP16P (50 or 75 g) was injected into the vitreous of one eye on four occasions 1 week apart. A photopic electroretinogram was performed before the first injection and 6 weeks after the last injection. All the eyes from the electroretinogram studies were fixed in formalin, placed in paraffin, then stained with haematoxylin and eosin and examined under a light microscope. To determine the time-course of the intraocular concentrations of VP16P a sequential pharmacokinetic study was performed using a further 12 rabbits. Each rabbit was injected with 50 g VP16P to one eye and 75 g VP16P to the other eye. Three of these rabbits were killed at 1, 3, 6 and 9 h after injection. Samples of vitreous were assayed for both VP16 and VP16P using HPLC. An in vitro dose response assay was performed using third-passage bovine retinal pigment epithelial (RPE) cells cultured in Dulbecco's modified Eagles medium with fetal calf serum. The effect of a log-dose increment of VP16P on the RPE cell proliferation was assessed using tritiated thymidine incorporation. RESULTS: The electroretinogram studies suggested that VP16 was toxic even with the 10 g dose. For VP16P a toxic effect was noted following injection of a single dose greater than 100 g. Multiple injections of 50 or 75 g VP16P did not produce a toxic response. Histological examination demonstrated significant abnormality only with the 500 g dose of VP16 or VP16P. VP16P was rapidly metabolized to VP16 in the eye, producing concentrations of 2.0 g/mL or more for up to 9 h following a 75-microg dose. This suggests that the electroretinogram findings following VP16 injections were confounded by a toxic effect of the ethanol solvent (which is absent from the VP16P preparation). VP16P was quite potent, the ID50 was about 0.1 g/mL for bovine RPE cells in the in vitro assay. DISCUSSION: These results indicate that multiple 75-gVP16P intravitreal injections were not toxic to the rabbit eye and provide a therapeutic intraocular concentration for up to 9 h after the injection.

Animals↗

Absence of ganglion cell subcomponents in multifocal luminance electroretinograms.

Multifocal flash electroretinograms (ERG) were recorded binocularly (n = 18). Areas were equal or scaled with excentricity. The latter were expected to increase the total amplitude if ganglion cell subcomponents were involved. Amplitudes were intercorrelated and the factor structure was established. Scaling had no influence on amplitudes or on factors. Reliability and sensitivity were high. The second kernel first slice from the nine hexagons across the midline showed differences near the macula but no component increasing in latency with distance from the disc. Thus, multifocal flash ERG have linear spatial summation and no ganglion cell subcomponents.

Electroretinography↗

Widespread choroidal insufficiency in primary open-angle glaucoma.

PURPOSE: The purpose of this study was to investigate choroidal perfusion in glaucoma, using histological and angiographic techniques. METHODS: We examined the choroidal vasculature in clinicopathological slides from 25 cases of primary open-angle glaucoma, five cases of optic atrophy, and 18 normal eyes. We measured choroidal thickness at fixed distances from the disk margin with light microscopy. Using a quantitative computer image analysis system, we established the depth of all vessels and the best fitting diameter and width-to-length ratio for each vessel in three pairs of eyes. Separate statistical analyses were done on the parapapillary area and the whole choroid. We compared standard fluorescein angiographic measures to peak choroidal filling time in a further 78 glaucoma and 84 normal eyes. RESULTS: Choroids were significantly (approximately 50 microns) thinner in glaucoma than in normal or optic atrophy irrespective of fundal position. Vessel frequency and mean diameter, relative to normal, showed greatest decrease near the choriocapillaris. Peak choroidal filling was the only fluorescein angiographic measure that was significantly delayed in glaucoma irrespective of age. CONCLUSIONS: Reduced choroidal thickness in primary open-angle glaucoma is primarily due to loss of the innermost choroidal vessels. Overall size decreases without significant flattening. These changes are not seen with optic atrophy alone and may be correlated with the delayed choroidal perfusion seen in fluorescein angiography.

Aged↗