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Biomedical subjects

Vaegan

Publications and source records attributed to Vaegan.

At least 19 recordsLinked to original sources
PubMed2000

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↗
PubMed2000

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↗
PubMed2000

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↗
PubMed1999

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↗
PubMed1999

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↗
PubMed1997

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↗
PubMed1997

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↗
PubMed1995

Amplitude scaling relationships of Burian-Allen, gold foil and Dawson, Trick and Litzkow electrodes.

The bipolar Burian-Allen electrode represents the International Society for Clinical Electrophysiology of Vision standard for recording the electroretinogram. With prolonged recording there is a high risk of corneal abrasion from the electrode, while alternatives such as gold foil electrodes or fibers represent less risk. The standards require that alternative electrodes be demonstrated to give equivalent waveform and amplitudes. Electroretinograms were recorded with the bipolar Burian-Allen electrode and four alternative electrode configurations: a unipolar Burian-Allen electrode, a bipolar and monopolar gold foil electrode and a Dawson, Trick and Litzkow fiber electrode with all other recording conditions identical. The results represent a guide for comparisons of electroretinograms between studies using these electrodes. Recordings were made from two subjects for all five electrode configurations and six additional subjects with unipolar gold foil and bipolar gold foil electrodes alone. Flash stimuli over a range of intensities from full intensity to -1.5 log units were used. Recordings were repeated in the one session and on a subsequent session to provide test-retest reliabilities. Significant (p < 0.0001) differences in b-wave amplitude resulting from electrode type and intensity were demonstrated. The unipolar Burian-Allen and unipolar gold foil electrodes produced the greatest amplitude responses. The alternatives to the bipolar Burian-Allen electrode were equally or more reliable. The Dawson, Trick and Litzkow electrode produced lower-amplitude response than the bipolar Burian-Allen electrode but was the only one with significantly greater between-session reliability.

Analysis of Variance↗
PubMed1995

Flash and pattern electroretinogram changes with optic atrophy and glaucoma.

We investigated recent reports that, contrary to common belief, glaucoma can affect flash as well as pattern electroretinograms. An extensive flash and pattern electroretinogram test protocol was used in a large sample of glaucoma patients and age-matched controls who were either visually normal or had other optic nerve diseases. All electroretinogram parameters were reduced and delayed in normal people > 55 years of age. The effect did not increase in later decades. In patients aged < or = 55 years, flash electroretinograms showed mild reductions and delays from optic atrophy alone. Glaucomatous ERG changes were larger and increased with disease severity. Pattern electroretinograms and oscillatory potentials were almost equally reduced in optic atrophy and all degrees of glaucoma. Mildly affected patients > 55 years of age had similar electroretinogram change to age-matched normals in most conditions. Advanced glaucoma patients showed similar differences from normal irrespective of age. This suggests that direct diagnostic application of these results to older patients will be difficult, that the ERG changes in glaucoma cannot be attributed simply to optic atrophy and that additional widespread outer retinal damage occurs in glaucoma.

Age Factors↗
PubMed1994

Effect of kainic acid and NMDA on the pattern electroretinogram, the scotopic threshold response, the oscillatory potentials and the electroretinogram in the urethane anaesthetized cat.

Kainic acid (KA, 12.5-100 nmol) or N-methyl-D-aspartate (NMDA 25-250 nmol) was injected into the vitreous of one eye of urethane anaesthetized cats. Pattern electroretinograms (PERGs) were recorded to transient contrast reversing bars. Scotopic luminance electroretinograms (ERGs) were recorded to blue flashes. All doses of KA reduced the oscillatory potentials (OPs), PERG and focal ERG (FERG). At 50 nmol KA, the b-wave and scoptic threshold response (STR) were normal. At 100 nmol KA, the STR was absent and the b-wave reduced by over 50%. OPs and STRs were reduced in all NMDA injected eyes. NMDA at 25 nmol enhanced the FERG, PERG, and b-wave and high doses (above 150 nmol) reduced them. Light microscopic examination of retinas showed 25 nmol KA only damaged dendrites of ganglion cells. NMDA damage was slight with < 200 nmol. These data show that the cat PERG has a proximal component which is very sensitive to low doses of KA; the PERG and FERG are very similar; the STR and PERG are generated by different structures and that the OPs and the FERG and PERG are all generated close to the ganglion cell layer, proximal to the STR.

Animals↗
PubMed1994

Development of pattern ERG and pattern VEP spatial resolution in kittens with unilateral esotropia.

PURPOSE: To follow the development of strabismic amblyopia longitudinally by comparing mean amplitudes and the visual spatial resolving ability of retinal and cortical pattern responses at various stages of postnatal development in unilateral iatrogenic convergent strabismic kittens. METHODS: Surgery to produce iatrogenic convergent strabismus was performed on 20 kittens at 3 weeks of age; three kittens were used for controls. The monocular transient pattern electroretinogram (PERG) and pattern visual evoked potential (PVEP) were recorded simultaneously on the 23 kittens throughout development. RESULTS: The PVEPs of the strabismic eyes were very reduced at 4 to 5 postnatal weeks (P < 0.01). The reduction increased at 6 to 16 weeks but was even worse at 17 to 30 weeks. The PERG of the squinting eye showed only a slight reduction in the first 4 to 5 weeks of age (P > 0.05), the decrease of responses was significant (P < 0.01) at 6 to 16 weeks and 17 to 30 weeks. At 4 to 8 weeks of age, the PVEP evoked through the unoperated eye in kittens consisted mainly of two positive components of similar amplitude. During development, the slow component decreased in comparison to the fast one, and its peak shifted forward until it merged into the fast (P100) component. CONCLUSIONS: Esotropic amblyopia did affect the PERG and the PVEP in the amblyopic eye, but the effect on the PERG was less severe, had slower onset, and did not continue as long as for the PVEP.

Amblyopia↗
PubMed1991

Selective reduction of oscillatory potentials and pattern electroretinograms after retinal ganglion cell damage by disease in humans or by kainic acid toxicity in cats.

We recorded pattern electroretinograms, scotopic threshold responses, oscillatory potentials and ganzfeld flash electroretinograms in patients with glaucoma or other optic nerve diseases and in cats with inner retinal damage caused by intravitreal injections of kainic acid. In both studies, the scotopic b-wave and the scotopic threshold responses were normal but the oscillatory potentials and pattern electroretinograms were not. The photopic b-wave was also often reduced in patients with scotopic oscillatory potential reduction, and the reduction was proportionate to the oscillatory potential change. Oscillatory potentials were as frequently reduced as pattern electroretinograms in both patient groups, and in the few cases where only one response was reduced, there was no bias toward either measure. In cats, the effects of intravitreal injection of various doses of kainic acid on the retina were evaluated electrophysiologically, and structural damage was assessed histologically. After 25 nmol of kainic acid, the pattern electroretinograms and oscillatory potentials were reduced but neither the b-waves nor the scotopic threshold responses, were affected. Histologic studies of retinas after this dose showed swollen dendrites that were restricted to the outer part (off-sublamina) of the inner plexiform layer. Serial semithin sections indicated that most, if not all, of the swelling was confined to dendrites of large ganglion cells. Our results indicate that the size and sensitivity of the oscillatory potential response may have a role in the diagnosis and management of early glaucoma and optic nerve disease, and that the photopic electroretinogram may give similar information.

Action Potentials↗
PubMed1991

High correlation between absolute psychophysical threshold and the scotopic threshold response to the same stimulus.

The scotopic threshold response (STR) is a negative potential to low intensity light recorded from the dark-adapted retina. It reflects inner retinal function. The STR is now recorded routinely as part of our electroretinography protocol. The projected absolute threshold calculated from the amplitude versus intensity function for the STR has been found to correlate well (r = 0.59) with the absolute subjective threshold to the same stimulus. The correlation holds for about 1.5 log units above normal. With further elevation the STR is usually abnormal or absent as b wave threshold is approached. The correlation would have been much greater were it not for this truncated range over which both are recordable. This report includes our findings in 127 patients and examines several disease groups. When the STR had a reduced and abnormal intensity series or was absent, the subjective threshold was elevated in almost all cases (92.2%). The converse relationship also held. When there was a discrepancy, recording problems were usually identified. Since the STR requires difficult, time consuming signal averaging for reliable recording, it may be adequate to record the subjective threshold alone to provide a relatively easily recordable indicator of inner retinal function. Additional STR recording will seldom be warranted.

Dark Adaptation↗
PubMed1990

Fundamental differences between the nonlinearities of pattern and focal electroretinograms.

We directly compared nonlinear kernels of normal human pattern electroretinograms (PERGs) and corresponding localized flash ERGs (FERGs). The FERG was triphasic and resembled an adaptive process because it decayed slowly without changing shape over several kernel orders and interpulse intervals. The PERG was biphasic in the slice nearest the diagonal of the second-order kernel, similar to the FERG in slices farther from this diagonal, and without power in higher-order kernels. The unique PERG features were short-term effects that immediately followed a contrast transition. The appearance-disappearance PERG had a triphasic first-order kernel and a biphasic second-order kernel. The latter was similar to, but half the size of, that for the contrast-reversal PERG. When the first off-diagonal slices of the two PERG second-order kernels were analyzed in detail, we found in both that the first positive peak was larger than the FERG at intermediate spatial frequencies. Both PERG peaks in the slice had a low contrast threshold and were linear with contrast. The three FERG peaks of the corresponding FERG slice had a higher threshold and were saturated with increasing contrast. These observations show that the PERG contains substantial pattern specific nonlinear components and cannot be dismissed as merely the nonlinear subcomponents of the corresponding FERG.

Contrast Sensitivity↗
PubMed1990

The effect of various anaesthetics on the spatial tuning of two major wave peaks in the transient pattern electroretinogram of the cat: evidence for pattern and luminance components.

The main PERG component of the transient contrast reversal pattern electroretinogram (PERG) in cats was a negative wave (3.5 microV average, SD 1.7 microV) peaking at about 130 msec (N130) with a spatial resolution above 5.5 c/deg, close to behavioural estimates. The early positivity (P35) was more variable, smaller and had lower spatial resolution. Different anaesthetic protocols affected both the waveform and the amplitude by spatial frequency functions. Responses of urethane anaesthetised cats were like those reported previously for decerebrate cats or cats paralysed and ventilated with N2O/O2/CO2 (75%/24%/1%). P35 was evoked only by coarse stimuli and N130 amplitude decreased linearly as spatial frequency increased. When the luminance response amplitude, predicted from the optical transfer function of the eye, was subtracted, spatial tuning appeared. An anaesthetic mixture of ketamine hydrochloride and xylazine depressed both P35 and N130 at low spatial frequencies while enhancing them at high frequencies. In paralysed animals ventilated with N2O/O2 (67%/33%) P35 was larger and recordable to 1.6 c/deg. Peak times were reduced and the inter-peak time halved. Other anaesthetics depressed the ERGs. These effects suggest that cats are a good model for studying N130 in isolation or its interaction with P35 and that both PERG peaks include luminance and pattern components.

Anesthetics↗
PubMed1990

Lateral interaction component and local luminance nonlinearities in the human pattern reversal ERG.

Two different mechanisms are presumed to contribute to pattern electroretinograms: non linearities of the local luminance response and nonlinear effects of lateral interactions. Previous attempts to discriminate the two components relied on the theoretical MTF of the optics. In this study, techniques of nonlinear systems analysis are used to extract the two components from the response to pattern reversal of different check sizes. The decomposition is based on the structure of the second order pattern reversal kernels alone. Detailed information about the two mechanisms can be gleaned from the kernel structure. The component properties are compared and discussed.

Contrast Sensitivity↗
PubMed1989

Urethane as a sole general anaesthetic in cats used for electroretinogram studies.

Cats are very sensitive to induction of anaesthesia by urethane. To anaesthetize cats with urethane, 1.0-1.3 g/kg, of freshly prepared urethane is administered intravenously at a rate of 1.92 g/h, while anaesthesia is maintained with 0.5% halothane in a 66%/33% nitrous oxide/carbogen gas mixture. Cats can then be maintained for up to 3 days by intravenous infusion at a rate of 4 ml/h of a 100 ml solution containing 50 IU heparin, 2.4 mg atropine, 4.7 g anhydrous D-glucose, and 240 mg urethane/kg. Using this anaesthetic, excellent electroretinograms can be recorded with no interfering eye movements.

Anesthesia↗