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Intravitreal moxifloxacin: retinal safety study with electroretinography and histopathology in animal models.

PURPOSE: To determine whether moxifloxacin can be used safely as an intraocular antibiotic, retinal safety of intravitreal moxifloxacin was studied with electroretinography (ERG) and histopathology in animal models. METHODS: Moxifloxacin was injected into mouse eyes at intravitreal concentrations of 5 to 500 microg/mL and into rabbit eyes at 150 microg/mL. As the control, the vehicle was injected into the fellow eyes of each animal. Four weeks after injection, ERG recordings were performed, and animal eyes were processed for histologic examination. RESULTS: ERG studies showed no significant difference between control and moxifloxacin-injected eyes at any dose in either the mouse or rabbit model. Histologic examination revealed no retinal abnormality in mice at 5 to 100 microg/mL or in rabbits at 150 microg/mL intravitreal moxifloxacin. In mice at 500 microg/mL, occasional focal retinal necroses were observed, suggesting isolated retinal toxicity at this concentration of moxifloxacin. CONCLUSIONS: Intravitreal moxifloxacin, up to 100 microg/mL in mice or 150 microg/mL in rabbits, caused no ERG or retinal histologic abnormality. These results indicate that moxifloxacin is a safe intravitreal antibiotic in mouse and rabbit animal models. If proven safe and efficacious by further study in humans, intravitreal injection of moxifloxacin could be considered as an alternative to currently used antibiotics in selected patients with resistance or allergy to the more traditional antibiotics.

Animals↗

Electroretinography using contact lens electrode with built-in light source in dogs.

Electroretinography (ERG) is an effective method for the diagnosis of retinal disease. In the dog, dependable ERG recording is difficult without the use of an expensive device like a Ganzfeld full-field stimulator. The International Society for Clinical Electrophysiology of Vision has defined the standard flash stimulus condition (SF) and evaluation of the retina using the b/a ratio in humans. In dogs, evaluation using the b/a ratio has not been reported, whereas the intensity of SF has been defined. In this study, we performed a convenient ERG recording method using a contact lens electrode with a built-in light source (LED-electrode), and confirmed SF as reported previously. ERG recordings were performed on 15 healthy beagle dogs under sedation. We performed bilateral ERG at 12 different intensities after 30 min dark adaptation. After 10 min light adaptation, we recorded single flash cone and flicker cone response using the SF determined in this study. In this study, SF of 3.0 cd/m(2)/sec (6,000 cd/m(2), 0.5 msec) resulted in b/a=2. The intensity for rod response that recorded only the b-wave was 0.0096 cd/m(2)/sec (80 cd/m(2), 0.12 msec). We could achieve ERG for each response easily and smoothly under sedation, and without general anesthesia. Using an LED-electrode, we could perform more quantitative and reproducible ERG examinations than with traditional methods. We propose that the b/a ratio is the most useful parameter in ERG reporting for evaluating retinal function.

Animals↗

L/M cone ratios in human trichromats assessed by psychophysics, electroretinography, and retinal densitometry.

Estimates of the relative numbers of long-wavelength-sensitive (L) and middle-wavelength-sensitive (M) cones vary considerably among normal trichromats and depend significantly on the nature of the experimental method employed. Here we estimate L/M cone ratios in a population of normal observers, using three psychophysical tasks-detection thresholds for cone-isolating stimuli at different temporal frequencies, heterochromatic flicker photometry, and cone contrast ratios at minimal flicker perception--as well as flicker electroretinography and retinal densitometry. The psychophysical tasks involving high temporal frequencies, specifically designed to tap into the luminance channel, provide average L/M cone ratios that significantly differ from unity with large interindividual variation. In contrast, the psychophysical tasks involving low temporal frequencies, chosen to tap into the red-green chromatic channel, provide L/M cone ratios that are always close to unity. L/M cone ratios determined from electroretinographic recordings or from retinal densitometry correlate with those determined from the high-temporal-frequency tasks. These findings suggest that the sensitivity of the luminance channel is directly related to the relative densities of the L and the M cones and that the red-green chromatic channel introduces a gain adjustment to compensate for differences in L and M cone signal strength.

Color Perception↗

A new electrode for electroretinography.

Clinical electroretinography is an uncomfortable, disquieting experience for a patient because of the contact lens electrodes used. Such electrodes are either expensive to buy or difficult to make. An aluminized Mylar electrode performs satisfactorily, elicits minimal patient apprehension or discomfort without topical anesthesia, is simple to make, and is disposable.

Aluminum↗

[The effect of brain-derived neurotrophic factor on the rat electroretinography after pressure-induced ischemic injury].

Brain-derived neurotrophic factor (BDNF) or normal goat serum (NGS) was injected intravitreously in each 11 wistar albino rats two days before the induction of ischemia. Retinal ischemia was induced in 22 rats by increasing intraocular pressure to the threshold level which extinguished the electroretinography (ERG) b-wave individually, and maintaining for 90 minutes. The ERG b-wave of the BDNF-treated rats recovered to 80.5 +/- 24.4% of their normal amplitude three days after ischemia, while that of the NGS-treated rats recovered only to 11.1 +/- 5.3%. Statistic analysis showed that the recovery level of ERG b-wave after ischemia in the BDNF and NGS treated rats was significantly different (P < 0.01). The results suggest that BDNF could promote the recovery of the retinal electrophysiologic function from ischemia induced by high intraocular pressure.

Animals↗

Evaluation of patients with visual field defects following macular hole surgery using multifocal electroretinography.

PURPOSE: To investigate patients with visual field defects following macular hole surgery to determine the cause of such defects, specifically with reference to ischemic damage versus mechanical trauma. METHODS: Five patients with known visual field defects following macular hole surgery were studied with Goldmann perimetry, Humphrey automated perimetry, and multifocal electroretinography (MERG). Three patients returned at a later date for nerve fiber layer analysis. RESULTS: None of the five patients demonstrated evidence of a- or b-wave loss on MERG in the regions corresponding to the visual field defects. Two of three patients studied with the nerve fiber layer analyzer demonstrated significant loss of nerve fiber layer thickness in the quadrant corresponding to the field defect. CONCLUSION: The normal MERG results indicate that the possibility of an arteriolar occlusion as the principal cause for the defects is unlikely in most cases. Data suggest that the site of damage is in the nerve fiber layer, although the specific cause of this damage remains to be determined.

Aged↗

A new method of cone electroretinography: the rapid random flash response.

A new procedure is described for cone electroretinography using a cross-correlation method of signal processing to give the response to flash stimuli which occur at randomly timed intervals. The output waveform is different than the usual repetitive flicker response, and can be presented on any desired time base. An unfamiliar aspect of this process is that most of the random time intervals between consecutive stimuli are shorter in duration than the output waveform. For the parameters described, the output waveform gives the response to approximately 1,640 stimuli in 65.5 sec., with a signal-to-noise ratio which is higher than that obtained when conventional averaging techniques are used over similar time periods. This allows more precise and statistically significant estimates to be made of the time and amplitude parameters of the cone response. Normal values are given for implicit (delay) time and amplitude, and examples are provided for comparison of the random flash response and conventional average electroretinograms (ERG's) in normal subjects and patients with retinal degeneration.

Adult↗

[Topographic mapping of retinal function with a scanning laser ophthalmoscope and multifocal electroretinography using short M-sequences].

A new method of multifocal electroretinography making use of scanning laser ophthalmoscope with a wavelength of 630 nm (SLO-m-ERG), evoking short spatial visual stimuli on the retina, is proposed. Algorithm of presenting the visual stimuli and analysis of distribution of local electroretinograms on the surface of the retina is based on short m-sequences. Mathematical cross correlation analysis shows a three-dimensional distribution of bioelectrical activity of the retina in the central visual field. In normal subjects the cone bioelectrical activity is the maximum in the macular area (corresponding to the density of cone distribution) and absent in the blind spot. The method detects the slightest pathological changes in the retina under control of the site of stimulation and ophthalmoscopic picture of the fundus oculi. The site of the pathological process correlates with the topography of changes in bioelectrical activity of the examined retinal area in diseases of the macular area and pigmented retinitis detectable by ophthalmoscopy.

Adult↗

[A case of cerebellar degeneration with schizophrenia-like psychosis, severe iron deficiency, hypoceruloplasminemia and abnormal electroretinography: a new syndrome?].

A 33-year-old male patient began to develop schizophrenia-like symptoms and slowly progressive cerebellar ataxia. He was 170 cm tall and he had mild frontal baldness. Psychiatrically he was aconative, only willing to do nothing all day long after admission. He had neither hallucinations nor delusions, and his mental acuity was normal. Neurological examination revealed positive cerebellar signs including clumsiness in F-N-T and K-H-T and dysdiadochokinesis. He could neither stand up nor walk because of ataxia. The brain MRI showed severe cerebellar atrophy with normal basal ganglia. His EEG and the value of NCV were within normal range, whereas electroretinography showed a notable abnormality, pointing to the extremely small b-wave, resulting in a negative shape of the ERG. Although he was eating sufficiently, the level of serum iron and ferritin remained constantly low. The serum copper level was within normal range, whereas the serum ceruloplasmin level was mildly decreased. A hepatic biopsy indicated no accumulation of copper or iron. This case suggests the importance of the investigation of the serum iron and ceruloplasmin levels in patients who have cerebellar degeneration with psychosis.

Adult↗

Toxic maculopathy part II: A result of quinine usage as demonstrated by fluorescein angiography and electroretinography.

In this paper, further investigation by fluorescein angiography and electroretinography (ERG) was undertaken to substantiate the possible toxic maculopathy due to quinine usage. Again, positive Amsler chart tests were found in 3 of 14 (21%) of the drug addicts with blurred vision, a common complaint among these patients. The results of 5 fluorescein angiography examinations demonstrated no leakage of dye, especially in the macula. Twenty-four ERG examinations revealed no statistical differences between the test group patients and the control subjects. It was concluded that there is a definite need to carefully examine the eyes of any person who has used quinine for a long time since positive Amsler chart tests were found in 37% of the drug addicts.

Electroretinography↗

Effect of intraocular pressure on optic disc topography, electroretinography, and axonal loss in a chronic pressure-induced rat model of optic nerve damage.

PURPOSE: To characterize the effect of intraocular pressure (IOP) on optic disc topography, retinal function, and axonal survival in a model of IOP-induced optic nerve damage in rat. METHODS: Hypertonic (1.75 M) saline was injected into an episcleral vein of one eye of 49 Brown Norway rats, with the fellow untreated eye serving as the control. During the 1 to 3 months of follow-up, IOP was measured twice weekly in conscious animals with a handheld tonometer, and changes in disc topography and retinal function were monitored with scanning laser tomography and electroretinography (ERG), respectively. Peak IOP elevation in the experimental eye compared with the fellow control eye (peak deltaIOP), integral of IOP elevation over time (deltaIOP integral), and days of IOP elevation were calculated. Axon counts were obtained from electron micrographs of the sectioned optic nerves. RESULTS: Progressive cupping was found in 9 (56.3%) of 16 eyes with peak deltaIOP of more than 15 mm Hg and in none of 21 eyes with peak deltaIOP less than 15 mm Hg. A strong correlation between deltaIOP integral and progressive cupping was also found, but not with days of IOP elevation. ERG abnormalities (limited to the b-wave) were found in 11 (64.7%) of 17 eyes with peak deltaIOP of more than 15 mm Hg and in 2 (8.7%) of 23 eyes with peak deltaIOP of less than 15 mm Hg. Neither of the other IOP parameters was predictive of ERG damage. The proportion of surviving axons was negatively correlated to both deltaIOP and deltaIOP integral (P <or= 0.001). Progressive cupping was evident only with more than 55% axonal loss. Similarly, ERG results remained mostly within normal limits for low to moderate axonal loss, but were markedly abnormal with more than 70% axonal loss. CONCLUSIONS: Structural and functional changes in this model are best correlated to peak deltaIOP and not to duration of IOP elevation, suggesting the existence of an IOP-related damage threshold.

Animals↗

[Optic disc pits and maculopathy (electroretinography study)].

An ERG examination according to the international standard was made in 55 patients with pits in the optic nerve disc. 19 of them suffered from concurrent maculopathy. Electroretinography revealed in scotopic responses a significant reduction of amplitudes of oscillatory potentials and reduction of potentials of the b wave in standard (maximal) reactions. Even more markedly the cone reactions and flicker were reduced--responses to intermittent (30 Hz) photostimulation. The authors consider maculopathies with pits a separate nosological unit with possible hereditary transmission. ERG signalizes a more extensive alteration of retinal structures than affection of the centre, probably on the basis of the circulation. Maculopathies with pits are also characterized by the fact that the dramatic drop of amplitudes is associated with the patient's age or the duration of the disease.

Adolescent↗

[The measurement of multifocal electroretinography].

PURPOSE: Discussing the testing procedure of multifocal electroretinography(ERG). METHODS: The testing procedure of 131 multifocal ERG records was reviewed. RESULTS: Some variable factors existed in the measurement of multifocal ERG. These factors included the subject's co-operation, the mounting of electrode, the fixation of tested eye and adjustment of focus. The good records of multifocal ERG depend upon the skill of the operator. CONCLUSION: The testing procedure of multifocal ERG must be standardized so as to ensure the reliability and repeatability of the results.

Adult↗

Evaluation of hydroxychloroquine retinopathy with multifocal electroretinography.

BACKGROUND AND OBJECTIVE: To describe the changes revealed by multifocal electroretinography (ERG) in patients taking hydroxychloroquine. PATIENTS AND METHODS: Six patients being treated for various inflammatory conditions with hydroxychloroquine for periods ranging from 8 months to 7 years were consecutively evaluated. Each examination included measurement of Snellen visual acuities, Amsler grid assessment, and automated visual field testing. In some cases, funduscopic examinations were complimented by photography and fluorescein angiography. Multifocal ERG was performed for all patients. RESULTS: Three patients (six eyes) were found to have distinctive abnormalities on multifocal ERG consisting of pericentral depression of ERG signals. The abnormalities on multifocal ERG corresponded with the patients' subjective descriptions and the visual field depiction of their pericentral scotomas. All affected patients had been taking hydroxychloroquine for at least 7 years. One patient with generalized depression on multifocal ERG had possible hydroxychloroquine retinopathy. Two patients (three eyes) had relatively normal results on multifocal ERG. CONCLUSION: Multifocal ERG objectively demonstrates depression of signals in the perifoveal region in visually symptomatic patients with long-term hydroxychloroquine use. Even patients with normal visual acuity and no fundus abnormalities can have abnormal results. Although we have not yet identified patients with abnormalities on multifocal ERG before the onset of symptoms, multifocal ERG may be useful in monitoring patients at risk and may provide an earlier opportunity to identify maculopathy.

Adult↗

[Electroretinography in the diagnosis and study of pathogenesis of X-linkage retinoschizis].

Due to an extensive variability of manifestations of X-linkage retinoschizis, there is a need in a differential diagnosis of it and of other hereditary retinal diseases. The method of electroretinography is often of primary importance in specifying a diagnosis in ophthalmology; it both enables the detection of new and more sensitive criteria of early and differential diagnosis and ensures a more profound understanding of changes occurring in the retina. A topical analysis of changes of the bioelectric activity taking place in different retinal layers and sections as well as a differential evaluation of the functional condition of neurons and glia Muller's cells in patients with X-linkage retinoschizis were accomplished within the framework of this study. The nature of the peak latency and of the b-wave amplitude in the electroretinogram (ERG) and in the mechano-electroretinogram (MERG) as well as of a low-frequency ERG is indicative of that Muller's cells are damaged; the damage severity is related with an intensity of the pathological process and can be objectively determined by the ERG examinations of patients. An analysis of sub-components of a low-frequency rheoelectroretinogram (RERG) shows weakened inhibitory inter-neuron connections in the retina, which is a sign of disease aggravation. The regularities of changes of retinal biopotential to blue light flashes under all registration conditions (ganz-feld, macular and rhythmical stimulation) differ from the ERG dynamics to other light stimuli, which is indicative of a significant role of the pathology of S-cone paths in the development of X-linkage retinoschizis.

Adolescent↗

[Electroretinography in nephronophthisis. Role of the Senior-Loken syndrome].

The authors report 20 cases of a syndrome named nephronophtisis and probably the same as the syndrome of medullar cystic disease. In all cases systematic electroretinography is performed. Nine cases show important deterioration of the outline. These cases can be included in the syndrome of Senior-Loken. The pathogenesis and familial character of this disease are discussed. The disturbances that appeared between the ocular and renal lesions suggest that there are probably two genes rather than a single pleiotropic gene.

Adolescent↗

[Clinical electroretinography in the dog. Part 3].

In this last part the preparation of the patient for the ERG is shown. Anesthesia, positioning, and retrobulbar injection technique are discussed. The protocol for recording the ERG is presented. The dog is dark adapted for 30 minutes. The level of adaptation is examined using a single flash of dim red light at various times. Rods and cones are stimulated separately by scotopically balanced red and blue flashes. After a single flash of bright white light the rods and cones are studied with flicker trains at 5, 12.5, 15 and 30 Hz. During dark adaptation the maximum b-wave amplitude increased from 13.8 +/- 8.4 microV to 49.3 +/- 16.3 microV. Bright white light stimuli resulted in b-wave amplitudes of 167.7 +/- 75.3 microV. There were always 6 oscillatory potentials visible on the b-wave. Scotopically balanced stimuli produced b-waves of 104 microV (red) and 116 microV (blue). It was found that older dogs had reduced b-wave amplitudes and longer peak times than younger dogs. The most common artefacts in electroretinography are discussed.

Acepromazine↗

[Flash full-field electroretinography in diseases with night blindness].

PURPOSE: The aim of this study is to present similarities and differences of electroretinograms in early stages of retinal diseases with nyctalopia. MATERIAL AND METHODS: Flash full-field electroretinography was done according to ISCEV standards and also with chromatic stimulations in patients with nyctalopia, who were diagnosed as various forms of congenital stationary night blindness and various types of retinitis pigmentosa, choroideremia, gyrate atrophy and also in patients with nyctalopia, because of unknown reason. ERG results were compared with normal values and with each other. RESULTS: In diseases with nyctalopia the function of peripheral retina is markedly abnormal and scotopic ERG is significantly reduced or even absent. In retinitis pigmentosa a-wave is small or absent especially scotopic but photopic ERG is also abnormal. Well preserved a-wave distinguished ERG of patients with stationary night blindness from the other progressive diseases of retina or choroid. CONCLUSIONS: In patients with nyctalopia using ERG is possible to obtain which retinal elements do not work but it is only start point to following diagnostic examinations, to make proper final diagnosis.

Adolescent↗