Retinal Dysfunction In Patients Research Articles

Multifocal electroretinogram changes in patients with retinal vein occlusion

Background Retinal vein occlusion (RVO) is one of the most common vascular retinal disorders that lead to macular edema. There is often discrepancy between visual prognosis and optical coherence tomography (OCT) changes. Multifocal electroretinogram (mfERG) provides useful information about retinal function in affected parts of the retina in patients with RVO.Purpose The aim of this study was to assess the functional changes in patients with RVO by mfERG and to correlate these changes with OCT findings in those patients.Patients and methods This is a prospective study of 30 eyes of patients with RVO, with their fellow eyes being taken as control. Thirteen eyes with central RVO, 12 eyes with branch RVO, and five eyes with hemi-RVO were included in the study. OCT to measure the central macular thickness was done in all patients. mfERG was also done in all patients. P wave amplitude and p wave implicit times were measured in the central area and all quadrants.Results mfERG responses were markedly affected in all quadrants in central RVO, in the affected quadrants in branch RVO, and in the affected hemiretina in hemi-RVO. The differences between the p amplitude and p implicit time between the affected eyes and the fellow eyes were statistically significant in all patients. There was a significant correlation between the central macular thickness and p amplitude in the affected half of the retina in hemi-RVO.Conclusion mfERG is a sensitive tool for assessment of retinal function in patients with RVO. mfERG can assess local retinal dysfunction in patients with RVO, which is sensitive to morphological changes detected by OCT.

Early and localized retinal dysfunction in patients with type 1 diabetes mellitus studied by multifocal electroretinogram.

To investigate the function of localized retinal areas in highly selected type 1 diabetes mellitus patients (DM1) with no or mild signs of diabetic retinopathy (NO DR and NPDR, respectively) and its correlation with age, diabetes duration and glycemic control. Multifocal electroretinograms (mfERG) were recorded in 35 eyes of 18 NO DR patients and 38 eyes of 19 NPDR patients. Thirty-one eyes of 17 normal subjects were enrolled as controls. N1-P1 response amplitude densities (RADs) and P1 implicit times (ITs) from isolated (R1: 0°-2.5°, R2: 2.5°-5°, R3: 5°-10°) and combined (R1 + R2, R2 + R3 and R1 + R2 + R3) annular rings and from four retinal sectors (nasal, N; temporal, T; superior, S and inferior, I) with increasing eccentricities up to 10° (S1, S2, S3, S1 + S2, S1 + S2 + S3) were measured. The statistical differences between DM1 groups and controls were tested by ANOVA. The electrophysiological data were correlated with age, duration of diabetes and glycated hemoglobin (HbA1c) level using the Pearson's test. MfERG RADs, but not ITs, from all isolated and combined rings and sectors up to 10° of foveal eccentricity were statistically different between DM1 groups compared to controls. No significant differences were found between NO DR and NPDR patients. The mfERG abnormalities of the central retinal areas were correlated significantly with age in both DM1 groups and with diabetes duration mainly in NPDR group. In DM1 patients, localized retinal dysfunction, described by reduced mfERG RAD, can be observed also in the absence of clinical signs of DR and it is related to aging.

Heteromeric KV2/KV8.2 Channels Mediate Delayed Rectifier Potassium Currents in Primate Photoreceptors.

Silent voltage-gated potassium channel subunits (KVS) interact selectively with members of the KV2 channel family to modify their functional properties. The localization and functional roles of these silent subunits remain poorly understood. Mutations in the KVS subunit, KV8.2 (KCNV2), lead to severe visual impairment in humans, but the basis of these deficits remains unclear. Here, we examined the localization, native interactions, and functional properties of KV8.2-containing channels in mouse, macaque, and human photoreceptors of either sex. In human retina, KV8.2 colocalized with KV2.1 and KV2.2 in cone inner segments and with KV2.1 in rod inner segments. KV2.1 and KV2.2 could be coimmunoprecipitated with KV8.2 in retinal lysates indicating that these subunits likely interact directly. Retinal KV2.1 was less phosphorylated than cortical KV2.1, a difference expected to alter the biophysical properties of these channels. Using voltage-clamp recordings and pharmacology, we provide functional evidence for Kv2-containing channels in primate rods and cones. We propose that the presence of KV8.2, and low levels of KV2.1 phosphorylation shift the activation range of KV2 channels to align with the operating range of rod and cone photoreceptors. Our data indicate a role for KV2/KV8.2 channels in human photoreceptor function and suggest that the visual deficits in patients with KCNV2 mutations arise from inadequate resting activation of KV channels in rod and cone inner segments.SIGNIFICANCE STATEMENT Mutations in a voltage-gated potassium channel subunit, KV8.2, underlie a blinding inherited photoreceptor dystrophy, indicating an important role for these channels in human vision. Here, we have defined the localization and subunit interactions of KV8.2 channels in primate photoreceptors. We show that the KV8.2 subunit interacts with different Kv2 channels in rods and cones, giving rise to potassium currents with distinct functional properties. Our results provide a molecular basis for retinal dysfunction in patients with mutations in the KCNV2 gene encoding KV8.2.

Vigabatrin can enhance electroretinographic responses in pigmented and albino rats

To evaluate the effects of the antiepileptic medication vigabatrin (VGB) on the retina of pigmented rats. Scotopic and photopic electroretinograms were recorded from dark- and light-adapted Long-Evans (pigmented) and Sprague Dawley (albino) rats administered, daily, 52-55 injections of 250 mg·kg(-1)·day(-1) VGB or 25-26 injections of 500 mg·kg(-1)·day(-1) VGB, or a corresponding number of sham injections. Sensitivity and saturated amplitude of the rod photoresponse (S, Rm(P3)) and postreceptor response (1/σ, Vm) were derived, as were sensitivity and amplitude of the cone-mediated postreceptor response (1/σ(cone), Vm(cone)). The oscillatory potentials and responses to a series of flickering lights (6.25, 12.5, 25 and 50 Hz) were studied in the time and frequency domains. A subset of rats' eyes was harvested for Western blotting or histology. Of the parameters derived from dark-adapted ERG responses, in both pigmented and albino rats, VGB repeatedly and reliably enhanced electroretinographic parameters; no significant ERG deficits were noted. No significant alterations were observed in ER/oxidative stress or in the Akt cell death/survival pathway. There were migrations of photoreceptor nuclei toward the RPE and outgrowths of bipolar cell dendrites into the outer nuclear layer in VGB-treated rats; these were never observed in sham-treated animals. Although VGB is associated with retinal dysfunction in patients and VGB toxicity has been demonstrated by other laboratories in the albino rat, in our pigmented and albino rats, VGB did not induce deficits in, but rather enhanced, retinal function. Nonetheless, retinal neuronal dysplasia was observed.

Comparison of different screening methods for chloroquine/hydroxychloroquine retinopathy: multifocal electroretinography, color vision, perimetry, ophthalmoscopy, and fluorescein angiography

To compare various screening methods for the early diagnosis of retinal dysfunction in patients with long-term chloroquine (CQ) and hydroxychloroquine (HCQ) treatment. Twenty patients with long-term CQ/HCQ treatment underwent ophthalmologic evaluation including visual acuity testing, ophthalmoscopy, fluorescein angiography, color vision tests, visual field and multifocal electroretinography (mfERG). In 14 patients, retinal dysfunction was indicated in the mfERG (reduced amplitudes and/or delayed implicit times) in the parafoveal area. Towards the periphery, the function was normal or only moderately reduced. Ophthalmoscopy and fluorescein angiography identified pathologic retinal changes in seven of these 14 patients. Six patients had normal mfERG, ophthalmoscopy, and fluorescein angiography. Results of color vision and visual field testing were variable even in patients with morphologic alterations. The use of mfERG may detect retinal dysfunction in a considerable number of eyes with normal ophthalmocopy and fluorescein angiography. The higher variability of color vision and visual field testing results suggests the use of mfERG as primary screening tool for retinal dysfunction in long-term CQ/HCQ treatment.

Retina in rheumatic diseases: Standard full field and multifocal electroretinography in hydroxychloroquine retinal dysfunction

Background: The purpose of this study was to evaluate and compare full‐field electroretinography (ERG) and multifocal electroretinography (mfERG) results in detecting retinal dysfunction in a large number of asymptomatic patients treated with hydroxychloroquine (Hy).Methods: Fifty eyes in 50 patients with rheumatic diseases who had been using Hy for a period of time ranging from 30-months to 15-years, and 25 eyes in 25 healthy controls, were evaluated. Receiver operator characteristic (ROC) curves were calculated to determine the sensitivity and specificity of abnormal values in patients compared to the normal controls.Results: Signal depression was observed on the mfERG of Hy‐treated patients. The most prevalent pattern was pericentral loss (19 eyes, 54.3 per cent), followed by full‐field loss (11 eyes, 31.4 per cent), and central loss (five eyes, 14.3 per cent). Conversely, depression of the amplitude responses to the full field ERG was observed in only 16 per cent of the cases. The areas under the ROC curves ranged from 0.4056 to 0.9012, with the mfERG values having the largest areas, whereas the full‐field ERG curves had the smallest area. The mfERG responses yielded the greatest sensitivity and specificity. In particular, the P1‐N1 wave amplitude (ring 2) and root mean square (RMS) amplitude (ring 1) had specificities of 76 and 88 per cent, respectively, at sensitivities of 90 and 86 per cent.Conclusion: A statistically significant retinal functional impairment was demonstrated by mfERG in the central two to 10 degrees in Hy‐treated patients. Therefore, mfERG may provide an objective measurement of retinal dysfunction in patients receiving Hy therapy.

Multifocal electroretinogram in retinal vein occlusion

Purpose To determine the effects of retinal vein occlusion (RVO) on multifocal electroretinogram (MF-ERG) parameters, to correlate MF-ERG and standard electroretinogram (ERG) and to correlate MF-ERG with findings of optical coherence tomography (OCT) in cases of RVO. Methods Both eyes of 50 patients with RVO and 50 eyes of 25 normal subjects were examined using MF-ERG, standard ERG, fluorescein angiography and OCT. The latency in millisecond (ms) and response density in nanovolt (nv/degenerations) were measured for each of four quadrant areas and central area. OCT was used to measure the foveal retinal thickness. Fluorescein angiography was used to measure retinal ischemia. Results Central retinal vein occlusion (CRVO) markedly affected all parameters of MF-ERG. In pathological quadrants in branch retinal vein occlusion, the response densities of MF-ERG were decreased and latencies of p-wave were prolonged. The MF-ERG responses obtained from eyes with RVO were significantly different ( P > 0.05) from derived from the fellow eyes. The amplitude of MF-ERG were abnormal in 40 eyes and implicit times were delayed in 48 eyes compared with normal subjects. While 30 Hz flicker implicit were abnormal in only 24 eyes with RVO. Implicit times were prolonged in eyes with macular ischemia than in eyes without ischemia. There were significant correlation between foveal retinal thickness measured by OCT and P response density MF-ERG in cases of retinal vein occlusion. Conclusion MF-ERG is more susceptible than standard ERG to eye changes of RVO due to the multiple frequencies of stimulation used to record MF-ERG response. MF-ERG could be sensitive indicator of underlying disease affecting the retinal in eyes with RVO. MF-ERG is useful for detecting local retinal dysfunction in patients with RVO and sensitive to morphological changes and functional disorders induced by RVO.

Evidence of Widespread Retinal Dysfunction in Patients with Stargardt Disease and Morphologically Unaffected Carrier Relatives

To characterize contrast sensitivity (CS) across the visual field for two achromatic spatial-temporal frequencies in 21 families with Stargardt disease (STGD) and to correlate psychophysical impairment with patterns of change in multifocal electroretinography (mfERG). Twenty-seven eyes from patients with STGD, 16 eyes from asymptomatic relatives, and 44 age-matched control eyes were included. Chromatic CS function was assessed by comparing protan, deutan, and tritan (Cambridge Color Test; Cambridge Research Systems Ltd., Rochester, UK) and anomaloscope measures (IF-2; Roland Consult, Wiesbaden, Germany). Achromatic CS measures were obtained with custom-made software in nine locations by using randomly interleaved staircases. The first task-low spatial frequency (LSF)-matched the known frequency-doubling method that is believed to activate the magnocellular pathway preferentially. The second included an intermediate spatial frequency (ISF, 3.5 cyc/deg). mfERGs (RETIscan; Roland Consult) were also obtained. Relatives were screened for ABCA4 mutations by ABCR400 microarray and direct sequencing. Central impairment of achromatic and chromatic CS (along the three isolation axes) was observed in STGD. LSF and ISF tasks revealed significant and widespread dysfunction in patients and their morphologically unaffected relatives, 80% of whom were found to be ABCA4 mutation carriers. Significant reduction of P1 amplitudes was also observed in both groups. CS function is impaired in patients with STGD at distinct spatial-temporal frequencies, which, in addition to the color vision deficits, suggests dual impairment of the magno- parvocellular pathways. STGD morphologically unaffected carriers may show patterns of psychophysical dysfunction that are mirrored by abnormal mfERG responses.

Electroretinographic abnormalities in multiple sclerosis: possible role for retinal autoantibodies

Multiple sclerosis (MS) has been associated with inflammation of the uveal tract, suggesting an immunological link between the uvea and central nervous system (CNS) in this disease. The retina is embryologically derived from the CNS, and it is conceivable that retinal antigens may also be recognized by the immune system in MS. Electroretinographic abnormalities, as well as retinal autoantibodies, have previously been described in MS. We performed this study to further explore the possibility of retinal autoimmunity in MS. Thirty-four patients with clinically definite MS and thirty-seven healthy controls were recruited. All patients and controls had standard electroretinographic (ERG) testing done, as well as a brightflash ERG protocol to isolate rod photoreceptor function. Patient and control sera were analyzed for the presence of antiretinal antibodies using Western blot techniques. We found statistically significant differences between MS patients and controls in four ERG parameters. In the MS group, implicit times of the rod-cone b-wave response, cone b-wave response, and rod photoreceptor response were increased. The amplitudes of the photopic oscillatory potentials were reduced in the MS group. Patients with the highest titres of retinal autoantibodies had delayed rod-cone b-wave implicit times and diminished photopic oscillatory potential amplitudes. We report ERG evidence of retinal dysfunction in patients with MS. We also report the first use of the brightflash ERG protocol in MS, which demonstrated rod photoreceptor dysfunction. Patients with the highest antiretinal antibody titres had abnormal ERG recordings. Retinal autoimmunity is a possible explanation for these observed ERG abnormalities in MS patients.

Retinal dysfunction in patients with chronic Chagas' disease is associated to anti‐Trypanosoma cruziantibodies that cross‐react with rhodopsin

To investigate retinal involvement in chronic Chagas' disease, we performed electroretinography and retinal fluorescein angiography studies in chagasic patients. Our results demonstrated a dissociated electrophysiological response characterized by both an abnormal reduction of the electroretinographic b-wave amplitude and a delayed latency, under the dark-adaptated condition. These alterations are compatible with a selective dysfunction of the rods. Antibodies raised against Trypanosoma cruzi that also interact with beta1-adrenergic receptor blocked light stimulation of cGMP-phosphodiesterase in bovine rod membranes. The specificity from the antibody-rhodopsin interaction was confirmed by Western blot analysis and antigenic competition experiments. Our results suggest an immunomediated rhodopsin blockade. T. cruzi infection probably induces an autoimmune response against rhodopsin in the chronic phase of Chagas' disease through a molecular mimicry mechanism similar to that described previously on cardiac human beta1-adrenergic and M2-cholinergic receptors, all related to the same subfamily of G-protein-coupled receptors.

Retinal dysfunction in patients receiving vigabatrin

Retinal dysfunction in patients receiving vigabatrin

Association for Research in Vision and Ophthalmology (ARVO) Annual Meeting, April 29???May 4, 2001

Association for Research in Vision and Ophthalmology (ARVO) Annual Meeting, April 29???May 4, 2001

Acute idiopathic blind spot enlargement syndrome: prolonged retinal dysfunction revealed by multifocal electroretinogram technique

PURPOSE: To report the multifocal electroretinographic findings of a patient with acute idiopathic blind spot enlargement syndrome recorded at 2 weeks and 4 months after the onset. METHODS: A 35-year-old patient underwent static visual field (Humphrey, 30-2) and multifocal electroretinogram testing at 2 weeks and 4 months after the onset of acute idiopathic blind spot enlargement. The stimulus array for the multifocal electroretinogram consisted of 61 hexagons, and the total recording time was about 4 minutes. RESULTS: At 2 weeks, the patient had a large, well-demarcated scotoma centered on the blind spot, and its margin extended to within 5 degrees of fixation. The multifocal electroretinograms were depressed in the areas corresponding to the scotoma. At 4 months, her visual symptoms disappeared and static visual fields showed normal sensitivities at almost all locations. However, the multifocal electroretinograms still revealed reduced focal responses in a broad area around the blind spot. CONCLUSION: These results suggest that multifocal electroretinograms may be used to detect subclinical retinal dysfunction in patients with acute idiopathic blind spot enlargement.

Outer retinal dysfunction in patients treated with vigabatrin

To assess early visual impairment related to vigabatrin prospectively in patients with and without visual symptoms. Vigabatrin acts as an inhibitor of gamma-aminobutyric acid (GABA) transaminase. GABA-induced ion transport changes in the retinal pigment epithelium have been described. The electro-oculogram (EOG) is a clinical test that reflects photoreceptor and pigment epithelium function. Of the 22 consecutive patients presenting with a history of partial seizures currently treated with vigabatrin, 20 were included in the study. A complete clinical ophthalmologic and neurologic examination was performed, including static 100-point perimetry, EOG, and electroretinogram (ERG). In 14 of 20 patients, the light/dark ratio (Arden ratio) of the standard EOG was reduced in at least one eye. The a- and b-wave amplitudes and implicit time of the ERG were within the normal range in all patients; however, ERG oscillatory potentials could not be recorded in 10 patients. Twelve patients had visual field constriction; five complained of visual symptoms. The most severe visual impairment was observed in patients treated with both vigabatrin and valproate. There is some evidence of outer retinal dysfunction in the patients treated with vigabatrin. EOG, a more sensitive diagnostic tool than ERG for screening vigabatrin-treated patients, also appears to be more specific.

The first and second harmonics of the macular flicker electroretinogram: differential effects of retinal diseases.

We evaluated the effects of retinal diseases on the macular electroretinogram first and second harmonic components, which are dominated by outer and inner retinal activity, respectively. Macular electroretinograms in response to a uniform field (9 degrees x 9 degrees) flickering sinusoidally at either 32 or 8 Hz (peak frequencies of the first and second harmonics, respectively) were recorded in 14 patients with maculopathies involving photoreceptors (e.g., age-related macular degeneration), in 16 patients with postreceptoral macular diseases (e.g., branch occlusion of central retinal artery), and in 38 normal controls. Amplitude and phase of the first and second harmonic response components were evaluated by Fourier analysis. When compared to controls, patients with photoreceptor diseases had reduction in both first and second harmonic mean amplitudes and second harmonic phase delay; patients with postreceptoral diseases had normal first harmonic components but reduced and delayed second harmonic components. A discriminant analysis, by using first and second harmonic values, correctly classified 13 of 14 patients with photoreceptor diseases and 14 of 16 patients with postreceptoral disorders. These results indicate that combined evaluation of the macular electroretinogram first and second harmonic components is a useful test for identifying the site(s) of retinal dysfunction in patients with macular diseases.

Taurine in infant nutrition

The importance of taurine in diet is poorly understood. The present evidence suggests that it is a conditionally essential aminoacid in man wherein deficiency states may result in adverse changes which will be improved with supplementation. It has a role in fat absorption in preterm infants and children with cystic fibrosis, retinal dysfunction in patients receiving TPN and those with blind loop gut syndromes. Taurine is also reported to improve maturation of ABER in pre-term infants and has a role in osmoregulation of CNS and may act as neuroinhibitor.

Visual system toxicity following intra-arterial chemotherapy.

We studied the effects of intra-arterial chemotherapy on the visual system of 29 consecutive patients with gliomas. As expected, infra-ophthalmic carotid infusion of cisplatin or carmustine (BCNU) was associated with clinically apparent anterior visual pathway lesions. Electroretinography revealed retinal dysfunction in patients without clinical abnormalities. Supra-ophthalmic carotid infusion of cisplatin or BCNU caused no retinal or optic nerve lesions. Electroretinography was abnormal in only one of these patients. Our results indicated that BCNU and cisplatin cause ischemic damage and are toxic to both retinal and neural tissue in patients with gliomas.