Reduced full-field electroretinogram (ERG) in a patient treated with methotrexate.

Purpose: To examine retinal function in a patient with decreased vision possibly due to treatment with methotrexate. Methods: Ophthalmological examination included testing of visual acuity (VA), fundus inspection, fundus photography and kinetic perimetry. Retinal function was tested objectively with three electrophysiological methods: full-field electroretinography (ERG), multifocal electroretinography (mfERG) and electro-oculography (EOG). Results: A 13-year-old boy with psoriasis arthritis had been treated with methotrexate on a weekly basis for 8.5 years. After terminating treatment, his VA, which was reduced to 0.3 in both eyes initially, improved during the following 3 years but did not return to normal. No visual field defects were found with kinetic perimetry. The rod and cone responses in the full-field ERG were markedly reduced in b-wave amplitude initially, but grew slowly to nearly normal values 3 years later. After withdrawal of the drug, the mfERG demonstrated normal responses in the macular region. The Arden index in the EOG was normal. Conclusion: Chronic treatment with methotrexate may affect VA, and may reversibly reduce rod and cone function. In patients who use systemic medication and whose vision is reduced, objective evaluation of retinal function with electrophysiological methods is recommended

Phenotypes and genotypes in families with hereditary tapetoretinal degenerations

The purpose of the study was to characterise the phenotype with emphasis on electroretinography in four different types of hereditary retinal degeneration and to correlate it to a genotype when possible. Two methods were used: full-field electroretinography for objective assessment of retinal function and mutation screening of blood samples for detection of gene alterations. Electroretinograms from patients with central areolar choroidal dystrophy demonstrated a reduction of the cone b-wave amplitude and a prolongation of the implicit time indicating a generalised cone disease which is slowly progressive. Patients with choroderemia and a deletion of the CHM gene presented two different phenotypes, one mild and one severe, even though the genotype was identical in all examined patients, indicating that the severity of the phenotype is not solely a function of the CHM gene. Three families with autosomal dominant retinitis pigmentosa and different mutations in the rhodopsin and the peripherin gene were studied. The rhodopsin mutation Arg-135-Try is associated with a severe phenotype while patients with the mutation Pro-267-Leu have a mild retinal degeneration with a nearly normal electroretinogram early in the natural course of the disease. The peripherin mutation Phe-211-Leu is associated with a phenotype including early loss of rod function and a macular degeneration. Three families with X-linked retinitis pigmentosa and mutations in the RPGR gene had severely reduced electroretinograms and in one of the families also the carriers were visually disabled. A family with progressive autosomal dominant cone-rod dystrophy had an intrafamiliar variability of the phenotype with different degrees of rod involvement. It is concluded that both full-field electroretinography and DNA analysis should be included in the investigation of patients with hereditary retinal degenerations in order to achieve a reliable diagnosis and prognosis

Electrophysiological evaluation of retinal function in children receiving vigabatrin medication

PURPOSE: To evaluate retinal function in children taking vigabatrin and to explore the influence of age and dose parameters on the results of full-field electroretinography (ff-ERG).METHODS: The ff-ERGs from 14 children receiving vigabatrin were compared with ff-ERGs from healthy controls. Treated children were further grouped according to age (pre-school = 12-71 months; older = 72-228 months). Parameters of drug dosage were compared.RESULTS: Treated children showed rod and cone dysfunction reflected by reduced b-wave amplitudes for the isolated rod response, the combined rod-cone response, and the 30-Hz flicker response. The a-wave amplitude and implicit time for the combined rod-cone response, reflecting photoreceptor function, were also altered. Further evaluation of age groups revealed similar findings in the pre-school group but not in the older group. Alterations in ff-ERG were seen in 57% of the treated children. Pre-school children had received significantly higher daily drug doses with start of medication at younger age. No differences were found concerning cumulative doses or duration of medication.CONCLUSION: Alterations in ff-ERG are as frequent in children as in adults and the results indicate that exposure to high daily doses of vigabatrin may be associated with increased risk of retinal dysfunction, including photoreceptor damage, not previously shown in children. Thus, recommendations of careful follow-up for children receiving vigabatrin are supported

Using multifocal electroretinography hard exudates affect macular function in eyes with diabetic retinopathy

To evaluate the influence of hard exudates on macular function in patients with diabetic retinopathy. METHODS: Thirty seven eyes from 27 diabetic patients, aged 57 +/- 14 years, diabetes duration 12.5 +/- 9 years, not previously treated with photocoagulation, underwent fundus photography, multifocal electroretinography (mfERG) and optical coherence tomography (OCT). Hard exudates were graded from fundus photography with superimposed OCT and a superimposed hexagonal pattern (mfERG) by one retinal specialist, unaware of mfERG and OCT results. We defined three groups; A = eyes with exudates in the analyzed zone, B = eyes with no exudates in the analyzed zone but elsewhere, and C = eyes with no exudates. The mfERG responses and OCT values from five defined areas in the macula were compared. RESULTS: MfERG showed that the implicit time was significantly prolonged in group A compared to group C in the central, middle and outer areas and in the nasal and temporal area (p = 0.045, 0.019, 0.017 and 0.035 and 0.016 respectively), in group B compared to group C in the central area (p = 0.016), and in group A compared to group B in the outer area (p = 0.035). Amplitude differed between group A and C in the middle area and outer area (14.2 +/- 5.2 nV/deg(2) vs 21.1 +/- 8.7 nV/deg(2), p = 0.037 and 14.1 +/- 3.9 nV/deg(2) vs 17.7 +/- 7.1 nV/deg(2) , p = 0.02 respectively), and between group B and C in the temporal area 14.5 +/- 2.2 nV/deg(2) vs 20.0 +/- 8.7 nV/deg(2), p = 0.017). Macular thickness assessed with OCT was similar between the groups. CONCLUSIONS: In eyes with diabetic retinopathy, hard exudates prolong the implicit time assessed with mfERG, compared to eyes without hard exudates, and independently of macular thickness. These results indicate that the hard exudates in the macular region, even at a distance from the fovea centre, have a deleterious effect on macular function

Multifocal electroretinography (mfERG) in insulin dependent diabetics with and without clinically apparent retinopathy

Purpose: To Study the retinal function, using multifocal electroretinography (mfERG), in diabetic patients with mild and moderate retinopathy, and in diabetics without clinically apparent retinopathy. Methods: Thirty-one patients with insulin dependent diabetes mellitus, eleven without any clinically apparent retinopathy, twelve with mild retinopathy and eight with moderate retinopathy, were studied. Ophthalmologic examination included testing Of Visual acuity, fundus inspection, fundus photography and mfERG. Sixteen subjects without eye disease and with normal visual acuity were used as controls for comparison of mfERG results. Results: The patients had a mean diabetes duration of 23 +/- 9 years. All patients and controls had a visual acuity of 1.0. In the first order component of the mfERG there were significantly higher ring amplitudes in the diabetics compared to the controls (p=0.001). In the second-order component of the mfERG, there was a significantly prolonged implicit time in the diabetics who had retinopathy compared to those without any retinopathy (p=0.026). The third positive waveform in the ring amplitudes of the second-order component, were absent in 15/31 of patients with diabetes, but were easily distinguished in all the controls; p < 0.001. This waveform was absent in 6/11 patients without retinopathy. Conclusion: Patients with insulin dependent diabetes have specific abnormalities in both the First and the second-order component of the mfERG. These abnormalities reflect both vascular changes in the retina and, probably simultaneously, pathology in inner retinal function, also in the diabetics without clinically apparent retinopathy

Multifocal electroretinogram (mfERG) in patients with diabetes mellitus and an enlarged foveal avascular zone (FAZ)

Purpose To assess the relationship between foveal microcirculation and central retinal function in diabetic patients having both an enlarged foveal avascular zone (FAZ) and a preserved visual acuity (0.6 or better). Methods Twenty-five patients with diabetes type 1 or 2 with an enlarged FAZ (largest diameter > 650 mum) measured in fluorescein angiograms were examined with multifocal ERG (mfERG). The largest FAZ diameter, the FAZ area as well as the adjacent perifoveal intercapillary area (PIA), was calculated from the fluorescein angiogram. The retinopathy level was mild to preproliferative. There was no macular edema and no eye had previously been treated with photocoagulation. Results The mean FAZ diameter was 0.92 +/- 0.17 mm and the mean summed area (FAZ and PIA) was 0.74 +/- 0.24 mm(2). There was a significant correlation between increasing FAZ diameter and increasing implicit time of the innermost concentric rings and of the third concentric ring in the first order kernel of the mfERG (P = 0.03 and P = 0.008, respectively). An increasing summed area (FAZ and PIA) was correlated to increasing implicit time in the same areas of the mfERG (P = 0.005 and P = 0.026, respectively). No correlation was seen between the ischemic areas and the mfERG amplitudes. Conclusion A correlation between the ischemic areas and prolonged implicit time in the mfERG indicates that alterations in neuronal macular function due to ischemia might precede the deterioration of visual acuity

Retinal function and histopathology in rabbits treated with Topiramate.

Purpose To evaluate retinal function and histopathology in rabbits treated orally with the antiepileptic drug topiramate. Methods Six rabbits were treated with a daily oral dose of topiramate during a period of eight months. Six rabbits receiving water served as controls. Blood samples were analyzed for determination of topiramate serum levels in order to ensure successful drug exposition. Standardized full-field electroretinograms (ERGs) were performed before treatment and then at 2, 3 and 8 months during the treatment period. After terminating treatment the rabbits were sacrificed and the morphology of the sectioned retina was studied. Results After eight months of treatment the fullfield ERG demonstrated normal rod function in treated and control rabbits, but the light adapted 30 Hz flicker b-wave amplitude was significantly reduced in the treated rabbits. This was the case for both the light adapted (Wilcoxon signed ranks test, P=0.046) and the dark adapted (Wilcoxon signed ranks test, P=0.028) 30 Hz flicker response from the treated rabbits. Retinal immunohistology revealed a severe accumulation of GABA in amacrine cells and in the inner plexiform layer in 4 of 6 treated rabbits compared to the controls. Conclusions Topiramate, orally administrated to rabbits, may cause a significant reduction of the retinal function demonstrated by the reduced b-wave amplitude in the full-field ERG, as well as changes in immunohistology characterized by a severe accumulation of GABA in the inner retina. The retinal dysfunction and the morphological changes indicate that topiramat may damage the retina, similarly to vigabatrin (another antiepileptic drug)