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- Kjellström, Ulrika, et al.
(författare)
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Attenuation of the retinal nerve fibre layer and reduced retinal function assessed by optical coherence tomography and full-field electroretinography in patients exposed to vigabatrin medication.
- 2014
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Ingår i: Acta Ophthalmologica. - : Wiley. - 1755-3768 .- 1755-375X. ; 92:2, s. 149-157
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Tidskriftsartikel (refereegranskat)abstract
- Purpose: To investigate the clinical value of assessment of peripapillary retinal nerve fibre layer (RNFL) thickness with OCT in addition to the evaluation of retinal function measured by full-field electroretinography (ff-ERG) in patients with suspected vigabatrin (VGB)-attributed visual field defects. Methods: Visual fields from adult patients in our clinical follow-up program for VGB medication were analysed. Twelve patients with suspected VGB-attributed visual field defects were selected for the study. They were re-examined with computerized kinetic perimetry, ff-ERG and OCT (2D circle scan). Results: Constricted visual fields were found in all patients. Comparative analysis of ff-ERG parameters showed reduced b-wave amplitudes for the isolated and the combined rod and cone responses (p < 0.0001). The a-wave, reflecting photoreceptor activity, was reduced (p = 0.001), as well as the summed amplitude of oscillatory potentials (p = 0.029), corresponding to inner retinal function. OCT measurements demonstrated attenuation of the RNFL in nine of 12 patients, most frequently superiorly and/or inferiorly. No temporal attenuation was found. Significant positive correlations were found between the total averaged RNFL thickness, superior and inferior RNFL thickness and reduced ff-ERG parameters. Positive correlations were also found between RNFL thickness and isopter areas. Conclusion: OCT measurements can detect attenuation of the RNFL in patients exposed to VGB medication. RNFL thickness correlates with reduced ff-ERG parameters and isopter areas of constricted visual fields, indicating that VGB is retino-toxic on several levels, from photoreceptors to ganglion cells. The study also supports previous studies, suggesting that OCT measurement of the RNFL thickness may be of clinical value in monitoring patients on vigabatrin therapy.
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- Kjellström, Ulrika, et al.
(författare)
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Electrophysiological evaluation of retinal function in children receiving vigabatrin medication
- 2011
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Ingår i: Journal of Pediatric Ophthalmology and Strabismus. - : SLACK, Inc.. - 0191-3913 .- 1938-2405. ; 48:6, s. 65-357
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Tidskriftsartikel (refereegranskat)abstract
- 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.
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- Kjellström, Ulrika
(författare)
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Ocular function and morphology in humans and rabbits exposed to vigabatrin medication
- 2010
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Vigabatrin is an antiepileptic drug that is known to cause visual field defects and retinal dysfunction measured by full-field electroretinography (ff-ERG). Underlying mechanisms have not yet been elucidated. The aims of this thesis were to investigate parameters of vigabatrin treatment; reversibility of visual dysfunction, prevalence of retinal dysfunction in children, role of drug-dose and evaluation of alternative methods for follow-up. A translational approach was applied, investigating issues in an experimental rabbit model and in clinical investigations. Reversibility of reduced retinal function was studied in our rabbit model, showing reduced cone function both during treatment and after withdrawal of medication. No changes in immuno labelling patterns of vimentin, glial fibrillary acidic protein (GFAP), γ-aminobutyric acid (GABA) and GAD (glutamic acid decarboxylase) were found. Re-evaluation of visual field defects and retinal function in patients five years after withdrawal of vigabatrin demonstrated irreversible reduction of the isolated rod and cone function and the combined rod-cone function. Also the 30 Hz flicker implicit time was altered. Indications of progressive decline of the combined response were observed. No changes in visual fields were found. In the rabbit model, dose-related changes of retinal function (rod, combined rod-cone and oscillatory potentials, OPs) and expression of proteins were found. In rod bipolar cells, protein kinase C-α (PKC- α) labelling showed a reduced number of labelled cells and translocation of enzyme activity. Müller cells showed deviant vimentin labelling. In children, vigabatrin medication was associated with reduced rod and cone function. Alterations of cone responses were found in 24% of treated children. Young children were affected more often, showing reduced retinal function in 33% of the subjects. The younger group had received higher daily drug-doses and had started medication at younger age than the older group. No differences were found concerning cumulative drug-doses. Alternative methods for detection of vigabatrin toxicity were tested, indicating that attenuation of the retinal nerve fibre layer (RNFL) can be detected with optical coherence tomography (OCT) in patients with vigabatrin-attributed visual field defects and ff-ERG alterations. Correlations between RNFL thickness and reduced ff-ERG amplitudes were found. Multi focal visual evoked potentials (mfVEP) were not useful.
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