Retinal Function Abnormalities in Patients Treated With Vigabatrin

Banin, Eyal; Shalev, Ruth S.; Obolensky, Alexey; Neis, Ruhama; Chowers, Itay; Gross‐Tsur, Varda

doi:10.1001/archopht.121.6.811

Cited by 32 publications

(20 citation statements)

References 36 publications

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“…The limitation of light exposure by eye pigmentation may explain why several years are required to induce cone dysfunction in vigabatrin-treated patients, despite higher light exposition under natural conditions. 39 Our observation of preferential S-opsin þ cone loss in GES-treated mice is consistent with the color vision dysfunction exhibited by vigabatrin-treated patients with a greater alteration of blue sensitivity. 40 This study suggests that taurine supplementation may provide neuroprotection in diseases of photoreceptor loss with earlier S-opsin þ cone degeneration.…”

Section: Taurine Depletion Causes Cone Loss In the Mouse Retinasupporting

confidence: 85%

Quantitative and Topographical Analysis of the Losses of Cone Photoreceptors and Retinal Ganglion Cells Under Taurine Depletion

Hadj-Saïd

Froger

Ivković

et al. 2016

Invest. Ophthalmol. Vis. Sci.

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Citation: Hadj-Saïd W, Froger N, Ivkovic I, et al. Quantitative and topographical analysis of the losses of cone photoreceptors and retinal ganglion cells under taurine depletion. Invest Ophthalmol Vis Sci. 2016;57:4692-4703. DOI:10.1167/ iovs.16-19535 PURPOSE. Taurine depletion is known to induce photoreceptor degeneration and was recently found to also trigger retinal ganglion cell (RGC) loss similar to the retinal toxicity of vigabatrin. Our objective was to study the topographical loss of RGCs and cone photoreceptors, with a distinction between the two cone types (S-and L-cones) in an animal model of induced taurine depletion. METHODS.We used the taurine transporter (Tau-T) inhibitor, guanidoethane sulfonate (GES), to induce taurine depletion at a concentration of 1% in the drinking water. Spectral-domain optical coherence tomography (SD-OCT) and electroretinograms (ERG) were performed on animals after 2 months of GES treatment administered through the drinking water. Retinas were dissected as wholemounts and immunodetection of Brn3a (RGC), S-opsin (S-cones), and L-opsin (L-cones) was performed. The number of Brn3a þ RGCs, and L-and S-opsin þ cones was automatically quantified and their retinal distribution studied using isodensity maps. RESULTS.The treatment resulted in a significant reduction in plasma taurine levels and a profound dysfunction of visual performance as shown by ERG recordings. Optical coherence tomography analysis revealed that the retina was thinner in the taurine-depleted group. Sopsin þ cones were more affected (36%) than L-opsin þ cones (27%) with greater cone cell loss in the dorsal area whereas RGC loss (12%) was uniformly distributed.CONCLUSIONS. This study confirms that taurine depletion causes RGC and cone loss. Electroretinograms results show that taurine depletion induces retinal dysfunction in photoreceptors and in the inner retina. It establishes a gradient of cell loss depending on the cell type from S-opsin þ cones, L-opsin þ cones, to RGCs. The greater cell loss in the dorsal retina and of the S-cone population may underline different cellular mechanisms of cellular degeneration and suggests that S-cones may be more sensitive to light-induced retinal toxicity enhanced by the taurine depletion.

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Section: Taurine Depletion Causes Cone Loss In the Mouse Retinasupporting

confidence: 85%

Quantitative and Topographical Analysis of the Losses of Cone Photoreceptors and Retinal Ganglion Cells Under Taurine Depletion

Hadj-Saïd

Froger

Ivković

et al. 2016

Invest. Ophthalmol. Vis. Sci.

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“…The slight tritan defect in the FM-100 hue test, observed in voriconazole-treated volunteers, might indicate an increased susceptibility of the short wavelength cones to side effects of voriconazole. This is a common observation with neurotropic drugs [15,16]. …”

Section: Discussionmentioning

confidence: 98%

Effects of Multiple Doses of Voriconazole on the Vision of Healthy Volunteers: A Double-Blind, Placebo-Controlled Study

Zrenner¹,

Tomaszewski²,

Hamlin³

et al. 2014

Ophthalmic Res

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Purpose: To investigate the effects, and their reversibility, of multiple oral voriconazole doses on a variety of visual tests in healthy male volunteers. Methods: Single-center, double-blind, randomized, placebo-controlled, parallel-group study in 36 volunteers who received voriconazole (n = 18, 400 mg every 12 h on day 1, then 300 mg every 12 h for 27.5 days) or matched placebo (n = 18). Electroretinograms (ERGs) and ophthalmological examinations were performed at screening, throughout the study and at follow-up. Results: Fifteen (83.3%) volunteers treated with voriconazole experienced ≥1 treatment-related visual adverse events (AEs); these included enhanced visual perceptions, blurred vision, color vision changes and photophobia. No serious AEs were reported. Voriconazole reduced from baseline scotopic maximal a- and b-wave amplitude, shortened implicit time and decreased oscillatory potential amplitude compared with placebo. Under photopic conditions, the 30-Hz flicker response amplitude was significantly reduced and was accompanied by a slight but nonsignificant prolongation of peak time. These effects did not progress in degree over the treatment period, and mean changes from baseline in ERG parameters were similar to placebo by day 43 (14 days after end of treatment). In the first week, color vision discrimination was impaired in the tritan axis, although this resolved by end of treatment and was similar to placebo by day 43. Mean deviation in the static visual field indicated increased sensitivity following voriconazole treatment, correlating with decreased amplitude in conjunction with shortened implicit time. Conclusions: Effects of voriconazole on altered visual perception, ERG, color vision and static visual field thresholds are nonprogressive over a treatment period and reversible. It is hypothesized that voriconazole has a pharmacological effect on rod and cone pathways including a possible mechanism of disinhibition that reversibly puts the retina in a more light-adapted state and leads to increased relative contrast sensitivity.

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“…Abnormal EOGs in VGB-treated patients implicate the retinal pigment epithelium and the retinal pigment epithelial-outer segment complex (9,(18)(19)(20). Abnormal ERGs implicate both the central and peripheral cone and rod systems (5,8,11,12,(19)(20)(21)(22). The findings are consistent with Müller and amacrine cell dysfunction (8,11,18,19).…”

mentioning

confidence: 80%

Acute Vigabatrin Retinotoxicity in Albino Rats Depends on Light But Not GABA

Izumi¹,

Ishikawa

Benz³

et al. 2004

Epilepsia

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Summary:Purpose: Vigabatrin (VGB) is an irreversible inhibitor of γ -aminobutyric acid (GABA) transaminase. Its use as an antiepileptic drug (AED) has been limited because it causes retinal dysfunction, leading to visual field defects (VFDs). We performed this study to identify factors contributing to acute VGB retinotoxicity.Methods: In ex vivo experiments, Sprague-Dawley rat retinas were isolated and incubated with VGB or GABA in the presence or absence of light. In in vivo experiments, Sprague-Dawley rats were given intraperitoneal injections of VGB and then exposed to light or kept in the dark. The retinas were analyzed histologically by using both light and electron microscopy.Results: Incubating retinas with 50-500 µM VGB under 20,000 Lux white light for ≤20 h caused a characteristic time-and dose-dependent degeneration limited to the outer retina. Incubating retinas with 500 µM VGB in darkness for 20 h caused no damage. Five hundred micromolar GABA and 50 µM tiagabine were not toxic in the presence or absence of light. Sprague-Dawley rats exposed to an intense white light for 20 h after a 1,000-mg/kg intraperitoneal injection of VGB showed damage in the outer retina, whereas those kept in the dark did not.Conclusions: Direct exposure of the retina to VGB causes acute retinotoxicity that depends on light exposure rather than GABA accumulation.

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Retinal Function Abnormalities in Patients Treated With Vigabatrin

Cited by 32 publications

References 36 publications

Quantitative and Topographical Analysis of the Losses of Cone Photoreceptors and Retinal Ganglion Cells Under Taurine Depletion

Quantitative and Topographical Analysis of the Losses of Cone Photoreceptors and Retinal Ganglion Cells Under Taurine Depletion

Effects of Multiple Doses of Voriconazole on the Vision of Healthy Volunteers: A Double-Blind, Placebo-Controlled Study

Acute Vigabatrin Retinotoxicity in Albino Rats Depends on Light But Not GABA

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