The Topographical Relationship between Visual Field Loss and Peripapillary Retinal Nerve Fibre Layer Thinning Arising from Long-Term Exposure to Vigabatrin

Abstract

Carlo 2019. The topographical relationship between visual field loss and peripapillary retinal nerve fibre layer thinning arising from long-term exposure to vigabatrin. CNS Drugs 33 (2) , pp. AbstractBackground The anti-epileptic drug vigabatrin is associated with visual field loss (VAVFL) and thinning of the peripapillary retinal nerve fibre layer (PPRNFL), thereby implicating retinal ganglion cell (RGC) dysfunction.Objective The objective of the study was to determine the relationship between the two outcomes in order to improve the risk/ benefit analysis of vigabatrin, particularly in those unable to undertake perimetry.Methods A retrospective cross-sectional observational design identified 40 adults who had received vigabatrin for refractory seizures and who had undergone a combined protocol of perimetry and optical coherence tomography (OCT) of the PPRNFL. Two established models successfully applied to other optic neuropathies were used to evaluate, topographically, the function-structure relationship for the superior and inferior retinal quadrants. ResultsThe function-structure relationship for each model was consistent with other optic neuropathies. With the first model, PPRNFL thinning, expressed in µm, asymptoted at an equivalent visual field loss of worse than approximately -10.0dB, thereby preventing assessment of more substantial thinning. The second model overcame the asymptote by transforming the outcomes to RGC soma and axon estimates, respectively; the latter were linearly related.Conclusions Concurrent use of perimetry and OCT, enabling reciprocal validation, is essential for the detection and assessment of vigabatrin toxicity. However, OCT affords a limited measurement range compared to perimetry: severity cannot be directly assessed when the PPRNFL quadrant thickness is less than approximately 65µm, depending upon the type of tomographer. This limitation can be overcome by transformation of thickness to remaining axons, an outcome requiring input from perimetry.

Evaluation of optical coherence tomography findings in adolescents with genetic generalized epilepsy

“…Vigabatrin (VGB) is associated with irreversible visual feld loss and its effect increases with the duration and extent of exposure to the drug. 18 Lawthom et al evaluated 27 patients with epilepsy receiving VGB and 13 patients with epilepsy receiving non-GABAergic AED monotherapy. All VGB groups exhibited abnormal average and nasal quadrant RNFL thicknesses and normal temporal quadrant thickness.…”

Transcriptome analysis in mice treated with vigabatrin identifies dysregulation of genes associated with retinal signaling circuitry

“…VGB carries a black box warning (https://www.sabril.net/) indicating a significant risk of permanent bilateral peripheral visual field constriction (pVFC) (Hawker et al, 2008). In addition to pVFC and thinning of the RNFL, additional toxic side effects with VGB have been reported, which may be grouped as follows: 1) structural (damage to rod/cone photoreceptors, reduced ocular/cerebral blood flow); 2) imaging (white matter spongiosis, restricted globus pallidus diffusion); 3) metabolic (amino acid (taurine, ornithine) anomalies, reduced glutamine synthetase and serum transaminase activities, oxidative stress); and 4) genomic alterations (dysregulation of genes active in autophagy, damage to DNA) (Wild et al, 2019;Pearl et al, 2018;Froger et al, 2014;Sorri et al, 2010;Hisama et al, 2001). Light exposure may also have a role, suggesting a link to the phototransduction cascade, the process by which a photon of light is translated into an electrical signal (Yang et al, 2012;Tao et al, 2016).…”

Visual field defects after vigabatrin treatment during infancy: retrospective population‐based study

“…OCT has shown thinning of the peripapillary retinal nerve fiber layer (RNFL) in adults exposed to vigabatrin. [15][16][17] OCT studies in children have been inconclusive. 18,19 For future optimal use of vigabatrin in infantile spasms, it is crucial to define the risk of VAVFD and to identify methods for assessing retinal toxicity as well as infants especially vulnerable to visual field defect.…”

“…After successful fixation, spectral‐domain OCT scans the optic nerve head within seconds. OCT has shown thinning of the peripapillary retinal nerve fiber layer (RNFL) in adults exposed to vigabatrin 15–17 . OCT studies in children have been inconclusive 18,19 …”