Optical coherence tomography to monitor vigabatrin toxicity in children

Origlieri, Catherine; Geddie, Brooke; Karwoski, Bethany; Berl, Madison M.; Elling, Nancy; McClintock, W.; Alexander, Janet; Bazemore, Marlet; Beaufort, Heather de; Hutcheson, Kelly A.; Miller, Michelle S.; Taylormoore, Jonathan; Jaafar, Mastura; Madigan, William P.

doi:10.1016/j.jaapos.2015.10.020

Cited by 19 publications

(21 citation statements)

References 21 publications

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“…In contrast, a recent study reported RNFL thinning in a cohort of patients with tuberous sclerosis; however, the investigators used time domain OCT, which has >40% coefficients of variability, 39,40 and although the study is described as "prospective," patient OCT data prior to initiating vigabatrin were not captured. 41 Despite the strengths of this study, some limitations should be considered when interpreting these data. The single-arm, open-label design does warrant some caution when interpreting these results.…”

Section: Discussionmentioning

confidence: 95%

“…Critical trial‐design features that improved the interpretability of the data included the collection of baseline patient vision data, the use of OCT devices from a single manufacturer running software with the lowest coefficient of variability of measurements across all sites, and two independent reading centers. In contrast, a recent study reported RNFL thinning in a cohort of patients with tuberous sclerosis; however, the investigators used time domain OCT, which has >40% coefficients of variability, and although the study is described as “prospective,” patient OCT data prior to initiating vigabatrin were not captured …”

Section: Discussionmentioning

confidence: 99%

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Retinal structure and function in vigabatrin‐treated adult patients with refractory complex partial seizures

et al. 2016

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SUMMARYObjective: Evaluate visual-field and retinal-structure changes following adjunctive vigabatrin treatment in vigabatrin-naive adults with refractory complex partial seizures (rCPS). Methods: Prospective, longitudinal, single-arm, open-label study (NCT01278173). Eligible patients (≥2 seizures/month who failed ≥3 therapies) who could reliably perform perimetry (Humphrey automated static) and retinal-structure assessment (spectraldomain optical coherence tomography) prior to vigabatrin exposure. Following vigabatrin initiation, testing occurred within 1 month (reference) and 3, 6, 9, and 12 months. End points included mean change from reference in mean deviation (dB) and average retinal nerve fiber layer (RNFL) thickness, visual-acuity changes from baseline, and number of patients who met predefined vision-parameter changes at two (confirmed) or three (persistent) consecutive visits. Results: Sixty-five of 91 screened patients received ≥1 vigabatrin dose (all-patientstreated set [APTS]); 55 had valid reference and ≥1 post-reference assessments (fullanalysis set [FAS]). Thirty-six APTS patients with valid pre-/post-reference values completed all planned visits (per-protocol set [PPS]). Thirty-eight (59%) APTS patients completed the study; 27 (42%) withdrew (none for visual-field changes); 32% and 15% had abnormally thin RNFL and abnormal visual acuity at baseline, respectively; 20% had abnormal central 30 degree visual fields in the reference period. No significant mean near visual-field changes were observed (PPS); mean change in average RNFL thickness increased significantly (1-year data: Left-eye: 6.37 lm, confidence interval (CI) 4.66-8.09; right-eye: 7.24 lm CI 5.47-9.01; PPS). No confirmed three-line decreases in visual acuity (FAS) were observed; five patients had predefined confirmed/persistent visual-field changes (FAS). All vision-related adverse events were nonserious; the most common was vision blurred (9%). Significance: Prior to vigabatrin initiation, rCPS patients may already exhibit vision deficits. Up to 1 year of adjunctive vigabatrin treatment did not significantly change population near visual fields. Five patients met predefined visual-field-change criteria. RNFL thickening of unknown clinical significance was observed. Limitations include single-arm, open-label design; patients' inability to perform ophthalmic/visual-field examinations; and limited vigabatrin-exposure duration.

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Section: Discussionmentioning

confidence: 95%

Section: Discussionmentioning

confidence: 99%

Retinal structure and function in vigabatrin‐treated adult patients with refractory complex partial seizures

et al. 2016

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“…The rate of freedom from partial seizures has been reported to be 16-46% in prospective and retrospective studies of TSC [22][23][24]. Retinal nerve fiber layer thinning and visual field deficits have been reported with vigabatrin and are a concern (boxed warning) [25,26]. Visual field constriction has been reported in approximately 34% of children and over 30% of adults [21,26,27].…”

Section: Overview Of the Marketmentioning

confidence: 99%

Everolimus as adjunctive therapy for tuberous sclerosis complex-associated partial-onset seizures

Lechuga

Franz

2019

Expert Review of Neurotherapeutics

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Introduction: Tuberous sclerosis complex (TSC) is a rare genetic disorder resulting in benign tumors in various organs. It is caused by mutations in TSC1 or TSC2 genes causing hyperactivation of the mammalian target of rapamycin (mTOR) pathway. The majority of patients with TSC develop epilepsy, and approximately two-thirds become refractory to antiepileptic drugs (AEDs). Recently, the mTOR inhibitor everolimus was approved as adjunctive therapy for TSC-associated partial seizures. Areas covered: This article covers different characteristics of everolimus, including major clinical trials leading to its approval in TSC-associated partial seizures, safety concerns, drug pharmacokinetics/ pharmacodynamics, and an overview of potential competitors and other agents used to treat TSCassociated seizures. Expert opinion: Unlike many other therapies for treating TSC-associated seizures, everolimus addresses the underlying pathophysiology of TSC, and since it has also been shown to improve other TSC manifestations such as subependymal giant cell astrocytomas and renal angiomyolipomas, everolimus provides a potential multisystemic therapy for TSC. An important avenue for future research is exploring the possible use of everolimus as a preventative treatment for seizures as there is the potential to prevent negative developmental outcomes associated with TSC.

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“…Monitoring children younger than 3 years of age for vision loss using traditional techniques is profoundly difficult 21 because of poor compliance with adultoriented procedures such as the Goldmann visual field perimetry and table-top OCT, [22][23][24][25][26][27][28] which require stable upright postures for a prolonged period of time. When vigabatrin is required for those under the age of 3 years, assessment is limited to fundus examination, confrontational visual fields and in some centres, ERGs.…”

Section: Introductionmentioning

confidence: 99%

Reliability of Handheld Optical Coherence Tomography in Children Younger Than Three Years of Age Undergoing Vigabatrin Treatment for Childhood Epilepsy

Wright

VandenHoven

et al. 2020

Trans. Vis. Sci. Tech.

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Purpose: Vigabatrin-associated retinal toxicity manifests as reduction in the clinical electroretinogram and retinal nerve fiber layer (RNFL) thinning. This observational investigation of RNFL thickness in young vigabatrin-treated children was to identify intravisit and intervisit reliabilities of peripapillary RNFL thickness measurements performed with Envisu (optical coherence tomography) OCT. Secondarily, a longitudinal assessment investigated the presence and extent of RNFL thinning. Methods:We measured the handheld OCT in sedated children to evaluate the RNFL thickness using segmentation software. Intraclass correlation coefficient (ICC) statistics identified intravisit and intervisit reliabilities for RNFL thickness.Results: Twenty-nine children (10.1 ± 6.0 months old) underwent handheld optical coherence tomography (OCT). Fourteen of these completed follow-up assessments. Intravisit reliability was good for the right eye (ICCs = 0.82−0.98) and the left eye (ICCs = 0.75−0.89) for each of the 4 retinal quadrants. Inter-visit ICCs for each of the 4 retinal quadrants were good (ICC = 0.82−0.98). There was no consistent change in RNFL thickness longitudinally. Conclusions:In this pediatric cohort, RNFL thickness measures using handheld OCT provided good reliability within a single visit and between consecutive visits supporting its use as an adjunctive tool in the clinical setting. Further long-term follow-up is required to understand RNFL thickness changes in this specific population and its association with vigabatrin toxicity.Translational Relevance: The findings of good reliability and clinical feasibility would provide an opportunity for the handheld OCT to monitor reliably for vigabatrinassociated retinal toxicity in children who often show noncompliance to traditional testing approaches.

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Optical coherence tomography to monitor vigabatrin toxicity in children

Cited by 19 publications

References 21 publications

Retinal structure and function in vigabatrin‐treated adult patients with refractory complex partial seizures

Retinal structure and function in vigabatrin‐treated adult patients with refractory complex partial seizures

Everolimus as adjunctive therapy for tuberous sclerosis complex-associated partial-onset seizures

Reliability of Handheld Optical Coherence Tomography in Children Younger Than Three Years of Age Undergoing Vigabatrin Treatment for Childhood Epilepsy

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