A lack of clinically apparent vision loss among patients treated with vigabatrin with infantile spasms: The UCLA experience

Madeline D. Schwarz; Menglu Li; Jackie Tsao; Raymond Zhou; Yvonne W. Wu; Raman Sankar; Joyce Y. Wu; Shaun A. Hussain

doi:10.1016/j.yebeh.2016.01.012

A lack of clinically apparent vision loss among patients treated with vigabatrin with infantile spasms: The UCLA experience

Madeline D. Schwarz, Menglu Li, Jackie Tsao, Raymond Zhou, Yvonne W. Wu, Raman Sankar, Joyce Y. Wu, Shaun A. Hussain^*

^*Corresponding author for this work

Pediatrics

Research output: Contribution to journal › Article › peer-review

26 Scopus citations

Abstract

Background: Vigabatrin (VGB) is one of two FDA-approved medications for treatment of infantile spasms. Despite demonstrated efficacy, its use has been curtailed by reports indicating a substantial risk of VGB-associated visual field loss (VAVFL). As these reports have conflicted with our clinical observations in routine practice, we systematically reviewed the experiences of patients treated with VGB at UCLA to estimate the prevalence of clinically apparent VAVFL. Methods: Patients with video-EEG-confirmed infantile spasms evaluated at our center between February 2007 and February 2014 were retrospectively identified. Among patients with VGB exposure, we documented relevant clinical factors and determined the duration of therapy, peak dosage, and cumulative dosage. Based on a review of serial neurologic and ophthalmologic reports and aided by electroretinography (ERG) assessments when available, we ascertained whether each patient had evidence of clinically apparent vision impairment (i.e., recognized by a neurologist or ophthalmologist during any follow-up visit) and whether or not the vision loss was attributed to VGB exposure (i.e., evidence of bilateral, symmetric, and peripheral visual field loss), either by the treating physician or on retrospective review by the study team. Results: During the study period, 257 patients with video-EEG-confirmed infantile spasms were identified. One hundred and forty-three (56%) patients received VGB. Although visual loss of any cause was common among patients with (31%) and without (32%) VGB exposure, there were no cases in which visual field defects were plausibly linked to VGB. We estimate that the risk of clinically significant VAVFL does not exceed 3.2% (95% CI upper bound). Vision loss was never characterized as exclusively peripheral and was always better explained by other causes (e.g., hemianopsia following hemispherectomy and cortical vision impairment after hypoxic ischemic encephalopathy). Precise quantitative exposure data were available for 104 (73%) patients treated with VGB, among whom the median duration of treatment was 8.6 (IQR: 3.7-16.2) months, the median peak dosage was 141.5 (IQR: 104.8-166.0) mg/kg/day, and the median cumulative dosage was 314 (IQR: 140.8-645.7) grams. Conclusions: We found that the risk of clinically apparent vision loss is quite low among young children treated for infantile spasms. Our estimate of risk contrasts with prior studies and likely reflects our ascertainment of vision loss without the aid of perimetry or serial ERG, the short treatment duration, and the relatively young age of our patients. In the treatment of infantile spasms, risk-benefit assessment should consider both the low prevalence of ERG-identified VAVFL among patients with brief (<. 6-9 months) exposure and the very low prevalence of clinically apparent VAVFL in this population.

Original language	English (US)
Pages (from-to)	29-33
Number of pages	5
Journal	Epilepsy and Behavior
Volume	57
DOIs	https://doi.org/10.1016/j.yebeh.2016.01.012
State	Published - Apr 1 2016

Funding

This investigator-initiated study was accomplished with an unrestricted grant (20130520) from Lundbeck, LLC. The sponsor did not contribute to the study design, data collection, analysis, interpretation, drafting of the manuscript, or decision to submit the article for publication. We thank Dr. Steven Nusinowitz for his critical review of the manuscript.Disclosures/potential conflict of interestsDr. Sankar serves on scientific advisory boards for and has received honoraria and funding for travel from Acorda Therapeutics, Cyberonics, UCB Pharma, Sunovion, Upsher-Smith, and Lundbeck Pharma; receives royalties from the publication of Pediatric Neurology, 3rd ed. (Demos Publishing, 2008) and Epilepsy: Mechanisms, Models, and Translational Perspectives (CRC Press, 2011); and serves on speakers'' bureaus for and has received speaker honoraria from UCB, Supernus, Cyberonics, and Lundbeck. He has also received research support from Bluebird Bio, Acorda Therapeutics, Insys Therapeutics, NIMH, and NINDS.Dr. J. Wu serves on the professional advisory board for the Tuberous Sclerosis Alliance, has received honoraria from and serves on the scientific advisory board and the speakers'' bureaus for Novartis Pharmaceuticals, Inc. and Lundbeck, and has received research support from the Tuberous Sclerosis Alliance, Novartis Pharmaceuticals, Inc., Today''s and Tomorrow''s Children Fund, the Department of Defense/Congressionally Directed Medical Research Program, and the NIH (U01NS082320, P20NS080199, R01NS082649, and U54NS092090).Dr. Hussain received an unrestricted grant from Lundbeck, LLC to conduct this study, has received research support from the Epilepsy Therapy Project, Milken Family Foundation, Hughes Family Foundation, the Elsie and Isaac Fogelman Endowment, Eisai, Inc., Insys Therapeutics, GW Pharmaceuticals, and the NIH (R34MH089299), and has received personal compensation for service on the scientific advisory boards of Questcor Pharmaceuticals and Upsher-Smith Laboratories and as a consultant to Eisai, Inc.Ms. Schwarz, Ms. Li, Mr. Zhou, Ms. Tsao, and Dr. Y. Wu have no financial disclosures to report. Dr. J. Wu serves on the professional advisory board for the Tuberous Sclerosis Alliance, has received honoraria from and serves on the scientific advisory board and the speakers' bureaus for Novartis Pharmaceuticals, Inc. and Lundbeck, and has received research support from the Tuberous Sclerosis Alliance , Novartis Pharmaceuticals, Inc. , Today's and Tomorrow's Children Fund , the Department of Defense/Congressionally Directed Medical Research Program , and the NIH ( U01NS082320 , P20NS080199 , R01NS082649 , and U54NS092090 ). Dr. Hussain received an unrestricted grant from Lundbeck, LLC to conduct this study, has received research support from the Epilepsy Therapy Project , Milken Family Foundation , Hughes Family Foundation , the Elsie and Isaac Fogelman Endowment , Eisai, Inc. , Insys Therapeutics , GW Pharmaceuticals , and the NIH ( R34MH089299 ), and has received personal compensation for service on the scientific advisory boards of Questcor Pharmaceuticals and Upsher-Smith Laboratories and as a consultant to Eisai, Inc.

Keywords

Epileptic spasms
Peripheral
Retina
Vision loss
West syndrome

ASJC Scopus subject areas

Clinical Neurology
Neurology
Behavioral Neuroscience

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10.1016/j.yebeh.2016.01.012

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@article{294bbe2214ac4046af1308ba41d2983e,

title = "A lack of clinically apparent vision loss among patients treated with vigabatrin with infantile spasms: The UCLA experience",

abstract = "Background: Vigabatrin (VGB) is one of two FDA-approved medications for treatment of infantile spasms. Despite demonstrated efficacy, its use has been curtailed by reports indicating a substantial risk of VGB-associated visual field loss (VAVFL). As these reports have conflicted with our clinical observations in routine practice, we systematically reviewed the experiences of patients treated with VGB at UCLA to estimate the prevalence of clinically apparent VAVFL. Methods: Patients with video-EEG-confirmed infantile spasms evaluated at our center between February 2007 and February 2014 were retrospectively identified. Among patients with VGB exposure, we documented relevant clinical factors and determined the duration of therapy, peak dosage, and cumulative dosage. Based on a review of serial neurologic and ophthalmologic reports and aided by electroretinography (ERG) assessments when available, we ascertained whether each patient had evidence of clinically apparent vision impairment (i.e., recognized by a neurologist or ophthalmologist during any follow-up visit) and whether or not the vision loss was attributed to VGB exposure (i.e., evidence of bilateral, symmetric, and peripheral visual field loss), either by the treating physician or on retrospective review by the study team. Results: During the study period, 257 patients with video-EEG-confirmed infantile spasms were identified. One hundred and forty-three (56%) patients received VGB. Although visual loss of any cause was common among patients with (31%) and without (32%) VGB exposure, there were no cases in which visual field defects were plausibly linked to VGB. We estimate that the risk of clinically significant VAVFL does not exceed 3.2% (95% CI upper bound). Vision loss was never characterized as exclusively peripheral and was always better explained by other causes (e.g., hemianopsia following hemispherectomy and cortical vision impairment after hypoxic ischemic encephalopathy). Precise quantitative exposure data were available for 104 (73%) patients treated with VGB, among whom the median duration of treatment was 8.6 (IQR: 3.7-16.2) months, the median peak dosage was 141.5 (IQR: 104.8-166.0) mg/kg/day, and the median cumulative dosage was 314 (IQR: 140.8-645.7) grams. Conclusions: We found that the risk of clinically apparent vision loss is quite low among young children treated for infantile spasms. Our estimate of risk contrasts with prior studies and likely reflects our ascertainment of vision loss without the aid of perimetry or serial ERG, the short treatment duration, and the relatively young age of our patients. In the treatment of infantile spasms, risk-benefit assessment should consider both the low prevalence of ERG-identified VAVFL among patients with brief (<. 6-9 months) exposure and the very low prevalence of clinically apparent VAVFL in this population.",

keywords = "Epileptic spasms, Peripheral, Retina, Vision loss, West syndrome",

author = "Schwarz, {Madeline D.} and Menglu Li and Jackie Tsao and Raymond Zhou and Wu, {Yvonne W.} and Raman Sankar and Wu, {Joyce Y.} and Hussain, {Shaun A.}",

note = "Publisher Copyright: {\textcopyright} 2016 Elsevier Inc.",

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doi = "10.1016/j.yebeh.2016.01.012",

language = "English (US)",

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T1 - A lack of clinically apparent vision loss among patients treated with vigabatrin with infantile spasms

T2 - The UCLA experience

AU - Schwarz, Madeline D.

AU - Li, Menglu

AU - Tsao, Jackie

AU - Zhou, Raymond

AU - Wu, Yvonne W.

AU - Sankar, Raman

AU - Wu, Joyce Y.

AU - Hussain, Shaun A.

PY - 2016/4/1

Y1 - 2016/4/1

N2 - Background: Vigabatrin (VGB) is one of two FDA-approved medications for treatment of infantile spasms. Despite demonstrated efficacy, its use has been curtailed by reports indicating a substantial risk of VGB-associated visual field loss (VAVFL). As these reports have conflicted with our clinical observations in routine practice, we systematically reviewed the experiences of patients treated with VGB at UCLA to estimate the prevalence of clinically apparent VAVFL. Methods: Patients with video-EEG-confirmed infantile spasms evaluated at our center between February 2007 and February 2014 were retrospectively identified. Among patients with VGB exposure, we documented relevant clinical factors and determined the duration of therapy, peak dosage, and cumulative dosage. Based on a review of serial neurologic and ophthalmologic reports and aided by electroretinography (ERG) assessments when available, we ascertained whether each patient had evidence of clinically apparent vision impairment (i.e., recognized by a neurologist or ophthalmologist during any follow-up visit) and whether or not the vision loss was attributed to VGB exposure (i.e., evidence of bilateral, symmetric, and peripheral visual field loss), either by the treating physician or on retrospective review by the study team. Results: During the study period, 257 patients with video-EEG-confirmed infantile spasms were identified. One hundred and forty-three (56%) patients received VGB. Although visual loss of any cause was common among patients with (31%) and without (32%) VGB exposure, there were no cases in which visual field defects were plausibly linked to VGB. We estimate that the risk of clinically significant VAVFL does not exceed 3.2% (95% CI upper bound). Vision loss was never characterized as exclusively peripheral and was always better explained by other causes (e.g., hemianopsia following hemispherectomy and cortical vision impairment after hypoxic ischemic encephalopathy). Precise quantitative exposure data were available for 104 (73%) patients treated with VGB, among whom the median duration of treatment was 8.6 (IQR: 3.7-16.2) months, the median peak dosage was 141.5 (IQR: 104.8-166.0) mg/kg/day, and the median cumulative dosage was 314 (IQR: 140.8-645.7) grams. Conclusions: We found that the risk of clinically apparent vision loss is quite low among young children treated for infantile spasms. Our estimate of risk contrasts with prior studies and likely reflects our ascertainment of vision loss without the aid of perimetry or serial ERG, the short treatment duration, and the relatively young age of our patients. In the treatment of infantile spasms, risk-benefit assessment should consider both the low prevalence of ERG-identified VAVFL among patients with brief (<. 6-9 months) exposure and the very low prevalence of clinically apparent VAVFL in this population.

AB - Background: Vigabatrin (VGB) is one of two FDA-approved medications for treatment of infantile spasms. Despite demonstrated efficacy, its use has been curtailed by reports indicating a substantial risk of VGB-associated visual field loss (VAVFL). As these reports have conflicted with our clinical observations in routine practice, we systematically reviewed the experiences of patients treated with VGB at UCLA to estimate the prevalence of clinically apparent VAVFL. Methods: Patients with video-EEG-confirmed infantile spasms evaluated at our center between February 2007 and February 2014 were retrospectively identified. Among patients with VGB exposure, we documented relevant clinical factors and determined the duration of therapy, peak dosage, and cumulative dosage. Based on a review of serial neurologic and ophthalmologic reports and aided by electroretinography (ERG) assessments when available, we ascertained whether each patient had evidence of clinically apparent vision impairment (i.e., recognized by a neurologist or ophthalmologist during any follow-up visit) and whether or not the vision loss was attributed to VGB exposure (i.e., evidence of bilateral, symmetric, and peripheral visual field loss), either by the treating physician or on retrospective review by the study team. Results: During the study period, 257 patients with video-EEG-confirmed infantile spasms were identified. One hundred and forty-three (56%) patients received VGB. Although visual loss of any cause was common among patients with (31%) and without (32%) VGB exposure, there were no cases in which visual field defects were plausibly linked to VGB. We estimate that the risk of clinically significant VAVFL does not exceed 3.2% (95% CI upper bound). Vision loss was never characterized as exclusively peripheral and was always better explained by other causes (e.g., hemianopsia following hemispherectomy and cortical vision impairment after hypoxic ischemic encephalopathy). Precise quantitative exposure data were available for 104 (73%) patients treated with VGB, among whom the median duration of treatment was 8.6 (IQR: 3.7-16.2) months, the median peak dosage was 141.5 (IQR: 104.8-166.0) mg/kg/day, and the median cumulative dosage was 314 (IQR: 140.8-645.7) grams. Conclusions: We found that the risk of clinically apparent vision loss is quite low among young children treated for infantile spasms. Our estimate of risk contrasts with prior studies and likely reflects our ascertainment of vision loss without the aid of perimetry or serial ERG, the short treatment duration, and the relatively young age of our patients. In the treatment of infantile spasms, risk-benefit assessment should consider both the low prevalence of ERG-identified VAVFL among patients with brief (<. 6-9 months) exposure and the very low prevalence of clinically apparent VAVFL in this population.

KW - Epileptic spasms

KW - Peripheral

KW - Retina

KW - Vision loss

KW - West syndrome

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A lack of clinically apparent vision loss among patients treated with vigabatrin with infantile spasms: The UCLA experience

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