Preclinical acute ocular safety study of combined intravitreal carboplatin and etoposide phosphate for retinoblastoma

Brian G. Mohney, Victor M. Elner, Andrew B. Smith, J. William Harbour, Brian D. Smith, David C. Musch, Stephen J. Smith

Research output: Contribution to journalArticle

1 Citation (Scopus)

Abstract

BACKGROUND AND OBJECTIVE: To describe the ocular toxicity of intravitreal carboplatin and etoposide phosphate (VP16P) in Dutch-Belted rabbits. MATERIALS AND METHODS: Twenty-two adult male Dutch-Belted rabbits (Cohort 1) each received a single, bilateral intravitreal injection (0.05 mL). For Cohort 1, safety was assessed via electroretinograms (ERGs) and ocular examination. Of nine total groups in Cohort 1, the frst fve received the following single agents: Group 1: normal saline; Group 2: VP16P 75 μg; Group 3: VP16P 100 μg; Group 4: carboplatin 4 μg; and Group 5: carboplatin 8 μg. Groups 6 through 9 received the following combination of carboplatin/VP16P, respectively: Group 6: 8 μg/75 μg, Group 7: 8 μg/50 μg, Group 8: 4 μg/50 μg, and Group 9: 2 μg/25 μg. Cohort 2 consisted of 15 Dutch-Belted rabbits in seven groups (Groups 10 through 16), each receiving a single, bilateral intravitreal injection. For Cohort 2, safety was assessed via histopathology. RESULTS: Groups 2 through 8 demonstrated a statistically signifcant decrease (relative to Group 1) in at least one ERG waveform amplitude obtained 4 weeks postinjection (P <.05). Group 9 (carbo 2 μg/VP16P 25 μg) did not manifest ERG toxicity. Fundoscopic toxicity consisted of slight-to-moderate attenuation of vessels in rabbits receiving doses above carbo 4 μg/VP16P 50 μg. Histopathologic retinal toxicity (Cohort 2) was dose-dependent, ranging from full-thickness atrophy in rabbits receiving the highest dose to normal in rabbits receiving carbo 2 μg/VP16P 25 μg. CONCLUSIONS: Combined carboplatin and VP16P may be compatible for intravitreal injection therapy, and a single dose of 2 μg/25 μg appears to be safe in a rabbit model. These agents may be a safer alternative to intravitreal melphalan (Alkeran; GlaxoSmithKline, Brentford, United Kingdom) for the treatment of vitreous seeds in retinoblastoma.

Original languageEnglish (US)
Pages (from-to)151-159
Number of pages9
JournalOphthalmic Surgery Lasers and Imaging Retina
Volume48
Issue number2
DOIs
StatePublished - Feb 1 2017

Fingerprint

Retinoblastoma
Carboplatin
Rabbits
Safety
Intravitreal Injections
Charcoal
Melphalan
etoposide phosphate
Atrophy
Seeds
Therapeutics

ASJC Scopus subject areas

  • Surgery
  • Ophthalmology

Cite this

Preclinical acute ocular safety study of combined intravitreal carboplatin and etoposide phosphate for retinoblastoma. / Mohney, Brian G.; Elner, Victor M.; Smith, Andrew B.; William Harbour, J.; Smith, Brian D.; Musch, David C.; Smith, Stephen J.

In: Ophthalmic Surgery Lasers and Imaging Retina, Vol. 48, No. 2, 01.02.2017, p. 151-159.

Research output: Contribution to journalArticle

Mohney, Brian G. ; Elner, Victor M. ; Smith, Andrew B. ; William Harbour, J. ; Smith, Brian D. ; Musch, David C. ; Smith, Stephen J. / Preclinical acute ocular safety study of combined intravitreal carboplatin and etoposide phosphate for retinoblastoma. In: Ophthalmic Surgery Lasers and Imaging Retina. 2017 ; Vol. 48, No. 2. pp. 151-159.
@article{985dedf730914f9a95ea6339d2e5c9b7,
title = "Preclinical acute ocular safety study of combined intravitreal carboplatin and etoposide phosphate for retinoblastoma",
abstract = "BACKGROUND AND OBJECTIVE: To describe the ocular toxicity of intravitreal carboplatin and etoposide phosphate (VP16P) in Dutch-Belted rabbits. MATERIALS AND METHODS: Twenty-two adult male Dutch-Belted rabbits (Cohort 1) each received a single, bilateral intravitreal injection (0.05 mL). For Cohort 1, safety was assessed via electroretinograms (ERGs) and ocular examination. Of nine total groups in Cohort 1, the frst fve received the following single agents: Group 1: normal saline; Group 2: VP16P 75 μg; Group 3: VP16P 100 μg; Group 4: carboplatin 4 μg; and Group 5: carboplatin 8 μg. Groups 6 through 9 received the following combination of carboplatin/VP16P, respectively: Group 6: 8 μg/75 μg, Group 7: 8 μg/50 μg, Group 8: 4 μg/50 μg, and Group 9: 2 μg/25 μg. Cohort 2 consisted of 15 Dutch-Belted rabbits in seven groups (Groups 10 through 16), each receiving a single, bilateral intravitreal injection. For Cohort 2, safety was assessed via histopathology. RESULTS: Groups 2 through 8 demonstrated a statistically signifcant decrease (relative to Group 1) in at least one ERG waveform amplitude obtained 4 weeks postinjection (P <.05). Group 9 (carbo 2 μg/VP16P 25 μg) did not manifest ERG toxicity. Fundoscopic toxicity consisted of slight-to-moderate attenuation of vessels in rabbits receiving doses above carbo 4 μg/VP16P 50 μg. Histopathologic retinal toxicity (Cohort 2) was dose-dependent, ranging from full-thickness atrophy in rabbits receiving the highest dose to normal in rabbits receiving carbo 2 μg/VP16P 25 μg. CONCLUSIONS: Combined carboplatin and VP16P may be compatible for intravitreal injection therapy, and a single dose of 2 μg/25 μg appears to be safe in a rabbit model. These agents may be a safer alternative to intravitreal melphalan (Alkeran; GlaxoSmithKline, Brentford, United Kingdom) for the treatment of vitreous seeds in retinoblastoma.",
author = "Mohney, {Brian G.} and Elner, {Victor M.} and Smith, {Andrew B.} and {William Harbour}, J. and Smith, {Brian D.} and Musch, {David C.} and Smith, {Stephen J.}",
year = "2017",
month = "2",
day = "1",
doi = "10.3928/23258160-20170130-09",
language = "English (US)",
volume = "48",
pages = "151--159",
journal = "Ophthalmic Surgery Lasers and Imaging Retina",
issn = "2325-8160",
publisher = "Slack Incorporated",
number = "2",

}

TY - JOUR

T1 - Preclinical acute ocular safety study of combined intravitreal carboplatin and etoposide phosphate for retinoblastoma

AU - Mohney, Brian G.

AU - Elner, Victor M.

AU - Smith, Andrew B.

AU - William Harbour, J.

AU - Smith, Brian D.

AU - Musch, David C.

AU - Smith, Stephen J.

PY - 2017/2/1

Y1 - 2017/2/1

N2 - BACKGROUND AND OBJECTIVE: To describe the ocular toxicity of intravitreal carboplatin and etoposide phosphate (VP16P) in Dutch-Belted rabbits. MATERIALS AND METHODS: Twenty-two adult male Dutch-Belted rabbits (Cohort 1) each received a single, bilateral intravitreal injection (0.05 mL). For Cohort 1, safety was assessed via electroretinograms (ERGs) and ocular examination. Of nine total groups in Cohort 1, the frst fve received the following single agents: Group 1: normal saline; Group 2: VP16P 75 μg; Group 3: VP16P 100 μg; Group 4: carboplatin 4 μg; and Group 5: carboplatin 8 μg. Groups 6 through 9 received the following combination of carboplatin/VP16P, respectively: Group 6: 8 μg/75 μg, Group 7: 8 μg/50 μg, Group 8: 4 μg/50 μg, and Group 9: 2 μg/25 μg. Cohort 2 consisted of 15 Dutch-Belted rabbits in seven groups (Groups 10 through 16), each receiving a single, bilateral intravitreal injection. For Cohort 2, safety was assessed via histopathology. RESULTS: Groups 2 through 8 demonstrated a statistically signifcant decrease (relative to Group 1) in at least one ERG waveform amplitude obtained 4 weeks postinjection (P <.05). Group 9 (carbo 2 μg/VP16P 25 μg) did not manifest ERG toxicity. Fundoscopic toxicity consisted of slight-to-moderate attenuation of vessels in rabbits receiving doses above carbo 4 μg/VP16P 50 μg. Histopathologic retinal toxicity (Cohort 2) was dose-dependent, ranging from full-thickness atrophy in rabbits receiving the highest dose to normal in rabbits receiving carbo 2 μg/VP16P 25 μg. CONCLUSIONS: Combined carboplatin and VP16P may be compatible for intravitreal injection therapy, and a single dose of 2 μg/25 μg appears to be safe in a rabbit model. These agents may be a safer alternative to intravitreal melphalan (Alkeran; GlaxoSmithKline, Brentford, United Kingdom) for the treatment of vitreous seeds in retinoblastoma.

AB - BACKGROUND AND OBJECTIVE: To describe the ocular toxicity of intravitreal carboplatin and etoposide phosphate (VP16P) in Dutch-Belted rabbits. MATERIALS AND METHODS: Twenty-two adult male Dutch-Belted rabbits (Cohort 1) each received a single, bilateral intravitreal injection (0.05 mL). For Cohort 1, safety was assessed via electroretinograms (ERGs) and ocular examination. Of nine total groups in Cohort 1, the frst fve received the following single agents: Group 1: normal saline; Group 2: VP16P 75 μg; Group 3: VP16P 100 μg; Group 4: carboplatin 4 μg; and Group 5: carboplatin 8 μg. Groups 6 through 9 received the following combination of carboplatin/VP16P, respectively: Group 6: 8 μg/75 μg, Group 7: 8 μg/50 μg, Group 8: 4 μg/50 μg, and Group 9: 2 μg/25 μg. Cohort 2 consisted of 15 Dutch-Belted rabbits in seven groups (Groups 10 through 16), each receiving a single, bilateral intravitreal injection. For Cohort 2, safety was assessed via histopathology. RESULTS: Groups 2 through 8 demonstrated a statistically signifcant decrease (relative to Group 1) in at least one ERG waveform amplitude obtained 4 weeks postinjection (P <.05). Group 9 (carbo 2 μg/VP16P 25 μg) did not manifest ERG toxicity. Fundoscopic toxicity consisted of slight-to-moderate attenuation of vessels in rabbits receiving doses above carbo 4 μg/VP16P 50 μg. Histopathologic retinal toxicity (Cohort 2) was dose-dependent, ranging from full-thickness atrophy in rabbits receiving the highest dose to normal in rabbits receiving carbo 2 μg/VP16P 25 μg. CONCLUSIONS: Combined carboplatin and VP16P may be compatible for intravitreal injection therapy, and a single dose of 2 μg/25 μg appears to be safe in a rabbit model. These agents may be a safer alternative to intravitreal melphalan (Alkeran; GlaxoSmithKline, Brentford, United Kingdom) for the treatment of vitreous seeds in retinoblastoma.

UR - http://www.scopus.com/inward/record.url?scp=85014950850&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85014950850&partnerID=8YFLogxK

U2 - 10.3928/23258160-20170130-09

DO - 10.3928/23258160-20170130-09

M3 - Article

C2 - 28195618

AN - SCOPUS:85014950850

VL - 48

SP - 151

EP - 159

JO - Ophthalmic Surgery Lasers and Imaging Retina

JF - Ophthalmic Surgery Lasers and Imaging Retina

SN - 2325-8160

IS - 2

ER -