Get 20M+ Full-Text Papers For Less Than $1.50/day. Start a 14-Day Trial for You and Your Team.

Learn More →

Superselective Intraophthalmic Artery Chemotherapy in a Nonhuman Primate Model

Superselective Intraophthalmic Artery Chemotherapy in a Nonhuman Primate Model ImportanceWe describe the histopathologic findings in a nonhuman primate (NHP) model of superselective intraophthalmic artery chemotherapy (SSIOAC), detailing ocular and orbital vascular adverse effects. ObjectiveTo further document, using comprehensive ocular and orbital histopathology, previously reported toxic effects observed with real-time ophthalmoscopy during SSIOAC in a NHP model. DesignComparative interventional case series. SettingPreclinical trial approved under the guidelines of the Institutional Animal Care and Utilization committee. ParticipantsSix adult male rhesus macaques (Macacca mulatta). InterventionsThe right eye of each NHP was treated with 3 cycles of SSIOAC using either melphalan (5 mg/30 mL) or carboplatin (30 mg/30 mL). Both eyes in each animal were enucleated 6 hours after the final procedure, before euthanasia and formalin perfusion of the NHP; we then performed orbital dissection of the arterial vasculature and optic nerves. Main Outcome MeasuresHistopathologic examination of the eyes, optic nerves, and orbital vessels of the 6 treated NHPs. ResultsWe found leukostasis with retinal arteriole occlusion in all treated eyes. Retinal endothelial cells stained positive for 2 inflammatory markers, intercellular adhesion molecule 1 and interleukin 8. Transmission electron microscopy revealed occlusion of the retinal vessels with ultrastructural changes in the endothelial cells and surrounding pericytes. Additional findings included nerve fiber layer infarcts, central retinal artery thrombosis, hypertrophy and occlusion of choroidal arteries with disruption of the internal elastic lamina, patchy choroidal inflammation, and birefringent intravascular foreign bodies. Orbital findings included ophthalmic artery and central retinal artery wall dissection, fracturing of the internal elastic lamina, intimal hyperplasia, and eyelid vessel damage. Optic nerves displayed hemorrhage, leukostasis, and foreign body crystallization. Control eyes, optic nerves, and orbital vessels were normal. Conclusions and RelevanceHistopathologic examination of our nonhuman primate model for SSIOAC revealed significant toxic effects in the ocular and orbital vasculature. These findings substantiate previous observations with real-time retinal imaging and parallel reported vascular toxic effects in children with retinoblastoma treated with SSIOAC. http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png JAMA Ophthalmology American Medical Association

Superselective Intraophthalmic Artery Chemotherapy in a Nonhuman Primate Model

Download PDF
9 pages
Read Article

Loading next page...
 
/lp/american-medical-association/superselective-intraophthalmic-artery-chemotherapy-in-a-nonhuman-erj30JkDPo
Publisher
American Medical Association
Copyright
Copyright 2013 American Medical Association. All Rights Reserved. Applicable FARS/DFARS Restrictions Apply to Government Use.
ISSN
2168-6165
eISSN
2168-6173
DOI
10.1001/jamaophthalmol.2013.2065
pmid
23619956
Publisher site
See Article on Publisher Site

Abstract

ImportanceWe describe the histopathologic findings in a nonhuman primate (NHP) model of superselective intraophthalmic artery chemotherapy (SSIOAC), detailing ocular and orbital vascular adverse effects. ObjectiveTo further document, using comprehensive ocular and orbital histopathology, previously reported toxic effects observed with real-time ophthalmoscopy during SSIOAC in a NHP model. DesignComparative interventional case series. SettingPreclinical trial approved under the guidelines of the Institutional Animal Care and Utilization committee. ParticipantsSix adult male rhesus macaques (Macacca mulatta). InterventionsThe right eye of each NHP was treated with 3 cycles of SSIOAC using either melphalan (5 mg/30 mL) or carboplatin (30 mg/30 mL). Both eyes in each animal were enucleated 6 hours after the final procedure, before euthanasia and formalin perfusion of the NHP; we then performed orbital dissection of the arterial vasculature and optic nerves. Main Outcome MeasuresHistopathologic examination of the eyes, optic nerves, and orbital vessels of the 6 treated NHPs. ResultsWe found leukostasis with retinal arteriole occlusion in all treated eyes. Retinal endothelial cells stained positive for 2 inflammatory markers, intercellular adhesion molecule 1 and interleukin 8. Transmission electron microscopy revealed occlusion of the retinal vessels with ultrastructural changes in the endothelial cells and surrounding pericytes. Additional findings included nerve fiber layer infarcts, central retinal artery thrombosis, hypertrophy and occlusion of choroidal arteries with disruption of the internal elastic lamina, patchy choroidal inflammation, and birefringent intravascular foreign bodies. Orbital findings included ophthalmic artery and central retinal artery wall dissection, fracturing of the internal elastic lamina, intimal hyperplasia, and eyelid vessel damage. Optic nerves displayed hemorrhage, leukostasis, and foreign body crystallization. Control eyes, optic nerves, and orbital vessels were normal. Conclusions and RelevanceHistopathologic examination of our nonhuman primate model for SSIOAC revealed significant toxic effects in the ocular and orbital vasculature. These findings substantiate previous observations with real-time retinal imaging and parallel reported vascular toxic effects in children with retinoblastoma treated with SSIOAC.

Journal

JAMA Ophthalmology – American Medical Association

Published: Jul 1, 2013

References

  • A phase I/II study of direct intraarterial (ophthalmic artery) chemotherapy with melphalan for intraocular retinoblastoma initial results [published online March 14, 2008].
    Abramson, DH; Dunkel, IJ; Brodie, SE; Kim, JW; Gobin, YP
  • Real-time ophthalmoscopic findings of superselective intraophthalmic artery chemotherapy in a nonhuman primate model.
    Wilson, MW; Jackson, JS; Phillips, BX
  • Clinicopathologic review of enucleated eyes after intra-arterial chemotherapy with melphalan for advanced retinoblastoma.
    Vajzovic, LM; Murray, TG; Aziz-Sultan, MA
  • Histopathologic findings of eyes enucleated after treatment with chemosurgery for retinoblastoma.
    Graeber, CP; Gobin, YP; Marr, BP
  • Enucleated eyes after failed intra-arterial infusion of chemotherapy for unilateral retinoblastoma: histopathologic evaluation of vitreous seeding.
    Kim, J; Do, H; Egbert, P
  • Histopathologic observations after intra-arterial chemotherapy for retinoblastoma.
    Eagle, RC; Shields, CL; Bianciotto, C; Jabbour, P; Shields, JA
  • Intra-arterial chemotherapy for retinoblastoma: report No. 1, control of retinal tumors, subretinal seeds, and vitreous seeds.
    Shields, CL; Bianciotto, CG; Jabbour, P
  • Superselective ophthalmic artery infusion of melphalan for intraocular retinoblastoma: preliminary results from 140 treatments [published online January 23, 2012].
    Venturi, C; Bracco, S; Cerase, A
  • Occurrence of sectoral choroidal occlusive vasculopathy and retinal arteriolar embolization after superselective ophthalmic artery chemotherapy for advanced intraocular retinoblastoma.
    Munier, FL; Beck-Popovic, M; Balmer, A; Gaillard, MC; Bovey, E; Binaghi, S
  • Retinoblastoma management: advances in enucleation, intravenous chemoreduction, and intra-arterial chemotherapy.
    Shields, CL; Shields, JA
  • Supraselective intra-arterial chemotherapy: evaluation of treatment-related complications in advanced retinoblastoma.
    Vajzovic, LM; Murray, TG; Aziz-Sultan, MA
  • Intra-arterial chemotherapy for retinoblastoma: report No. 2, treatment complications.
    Shields, CL; Bianciotto, CG; Jabbour, P
  • Intra-arterial chemotherapy for the management of retinoblastoma: four-year experience.
    Gobin, YP; Dunkel, IJ; Marr, BP; Brodie, SE; Abramson, DH
  • Efficacy and complications of super-selective intra-ophthalmic artery melphalan for the treatment of refractory retinoblastoma.
    Muen, WJ; Kingston, JE; Robertson, F; Brew, S; Sagoo, MS; Reddy, MA
  • Intra-ophthalmic artery chemotherapy triggers vascular toxicity through endothelial cell inflammation and leukostasis.
    Steinle, JJ; Zhang, Q; Thompson, KE
  • High-dose intravenous melphalan: a review.
    Samuels, BL; Bitran, JD
  • Isolated limb perfusion with melphalan in the treatment of malignant melanoma of the extremities: a systematic review of randomised controlled trials.
    Lens, MB; Dawes, M
  • Real-time ophthalmoscopic findings of intraophthalmic artery chemotherapy in retinoblastoma.
    Fallaha, N; Dubois, J; Carret, AS; Callejo, SA; Hamel, P; Superstein, R
  • Restenosis after percutaneous transluminal coronary angioplasty: pathologic observations in 20 patients.
    Nobuyoshi, M; Kimura, T; Ohishi, H
  • Restenosis after balloon angioplasty: a practical proliferative model in porcine coronary arteries.
    Schwartz, RS; Murphy, JG; Edwards, WD; Camrud, AR; Vliestra, RE; Holmes, DR
  • Superselective ophthalmic artery chemotherapy as primary treatment for retinoblastoma (chemosurgery).
    Abramson, DH; Dunkel, IJ; Brodie, SE; Marr, B; Gobin, YP
  • Validating a nonhuman primate model of super-selective intraophthalmic artery chemotherapy: comparing ophthalmic artery diameters.
    Ditta, LC; Choudhri, AF; Tse, BC

You’re reading a free preview. Subscribe to read the entire article.

Try 2 weeks free now

DeepDyve is your
personal research library

It’s your single place to instantly
discover and read the research
that matters to you.

Enjoy affordable access to
over 18 million articles from more than
15,000 peer-reviewed journals.

All for just $49/month

Explore the DeepDyve Library

or browse the journals available

Search

Query the DeepDyve database, plus search all of PubMed and Google Scholar seamlessly

Organize

Save any article or search result from DeepDyve, PubMed, and Google Scholar... all in one place.

Access

Get unlimited, online access to over 18 million full-text articles from more than 15,000 scientific journals.

Your journals are on DeepDyve

Read from thousands of the leading scholarly journals from SpringerNature, Wiley-Blackwell, Oxford University Press and more.

All the latest content is available, no embargo periods.

See the journals in your area

DeepDyve

Freelancer

DeepDyve

Pro

Price

FREE

$49/month
$499/year

Save searches from
Google Scholar,
PubMed

Create folders to
organize your research

Export folders, citations

Read DeepDyve articles

Abstract access only

Unlimited access to over
18 million full-text articles

Print

20 pages / month

Sign up
for free
Start 14 day
Free Trial