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Orbital Swelling in a Child With Retinoblastoma Following Intra-arterial Chemotherapy

Educational Objective
Based on this clinical scenario and the accompanying image, understand how to arrive at a correct diagnosis.
1 Credit CME

A 9-month-old girl presented to the emergency department with significant left periocular edema and erythema 3 days after receiving intra-arterial chemotherapy (IAC) with 0.4 mg/kg of melphalan, 50 mg of carboplatin, and 2 mg of topotecan (with routine intravenous dexamethasone therapy, 0.5 mg/kg) for treatment of unilateral International Classification of Retinoblastoma group C retinoblastoma in the left eye (Figure, A). At the time of IAC, she had an upper respiratory tract infection (coughing, congestion, rhinorrhea, fever [temperature of 38.9 °C]). On postoperative day 1, her temperature reached 39.4 °C, and she was diagnosed as having bilateral acute otitis media and discharged with amoxicillin therapy. On postoperative day 3, she returned to the emergency department with left eye swelling, continued fever, and poor oral intake. On physical examination, her temperature was 40.2 °C, and periorbital swelling and erythema were present without drainage. Dilated fundus examination at the bedside showed the known large retinoblastoma tumor. A large exudative retinal detachment was noted, which was not present prior to treatment. Blood bacterial culture testing showed no growth, respiratory viral testing revealed rhinovirus, and results of comprehensive metabolic testing were unremarkable. Complete blood cell count showed mild leukopenia (2700/μL [to convert to ×109 per liter, multiply by 0.001]) and anemia (hemoglobin, 9.2 g/dL [to convert to grams per liter, multiply by 10]) but were otherwise within reference ranges. Computed tomography scan of the orbits, recommended by the on-call general ophthalmologist, demonstrated preseptal and periorbital soft tissue swelling and edema with subtle retrobulbar stranding, without substantial proptosis, along with retinal detachment (Figure, B). She was admitted for intravenous fluids for her noted dehydration.

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Periorbital edema related to administration of IAC

C. Start systemic corticosteroids

The differential diagnosis of eye swelling in a patient with cancer receiving chemotherapy includes infectious (preseptal/orbital cellulitis), neoplastic (extraocular/orbital tumor), and inflammatory causes. IAC involves delivering chemotherapy into the ophthalmic artery via endovascular microcatheter, navigated under fluoroscopic guidance, either directly, balloon assisted, or via an external carotid artery anastomosis.1 IAC is increasingly used for retinoblastoma, both as first-line and salvage therapy after failed intravenous chemotherapy, due to increased efficacy of IAC for advanced intraocular disease.2 Globe salvage rates for International Classification of Retinoblastoma group D eyes with IAC (85.1%) exceed published rates for intravenous chemoreduction (36.7%).3

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Article Information

Corresponding Author: Anthony B. Daniels, MD, MSc, Division of Ocular Oncology and Pathology, Department of Ophthalmology and Visual Sciences, Vanderbilt Eye Institute, Vanderbilt University Medical Center, 2311 Pierce Ave, Ste 2252, Nashville, TN 37205 (anthony.b.daniels@vumc.org).

Published Online: January 21, 2021. doi:10.1001/jamaophthalmol.2020.4675

Conflict of Interest Disclosures: Dr Froehler has received grants from the National Institutes of Health, Genentech, Medtronic, Stryker, Microvention, and Penumbra and personal fees from Genentech, Medtronic, Stryker, Balt, Cerenovus, Viz.ai, and Corindus. Dr Daniels has received grants from the National Eye Institute and Research to Prevent Blindness Foundation during the conduct of the study and grants from Spectrum Pharmaceuticals and Alcon Research Institute outside the submitted work; and has a patent with Vanderbilt University Medical Center. No other disclosures were reported.

Funding/Support: This work was supported by grant K08 EY 027464 from the National Eye Institute (Dr Daniels), by a Research to Prevent Blindness Career Development Award (Dr Daniels), and by an unrestricted grant from Research to Prevent Blindness to the Vanderbilt Department of Ophthalmology and Visual Sciences.

Role of the Funder/Sponsor: The funders had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; and decision to submit the manuscript for publication.

Additional Contributions: We thank the mother of the patient for granting permission to publish this information.

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Abramson  DH , Daniels  AB , Marr  BP ,  et al.  Intra-arterial chemotherapy (ophthalmic artery chemosurgery) for group D retinoblastoma.   PLoS One. 2016;11(1):e0146582. doi:10.1371/journal.pone.0146582PubMedGoogle Scholar
Yuan  S , Friedman  DL , Daniels  AB .  Alternative chemotherapeutic agents for the treatment of retinoblastoma using the intra-arterial and intravitreal routes: a path forward toward drug discovery.   Int Ophthalmol Clin. 2017;57(1):129-141. doi:10.1097/IIO.0000000000000154PubMedGoogle ScholarCrossref
Chen  Q , Zhang  B , Dong  Y ,  et al.  Intra-arterial chemotherapy as primary or secondary treatment for infants diagnosed with advanced retinoblastoma before 3 months of age.   BMC Cancer. 2019;19(1):693. doi:10.1186/s12885-019-5844-5PubMedGoogle ScholarCrossref
Daniels  AB , Froehler  MT , Nunnally  AH ,  et al.  Rabbit model of intra-arterial chemotherapy toxicity demonstrates retinopathy and vasculopathy related to drug and dose, not procedure or approach.   Invest Ophthalmol Vis Sci. 2019;60(4):954-964. doi:10.1167/iovs.18-25346PubMedGoogle ScholarCrossref
Oatess  TL , Chen  PH , Daniels  AB , Himmel  LE .  Severe periocular edema after intraarterial carboplatin chemotherapy for retinoblastoma in a rabbit (Oryctolagus cuniculus) model.   Comp Med. 2020;70(2):176-182. doi:10.30802/AALAS-CM-18-000146PubMedGoogle ScholarCrossref
Moore  GH , Rootman  DB .  Orbital inflammatory disease management.   Expert Rev Ophthalmol. 2016;11(6):415-428. doi:10.1080/17469899.2016.1233399Google ScholarCrossref
Santapuram  PR , Schremp  EA , Friedman  DL , Koyama  T , Froehler  MT , Daniels  AB .  Adverse events, treatment burden, and outcomes of intravenous versus intra-arterial chemotherapy for retinoblastoma.   Ophthalmol Retina. Published online September 11, 2020. doi:10.1016/j.oret.2020.09.006PubMedGoogle Scholar
Wong  FL , Boice  JD  Jr , Abramson  DH ,  et al.  Cancer incidence after retinoblastoma. radiation dose and sarcoma risk.   JAMA. 1997;278(15):1262-1267. doi:10.1001/jama.1997.03550150066037PubMedGoogle ScholarCrossref
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Credit Designation Statement: The American Medical Association designates this Journal-based CME activity activity for a maximum of 1.00  AMA PRA Category 1 Credit(s)™. Physicians should claim only the credit commensurate with the extent of their participation in the activity.

Successful completion of this CME activity, which includes participation in the evaluation component, enables the participant to earn up to:

  • 1.00 Medical Knowledge MOC points in the American Board of Internal Medicine's (ABIM) Maintenance of Certification (MOC) program;;
  • 1.00 Self-Assessment points in the American Board of Otolaryngology – Head and Neck Surgery’s (ABOHNS) Continuing Certification program;
  • 1.00 MOC points in the American Board of Pediatrics’ (ABP) Maintenance of Certification (MOC) program;
  • 1.00 Lifelong Learning points in the American Board of Pathology’s (ABPath) Continuing Certification program; and
  • 1.00 CME points in the American Board of Surgery’s (ABS) Continuing Certification program

It is the CME activity provider's responsibility to submit participant completion information to ACCME for the purpose of granting MOC credit.

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