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Brief Report
December 2017

Risk of Extraocular Extension in Eyes With Retinoblastoma Receiving Intravitreous Chemotherapy

Author Affiliations
  • 1Ophthalmic Oncology Service, Memorial Sloan Kettering Cancer Center, New York, New York
  • 2Department of Ophthalmology, Weill-Cornell Medical Center, New York, New York
  • 3Department of Ophthalmology, Xin Hua Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
  • 4Ocular Oncology Service, Wills Eye Hospital, Thomas Jefferson University, Philadelphia, Pennsylvania
  • 5Pediatric Oncology Institute, Federal University of São Paulo, São Paulo, Brazil
  • 6Department of Pediatric Oncology, Santa Marcelina Hospital, São Paulo, Brazil
  • 7Department of Ophthalmology, Children's Memorial Hermann Hospital, University of Texas, Houston
  • 8Institut Curie PSL (Paris Science Letter), René Descartes Paris V Universities, Paris, France
  • 9Department of Ophthalmology, University of Siena, Siena, Italy
  • 10Children's Hospital Los Angeles, Roski Eye Institute, University of Southern California, Los Angeles
  • 11Department of Ophthalmology, Hadassah Medical Center, Jerusalem, Israel
  • 12Department of Ophthalmology, Jules-Gonin Eye Hospital, Lausanne, Switzerland
JAMA Ophthalmol. 2017;135(12):1426-1429. doi:10.1001/jamaophthalmol.2017.4600
Key Points

Question  What is the risk of extraocular extension from injecting chemotherapy into eyes with retinoblastoma?

Findings  This 10-center cohort study, with an accumulated 3553 injections in 655 patients, identified no events of extraocular tumor that could be attributed to prior intravitreous chemotherapy injections.

Meaning  These data suggest that the occurrence of extraocular tumor in eyes with retinoblastoma receiving intravitreous chemotherapy is possible but unlikely.


Importance  The risk of extraocular extension from injecting chemotherapy into eyes with retinoblastoma is minimally understood; however, understanding this risk is important because of the increasing use of intravitreous chemotherapy.

Objective  To evaluate the risk of extraocular extension in eyes with retinoblastoma that have received intravitreous chemotherapy injections.

Design, Setting, and Participants  This retrospective cohort study was performed in 655 patients at 10 retinoblastoma centers in North and South American, European, Israeli, and Chinese centers. Physicians at the retinoblastoma centers administered more than 120 intravitreous chemotherapy injections in eyes with retinoblastoma from February 1, 1999, through February 28, 2017.

Main Outcomes and Measures  Risk of extraocular extension with secondary observational variables, including injection and precautionary techniques.

Results  A total of 3553 intravitreous chemotherapy injections (3201 melphalan hydrochloride, 335 topotecan hydrochloride, and 17 methotrexate sodium) were administered to 704 eyes in 655 patients with retinoblastoma (mean [SD] age of patients at the time of the initial injections, 31.6 [11.6] months; 348 male [53.1%]). There were no extraocular tumor events related to prior intravitreous injections. This finding resulted in a calculated proportion of zero extraocular events per eye. According to the rule of 3, the risk is no greater than 0.08% injections. All 10 centers included in this study used at least 2 presumed precautionary injection methods (lowering of intraocular pressure, cryotherapy, ocular surface irrigation, ultrasonic biomicroscopy surveillance of the injection site, and subconjunctival chemotherapy deposition).

Conclusions and Relevance  With use of at least 2 presumed precautionary safety methods, no extraocular extension of tumor events occurred. According to the rule of 3, this finding suggests that the risk is no greater than 0.08% injections.