**5. Periocular chemotherapy for retinoblastoma**

Periocular chemotherapy (POC) administration was designed to allow delivery of a higher concentration of the tumoricidal drugs locally. This route was firstly tested in retinoblastoma animal models using carboplatin and it had been shown that this route produces vitreous concentrations 8–10 folds more than the intravenous route [75, 76]. These preclinical results led to the conduction of a trial in which children with retinoblastoma were treated using subconjunctival carboplatin and the results were promising [77]. Thereafter, POC grew in popularity and it was consequently incorporated into the multimodal treatment algorithm of retinoblastoma. Currently, it is a part of the prospective multicenter Children's Oncology Group trials for retinoblastoma. In this section, POC will be tackled comprehensively.

#### **5.1 Indications for periocular chemotherapy**

POC is used predominantly as an adjunctive therapy to systemic chemotherapy as presently there is no evidence promoting it as a stand-alone therapy [78]. It is indicated principally in patients with recurrent localized tumor and in advanced disease (group D and E) where chemotherapy can be desirably infused in higher concentrations without exposing the patient to increased systemic toxicity [7]. It can also be utilized in patients who are not fit to receive systemic chemotherapy as well as patients with recurrent or persistent viable non-calcified vitreous seeds [78].

#### **5.2 Chemotherapeutic agents**

The common chemotherapeutic agents that are mostly used are carboplatin and topotecan. Experimental work showed that carboplatin peaks in the vitreous after 30 min of periocular injection and lasts for hours. Its concentration in the vitreous is approximately seven times more than that achieved by intravenous chemotherapy [76]. Several periocular drug administrative devices were explored and these include: plain liquid, Lincoff balloon, fibrin sealant, nanoparticles and iontophoresis [76, 79–81].

#### **5.3 Complications**

This treatment modality fortunately has no systemic side effects. Ocular complications do occur, and these mostly affect the periorbital tissue possibly owing to local toxicity. The most common observed side effects are lid edema, lid erythema, periorbital pseudocellulitis, ptosis, orbital fat atrophy, optic nerve atrophy and muscle fibrosis causing ocular motility changes [7, 77, 78, 82, 83]. Concerns were raised regarding the toxic effect on the extraocular muscles; yet, a study examining the effect of sub-tenon topotecan on the extraocular muscles of 10 eyes concluded that it had no toxic effect on the muscles and it is a safe and effective alternative [84].

#### **5.4 Outcomes and success rate**

Although the number of studies on POC is limited overall, it had been shown that POC is principally effective when combined with other modalities of antineoplastic therapies. One long-term follow up study demonstrated that 39% (n = 33 eyes) of the enrolled eyes were saved when treated with POC in addition to other concurrent treatment modalities. The same report indicated that two eyes treated by POC as monotherapy were cured and remained disease free on follow up [82].

### **6. Conclusions**

In the last two decades, significant new approaches have been employed in the treatment of retinoblastoma which is a curable disease when diagnosed early. Modalities to avoid enucleation and minimize the short and long term effects of exposure to systemic chemotherapy and radiation therapy continue to evolve and now set the platform in the treatment of retinoblastoma. Despite new techniques such as selective intra-arterial and intravitreal chemotherapy, it is paramount to individualize therapy according to multiple factors including patient age, tumor location, stage of disease, size, and extension, along with realistic visual expectations. Personalized medicine will be able to tailor therapy with the best response and safety in children with retinoblastoma.

### **Acknowledgements**

We would like to thank the College of Medicine Research Center, Deanship of Scientific Research, and Ophthalmology Department at King AbdulAziz University Hospital under King Saud University, Riyadh, Saudi Arabia for funding and supporting this chapter.

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**Author details**

Amani Al Kofide1

Riyadh, Saudi Arabia

*Retinoblastoma Management: Advances in Chemotherapy*

The authors have no conflict of interest to disclose.

\* and Eman Al-Sharif<sup>2</sup>

and Research Centre (Gen. Org.), Riyadh, Saudi Arabia

\*Address all correspondence to: kofide@kfshrc.edu.sa

provided the original work is properly cited.

1 Department of Pediatric Hematology/Oncology, King Faisal Specialist Hospital

© 2019 The Author(s). Licensee IntechOpen. This chapter is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/ by/3.0), which permits unrestricted use, distribution, and reproduction in any medium,

2 Department of Ophthalmology, College of Medicine, King Saud University,

*DOI: http://dx.doi.org/10.5772/intechopen.86820*

**Conflict of interest**

*Retinoblastoma Management: Advances in Chemotherapy DOI: http://dx.doi.org/10.5772/intechopen.86820*
