Figure 44.2  Retinoblastoma after chemoreduction.

complications include rhegmatogenous retinal detachment noted next to cryotherapy scars38 and intraocular cholesterolosis.39

INTRA-ARTERIAL CHEMOTHERAPY

Using selective intra-arterial cannulation, some experts have pioneered the delivery of melphalan directly into the ophthalmic artery.47 At the present time, this technology remains experimental but may hold promise as a novel treatment modality for retinoblastoma and other intraocular tumors in the future.

ADJUVANT CHEMOTHERAPY

In the absence of overt metastatic disease, there are some definitive conclusions – and some controversial considerations – regarding the role of postenucleation adjuvant chemotherapy based on histopathologic findings. Such findings thought to be associated with increased risk of relapse include involvement of the choroid, sclera, or cut margin of the optic nerve.48 Other debatable risk factors for metastases include anterior-chamber seeding, iris infiltration, ciliary body infiltration, and invasion of the optic nerve lamina cribrosa.49 There is no consensus on the best chemotherapy regimen for adjuvant treatment. Though treatment protocols vary by center, many experts use cyclophosphamide and vincristine with or without EBRT.50–52 Others have used vincristine, doxorubicin, and cyclophosphamide, or vincristine, etoposide, and carboplatin.49

CHEMOTHERMOTHERAPY

Chemothermotherapy involves laser thermotherapy in conjunction with intravenous carboplatin. This technique is used for smaller retinoblastomas, those with minimal seeding or subretinal fluid, in effort to limit the amount of chemotherapy administered. In a study of 103 small to medium-sized tumors (1.5–12 mm in diameter), 92% were treated without EBRT.40

NO CHOROIDAL, SCLERAL, OR POSTLAMINAR OPTIC NERVE INVOLVEMENT

Patients with no risk factors for extraocular relapse, those with at most prelaminar optic nerve invasion without choroidal or scleral involvement, boast excellent survival rates and no relapse after enucleation alone. Adjuvant chemotherapy is not recommended for this cohort.48

PERIOCULAR AND SUBCONJUNCTIVAL CHEMOTHERAPY

In primates, peribulbar and episcleral carboplatin was found to have increased intraocular concentrations compared to intravenous delivery.41 Subconjunctival carboplatin was administered to 13 human eyes with retinoblastoma. Vitreal seeds responded well, unlike subretinal lesions.42 There was one case of optic neuropathy. A subsequent study reported four cases of optic nerve atrophy after periocular carboplatin treatment, finding ischemic necrosis and atrophy in the retrobulbar optic nerve along with dystrophic calcification and inflammation in the

CHOROIDAL INVASION

Adjuvant chemotherapy for patients with isolated choroidal invasion remains controversial. The overall survival is greater than 95%, with low rates of extraocular relapse.49,53,54 Some authors recommend adjuvant treatment only for massive choroidal involvement,55 though the definition of “massive” is variably defined in the literature.48 In a study of 55 patients, 94% were relapse-free at 3 years. All patients survived, including the three who relapsed and were then treated. Given the low mortality and relapse rates, the researchers did not recommend adjuvant chemotherapy for any degree of isolated choroidal invasion.48