Retinoblastoma is a rare and curable malignancy affecting the pediatric population. For advanced stage intraocular retinoblastoma, enucleation remains the primary treatment modality, although the use of laser photocoagulation, cryotherapy, radiotherapy and chemotherapy are frequently used, particularly in the setting of bilateral disease. Intravenous chemotherapy is the long-standing method of delivery, but local administration (subtenon, intravitreal or intra-arterial) is gaining in popularity because of the reduced side effects related to systemic administration. Of these newer methods, intra-arterial infusion has demonstrated technical feasibility, few procedural complications and robust tumor response. A case is described where a collateral supply to the affected ophthalmic artery was via the zygomatico-orbital branch of the ipsilateral superficial temporal artery. Melphalan infusion was performed via this pathway without incident.
- arteriovenous malformation
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Intraocular retinoblastoma is a rare pediatric solid tumor with fewer than 300 cases diagnosed each year in the USA and <10 000 worldwide.1 In the developed world 5-year mortality rates exceed 95%, with evidence supporting the use the external beam radiation, systemic chemotherapy and enucleation.1 2 Despite such therapies, additional strategies have been attempted aimed at preserving the affected eye(s) as well as reducing the comorbidities related to treatment such as gastrointestinal toxicity, myelosuppression and secondary malignancy.
Intra-arterial infusion has been used for retinoblastoma for over 20 years, although not until recently had it been performed in a superselective manner.3 Abramson et al described a technique using a flow catheter to select the ophthalmic artery (OA) for drug delivery.4 In their series they were successful in 9 out of 10 patients in accessing and delivering a chemotherapeutic agent into the OA. The single case that was unsuccessful was secondary to an anomalous (middle meningeal artery, MMA) origin of the OA. Although only a single case, the variant anatomy and collateral supply to the OA may necessitate alternative routes for therapeutic infusion to the globe.
We describe a case where a collateral supply to the affected OA was via the zygomatico-orbital artery (ZOA) of the ipsilateral superficial temporal artery (STA). Melphalan infusion was performed via this collateral pathway without technical incident.
A 2.5-year-old boy weighing18 kg was noted to have a white reflex in his right eye and referred for management. Funduscopy and MRI (figure 1) demonstrated bilateral International Intraocular Retinoblastoma Classification (IIRC) stage E retinoblastoma. Given the patient's late clinical presentation and advanced staging, prompt enucleation of the right eye was recommended and intra-arterial melphalan was sought as first-line therapy for the left eye in an attempt to preserve vision.
The patient was placed under general anesthesia and underwent standard sterile preparation and drape. The patient's baseline activated clotting time was measured and a 70 mg/kg intravenous bolus of heparin was administered. 0.25 inch of nitropaste was placed on the patient's chest to reduce the risk of catheter-induced vasospasm. A 4 F guide catheter was positioned within the left internal carotid artery (ICA) via a 4 F femoral arterial sheath. A 1.5 F Balt Magic flow-guided catheter (Balt Extrusion Inc, Montmorency, France) was primed with a 0.008 inch Mirage microwire (ev3 Inc, Irvine, California, USA). A guide catheter angiogram (figure 2A) demonstrated the proximal OA, but with limited filling of its subsequent branches including the central retinal artery and evidence of washout from a collateral source. A microcatheter angiogram of the left OA (figure 2B) confirmed these findings as well as the absence of choroidal blush. Given the absence of choroidal blush, evidence of washout from a collateral arterial supply and the limited stability of the microcatheter within the OA secondary to tortuosity of the carotid siphon and the angulation of the OA origin, we examined the external carotid circulation.
The guide catheter was repositioned within the left external carotid artery (ECA) and angiography demonstrated retrograde filling of the OA via the ZOA of the STA (figure 3A,B). An Excelsior SL10 microcatheter (Boston Scientific Inc, Natick, Massachusetts, USA) was then primed with a Transcend microwire (Boston Scientific Inc) and positioned within the ZOA collateralizing to the ipsilateral OA, with evidence of choroidal blush (figure 3C–E). Through the microcatheter, a pulsed infusion of 5 mg melphalan suspended in 30 ml normal saline was given over a 30 min interval. Repeat angiography showed no evidence of thromboembolic complications.
Within 2 weeks of receiving the intra-arterial infusion the patient was started on systemic chemotherapy based on the pathological results of the enucleated eye, noting tumor along the cut margin of the optic nerve. Given the decision to use systemic therapy, an examination under anesthesia (EUA) to assess the response to intra-arterial treatment was delayed until a later date. The first EUA was therefore not performed until the patient had undergone multiple cycles of systemic chemotherapy, thus limiting a deterministic effect of the intra-arterial melphalan infusion. Nonetheless, the patient clinically improved with subsequent EUA, showing a reduction in vitreal seeding and decreased retinal tumor burden with no lesions requiring laser treatment.
This case illustrates the feasibility of chemotherapeutic delivery to the OA from an ECA collateral and the importance of recognizing such variant anatomy by the operator. This case is unique in its success in accessing the OA origin using the flow catheter technique described by Abramson et al, although an over-the-wire system has also been employed in settings where the OA originated in a more distal location from the supraclinoid ICA segment.4 5 The authors have not used the balloon occlusion method to date.3
The OA can be subdivided into three segments: intracranial (coursing below the optic nerve), intracanicular (anastomosis lateral or medial to the nerve) and intraorbital.6 7 The OA arises most often within the subarachnoid space (83%), although it can arise in an extradural location from the cavernous ICA segment, in a combination of intradural and extradural sites or, in a small number of cases (2–3%), from the MMA.5–7 In addition to these anomalous origins, there are multiple collateral pathways to the OA from ECA branches including the meningolacrimal and sphenoidal branches from the MMA, the anterior deep temporal and palatine branches from the internal maxillary artery and the angular branch of the facial artery.7 The STA is also an alternative route with connections to the orbit via its medial and lateral frontal and zygomatico-orbital branches.7
The STA is an end division of the ECA and supplies the scalp and face. It has two primary frontal and parietal divisions with secondary anterior auricular, deep temporal, masseteric and zygomatico-orbital arterial branches.7 The last of these is usually present although, depending on the branch pattern of the frontal division, may be absent in 22% of cases.8 The ZOA connects to the lateral aspect of the orbit and communicates with the lacrimal branch of the OA through the superior and lateral palpebral arteries.9 It may even connect to the medial aspect of the orbit via the marginal arcade and transverse facial artery.7 9
In the setting where the OA does not fill expectantly, in addition to searching for ECA connections the operator must be aware of possible catheter-induced spasm. This may occur surrounding the guide catheter limiting antegrade flow into the carotid siphon, or at the microcatheter limiting flow into the OA. In both instances verapamil (0.1 mg/kg) may be used to alleviate spasm, although it is not recommended in children aged <6 months.10 Overall, intra-arterial chemotherapy has been shown to be technically feasible with good response rates and side effect profiles.1–4 Over a 3-year period, Abramson et al prospectively studied 23 patients (28 eyes) who underwent chemotherapeutic infusions.2 There were no deaths or major technical or systemic complications, with only a single enucleation for progressive disease and 89% were enucleation-free at 2 years. These early efforts are promising, although in time we will have a greater understanding of the potential complications of intra-arterial infusion and the durability of clinical success.
Competing interests None.
Patient consent Obtained.
Provenance and peer review Not commissioned; externally peer reviewed.
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