Visual outcomes in treated eyes are of great interest, although little data have been published to date. Brodie et al. have monitored electroretinograms (ERGs) during sequential cycles of SSIOAC as surrogate for visual outcomes in this predominantly preverbal population. Retinal function has been observed to improve initially, remain stable, and later decline [17]. Tsimpida and colleagues looked at 12 eyes with refractory retinoblastoma that had good visual potential based on healthy foveolas as noted by ophthalmoscopy and optical coherence tomography prior to SSIOAC [18]. Five out of 12 eyes (42 %) sustained a reduction in visual acuity, with 2 suffering severe vision loss. Reasons for vision loss included diffuse retinal detachment (n = 1), diffuse choroidal ischemia (n = 2), and sectoral choroidal ischemia involving the fovea (n = 2). Four of the five eyes sustaining vision loss, however, had been previously treated with either EBRT or plaque brachytherapy, suggesting that previous radiation may predispose SSIOAC patients to visual loss. However, two patients with macula-sparing choroidal ischemia had no prior radiation exposure, which supports prior evidence that SSIOAC can lead to vasculopathy. Posttreatment ERGs deteriorated in four of eight eyes. Additional prospective, long-term follow-up studies on survival, metastasis rates, ocular survival, visual outcomes, and ocular toxicities are still needed.

SSIOAC for the treatment of retinoblastoma has quickly disseminated worldwide. Though the outcomes (eye salvage rates) appear promising, the reported case series have many confounding factors that limit the generalizability of this technique. Many patients have been treated previously, concurrently, or subsequently with other therapies. Various doses and agents have been utilized, sometimes with dose titrated to effect. It is difficult to assess the overall efficacy of SSIOAC, and thus, the singular effect of SSIOAC remains unknown.

Reported complications following SSIOAC are limited to case reports, as this therapy has not yet been evaluated as part of a large prospective retinoblastoma clinical trial. As such, these reports have been sporadic, including sectoral choroidal occlusion, retinal arteriolar emboli, retinal detachment, vitreous hemorrhage, transient retinal ischemia, ophthalmic artery obstruction, and cataract formation. Periocular inflammation and edema, cranial nerve III palsies, strabismus, and eyelash loss are reported orbital and adnexal side effects [10, 13, 14, 19–22]. Additionally, Fallaha et al. documented retinal vascular precipitates during the administration of melphalan into the ophthalmic artery [23].

Histopathology studies of eyes with retinoblastoma treated with SSIOAC have documented findings that have been attributed to the toxicities of SSIAOC. Eagle and coworkers examined eight eyes enucleated after SSIOAC and observed ischemic atrophy involving the outer retina and choroid (n = 4) (Fig. 12.4), orbital vascular occlusion and sub-endothelial smooth muscle hyperplasia (n = 1), and thrombosed blood vessels involving the retrobulbar ciliary arteries (n = 5), scleral emissary canals (n = 1), small choroidal vessels (n = 1), and CRA (n = 1) [24]. Intravascular birefringent foreign material was noted in five eyes and classified as cellulose fibers (n = 3), synthetic fabric fibers (n = 1), or unknown composition (n = 2). Other histopathology studies have focused principally on residual viable tumor [25–27]. In these eyes that were enucleated for progression of disease, partial response to IAC was seen in most cases, although many also had areas of non-necrotic, viable tumor and vitreous seeding still present. None of these papers reported evidence of ocular toxicity to the surrounding tissues from IAC.

Melphalan, a potent alkylator, has known vascular toxicities [28]. In a 2011 editorial, Wilson et al. attributed the reported vascular complications of SSIOAC to concentration of melphalan being used [29]. A preclinical model was developed to study the vascular sequelae of SSIOAC [30]. Using techniques and protocols similar to those previously published, a cohort of six non-human primates were treated with SSIOAC, and real-time ophthalmoscopic findings were documented during each infusion. Visible pulsatile pallor of the optic nerve, choroidal blanching, and retinal arterial narrowing were observed (Fig. 12.5). Sectoral choroidal non-perfusion and diffuse capillary dropout were seen on fluorescein angiography immediately following chemotherapy infusion (Fig. 12.5). Orbital and ocular histopathology revealed drug-induced toxicity to retinal endothelial cells as well as technique-induced changes to the orbital vasculature, including intimal hyperplasia, fracturing of the internal elastic lamina, and arterial wall dissection involving the ophthalmic, and central retinal arteries [31].

Stay updated, free articles. Join our Telegram channel

Join