Atypical Event Profiling of Intra-Arterial Chemotherapy Austin Bach, DO, MPH, Victor Villegas, MD, Aaron S Gold, OD, Andrea C Wildner, CRA, Jennifer Thomson, CRA, Fiona J Ehlies, BSc (Hons), CDOS, Timothy G Murray, MD, MBA Introduction: Retinoblastoma is the most common intraocular pediatric cancer in the world with a mortality rate of up to 70% in undeveloped nations. With the recent advent of intraarterial chemotherapy, there has been a dramatic decline in enucleation, deaths, and extraocular side effects from treatments of the retinoblastoma. There have been several local and distal atypical events reported for intraarterial melphalan. This case series will present three cases with radically different atypical events of intraarterial melphan. Case 1: A six year old male was referred for treatment of a late onset retinoblastoma in his right eye (OD) without any extension or metastasis of the tumor. He underwent one round of intraarterial melphalan into the right ophthalmic artery together with a laser ablation of the lesion. Postoperatively, his uncorrected visual acuity (UCVA) OD was 20/30 and his best corrected visual acuity (BCVA) OD was 20/20. His intraocular pressure (IOP) OD was 17. He had no systemic or local symptoms at his initial postoperative appointment. Within a few months after treatment, the patient noticed a subjective tinnitus, “ringing and train whistles.” Two years after this therapy, he was seen by an otorhinolaryngologist and was noted to have total hearing loss in his right ear. To date, two years after the diagnosis of total right sided hearing loss, he shows no other systemic side effects or signs of reactivation of the tumor and is being monitored closely by audiology. Case 2: A 17 month old female was referred for treatment of a unilateral Retinoblastoma, OD, without any extension or metastasis. She underwent four treatments of intraarterial melphalan and transpupillary thermotherapy (TTT). The fourth uneventful intraarterial treatment was done through the middle meningeal artery. After the treatment, she was noted to have cutaneous preauricular erythema (Figure 2) due to extravasation of the melphalan. The plan for further intraarterial treatments was discontinued and she underwent systemic chemotherapy and follow up TTT. Case 3: A 2 year old male was referred for treatment of a unilateral Retinoblastoma, OS, without any extension or metastasis. Along with laser therapy, he underwent three uneventful intraarterial treatments of Melphalan, Topatecan, Carbaplatin. This was followed by one intravitreal injection of Melphalan and another intraarterial Melphalan injection with improvement following all uneventful therapies. During the fifth intraarterial therapy, the patient developed intraoperative resistance to infusion and acute proptosis. The procedure was stopped due to this event. Ultrasound examination 5 minutes after developing proptosis showed retrobulbar fluid (Figure 3). This was followed by an MRI which confirmed the retrobulbar fluid. On examination, he was noted to have taught lids, minimized lid fissure (Figure 4), and an IOP of 54. There was persistent, but minimal perfusion of the optic nerve, with optic nerve head elevation. Emergent treatment was administered with Cosopt and globe massage until the pressure was stabilized below 30. An MRI was done (Figure 5), which showed infiltration and thickening of the medial rectus. Further treatment was changed to include only intravitreal injections without further complications. Discussion / Conclusion: Retinoblastoma is the most common intraocular pediatric tumor with, up to, a 70% mortality rate when not treated early enough or with the proper advanced treatments. Current day, advanced treatments of retinoblastoma have caused this tumor to have one of the lowest mortality rates among pediatric malignancies. Intraarterial chemotherapy with triethylene melamine delivered into the ophthalmic artery was first reported in 1958. This was done to minimize systemic side effects of the chemotherapy. Even with intraarterial melphalan having much fewer atypical events when compared to the other treatment methods, one must be aware of the possible side effects of this treatment. Reported intraocular side effects include conjunctival edema, retinal ischemia6, ophthalmic artery thrombosis, choroidal nonperfusion, ischemic retinal and choroidal atrophy, intravascular birefringent foreign material in the vessels, retinal detachment, vitreous hemorrhage, pre/subretinal hemorrhage, phthisis, central retinal artery occlusion, hyphema, and neovascular glaucoma. The intraorbital and adnexal side effects include lid edema, madarosis, orbital edema, ptosis, periocular hyperemia, ocular dysmotility. The more distal side effects include third nerve palsy, and neutropenia. The three cases that were presented include a range of severity of atypical events noted from intraarterial melphalan treatment. Extravasation of the chemotherapeutic agent, and hearing loss have yet to be reported. Extravasation can cause unwanted local side effects due to high concentration of the chemotherapeutic agent. Distal cranial nerve palsies can cause life altering and life threatening events. Along with the case of severe orbital edema, these atypical events can have devastating long term side effects on these patients who are likely to live for many decades past their treatment. 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