The management of retinoblastoma is complex. With increasing treatment modalities and increasing experience with each treatment modality, the globe salvage rates have drastically improved with time. Aqueous seeding in an eye with retinoblastoma is classified as group E based on International Classification of Intraocular Retinoblastoma, and most group E eyes were enucleated a decade earlier. Newer modalities of treatment have improved the globe salvage rates in group E eyes including those with aqueous seeding. Various globe salvage treatment modalities attempted for the management of aqueous seeds include external beam radiotherapy, plaque radiotherapy, intra-arterial chemotherapy, periocular chemotherapy, intravitreal chemotherapy and intracameral chemotherapy. Of all treatment modalities, intracameral chemotherapy holds promise for the management of aqueous seeds in selected patients, but it should be done with the utmost care by a trained ocular oncologist. Enucleation is still the preferred modality of treatment for eyes with advanced retinoblastoma and anterior segment invasion. This review focuses on the current evidence on aqueous seeding, highlighting the pathogenesis, classification, clinical presentation, treatment and outcomes.
Christina Stathopoulos, Bruno Bartolini, Guillaume Marie, Maja Beck-Popovic, Guillaume Saliou, Francis L. MunierRead More
To identify risk factors for acute choroidal ischemia (ACI) after intra-arterial chemotherapy (IAC) for retinoblastoma.
Retrospective cohort study.
Two hundred twenty patients (248 eyes) treated with IAC in Lausanne between November 2008 and September 2019 (665 procedures). All patients were evaluated on a monthly basis with fundus photography and fluorescein angiography before and after each IAC injection.
Acute choroidal ischemia, defined as any new choroidal ischemia clinically diagnosed within 35 days after an IAC injection, were noted. Eyes with choroidal complications diagnosed later than 35 days after the last IAC injection (n = 7) or those for which the status of the choroid was not assessable (n = 35) were excluded. Specific procedure parameters and treatment regimens were compared between the group of eyes with and without ACI.
Main Outcome Measures
Procedure-related risk factors for ACI after IAC injection and visual acuity assessment in the group of eyes with ACI.
Acute choroidal ischemia developed in 35 of 206 included eyes after a mean of 2 injections. No differences were found between the two study groups regarding age at first IAC injection, disease grouping at diagnosis, previously administered treatments, number of IAC injections, drug dose, mean injection time, injection method (pulsatile vs. continuous), or concomitant intravitreal melphalan use. Treatment regimen (melphalan vs. combined melphalan plus topotecan; P < 0.05), catheterization route (internal carotid artery vs. external carotid or posterior communicating artery; P < 0.001), and catheterization type (occlusive into the ophthalmic artery [OA] vs. nonocclusive; P < 0.001) were included in multivariate analysis, and occlusive catheterization was identified as an independent risk factor for ACI (P < 0.001). In the subgroup undergoing an occlusive procedure, placement of the catheter tip into the OA distal third versus medial and proximal thirds (P = 0.04) and a mean catheter diameter-to-OA lumen ratio of 0.6 or more (P < 0.001) were correlated significantly with ACI. Complete vision loss was noted in 27% of the eyes with ACI that were old enough for visual assessment (n = 9/33), whereas 33% maintained a useful vision ranging between 0.1 and 0.8 (n = 11/33).
Catheterization of the OA should be attempted from an ostial position or an external carotid approach to minimize the risk of potentially vision-threatening choroidal complications.
Successful salvage intravenous chemotherapy after tandem selective ophthalmic artery infusion chemotherapy in bilateral retinoblastoma
Hyun J Kim, Maura Di Nicola, James J Augsburger, Basil K WilliamsRead More
We report the case of a 9-month-old girl with bilateral retinoblastoma who had incomplete tumor resolution after selective ophthalmic artery infusion chemotherapy (SOAIC). Systemic chemotherapy, rarely used as salvage therapy after SOAIC, with systemic carboplatin, etoposide, and vincristine achieved complete and sustained regression in both eyes.
David Ancona-Lezama, Lauren A Dalvin, Carol L ShieldsRead More
Retinoblastoma management remains complex, requiring individualized treatment based on International Classification of Retinoblastoma (ICRB) staging, germline mutation status, family psychosocial factors and cultural beliefs, and available institutional resources. For this 2020 retinoblastoma review, PubMed was searched for articles dated as early as 1931, with an emphasis on articles from 1990 to the present day, using keywords of retinoblastoma, chemotherapy, intravenous chemotherapy, chemoreduction, intra-arterial chemotherapy, ophthalmic artery chemosurgery, intravitreal chemotherapy, intracameral chemotherapy, cryotherapy, transpupillary thermotherapy, laser, radiation, external beam radiotherapy, plaque radiotherapy, brachytherapy, and enucleation. We discuss current treatment modalities as used in the year 2020, including intravenous chemotherapy (IVC), intra-arterial chemotherapy (IAC), intravitreal chemotherapy (IvitC), intracameral chemotherapy (IcamC), consolidation therapies (cryotherapy and transpupillary thermotherapy [TTT]), radiation-based therapies (external beam radiotherapy [EBRT] and plaque radiotherapy), and enucleation. Additionally, we present a consensus treatment algorithm based on the agreement of three North American retinoblastoma treatment centers, and encourage further collaboration amongst the world’s most expert retinoblastoma treatment centers in order to develop consensus management plans and continue advancement in the identification and treatment of this childhood cancer.
Eva Maria Biewald, Norbert Bornfeld, Klaus A Metz, Sabrina Schlüter, Tobias Kiefer, Alexander Radbruch, Sophia Göricke, Selma Sirin, Petra Ketteler, Nikolaos E BechrakisRead More
Background To demonstrate histopathological findings in retinoblastoma eyes enucleated after intra-arterial chemotherapy (IAC) with special emphasis on vascular toxicity and local tumour control.
Methods Retrospective study with a consecutive series of 23 retinoblastoma eyes enucleated after IAC where histopathological work-up was available.
Results From November 2010 to June 2019 23 eyes were enucleated after the attempt of eye salvaging therapy with IAC using melphalan. IAC was the first line treatment in nine and salvage treatment in 14 eyes. Doses of melphalan ranged from 3 to 7.5 mg, whereby a strict protocol with age-appropriate dosage was not used until 2015. The mean number of treatment cycles was 1.8. The main indications for enucleation were poor treatment response or tumour progression in 14 eyes, severe vascular complications in five eyes and a total exudative retinal detachment with amaurosis in the remaining four eyes. We found active disease in 15 eyes with an indication for adjuvant chemotherapy due to high risk factors for metastases in four eyes. To date none of these patients developed metastatic disease. Concerning vascular toxicity, we detected a central retinal artery occlusion in three eyes, severe vasculitis in another three, ischaemic outer retina atrophy and choroidal ischaemia in seven eyes with one eye developing a severe proliferative retinopathy.
Conclusion IAC is a highly effective treatment option for advanced retinoblastoma, but the described potential risks should be kept in mind. These include severe vascular complications, as well as the possibility of persisting vital tumour cells fulfilling high-risk criteria for adjuvant chemotherapy.
Li‐Anne S. Lim MB BS Lauren A. Dalvin MD David Ancona‐Lezama MD Michael D. Yu BS Pascal Jabbour MD Carol L. Shields MDRead More
Retinoblastoma is a life‐ and sight‐threatening malignancy.
To assess the relationship between tumour perfusion and intra‐arterial chemotherapy (IAC) requirements to achieve retinoblastoma control.
Retrospective case series at the Ocular Oncology Service of Wills Eye Hospital (Philadelphia, Pennsylvania).
Fifty‐nine eyes of 55 patients.
Review of medical and fluorescein angiography (FA) records for retinoblastoma treated with primary or secondary IAC from 2012 to 2017. Vascular supply of the main tumour was evaluated in the pre‐treatment FA.
Main Outcome Measures
Tumour fluorescence was classified as partial <67% or complete tumour perfusion >67%. Partially vs completely perfused tumours were compared for IAC cycle requirements.
There were 59 eyes of 55 patients with pre‐treatment FA managed with IAC. Partially perfused tumours (n = 20, 34%) required fewer IAC infusions than completely perfused tumours (n = 39, 66%) (2.5 vs 3.7 infusions, P = .02), even after adjustment for confounding factors (tumour diameter, thickness and drug scheme, adjusted P = .04). Tumour perfusion correlated with number of IAC cycles required for tumour control (r = 0.46, P < .001). For primary IAC (n = 18, 31%), tumour perfusion was not associated with number of IAC cycles (P = .63). For secondary IAC (n = 41, 69%), partially perfused tumours (n = 15, 37%) required fewer IAC infusions than completely perfused tumours (n = 26, 63%) (2.1 vs 3.7 infusions, P < .01).
Conclusions and Relevance
FA demonstrating partial retinoblastoma tumour perfusion is associated with fewer IAC cycle requirements for secondary but not primary IAC. FA might be useful in judging anticipated treatment cycles of retinoblastoma managed with primary or secondary IAC.
Histopathologic findings after selective ophthalmic arterial injection of melphalan for retinoblastoma
Ho-Min Chen, Sherine Jue Ong, An-Ning Chao, Kuan-Lyin Liou, Shih-Ming Jung, Ling-Yuh KaoRead More
PURPOSE: The aim is to describe histopathologic observations in eyes enucleated after selective ophthalmic arterial injection (SOAI) of melphalan for retinoblastoma (RB). STUDY DESIGN: This is retrospective clinical study. PATIENTS AND METHODS: Histopathologic analysis of 14 eyes (13 patients) from May 2008 through January 2015 at Chang Gung Memorial Hospital. RESULTS: The eyes after SOAI were enucleated due to tumor viability (n = 7, 2 with vitreous hemorrhage), neovascular glaucoma (n = 4), lens drop to vitreous with total hyphema and elevated intraocular pressure (n = 1), retinal detachment (RD) progressed (n = 1), and persistent RD with phthisis change (n = 1). Almost all of the eyes showed vitreous seeding (n = 11 eyes) before treatment. After the treatment of SOAI, the histopathological examination revealed complete regression in four eyes with one was clinically diagnosed as viable tumor and progression, one with RD progression, and two as neovascular glaucoma. Six eyes showed invasion into the optic nerves, reaching the lamina cribrosa in five eyes, and six eyes with invasion into the choroid were observed. All of the cases with lamina cribrosa involvement showed tumor progression before enucleation, four cases with lamina cribrosa involvement expired later. CONCLUSION: Although some cases of RB can be controlled effectively with SOAI, but for refractory cases after SOAI, earlier decision of enucleation may be needed.
Fairooz P Manjandavida, Christina Stathopoulos, Jing Zhang, Santhosh G Honavar, Carol L ShieldsRead More
Intra-arterial chemotherapy (IAC), also known as superselective ophthalmic artery chemotherapy or chemosurgery, is currently widely accepted as one of the primary treatment modalities for intraocular retinoblastoma worldwide. Following the introduction of the technique in 1998, IAC has evolved over the past decades to be safer and more effective. Accumulated evidence shows that IAC is more effective in providing eye salvage in group D and E retinoblastoma as compared to conventional systemic intravenous chemotherapy (IVC). In contrast to IVC, IAC has the added benefits of reduced overall treatment duration and minimal systemic toxicity. This review provides a comprehensive update on the history, technique, indications, contraindications, and outcome of IAC. We have also identified the strengths, weaknesses, opportunities and threats (SWOT analysis) of the technique in this review.
Choroidal Ischemia Sparing the Watershed Zone following Intra-Arterial Chemotherapy for Retinoblastoma
Ancona-Lezama D.A. · Dalvin L.A. · Lucio-Alvarez J.A. · Jabbour P. · Shields C.L.Read More
Purpose: Intra-arterial chemotherapy (IAC) has become a mainstay in the management of retinoblastoma, especially in advanced or refractory disease. However, IAC is not without complications, and chemotherapy toxic effects can lead to partial or complete choroidal ischemia, often causing vision loss. Methods: This is a case report. Results: A 4-month-old girl with bilateral retinoblastoma was treated with secondary IAC (melphalan 5 mg) for recurrent tumor following intravenous chemotherapy. One month later, complete tumor control was achieved. However, she demonstrated broad choroidal ischemia in the nasal and temporal quadrants but sparing of the watershed zone superior and inferior to the optic disc and in the papillomacular region. Fluorescein angiography revealed poor perfusion of the choriocapillaris with visibility of the large choroidal vessels in the nasal and temporal areas but preserved perfusion of the watershed zone. The watershed zone remained intact on the 10-month follow-up, and the final visual acuity was fix and follow without strabismus. Conclusion: The pathophysiology of choroidal ischemia is not well understood, but the fortuitous watershed zone preservation in this case could represent uneven distribution of the chemotherapeutic drug, resulting in partial chemo-dilution of the medication in the watershed region, which represents the final downstream overlapping choroidal perfusion from both medial and lateral posterior ciliary arteries.
Primary Intra-Arterial Chemotherapy for Retinoblastoma in the Intravitreal Chemotherapy Era: Five Years of Experience
Dalvin L.A. · Kumari M. · Essuman V.A. · Shohelly Shipa S. · Ancona-Lezama D. · Lucio-Alvarez J.A. · Jabbour P. · Shields C.L.Read More
Purpose: To report our 5-year experience with intra-arterial chemotherapy (IAC) in the intravitreal chemotherapy (IvitC) era. Methods: Retrospective review of retinoblastoma treated with primary unilateral IAC in the IvitC era (2012–2017). Results: There were 34 eyes treated with IAC alone versus 20 eyes treated with IAC plus IvitC for vitreous seeds. IAC (IAC alone vs. IAC plus IvitC) consisted of melphalan (41 vs. 10%) or melphalan plus topotecan (59 vs. 90%, p = 0.03). IvitC consisted of melphalan (60%) or melphalan plus topotecan (40%). Tumor control and globe salvage were achieved in 100% of group B and C eyes without IvitC. Despite more extensive vitreous seeds in the IvitC group (p < 0.01), comparison of IAC alone versus IAC plus IvitC revealed no difference in tumor control for group D (88 vs. 69%, p = 0.36) or group E (67 vs. 100%, p = 0.25) and no difference in globe salvage for group D (88 vs. 69%, p = 0.36) or group E (58 vs. 57%, p = 0.39). Conclusions: IAC is effective as primary therapy for unilateral group B, C, D, and E retinoblastoma. IvitC is an important adjuvant therapy to achieve comparable globe salvage rates for group D and E eyes with persistent active vitreous seeds.