[Skip to Content]
Access to paid content on this site is currently suspended due to excessive activity being detected from your IP address 54.166.5.76. Please contact the publisher to request reinstatement.
[Skip to Content Landing]
Download PDF
Figure.
Kaplan-Meier Analysis of Orbital Recurrence–Free Survival of Eyes Treated With Either Ophthalmic Artery Chemosurgery or Enucleation, With P = .049 by Log-Rank Test
Kaplan-Meier Analysis of Orbital Recurrence–Free Survival of Eyes Treated With Either Ophthalmic Artery Chemosurgery or Enucleation, With P = .049 by Log-Rank Test
Table.  
Clinical Characteristics of Naive Eyes With Advanced-Stage Retinoblastoma Treated With Ophthalmic Artery Chemosurgery or Enucleation
Clinical Characteristics of Naive Eyes With Advanced-Stage Retinoblastoma Treated With Ophthalmic Artery Chemosurgery or Enucleation
1.
Grigorovski  N, Lucena  E, Mattosinho  C,  et al.  Use of intra-arterial chemotherapy for retinoblastoma: results of a survey. Int J Ophthalmol. 2014;7(4):726-730.
PubMed
2.
Gobin  YP, Dunkel  IJ, Marr  BP, Brodie  SE, Abramson  DH.  Intra-arterial chemotherapy for the management of retinoblastoma: four-year experience. Arch Ophthalmol. 2011;129(6):732-737.
PubMedArticle
3.
Suzuki  S, Yamane  T, Mohri  M, Kaneko  A.  Selective ophthalmic arterial injection therapy for intraocular retinoblastoma: the long-term prognosis. Ophthalmology. 2011;118(10):2081-2087.
PubMedArticle
4.
Shields  CL, Manjandavida  FP, Lally  SE,  et al.  Intra-arterial chemotherapy for retinoblastoma in 70 eyes: outcomes based on the International Classification of Retinoblastoma. Ophthalmology. 2014;121(7):1453-1460.
PubMedArticle
5.
Peterson  EC, Elhammady  MS, Quintero-Wolfe  S, Murray  TG, Aziz-Sultan  MA.  Selective ophthalmic artery infusion of chemotherapy for advanced intraocular retinoblastoma: initial experience with 17 tumors. J Neurosurg. 2011;114(6):1603-1608.
PubMedArticle
6.
Gobin  YP, Dunkel  IJ, Marr  BP, Francis  JH, Brodie  SE, Abramson  DH.  Combined, sequential intravenous and intra-arterial chemotherapy (bridge chemotherapy) for young infants with retinoblastoma. PLoS One. 2012;7(9):e44322.
PubMedArticle
7.
Abramson  DH, Marr  BP, Dunkel  IJ,  et al.  Intra-arterial chemotherapy for retinoblastoma in eyes with vitreous and/or subretinal seeding: 2-year results. Br J Ophthalmol. 2012;96(4):499-502.
PubMedArticle
8.
Abramson  DH, Francis  JH, Dunkel  IJ, Marr  BP, Brodie  SE, Gobin  YP.  Ophthalmic artery chemosurgery for retinoblastoma prevents new intraocular tumors. Ophthalmology. 2013;120(3):560-565.
PubMedArticle
9.
Hungerford  J, Kingston  J, Plowman  N.  Orbital recurrence of retinoblastoma. Ophthalmic Paediatr Genet. 1987;8(1):63-68.
PubMedArticle
10.
Khelfaoui  F, Validire  P, Auperin  A,  et al.  Histopathologic risk factors in retinoblastoma: a retrospective study of 172 patients treated in a single institution. Cancer. 1996;77(6):1206-1213.
PubMedArticle
11.
Kim  JW, Kathpalia  V, Dunkel  IJ, Wong  RK, Riedel  E, Abramson  DH.  Orbital recurrence of retinoblastoma following enucleation. Br J Ophthalmol. 2009;93(4):463-467.
PubMedArticle
12.
Doz  F, Khelfaoui  F, Mosseri  V,  et al.  The role of chemotherapy in orbital involvement of retinoblastoma: the experience of a single institution with 33 patients. Cancer. 1994;74(2):722-732.
PubMedArticle
13.
Singh  AD, Shields  CL, Shields  JA.  Prognostic factors in retinoblastoma. J Pediatr Ophthalmol Strabismus. 2000;37(3):134-141.
PubMed
14.
Kopelman  JE, McLean  IW, Rosenberg  SH.  Multivariate analysis of risk factors for metastasis in retinoblastoma treated by enucleation. Ophthalmology. 1987;94(4):371-377.
PubMedArticle
15.
Rubin  CM, Robison  LL, Cameron  JD,  et al.  Intraocular retinoblastoma group V: an analysis of prognostic factors. J Clin Oncol. 1985;3(5):680-685.
PubMed
16.
Baez  KA, Ulbig  MW, Cater  J, Shields  CL, Shields  JA.  Iris neovascularization, increased intraocular pressure and vitreous hemorrhage as risk factors for invasion of the optic nerve and choroid in children with retinoblastoma [in German]. Ophthalmologe. 1994;91(6):796-800.
PubMed
17.
Shields  CL, Shields  JA, Baez  KA, Cater  J, De Potter  PV.  Choroidal invasion of retinoblastoma: metastatic potential and clinical risk factors. Br J Ophthalmol. 1993;77(9):544-548.
PubMedArticle
18.
Chantada  GL, Gonzalez  A, Fandino  A,  et al.  Some clinical findings at presentation can predict high-risk pathology features in unilateral retinoblastoma. J Pediatr Hematol Oncol. 2009;31(5):325-329.
PubMedArticle
19.
Shields  CL, Shields  JA.  Intra-arterial chemotherapy for retinoblastoma: the beginning of a long journey. Clin Experiment Ophthalmol. 2010;38(6):638-643.
PubMedArticle
20.
Jabbour  P, Chalouhi  N, Tjoumakaris  S,  et al.  Pearls and pitfalls of intraarterial chemotherapy for retinoblastoma. J Neurosurg Pediatr. 2012;10(3):175-181.
PubMedArticle
21.
Ellsworth  RM.  Orbital retinoblastoma. Trans Am Ophthalmol Soc. 1974;72:79-88.
PubMed
Original Investigation
September 2015

Enucleation vs Ophthalmic Artery Chemosurgery for Advanced Intraocular RetinoblastomaA Retrospective Analysis

Author Affiliations
  • 1Ophthalmic Oncology Service, Memorial Sloan-Kettering Cancer Center, New York, New York
  • 2Department of Ophthalmology, Weill Cornell Medical College, New York, New York
  • 3Department of Pediatrics, Weill Cornell Medical College, New York, New York
  • 4Department of Pediatrics, Memorial Sloan-Kettering Cancer Center, New York, New York
  • 5Service of Interventional Neuroradiology, Department of Neurology and Radiology, Weill Cornell Medical College, New York, New York
JAMA Ophthalmol. 2015;133(9):1062-1066. doi:10.1001/jamaophthalmol.2015.2243
Abstract

Importance  Ophthalmic artery chemosurgery (OAC) has emerged as a primary treatment for advanced-stage retinoblastoma. To our knowledge, the incidence of orbital recurrence in eyes treated with OAC has not been described.

Objective  To determine the incidence of orbital recurrence following enucleation or OAC as primary treatments for advanced-stage retinoblastoma.

Design, Setting, and Participants  Single-institution cohort study with retrospective record review at an academic ophthalmic oncology practice. A total of 140 eyes in 135 patients who presented between February 14, 2006, and March 4, 2014, and were classified as having Reese-Ellsworth group 5 or International Classification of Retinoblastoma (Children’s Oncology Group) group D or E retinoblastoma were included; 63 patients (63 eyes) were primarily treated with enucleation and 72 patients (77 eyes) were primarily treated with OAC. This analysis was conducted between August 1, 2014, and March 1, 2015.

Main Outcomes and Measures  Incidence of and time to orbital recurrence, metastasis, and death.

Results  There were 5 orbital recurrences (incidence, 7.9%) in the primary enucleation group and 1 orbital recurrence (incidence, 1.3%) in the primary OAC group during median follow-up times of 42.6 months (range, 6.2-97.1 months) and 38.7 months (range, 9.0-104.3 months), respectively. The 24-month Kaplan-Meier estimate for orbital recurrence–free survival was worse for the enucleation group (92.1%; 95% CI, 82.0-96.7) than for the OAC group (100%) (log-rank test, P = .049). The enucleation group had 5 cases of metastatic disease (7.9%) and 2 deaths (3.2%). In the OAC group, there were 3 cases of metastatic disease (4.2%) and no deaths. Kaplan-Meier analysis of metastasis-free survival and overall survival yielded no differences between the 2 treatment groups. Analysis of a number of features of the 2 groups revealed more eyes with iris neovascularization in the enucleation group (25.4%) than in the OAC group (5.2%) and more eyes with group E retinoblastoma in the enucleation group (87.3%) than in the OAC group (29.9%), although neither of these factors was an independent predictor of orbital relapse in a Cox proportional hazards model.

Conclusions and Relevance  In this single-institution retrospective study of advanced intraocular retinoblastoma, there were more orbital recurrences in the group primarily treated with enucleation. Ophthalmic artery chemosurgery for advanced intraocular retinoblastoma was not found to increase the chance of orbital recurrence, metastatic disease, or death compared with primary enucleation.

Introduction

During the past several years, ophthalmic artery chemosurgery (OAC) has emerged as a safe and effective treatment for advanced retinoblastoma. A recent survey revealed that 74% of retinoblastoma treatment centers worldwide are using OAC as first-line therapy for advanced unilateral disease.1 Eyes treated initially with OAC have been shown to have ocular event-free survival rates at 2 years of greater than 80% despite their advanced stage.2 These findings have been replicated at multiple centers, demonstrating that OAC as a primary therapy35 or with intravenous chemotherapy as a bridge6 may achieve globe salvage and tumor control in a high percentage of eyes with group D and E retinoblastoma. Further, OAC has been shown to be useful in the treatment of vitreous seeds7 and to prevent the development of new intraocular tumors, suggesting that it may affect ophthalmoscopically undetectable tumors present at initial diagnosis.8

While the multiple benefits and favorable risk profile of OAC have been documented in the literature, the incidence of orbital recurrence in patients treated with this modality has not been previously described, to our knowledge. Several prior studies have documented rates of orbital recurrence after primary enucleation ranging from 5%9 to 7.6%,10 although these series included eyes that presented with extraocular disease. The one study that was limited to patients who presented with intraocular disease revealed an incidence of only 4.2% during the course of almost 100 years, ranging between 3.7% and 5.1% when calculated using 20-year periods.11

Because orbital involvement carries a poor prognosis and is commonly associated with metastatic disease both outside and within the central nervous system,1214 the characterization of orbital recurrence in the context of OAC is of significant interest. Eighty-five percent of patients with orbital recurrence have been reported to develop metastatic disease and 75% die from metastatic retinoblastoma, although mortality rates have decreased in the modern era.11 The purpose of this study was to reexamine orbital recurrence in advanced retinoblastoma after treatment with OAC and to compare these rates with those in eyes treated with enucleation during the same period in the same institution.

Box Section Ref ID

At a Glance

  • Ophthalmic artery chemosurgery has emerged as a leading therapy for advanced retinoblastoma.

  • Orbital retinoblastoma carries a poor prognosis and is often associated with metastatic disease.

  • This retrospective study compares orbital recurrence, metastatic disease, and overall survival in naive eyes treated primarily with either ophthalmic artery chemosurgery or enucleation.

  • More orbital recurrences were found in the enucleation group than in the ophthalmic artery chemosurgery group.

Methods
Data Collection

This single-institution cohort study is a retrospective record review of patients primarily treated at Memorial Sloan-Kettering Cancer Center (MSKCC) who presented between February 14, 2006, and March 4, 2014, with advanced intraocular retinoblastoma that fulfilled criteria for Reese-Ellsworth group 5 or International Classification of Retinoblastoma (ICRB; Children’s Oncology Group) group D or E. This analysis was conducted between August 1, 2014, and March 1, 2015. Eyes with Reese-Ellsworth group 5 retinoblastoma are defined as having massive tumor involving more than 50% of the retina and vitreous seeding. Eyes with ICRB (Children’s Oncology Group) group D retinoblastoma are defined as having diffuse disease with significant vitreous or subretinal seeding, with or without subretinal fluid or up to total retinal detachment. In contrast, eyes with group E retinoblastoma have 1 or more poor prognostic features, including tumor touching the lens, tumor anterior to the anterior vitreous face or involving the ciliary body or anterior segment, diffuse infiltrating retinoblastoma, neovascular glaucoma, opaque media from hemorrhage, tumor necrosis with aseptic orbital cellulitis, or phthisis bulbi.

Patients were treated initially with either enucleation at MSKCC or OAC at New York–Presbyterian Hospital (Weill Cornell Medical College) and then followed up at MSKCC. The start date of this series represents the advent of OAC at our institutions. Clinical characteristics, including sex, age at presentation, laterality of disease, treatment history, presence of iris neovascularization on clinical examination at initial presentation, and postenucleation pathology, were collected via the electronic medical record.

Orbital recurrence was initially assessed by clinical examination and magnetic resonance imaging. When there was suspicion for orbital disease, cases were confirmed with biopsy and histopathology. Metastatic disease was assessed by computed tomography, bone scan, bone marrow biopsy or aspirate, and magnetic resonance imaging. Eyes treated primarily with OAC but eventually enucleated were included in the OAC group and not the enucleation group. Eyes that had received systemic, intra-arterial, or intravitreal chemotherapy or external beam or plaque radiotherapy prior to enucleation were excluded from the analysis. Other exclusion criteria were follow-up time less than 6 months, orbital or extraocular retinoblastoma at initial presentation, or trilateral retinoblastoma.

The study was approved by the MSKCC Institutional Review Board. Informed consent was not required owing to the retrospective nature of the study.

Statistical Analysis

SPSS version 21 (IBM Corp) and Prism (GraphPad Software) were used to construct Kaplan-Meier (KM) curves of orbital recurrence–free survival, metastasis-free survival, and overall survival. The KM curves were then compared using a log-rank test. A multivariate Cox proportional hazards regression model was used to assess for associations between treatment (OAC vs enucleation), presence of iris neovascularization, and ICRB group E classification and the outcome measure of orbital recurrence–free survival using Wald stepwise backward elimination.

Results
Baseline Characteristics

Clinical characteristics of each group are depicted in the Table. There were 72 patients (77 eyes) in the OAC group and 63 patients (63 eyes) in the enucleation group. There were more eyes from patients with bilateral retinoblastoma in the OAC group (36.4%) than in the enucleation group (11.1%). The mean age at diagnosis was 19.3 months in the OAC group compared with 23.2 months in the enucleation group. The mean age at first treatment was 20.7 months in the OAC group vs 25.2 months in the enucleation group. Only 5.2% of eyes in the OAC group had iris neovascularization on clinical examination at initial presentation, while 25.4% of eyes in the enucleation group had iris neovascularization. There were more eyes with group E retinoblastoma in the enucleation group (87.3%) than in the OAC group (29.9%).

Among eyes treated primarily with OAC, 84.4% received additional subsequent treatments, including thermal laser therapy (58.4%), cryotherapy (44.2%), external beam radiotherapy (1.3%), plaque radiotherapy (15.6%), retinal surgery (3.9%), periocular chemotherapy (3.9%), triamcinolone acetonide injection into the sub-Tenon capsule (2.6%), intravitreal chemotherapy (9.1%), and intravenous chemotherapy (6.5%). Among the eyes treated with OAC, 13.0% were eventually enucleated. In the enucleation group, 11.1% of eyes received additional subsequent therapy, including external beam radiotherapy (1.6%) and intravenous chemotherapy (9.5%).

All eyes for which pathology results were available in the OAC and enucleation groups had negative optic nerve margins. Overall, 1 of 10 enucleated eyes (10.0%) in the OAC group and 11 of 63 eyes (17.5%) in the primary enucleation group had higher-risk features as defined by optic nerve invasion past the lamina cribrosa, massive choroidal invasion, or scleral invasion.

Orbital Recurrences

There was 1 orbital recurrence (1.3%) in the primary OAC group and there were 5 orbital recurrences (7.9%) in the primary enucleation group during median follow-up times of 38.7 months (range, 9.0-104.3 months) and 42.6 months (range, 6.2-97.1 months), respectively. The KM analysis of orbital recurrence–free survival is depicted in the Figure. The 24-month KM estimate for orbital recurrence–free survival was worse for the enucleation group (92.1%; 95% CI, 82.0-96.7) than for the OAC group (100%) (log-rank test, P = .049).

The lone orbital recurrence in the OAC group occurred in a boy who presented at 88.5 months with group 5/D unilateral retinoblastoma. The eye was normotensive on initial presentation without evidence of iris neovascularization. The patient was first treated with 3 cycles of OAC with melphalan and later received laser therapy, cryotherapy, intravenous chemotherapy, and eventually enucleation, where pathology findings were notable for ciliary body invasion and neovascular glaucoma. Orbital recurrence occurred at 24.2 months after initial treatment with OAC, and a subsequent workup revealed metastatic disease. This patient was later treated for his metastatic disease and is still alive without signs of metastases, 84.2 months after initial presentation.

In the enucleation group, the 5 cases of orbital recurrence occurred in 3 boys and 2 girls. All cases were group 5/E at presentation and were unilateral. Only 1 of the 5 patients in this group had iris neovascularization on initial clinical examination or subsequently on pathology. The mean age at enucleation was 24.0 months; 1 patient eventually received external beam radiotherapy to the orbit, while all 5 eventually received systemic chemotherapy. Pathology results revealed that 2 of the 5 eyes had higher-risk features after enucleation, and each of these patients was offered intravenous chemotherapy. One of these patients received chemotherapy directly after enucleation, but the other family elected for observation and this patient was not treated with chemotherapy until he developed orbital disease. The mean time to orbital recurrence was 4.1 months. Of the 5 patients with an orbital recurrence, 1 never developed disease outside the orbit and 4 were found to have metastatic disease outside the orbit on subsequent workup directly after the orbital recurrence. One of the patients with metastatic disease eventually died 38.6 months after initial treatment.

Metastatic Disease and Death

In the OAC group, there were 3 cases of metastatic disease (4.2%) and no deaths. The enucleation group had 5 cases of metastatic disease (7.9%) and 2 deaths (3.2%). The 24-month KM estimate of metastasis-free survival was 92.0% (95% CI, 81.9-96.6) for the enucleation group and 98.6% for the OAC group (95% CI, 90.3-99.8) (log-rank test, P = .32). With respect to overall survival, the 24-month KM estimate was 97.9% (95% CI, 85.9-99.7) for the enucleation group and 100% for the OAC group (log-rank test, P = .13).

Cox Multivariate Regression Analysis

A Cox proportional hazards regression model was used to assess for associations between 3 covariates (treatment with OAC vs enucleation, presence of iris neovascularization, and ICRB group E classification) and the main outcome measure of orbital recurrence. Using a Wald stepwise backward elimination method, both iris neovascularization and group E classification were eliminated from the model. Only treatment with OAC remained as an independent predictor of orbital recurrence, with a hazard ratio of 0.153 (95% CI, 0.018-1.314; P = .09).

Discussion

In this single-institution retrospective study of advanced intraocular retinoblastoma, there were more orbital recurrences in the group primarily treated with enucleation (7.9%) than in the OAC group (1.3%). We also detected more metastases in the enucleation group than in the OAC group (7.9% vs 4.2%, respectively) and deaths only in the enucleation group. Eyes treated with OAC were associated with a lower rate of orbital recurrence in the KM univariate analysis (P = .049). In our Cox proportional hazards model, treatment with OAC remained in the model as an independent predictor of orbital recurrence, but P = .09, likely because there was insufficient statistical power to show a meaningful difference.

When combining both the primary OAC and primary enucleation cohorts, the total rate of recurrence in this series was 4.3%, which aligns with the incidence of orbital disease (4.2%) in a previously reported larger cohort from our institution.11 However, it is notable that these historical estimates were based on enucleated eyes of multiple stages, not just those classified as Reese-Ellsworth group 5 or ICRB group D or E. Because prior estimates of orbital disease might be diluted by a lower rate of orbital recurrence within eyes with retinoblastoma not as advanced as the cohort in this study, our overall recurrence rate of 4.2% may in fact represent a decrease in the total number of orbital recurrences in eyes with advanced retinoblastoma driven by a lower incidence within the OAC group.

The main difference between the patients receiving OAC and those receiving enucleation in this series is the presence of iris neovascularization and the distribution of eyes with group E retinoblastoma, which were both higher in the enucleation group. Iris neovascularization15,16 has previously been found to be a poor prognostic feature in advanced retinoblastoma. Further, it has been associated with higher-risk histopathological findings and metastatic disease.17,18

However, within our entire cohort, we did not identify an association between iris neovascularization or ICRB group E classification and orbital recurrence survival in our Cox proportional hazards model. This is driven by the fact that only 1 of the total 6 patients in the entire cohort with an orbital recurrence had iris neovascularization. Therefore, the difference in incidence of orbital recurrence cannot be explained by the selection bias (of iris neovascularization or ICRB group classification) within the enucleation group.

The question of whether OAC as a primary treatment for advanced intraocular disease increases the chance of metastatic disease has been raised in the literature.19,20 However, our study shows that there is no increased risk of metastatic disease or death in patients treated with OAC. In fact, there were fewer cases of metastatic disease and no metastatic deaths in the OAC group, although the study was underpowered to demonstrate statistical differences.

Orbital disease, in much of the world, represents direct extension of disease through the sclera into the orbit. In the United States and other more developed countries, however, it is a marker for metastatic disease. Eighty percent of patients in the United States who present with orbital disease are found to have concurrent widespread metastases,21 and the orbital disease can be considered a surrogate of metastatic disease. Therefore, it is plausible that orbital disease, as well as metastatic disease, is present microscopically at the time of treatment with enucleation or first OAC. A possible mechanism by which OAC reduces the incidence of orbital disease but not of metastases is that OAC, with its high ocular concentration of drug, effectively obliterates microscopic orbital foci, but because the systemic dose is so low, it has no impact on distant metastatic disease.

A limitation of our study is its retrospective design. Our center typically recommends primary enucleation for eyes with poor prognostic features such as iris neovascularization, neovascular glaucoma, or phthisis bulbi. This explains the larger percentage of eyes with advanced group E retinoblastoma and iris neovascularization in the enucleated group. However, these differences were addressed in our regression analysis.

Conclusions

This study demonstrates that treatment-naive eyes with advanced retinoblastoma treated in our institutions with OAC had fewer orbital recurrences and that no differences in metastatic disease could be identified compared with enucleation. Additional studies on orbital and metastatic disease in eyes treated with OAC could help to support or refute our findings.

Back to top
Article Information

Corresponding Author: David Harold Abramson, MD, Ophthalmic Oncology Service, Memorial Sloan-Kettering Cancer Center, 1275 York Ave, New York, NY 10065 (abramsod@mskcc.org).

Submitted for Publication: March 20, 2015; final revision received May 28, 2015; accepted May 29, 2015.

Published Online: July 16, 2015. doi:10.1001/jamaophthalmol.2015.2243.

Author Contributions: Drs Yannuzzi and Abramson had full access to all of the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis.

Study concept and design: Yannuzzi, Francis, Marr, Gobin, Abramson.

Acquisition, analysis, or interpretation of data: Yannuzzi, Francis, Marr, Belinsky, Dunkel, Gobin.

Drafting of the manuscript: Yannuzzi.

Critical revision of the manuscript for important intellectual content: All authors.

Statistical analysis: Yannuzzi.

Obtained funding: Abramson.

Administrative, technical, or material support: Belinsky, Gobin, Abramson.

Study supervision: Francis, Marr, Belinsky, Dunkel, Gobin, Abramson.

Conflict of Interest Disclosures: All authors have completed and submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Dr Dunkel reported receiving personal fees from Bristol-Myers Squibb, Bayer, and Ipsen. No other disclosures were reported.

Funding/Support: This work was supported in part by The Fund for Ophthalmic Knowledge, Inc.

Role of the Funder/Sponsor: The funder had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; and decision to submit the manuscript for publication.

References
1.
Grigorovski  N, Lucena  E, Mattosinho  C,  et al.  Use of intra-arterial chemotherapy for retinoblastoma: results of a survey. Int J Ophthalmol. 2014;7(4):726-730.
PubMed
2.
Gobin  YP, Dunkel  IJ, Marr  BP, Brodie  SE, Abramson  DH.  Intra-arterial chemotherapy for the management of retinoblastoma: four-year experience. Arch Ophthalmol. 2011;129(6):732-737.
PubMedArticle
3.
Suzuki  S, Yamane  T, Mohri  M, Kaneko  A.  Selective ophthalmic arterial injection therapy for intraocular retinoblastoma: the long-term prognosis. Ophthalmology. 2011;118(10):2081-2087.
PubMedArticle
4.
Shields  CL, Manjandavida  FP, Lally  SE,  et al.  Intra-arterial chemotherapy for retinoblastoma in 70 eyes: outcomes based on the International Classification of Retinoblastoma. Ophthalmology. 2014;121(7):1453-1460.
PubMedArticle
5.
Peterson  EC, Elhammady  MS, Quintero-Wolfe  S, Murray  TG, Aziz-Sultan  MA.  Selective ophthalmic artery infusion of chemotherapy for advanced intraocular retinoblastoma: initial experience with 17 tumors. J Neurosurg. 2011;114(6):1603-1608.
PubMedArticle
6.
Gobin  YP, Dunkel  IJ, Marr  BP, Francis  JH, Brodie  SE, Abramson  DH.  Combined, sequential intravenous and intra-arterial chemotherapy (bridge chemotherapy) for young infants with retinoblastoma. PLoS One. 2012;7(9):e44322.
PubMedArticle
7.
Abramson  DH, Marr  BP, Dunkel  IJ,  et al.  Intra-arterial chemotherapy for retinoblastoma in eyes with vitreous and/or subretinal seeding: 2-year results. Br J Ophthalmol. 2012;96(4):499-502.
PubMedArticle
8.
Abramson  DH, Francis  JH, Dunkel  IJ, Marr  BP, Brodie  SE, Gobin  YP.  Ophthalmic artery chemosurgery for retinoblastoma prevents new intraocular tumors. Ophthalmology. 2013;120(3):560-565.
PubMedArticle
9.
Hungerford  J, Kingston  J, Plowman  N.  Orbital recurrence of retinoblastoma. Ophthalmic Paediatr Genet. 1987;8(1):63-68.
PubMedArticle
10.
Khelfaoui  F, Validire  P, Auperin  A,  et al.  Histopathologic risk factors in retinoblastoma: a retrospective study of 172 patients treated in a single institution. Cancer. 1996;77(6):1206-1213.
PubMedArticle
11.
Kim  JW, Kathpalia  V, Dunkel  IJ, Wong  RK, Riedel  E, Abramson  DH.  Orbital recurrence of retinoblastoma following enucleation. Br J Ophthalmol. 2009;93(4):463-467.
PubMedArticle
12.
Doz  F, Khelfaoui  F, Mosseri  V,  et al.  The role of chemotherapy in orbital involvement of retinoblastoma: the experience of a single institution with 33 patients. Cancer. 1994;74(2):722-732.
PubMedArticle
13.
Singh  AD, Shields  CL, Shields  JA.  Prognostic factors in retinoblastoma. J Pediatr Ophthalmol Strabismus. 2000;37(3):134-141.
PubMed
14.
Kopelman  JE, McLean  IW, Rosenberg  SH.  Multivariate analysis of risk factors for metastasis in retinoblastoma treated by enucleation. Ophthalmology. 1987;94(4):371-377.
PubMedArticle
15.
Rubin  CM, Robison  LL, Cameron  JD,  et al.  Intraocular retinoblastoma group V: an analysis of prognostic factors. J Clin Oncol. 1985;3(5):680-685.
PubMed
16.
Baez  KA, Ulbig  MW, Cater  J, Shields  CL, Shields  JA.  Iris neovascularization, increased intraocular pressure and vitreous hemorrhage as risk factors for invasion of the optic nerve and choroid in children with retinoblastoma [in German]. Ophthalmologe. 1994;91(6):796-800.
PubMed
17.
Shields  CL, Shields  JA, Baez  KA, Cater  J, De Potter  PV.  Choroidal invasion of retinoblastoma: metastatic potential and clinical risk factors. Br J Ophthalmol. 1993;77(9):544-548.
PubMedArticle
18.
Chantada  GL, Gonzalez  A, Fandino  A,  et al.  Some clinical findings at presentation can predict high-risk pathology features in unilateral retinoblastoma. J Pediatr Hematol Oncol. 2009;31(5):325-329.
PubMedArticle
19.
Shields  CL, Shields  JA.  Intra-arterial chemotherapy for retinoblastoma: the beginning of a long journey. Clin Experiment Ophthalmol. 2010;38(6):638-643.
PubMedArticle
20.
Jabbour  P, Chalouhi  N, Tjoumakaris  S,  et al.  Pearls and pitfalls of intraarterial chemotherapy for retinoblastoma. J Neurosurg Pediatr. 2012;10(3):175-181.
PubMedArticle
21.
Ellsworth  RM.  Orbital retinoblastoma. Trans Am Ophthalmol Soc. 1974;72:79-88.
PubMed
×