Jesse L. Berry

Long-term outcomes of Group D eyes in bilateral retinoblastoma patients treated with chemoreduction and low-dose IMRT salvage.

To evaluate outcomes of Group D eyes of bilateral retinoblastoma patients treated with primary chemoreduction and external beam radiation as salvage.

Outcomes of Choroidal Melanomas Treated With Eye Physics: A 20-Year Review

IMPORTANCE The University of Southern California Eye Physics plaques compare favorably with the Collaborative Ocular Melanoma Study plaques in terms of late adverse effects from radiation, metastasis, and local tumor recurrence. OBJECTIVE To review the University of Southern California experience using Eye Physics plaques and Plaque Simulator software to treat choroidal melanomas and compare the outcomes with published results of the Collaborative Ocular Melanoma Study. DESIGN, SETTING, AND PARTICIPANTS A retrospective case series of 82 patients treated for medium-sized choroidal melanoma from January 1, 1990, through December 30, 2010, using iodine 125 plaques and treatment simulation software developed at the University of Southern California. The dosimetric goal was 85 Gy in 7 days to a conformal volume enclosing the apex and a 2-mm margin surrounding the tumor base. Plaque localization was guided by the Plaque Simulator computer modeling system using preoperative imaging studies. MAIN OUTCOMES AND MEASURES Primary outcome measures were local tumor control, globe preservation, and metastases. Secondary outcome measures were late radiation adverse effects including postoperative vision changes, optic neuropathy, radiation retinopathy, and cataract. RESULTS The median follow-up for 82 patients was 46.8 months (range, 1-171 months). Globe preservation was achieved in 80 patients (97.6%); 2 patients underwent enucleation for local recurrence. Metastatic disease developed in 9 patients (11.0%). Retinopathy was seen in 31 patients (37.8%), optic neuropathy in 12 (14.6%), and cataracts in 26 (31.7%). Postoperatively, 21 patients (25.6%) lost more than 6 lines of Snellen visual acuity. CONCLUSIONS AND RELEVANCE When considering rates of local recurrence, metastases, and late radiation adverse effects, the University of Southern California results for medium-sized choroidal melanomas using Eye Physics plaques compared favorably with Collaborative Ocular Melanoma Study data. The Plaque Simulator 3-dimensional tumor-modeling program developed at the University of Southern California is a reliable method for determining plaque positioning preoperatively and for treating this cohort of patients.

Sonoporation Enhances Chemotherapeutic Efficacy in Retinoblastoma Cells In Vitro

PURPOSE To study the ability of ultrasound (US) and microbubbles (MB) to enhance chemotherapeutic efficacy against retinoblastoma Y79 cells in vitro. METHODS The experiment was performed in three stages. The authors first compared cell viability of Y79 cells exposed to doxorubicin versus cells exposed to doxorubicin combined with low-intensity, low-frequency US + MB. They then evaluated enhanced cell permeability by studying the intensity of intracellular fluorescence in cells exposed to doxorubicin versus those exposed to doxorubicin with US + MB. Lastly they evaluated the morphologic characteristics of the cells by scanning electron microscopy (SEM) to identify the presence of pores. RESULTS The Y79 cells exposed to doxorubicin with US + MB showed a significant decrease in cell viability at 72 hours compared with those exposed to doxorubicin alone (P = 0.02). Cells also showed immediate increased permeability to doxorubicin with the addition of US + MB compared with doxorubicin alone, which continued to increase over 60 minutes. SEM did not demonstrate physical pores at the lowest US + MB intensity shown to enhance intracellular doxorubicin fluorescence. CONCLUSIONS US + MB facilitates the uptake of chemotherapy in retinoblastoma Y79 cells in vitro. This occurs in the absence of visible pores, suggesting a possible secondary mechanism for increased drug delivery. This experiment is the first step toward enhancing chemotherapy with sonoporation in the treatment of intraocular tumors. This technique may lead to more effective chemotherapy treatments with less collateral damage to ocular tissues and may allow reduced systemic dosage and systemic side effects.

Histopathologic findings of eyes enucleated after treatment with chemosurgery for retinoblastoma

Introduction: Intra-arterial chemotherapy (chemosurgery) for the treatment of retinoblastoma has been performed more than 1600 times (more than 1400 times in Japan and 200 times in New York) over the past 20 years.Despite this treatment’s success some eyes cannot be saved and require enucleation. Here we report the histopathologic findings of the remaining intraocular tumor of eyes that were enucleated following treatment that included chemosurgery in New York City. Materials and Methodology: Independent histopathologic review of the enucleated eyes was correlated with the clinical findings that prompted enucleation. Results: Between May 1, 2006 and April 30, 2009, 56 eyes received chemosurgery at our institution, and 10 of these were enucleated subsequently. All were Reese Ellsworth Group 5 at enucleation. Of the 21 eyes that were treated with chemosurgery as the primary treatment, 1 (5%) was enucleated subsequently; its histopathology revealed residual non-necrotic, non-calcified tumor. Of the 34 eyes treated with chemosurgery after other treatments, 9 (24%) were enucleated, and 5 of these eyes contained non-calcified, non-necrotic tumor. None was enucleated for complications of chemosurgery. All patients were alive and free of metastatic disease as of September 2009. Conclusions: A significant number of eyes with advanced intraocular retinoblastoma avoided enucleation as a result of chemosurgery. The rate of eyes that were enucleated was higher when chemosurgery was the secondary rather than the primary treatment. Of the eight eyes enucleated for progressive disease six had non-necrotic, non-calcified tumor cells.

Detection and Intraretinal Localization of an 'Invisible' Retinoblastoma Using Optical Coherence Tomography.

Purpose: To report the use of handheld spectral-domain optical coherence tomography (HHSD OCT) to identify and define the intraretinal location of a small retinoblastoma that was not detectable by indirect ophthalmoscopy. Methods: This is a retrospective case report of a tumor identified with HHSD OCT in a single patient. Results: A 7-week-old male was diagnosed with unilateral group E retinoblastoma in the right eye. An enucleation was completed successfully with histopathologic confirmation of the diagnosis. The normal left eye was monitored for the development of retinoblastoma, and 10 weeks after diagnosis, three new small retinoblastomas were noted in the posterior pole. Identification of the smallest of the three tumors was facilitated by HHSD OCT; it was adjacent to the optic nerve head, and involved the outer nuclear layer, outer plexiform layer, and inner nuclear layer, with the inner retina draping over the tumor. Conclusion: HHSD OCT can aid the ocular oncologist in the identification of very small retinoblastomas before they are visible to the eye, which allows for earlier and potentially vision-sparing treatment of these lesions. Additionally, the ability to identify these very small tumors and to localize them anatomically within the retinal layers may aid in our understanding of retinoblastoma tumorigenesis.

Low-Dose Chemoreduction for Infants Diagnosed with Retinoblastoma before 6 Months of Age.

Aim: The purpose of this study was to evaluate the outcomes of infants diagnosed with retinoblastoma before 6 months of age, including the need for chemoreduction (CRD). In this age group, dosage of CRD was reduced due to its potential for toxicity. Methods: This is a retrospective review from 2000 to 2009 that includes 126 eyes of 72 infants (18 unilateral, 54 bilateral). Systemic CRD was administered when local modalities failed or were considered inadequate. Primary outcome measures were the need for CRD and globe salvage. Results: Of the 72 infants diagnosed before 6 months of age, 48 (67%) ultimately required CRD for globe salvage, 40 (56%) patients before 6 months of age. Globe salvage was achieved in 62% (78/126) of eyes overall and in 93% (68/73) of eyes with Group A-C disease. No patient was hospitalized for CRD-related illness; survival was 100%. The mean follow-up was 52.9 months (range 1-148 months). Conclusion: Utilizing a combination of focal modalities and reduced-dose CRD, children diagnosed with retinoblastoma before 6 months of age attain globe salvage rates comparable to those of older age groups. Two thirds of the infants ultimately required CRD for globe salvage. Bilateral disease as well as Group D and E classification in at least one eye at presentation increased the chance of requiring CRD (p < 0.0001 and p < 0.016, respectively).

Risk of metastasis and orbital recurrence in advanced retinoblastoma eyes treated with systemic chemoreduction versus primary enucleation

The purpose of this study was to evaluate the risk of metastatic disease and orbital recurrence in advanced retinoblastoma treated with systemic chemoreduction versus primary enucleation.

Long-Term Outcomes of Group B Eyes in Patients with Retinoblastoma Treated with Short-Course Chemoreduction: Experience from Children's Hospital Los Angeles/University of Southern California

Background/Aims: Chemoreduction protocols for retinoblastoma vary widely across institutions. Herein, we compare a 3- versus 6-cycle chemotherapy approach for group B retinoblastoma. Methods: A nonrandomized, retrospective review of patients diagnosed with group B retinoblastoma from 1991-2011 at Childrens Hospital Los Angeles was performed. A total of 72 eyes of 63 patients were analyzed. Mean follow-up time was 82 months (range 6-272 months). Main outcome measures were globe salvage and need for external beam radiation. Results: Forty-six patients (55 eyes) were treated upfront with 3 cycles of carboplatin, etoposide, and vincristine; 17 patients (17 eyes) received 6 cycles. Thirty-seven eyes (67%) in the 3-cycle group were cured with initial chemoreduction alone. An additional 10 eyes with persistent or recurrent tumors were rescued with 3 more cycles for a total salvage rate of 85% (47/55 eyes). In the 6-cycle group, 16 of 17 eyes (94%) avoided radiation and enucleation. Conclusion: The initial recurrence rate was higher for the 3-cycle group (p = 0.03). However, eyes failing short-course chemoreduction were rescued with 3 additional cycles and achieved a similar overall event-free survival rate (p = 0.16). In our cohort, this short-course approach spared 63% (29/46) of patients with group B retinoblastoma the extra 3 cycles of systemic chemotherapy.

Factors predictive of long-term visual outcomes of Group D eyes treated with chemoreduction and low-dose IMRT salvage: The Children's Hospital Los Angeles experience

Aim To evaluate clinical factors predictive of visual outcomes in Group D retinoblastoma eyes. Methods Retrospective chart review of patients with Group D retinoblastoma from January 2000 to December 2009. All patients were treated with systemic chemoreduction and external beam radiation as salvage therapy when indicated. Primary outcome measure was visual acuity. Clinical factors evaluated include quadrants of subretinal fluid, extent of vitreous seeding, involvement of more/less than 50% of the macula, endophytic/exophytic tumour classification, and presence of tumour behind the lens at diagnosis. Results Fifty-two Group D eyes of 41 patients were included; 10 eyes with visual acuity better than 20/80, 32 eyes with vision worse than 20/100 and 10 eyes with indeterminate vision (fix and follow). Complete retinal detachment (p=0.002), involvement of >50% of the macula (p=0.01), and seeding >3 quadrants (p=0.05) were associated with worse visual outcome. Average follow-up was 50.0 months (range: 10–118 months). Conclusions At presentation, it is difficult to predict which Group D eyes will be salvaged with useful vision following systemic chemotherapy. The presence of complete retinal detachment, macular involvement and extensive seeding on presentation were factors associated with a worse visual prognosis in this study. These findings can guide the ophthalmologist in clinical decision making, as well as in counselling parents.

An international survey of classification and treatment choices for group D retinoblastoma

AIM To determine which IIRC scheme was used by retinoblastoma centers worldwide and the percentage of D eyes treated primarily with enucleation versus globe salvaging therapies as well as to correlate trends in treatment choice to IIRC version used and geographic region. METHODS An anonymized electronic survey was offered to 115 physicians at 39 retinoblastoma centers worldwide asking about IIRC classification schemes and treatment patterns used between 2008 and 2012. Participants were asked to record which version of the IIRC was used for classification, how many group D eyes were diagnosed, and how many eyes were treated with enucleation versus globe salvaging therapies. Averages of eyes per treatment modality were calculated and stratified by both IIRC version and geographic region. Statistical significance was determined by Chi-square, ANOVA and Kruskal-Wallis tests using Prism. RESULTS The survey was completed by 29% of physicians invited to participate. Totally 1807 D eyes were diagnosed. Regarding IIRC system, 27% of centers used the Childrens Hospital of Los Angeles (CHLA) version, 33% used the Childrens Oncology Group (COG) version, 23% used the Philadelphia version, and 17% were unsure. The rate for primary enucleation varied between 0 and 100% and the mean was 29%. By IIRC version, primary enucleation rates were: Philadelphia, 8%; COG, 34%; and CHLA, 37%. By geographic region, primary enucleation rates were: Latin America, 57%; Asia, 40%; Europe, 36%; Africa, 10%, US, 8%; and Middle East, 8%. However, systemic chemoreduction was used more often than enucleation in all regions except Latin America with a mean of 57% per center (P<0.0001). CONCLUSION Worldwide there is no consensus on which IIRC version is used, systemic chemoreduction was the most frequently used initial treatment during the study period followed by enucleation and primary treatment modality, especially enucleation, varied greatly with regards to IIRC version used and geographic region.