Local and Systemic Toxicity of Intravitreal Melphalan for Vitreous Seeding in Retinoblastoma

Francis, Jasmine H.; Schaiquevich, Paula; Buitrago, Emiliano; Solé, María; Zapata, Gustavo; Croxatto, J. Oscar; Marr, Brian P.; Brodie, Scott E.; Berra, Alejandro; Chantada, Guillermo; Abramson, David H.

doi:10.1016/j.ophtha.2014.03.028

Cited by 151 publications

(140 citation statements)

References 16 publications

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“…While the grading system proposed by Munier [14] was not used in this (and other) studies, “widespread” likely indicates at least greater than grade 3. It has been suggested that doses > 30 µg may increase toxicity [16], although acute and diffuse toxicity have been described recently by Chao et al [26] after only 1 low-dose injection and by Aziz et al [27] at doses lower than 30 µg. Although our study observed a higher rate of retinal toxicity than prior ocular oncology literature, our cohort is small, and, additionally, the variation in the determination of retinal toxicity limits any direct comparison with the clinical grading we utilized as proposed by Munier [14].…”

Section: Discussionmentioning

confidence: 99%

“…Although a standardized dosage of melphalan has not been fully established due to the relative novelty of the treatment modality, previous publications support the usage of 20–40 µg. After Francis et al’s [16] report of electroretinogram amplitude decrease after 30 µg of melphalan, IVM dosing was limited to maximally 30 µg; at our center, 25 µg is the most frequently used dose with modifications made for the clinical burden of seeding.…”

Section: Methodsmentioning

confidence: 99%

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Integrated Treatment during the Intravitreal Melphalan Era: Concurrent Intravitreal Melphalan and Systemic Chemoreduction

et al. 2018

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Background: Intravitreal injection of melphalan (IVM) is safe and effective for the treatment of seeding in retinoblastoma. Current protocols require weekly injections during examination under anesthesia (EUA). To avoid additional anesthesia exposure for these children, IVM was initiated at the EUA concurrent with the 4th cycle of systemic chemoreduction in a series of 6 patients with persistent seeding. Methods: A retrospective review was completed to assess treatment response compared to all patients at our center treated with IVM and systemic chemotherapy. Overall, 6 eyes of 6 patients were included; salvage therapy included systemic chemoreduction with vincristine, etoposide, and carboplatin and IVM for persistent seeding. Results: IVM was initiated in all eyes at cycle 4 of their chemotherapy. Success in eradicating vitreous seeds was 100%; overall salvage rate was 67%. Anterior toxicity was observed in 2 out of 6 eyes and posterior toxicity in 4 out of 6 eyes. Conclusion: The concurrent chemoreduction and IVM protocol demonstrated a similar efficacy of globe salvage while sparing children additional EUAs. However, the increased rates of observed melphalan-related toxicities for concurrent therapy are concerning. Further clinical experience is necessary to define the best initiation time and dosing schedule for IVM.

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Section: Discussionmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Integrated Treatment during the Intravitreal Melphalan Era: Concurrent Intravitreal Melphalan and Systemic Chemoreduction

et al. 2018

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“…While there has been tremendous success in the last decade in globe salvaging therapy for advanced retinoblastoma, persistently active or recurrent vitreous seeding remains the most common reason for therapeutic failure [2]. After modification of the drug delivery technique in 2012, intravitreal melphalan injection has emerged as an effective therapy for vitreous seeding in retinoblastoma, with an overall acceptable safety profile [3,4,5]. …”

Section: Introductionmentioning

confidence: 99%

“…For example, Francis et al [3] demonstrated that weekly injections of melphalan resulted in a dose-dependent decrease in the electroretinogram (ERG) response in both humans and rabbits; thus, they cautioned against doses higher than 30 μg. Ghassemi and Amoli [6] described ischemic necrosis in the retina and choroid, severe gliosis and phthisis bulbi, and secondary neovascularization in a histopathologic analysis of enucleated eyes after receiving 50 μg of intravitreal melphalan.…”

Section: Introductionmentioning

confidence: 99%

Acute Hemorrhagic Retinopathy following Intravitreal Melphalan Injection for Retinoblastoma: A Report of Two Cases and Technical Modifications to Enhance the Prevention of Retinal Toxicity

et al. 2016

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Aims: To report the occurrence of acute hemorrhagic retinopathy following intravitreal melphalan injection for retinoblastoma. Methods: This is a retrospective case series of 2 patients with retinoblastoma treated with intravitreal melphalan for vitreous seeding who developed acute hemorrhagic retinopathy. Results: Patient 1 is a 6-month-old female with bilateral retinoblastoma (Group D right eye and Group B left eye) treated with 4 cycles of systemic chemotherapy and 2 intravitreal melphalan injections in each eye. Patient 2 is a 10-month-old male with unilateral Group D retinoblastoma treated with 6 cycles of systemic chemotherapy and 2 injections of intravitreal melphalan. At the 1-week follow-up after the second injection, both patients had an acute hemorrhagic retinopathy that resulted in chorioretinal toxicity with a sharp demarcation line between the normal and abnormal retina. At the last follow-up (22 and 12 months, respectively), there was total tumor control and resolution of vitreous seeding in both patients. Conclusions: Although intravitreal melphalan injection is effective for vitreous seeding in eyes with retinoblastoma, acute hemorrhagic retinopathy and diffuse chorioretinal atrophy is a possible complication of this treatment modality. Given the clinical findings observed in these patients, the development of this retinal toxicity most likely results from a retrohyaloid overdose. Consequently we suggest preventive measures aimed at limiting the risk of retrohyaloid injection.

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“…Without a blood supply, they often persist following systemic and/or intra-arterial chemotherapy and are not amenable to treatment with focal modalities. Persistent vitreous seeding is a common cause for treatment failure and the need for secondary enucleation in retinoblastoma [2, 3]. …”

Section: Introductionmentioning

confidence: 99%

Posterior Vitreous Detachment and the Associated Risk of Retinal Toxicity with Intravitreal Melphalan Treatment for Retinoblastoma

et al. 2018

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Background/Aims: The presence of a posterior vitreous detachment (PVD) may play a role in the development of severe retinal toxicity following intravitreal melphalan (IVM) injection for vitreous seeding. We aimed to evaluate the incidence of PVD in retinoblastoma eyes and its association with retinal toxicity after IVM. Methods: We reviewed 112 eyes of 81 retinoblastoma patients with B-scan images available for review from 2010 to 2017. A cohort with vitreous seeding treated with IVM was compared to a cohort that did not undergo injection. The primary outcome measure was the presence of PVD at diagnosis and after treatment. Secondary measures included IVM-associated retinal toxicity and other ocular complications. Results: The incidence of PVD was 20% at diagnosis, and in eyes with B-scans available both at diagnosis and after treatment 18% of eyes developed a PVD over the course of therapy, more frequently after IVM (p = 0.05). Of 34 eyes receiving IVM treatment, the incidences of posterior segment toxicity and globe salvage were similar between eyes with and without PVD (p = 0.4015 and 0.52, respectively). Conclusion: In this cohort of patients, there did not appear to be an association with the presence of PVD during IVM and the development of retinal toxicity.

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Local and Systemic Toxicity of Intravitreal Melphalan for Vitreous Seeding in Retinoblastoma

Cited by 151 publications

References 16 publications

Integrated Treatment during the Intravitreal Melphalan Era: Concurrent Intravitreal Melphalan and Systemic Chemoreduction

Integrated Treatment during the Intravitreal Melphalan Era: Concurrent Intravitreal Melphalan and Systemic Chemoreduction

Acute Hemorrhagic Retinopathy following Intravitreal Melphalan Injection for Retinoblastoma: A Report of Two Cases and Technical Modifications to Enhance the Prevention of Retinal Toxicity

Posterior Vitreous Detachment and the Associated Risk of Retinal Toxicity with Intravitreal Melphalan Treatment for Retinoblastoma

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