Safety and Efficacy of Intravitreal Chemotherapy (Melphalan) to Treat Vitreous Seeds in Retinoblastoma

Yousef, Yacoub A.; Jboor, Mays Al; Mohammad, Mona; Mehyar, Mustafa; Toro, Mario Damiano; Nazzal, Rashed Mustafa; Alzureikat, Qusai H; Rejdak, Magdalena; Elfalah, Mutasem; Sultan, Iyad; Ręjdak, Robert; Al‐Hussaini, Maysa; Al-Nawaiseh, Ibrahim

doi:10.3389/fphar.2021.696787

Cited by 15 publications

(6 citation statements)

References 38 publications

(55 reference statements)

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“…However, drug-induced retinal toxicity remains a major drawback of local chemotherapy. Melphalan and topotecan have been reported to cause retinal toxicity, as measured by reductions in electroretinography [ 8 – 12 ], particularly when administered intravitreally alone or in combination with intra-arterial chemotherapy for the management of vitreous disease in RB. This means that the choice of chemotherapeutic agents is crucial to advance the treatment.…”

Section: Discussionmentioning

confidence: 99%

“…However, some tumors are resistant to even local administration of maximum feasible drug dosages, and surgical removal of the eye becomes necessary to prevent death associated with extraocular dissemination [ 2 , 3 , 6 ]. In other cases, tumor control is effective and the globe can be preserved, but at the cost of drug-induced retinal toxicity and loss of vision [ 8 – 12 ]. Thus, there is an urgent need to identify drugs with improved antitumor activity and more favorable retinal toxicity profiles for the treatment of RB.…”

Section: Introductionmentioning

confidence: 99%

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Sunitinib efficacy with minimal toxicity in patient-derived retinoblastoma organoids

Srimongkol

Laosillapacharoen

Saengwimol

et al. 2023

J Exp Clin Cancer Res

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Background Recurrence of retinoblastoma (RB) following chemoreduction is common and is often managed with local (intra-arterial/intravitreal) chemotherapy. However, some tumors are resistant to even local administration of maximum feasible drug dosages, or effective tumor control and globe preservation may be achieved at the cost of vision loss due to drug-induced retinal toxicity. The aim of this study was to identify drugs with improved antitumor activity and more favorable retinal toxicity profiles via screening of potentially repurposable FDA-approved drugs in patient-derived tumor organoids. Methods Genomic profiling of five RB organoids and the corresponding parental tissues was performed. RB organoids were screened with 133 FDA-approved drugs, and candidate drugs were selected based on cytotoxicity and potency. RNA sequencing was conducted to generate a drug signature from RB organoids, and the effects of drugs on cell cycle progression and proliferative tumor cone restriction were examined. Drug toxicity was assessed with human embryonic stem cell-derived normal retinal organoids. The efficacy/toxicity profiles of candidate drugs were compared with those of drugs in clinical use. Results RB organoids maintained the genomic features of the parental tumors. Sunitinib was identified as highly cytotoxic against both classical RB1-deficient and novel MYCN-amplified RB organoids and inhibited proliferation while inducing differentiation in RB. Sunitinib was a more effective suppressor of proliferative tumor cones in RB organoids and had lower toxicity in normal retinal organoids than either melphalan or topotecan. Conclusion The efficacy and retinal toxicity profiles of sunitinib suggest that it could potentially be repurposed for local chemotherapy of RB.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Sunitinib efficacy with minimal toxicity in patient-derived retinoblastoma organoids

Srimongkol

Laosillapacharoen

Saengwimol

et al. 2023

J Exp Clin Cancer Res

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“…IVitC (Melphalan) avoided enucleation and radiation therapy. 14 Vitreous seeds are classified as dust (23.1%), sphere (61.5%), and cloud (15.4%). IVitC melphalan of 30-40 µg in 1 or 2 injections was proved effective treatment in 69.2% of eyes with regression of vitreous seeds.…”

Section: Discussionmentioning

confidence: 99%

“…Ocular side effects may occur in patients after standard Melphalan IVitC. 14,21 Brodie et al reported that a dosage of 20-30 µg of melphalan injection could not affect the retinal function of photopic ERG. 22 Whereas Francis et al have reported on reduced ERG amplitude, indicating permanent retinal toxicity.…”

Section: Discussionmentioning

confidence: 99%

Intravitreal chemotherapy (IVitC): An adjuvant eye salvage modality

Kadir¹

2022

IJOOO

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“…These images may affect surgical planning based on the status of each eye. 25,26 Knowledge about normative data about biometrics of the anterior part of the eye including the thickness of the CB and the iris are needed as normative comparative data to evaluate the pathology based on normal reference measurements. 25 Unfortunately, very few UBM and anterior segment OCT studies looked at the normal eyes and came with measurable normative data.…”

Section: Introductionmentioning

confidence: 99%

Ultrasound Biomicroscopy Measurements of the Normal Thickness for the Ciliary Body and the Iris in a Middle East Population

Yousef¹,

Mohammad²,

Al-Nawaiseh³

et al. 2022

OPTH

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Purpose: Ciliary body (CB) and iris thicknesses may change with certain eye diseases as well as between different populations. Here, we report Ultrasound Biomicroscopy Measurements (UBM) of the normal thickness for the CB and the iris from a homogenous population in the Middle East. Patients and Methods: Sonomed 35-MHz (SONOMED, INC. New York, USA) images were obtained at 4 radial meridians, and the thickness was measured at 3 locations along the radial length of the iris and at the thickest part of the CB. Parameters included mean thickness, median thickness, range, and standard deviation. Results: Of 46 adult patients, 83 normal eyes were included in this analysis. The overall mean, median iris thicknesses at the iris root, midway along the radial length of the iris, and at the juxtapupillary margin in mm were 0.42, 0.41 ± 0.08, 0.52, 0.51± 0.08, and 0.72, 0.71± 0.1, respectively. The overall mean, median thicknesses of the CB and CB + ciliary processes in mm were 0.72, 0.71 ± 0.1, and 1.42, 1.37 ± 0.2 respectively. Gender, age, side, and height had no impact on iris and/or CB thickness (p>0.05). However, the iris thickness was significantly thicker in the superior quadrant than inferiorly, and in the nasal quadrant than the temporal quadrant (p=0.04), and the CB thickness and the CB + ciliary processes thickness were significantly thicker in the superior quadrant than inferiorly (P = 0.04 and 0.02 consecutively). Conclusion:We measured in this study the normal thickness of the CB and the iris in normal eyes from homogenous population in the Middle East using ultrasound biomicroscopy. Our findings are essential for the ophthalmic community worldwide and in the Middle East region and can be used as a normative thickness data for the iris and CB in healthy eyes.

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Safety and Efficacy of Intravitreal Chemotherapy (Melphalan) to Treat Vitreous Seeds in Retinoblastoma

Cited by 15 publications

References 38 publications

Sunitinib efficacy with minimal toxicity in patient-derived retinoblastoma organoids

Sunitinib efficacy with minimal toxicity in patient-derived retinoblastoma organoids

Intravitreal chemotherapy (IVitC): An adjuvant eye salvage modality

Ultrasound Biomicroscopy Measurements of the Normal Thickness for the Ciliary Body and the Iris in a Middle East Population

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