Dataset Information

Intracameral Chemotherapy (Melphalan) for Aqueous Seeding in Retinoblastoma: Bicameral Injection Technique and Related Toxicity in a Pilot Case Study.

ABSTRACT:

Background

The anterior chamber has been shown by pharmacokinetic studies to represent a sanctuary never achieving a tumoricidal dose with the present administration routes, such as systemic, intra-arterial, or intravitreal injections.

Method

A novel intracameral chemotherapy technique is described to control aqueous seeding in a pilot unilateral group E retinoblastoma case with primary aqueous seeding. Anterior segment toxicity was carefully monitored.

Results

Control of the retinal tumor and vitreous seeding was achieved by intra-arterial and intravitreal chemotherapies. Sterilization of the aqueous was achieved after a first cycle of 7 melphalan injections in the anterior chamber, but relapse was noted 3.5 months later. This relapse was finally controlled with a second cycle of 6 intracameral injections targeting the posterior chamber. Corneal endothelial cell density remained stable over the injection period. Heterochromia and a progressive cataract developed, which required cataract surgery. At 5 years' follow-up, the patient is tumor free with normal vision (20/20 in both eyes), full binocularity, and no metastasis.

Conclusions

The present bicameral injection technique appears to be safe and effective with limited toxicity. Melphalan-induced side effects were noted on the iris and lens but with no impact on the final visual function.

SUBMITTER: Munier FL

PROVIDER: S-EPMC5566720 | biostudies-literature | 2017 Jul

REPOSITORIES: biostudies-literature

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Publications

Intracameral Chemotherapy (Melphalan) for Aqueous Seeding in Retinoblastoma: Bicameral Injection Technique and Related Toxicity in a Pilot Case Study.

Munier Francis L FL Gaillard Marie-Claire MC Decembrini Sarah S Bongiovanni Massimo M Beck-Popovic Maja M

Ocular oncology and pathology 20161229 2

<h4>Background</h4>The anterior chamber has been shown by pharmacokinetic studies to represent a sanctuary never achieving a tumoricidal dose with the present administration routes, such as systemic, intra-arterial, or intravitreal injections.<h4>Method</h4>A novel intracameral chemotherapy technique is described to control aqueous seeding in a pilot unilateral group E retinoblastoma case with primary aqueous seeding. Anterior segment toxicity was carefully monitored.<h4>Results</h4>Control of t ...[more]

PMID: 28868287

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Project description:PurposeRetinoblastoma (Rb) is the most common primary intraocular cancer in children. Unlike with most solid tumors, direct biopsy is contraindicated due to risk of tumor dissemination. However, recent therapeutic techniques have allowed for the safe extraction of aqueous humor (AH) from eyes undergoing therapy, providing the unique opportunity to use AH as a liquid biopsy for Rb. Although the extraction of AH in Rb eyes undergoing therapy is new, the consideration of whether there are tumor biomarkers in the AH is not. The current manuscript is a systematic review of all studies that have examined biomarkers in the AH of Rb eyes. The authors hypothesized that AH sampling and analysis of tumor biomarkers may have new clinical relevance for the diagnosis, prognosis, and/or management of Rb.MethodsA comprehensive database search (PubMed, Web of Science, Embase, and Cochrane Databases) was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement to identify articles on AH markers in Rb eyes. Inclusion criteria included English language articles with original reports on AH markers in the eyes of patients with confirmed Rb. Data on marker type, number of eyes, marker means and ranges, and when available, control values and clinicopathological correlations were collected. Articles were stratified based on marker type, and assessed quantitatively and qualitatively.ResultsAn initial database search produced 325 articles, and an additional 11 articles were identified through searching citations. After removing duplicates and applying the eligibility criteria, we selected 27 articles to be included in the current review. A total of 463 eyes with histologically confirmed Rb were included in this review. The various markers and their values, with comparison to controls and clinicopathological correlations, are discussed.ConclusionsAH sampling and tumor biomarker analysis in eyes without undergoing enucleation have the potential to revolutionize the management of Rb.Translational relevanceAlthough previous studies evaluated markers in the AH only after enucleation and not at diagnosis or during therapy, the clinical relevance of these markers was limited. However, recent changes in the management of Rb have allowed for safe sampling of the aqueous during therapy and, thus, correlation of tumor biomarkers with disease course. Thus, the authors felt it important to revisit previous research to evaluate whether these markers may now be applicable for the diagnosis, prognosis, or management of Rb.

Project description:Investigation of neurodegeneration in glaucoma, a leading cause of irreversible blindness worldwide, has been obfuscated by the lack of an efficient model that provides chronic, mild to moderate elevation of intraocular pressure (IOP) with preservation of optical media clarity for long term, in vivo interrogation of the structural and functional integrity of the retinal ganglion cells (RGCs). Here, we designed and formulated an injectable hydrogel based on in situ cross-linking of hyaluronic acid functionalized with vinyl sulfone (HA-VS) and thiol groups (HA-SH). Intracameral injection of HA-VS and HA-SH in C57BL/6J mice exhibited mild to moderate elevation of IOP with daily mean IOP ranged between 14?±?3 and 24?±?3?mmHg, which led to progressive, regional loss of RGCs evaluated with in vivo, time-lapse confocal scanning laser ophthalmoscopy; a reduction in fractional anisotropy in the optic nerve and the optic tract projected from the eye with increased IOP in diffusion tensor magnetic resonance imaging; a decrease in positive scotopic threshold response in electroretinography; and a decline in visual acuity measured with an optokinetic virtual reality system. The proportion of RGC loss was positively associated with the age of the animals, and the levels and the duration of IOP elevation. The new glaucoma model recapitulates key characteristics of human glaucoma which is pertinent to the development and pre-clinical testing of neuroprotective and neuroregenerative therapies. STATEMENT OF SIGNIFICANCE: A new model to study chronic neurodegeneration in glaucoma has been developed via intracameral injection of a specifically designed hyaluronic acid functionalized with vinyl sulfone and thiol groups for cross-linking. Intracameral injection of the chemically cross-linked hydrogel generates mild to moderate IOP elevation, resulting in progressive degeneration of the retinal ganglion cells, optic nerve, and optic tract, and a decline in visual function. The model recapitulates the key features of neurodegeneration in human glaucoma, which will facilitate and expedite the development of neuroprotective and neuroregenerative therapies.

Dataset Information

Intracameral Chemotherapy (Melphalan) for Aqueous Seeding in Retinoblastoma: Bicameral Injection Technique and Related Toxicity in a Pilot Case Study.

Background

Method

Results

Conclusions

Publications

Intracameral Chemotherapy (Melphalan) for Aqueous Seeding in Retinoblastoma: Bicameral Injection Technique and Related Toxicity in a Pilot Case Study.

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