New melphalan derivatives for the treatment of retinoblastoma in combination with thermotherapy.

Of the different modalities used to treat retinoblastoma, a chemothermotherapeutic regimen combining carboplatin and thermotherapy (also termed focal therapy), and the application of melphalan as a monotherapy, are particularly successful. Some studies indicate that melphalan shows potential when applied in combination with focal therapy, and yet is not applied in this combination. Here we describe a series of synthetically modified melphalan derivatives that display enhanced cytotoxicity relative to melphalan itself, with some displaying further enhancements in cytotoxicity when applied in combination with heat (used as a model for thermotherapy).

MR Imaging of Adverse Effects and Ocular Growth Decline after Selective Intra-Arterial Chemotherapy for Retinoblastoma.

This retrospective multicenter study examines therapy-induced orbital and ocular MRI findings in retinoblastoma patients following selective intra-arterial chemotherapy (SIAC) and quantifies the impact of SIAC on ocular and optic nerve growth. Patients were selected based on medical chart review, with inclusion criteria requiring the availability of posttreatment MR imaging encompassing T2-weighted and T1-weighted images (pre- and post-intravenous gadolinium administration). Qualitative features and quantitative measurements were independently scored by experienced radiologists, with deep learning segmentation aiding total eye volume assessment.

IC3D Classification of Corneal Dystrophies-Edition 3.

Purpose: The International Committee for the Classification of Corneal Dystrophies (IC3D) was created in 2005 to develop a new classification system integrating current information on phenotype, histopathology, and genetic analysis. This update is the third edition of the IC3D nomenclature.

Methods: Peer-reviewed publications from 2014 to 2023 were evaluated.

When the second comes first- rhabdomyosarcoma preceding heritable retinoblastoma- a case report.

Background: Retinoblastoma (rb) is the most frequent intraocular tumor, accounting for 3% of all childhood cancers. Heritable rb survivors are germline carriers for an RB1 mutation and have a lifelong risk to develop non-ocular second primary tumors (SPTs) involving multiple other organs like the bones, soft tissues, or skin. These SPTs usually become manifest several years succeeding the diagnosis of rb.

Frail inner limiting membrane maculopathy suggested to describe a new retinal Alport-like condition with two variants in three generations of females.

Background: We report a three-generation family with isolated Alport-like retinal abnormalities in the absence of lenticonus, hearing loss, kidney disease, and detectable molecular genetic defects in known Alport-related genes.

Methods: Clinical examination includes ocular biomicroscopy, fundus photography, optical coherence tomography, dipstick urinalysis, serum creatinine assessment, and molecular genetic analysis.

Results: The proband, her mother, and her maternal grandmother had normal best-corrected visual acuity and normal visual fields in both eyes.

Genetics of Retinitis Pigmentosa and Other Hereditary Retinal Disorders in Western Switzerland.

Introduction: Mutational screening of inherited retinal disorders is prerequisite for gene targeted therapy. Our aim was to report and analyze the proportions of mutations in inherited retinal disease (IRD)-causing genes from a single center in Switzerland in order to describe the distribution of IRDs in Western Switzerland.

Methods: We conducted a retrospective study of patient records.

Translational screening platform to evaluate chemotherapy in combination with focal therapy for retinoblastoma.

Retinoblastoma is the most common pediatric eye cancer. It is currently treated with a limited number of drugs, adapted from other pediatric cancer treatments. Drug toxicity and relapse of the disease warrant new therapeutic strategies for these young patients.

Absorbable gelatin compressed sponge (Gelfoam) embolization of distal external carotid artery branches in intra-arterial chemotherapy for retinoblastoma.

Background: In intra-arterial chemotherapy for retinoblastoma, a backflow from unreachable external carotid artery branches in the ophthalmic artery can be challenging.

Objective: To describe a new endovascular technique using Gelfoam pledgets to temporarily occlude distal branches of the external carotid artery to reverse the competitive backflow into the ophthalmic artery in order to perform intra-arterial chemotherapy via the ostium of the ophthalmic artery in selected cases.

Methods: We queried our prospectively collected database of 327 consecutive patients treated for retinoblastoma by intra-arterial chemotherapy and identified those employing Gelfoam pledgets.

The predictive capacity of in vitro preclinical models to evaluate drugs for the treatment of retinoblastoma.

Retinoblastoma is a rare childhood cancer of the eye. Of the small number of drugs are used to treat retinoblastoma, all have been repurposed from drugs developed for other conditions. In order to find drugs or drug combinations better suited to the improved treatment of retinoblastoma, reliable predictive models are required, which facilitate the challenging transition from in vitro studies to clinical trials.

Ten-year experience with intracameral chemotherapy for aqueous seeding in retinoblastoma: long-term efficacy, safety and toxicity.

Aims: To report long-term results of intracameral chemotherapy (ICC) for aqueous seeding (AS) in retinoblastoma.

Methods: Retrospective study including 20 patients with primary (n=4) or secondary non-iatrogenic (n=16) AS treated with ICC according to a previously described technique between 2011 and 2020 with at least 1-year follow-up.

Results: AS control was initially achieved in all cases with a mean 5 injections of melphalan (n=13) or topotecan (n=7).

Proteomics of Aqueous Humor as a Source of Disease Biomarkers in Retinoblastoma.

Aqueous humor (AH) can be easily and safely used to evaluate disease-specific biomarkers in ocular disease. The aim of this study was to identify specific proteins biomarkers in the AH of retinoblastoma (RB) patients at various stages of the disease. We analyzed the proteome of 53 AH samples using high-resolution mass spectrometry.

Retinal and optic nerve relapse in retinoblastoma secondary to epiretinal and epipapillary vitreous seeds implantation documented by optical coherence tomography.

Background: Retinal retinoblastoma growth phenotypes can be endophytic, exophytic, diffuse infiltrating or anterior diffuse. Herein, we describe a novel tumor growth pattern in two patients.

Material And Methods: Imaging with spectral-domain optical coherence tomography (SD-OCT).

New COL6A6 Variant Causes Autosomal Dominant Retinitis Pigmentosa in a Four-Generation Family.

Purpose: To report that variants in the gene for a large lamina basal component protein, COL6A6 (collagen type VI alpha 6 chain, Col6α6), linked to chromosome 3p22.1 causes retinitis pigmentosa (RP) in patients with autosomal dominant transmission (adRP).

Methods: A positional-cloning approach, whole exome sequencing, and modeling were used.

Phenotype of Coats disease in females.

Objective: To determine whether the clinical presentation of Coats disease differs between males and females.

Methods And Analysis: Records of patients diagnosed with Coats disease at a single institution were retrospectively reviewed. Demographic data, main reason for initial consultation, comprehensive ocular examination at diagnosis and modalities of treatments during the follow-up were recorded.

Comparative Natural History of Visual Function From Patients With Biallelic Variants in BBS1 and BBS10.

Purpose: The purpose of this study was to compare the natural history of visual function change in cohorts of patients affected with retinal degeneration due to biallelic variants in Bardet-Biedl syndrome genes: BBS1 and BBS10.

Methods: Patients were recruited from nine academic centers from six countries (Belgium, Canada, France, New Zealand, Switzerland, and the United States). Inclusion criteria were: (1) female or male patients with a clinical diagnosis of retinal dystrophy, (2) biallelic disease-causing variants in BBS1 or BBS10, and (3) measures of visual function for at least one visit.

Defining High-risk Retinoblastoma: A Multicenter Global Survey.

Importance: High-risk histopathologic features of retinoblastoma are useful to assess the risk of systemic metastasis. In this era of globe salvage treatments for retinoblastoma, the definition of high-risk retinoblastoma is evolving.

Objective: To evaluate variations in the definition of high-risk histopathologic features for metastasis of retinoblastoma in different ocular oncology practices around the world.

Crystals deposits in the anterior and posterior lens cortex in Bietti corneo-retinal dystrophy.

Background: Whereas crystals deposit in the retina, the cornea and limbus in Bietty corneo-retinal dystrophy (BCD) is now well established and documented, only two published cases report their findings in the lens and no cases deep in the lens cortex.

Material And Methods: Four consecutive adult patients from three different unrelated families presenting lens crystals associated with advanced genetically confirmed BCD were enrolled with advanced disease and long follow up (>12 years). Demographics, visual acuity, slit lamp biomicroscopy, lens and posterior pole photography, optical coherence tomography (OCT), autofluorescence, and screening for CYP4V2 type of mutation were performed.

Current Indications of Secondary Enucleation in Retinoblastoma Management: A Position Paper on Behalf of the European Retinoblastoma Group (EURbG).

Secondary enucleation (SE) puts an irreversible end to eye-preserving therapies, whenever their prolongation is expected to violate the presumed state of metastatic grace. At present, it must be acknowledged that clear criteria for SE are missing, leading to empiric and subjective indications commonly related to disease progression or relapse, disease persistence masking the optic nerve head or treatment-related complications obscuring the fundus view. This absence of evidence-based consensus regarding SE is explained by the continuously moving frontiers of the conservative management as a result of diagnostic and therapeutic advances, as well as by the lack of studies sufficiently powered to accurately stratify the risk of metastasis in conservatively treated patients.

Sex, gender, and retinoblastoma: analysis of 4351 patients from 153 countries.

Objective: To investigate in a large global sample of patients with retinoblastoma whether sex predilection exists for this childhood eye cancer.

Methods: A cross-sectional analysis including 4351 treatment-naive retinoblastoma patients from 153 countries who presented to 278 treatment centers across the world in 2017. The sex ratio (male/female) in the sample was compared to the sex ratio at birth by means of a two-sided proportions test at global level, country economic grouping, continent, and for selected countries.