Optical Density Ratio of Subretinal Fluid in Choroidal Melanomas Versus Choroidal Naevi Assessed by Optical Coherence Tomography.

Purpose: The purpose of this study was to determine whether optical density ratio (ODR) of subretinal fluid (SRF) on optical coherence tomography (OCT) differs between choroidal naevi and melanomas. Methods: One hundred ninety-nine patients (one eye per patient) presenting choroidal melanoma or choroidal naevus with SRF on OCT, evaluated between February and June 2019, were retrospectively included. Other retinal conditions, opaque media, and low-quality OCT were excluded. Mean pixel intensity of SRF (range = 0-255) was quantified using a semi-automated procedure by a masked observer on standard horizontal OCT sections. Mean vitreous intensity served as the reference for ODR. Results: One hundred twenty-eight patients with choroidal melanoma and 71 patients with choroidal naevus were included in this study. ODR (mean ± SD) was higher in melanomas (181 ± 64) than in naevi (78 ± 48, P < 0.0001). ODR was correlated to lesion thickness (P < 0.0001, r = 0.27), largest basal diameter (P = 0.028, r = 0.16) and, among naevi, to the number of risk factors for growth into melanoma (P = 0.032, r = 0.22). Among 110 patients with naevi or melanoma who underwent fluorescein angiography, ODR was 120.7 ± 550.1 in eyes presenting angiographic pinpoints versus 14.19 ± 26.0 in eyes that did not (P = 0.06). Fourteen eyes with naevi that transformed into melanoma over 3 years had a mean baseline ODR of 94.7 ± 243.5 compared to 4.01 ± 9.74 in 28 matched naevi eyes of similar size that did not transform (P = 0.027). Conclusions: SRF ODR is higher in choroidal melanoma compared to choroidal naevi. This OCT-derived imaging marker is also higher in choroidal naevi with the potential to transform into melanoma, compared to stationary naevi.

Diffuse Infiltrating Retinoblastoma with Anterior Chamber Involvement: Conservative Management and Identification of RB1 Alterations in Aqueous Humor.

Introduction: The aim of the study was to describe the successful conservative management of diffuse infiltrating retinoblastoma (DIR). Identification of RB1 pathogenic variant was done after cell-free DNA (cfDNA) analysis in aqueous humor. Case presentation: Herein, we report 2 patients with unilateral, non-familial DIR with anterior and posterior involvement. Both patients underwent liquid biopsy for tumor cfDNA analysis in aqueous humor. Treatment consisted of a combination of systemic and intra-arterial chemotherapy, with consecutive intracameral and intravitreal injections of melphalan. One patient also required iodine-125 brachytherapy. In both cases, tumor cfDNA analysis revealed biallelic somatic alterations of the RB1 gene. These alterations were not found in germline DNA. Both patients retained their eyes and had a useful vision after a follow-up of 2 years. Conclusion: In selected cases, conservative management of DIR is safe and effective. Tumor cfDNA analysis in aqueous humor is an effective technique to disclose RB1 somatic alterations that guide the germline molecular explorations and improve genetic counseling after conservative treatment.

Germline HPF1 retrogene insertion in RB1 gene involved in cancer predisposition.

About half of the human genome is composed of repeated sequences derived from mobile elements, mainly retrotransposons, generally without pathogenic effect. Familial forms of retinoblastoma are caused by germline pathogenic variants in RB1 gene. Here, we describe a family with retinoblastoma affecting a father and his son. No pathogenic variant was identified after DNA analysis of RB1 gene coding sequence and exon-intron junctions. However, RB1 mRNA analysis showed a chimeric transcript with insertion of 114 nucleotides from HPF1 gene inside RB1 gene. This chimeric transcript led to an insertion of 38 amino acids in functional domain of retinoblastoma protein. Subsequent DNA analysis in RB1 intron 17 revealed the presence of a full-length HPF1 retrogene insertion in opposite orientation. Functional assay shows that this insertion has a deleterious impact on retinoblastoma protein function. This is the first report of a full-length retrogene insertion involved in human Mendelian disease leading to a chimeric transcript and a non-functional chimeric protein. Some retrogene insertions may be missed by standard diagnostic genetic testing, so contribution of retrogene insertions to human disease may be underestimated. The increasing use of whole genome sequencing in diagnostic settings will help to get a more comprehensive view of retrogenes.

Tumour growth rate improves tumour assessment and first-line systemic treatment decision-making for immunotherapy in patients with liver metastatic uveal melanoma.

BACKGROUND: The RECIST-based response variably matches the clinical benefit of systemic therapies for liver metastatic uveal melanoma (LMUM). The aims were to determine whether the tumour growth rate (TGR) can help predict the survival in patients with LMUM and to provide information for the management of first-line systemic treatment. METHODS: This retrospective study included 147 (training: n = 110, validation: n = 37) patients with LMUM treated with first-line systemic treatment between 2010 and 2021. Two TGR-derived parameters were calculated, TGR0 and TGR3m. Multivariate Cox analyses identified independent predictors of progression-free survival (PFS) and overall survival (OS). RESULTS: TGR3m was a strong independent prognostic factor of PFS and OS (p < 0.001). The RECIST-based response was no longer significant in the OS analyses. Only immunotherapy regimens correlated with higher OS (HR = 0.2; 95% CI, 0.1-0.5; p < 0.001) in the low-TGR3m (≤50%/m) subgroup. These findings were confirmed in the validation cohort. TGR0, disease-free interval (DFI), and the sum of target lesions at baseline were predictive factors of low TGR3m. DISCUSSION: The use of TGR3m would improve tumour assessment by identifying patients who would benefit from first-line immunotherapy regimens despite PD. TGR0, DFI and the sum of target lesions were correlated with TGR3m, which can support first-line treatment decision-making for immunotherapy.

Highly Sensitive Detection Method of Retinoblastoma Genetic Predisposition and Biomarkers.

Retinoblastoma is a malignant tumor of the infant retina. Nearly half of patients are predisposed to retinoblastoma by a germline RB1 pathogenic variant. Nonhereditary retinoblastoma is mainly caused by inactivation of both RB1 alleles at a somatic level. Several polymorphisms have been reported as biomarkers of retinoblastoma risk, aggressiveness, or invasion. The most informative genetic testing is obtained from tumor DNA. Historically, access to tumor DNA has been warranted by the frequent indication of enucleation, which has decreased because of advances in conservative approaches. Recent studies showed that tumor cell-free DNA can be analyzed in aqueous humor from retinoblastoma patients. This report describes a next-generation sequencing method relying on unique molecular identifiers for a highly sensitive detection of retinoblastoma genetic predisposition and biomarkers in a single analysis. It is the first use of unique molecular identifiers for retinoblastoma genetics. This gene panel enables the detection of RB1 point variants, large genome rearrangements, and loss of heterozygosity. It is adapted for genomic DNA extracted from blood or tumor DNA extracted from tumor fragment, aqueous humor, or plasma. The access to tumor cell-free DNA improves the diagnosis of genetic predisposition in case of conservative ocular therapy and provides access to biomarkers guiding the treatment strategy. The analysis of a gene panel is cost-effective and can be easily implemented in diagnostic laboratories.

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. In this position paper of the European Retinoblastoma Group (EURbG), we give an overview of the progressive shift in the indications for SE over the past decades and propose guidelines to assist decision-making with respect to when SE becomes imperative or recommended, with corresponding absolute and relative SE indications. Further studies and validation of biologic markers correlated with the risk of metastasis are expected to set more precisely the frontiers of conservative management and thus consensual criteria for SE in the future.

Selective Ophthalmic Artery Chemotherapy with Melphalan in the Management of Unilateral Retinoblastoma: A Prospective Study.

PURPOSE: To determine prospectively the efficacy and to assess potential side effects of melphalan selective ophthalmic artery chemotherapy (SOAC) as first-line treatment for unilateral retinoblastoma. DESIGN: Phase 2 nonrandomized, prospective study. PARTICIPANTS: Patients with unilateral retinoblastoma group B, C, or D of the International Classification for Intraocular Retinoblastoma (IRC). Group D eyes with massive vitreous seeding were not eligible. METHODS: Melphalan SOAC associated with diode laser thermotherapy, cryotherapy, or both at 4-week intervals (3-6 cycles). For persistent vitreous seeding, intravitreal melphalan chemotherapy also was used. MAIN OUTCOME MEASURES: The primary outcome was globe preservation rate. Secondary outcomes were tumor relapse rate, occurrence of ocular or systemic adverse events, and measurement of the dose area product (DAP). RESULTS: Between 2012 and 2017, 39 patients (39 eyes) with unilateral retinoblastoma were included prospectively. Three included patients did not receive SOAC (2 catheterization failures and 1 case of viral syndrome) and were considered failures. At diagnosis, IRC groups for the 36 treated patients were: B, n = 4 (11%); C, n = 13 (36%); and D, n = 19 (53%); median age was 21.5 months (range, 3.2-61.6 months). Median number of SOAC cycles was 3.9 (range, 1-6 cycles), and median melphalan dose was 4.9 mg/procedure. The median DAP was 1.24 Gy.cm2/procedure. Median follow-up was 63 months (range, 34-93 months). SOAC was associated with local treatments for 31 patients (86%): diode laser thermotherapy for all of them and cryotherapy or intravitreal chemotherapy for 10 (32%) and 9 patients (25%), respectively. SOAC treatment was interrupted in 5 patients because of severe ophthalmic (ptosis, n = 2; retinal ischemia, n = 2) or systemic (hypotension, n = 1) adverse events. At the cutoff date analysis, all patients were alive without metastasis. The 18-month eye preservation rate was 80% (range, 68.6%-94.6%). After a follow-up of at least 30 months, the ocular preservation rate was 69% (n = 24 preservations). CONCLUSIONS: This first prospective trial demonstrated that SOAC with melphalan alone as first-line treatment for retinoblastoma is efficient and well tolerated with no metastatic events, although ocular ischemic complications were observed.

Prospective phase II study of children affected by bilateral intraocular retinoblastoma with macular involvement of both eyes or in the only preserved eye. Macular tumor control, eye preservation rate, and visual outcome.

BACKGROUND: Conservative treatments of intraocular retinoblastoma often consist of chemotherapy and focal treatments. The protocols vary and currently may combine two or three drugs, with different number of cycles, associated to the ocular treatments. In case of macular/paramacular involvement, tumor location and retinal scars induced by focal treatments often have a major negative impact on final visual outcome. METHODS: This study aimed to include children affected by bilateral intraocular macular/paramacular retinoblastoma in a prospective phase II study. The protocol consisted of six cycles of a three-drug combination (vincristine, etoposide, carboplatin), and the addition of macula-sparing transpupillary thermotherapy (TTT) to the third cycle. The primary endpoint was the local control rate without external beam radiotherapy (EBR) and/or enucleation. RESULTS: Nineteen patients (26 eyes) were included from July 2004 to November 2009. Thirteen eyes belonged to group V of the Reese-Ellsworth classification and 10 to group D of the International Intraocular Retinoblastoma Classification. Macular/paramacular tumors were treated with chemotherapy alone in nine eyes, and with chemotherapy associated with macula-sparing TTT in 17 eyes. Four eyes experienced macular relapse. At a median follow up of 77 months, 23 eyes (88.5%) were saved without EBR, two were enucleated and one received EBR. The median visual acuity of the 24 saved eyes was 20/50. No severe adverse effect was observed. CONCLUSION: Six cycles of a three-drug combination associated with macula-sparing TTT achieved good tumor control, improved eye preservation rates without EBR, and decreased macular damage, often providing satisfactory visual results with long-term follow up.

Association Between Genotype and Phenotype in Consecutive Unrelated Individuals With Retinoblastoma.

Importance: Retinoblastoma (RB) is the most common pediatric intraocular neoplasm. RB is a complex model in which atypical pathogenic variants, modifier genes, imprinting, and mosaicism are known to be associated with the phenotype. In-depth understanding of RB therefore requires large genotype-phenotype studies. Objective: To assess the association between genotype and phenotype in patients with RB. Design, Setting, and Participants: This single-center, retrospective cohort study, conducted from January 1, 2000, to September 30, 2017, enrolled 1404 consecutive ascertained patients with RB who consulted an oncogeneticist. All patients had their genotype and phenotype recorded. Statistical analysis was performed from July 1, 2018, to December 31, 2018. Main Outcomes and Measures: RB1 germline and somatic pathogenic variant types, family history, and disease presentation characteristics (ie, age at diagnosis, sex, laterality, and International Intraocular Retinoblastoma Classification group). Results: Among 1404 patients with RB (734 [52.3%] female; mean [SD] age, 20.2 [21.2] months), 866 cases (61.7%) were unilateral and 538 cases (38.3%) were bilateral. Loss of function variants were found throughout the coding sequence, with 259 of 272 (95.2%) somatic pathogenic variants and 537 of 606 (88.6%) germline pathogenic variants (difference, 6.6%; 95% CI, 4.0%-9.2%; P < .001) after excluding tumor-specific pathogenic variants (ie, promoter methylation and loss of heterozygosity); a novel low-penetrance region was identified in exon 24. Compared with germline pathogenic variants estimated to retain RB protein expression, germline pathogenic variants estimated to abrogate RB protein expression were associated with an earlier mean (SD) age at diagnosis (12.3 [11.3] months among 457 patients vs 16.3 [13.2] months among 55 patients; difference, 4 months; 95% CI, 1.9-6.1 months; P = .01), more frequent bilateral involvement (84.2% among 452 patients vs 65.2% among 45 patients; difference, 18.9%; 95% CI, 14.5%-23.3%; P < .001), and more advanced International Intraocular Retinoblastoma Classification group (85.3% among 339 patients vs 73.9% among 34 patients; difference: 11.4%; 95% CI, 6.5%-16.3%; P = .047). Among the 765 nongermline carriers of an RB1 pathogenic variant, most were female (419 females [54.8%] vs 346 males [45.2%]; P = .008), and males were more likely to have bilateral RB (23 males [71.4%] vs 12 females [34.3%]; P = .01). Conclusions and Relevance: These results suggest that RB risk is associated with the germline pathogenic variant and with maintenance of RB protein and that there is a sex-linked mechanism for nongermline carriers.

Management of advanced uni- or bilateral retinoblastoma with macroscopic optic nerve invasion.

BACKGROUND: Retinoblastoma with macroscopic optic nerve (ON) invasion depicted by imaging at diagnosis remains a major problem and carries a poor prognosis. We sought to describe the treatment and outcome of these high-risk patients. METHODS: Retrospective mono-institutional clinical, radiological, and histological review of patients with uni- or bilateral retinoblastoma with obvious ON invasion, defined by radiological optic nerve enlargement (RONE) depicted by computed tomography scan or magnetic resonance imaging (MRI), was performed. RESULTS: Between 1997 and 2014, among the 936 patients with retinoblastoma treated at Institut Curie, 11 had detectable RONE. Retinoblastoma was unilateral in 10 and bilateral in one. Median age at diagnosis was 28 months (range, 11-96). ON enlargement extended to the orbital portion in three patients, to the optic canal in five, to the prechiasmatic portion in two, and to the optic chiasm in one. Nine patients received neoadjuvant chemotherapy and partial response was obtained in all. Enucleation was performed in 10/11 patients-by an anterior approach in three and by anterior and subfrontal approaches in seven. Three patients had a positive ON resection margin (2/3 after primary enucleation). All enucleated patients received adjuvant treatment (conventional chemotherapy: 10, high-dose chemotherapy: seven, radiotherapy: five). Leptomeningeal progression occurred in four patients. Seven are in first complete remission (median follow up: 8 years [3.5-19.4]). CONCLUSION: Neoadjuvant chemotherapy and microscopic complete resection have a pivotal role in the management of retinoblastoma with RONE. MRI is recommended for initial and pre-operative accurate staging. Surgery should be performed by neurosurgeons in case of posterior nerve invasion. Radiotherapy is required in case of incomplete resection.

Diffuse Iris Melanoma: Conservative Treatment with Proton Beam Therapy after Limbal Stem Cell Preservation or Enucleation?

OBJECTIVES: Iris melanomas represent 2-3% of uveal melanomas; the diffuse variant accounts for approximately 10% of all iris melanomas. Different treatment modalities for diffuse iris melanomas (DIM) have been proposed depending on the local status as well as the age and general condition of the patient. METHODS: This study is a single-centre retrospective case series describing the diagnosis, treatments and outcomes of DIM. Treatment consisted of enucleation or proton beam therapy (PT) of the whole anterior segment. Patients who were treated with PT benefitted from limbal stem cell preservation before irradiation. RESULTS: Between 1996 and 2016, a total of 14 patients with DIM presented to our institution and were included in the database. The global survival was 86%. The median follow-up was 4.6 years (range 4 months to 15 years). Only 1 patient (7%) developed metastatic disease of the DIM (gastric location). No patient developed liver metastasis. Seven patients were treated by enucleation and 7 by PT after limbal stem cell preservation. After a conservative attempt, local tumour recurrence occurred in 2 patients at 2 years, requiring enucleation. The cornea was clear after irradiation in all patients. Cataract (n = 6) and glaucoma (n = 4) were the main complications after irradiation. CONCLUSIONS: DIM is a very rare tumour. The global survival is excellent. Conservative treatment with PT is an efficient alternative to enucleation and allows good local tumour control. Cataract and glaucoma are the main radiation-related complications, but the corneal status was excellent due to the stem cell harvest prior to radiotherapy.

Osteosarcoma without prior retinoblastoma related to RB1 low-penetrance germline pathogenic variants: A novel type of RB1-related hereditary predisposition syndrome?

BACKGROUND: Retinoblastoma (Rb) is a rare intraocular malignant tumor in children with high overall survival. Predisposition to Rb is linked to RB1 germline mutations with high penetrance, but rare RB1 low-penetrance variants are also known. Rb survivors are at risk of second primary malignancies (SPMs), mostly osteosarcoma and soft-tissue sarcoma. Nevertheless, the risk of primary osteosarcoma developing without prior Rb has not been reported in RB1 germline mutation carriers. METHODS: We report a patient in whom osteosarcoma developed at age 17 as a first primary malignancy within a family context of sarcoma. RESULTS: Unexpectedly, genetic testing identified a low-penetrance germline mutation in RB1 [NM_000321.2: c.45_76dup; p.(Pro26Leufs*50)]. In eight additional similar cases from published and unpublished reports of families, first primary osteosarcomas and sarcomas mostly developed in RB1 low-penetrance mutation carriers without prior Rb. CONCLUSION: We propose that first primary sarcoma and osteosarcoma could be a novel clinical presentation of a RB1-related hereditary predisposition syndrome linked to RB1 low-penetrance germline mutations. In these families, careful screening of primary non-Rb cancer and SPMs is required by maintaining enhanced clinical vigilance. Implementing lifelong periodic whole-body MRI screening might be a complementary strategy for unaffected carrier relatives in these families.

Comparative Cytogenetic Abnormalities in Paired Choroidal Melanoma Samples Obtained Before and After Proton Beam Irradiation by Transscleral Fine-Needle Aspiration Biopsy and Endoresection.

This study compared the cytogenetic profiles of choroidal melanoma samples retrieved before and after proton beam irradiation. Twenty-four consecutive patients who underwent both fine-needle aspiration biopsy (FNAB) during tantalum clip positioning, and endoresection within three months of irradiation, were retrospectively included. Chromosome alterations were explored by array comparative genomic hybridization. Age at diagnosis was 50 ± 14 years, tumor thickness was 8.6 ± 1.7 mm and tumor diameter was 12.4 ± 2.3 mm. Six FNAB samples were non-contributive (25%), versus one endoresection sample (4%) (p = 0.049). Among 17 cases with paired contributive samples, the profiles of chromosomes 3 and 8 were identical in all cases, except one with partial chromosome 3 loss on the FNAB sample only. Three cases presented additional discordant aberrations on chromosomes other than 3 or 8q. Overall, we identified monosomy 3 in two cases, 8q gain in six cases, and both alterations in three cases. All cases presented GNAQ or GNA11 mutations assessed by a custom next-generation sequencing panel. Among the six cases with non-contributive initial FNAB, three cases presented abnormal 3 or 8q chromosomes detected on the endoresection material. These results demonstrate the higher rentability of endoresection material for cytogenetic analysis compared to FNAB, and provide clinical evidence of tumor heterogeneity in choroidal melanoma.

TREATMENT OF EXUDATIVE CIRCUMSCRIBED CHOROIDAL HEMANGIOMA: Efficacy of Fractionated Proton Therapy (20 Gray Relative Biological Effectiveness in 8 Fractions).

PURPOSE: To evaluate treatment of circumscribed choroidal hemangioma by hyperfractionated proton beam therapy protocol (20 gray relative biological effectiveness in 8 fractions) on tumor control, attachment of retina and visual function. METHODS: Retrospective review of patients treated between January 2010 and April 2015 with at least 6 months of follow-up. RESULTS: Forty-three patients with exudative and symptomatic circumscribed choroidal hemangioma were included. Before treatment, 41 (95%) presented an exudative retinal detachment, median visual acuity was 20/63 and median tumor thickness was 3.3 mm. Mean follow-up was 26 months (7-62). At last follow-up, all patients presented regression of ultrasound tumor thickness and 23/43 (53.5%) a totally flat scar. The mean time to achieve a flat scar was 20 months. Retina was reattached in all patients except one with 9 months of follow-up. Visual acuity was improved or stabilized in 37 patients (86%) and final median visual acuity was 20/25. No patient presented radiation maculopathy or papillopathy. CONCLUSION: Proton beam therapy with a dose of 20 gray relative biological effectiveness delivered in 8 fractions provides excellent anatomical and functional results and are comparable with those obtained with the same dose delivered in 4 fractions. Longer follow-up is required to determine the long-term radiation sequelae.

Iterative Variance Stabilizing Transformation Denoising of Spectral Domain Optical Coherence Tomography Images Applied to Retinoblastoma.

BACKGROUND: Due to the presence of speckle Poisson noise, the interpretation of spectral domain-optical coherence tomography (SD-OCT) images frequently requires the use of data averaging to improve the signal-to-noise ratio. This implies long acquisition times and requires patient sedation in some cases. Iterative variance stabilizing transformation (VST) is a possible approach by which to remove speckle Poisson noise on single images. METHODS: We used SD-OCT images of human and murine (LH Beta-Tag mouse model) retinas with and without retinoblastoma acquired with 2 different imaging devices (Bioptigen and Micron IV). These images were processed using a denoising workflow implemented in Matlab. RESULTS: We demonstrated the presence of speckle Poisson noise, which can be removed by a VST-based approach. This approach is robust as it works in all used imaging devices and in both human and mouse retinas, independently of the tumor status. The implemented algorithm is freely available from the authors on demand. CONCLUSIONS: On a single denoised image, the proposed method provides results similar to those expected from the SD-OCT averaging. Because of the friendly user interface, it can be easily used by clinicians and researchers in ophthalmology.

Retinal cavernous haemangioma treated by proton beam therapy.

As one of intraocular tumours, retinal cavernous haemangioma is a benign vascular lesion that is mostly unilateral. Very few cases about cavernous haemangioma treatment are reported, and there is currently no consensus on the most effective treatment. This clinical case reports on a 40-year-old male, presenting a peripheral retinal cavernous haemangioma, complicated with a repetitive vitreous haemorrhage causing bad vision. Several therapeutic methods were unsuccessfully attempted to stop haemorrhagic recurrences. Thanks to proton beam irradiation, a good collapse of aneurismal dilatations was obtained, with no recurrence of bleeding. This case study confirms that proton beam therapy is a good alternative in treating cavernous haemangiomas, leading to a total tumour regression without complications.

Prospective analysis of serious cardiorespiratory events in children during ophthalmic artery chemotherapy for retinoblastoma under a deep standardized anesthesia.

BACKGROUND AND OBJECTIVE: Serious adverse cardiorespiratory events complicate super selective ophthalmic artery chemotherapy for retinoblastoma in anesthetized children. Their mechanism remains unclear but may be attributed to an autonomic nervous reflex induced by the catheter close to the ophthalmic artery. Inadequate depth of anesthesia during catheter stimulation might be an aggravating factor. Thus, we tested whether deep general anesthesia reduced the incidence of serious cardiorespiratory events. METHODS: Children were prospectively included in this observational study. Standardized deep general anesthesia with sevoflurane, rocuronium, and sufentanil was administered. Sevoflurane MAC was kept between 1.5 and 1.7 and additional sufentanil administered. Serious cardiorespiratory event criteria were predefined and included arterial hypotension, bradycardia, and severe decrease in lung compliance. They were recorded and the factors influencing their occurrence were investigated. RESULTS: One hundred fifteen procedures were performed on 32 children. The median MAC of sevoflurane was 1.5 and median BIS value was 44. Serious cardiorespiratory events occurred in 20% of procedures and were mainly severe decrease in lung compliance (83% of events). All of them required active treatment. One procedure was aborted due to cardiorespiratory compromise and required an epinephrine infusion. All severe decreases in lung compliance occurred within 2 minutes after catheter insertion in the ophthalmic artery. No recorded demographic and endovascular characteristics were associated with serious cardiorespiratory events. CONCLUSION: Serious cardiorespiratory events occur commonly during super selective ophthalmic artery chemotherapy. Standardized deep anesthesia with analgesia did not appear to be protective. No predictive factors were identified, but these events systematically arose within 2 minutes after ophthalmic artery catheter insertion. Anesthetists and neuroradiologists should be prepared to manage these serious complications and parents should be informed of the risks.

Eye Salvage with Combination of Intravitreal and Intracameral Melphalan Injection for Recurrent Retinoblastoma with Anterior Chamber Involvement: Report of a Case.

AIMS: Herein we report successful eye salvage following combined intravitreal and intracameral administration of melphalan for anterior chamber recurrence of retinoblastoma. METHODS: A 12-month-old boy was referred with a sporadic bilateral retinoblastoma staged as group D and V in the right eye and group E and V in the left eye. Treatment initially involved 6 cycles of 3 drugs followed by focal treatments. The left eye was enucleated. Three months after the end of systemic chemotherapy, multiple recurrent lesions were noted in the ciliary body and the anterior chamber. A series of intravitreal (IVT) and intracameral (IC) injections of melphalan combined with a 7th cycle of systemic chemotherapy was performed. The therapeutic schedule alternated: week A an IVT of melphalan (30 µg/0.1 mL) for a total of 4 versus week B IC injections of melphalan (15 µg/0.05 mL) 4 IC in total. Each injection was preceded by an anterior chamber. Cryotherapy to the injection punctures was systematically performed. RESULTS: Rapidly, iris and ciliary body nodules regressed completely based on clinical and ultrasound biomicroscopic examinations. After 3 years of follow-up, the patient has shown no evidence of recurrence. CONCLUSION: In our patient, combined IVT and IC administration of melphalan proved highly efficacious in eradicating the ciliary body and anterior chamber disease and salvage of his one remaining functional eye.

Optical Coherence Tomography Angiography of Macular Features After Proton Beam Radiotherapy for Small Choroidal Melanoma.

PURPOSE: To describe the macular features of patients treated with proton beam therapy for choroidal melanoma (CM), using optical coherence tomography angiography (OCTA). DESIGN: Retrospective case-control study. METHODS: This study included patients treated with proton beam radiotherapy (PBR) for a small CM. Only patients who had received 100% of the dose of 60 Gy external beam radiation to the macular area were included in the analysis. All the patients had undergone a full ophthalmologic examination, including visual acuity, optical coherence tomography B-scan, and OCTA. Qualitative and quantitative vascular features of the retinal plexus and the choriocapillaris were analyzed on OCTA and compared with those in healthy subjects matched on age and sex. RESULTS: Thirty-seven patients had undergone an OCTA after PBR for a small CM. Seventeen patients (9 men and 8 women) were included. The mean age of the patients was 56.6 years (range, 28-86). At presentation, the mean tumor thickness was 3.39 mm (range, 1.3-7.0 mm). The mean follow-up duration was 35.8 months (range, 11-72 months). Thirteen patients (76.5%) had a clinical radiation maculopathy; 8 patients (47.1%) had macular cysts on OCT-B scan. All patients (100%) had abnormalities on OCTA. Some "signal void" spots were detected at the level of the choriocapillaris in 15 patients (88.2%). The mean vascular density (regarding the full retina) was significantly lower in the patients treated with PBR than in healthy subjects (P < .0001). CONCLUSION: Patients treated with PBR for CM (with 100% of the dose given to the macula) present major changes at both plexuses but also a vascular rarefaction of the choriocapillaris.

Retinoblastoma / Rétinoblastome

Retinoblastoma. Retinoblastoma is the most frequent malignant intraocular tumour of childhood. It is a rare disease occurring in very young children. It is a genetic disease due to the mutation of the RB1gene. Today survival is excellent (98%) in developed countries, however lower survival rates are observed in the developing world where children still die of the disease. Visual prognosis depends on the possibility to realize a conservative treatment as well as the size and location of the tumors. The two main presenting signs of retinoblastoma are leukocoria and strabismus. Every suspicion of leukocoria requires prompt fundus examination.

Rétinoblastome. Le rétinoblastome est la tumeur maligne primitive intraoculaire de l'enfant la plus fréquente. C'est une maladie rare qui atteint principalement de très jeunes enfants. Il s'agit d'une maladie génétique liée à une mutation du gène RB1. Son pronostic vital est excellent (98 %) dans les pays développés, il reste par contre menacé dans le pays émergents où les décès sont encore fréquents. Le pronostic visuel de ces enfants dépend de la possibilité ou pas de conservation oculaire mais aussi de la taille et la position des tumeurs dans l'oeil. Les deux principaux signes d'appel du rétinoblastome sont la leucocorie et le strabisme. Toute suspicion de leucocorie, nécessite la réalisation d'un fond d'oeil en urgence.