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PURPOSE: Aplasia of lacrimal and salivary glands (ALSG) is a syndromic disorder characterized by aplasia of lacrimal and salivary systems. Reported ophthalmic manifestations of ALSG include aplasia of lacrimal glands, punctal agenesis, lacrimal sac mucocele, and membranous congenital nasolacrimal duct obstruction (CNLDO). Bony CNLDO, a rare clinical entity, has not been associated with any syndromic disorder. This study investigated the relationship between genetic mutations and bony CNLDO in 3 Chinese families with ALSG. DESIGN: Single-center observational case study. PARTICIPANTS: Three Chinese families with bony CNLDO, including 7 affected and 9 healthy family members. METHODS: Slit-lamp ophthalmic examination, comprehensive physical examination, orbital computed tomography (CT) imaging, cervicofacial magnetic resonance imaging, audiometry, and whole exome sequencing on periphery blood were performed. Variants were cross-referenced with 1000 control genomes and various population databases. Pathologic variants were identified using bioinformatic tools. MAIN OUTCOME MEASURES: Clinical examination, diagnostic imaging, whole exome sequencing, and bioinformatic analysis findings. RESULTS: Affected patients showed decreased tear production on the Schimer I test and reduced tear breakup time. Bony CNLDO was observed on CT, showing unilateral or bilateral bony termination at the middle or terminal segment of the nasolacrimal canal. Magnetic resonance imaging showed aplasia or absence of lacrimal, parotid, and submandibular glands. Physical examination revealed normal ears, digits, and facial morphology. Audiometry and dental assessment were conducted on the pediatric patients and yielded normal results. The clinical characteristics of patients aligned with a diagnosis of ALSG. Genomic analysis revealed 3 novel heterozygous missense mutations of the Fgf10 gene: c.316TâC, c.327CâG, and c.332TâG. The inheritance pattern was autosomal dominant with variable penetrance. These variants were not observed in 1000 control genomes and population databases. These variant positions also were shown to be highly conserved across various animal species. Mutated genes and proteins were predicted as deleterious with most computational models, with a few suggesting they may be benign. CONCLUSIONS: Bony CNLDO was identified as a novel phenotype of ALSG implicated by missense mutations of highly conserved residues in the Fgf10 gene. These cases broadened our knowledge of Fgf10-related phenotypes and prompted clinicians to consider syndromic associations in patients with bony CNLDO. FINANCIAL DISCLOSURE(S): The author(s) have no proprietary or commercial interest in any materials discussed in this article.
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PURPOSE: Attempted eye salvage for unilateral (cT2b/group D) retinoblastoma may risk tumor spread compared with primary enucleation. Identification of clinical features predictive of low histopathologic risk support safe trial salvage. DESIGN: Retrospective, noncomparative single-institutional observational case series. PARTICIPANTS: Children with unilateral cT2b/group D retinoblastoma managed with primary enucleation at the Hospital for Sick Children, Toronto, Canada, January 2008 through February 2018. METHODS: Data included clinical features (intraocular pressure, optic nerve obscuration, macular involvement, tumor seeding, and serous retinal detachment [RD] >1 quadrant), timing to enucleation, histopathologic features, and follow-up. MAIN OUTCOME MEASURES: Primary outcome was low-risk (LR; pT1/pT2) versus high-risk (HR; pT3/pT4) histopathologic features with clinicopathologic correlations. Secondary outcomes were positive predictive (probability that certain clinical features would predict LR histopathologic features) and negative predictive values (probability that absence of these clinical features would predict HR histopathologic features). RESULTS: Thirty-eight eyes were eligible and showed vitreous seeding and normal intraocular pressure. The median diagnosis to enucleation interval was 4 days (range, 0-14 days). Histopathologic analysis diagnosed 4 (10.5%) HR and 34 (89.5%) LR eyes. High-risk eyes demonstrated massive choroidal invasion (4/38) or trans-scleral, extraocular, and postlaminar optic nerve invasion (1/38). Clinical findings included macular involvement (31/38), complete optic nerve obscuration (27/38), and RD (28/38). The proportion of eyes with HR histopathologic features was 13% (4/31; 95% confidence interval [CI], 1%-25%) with macular involvement, 15% (4/27; 95% CI, 1%-28%) with complete optic nerve obscuration, and 14% (4/28; 95% CI, 1%-27%) with RD. The predictability of LR histopathologic features was 100% with macular sparing (7/7; 95% CI, 47%-100%), optic nerve visibility (10/10; 95% CI, 63%-100%), and less than 1 quadrant of RD (10/10; 95% CI, 63%-100%). In 1 child lacking all 3 clinical LR predictive features with HR histopathologic features (pT3a), metastases developed and the patient died; other children are alive and well (mean follow-up, 65 months). CONCLUSIONS: Presence of macular sparing, optic nerve visibility, less than 1 quadrant of RD, or a combination thereof predicted LR histopathologic features at primary enucleation, suggesting safe trial eye salvage. No clinical sign predicted HR histopathologic features.
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Neoplasias de la Retina/patología , Retinoblastoma/patología , Preescolar , Coroides/patología , Enucleación del Ojo , Femenino , Humanos , Lactante , Presión Intraocular/fisiología , Imagen por Resonancia Magnética , Masculino , Invasividad Neoplásica , Metástasis de la Neoplasia , Siembra Neoplásica , Estadificación de Neoplasias , Nervio Óptico/patología , Desprendimiento de Retina/diagnóstico , Neoplasias de la Retina/diagnóstico por imagen , Neoplasias de la Retina/cirugía , Retinoblastoma/diagnóstico por imagen , Retinoblastoma/cirugía , Estudios Retrospectivos , Factores de Riesgo , Tomografía de Coherencia ÓpticaRESUMEN
Purpose: The purpose of this study was to investigate the effect of adjuvant chemotherapy on outcomes of children with massive choroidal invasion (MCI). Methods: In this study, we reviewed the 5-year relapse-free survival (RFS) and overall survival (OS) of children diagnosed with MCI, managed with or without adjuvant chemotherapy. Excluded were children with additional other high-risk features (post-laminar optic nerve invasion, scleral invasion, or overt extraocular disease). Results: Of 3566 children diagnosed with retinoblastoma, 2023 had enucleation, and 60 eyes of 60 children had pathology showing MCI without concomitant high-risk features. Enucleation was primary (22, 37%), or secondary (38, 63%) after failed eye salvage. Adjuvant systemic chemotherapy (median = 4, range = 1-8 cycles) was given to 48 of 60 (80%) children; 12 of 60 (20%) children had no adjuvant therapy. Five-year RFS was 88.5% (95% confidence interval [CI] = 79.7%-97.3%) and 5-year OS was 90.1% (95% CI = 81.7%-98.5%). Pre-enucleation chemotherapy did not affect RFS (89.7% vs. 75.0%; P = 0.657). Adjuvant chemotherapy improved RFS (97.2% vs. 55.6%; P < 0.001) and OS (97.2% vs. 66.7%; P < 0.001). In subgroup analysis, adjuvant chemotherapy improved RFS for both primarily enucleated (5-year RFS 100% vs. 50.0%; P = 0.002) and secondarily enucleated children (5-year RFS 95.8% vs. 60.0%; P = 0.005). The number of children treated with adjuvant chemotherapy to prevent one post-enucleation systemic relapse or death is three. Conclusions: Adjuvant chemotherapy significantly decreased the risk of tumor relapse and death for children with pathological MCI. For every three children treated with adjuvant chemotherapy, one systemic relapse or death could be prevented.
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Neoplasias de la Retina , Retinoblastoma , Niño , Humanos , Quimioterapia Adyuvante , Coroides , Terapia Combinada , Neoplasias de la Retina/tratamiento farmacológico , Retinoblastoma/tratamiento farmacológicoRESUMEN
OBJECTIVE: Aromatase inhibitors (AIs) are a class of medications used for adjuvant treatment of breast cancer. Recent case reports suggest that AIs may be associated with various ocular adverse events (AEs). This study evaluates the risk of ocular AEs in patients who take AIs. METHOD: Disproportionality analysis was performed using data from the U.S. Food and Drug Administration's Adverse Events Reporting System database from 2004 to 2022. All cases of vitreomacular traction, macular edema, retinal deposits, retinal artery occlusion, macular hole, retinal hemorrhage, uveitis, retinal tear, retinal detachment, dry eye disease, blepharitis, and optic neuropathy were searched for the 3 AIs anastrozole, letrozole, and exemestane. A search also was performed on trastuzumab as a control. Reported odds ratios (RORs) and corresponding 95% CIs were computed. RESULTS: We identified 322 ocular AEs of interest for the 3 AIs and 55 for trastuzumab. Anastrozole had the most AEs (nâ¯=â¯163) and was found to have strong associations with vitreomacular traction (RORâ¯=â¯665; 95% CI, 352-1255), macular edema (RORâ¯=â¯37; 95% CI, 25-54), retinal deposits (RORâ¯=â¯11; 95% CI, 2-77), and uveitis (RORâ¯=â¯6; 95% CI, 4-9). Letrozole had strong associations with retinal deposits (RORâ¯=â¯8, 95% CI, 1-57) and retinal artery occlusion (RORâ¯=â¯6; 95% CI, 3-11). Exemestane had a strong association with macular holes (RORâ¯=â¯10; 95% CI, 3-30). CONCLUSION: Disproportionality analysis revealed an increased risk of ocular AEs with each of the AIs. This study calls for clinicians, especially oncologists and ophthalmologists, to be vigilant in patients who are on AI therapy, allowing them to provide prompt interventions to mitigate further ocular morbidities.
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BACKGROUND/AIM: Laser photocoagulation is less invasive than chemotherapy (systemic, intra-arterial or periocular) and brachytherapy. We studied the safety and efficacy of laser as primary monotherapy for discrete retinoblastoma with well-defined borders and attached retina. METHODS: A single-institution retrospective non-comparative review (2004-2018) of discrete retinoblastoma tumours managed with primary laser (532 or 810 nm wavelength, 0.5-1 s duration and power titrated until desired tumour whitening). Efficacy was evaluated by tumour long-term stability avoiding non-laser therapies. Safety was evaluated by frequency of laser-related complications and uncontrollable tumour progression. RESULTS: Eligible were 112 tumours in 55 eyes of 44 patients. Laser monotherapy (median 2 sessions) achieved initial remission in 95/112 (85%) tumour. Initial encircling only laser photocoagulation was associated with tumour progression (9/11, one tumour had vitreous seeding) compared with direct or combined photocoagulation techniques (0/94 and 0/7 tumours, respectively, p<0.001). Direct laser had no vitreous seeding, haemorrhage or injury to vital structures. Tumour recurrences developed in 52/112 (46%) tumour but repeat laser achieved long-term stability, except five tumour recurrences that required invasive therapy. Receiver operating characteristic analysis identified threshold largest basal diameter of 3 disc diameters (DD) for successful laser monotherapy, where 92/106 (87%) of tumours ≤3 DD and 0/6>3 DD achieved long-term stability with laser monotherapy (p<0.001). Overall, 35/55 (64%) eyes and 24/44 (55%) patients achieved long-term stability with laser monotherapy. No eye was enucleated for uncontrollable tumour progression. CONCLUSIONS: Discrete retinoblastoma ≤3 DD can be effectively and safely managed with laser monotherapy, sparing a significant proportion of patients/eyes from more invasive therapies.
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Terapia por Láser , Neoplasias de la Retina , Retinoblastoma , Humanos , Lactante , Rayos Láser , Recurrencia Local de Neoplasia , Neoplasias de la Retina/radioterapia , Neoplasias de la Retina/cirugía , Retinoblastoma/radioterapia , Retinoblastoma/cirugía , Estudios RetrospectivosRESUMEN
The authors present a case of bilateral painless progressive proptosis. A diagnosis of ocular juvenile xanthogranuloma was made based on clinical manifestations, histopathology, and immunohistochemistrical staining. Genetic testing discovered the BRAF V600E mutation. This patient did not respond to standard chemotherapy; however, he demonstrated regression after anti-BRAF targeted therapy. [J Pediatr Ophthalmol Strabismus. 2021;58(4):e19-e21.].
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Proteínas Proto-Oncogénicas B-raf , Xantogranuloma Juvenil , Niño , Ojo , Humanos , Masculino , Mutación , Proteínas Proto-Oncogénicas B-raf/genética , Xantogranuloma Juvenil/diagnóstico , Xantogranuloma Juvenil/genéticaRESUMEN
Intraocular surgery is tabooed in retinoblastoma management, due to the concern of lethal extraocular spread. We reviewed the outcomes of consecutive children with intraocular retinoblastoma diagnosed at 29 Chinese centers between 2012-2014. We compared the outcomes of three categories of treatment: eye salvage including tylectomy (Group I), eye salvage without tylectomy (Group II), and primary enucleation (Group III). A total of 960 patients (1243 eyes) were diagnosed: 256 in Group I, 370 in Group II, and 293 in Group III; 41 patients abandoned treatment upfront. The estimated 5-year overall survivals (OS) were, for Group I, 94%, for Group II 89%, and for Group III 95%. The estimated 5-year disease-specific survivals (DSS) were, for Group I, 96%, for Group II 90%, and for Group III 95%. Patients in Group I had a significantly higher 5-year DSS than patients in Group II (p = 0.003) and not significantly different than patients in Group III (p = 0.367). Overall survival was not compromised by the inclusion of tylectomy in eye salvage therapy compared to eye salvage without tylectomy or primary enucleation. Disease-specific survival was better when tylectomy was included in eye salvage treatments. Tylectomy as part of multimodal treatment may contribute to the care of retinoblastoma patients with chemotherapy-resistant tumor, eyes with concomitant ocular complications, or at the risk of treatment abandonment.
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We report the clinical features, treatments, and outcomes of 9 infants with glaucoma secondary to congenital fibrovascular pupillary membrane. The clinical features included unilateral low vision, high intraocular pressure (IOP), enlarged and cloudy cornea, loss of anterior chamber, and pupillary membrane. All patients underwent membranectomy, peripheral iridectomy, pupilloplasty, and goniosynechialysis as primary treatment. The membranes were posterior to the iris in all 9 eyes. In 5 eyes, the membrane covered the ciliary processes, and in 1 eye the membrane reached the posterior lens capsule. Following primary surgery, 3 patients developed membrane recurrence, 4 had refractory elevated IOP, and 2 developed lens opacities. All 4 eyes with poor postoperative IOP control had iris root insertion anterior to the scleral spur. Five patients received additional surgeries including membranectomy, pupilloplasty, goniosynechialysis, cyclocryotherapy, ciliary photocoagulation, Amhed valve implantation, and lensectomy. One patient had refractory elevated IOP at last follow-up. IOP in the other 8 eyes was well controlled. None of the affected eyes was able to fix and follow at last follow-up.
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Glaucoma , Cuerpo Ciliar , Glaucoma/etiología , Glaucoma/cirugía , Humanos , Lactante , Presión Intraocular , Iridectomía , Iris/cirugía , PupilaRESUMEN
PURPOSE: Primary enucleation is a well-established method to achieve cure for advanced intraocular retinoblastoma. Recent treatment advances have induced a trend toward trial eye salvage using chemotherapy or other modalities. We investigated how pre-enucleation/postenucleation systemic chemotherapy and the resulting delayed enucleation affect patient survival after failed trial eye salvage. DESIGN: Multicenter, retrospective cohort study. PARTICIPANTS: Children with Group D and E retinoblastoma primarily or secondarily enucleated at 29 Chinese treatment centers. METHODS: Data reviewed included clinical staging, time from diagnosis to enucleation, numbers of cycles of carboplatin, etoposide/teniposide and vincristine chemotherapy, disease-specific survival (DSS), histopathology, and follow-up. MAIN OUTCOME MEASURES: Primary outcome was DSS. Secondary outcome was histopathology of enucleated eyes. RESULTS: Primarily enucleated eyes had significantly shorter delay from diagnosis to enucleation than eyes treated with pre-enucleation chemotherapy (P < 0.001). Delay between diagnosis and enucleation >3.5 months (Group D) and >2 months (Group E) decreased survival (Group D: P = 0.018; Group E: P = 0.017). Compared with primarily enucleated children, children with 1 to 3 cycles of pre-enucleation chemotherapy for Group E eyes had no significant difference in survival (P = 0.74), but those who received ≥4 cycles had worse survival (P = 0.025). After pre-enucleation chemotherapy, more children with Group E (but not Group D) eyes had high-risk histopathology (pT3/pT4) (Group D: P = 0.076; Group E: P < 0.001) and worse survival than those primarily enucleated (P < 0.001). Postenucleation chemotherapy improved survival of children with high-risk histopathology (pT3/pT4) (P = 0.001) but did not change survival of children with low-risk histopathology (pT1/pT2) (P = 0.52). CONCLUSIONS: We observed that pre-enucleation chemotherapy offered no survival benefit and timely enucleation minimized risk of metastatic death. Postenucleation chemotherapy improved survival of children with high-risk histopathology but was not useful for those with low-risk histopathology. These findings facilitate informed discussion on the risks and benefits of delayed enucleation, the use of systemic chemotherapy for trial salvage of eyes with advanced intraocular retinoblastoma, and the specific children who benefit from postenucleation chemotherapy.