Unusual anterior and posterior segment features of coats disease.

PURPOSE: To report the clinical course and management of unusual anterior and posterior segment features of Coats disease and their relation to the age of the patients to increase the awareness towards these rare clinical features rarely described in the current literature. METHODS: A retrospective descriptive review of 45 eyes of 45 patients affected by Coats disease was conducted at the Retinoblastoma Referral Center and Ophthalmology Unit of the University of Siena in Italy analyzing data from 2000 to 2022. Medical records and images were revised to find some cases presenting unusual anterior and posterior segment features in patients affected by Coats disease.We identified therefore 4 unusual clinical conditions: retinal macrocysts, anterior chamber cholesterolosis, fovea-sparing Coats disease and secondary vasoproliferative tumor. RESULTS: Two patients presented with retinal macrocyst (2/45 = 4.4%), one with anterior chamber cholesterolosis (1/45 = 2.2%), two with fovea sparing Coats disease (2/45 = 4.4%) and one with vasoproliferative tumor associated (1/45 = 2.2%) for a total of six (6/45 = 13.3%) patients manifesting unusual anterior or posterior segment features in Coats disease. CONCLUSION: Unusual anterior and posterior segment features of Coats disease such as retinal macrocyst and anterior chamber cholesterolosis have been more frequently reported in younger children while fovea-sparing and vasoproliferative tumors have been more commonly described in older patients. Age is then a strong prognostic marker which allows to distinguish two different phenotypes of Coats disease: patients younger and older than 3 years old with more aggressive and milder phenotype respectively.

Corrigendum: Spondyloocular syndrome: A novel XYLT2 variant with description of the neonatal phenotype.

[This corrects the article DOI: 10.3389/fgene.2021.761264.].

Very late orbital recurrence of choroidal melanoma four decades post enucleation.

Orbital recurrence of malignant choroidal melanoma is quite uncommon, occurring in about 3% of patients undergoing enucleation for large tumors. Orbital recurrences after more than 10 years from enucleation are even rarer. In literature, only few reports described orbital recurrence that occurred between 10 and 40 years after primary diagnosis. Herein we report a very late choroidal melanoma recurrence, 40 years post enucleation, of a 52 year-old female who had undergone left enucleation at the age of 12. She presented to our clinic for consultation in 2017, complaining of difficulty to contain the prosthesis, as well as, presence of small pigmented palpable nodules inferiorly in her anophthalmic socket. The patient was not aware of the medical condition which had lead to the enucleation. We requested her medical reports and detailed history through her family. We realized after reviewing her charts 40 years back, that her enucleation was due to malignant choroidal melanoma (CMM). Full screening was performed. After magnetic resonance imaging (MRI), that showed the presence of nodular masses in the anophthalmic socket, an excisional biopsy was performed. Histopathology confirmed the diagnosis of CMM (epithelioid and spindle cell type), supporting the hypothesis that residual melanoma cells may remain clinically dormant for long periods, even for decades. A literature review was performed in order to review similar cases and to understand and discuss multiple factors, which may explain this extremely delayed recurrence. To the best of our knowledge, this is the third case to be reported in the literature.

Novel retinal finding in a patient with 4q12 deletion.

BACKGROUND: Chromosome 4q deletions are rare disorders phenotypically characterized by several features. The most commonly described ocular abnormalities include unilateral microphthalmia with bilateral colobomata, blue sclerae with pigmented retinal clumps, hypermetropia, and a divergent squint. PURPOSE: To report a case of 4q12 deletion with a singular retinal feature. MATERIALS AND METHODS: Case report. RESULTS: A 20-year-old Caucasian female with a history of poliosis, progressive appearance of small areas of skin depigmentation along trunk and limbs since birth and diagnosis of learning deficit was referred for a complete ocular examination. The genetic counseling showed microdeletion in the 4q12 region. An audiometric test was performed, showing a progressive bilateral neurosensorial hypoacusia. Ocular examination showed the presence of multifocal, tiny, whitish deposits in the posterior pole. Multimodal imaging defined the lesions as small elevations of the retinal pigment epithelium with slight hyper-autofluorescence and staining in the late phase of fluoresceine angiography (FA). Visual acuity was 20/20. The retinal findings did not change during the three-month follow-up. CONCLUSIONS: Although the findings herein reported have never been described before in patients affected by 4q12 mutations, we do not exclude that they could represent a manifestation of the peculiar genetic asset of the patient, related to dysfunction in pigment epithelium/neuroretinal metabolic activity.

Spondyloocular Syndrome: A Novel XYLT2 Variant with Description of the Neonatal Phenotype.

Spondyloocular syndrome (SOS) is a skeletal disorder caused by pathogenic variants in XYLT2 gene encoding a xylotransferase involved in the biosynthesis of proteoglycans. This condition, with autosomal recessive inheritance, has a high phenotypic variability. It is characterized by bone abnormalities (osteoporosis, fractures), eye and cardiac defects, hearing impairment, and varying degrees of developmental delay. Until now only 20 mutated individuals have been reported worldwide. Here, we describe two siblings from consanguineous healthy parents in which a novel homozygous frameshift variant c.1586dup p(Thr530Hisfs*) in the XYLT2 gene was detected by exome sequencing (ES). The first patient (9 years) presented short stature with skeletal defects, long face, hearing loss and cataract. The second patient, evaluated at a few days of life, showed macrosomia, diffuse hypertrichosis on the back, overabundant skin in the retronucal area, flattened facial profile with drooping cheeks, elongated eyelid rims, wide and flattened nasal bridge and turned down corners of the mouth. During the prenatal period, high nuchal translucency and intestinal hyperechogenicity were observed at ultrasound. In conclusion, these two siblings with a novel pathogenic variant in XYLT2 further expand the clinical and mutational spectrum of SOS.

13q Deletion Syndrome Involving RB1: Characterization of a New Minimal Critical Region for Psychomotor Delay.

Retinoblastoma (RB) is an ocular tumor of the pediatric age caused by biallelic inactivation of the RB1 gene (13q14). About 10% of cases are due to gross-sized molecular deletions. The deletions can involve the surrounding genes delineating a contiguous gene syndrome characterized by RB, developmental anomalies, and peculiar facial dysmorphisms. Overlapping deletions previously found by traditional and/or molecular cytogenetic analysis allowed to define some critical regions for intellectual disability (ID) and multiple congenital anomalies, with key candidate genes. In the present study, using array-CGH, we characterized seven new patients with interstitial 13q deletion involving RB1. Among these cases, three patients with medium or large 13q deletions did not present psychomotor delay. This allowed defining a minimal critical region for ID that excludes the previously suggested candidate genes (HTR2A, NUFIP1, PCDH8, and PCDH17). The region contains 36 genes including NBEA, which emerged as the candidate gene associated with developmental delay. In addition, MAB21L1, DCLK1, EXOSC8, and SPART haploinsufficiency might contribute to the observed impaired neurodevelopmental phenotype. In conclusion, this study adds important novelties to the 13q deletion syndrome, although further studies are needed to better characterize the contribution of different genes and to understand how the haploinsufficiency of this region can determine ID.

Retinoblastoma Is Characterized by a Cold, CD8+ Cell Poor, PD-L1- Microenvironment, Which Turns Into Hot, CD8+ Cell Rich, PD-L1+ After Chemotherapy.

Purpose: To investigate the impact of chemotherapy (CHT) on human retinoblastoma (RB) tumor microenvironment (TME). Cases and Methods: Ninety-four RBs were studied, including 44 primary RBs treated by upfront surgery (Group 1) and 50 primary RBs enucleated after CHT (CHT), either intra-arterial (IAC; Group 2, 33 cases) or systemic (S-CHT; Group 3, 17 cases). Conventional and multiplexed immunohistochemistry were performed to make quantitative comparisons among the three groups, for the following parameters: tumor-infiltrating inflammatory cells (TI-ICs); programmed cell death protein 1 (PD-1) positive TI-ICs; Ki67 proliferation index; gliosis; PD-1 ligand (PD-L1) protein expression; vessel number. We also correlated these TME factors with the presence of histological high-risk factors (HHRF+) and RB anaplasia grade (AG). Results: After CHT, a decrease in both RB burden and Ki67 positivity was observed. In parallel, most subsets of TI-ICs, PD-1+ TI-ICs, gliosis, and PD-L1 protein expression significantly increased (P < 0.001, P = 0.02, P < 0.001, respectively). Vessel number did not significantly vary. Age, HHRFs+ and AG were significantly different between primary and chemoreduced RBs (P < 0.001, P = 0.006, P = 0.001, respectively) and were correlated with most TME factors. Conclusions: CHT modulates host antitumor immunity by reorienting the RB TME from anergic into an active, CD8+, PD-L1+ hot state. Furthermore, some clinicopathological characteristics of RB correlate with several factors of TME. Our study adds data in favor of the possibility of a new therapeutic scenario in human RB.

Bilateral retinoblastoma and osteogenesis imperfecta, a very rare association: Two cases.

INTRODUCTION: This case report presents two patients affected by a very rare association of bilateral retinoblastoma and osteogenesis imperfecta. CASE REPORT: Two Caucasian males with familial history and clinical signs of osteogenesis imperfecta came to our attention for bilateral leukocoria. The ocular fundus examination revealed bilateral retinoblastoma. Proper therapies were dispensed in order to achieve full regression. Genetic counseling was performed. DISCUSSION: The primary role of genetics in retinoblastoma pathogenesis in widely known, and different genes have been identified. Osteogenesis imperfecta is a rare connective tissue disorders, caused by mutated genes encoding for collagen. The single gene defect in osteogenesis imperfecta type VI is Serpin Family F Member 1 (SERPINF1), a neurotrophic factor for the neuronal differentiation in retinoblastoma cells. The association of bilateral retinoblastoma and osteogenesis imperfecta could be the result of the mutation of a single gene playing a role in a hypothetical common pathway.

The Addition of Topotecan to Melphalan in the Treatment of Retinoblastoma with Intra-arterial Chemotherapy.

PURPOSE: To evaluate the effect of adding topotecan to melphalan for the treatment of retinoblastoma using intra-arterial chemotherapy (IAC). DESIGN: Single-center, consecutive case series. PARTICIPANTS: All eyes treated with IAC at the University of Siena, Siena, Italy, from 2008 to 2019. METHODS: Eyes were treated via IAC with either melphalan monotherapy or melphalan plus topotecan. The characteristics and outcomes of these 2 groups were compared. MAIN OUTCOME MEASURES: The main outcome measure was globe salvage rate. Additionally, a complete summary of all adverse events for all eyes was compared between groups and included local, regional, and systemic events causing both transient and permanent effects. RESULTS: A total of 193 patients and 208 eyes were treated with IAC between April 2008 and October 2019. Melphalan alone (MA) was used to treat 44 patients and 50 eyes for a total of 191 procedures. The combination of melphalan plus topotecan (MPT) was used to treat 149 patients and 158 eyes for a total of 780 procedures. Groups were similar in terms of age at presentation. The MPT group included more advanced eyes (P < 0.001) and had shorter follow-up time (mean 47 vs. 120 months in the MA group, P < 0.001). The MPT group required less laser and cryotherapy after treatment (32% of eyes vs. 50% of eyes in the MA group, P < 0.001); there was no other difference in the number of adjuvant treatments required between groups. There was no difference in the number of acute adverse events, both systemic and local, between groups. There was no difference in the number of transient or permanent intraocular side effects between groups. Kaplan-Meier survival analysis estimated a better globe salvage rate in the MPT group (66%) compared with the MA group (58%, P = 0.05). CONCLUSIONS: In this case series, the addition of topotecan to melphalan did not alter the IAC side effect profile and may contribute to improved globe salvage.

Fovea-sparing coats disease: A rare clinical entity.

PURPOSE: To evaluate the rarity, clinical features and management of Coats disease characterized by fovea-sparing enhancing the importance of pediatric retinal screening and early management to maintain a good visual acuity. METHODS: Retrospective analysis of approximately 40 patients affected by Coats disease between 2000 and 2020 at the Retinoblastoma Referral Center and Ophthalmology unit of the University of Siena in Italy. RESULTS: Two patients with fovea sparing Coats disease were included. Both presented an extrafoveal Coats disease (stage 2A by Shields classification) when they were 5 and 6 years old respectively.They had no anterior findings and a presenting visual acuity of 20/20 reflecting the early stage and a milder phenotype of the disease which are indeed more likely to be found in patients older than 3 years at presentation.Both presented telangiectasia and retinal exudation in the affected eye. Standard Argon laser photocoagulation and subsequently Cryotherapy were performed in the telangiectatic retinal periphery of both patients obtaining an excellent control and regression of the disease. CONCLUSIONS: Careful pediatric retinal screening and early management are crucial to ensure a good visual prognosis in such an early feature of Coats disease as fovea sparing since this condition unfortunately tends to recall the physician's attention in more advanced stages.Due to the extremely poor number of articles regarding such a rare feature of Coats disease like fovea sparing, we report our experience.

MR Imaging Features to Differentiate Retinoblastoma from Coats' Disease and Persistent Fetal Vasculature.

Retinoblastoma mimickers, or pseudoretinoblastoma, are conditions that show similarities with the pediatric cancer retinoblastoma. However, false-positive retinoblastoma diagnosis can cause mistreatment, while false-negative diagnosis can cause life-threatening treatment delay. The purpose of this study is to identify the MR imaging features that best differentiate between retinoblastoma and the most common pseudoretinoblastoma diagnoses: Coats' disease and persistent fetal vasculature (PFV). Here, six expert radiologists performed retrospective assessments (blinded for diagnosis) of MR images of patients with a final diagnosis based on histopathology or clinical follow-up. Associations between 20 predefined imaging features and diagnosis were assessed with exact tests corrected for multiple hypothesis testing. Sixty-six patients were included, of which 33 (50%) were retinoblastoma and 33 (50%) pseudoretinoblastoma patients. A larger eye size, vitreous seeding, and sharp-V-shaped retinal detachment were almost exclusively found in retinoblastoma (p < 0.001-0.022, specificity 93-97%). Features that were almost exclusively found in pseudoretinoblastoma included smaller eye size, ciliary/lens deformations, optic nerve atrophy, a central stalk between optic disc and lens, Y-shaped retinal detachment, and absence of calcifications (p < 0.001-0.022, specificity 91-100%). Additionally, three newly identified imaging features were exclusively present in pseudoretinoblastoma: intraretinal macrocysts (p < 0.001, 38% [9/24] in Coats' disease and 20% [2/10] in PFV), contrast enhancement outside the solid lesion (p < 0.001, 30% [7/23] in Coats' disease and 57% [4/7] in PFV), and enhancing subfoveal nodules (38% [9/24] in Coats' disease). An assessment strategy was proposed for MR imaging differentiation between retinoblastoma and pseudoretinoblastoma, including three newly identified differentiating MR imaging features.

Intra-arterial chemotherapy for retinoblastoma: the dosimetric impact.

PURPOSE: Purposes are (1) to measure main radiation parameters and (2) to propose a method to estimate the absorbed doses of internal organs starting from DAP values. Measuring the exposition of internal organs by repeated irradiations on an anthropomorphic phantom with the same settings used in vivo, we could establish correlations between (1) DAP and the dose recorded by a dosimeter placed along the X-ray beam entrance pathway; (2) the dose recorded by the same dosimeter and the absorbed dose in internal organs. METHODS: Forty-four consecutive patients (16 males, 28 females) (mean age 35.4 months) treated at our institution with IAC (216 procedures: 196 via the ICA and 20 into branches of the ECA) were included in this prospective study. IAC was divided into 5 phases. Fluoroscopic time, DAP, and ESD were measured. RESULTS: The mean DAP was 595 ± 445 cGy cm2 and the mean fluoroscopic time was 540 ± 403 s. ESD was on average 9.59 mGy (range 0.8-165 mGy). The absorbed dose was lower than 12.1 mGy in the left retina (the more exposed organ) in 75% of single treatments and lower than 25 mGy in 95% of treatments. In the cases of 3 and 6 sessions, the left retina of 75% of patients absorbed respectively less than 36.3 and 72.7 mGy, whereas the left retina of 95% of patients received less than 75.2 and 150.4 mGy. Other organs were less exposed. CONCLUSION: This paper describes a method of absorbed dose estimation providing ranges used clinically in a single practice and the basis for further prospective studies.

Uveal Melanoma: A European Network to Face the Many Challenges of a Rare Cancer.

Uveal melanoma (UM) is the most frequent primary ocular cancer in adults, accounting for 5% of all melanomas. Despite effective treatments for the primary tumour, up to 50% of UM patients will develop metastasis, leading to a very poor prognosis and a median overall survival of 6 to 12 months, with no major improvements in the last 30 years. There is no standard oncological treatment available for metastatic UM patients, and BRAF/MEK and immune checkpoint inhibitors show disappointing results when compared to cutaneous melanoma (CM). Recent advances in biology, however, identified specific gene and chromosome alterations, potentially permitting an actively tailored surveillance strategy, and dedicated clinical studies. Being a rare cancer, UM patients have to overcome issues such as identifying referral centres, having access to information, and partnering with oncologists for specific management strategies and research priorities. Here, we describe how the EUropean Rare Adult solid CAacer Network (EURACAN) will help in addressing these challenges and accelerating international collaborations to enhance the development of innovative treatments in UM.

Evidence of predisposing epimutation in retinoblastoma.

Retinoblastoma (RB), which represents the most common childhood eye cancer, is caused by biallelic inactivation of RB1 gene. Promoter hypermethylation is quite frequent in RB tissues but conclusive evidence of soma-wide predisposing epimutations is currently scant. Here, 50 patients who tested negative for RB1 germline sequence alterations were screened for aberrant promoter methylation using methylation-specific MLPA. The assay, performed on blood, identified a sporadic patient with methylation of CpG106, absent in parents' DNA. Bisulfite pyrosequencing accurately quantified CpG methylation in blood DNA (mean ∼49%) and also confirmed the aberration in DNA isolated from oral mucosa although at lower levels (mean ∼34%). Using a tag-SNP, methylation was demonstrated to affect the maternal allele. Real-time qPCR demonstrated RB1 transcriptional silencing. In conclusion, we documented that promoter methylation can act as the first "hit" in Knudson's model. This mosaic epimutation mimics the effect of an inactivating mutation and phenocopies RB onset.

Parent-of-origin effect of hypomorphic pathogenic variants and somatic mosaicism impact on phenotypic expression of retinoblastoma.

Retinoblastoma is the most common eye cancer in children. Numerous families have been described displaying reduced penetrance and expressivity. An extensive molecular characterization of seven families led us to characterize the two main mechanisms impacting on phenotypic expression, as follows: (i) mosaicism of amorphic pathogenic variants; and (ii) parent-of-origin-effect of hypomorphic pathogenic variants. Somatic mosaicism for RB1 splicing variants (c.1960+5G>C and c.2106+2T>C), leading to a complete loss of function was demonstrated by high-depth NGS in two families. In both cases, the healthy carrier parent (one with retinoma) showed a variant frequency lower than that expected for a heterozygous individual, indicating a 56-60% mosaicism level. Previous evidences of a ~3-fold excess of RB1 maternal canonical transcript led us to hypothesize that this differential allelic expression could influence phenotypic outcome in families at risk for RB onset. Accordingly, in five families, we identified a higher tumor risk associated with paternally inherited hypomorphic pathogenic variants, namely a deletion resulting in the loss of 37 amino acids at the N-terminus (c.608-16_608del), an exonic substitution with a "leaky" splicing effect (c.1331A>G), a partially deleterious substitution (c.1981C>T) and a truncating C-terminal variant (c.2663+2T>C). The identification of these mechanisms changes the genetic/prenatal counseling and the clinical management of families, indicating a higher recurrence risk when the hypomorphic pathogenic variant is inherited from the father, and suggesting the need for second tumor surveillance in unaffected carriers at risk of developing adult-onset cancer such as osteosarcoma or leiomyosarcoma.

Metastatic deaths in retinoblastoma patients treated with intraarterial chemotherapy (ophthalmic artery chemosurgery) worldwide.

BACKGROUND: Ophthalmic artery chemosurgery [OAC, intra-arterial chemotherapy (IAC)] was introduced in 2006 as treatment modality for intraocular retinoblastoma. The purpose of this commentary is to retrospectively review the incidence of metastatic deaths in retinoblastoma patients treated with OAC worldwide over a 10 year period. Retrospective data regarding metastatic deaths was collected from six international retinoblastoma centers (New York City USA, Philadelphia USA, Sao Paulo Brazil, Siena Italy, Lausanne Switzerland and Buenos Aires Argentina). All retinoblastoma patients from these centers (naive and recurrent, unilateral and bilateral) treated with OAC/IAC since 2006 have been included in this study. Data regarding number of patients, number of OAC/IAC infusions, number unilateral and bilateral, number treated for naive disease or salvage and number of metastatic deaths have been assessed. Over a 10-year period of time 1139 patients received OAC/IAC for 4396 infusions. At last follow-up there were only three metastatic deaths (all treated in Buenos Aires). CONCLUSION: The current survey assessed the recorded risk of metastatic deaths in six retinoblastoma centers worldwide in children with retinoblastoma (unilateral or bilateral) treated with OAC/IAC as primary or secondary therapy. Overall, the observed risk for metastatic deaths from retinoblastoma was <1% in OAC/IAC treated children.

Neonatal Retinoblastoma.

From 7% to 10% of all retinoblastomas and from 44% to 71% of familial retinoblastomas in developed countries are diagnosed in the neonatal period, usually through pre- or post-natal screening prompted by a positive family history and sometimes serendipitously during screening for retinopathy of prematurity or other reasons. In developing countries, neonatal diagnosis of retinoblastoma has been less common. Neonatal retinoblastoma generally develops from a germline mutation of RB1, the retinoblastoma gene, even when the family history is negative and is thus usually hereditary. At least one-half of infants with neonatal retinoblastoma have unilateral tumors when the diagnosis is made, typically the International Intraocular Retinoblastoma Classification (Murphree) Group B or higher, but most germline mutation carriers will progress to bilateral involvement, typically Group A in the fellow eye. Neonatal leukokoria usually leads to the diagnosis in children without a family history of retinoblastoma, and a Group C tumor or higher is typical in the more advanced involved eye. Almost all infants with neonatal retinoblastoma have at least one eye with a tumor in proximity to the foveola, but the macula of the fellow eye is frequently spared. Consequently, loss of reading vision from both eyes is exceptional. A primary ectopic intracranial neuroblastic tumor known as trilateral retinoblastoma is no more common after neonatal than other retinoblastoma. For many reasons, neonatal retinoblastoma may be a challenge to eradicate, and the early age at diagnosis and relatively small tumors do not guarantee the preservation of both eyes of every involved child. Oncology nurses can be instrumental in contributing to better outcomes by ensuring that hereditary retinoblastoma survivors receive genetic counseling, by referring families of survivors to early screening programs when they are planning for a baby, and by providing psychological and practical support for parents when neonatal retinoblastoma has been diagnosed.

A Case of Anterior Chamber Cholesterolosis Due to Coats' Disease and a Review of Reported Cases.

PURPOSE: To present the case of an 18 month old boy with Coats' disease who was found to have anterior chamber cholesterolosis. METHODS: Case presentation and review of reported cases. RESULTS: An 18 month old boy presented with unilateral stage 3B Coats' disease without other clinical findings. Two weeks after presentation he returned with xanthocoria due to anterior chamber cholesterolosis. He subsequently developed hyphema, neovascular glaucoma, and was enucleated. His case is compared to all previously reported cases of Coats' disease leading to anterior chamber cholesterolosis. CONCLUSION: The presentation of anterior chamber cholesterolosis in Coats' disease can range from the incidental finding in an asymptomatic patient to acute angle closure glaucoma with pain and acutely decreased vision. Clinicians should be aware of this potential complication of Coats' disease as it denotes a poor visual prognosis.

Transorbital anastomotic pathways between the external and internal carotid systems in children affected by intraocular retinoblastoma.

PURPOSE: It is well known that many anastomoses can join the external carotid system and the ophthalmic artery. However, their frequency has never been reported. Since they can be relevant for interventional radiologists operating in the orbit, we decided to illustrate and determine the frequency of the anastomoses that can be found in children. METHODS: A retrospective study of 443 angiographic procedures (via ophthalmic artery and/or external carotid artery) carried out on 97 children affected by intraocular retinoblastoma was made to investigate the arterial anatomy of 106 orbits. RESULTS: Anastomoses were observed in 44.33 % of orbits. However, their true frequency is likely much higher as the rate of visualization increased up to 91.11 % of orbits when the angiographic study was extended to the external carotid artery. In order of frequency we detected the following anastomoses: lacrimal artery-middle meningeal artery, lacrimal artery-anterior deep temporal artery, ophthalmic artery-middle meningeal artery, ophthalmic artery-facial artery, supraorbital artery-superficial temporal artery, supratrochlear artery-superficial temporal artery, supraorbital artery-middle meningeal artery, dorsal nasal artery-infraorbital artery, supraorbital artery-zygomaticoorbital artery, lacrimal artery-zygomaticoorbital artery. CONCLUSION: When properly searched, anastomoses between the ophthalmic artery and the external carotid artery are almost constant in children. Depending on the clinical scenario, they can represent dangers or valuable alternative routes for collateral circulations and intraarterial chemotherapy.

Two masquerade presentations of retinoblastoma.

Masquerade syndromes are disorders occurring with intraocular inflammation misdiagnosed as uveitis. The underlying causes may be benign or malignant conditions, and one of the most important diagnoses to take into consideration in children is retinoblastoma. We present two cases with uncertain early misdiagnosis whose definite diagnosis eventually was retinoblastoma.