NF1 mutation drives neuronal activity-dependent initiation of optic glioma.

Neurons have recently emerged as essential cellular constituents of the tumour microenvironment, and their activity has been shown to increase the growth of a diverse number of solid tumours1. Although the role of neurons in tumour progression has previously been demonstrated2, the importance of neuronal activity to tumour initiation is less clear-particularly in the setting of cancer predisposition syndromes. Fifteen per cent of individuals with the neurofibromatosis 1 (NF1) cancer predisposition syndrome (in which tumours arise in close association with nerves) develop low-grade neoplasms of the optic pathway (known as optic pathway gliomas (OPGs)) during early childhood3,4, raising  the possibility that postnatal light-induced activity of the optic nerve drives tumour initiation. Here we use an authenticated mouse model of OPG driven by mutations in the neurofibromatosis 1 tumour suppressor gene (Nf1)5 to demonstrate that stimulation of optic nerve activity increases optic glioma growth, and that decreasing visual experience via light deprivation prevents tumour formation and maintenance. We show that the initiation of Nf1-driven OPGs (Nf1-OPGs) depends on visual experience during a developmental period in which Nf1-mutant mice are susceptible to tumorigenesis. Germline Nf1 mutation in retinal neurons results in aberrantly increased shedding of neuroligin 3 (NLGN3) within the optic nerve in response to retinal neuronal activity. Moreover, genetic Nlgn3 loss or pharmacological inhibition of NLGN3 shedding blocks the formation and progression of Nf1-OPGs. Collectively, our studies establish an obligate role for neuronal activity in the development of some types of brain tumours, elucidate a therapeutic strategy to reduce OPG incidence or mitigate tumour progression, and underscore the role of Nf1mutation-mediated dysregulation of neuronal signalling pathways in mouse models of the NF1 cancer predisposition syndrome.

Longitudinal changes in retinal ganglion cell function in optic pathway glioma evaluated by photopic negative response.

Photopic negative response (PhNR), an index of retinal ganglion cell (RGC) function, is impaired in patients with optic pathway gliomas (OPGs). The aim of this longitudinal study was to evaluate whether PhNR deteriorates over time in OPG patients. Fourteen pediatric patients affected by OPG (4 males and 10 females, mean age 12.4 ± 5.7 years, 8 with neurofibromatosis type 1 [NF1]) with ≥12 months of follow-up and ≥2 evaluations, were included in this retrospective study. All patients had received chemotherapy, with or without OPG surgical resection, at least 5 years prior to the study. At baseline, all patients underwent a complete ophthalmological examination. Follow-up included clinical examination and PhNR measurement as well as brain MRI (according to pediatric oncologist indications) every 6 or 12 months. Mean follow-up duration was 16.7 ± 7.5 months (range 12-36 months). Photopic electroretinograms were elicited by 2.0 cd-s/m2 Ganzfeld white flashes presented on a steady 20 cd/m2 white background. The PhNR amplitude was measured as the difference between baseline and the maximal negative amplitude (minimum) of the negative wave, following the photopic b-wave. Compared to baseline, mean PhNR amplitude was significantly decreased at the end of follow-up (p = 0.008). NF1-related OPGs exhibited a decline in PhNR amplitude (p = 0.005) and an increase in PhNR peak-time during the follow-up (p = 0.013), whereas sporadic OPGs showed no significant changes. Tumor size remained stable in all patients on MRI. PhNR amplitude decreased over the observation period, suggesting progressive RGC dysfunction in NF1-related pediatric OPGs, despite stable size on MRI imaging. PhNR could serve as a non-invasive objective tool for assessing longitudinal changes in RGC function in the clinical management of childhood OPG.

Treatment evaluation by volumetric segmentation in pediatric optic pathway glioma: evaluation of the effect of bevacizumab on intra-tumor components.

PURPOSE: Progressive pediatric optic pathway gliomas (OPGs) are treated by diverse systemic antitumor modalities. Refined insights on the course of intra-tumoral components are limited. METHODS: We performed an exploratory study on the longitudinal volumetric course of different (intra-)tumor components by manual segmentation of MRI at the start and after 3, 6 and 12 months of bevacizumab (BVZ) treatment. RESULTS: Thirty-one patients were treated with BVZ (median 12 months, range: 2-39 months). During treatment the total tumor volume decreased with median 19.9% (range: - 62.3 to + 29.7%; n = 30) within the first 3 months, decreased 19.0% (range: - 68.8 to + 96.1%; n = 28) between start and 6 months and 27.2% (range: -73.4 to + 36.0%; n = 21) between start and 12 months. Intra-tumoral cysts were present in 12 OPGs, all showed a decrease of volume during treatment. The relative contrast enhanced volume of NF1 associated OPG (n = 11) showed an significant reduction compared to OPG with a KIAA1549-BRAF fusion (p < 0.01). Three OPGs progressed during treatment, but were not preceded by an increase of relative contrast enhancement. CONCLUSION: Treatment with BVZ of progressive pediatric OPGs leads to a decrease of both total tumor volume and cystic volume for the majority of OPGs with emphasis on the first three months. NF1 and KIAA1549-BRAF fusion related OPGs showed a different (early) treatment effect regarding the tumor enhancing component on MRI, which did not correlate with tumor volume changes. Future research is necessary to further evaluate these findings and its relevance to clinical outcome parameters.

Treatment of isolated pediatric optic nerve glioma: A nationwide retrospective cohort study and systematic literature review on visual and radiological outcome.

BACKGROUND: Progressive isolated optic nerve glioma (ONG) in children is a rare disease, treated with various modalities. A global treatment consensus is not available. METHODS: We conducted a national retrospective multicenter cohort study (1995-2020) to investigate how different treatment strategies impact outcome for ONG in children, by assessing treatment responses to systemic anticancer therapy (SAT), surgery, and radiotherapy for ONG. The primary endpoints included changes in best-corrected visual acuity (BCVA) and tumor volume (TV) on MRI, both evaluated at the start and end of therapy and at long-term follow up. RESULTS: A total of 21 ONGs (20 patients) received SAT (n = 14 (66.7%)), surgery (n = 4 (19.0%)), and radiotherapy (n = 3 (14.3%)). After SAT BCVA stabilized or improved in 66.6% (n = 4) and the TV decreased by a median of 45.1% (range: -88.6% to +31.5%) (n = 13). Before resection two eyes were already blind. After resection BCVA decreased to blindness in one eye. In total all four eyes were blind after resection. After first-line RT BCVA decreased in 66.7% of ONG to counting fingers or less, TV increased <3 months after RT by a median of 47.3% (range: -42.8% to +245.1%) (n = 3), followed by a long-term decrease of 94.4 and 13.8% (n = 2), respectively. CONCLUSION: SAT appears to be the preferred modality for progressive ONG in case of potential rescue of visual functions. Complete resection of ONG appears effective to reduce proptosis in case of preexisting blindness. The use of radiotherapy requires careful consideration due to the risk of severe visual impairment and secondary disease.

Optic pathway gliomas in children: Clinical characteristics, treatment, and outcome of 95 patients in a single center over a 31-year period. Can we avoid radiotherapy?

BACKGROUND: Optic pathway gliomas (OPG) are rare tumors in children. Lesion extent, visual functions, neurofibromatosis 1 (NF1), and age are factors that guide treatment. This study evaluates the clinical characteristics, treatment, and outcome of children and adolescents with OPG treated over a 31-year period in a single center. METHODS: Ninety-five patients with OPG diagnosed between January 1990 and December 2021 were retrospectively evaluated. First-line chemotherapy regimen consisted of vincristine and carboplatinum for 1 year. Radiotherapy was not used as first-line treatment and tried to be avoided in the ones who progressed after first-line treatment. RESULTS: Ninety-five children (44 male, 51 female) with a median age of 52 (1-216) months were evaluated. Sixty-three (66.3%) had NF1 and 10 (10,5%) diencephalic syndrome. The most common presenting symptoms were visual abnormalities and/or proptosis, nistagmus, and behavioral changes. Twenty-one (22.1%) patients with NF1 had stable disease throughout the follow-up period and received no treatment. Sixty-three of 74 patients received treatment at diagnosis and 11 due to progression during follow-up. Only one adolescent received radiotherapy at progression. Patients who progressed, received further line systemic treatment (vinblastine; bevacizumab; vincristine-cisplatinum-etoposide). Ten-year overall survival in all patients, in patients with NF1, and without NF1 were 97.2%, 98%, and 95.8% (p > .05), respectively; 10-year progression-free survival (PFS) in all patients, in patients with NF1, and without NF1 were 71.6%, 85.7%, and 54.2% (p = .001), respectively. CONCLUSIONS: In children with symptomatic/progressive OPG, chemotherapy consisting of vincristine-carboplatinum (VC) is effective. Radiotherapy may be avoided, especially in patients with NF1.

The role of surgery for optic pathway gliomas in the era of precision medicine.

Optic pathway gliomas (OPGs) represent a unique subset of brain tumours that primarily affect the paediatric population. Traditionally, these tumours are managed conservatively due to their location to and association with vital structures. This article explores the evolving role of surgery in the management of OPGs, particularly in the context of advancements in precision medicine. The advent of targeted therapy, especially for tumours with specific genetic alterations, such as BRAF V600E mutations, has revolutionized the treatment landscape, offering new avenues for patient-specific therapy. However, surgery still plays a crucial role, especially for debulking in cases of hydrocephalus or when standard therapies are ineffective. Advances in surgical techniques, including neuronavigation, endoscopic approaches, and intraoperative neurophysiological monitoring, have enhanced the safety and efficacy of operative interventions. Despite these developments, the complexity of OPGs necessitates a multidisciplinary approach, focusing on long-term outcomes and quality of life. Future research is needed to further elucidate the role of surgery in an era increasingly dominated by molecular genetics and targeted therapies.

Clinical signs and genetic evaluation of patients with neurofibromatosis type 1 with and without optic pathway gliomas in a center in Turkey.

PURPOSE: Optic pathway gliomas (OPGs) occur in 15% of patients with neurofibromatosis type 1 (NF1). Their location renders biopsy or surgical resection difficult because of the risk of vision loss. Therefore, only a few NF1-OPGs have been used for tissue diagnosis, and only a few analyses have been published on the molecular changes that drive tumorigenesis. METHODS: Due to this reason, we evaluated 305 NF1 patients, 34 with OPG and 271 without OPG for germ line mutations. All subjects underwent clinical examination and DNA analysis of NF1, confirming the diagnosis of NF1. RESULTS: Clinically, the group with OPG had a significantly higher incidence of bone dysplasia (P < 0.001) and more café-au-lait spots (P = 0.001) compared to those in the group without OPG. The frequency of Lisch nodules was on the borderline of statistical significance (P = 0.058), whereas the frequency of neurofibromas did not differ significantly (cutaneous, P = 0.64; plexiform, P = 0.44). Individuals with OPG mostly had mutations in the first one-third of the NF1 gene compared with that in patients who did not have OPG. Some identical mutations were detected in unrelated families with NF1-OPG. CONCLUSION: The observation of certain phenotypic features and the correlation between genotype and phenotype might help to determine the risk of developing OPG with NF1.

Complications and visual outcomes following surgical resection of pediatric optic pathway/hypothalamic gliomas: a systematic review and meta-analysis.

Pediatric optic pathway/hypothalamic gliomas (OPHG) pose challenges in treatment due to their location and proximity to vital structures. Surgical resection plays a key role in the management of OPHG especially when the tumor exhibits mass effect and causes symptoms. However, data regarding outcomes and complications of surgical resection for OPHG remains heterogenous. The authors performed a systematic review on pediatric OPHG in four databases: PubMed, EMBASE, Cochrane Library, and Google Scholar. We included studies that reported on the visual outcomes and complications of OPHG resection. A meta-analysis was performed and reported per the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement. A total of 26 retrospective studies were included. Seven hundred ninety-seven pediatric patients with OPHG undergoing surgical resection were examined. A diagnosis of NF1 was confirmed in 9.7%. Gross total resection was achieved in 36.7%. Intraorbital optic pathway gliomas showed a significantly higher gross total resection rate compared to those located in the chiasmatic/hypothalamic region (75.8% vs. 9.6%). Postoperatively, visual acuity improved in 24.6%, remained unchanged in 68.2%, and worsened in 18.2%. Complications included hydrocephalus (35.4%), anterior pituitary dysfunction (19.6%), and transient diabetes insipidus (29%). Tumor progression post-resection occurred in 12.8%, through a mean follow-up of 53.5 months. Surgical resection remains an essential strategy for treating symptomatic and large pediatric OPHG and can result in favorable vision outcomes in most patients. Careful patient selection is critical. Patients should be monitored for hydrocephalus development postoperatively and followed up to assess for tumor progression and adjuvant treatment necessity.

Pediatric Optic Pathway Gliomas Resource Utilization and Prevalence in the OptumLabs Data Warehouse.

BACKGROUND: Although significant progress has been made in improving the rate of survival for pediatric optic pathway gliomas (OPGs), data describing the methods of diagnosis and treatment for OPGs are limited in the modern era. This retrospective study aims to provide an epidemiological overview in the pediatric population and an update on eye care resource utilization in OPG patients using big data analysis. METHODS: Using the OptumLabs Data Warehouse, 9-11 million children from 2016 to 2021 assessed the presence of an OPG claim. This data set was analyzed for demographic distribution data and clinical data including average ages for computed tomography (CT), MRI, strabismus, and related treatment (surgery, chemotherapy, and radiation), as well as yearly rates for optical coherence tomography (OCT) and visual field (VF) examinations. RESULTS: Five hundred fifty-one unique patients ranging in age from 0 to 17 years had an OPG claim, with an estimated prevalence of 4.6-6.1 per 100k. Among the 476 OPG patients with at least 6 months of follow-up, 88.9% had at least one MRI and 15.3% had at least one CT. Annual rates for OCT and VF testing were similar (1.26 vs 1.35 per year), although OCT was ordered for younger patients (mean age = 9.2 vs 11.7 years, respectively). During the study period, 14.1% of OPG patients had chemotherapy, 6.1% had either surgery or radiation, and 81.7% had no treatment. CONCLUSIONS: This study updates OPG demographics for the modern era and characterizes the burden of the treatment course for pediatric OPG patients using big data analysis of a commercial claims database. OPGs had a prevalence of about 0.005% occurring equally in boys and girls. Most did not receive treatment, and the average child had at least one claim for OCT or VF per year for clinical monitoring. This study is limited to only commercially insured children, who represent approximately half of the general child population.

The Relationship Between Choroidal Abnormalities and Visual Outcomes in Pediatric Patients With NF1-Associated Optic Pathway Gliomas.

BACKGROUND: Choroidal abnormalities (CAs) visualized on near-infrared reflectance (NIR) imaging are a new diagnostic criterion for neurofibromatosis type 1 (NF1), but the association between the presence of CAs and visual function remains unknown. This study evaluated the relationship between visual acuity (VA) with the presence, number, or total area of CAs visualized by NIR in children with NF1-associated optic pathway gliomas (NF1-OPGs). METHODS: Patients (<18 years) enrolled in a prospective longitudinal study of children with NF1-associated OPGs from 3 institutions were eligible if they had optical coherence tomography (OCT) of the macula (Heidelberg Spectralis) with ≥1 year of follow-up. The central 30° NIR images were reviewed by 2 neuro-ophthalmologists who manually calculated the number and total area of CAs. VA (logMAR) was measured using a standardized protocol. Cross-sectional associations of presence, number, and total area of CAs with VA, retinal nerve fiber layer thickness (RNFL), and ganglion cell-inner plexiform layer thickness were evaluated at the first and most recent visits using regression models. Intereye correlation was accounted for using generalized estimating equations. RESULTS: Eighty-two eyes of 41 children (56% female) were included. The mean ± SD age at the first OCT was 10.1 ± 3.3 years, with a mean follow-up of 20.4 ± 7.2 months. At study entry, CAs were present in 46% of eyes with a mean number of 2.1 ± 1.7 and a mean total area of 2.0 ± 1.7 mm 2 per eye. At the most recent follow-up, CAs were present in 48% of eyes with a mean number of 2.2 ± 1.8 lesions and a mean total area of 2.3 ± 2.1 mm 2 per eye. Neither VA nor OCT parameters at first and follow-up visits were associated with the presence, number, or total area of CAs (all P > 0.05). CONCLUSIONS: CAs are prevalent but not ubiquitous, in children with NF1-OPGs. Although CAs are a diagnostic criterion for NF1, their presence and size do not appear to be associated with visual function.

Optic pathway glioma and endocrine disorders in patients with and without NF1.

BACKGROUND: Optic pathway gliomas (OPGs) are classified by anatomic location and the association with neurofibromatosis type 1 (NF1). Children with OPGs face sequelae related to tumor location and treatment modalities. We assessed the prevalence of endocrine dysfunction in children with OPGs and compared outcomes between those with and without NF1. METHODS: We performed a retrospective medical record review of medical history, and clinical and laboratory data, of children diagnosed with OPGs (n = 59, 61% with NF1) during 1990-2020, followed at a tertiary endocrine clinic. Growth and puberty parameters and occurrence of endocrine dysfunction were evaluated. RESULTS: Isolated optic nerve involvement was higher among patients with than without NF1. Patients without NF1 were younger at OPG diagnosis and more often treated with debulking surgery or chemotherapy. At the last endocrine evaluation, patients without NF1 had comparable height SDS, higher BMI SDS, and a higher rate of endocrine complications (78.3% vs. 41.7%, p = 0.006). Younger age at diagnosis, older age at last evaluation, and certain OPG locations were associated with increased endocrine disorder incidence. CONCLUSIONS: Endocrine dysfunction was more common in patients without NF1; this may be related to younger age at presentation, tumor locations, a greater progressive rate, and more aggressive treatments. IMPACT: The literature is sparse regarding sporadic OPGs, and the mean duration of follow-up is shorter than at our study. Our data show a higher rate of endocrine dysfunction in patients with OPGs than previously described. We also found a higher prevalence of endocrine dysfunctions among patients without compared to those with NF-1. A better understanding of the true prevalence of endocrine disabilities that may evolve along time can help in guiding physicians in the surveillance needed in patients with OPG.

The impact of changes in gadolinium-enhancement on disease progression in children with neurofibromatosis type 1-associated optic pathway glioma: a retrospective analysis.

PURPOSE: There has been limited investigation of imaging features associated with visual acuity (VA) decline and initiation of treatment for patients with neurofibromatosis type 1 (NF1) and optic pathway glioma (OPG). METHODS: To evaluate the association of increased gadolinium enhancement with decline in VA, initiation of chemotherapy, and tumor growth, we performed a retrospective cohort study of children diagnosed with NF1-OPG between January 2006 to June 2016. Two cohorts were defined: a new diagnosis and a longitudinal cohort. Outcomes were examined at 1 and 2 years from initial diagnosis, and 1 and 2 years from initial increase in enhancement in the longitudinal cohort. RESULTS: Eighty patients were eligible; all 80 contributed to the new diagnosis cohort and 73 to the longitudinal cohort. Fifty-six patients (70%) demonstrated enhancing NF1-OPG at diagnosis. 39% of patients in the new diagnosis cohort and 45% of those in the longitudinal cohort developed increased enhancement during the study period. There was no significant association between increases in enhancement and VA decline in the newly diagnosed or longitudinal cohorts, as well as with initiation of treatment in the longitudinal cohort. Although there was an association of enhancement increase with treatment in the new diagnosis cohort, this association was not maintained when stratified by concurrent change in tumor size. CONCLUSION: Increased gadolinium-enhancement independent of a concurrent increase in tumor size on MRI should not be used as a marker of NF1-OPG progression and does not appear to be associated with visual decline or initiation of chemotherapy.

Pediatric Optic Pathway Gliomas: A Report From Northern Greece.

Optic pathway gliomas (OPGs) are the most common pediatric optic nerve tumors. Their behavior ranges between rapid growth, stability, or spontaneous regression. Τhey are characterized by low mortality albeit with significant morbidity. We present the characteristics, management, and outcome of 23 OPG patients (16 females, median age: 4.8 y) managed in a Pediatric Oncology Department in Northern Greece over a 25-year period. Overall, 57% had a background of neurofibromatosis type 1. Diagnosis was based on imaging (10 patients) or biopsy (13 patients). Presenting symptoms were mostly visual impairment/squint (52%). Proptosis/exophthalmos, raised intracranial pressure, and headache were also noted. In 2 occasions, it was detected with surveillance magnetic resonance imaging in the context of neurofibromatosis type 1. Eight patients had unilateral and 2 bilateral optic nerve tumors (Modified Dodge Classification, stage 1a/1b), 3 had chiasmatic (stage 2a/b), and 10 had multiple tumors (stage 3/4). Predominant histology was pilocytic astrocytoma (77%). Management included: observation (4), chemotherapy only (9), surgery only (3), or various combinations (7). Chemotherapy regimens included vincristine and carboplatin, vinblastine, or bevacizumab with irinotecan. Most patients demonstrated a slow disease course with complete response/partial response to chemotherapy and/or surgery, whereas 39% presented ≥1 recurrences. After a median follow-up of 8.5 years (range to 19 y), 20 patients (87%) are still alive with stable disease, in partial/complete remission, or on treatment.

Treatment of NF1-Associated Optic Pathway/Hypothalamic Gliomas in Patients With Diencephalic Syndrome.

Diencephalic syndrome is usually associated with tumors in the hypothalamic region, rarely occurring in patients with neurofibromatosis type 1 (NF1)-associated gliomas. We describe the clinical presentation and response to treatment in 3 patients with NF1 presenting with diencephalic syndrome as first symptom of optic pathway/hypothalamic glioma (OPHG). Because of the rarity of this constellation, knowledge about the clinical course and best treatment options for patients with NF1-associated OPHG and diencephalic syndrome is still limited. All 3 patients showed good response to treatment with normalization of body mass index and decrease in tumor volume within 6 months.

Ganglioneuroblastoma in a Child With Neurofibromatosis Type 1: A Case Report and Literature Review.

Neurofibromatosis type 1 (NF1) is a genetic condition commonly associated with a predisposition to tumor development. Affected individuals have an increased risk of benign and malignant tumors of the central and peripheral nervous system. Though pediatric patients with NF1 have an increased risk of tumors such as optic gliomas and neurofibromas during childhood, neuroblastic tumors are less often observed in this population. We report a rare case of a 5-year-old female with ganglioneuroblastoma intermixed and known history of NF1 and review the existing literature on the occurrence of ganglioneuroblastoma in pediatric patients with NF1.

The role of visual electrodiagnostics in management of children with neurofibromatosis type 1.

PURPOSE: To evaluate the role of visual electrodiagnostic testing in children with neurofibromatosis type 1 (NF1) despite improved accessibility to magnetic resonance imaging (MRI). METHODS: The records from 39 children (78 eyes, 15 boys, 24 girls, average age at last visit of 11.5 ± 4.3 years, average follow-up time of 7.8 ± 3.9 years) with genetically confirmed NF1 were retrospectively analysed. They all underwent a thorough ophthalmological investigation, including age-appropriate visual acuity testing, anterior segment evaluation for Lisch nodules and a dilated fundus examination. If children were cooperative enough, colour vision was tested using the Hardy-Rand-Rittler test, visual fields were evaluated with Goldmann perimetry. All performed MRI of the brain and orbits as part of the standard of care protocol. Visual electrodiagnostics included electroretinography (ERG) and visual evoked potentials (VEP) using a standard protocol in older children, whereas with less cooperative children a modified protocol according to the Great Ormond Street Hospital (GOSH protocol) was used. RESULTS: The average visual acuity was 0.8 ± 0.3, colour vision was abnormal in 6%, perimetry in 8%, Lisch nodules were present in 62%, and the optic disc was pale in 66% of all eyes. Plexiform neurofibroma of the eyelid/orbit was present in 4%. Optic pathway glioma (OPG) was detected with MRI in 22 (57%) and in 6/22 treatment was indicated. Other intracranial NF1-related lesions were documented in 70% of children. VEP were abnormal in 16/39 of all children with NF1 (41%) comprising 14/22 (65%) of children with confirmed OPG and 2/17 (12%) of children without OPG. All full-field and pattern ERG responses were within normal limits. All individual VEP results are described and three cases from this cohort of children are presented in detail to illustrate the importance of VEP testing. In Case 1, VEP abnormality suggested subsequent MRI of the brain under general anaesthesia, which was otherwise contraindicated according to normal clinical findings and his young age. In Cases 2 and 3, VEP provided more precise functional information during the follow-up of OPG, while other psychophysical tests remained unchanged. CONCLUSIONS: Electrodiagnostics has multifactorial role and importance in children with NF1, either when visual pathway function is impaired in young children, even before MRI under general anaesthesia and other psychophysical tests can be performed, as well as for a more precise monitoring of the visual pathway function before potential treatment of OPG, or after it, to evaluate its success.

Optic Pathway Gliomas: The Trends of Basic Research to Reduce the Impact of the Disease on Visual Function.

Pediatric optic pathway gliomas (OPG) are low-grade brain tumors characterized by slow progression and invalidating visual loss. Common therapeutic strategies include surgery, radiotherapy, chemotherapy, and combinations of these modalities, but despite the different treatment strategies, no actual treatment exists to prevent or revert visual impairment. Nowadays, several reports of the literature show promising results regarding NGF eye drop instillation and improvement of visual outcome. Such results seem to be related with the NGF-linked prevention in caspase activation, which reduces retinal ganglion cell loss.Reducing retinal ganglion cell loss results clinically in visual field improvement as well as visual electric potential and optical coherence tomography gain. Nonetheless, visual acuity fails to show significant changes.Visual impairment represents nowadays one of the major issues in dealing with OPGs. Secondary to the interesting results offered by NGF eye drop administration, further studies are warranted to better comprehend potential treatment strategies.

Transorbital neuroendoscopy-assisted resection of a giant optic pathway glioma in a neonate.

Congenital giant orbital tumors in infancy are relatively rare, especially when the tumors are associated with significant intracranial extension. We describe the use of a transorbital neuroendoscopy-assisted resection of such a lesion. While this approach is increasingly gaining popularity for certain anterior and middle skullbase lesions in adults, this report represents the youngest patient reported on where this minimally invasive approach has been successfully used to resect the intracranial tumor. This surgical approach obviated the need for a separate craniotomy, with the additional benefit of minimizing blood loss.

Endoscopic debulking canalization for optic pathway glioma with obstructive hydrocephalus.

Optic pathway gliomas (OPGs) are benign tumors that can stop growing or even shrink. In recent years, surgical resection has not been considered the first-line treatment because of its high risk of complications. Chemotherapy is the mainstay of treatment for growing OPGs. Surgical treatment for OPGs with obstructive hydrocephalus is required. Ventriculoperitoneal shunting is effective for all types of hydrocephalus. However, long-term management is required, especially in pediatric cases, and there is a risk of shunt-related complications over a long lifespan. Debulking surgery for OPGs allows us to avoid shunt placement by creating a waterway and releasing the hydrocephalus. To reduce the surgical risk and invasiveness, we used an endoscopic canalization technique with a small-diameter cylinder. In this article, we present a case of endoscopic canalization of an obstructive hydrocephalus caused by OPGs in a 14-year-old female to illustrate our surgical technique.(Trial registration Registry name and number: Efficacy and safety of the neuro-endoscopic treatment for brain tumors (2019-0254)).

An unusual presentation of bilateral optic pathway glioma in Crouzon Syndrome.

Crouzon Syndrome is a genetic craniosynostosis disorder associated with a high risk of ophthalmologic sequelae secondary to structural causes. However, ophthalmologic disorders due to intrinsic nerve aberrations in Crouzon Syndrome have not been described. Optic pathway gliomas (OPGs) are low grade gliomas that are intrinsic to the visual pathway, frequently associated with Neurofibromatosis type 1 (NF-1). OPGs involving both optic nerves without affecting the optic chiasm are rarely seen outside of NF-1. We report an unusual case of bilateral optic nerve glioma without chiasmatic involvement in a 17-month-old male patient with Crouzon Syndrome without any clinical or genetic findings of NF-1. This case suggests that close ophthalmologic follow up and orbital MRIs may benefit patients with Crouzon Syndrome.