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 Present and Future of Optic Pathway Glioma Therapy.

Optic pathway gliomas (OPGs) encompass two distinct categories: benign pediatric gliomas, which are characterized by favorable prognosis, and malignant adult gliomas, which are aggressive cancers associated with a poor outcome. Our review aims to explore the established standards of care for both types of tumors, highlight the emerging therapeutic strategies for OPG treatment, and propose potential alternative therapies that, while originally studied in a broader glioma context, may hold promise for OPGs pending further investigation. These potential therapies encompass immunotherapy approaches, molecular-targeted therapy, modulation of the tumor microenvironment, nanotechnologies, magnetic hyperthermia therapy, cyberKnife, cannabinoids, and the ketogenic diet. Restoring visual function is a significant challenge in cases where optic nerve damage has occurred due to the tumor or its therapeutic interventions. Numerous approaches, particularly those involving stem cells, are currently being investigated as potential facilitators of visual recovery in these patients.

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.

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.

Neurofibromatosis type 1-associated optic pathway gliomas: pathogenesis and emerging treatments.

Neurofibromatosis type 1 (NF1) is an autosomal dominant genetic disorder associated with an increased risk of developing a variety of benign and malignant tumors. Fifteen to 20% of children with NF1 are diagnosed with an optic pathway glioma (NF1-OPG) before 7 years of age, and more than half of them experience visual decline. At present, no effective therapy is available for prevention, restoration, or even stabilization of vision loss in subjects affected by NF1-OPG. This paper aims to review the main emerging pharmacological approaches that have been recently assessed in preclinical and clinical settings. We performed a search of the literature using Embase, PubMed, and Scopus databases to identify articles regarding NF1-OPGs and their treatment up to July 1st, 2022. The reference lists of the analyzed articles were also considered a source of literature information. To search and analyze all relevant English articles, the following keywords were used in various combinations: neurofibromatosis type 1, optic pathway glioma, chemotherapy, precision medicine, MEK inhibitors, VEGF, nerve growth factor. Over the past decade, basic research and the development of genetically engineered mice models of NF1-associated OPG have shed light on the cellular and molecular mechanisms underlying the disease and inspired animal and human testing of several compounds. A promising line of research is focusing on the inhibition of mTOR, a protein kinase controlling proliferation, protein synthesis rate and cell motility that is highly expressed in neoplastic cells. Several mTOR blockers have been tested in clinical trials, the most recent of which employed oral everolimus with encouraging results. A different strategy aims at restoring cAMP levels in neoplastic astrocytes and non-neoplastic neurons, since reduced intracellular cAMP levels contribute to OPG growth and, more importantly, are the major determinant of NF1-OPG-associated visual decline. So far, however, this approach has only been attempted in preclinical studies. Stroma-directed molecular therapies - seeking to target Nf1 heterozygous brain microglia and retinal ganglion cells (RGCs) - are another fascinating field. Microglia-inhibiting strategies have not yet reached clinical trials, but preclinical studies conducted over the last 15 years have provided convincing clues of their potential. The importance of NF1-mutant RGCs in the formation and progression of OPGs also holds promise for clinical translation. The evidence of Vascular Endothelial Growth Factor (VEGF)- Vascular Endothelial Growth Factor (VEGFR) signaling hyperactivity in pediatric low-grade gliomas prompted the use of bevacizumab, an anti-VEGF monoclonal antibody, which was tested in children with low-grade gliomas or OPGs with good clinical results. Neuroprotective agents have also been proposed to preserve and restore RGCs and topical eye administration of nerve growth factor (NGF) has demonstrated encouraging electrophysiological and clinical results in a double-blind, placebo-controlled study. Traditional chemotherapy in patients with NF1-OPGs does not significantly ameliorate visual function, and its effectiveness in halting tumor growth cannot be considered a satisfactory result. Newer lines of research should be pursued with the goal of stabilizing or improving the vision, rather than reducing tumor volume. The growing understanding of the unique cellular and molecular characteristics of NF1-OPG, coupled with the recent publication of promising clinical studies, raise hope for a shift towards precision medicine and targeted therapies as a first-line treatment.

[Clinical diagnosis and treatment of optic nerve glioma: a review].

Optic nerve glioma (ONG) is a relatively rare central nervous system tumor that mainly affects children and adolescents. It can be classified into sporadic and neurofibromatosis type 1 (NF1)-associated types. The histological type is mainly a low-grade pilocytic astrocytoma. The typical clinical manifestations are visual impairment and painless eye protrusion, and the imaging features mainly present as fusiform swelling or irregular masses. Chemotherapy is still the first-line treatment for ONG, and other treatment options include radiotherapy, surgical resection, and molecular targeted therapy. Screening and monitoring of NF1 patients are also crucial. The prognosis of ONG is difficult to predict, and close monitoring and timely effective intervention are necessary.

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.

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.

Precocious and accelerated puberty in children with neurofibromatosis type 1: results from a close follow-up of a cohort of 45 patients.

PURPOSE: Central precocious puberty (CPP) in neurofibromatosis type 1 (NF1) occurs mainly in association with optic pathway glioma (OPG), but it can also develop in the absence of OPG. The aim of this study was to analyze the prevalence of puberty disorders in children with NF1 and its association with OPG and its location. METHODS: A retrospective study of 45 children with NF1 (68.9% boys) followed at our center between 2008 and 2020 was conducted. A cerebral MRI scan was performed in all children. We analyzed auxological, laboratory, and imaging data of children with CPP or accelerated puberty (AP). Treatments used for CPP/AP and their effect on height were also evaluated. RESULTS: The prevalence of puberty disorders in our cohort was 17.8% (male to female ratio of 7:1). CPP and AP were diagnosed in 8/45 (17.8%) NF1 children. Among children with puberty disorders, 5/8 (62.5%) had an OPG with chiasm involvement, 1/8 (12.5%) had an isolated optic nerve tumor, and 2/8 (25%) did not have any evidence of OPG on MRI. Fisher's exact test showed an association between CPP/AP and chiasm OPG (p = 0.025). Treatment with triptorrelin was initiated in 5/8 children, of whom four attained final predicted height. CONCLUSION: Our study confirms the higher prevalence of CPP/AP in NF1 patients, as well as an association between chiasm OPG and puberty disorders. However, CPP/AP also occurred in the absence of OPG with an incidence of 9.1%. Comprehensive evaluation of every child with NF1 regardless of the presence of OPG is therefore essential.

Multiple sclerosis in a child with neurofibromatosis type I - clinical management of a challenging case.

A 13-year-old girl with neurofibromastosis (NF1) was admitted to the Department of Paediatric Haematology, Oncology and Transplantology due to progressive vision loss in September 2018. The patient was diagnosed with optic nerve gliomas and chemotherapy was initiated. During the treatment, the girl experienced muscle weakness in the lower limbs, and uncharacteristic lesions were detected in the spinal cord. Eventually, the girl was diagnosed with MS. The described case is one of the few reports of a child with coexisting NF1 and MS. The coincidence of these diseases is unusual and requires a multidisciplinary approach. Vision impairment in patients suffering from NF1 is typically associated with optic nerve gliomas, although it can be caused by other factors, such as MS, which is proven to have a higher prevalence in the NF1 population. Extensive ophthalmological diagnostics may not be conclusive, thus there is a need for the thorough neurological evaluation of patients with NF1 and visual deficits.

The Utility of Early Brain MRI for Patients with Neurofibromatosis Type 1 and Optic Pathway Glioma: A Long-Term Follow-Up in a Tertiary Referral Hospital.

Screening studies have shown detection of optic pathway gliomas (OPGs) in 8 to 31% of children with neurofibromatosis type 1 (NF1). Many of those affected show prolonged indolent phases, but others develop vision disturbances even before diagnosis and treatment. We assessed the clinical presentation at diagnosis, location, natural progression, and risk factors for impaired vision of OPG. The clinical database of the NF1 multidisciplinary clinic of Schneider Children's Medical Center of Israel was reviewed for all patients diagnosed and followed with NF1 during 2007 to 2019. OPG was diagnosed by hyperintensity and thickening along the optic pathway on T2-weighted brain magnetic resonance imaging (MRI), with or without contrast enhancement. Of 257 children with NF1 who underwent MRI, 57 (22%) were diagnosed with OPG; 31 (54%) were females. Twenty-five (44%) had familial NF1. Fifteen (26%) who exhibited tumor progression and worsening in ophthalmic examinations required treatment. Post-chiasmatic glioma was a predictive factor for treatment (p < 0.05), whereas MRI done later and female gender were not significant. Four patients who eventually needed therapy had normal ophthalmic examinations at least 1 year prior to their first MRI. For 6 (40%) of the patients treated, vision continued to worsen. Our findings demonstrate that normal ophthalmic examinations do not always exclude OPG in children with NF1. Early brain MRI before age 36 months may detect OPG, lead to better follow-up and early treatment, and help improve vision outcome.

Treatment during a developmental window prevents NF1-associated optic pathway gliomas by targeting Erk-dependent migrating glial progenitors.

The mechanism of vulnerability to pediatric low-grade gliomas (pLGGs)-the most common brain tumor in children-during development remains largely unknown. Using mouse models of neurofibromatosis type 1 (NF1)-associated pLGGs in the optic pathway (NF1-OPG), we demonstrate that NF1-OPG arose from the vulnerability to the dependency of Mek-Erk/MAPK signaling during gliogenesis of one of the two developmentally transient precursor populations in the optic nerve, brain-derived migrating glial progenitors (GPs), but not local progenitors. Hyperactive Erk/MAPK signaling by Nf1 loss overproduced GPs by disrupting the balance between stem-cell maintenance and gliogenesis of hypothalamic ventricular zone radial glia (RG). Persistence of RG-like GPs initiated NF1-OPG, causing Bax-dependent apoptosis in retinal ganglion cells. Removal of three Mek1/Mek2 alleles or transient post-natal treatment with a low-dose MEK inhibitor normalized differentiation of Nf1-/- RG-like GPs, preventing NF1-OPG formation and neuronal degeneration. We provide the proof-of-concept evidence for preventing pLGGs before tumor-associated neurological damage enters an irreversible phase.

Targeted genetic and molecular therapies in neurofibromatosis - A review of present therapeutic options and a glimpse into the future.

Neurofibromatosis type 1, the most common phakomatoses, can present with a host of signs and symptoms, usually involving the skin and the peripheral nervous system. It is characterized by a mutation in the neurofibromatosis type 1 gene on chromosome 17q11.2 that codes for the protein neurofibromin. Neurofibromin acts as a tumor suppressor gene by inhibiting rat sarcoma (Ras) activity and its deficiency leads to increased Ras activity, cellular proliferation and tumor formation. This review was conducted to analyze the various targeted therapies at the genetic and molecular level employed to manage the tumors and other clinical presentations associated with neurofibromatosis type 1. Twenty-eight studies of treatment modalities for the conditions associated with neurofibromatosis and which involved either targeted gene therapy or molecular level therapies, including the latest advances, were included in this review. Mitogen-activated protein kinase kinase inhibition, mammalian target of Rapamycin inhibition and Tyrosine kinase inhibition, represent some of the newer treatment options in this category. Although there are a number of trials for providing therapeutic options at the genetic and molecular level for the various physical and psychological morbidities associated with neurofibromatosis type 1, most of them are in the preclinical stage. Increased clinical trials of the molecules and gene therapies could significantly help in managing the various chronic and sometimes, life-threatening conditions associated with neurofibromatosis 1 and these will probably represent the preferred treatment direction of the future.

Vision Outcomes for Pediatric Patients With Optic Pathway Gliomas Associated With Neurofibromatosis Type I: A Systematic Review of the Clinical Evidence.

Children with neurofibromatosis type I (NF1) have a higher predisposition for low-grade astrocytomas of the optic pathway, commonly referred to as optic pathway gliomas (OPGs). OPGs can result in visual deterioration. Treatment outcomes in OPG-NF1 management are often reported around tumor stabilization. We sought to compare vision outcomes associated with different OPG treatment strategies to inform about this important functional metric. A meta-analysis exploring the different modalities to treat children with OPG-NF1 was conducted following Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines using multiple databases. Of the 113 articles identified in the search, 23 full text articles, representing 564 patients, were included for review. These articles included retrospective, prospective, and randomized controlled studies on observation (n=9), chemotherapy (n=19), radiation therapy (n=6), and surgery (n=7). Of the patients undergoing observation, 87% (60/69) demonstrated stable acuity. In the chemotherapy studies, 27.3% (72/264) demonstrated improved acuity/visual field and/or visual-evoked potential amplitudes, 39.4% (104/264) stable acuity, and 33.3% (88/264) deterioration. Both the radiation and surgical treatments reported worsening acuity at 90.9% (10/11) and 73.3% (11/15), respectively. Causal associations are not known. Indications for and timing of treatment choice warrant larger scale study to provide further understanding.

Neurofibromatosis Type 1-Associated Optic Pathway Glioma in Children: A Follow-Up of 10 Years or More.

PURPOSE: This study reports on neurofibromatosis type 1 (NF1)-associated optic pathway gliomas (OPGs) and a follow-up period of at least 10 years in a cohort of children. OPGs are a common manifestation of NF1 and can cause significant visual morbidity. Long-term follow-up in children with NF1-associated OPGs has not been reported previously. DESIGN: Retrospective observational case series. METHODS: This study included children with a documented follow-up of at least 10 years. Three final outcomes were evaluated: visual acuity (VA) per eye (i.e., in the more severely affected eye), VA per patient (i.e., VA when both eyes were open), and the presence of optic nerve head pallor. RESULTS: A total of 45 children were included, followed for a mean of 14 years (range, 10-21 years). At the end of follow-up, abnormal VA (considered moderate to severe impairment) in the more severely affected eye was present in 36% of the patients and in both eyes in 11%. Optic nerve head pallor of 1 or both nerves was present in 62%. In multivariate analysis, only initial VA and optic nerve head appearance at presentation were found to predict the final outcomes. All patients, except for 1, were asymptomatic at presentation and had normal VA and nerves that appeared normal, preserved their good vision in both eyes. Only 1 patient, who had normal VA and normal appearing nerves at presentation, had moderate to severe VA loss at long term follow-up. CONCLUSIONS: In this study, children with NF1-associated OPG whose examination signs and symptoms were normal had a normal initial examination and excellent long-term visual and anatomical outcomes. VA and the appearance of the optic nerve head at presentation predict long-term outcome.

NF1 optic pathway glioma: analyzing risk factors for visual outcome and indications to treat.

BACKGROUND: The aim of the project was to identify risk factors associated with visual progression and treatment indications in pediatric patients with neurofibromatosis type 1 associated optic pathway glioma (NF1-OPG). METHODS: A multidisciplinary expert group consisting of ophthalmologists, pediatric neuro-oncologists, neurofibromatosis specialists, and neuro-radiologists involved in therapy trials assembled a cohort of children with NF1-OPG from 6 European countries with complete clinical, imaging, and visual outcome datasets. Using methods developed during a consensus workshop, visual and imaging data were reviewed by the expert team and analyzed to identify associations between factors at diagnosis with visual and imaging outcomes. RESULTS: Eighty-three patients (37 males, 46 females, mean age 5.1 ±â€…2.6 y; 1-13.1 y) registered in the European treatment trial SIOP LGG-2004 (recruited 2004-2012) were included. They were either observed or treated (at diagnosis/after follow-up).In multivariable analysis, factors present at diagnosis associated with adverse visual outcomes included: multiple visual signs and symptoms (adjusted odds ratio [adjOR]: 8.33; 95% CI: 1.9-36.45), abnormal visual behavior (adjOR: 4.15; 95% CI: 1.20-14.34), new onset of visual symptoms (adjOR: 4.04; 95% CI: 1.26-12.95), and optic atrophy (adjOR: 3.73; 95% CI: 1.13-12.53). Squint, posterior visual pathway tumor involvement, and bilateral pathway tumor involvement showed borderline significance. Treatment appeared to reduce tumor size but improved vision in only 10/45 treated patients. Children with visual deterioration after primary observation are more likely to improve with treatment than children treated at diagnosis. CONCLUSIONS: The analysis identified the importance of symptomatology, optic atrophy, and history of vision loss as predictive factors for poor visual outcomes in children with NF1-OPG.

Neurofibromatosis 1-associated optic pathway gliomas.

BACKGROUND: Optic Pathway Gliomas (OPG) are the most common brain tumor in Neurofibromatosis 1 patients (NF1). They are found along the optic pathway and may involve the optic nerves, chiasm, retro-chiasmatic structures, and the optic radiations. NF1 associate OPG (NF1-OPG) have variable presentation, disease course and response to treatment. The optimal management is patient-specific and should be tailored by a multidisciplinary team. Age, sex, histology, and molecular markers may be important factors in the individualized decision-making process. Chemotherapy is the first-line treatment in cases of progressive tumors, and visual preservation is the main goal of treatment. PURPOSE: In this paper we will review the disease, practical management, and recent advances of NF1-OPG.

A systematic review of ongoing clinical trials in optic pathway gliomas.

INTRODUCTION: Optic pathway gliomas (OPGs), also known as Visual Pathway Gliomas, are insidious, debilitating tumours. They are most commonly WHO grade 1 pilocytic astrocytomas and frequently occur in patients with neurofibromatosis type 1. The location of OPGs within the optic pathway typically precludes complete resection or optimal radiation dosing, hence outcomes remain poor compared to many other low-grade gliomas. The aim of this systematic review was to formulate a comprehensive list of all current ongoing clinical trials that are specifically looking at clinical care of OPGs in order to identify trends in current research and provide an overview to guide future research efforts. METHODS: This systematic review was conducted in line with the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines. The Cochrane Controlled Register of Trials (CENTRAL) and ClinicalTrials.gov were searched. Inclusion and exclusion criteria were applied and final results were reviewed. RESULTS: 501 clinical trials were identified with the search strategy. All were screened and eligible studies extracted and reviewed. This yielded 36 ongoing clinical trials, 27 of which were pharmacological agents in phase I-III. The remaining trials were a mixture of biological agents, radiation optimisation, diagnostic imaging, surgical intervention, and a social function analysis. CONCLUSION: OPG is a complex multifaceted disease, and advances in care require ongoing research efforts across a spectrum of different research fields. This review provides an update on the current state of research in OPG and summarises ongoing trials.

Current treatment of optic nerve gliomas.

PURPOSE OF REVIEW: Optic pathway gliomas are low-grade neoplasms that affect the precortical visual pathway of children and adolescents. They can affect the optic nerve, optic chiasm, optic tracts and radiations and can either be sporadic or associated with neurofibromatosis type one. Gliomas isolated to the optic nerve (ONG) represent a subgroup of optic pathway gliomas, and their treatment remains controversial. New developments in ONG treatment have emerged in recent years, and it is necessary for clinicians to have a current understanding of available therapies. RECENT FINDINGS: The current review of the literature covers the background of and recent developments in ONG treatment, with a focus on standard chemotherapy, new molecularly targeted therapies, radiation therapy and surgical resection and debulking. SUMMARY: Although standard chemotherapy remains the mainstay of ONG treatment, newer molecularly targeted therapies such as mitogen-activated protein kinase kinase inhibitors and bevacizumab represent a promising new treatment modality, and clinical studies are ongoing.