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Asia-Pacific Journal of Ophthalmology... 2019Neurofibromatosis type 1 is an autosomal dominant neurocutaneous disorder affecting 1 in 3000 births. This familial tumor predisposition syndrome is diagnosed clinically... (Review)
Review
Neurofibromatosis type 1 is an autosomal dominant neurocutaneous disorder affecting 1 in 3000 births. This familial tumor predisposition syndrome is diagnosed clinically and affects the skin, bones, and nervous system. Malignant tumors can arise in childhood or adulthood and are the most common cause of mortality in this population. Early diagnosis and management led by a multidisciplinary team remains the standard of care, particularly in the management of optic pathway glioma. Emerging concepts in the genetic patterns of this condition have led to the introduction of new treatment modalities that target the mitogen-activated protein kinase and the mammalian target of rapamycin pathways. In this review, the role of the ophthalmologist and approach to screening for optic pathway glioma are outlined based on previous recommendations. Updates on choroidal involvement, as a diagnostic criterion, will also be discussed, further highlighting the pivotal role of the ophthalmologist in the diagnosis and management of this complex condition.
Topics: Antineoplastic Agents; Choroid; Humans; Mass Screening; Neurocutaneous Syndromes; Neurofibromatosis 1; Neurofibromin 1; Ophthalmologic Surgical Procedures; Optic Nerve Glioma; Protein Kinase Inhibitors
PubMed: 30387339
DOI: 10.22608/APO.2018182 -
Arquivos Brasileiros de Oftalmologia 2022This article reports the case of an 11-year-old male patient with a history of proptosis and low progressive visual acuity in the left eye. He presented with a best...
This article reports the case of an 11-year-old male patient with a history of proptosis and low progressive visual acuity in the left eye. He presented with a best corrected visual acuity of 20/25 in the right eye and light perception in the left eye. Exotropia and limitation in adduction were observed in the left eye. On automated perimetry, inferiortemporal quadrantopsia was observed in the right eye, while total scotoma was observed in the left eye. On magnetic resonance imaging, there was an expansive lesion in the left optic nerve, extending to the brainstem with chiasmatic involvement. This article aims to report a case of optic pathway glioma, as well as to discuss its clinical findings and their interconnection with the current literature.
Topics: Male; Humans; Child; Optic Nerve; Optic Nerve Glioma; Vision Disorders; Visual Field Tests; Eye; Magnetic Resonance Imaging
PubMed: 35857979
DOI: 10.5935/0004-2749.2021-0246 -
Orphanet Journal of Rare Diseases Nov 2021Low-grade optic pathway glioma (OPG) develops in 15-20% of children with neurofibromatosis type 1 (NF1). OPGs are symptomatic in 30-50% and one-third of these require...
BACKGROUND
Low-grade optic pathway glioma (OPG) develops in 15-20% of children with neurofibromatosis type 1 (NF1). OPGs are symptomatic in 30-50% and one-third of these require treatment. A few studies have suggested female sex as a risk factor for visual impairment associated with NF1-OPG. This descriptive study investigated the correlation between NF1-OPG growth, sex and visual impairment.
METHOD
We based our cross-sectional study on a systematic, retrospective data collection in a NF1 cohort of children and adolescents below 21 years of age followed at Center for Rare Diseases, Aarhus University Hospital, Denmark. For each patient with OPG a medical chart review was performed including demographics, ophthalmological examinations and magnetic resonance imaging (MRI) of OPG.
RESULTS
Of 176 patients with NF1 (85 females, 91 males), we identified 21 patients with OPG (11.9%) with a preponderance of females, p = 0.184. Eight females (62%) and one male (13%) had visual impairment at the last ophthalmological evaluation. Five out of 21 children with OPG (24%) underwent diagnostic MRI because of clinical findings at the ophthalmological screening. Nine children (43%) had symptoms suggestive of OPG and seven (33%) experienced no OPG-related symptoms before the diagnostic MRI. Of eight children diagnosed with OPG ≤ two years of age, one had visual impairment. Of 13 children diagnosed > two years of age, eight had visual impairment; in each group, four of the children were treated with chemotherapy. The study suggested no correlation between NF1-OPG growth and sex.
CONCLUSION
Our data suggest sex as a risk factor for visual impairment, while an OPG diagnose ≤ two years of age was a protective factor for visual impairment. Females with NF1-OPG had a higher prevalence of visual impairment outcome compared to males. Interestingly, our data also suggest a better response to treatment in children with OPG diagnosed ≤ two years of age compared to older children. The findings in our study suggest sex as a potential prognostic factor for visual impairment.
Topics: Adolescent; Child; Cross-Sectional Studies; Female; Humans; Magnetic Resonance Imaging; Male; Neurofibromatosis 1; Optic Nerve Glioma; Retrospective Studies
PubMed: 34809690
DOI: 10.1186/s13023-021-02121-8 -
Frontiers in Surgery 2022Clinical and diagnostic evaluation in the follow-up of optic glioma patients with neurofibromatosis type 1 (NF-1) can be difficult. Determining whether and when to... (Review)
Review
PURPOSE
Clinical and diagnostic evaluation in the follow-up of optic glioma patients with neurofibromatosis type 1 (NF-1) can be difficult. Determining whether and when to provide treatment is a significant challenge in best managing these patients. Update on current information and future directions in management is included in this review.
CURRENT PRACTICE
NF-associated optic pathway gliomas (OPGs) present a significant management challenge with high stakes for visual outcomes. Monitoring vision and diagnostic tests are challenging in patients of a younger age. Regardless of whether few or many optic gliomas are encountered during clinical practice.
SUMMARY
This review of optic gliomas-NF1-associated gliomas includes the current approach and knowledge of OPG-NF1 and future directions in OPG-NF1 management. This includes the ongoing Multicenter Natural History Study and other clinical trials and outcomes in NF-1 patients with OPG.
PubMed: 36117804
DOI: 10.3389/fsurg.2022.908573 -
Cancers Nov 2019Type 1 neurofibromatosis (NF1) is a dominantly inherited condition predisposing to tumor development. Optic pathway glioma (OPG) is the most frequent central nervous... (Review)
Review
Type 1 neurofibromatosis (NF1) is a dominantly inherited condition predisposing to tumor development. Optic pathway glioma (OPG) is the most frequent central nervous system tumor in children with NF1, affecting approximately 15-20% of patients. The lack of well-established prognostic markers and the wide clinical variability with respect to tumor progression and visual outcome make the clinical management of these tumors challenging, with significant differences among distinct centers. We reviewed published articles on OPG diagnostic protocol, follow-up and treatment in NF1. Cohorts of NF1 children with OPG reported in the literature and patients prospectively collected in our center were analyzed with regard to clinical data, tumor anatomical site, diagnostic workflow, treatment and outcome. In addition, we discussed the recent findings on the pathophysiology of OPG development in NF1. This review provides a comprehensive overview about the clinical management of NF1-associated OPG, focusing on the most recent advances from preclinical studies with genetically engineered models and the ongoing clinical trials.
PubMed: 31739524
DOI: 10.3390/cancers11111790 -
Journal of Clinical Medicine Oct 2023In this paper, the authors present a clinical picture of the diagnosis and current treatment regimens of optic pathway glioma in the pediatric population, with an... (Review)
Review
UNLABELLED
In this paper, the authors present a clinical picture of the diagnosis and current treatment regimens of optic pathway glioma in the pediatric population, with an emphasis on the role of an ophthalmic diagnosis in the differentiation and monitoring of lesions. Glioma is the most common optic nerve tumor in children.
MATERIAL
Articles in PubMed, Scholar and Website were reviewed, taking into account current standards of management related to sporadic or NF1-related optic glioma, epidemiology, location, course of the disease, clinical manifestations, histological types of the tumor, genetic predisposition, diagnostic ophthalmic tests currently applicable in therapeutic monitoring of the tumor, neurological diagnosis, therapeutic management and prognosis. The importance of current screening recommendations, in line with standards, was emphasized.
RESULTS
Glioma occurs in children most often in the first decade of life. Initially, they may be asymptomatic, and clinically ophthalmic changes are associated with the organ of vision or with systemic changes. Gliomas associated with the mutation have a better prognosis for sporadic gliomas. Diagnosis includes radiological imaging methods/MRI/ophthalmology/OCT and visual acuity log MAR assessment. The basis of treatment is clinical observation. In the case of disease progression, surgical treatment, chemotherapy and targeted therapy are used.
CONCLUSION
Further research into novel techniques for detecting gliomas would allow for early monitoring of the disease.
PubMed: 37959175
DOI: 10.3390/jcm12216709 -
European Review For Medical and... Jun 2023Neurofibromatosis type 1 (NF1) is an autosomal dominant genetic disorder associated with an increased risk of developing a variety of benign and malignant tumors.... (Randomized Controlled Trial)
Randomized Controlled Trial
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.
Topics: Mice; Animals; Humans; Child; Neurofibromatosis 1; Vascular Endothelial Growth Factor A; Optic Nerve Glioma; TOR Serine-Threonine Kinases; Nerve Growth Factors
PubMed: 37401302
DOI: 10.26355/eurrev_202306_32804 -
Ceska a Slovenska Oftalmologie :... 2019Evaluate the effectiveness of treatment of patients with optic pathway glioma.
PURPOSE
Evaluate the effectiveness of treatment of patients with optic pathway glioma.
MATERIALS AND METHODS
Comparison of literature research on neurofibromatosis and optic pathway glioma with a cohort of pediatric patients treated at the Childrens Ophthalmology Clinic of the University Hospital in Brno from January 2013 until June 2018.
DISCUSSION
The main challenge of this and other retrospective studies is variable intervals between ophthalmologic examinations. In some pediatric patients it is also difficult to objectively assess visual functions. The main risk factors are age at the time of treatment and tumor localization. Tumor progression itself does not always correlate with worse visual acuity outcomes, and it remains to be evaluated whether some patients would be better off without treatment. As of now, there are no clinical biomarkers able to predict impending visual acuity loss.
CONCLUSION
The cohort outcome agrees with literature. Chemotherapy remains a treatment of choice and its most likely outcome is visual acuity stabilization. In order to properly evaluate the treatments effectiveness, better collaboration between medical specialists and regular standardized ophthalmology examinations are required.
Topics: Child; Humans; Neurofibromatosis 1; Optic Nerve Glioma; Retrospective Studies; Vision Disorders; Visual Acuity
PubMed: 32397722
DOI: 10.31348/2019/4/4 -
Neurologia Jun 2022Neurofibromatosis type 1 (NF1) is a progressive multisystem disorder following an autosomal dominant inheritance pattern that presents with multiple neurological... (Review)
Review
INTRODUCTION
Neurofibromatosis type 1 (NF1) is a progressive multisystem disorder following an autosomal dominant inheritance pattern that presents with multiple neurological manifestations.
METHODS
We reviewed medical histories of patients with NF1 followed up at our hospital's paediatric neurology department from May 1990 to 31 December 2018. We collected data on neurological symptoms.
RESULTS
A total of 128 patients with NF1 were identified. Mean age (SD) at NF1 diagnosis was 4.43 (3.38) years (range, 0.5-14.5 years). There was a slight female predominance (53.1%). Macrocephaly (head circumference over 2 SDs above average for age) was present in 37.5% of cases. Attention-deficit/hyperactivity disorder was recorded in 28.9% of patients (37): combined type in 20 patients, predominantly inattentive in 15, and predominantly impulsive/hyperactive in 2. Other manifestations included headache (18.6%), cognitive impairment (7.8%), motor deficit (6.2%), and epilepsy (4.68%). Brain MRI was performed in 85 patients, revealing T2-weighted hyperintensities in the basal ganglia and/or cerebellum in 60 patients (70.5%), Chiari malformation type 1 in 4 cases, and arachnoid cysts in 3. Optic nerve gliomas were identified by MRI in 22 patients (25.8%). Other MRI findings included plexiform neurofibromas (9.3%) and central nervous system gliomas (3.1%).
CONCLUSIONS
The neurological manifestations identified in our sample are consistent with those reported in the literature. Effective transfer strategies from paediatric neurology departments and subsequent clinical follow-up by adult neurology departments are needed to prevent loss to follow-up in adulthood.
Topics: Adolescent; Adult; Attention Deficit Disorder with Hyperactivity; Child; Child, Preschool; Epilepsy; Female; Headache; Humans; Infant; Magnetic Resonance Imaging; Male; Neurofibromatosis 1
PubMed: 35672119
DOI: 10.1016/j.nrleng.2019.05.008 -
Frontiers in Medicine 2022Optic tract lesions (OTL) are often difficult to diagnose. We suggest an algorithm to simplify the often-challenging diagnosis of OTL. Clinical and imaging data were...
Optic tract lesions (OTL) are often difficult to diagnose. We suggest an algorithm to simplify the often-challenging diagnosis of OTL. Clinical and imaging data were retrospectively collected from the electronic files of 6 patients diagnosed with OTL at a tertiary medical center in 2016-2020. The series included 4 children and 2 adults with an OTL caused by a glioma ( = 5) or motor vehicle accident ( = 1). Magnetic resonance imaging (MRI) revealed a suprasellar glioma involving the chiasm and tract alone (n = 1) and the ipsilateral optic nerve (n = 2) and only optic tract (3). Perimetry showed incongruent homonymous hemianopia in 3 patients. In two patients, perimetry could only be performed in one eye, and demonstrated hemianopia. In one patient perimetry was unreliable. Fundus examination revealed bow-tie atrophy in all patients. On optical coherence tomography (OCT) of the peripapillary retinal nerve fiber layer (RNFL) horizontal thinning was observed in the contralateral eye ( = 6). By presenting the information in a predefined order-visual field damage, OCT RNFL thickness, and MRI-the diagnosis could be easily reached even in children, and when other structures like the chiasm were involved. Fundus photographs easily detect bow tie atrophy in children. Systematic presentation of the data in a predefined order can ease the diagnostic process of OTLs.
PubMed: 36388882
DOI: 10.3389/fmed.2022.1029829