Background

Optic nerve sheath gliomas (ONSG) are rare tumors that primarily affect the optic nerve and its surrounding sheath. Gliomas, in general, are tumors that arise from glial cells, which supportive cells in the central nervous system. Optic nerve sheath gliomas are most diagnosed in children, often presenting before the age of 10. They are a type of low-grade glioma, typically classified as pilocytic astrocytomas.

These tumors may arise sporadically or, in some cases, be associated with genetic conditions such as neurofibromatosis type 1 (NF1). Patients with optic nerve sheath gliomas may present with visual disturbances, including vision loss or changes in visual acuity. Proptosis (bulging of the eye), optic nerve head swelling, and strabismus (misalignment of the eyes) are also common clinical features. The slow-growing nature of these tumors can make diagnosis challenging, as symptoms may be subtle and progress over time. 

Epidemiology

• Age Distribution: ONSGs are most diagnosed in children, with the majority of cases occurring in the first decade of life. The peak age of onset is often between 2 and 5 years old. The rarity of these tumors in adults makes them primarily a pediatric condition. 
• Association with Neurofibromatosis Type 1 (NF1): There is a notable association between optic nerve sheath gliomas and neurofibromatosis type 1 (NF1), characterized by development of multiple neurofibromas (benign tumors) throughout the nervous system. In individuals with NF1, the risk of developing an optic nerve sheath glioma is increased. However, not all cases of ONSG are associated with NF1. 
• Gender Predilection: Optic nerve sheath gliomas can affect both males & females, with no gender predilection reported in the literature. 
• Incidence and Prevalence: ONSGs are considered rare, accounting for a small percentage of all central nervous system tumors. The exact incidence and prevalence rates may vary, and the rarity of these tumors makes it challenging to establish precise epidemiological figures. 
• Bilateral Involvement: Bilateral optic nerve sheath gliomas can occur, particularly in the context of neurofibromatosis type 1. Bilateral involvement may further complicate visual outcomes. 
• Clinical Presentation: Patients with optic nerve sheath gliomas commonly present with visual disturbances, including vision loss or changes in visual acuity. Other clinical features may include proptosis (bulging of the eye), optic nerve head swelling, and strabismus (misalignment of the eyes). 
• Slow-Growing Nature: Optic nerve sheath gliomas tend to be slow-growing tumors, and symptoms may develop gradually over time. The indolent nature of these tumors can contribute to delays in diagnosis.

Anatomy

Pathophysiology

• Glioma Origin: ONSGs are gliomas, tumors that arise from glial cells, which are supportive cells in the central nervous system. In the case of ONSGs, they often originate from astrocytes, leading to their classification as astrocytomas. 
• Location and Infiltration: ONSGs primarily affect the optic nerve and its surrounding sheath. These tumors may infiltrate the optic nerve, causing enlargement and thickening. The location of the tumor within the optic nerve sheath can lead to compression of the optic nerve and interference with the transmission of visual signals. 
• Slow Growth: ONSGs are slow-growing tumors, and their indolent nature contributes to the insidious onset of symptoms. The gradual progression of the tumor may make early detection challenging. 
• Association with Neurofibromatosis Type 1 (NF1): ONSGs are often associated with neurofibromatosis type 1 (NF1), a genetic disorder caused by mutations in NF1 gene. NF1 is characterized by the development of multiple neurofibromas, and individuals with NF1 have an increased risk of developing ONSGs. The genetic alterations in NF1 contribute to the predisposition to tumor development in various parts of the nervous system. 
• Bilateral Involvement: ONSGs can occur unilaterally or bilaterally. In cases of bilateral involvement, both optic nerves may be affected. Bilateral tumors are more commonly associated with NF1. 

• Visual Impairment: The growth of ONSGs within the optic nerve and its sheath can lead to compression and damage to the nerve fibers. This can result in visual disturbances, including progressive vision loss, changes in visual acuity, and other visual abnormalities. 
• Optic Nerve Head Swelling: ONSGs can cause swelling of the optic nerve head (papilledema). The increased intracranial pressure associated with optic nerve sheath involvement may contribute to this swelling.

Etiology

• Neurofibromatosis Type 1 (NF1): One of the most significant associations with optic nerve sheath gliomas is neurofibromatosis type 1 (NF1), a genetic disorder caused by mutations in the NF1 gene. 
• Genetic Predisposition: While NF1 is a well-established genetic factor, there may be other genetic factors or mutations that contribute to the development of ONSGs in cases not associated with NF1. Ongoing research aims to identify additional genetic markers or predisposing factors that may increase the risk of ONSGs. 
• Spontaneous Mutations: In some cases, ONSGs may occur sporadically without a clear genetic predisposition. Spontaneous mutations or alterations in specific genes related to glial cell growth and regulation may contribute to the development of these tumors. 
• Cellular Changes and Gliomagenesis: Gliomagenesis refers to the process by which gliomas, including ONSGs, develop. The transformation of normal glial cells into tumor cells involves complex molecular and cellular changes. Dysregulation of cell cycle control, abnormal signalling pathways, and alterations in genes involved in cell growth and differentiation are contributors to gliomagenesis. 
• Environmental Factors: The environmental factors in ONSG development are not well-established. However, the specific environmental factors influencing the development of ONSGs require further investigation. 
• Inflammatory and Immune Responses: The role of inflammatory processes and immune responses in glioma development is an area of ongoing research. Immune system dysregulation or chronic inflammation in the central nervous system may contribute to the development of gliomas.

Genetics

Prognostic Factors

• Age: Younger age at the time of diagnosis is associated with a better prognosis. Optic nerve sheath gliomas often present in childhood, and pediatric patients may have a more favourable outcome compared to adults. 
• Extent of Tumor Involvement: The extent of tumor involvement, including the size and location of the tumor within the optic nerve and its sheath, is a crucial prognostic factor. Smaller, localized tumors may have a more favourable prognosis than larger or diffusely infiltrating tumors. 
• Bilateral Involvement: Bilateral optic nerve sheath gliomas, especially when associated with neurofibromatosis type 1 (NF1), may present unique challenges. Bilateral tumors can complicate treatment and may have a different prognosis compared to unilateral tumors. 
• Association with Neurofibromatosis Type 1 (NF1): ONSGs associated with NF1 may have different clinical behaviors. The presence of NF1 can influence the course of the disease and may be associated with a higher risk of complications. 
• Visual Function at Diagnosis: The initial level of visual function at the time of diagnosis is an important prognostic factor. Patients with less severe visual impairment at presentation may have a better prognosis compared to those with advanced visual deficits. 
• Rate of Tumor Growth: The rate of tumor growth, as assessed through imaging studies over time, can provide insights into the aggressiveness of the tumor. Slower-growing tumors may have a more favorable prognosis. 
• Recurrence and Progression: The recurrence of tumors or progression despite treatment is an adverse prognostic factor. Tumors that exhibit aggressive behavior or resistance to therapy may have a less favorable outcome.

Clinical History

Age at Presentation: ONSGs are most diagnosed in children, with the peak incidence typically occurring before the age of 10. Therefore, the clinical history often begins with the age of the patient at the time of initial presentation. 

Physical Examination

• Visual Acuity Testing: Measurement of visual acuity in each eye using standardized charts (e.g., Snellen chart). Changes in visual acuity can be indicative of optic nerve involvement. 
• Visual Field Examination: Assessment of visual fields to detect any peripheral vision loss or abnormalities. ONSGs can cause visual field defects, and perimetry is commonly used to evaluate these changes. 
• Pupillary Examination: Examination of pupillary reactions to light and accommodation. Optic nerve involvement may affect the afferent pupillary response, leading to abnormalities such as a relative afferent pupillary defect (RAPD). 
• Color Vision Testing: Assessment of color vision using color charts or pseudoisochromatic plates. Deficits in color vision may be present with optic nerve pathology. 
• Ocular Alignment and Motility: Evaluation of ocular alignment to identify any strabismus (misalignment of the eyes). ONSGs can cause strabismus due to pressure on the optic nerve and surrounding structures. 
• External Eye Examination: The external structures of the eye, including eyelids, conjunctiva, and the appearance of the globe. Proptosis (bulging of the eye) may be observed in some cases. 
• Ophthalmoscopy: Direct and indirect ophthalmoscopy to examine the optic nerve head and surrounding structures. ONSGs can cause optic nerve head swelling (papilledema), and changes in the appearance of the optic disc may be noted. 
• Palpation of Orbital Structures: Palpation of the orbital region to assess for any masses or abnormalities. Although ONSGs are not typically palpable, examination for signs of orbital involvement is important. 

Age group

Associated comorbidity

• Neurofibromatosis Type 1 (NF1): A significant proportion of ONSGs are associated with neurofibromatosis type 1 (NF1). In patients with NF1, the presence of multiple neurofibromas increases the risk of developing optic nerve sheath gliomas. 
• Other Genetic Conditions: Although less common, there may be cases of ONSGs associated with other genetic conditions or familial predispositions. A detailed family history is essential to identify any potential genetic factors. 

Associated activity

Acuity of presentation

• Visual Disturbances: Patients often present with visual symptoms, including decreased visual acuity, vision loss, or changes in visual fields. Visual disturbances are a hallmark of ONSGs due to the tumor’s impact on the optic nerve. 
• Proptosis and Strabismus: Some patients may also report proptosis (bulging of the eye) and strabismus (misalignment of the eyes), particularly if the tumor causes structural changes around the eye. 

Differential Diagnoses

• Optic Neuritis: Inflammatory conditions affecting optic nerve, often associated with demyelination. It can present with sudden vision loss, pain with eye movement, and changes in visual acuity. Multiple sclerosis is a common underlying cause of optic neuritis. 
• Optic Nerve Meningioma: Meningiomas originating from the optic nerve sheath can mimic ONSGs. These tumors may cause proptosis, optic nerve head swelling, and visual disturbances. Imaging studies, such as MRI, help differentiate meningiomas from gliomas. 
• Orbital Cellulitis: Infection involving the tissues surrounding the eye, including the optic nerve sheath. It can cause eye pain, swelling, and redness. Fever and systemic signs of infection may be present. 
• Idiopathic Intracranial Hypertension (IIH): Elevated intracranial pressure without an identifiable cause. IIH can lead to optic nerve head swelling (papilledema) and visual disturbances. Common in overweight females of childbearing age. 
• Ischemic Optic Neuropathy: Impaired blood flow to the optic nerve, leading to sudden vision loss or visual field defects. It may be arteritic or non-arteritic. 
• Congenital Optic Disc Anomalies: Congenital anomalies of optic disc, such as optic disc drusen or morning glory disc anomaly, may mimic optic nerve head swelling. Typically present since birth and may be identified on ophthalmoscopy. 
• Retinoblastoma: Intraocular tumor affecting the retina, particularly in children. It may present with leukocoria (white pupillary reflex), strabismus, or vision loss. Retinoblastoma can extend into the optic nerve and mimic the presentation of optic nerve tumors. 

Laboratory Studies

Imaging Studies

Procedures

Histologic Findings

Staging

Treatment Paradigm

Surgery:

Surgical intervention may be considered for optic nerve sheath gliomas that cause compression, significant visual impairment, or other symptoms. However, complete surgical removal is often challenging due to the delicate nature of the optic nerve and the infiltrative nature of these tumors. 

Radiation Therapy: 

• Conventional Radiation: External beam radiation therapy may be used to target the tumor and control its growth. It is particularly considered when surgery is not feasible, and the tumor is causing significant visual deficits. 
• Proton Beam Therapy: Proton beam therapy, with its ability to precisely target tumors and spare surrounding tissues, may be considered to reduce the risk of radiation-induced damage to adjacent structures. 

Chemotherapy:

Chemotherapy is often considered for optic nerve sheath gliomas, especially in cases where the tumor is progressive or causing visual impairment. Agents such as carboplatin, vincristine, and vinblastine are among those commonly used. The choice of chemotherapy may vary based on the specific characteristics of the tumor and the patient’s overall health. 

Targeted Therapies:

Emerging targeted therapies, including those aimed at specific molecular pathways involved in glioma growth, are being investigated in clinical trials. These therapies aim to provide more precise and effective treatment options. 

Supportive Care:

Supportive care measures focus on managing symptoms and optimizing the patient’s quality of life. This may include addressing pain, managing side effects of treatments, and providing psychological support. 

Long-Term Follow-Up:

Due to the recurrence and the indolent nature of these tumors, long-term follow-up is essential. Regular monitoring with imaging studies and ophthalmologic evaluations helps detect any changes in tumor size or visual function. 

by Stage

by Modality

Chemotherapy

Radiation Therapy

Surgical Interventions

Hormone Therapy

Immunotherapy

Hyperthermia

Photodynamic Therapy

Stem Cell Transplant

Targeted Therapy

Palliative Care

non-pharmacological-treatment-of-optic-nerve-sheath-gliomas

Lifestyle modifications: 

• Healthy Diet: A balanced diet to support overall health. While there is no specific diet for treating ONSGs, a healthy diet can lead to overall well-being. 
• Physical Activity: The regular physical activity as recommended by healthcare providers. Exercise can promote general health and may contribute to well-being. 
• Stress Management: Stress-reduction techniques, like mindfulness, meditation, or yoga, to cope with the emotional impact of the diagnosis and treatment. 
• Adequate Sleep: Ensure sufficient and quality sleep. Rest is important for overall health and may support the body’s healing processes. 
• Vision Rehabilitation: Work with rehabilitation specialists, such as occupational therapists or vision therapists, to optimize visual function and adapt to changes resulting from the tumor or its treatment. 
• Psychosocial Support: Seek psychosocial support through counselling, support groups, or other mental health services to address emotional and psychological aspects of living with an optic nerve sheath glioma. 
• Sun Protection: Wearing sunglasses with UV protection to shield the eyes from harmful ultraviolet rays. This is good eye care practice and may be particularly relevant in cases of eye tumors. 

Use of Chemotherapy in the treatment of Optic nerve sheath gliomas

Chemotherapy, including the use of vincristine and carboplatin, is one of the treatment modalities employed in the management of optic nerve sheath gliomas (ONSG).

Chemotherapy is often considered when surgical intervention is not feasible or when the tumor is causing significant visual impairment. Here is a brief overview of the use of vincristine and carboplatin in the treatment of ONSG: 

Vincristine: 

• Vincristine is a vinca alkaloid that interferes with microtubule formation during cell division. It disrupts the mitotic spindle, preventing proper separation of chromosomes and inhibiting cell proliferation. Vincristine is typically administered intravenously. 

Carboplatin: 

• Carboplatin is a platinum-based chemotherapy agent that forms DNA adducts, interfering with DNA replication and transcription. This leads to cell death. Carboplatin is usually administered intravenously. 

Use of <a class="wpil_keyword_link" href="https://medtigo.com/drug/bevacizumab/" title="Bevacizumab" data-wpil-keyword-link="linked">Bevacizumab</a> in the treatment of Optic nerve sheath gliomas

Bevacizumab specifically targets and inhibits vascular endothelial growth factor (VEGF). VEGF is a signaling protein which plays a crucial role in promoting angiogenesis, the process by which new blood vessels form.

Optic nerve sheath gliomas are characterized by slow growth and can cause compression of the optic nerve, leading to visual impairment. VEGF expression in tumors may contribute to angiogenesis and tumor growth.

Bevacizumab is considered in cases where other treatment options, such as surgery, radiation therapy, or conventional chemotherapy, may be less effective or associated with significant risks. 

Bevacizumab is typically administered intravenously. The specific dosage and frequency of administration are determined based on the patient’s individual characteristics, including age, overall health, and the extent of the tumor. 

Regular monitoring, including imaging studies (such as MRI), is conducted to assess treatment response and evaluate changes in tumor size. 

Bevacizumab may be associated with side effects, including hypertension, bleeding, and impaired wound healing. Close monitoring and management of these potential side effects are essential. 

surgical-therapies-involved-in-optic-nerve-sheath-gliomas

• Biopsy: Surgical biopsy is often performed to obtain a tissue sample for histological analysis, confirming the diagnosis of optic nerve sheath glioma. Biopsy may involve a stereotactic needle biopsy or open biopsy, depending on the location and size of the tumor. 
• Debulking: Debulking surgery involves removing a portion of the tumor to relieve compression on the optic nerve and surrounding structures. In some cases, debulking surgery may lead to partial improvement in visual function. 
• Resection (Partial): Partial resection aims to remove the tumor as possible without causing undue damage to the optic nerve or adjacent critical structures. The extent of resection depends on tumor location, size, and the surgeon’s assessment of feasibility. 
• Optic Nerve Decompression: Surgical decompression of optic nerve involves relieving pressure on the nerve to improve blood flow and potentially preserve or enhance visual function. Decompression may involve removing part of the bony canal (optic canal decompression) or releasing the surrounding sheath of the optic nerve. 
• Neurophysiological Monitoring: During surgery, neurophysiological monitoring may be employed to assess and monitor the functional integrity of the optic nerve and surrounding structures. 
• Neuronavigation: Neuronavigation systems may be used to provide real-time guidance for precise localization and navigation within the surgical field. Neuronavigation aids in optimizing the accuracy of surgical interventions, particularly in areas with complex anatomy. 

radiotherapy-involved-in-the-treatment-of-optic-nerve-sheath-gliomas

• External Beam Radiation Therapy (EBRT): EBRT is the most common form of radiotherapy for ONSG. It uses high-energy external beams to target and treat the tumor. Radiation is typically delivered in divided doses (fractions) over multiple sessions to minimize damage to surrounding healthy tissues. 
• Proton Beam Therapy: It is a type of external beam radiation that uses proton particles. Protons have unique properties that allow targeting of the tumor and minimizing radiation exposure to surrounding tissues. Proton therapy may be considered in ONSG to reduce the risk of optic nerve damage. 
• Brachytherapy: It involves the placement of radioactive sources directly within or close to the tumor. While less common for ONSG, it may be considered in specific cases. 
• Radiosurgery: Radiosurgery, such as Gamma Knife or CyberKnife, is a form of stereotactic radiosurgery that delivers precise and highly focused radiation to the tumor. 
• Optic Nerve Sparing Techniques: Special attention is paid to limiting radiation dose to the optic nerve and surrounding critical structures to minimize the risk of radiation-induced damage to vision. Advanced treatment planning techniques, such as three-dimensional conformal radiation therapy (3D-CRT) or intensity-modulated radiation therapy (IMRT), help tailor the radiation dose to the tumor while sparing adjacent healthy tissues. 

management-of-optic-nerve-sheath-gliomas

Acute Phase: 

• Diagnostic Evaluation: Initiate the diagnostic process, including clinical evaluation, imaging studies (MRI or CT scans), and, if necessary, biopsy for histological confirmation. 
• Symptomatic Management: Address acute symptoms, such as visual impairment, pain, or proptosis, through supportive measures and interventions to enhance quality of life. 
• Multidisciplinary Consultation: Engage a multidisciplinary team of neurologists, neurosurgeons, ophthalmologists, and oncologists to collaboratively determine the most appropriate treatment approach. 
• Emergency Interventions (if needed): Consider emergency interventions if there are urgent complications, such as severe visual impairment or signs of increased intracranial pressure. 

Chronic Phase: 

• Continued Monitoring: Implement a regular monitoring schedule with imaging studies (MRI) to assess tumor response to treatment and detect any changes in size or characteristics. 
• Visual Rehabilitation: If visual impairment persists or worsens, initiate visual rehabilitation strategies to enhance the patient’s adaptation to visual deficits. 
• Ongoing Symptom Management: Continue to manage chronic symptoms, such as pain or vision-related issues, through a combination of medical interventions and supportive care. 
• Adjustment of Treatment Plan: Based on the response to initial treatment, consider adjustments to the treatment plan, including modifications to radiation therapy, changes in chemotherapy agents, or additional surgeries if necessary. 
• Long-Term Follow-Up: Establish a long-term follow-up plan to monitor for potential recurrence, treatment-related complications, and the overall health of the patient.

Medication

Future Trends

Media Gallary

References

Optic Nerve Glioma – StatPearls

Current treatment of optic nerve gliomas -PMC