Optic Nerve Glioma

What is Optic Nerve Glioma?

Optic nerve gliomas are non-cancerous tumors that are a type of pilocytic astrocytomas. These tumors mainly occur in the optic nerve, the nerve that connects the eye to the brain, and account for about half of all such tumors, and 1.5% to 4% of all orbital (eye socket) tumors. Optic nerve gliomas, along with a type of tumor known as meningiomas, present challenges in diagnosis and treatment, as medical professionals are still learning about their typical progression and the best strategies for treatment.

There are only a few types of primary tumors, or tumors that start in the optic nerve, and they include not just optic nerve glioma, but also malignant optic nerve glioma, optic nerve sheath meningioma, a type of rare tumor called ganglioglioma, and primary lymphoma, a type of cancer that starts in the cells that fight infections. Despite being rare, they represent a range of conditions that have different properties and behaviors.

What Causes Optic Nerve Glioma?

Optic pathway gliomas are slow-growing tumors that develop in the sections of the optic pathways before they reach the brain’s cortex. These tumors can occur in various parts of the eye and brain, including the optic nerve, optic chiasm, optic tracts, optic radiations, or the hypothalamus. They may occur spontaneously or in conjunction with a condition called neurofibromatosis type 1 (NF1).

Because of this association with NF1, doctors usually recommend genetic testing for the disease. When optic pathway gliomas are linked to NF1, it generally means that a specific anti-tumor gene, called neurofibromin on chromosome 17q, was turned off, which in turn activates the RAS signaling pathways leading to the formation of RAS-induced tumors. When these tumors occur spontaneously, however, genetic changes involving a complexity called the BRAF-KIAA1549 fusion are commonly found.

Studies have shown that patients with NF1 tend to have a better prognosis – meaning their condition progresses more slowly and the quality of their vision remains better – than those with spontaneous gliomas. Therefore, regular eye exams and vision assessments are essential for all glioma patients. In very young patients, where a vision exam can be difficult, an alternative testing method known as an electrophysiological assessment may be required.

Risk Factors and Frequency for Optic Nerve Glioma

Optic pathway gliomas, a type of brain tumor, mainly affect children 10 and under, making up 3% to 5% of all childhood brain tumors. However, these tumors can actually occur at any age, from birth to 79. It’s worth noting that most cases (71%) happen within the first ten years of life and 90% are diagnosed within the first 20 years. The average age when people get diagnosed with optic gliomas is around 9 years old.

People with a condition called NF1 have a 15% to 20% risk of developing optic pathway gliomas. However, only 30% to 50% of these people will actually have symptoms. The number of people with NF1 who get optic nerve gliomas varies quite a bit, from 10% to 70%, but it’s around 29% on average.

Generally, males and females are equally likely to get optic pathway gliomas. But when the tumor is only on the optic nerve, 65% of patients are females while 35% are males. But when the tumor involves the optic chiasm, a part of the brain where the optic nerves cross, men and women are equally likely to be affected.

• 25% of the time, the tumors are only on the optic nerve.
• In 75% of cases, the tumor involves the optic chiasm.
• When the chiasm is involved, 40% will have their tumor extend to the hypothalamus or the third ventricle, which are other parts of the brain.

Signs and Symptoms of Optic Nerve Glioma

Children with optic gliomas, or tumors in the optic pathway, often show symptoms based on where the tumor is located. These symptoms can include things like a loss of vision, an eye bulging out of its socket (known as proptosis), or headaches and pain.

Most kids might not express a loss of vision, but 85% of patients with glioma experience it to some extent. In the long run, about 25% maintain relatively good vision while 60% have vision worse than 20/300. Eye doctors might notice certain changes in an eye exam like optic nerve atrophy and optic disc edema. Patients with tumors in certain parts of the optic pathway might exhibit these findings differently.

Proptosis is seen in 95% of patients with optic glioma, even though it’s less common if the tumor affects only a specific part of the optic pathway. In such cases, the optic nerve is almost always involved as well. Some eye movement limitations can be seen in a handful of patients as well.

Headaches are the most common symptom and appear in around 30% of patients. Other indications range from eye conditions such as nystagmus and strabismus to more general symptoms like nausea, dizziness, and developmental regression. As the tumor spreads, certain complications can arise that can affect hormone production and cause conditions like precocious puberty and growth hormone deficiency.

• Early vision loss (88% of patients)
• Optic disc swelling (35% of patients)
• Optic nerve head atrophy (59% of patients)
• Proptosis in orbital tumors (94% of patients)
• Proptosis in chiasmal tumors (22% of patients)
• Nystagmus (24% of patients)
• Hypothalamic signs (26% of patients)
• Increased intracranial pressure (27% of patients)

Testing for Optic Nerve Glioma

When investigating certain brain and eye conditions, doctors often use an imaging technique called magnetic resonance imaging (MRI). Research has shown that around 80% of patients show progression in their condition when viewed through MRI. This tool helps to identify any swelling in the optic nerve (which connects the eye to the brain), which is common in 80% of patients with optic nerve involvement. About a quarter of patients with a type of tumor called chiasmal glioma might also present enlargement of certain parts of their brain as showcased in their MRI tests. MRI has been proven to be more effective than another imaging technique, the computed tomography scan (CT scan), in evaluating certain types of tumors.

On an MRI, gliomas are types of tumors that typically show up as slightly dull or equally intense compared to the normal optic nerve. These tumors appear brighter than the optic nerve in another type of MRI called T2-weighted images. On the other hand, CT scans might reveal an expanded optic nerve or a location named “chiasm.” When taking a closer look, the enhancement after adding contrast is less than what you would find in conditions like optic nerve sheath meningiomas. In conditions like optic pathway gliomas, it’s not usual to detect calcifications, but it can occur.

Doctors also look at family history and perform genetic testing for a condition called neurofibromatosis, which affects the nervous system. A tissue sample or biopsy isn’t typically needed because the diagnosis is based on imaging results and clinical examination. However, genetic testing might become more useful as we develop therapies that are specifically targeted at certain genes.

Both optic nerve gliomas (a type of tumor) and meningiomas (another type of tumor) can cause the optic nerve to enlarge. Meningiomas have a distinctive characteristic known as “tram-tracks.” These are lines caused by a thickened optic nerve sheath (a protective layer around the nerve) that create a light space representing the residual optic nerve. Calcification, or the accumulation of calcium, can occur in 20% to 50% of meningiomas but is rare in gliomas. Meningiomas look brighter than the normal nerve on both T1- and T2-weighted MRI sequences, while an optic nerve glioma appears as equally bright or slightly dull on T1-weighted sequences and brighter on T2-weighted sequences.

Treatment Options for Optic Nerve Glioma

Gliomas are slow-growing tumors that can spread to neighbouring tissue, including around the optic nerve and the brain. While vision remains steady in most patients, about 40% may experience growth of the tumor. The only way to officially diagnose these tumors is by taking a small sample of it (biopsy) and examining the sample under a microscope.

Your healthcare team, which may include eye specialists, cancer doctors, plastic surgeons specialized in eye surgery, and radiation oncologists, will create a personalized treatment plan based on several factors. They’ll consider your symptoms, how the tumor behaves, changes in your vision, your medical history, the tumor’s genetic makeup, your age, and your personal preferences. Usually, treatment isn’t started right away unless the tumor causes significant vision problems or its growth accelerates.

In most patients, vision may get worse in the beginning and then stabilize. But even though vision has stabilized, the tumor might still grow. If that’s the case, it doesn’t mean the condition is worsening. Regular monitoring without aggressive treatment is common in such cases, yielding a good survival rate.

Here’s the general plan for managing different types of gliomas:

– Optic nerve glioma: If the tumor is stable, your healthcare team will watch it with regular eye exams and imaging tests. Surgery might be considered if vision loss occurs or the eyeball bulges forward (a condition called proptosis). If the tumor spreads towards the back, surgery may also be suggested to prevent it from reaching the optic chiasm or other tissues.

– Optic chiasm glioma: If the tumor is stable, you will undergo regular imaging tests. If the tumor grows in patients 10 years old or younger, chemotherapy might be considered. For patients older than 10, a combination of chemotherapy and radiotherapy may be recommended.

– Midbrain glioma: If the tumor is stable in patients who have had it for more than 10 years, doctors might suggest chemotherapy and radiotherapy. Similarly, in patients aged 10 or younger, chemotherapy might be suggested if the tumor is stable. If the tumor grows, a combination of chemotherapy and radiotherapy might be considered.

A less common and more aggressive type of glioma happens in older patients, often arising at the optic chiasm, which is usually bilateral, meaning it affects both sides. About 23% of these tumors can extend into the eye’s optic nerve, while 50% may spread to the back, to areas like the hypothalamus or the temporal lobe.

Patients with this aggressive type of glioma often experience fast vision loss, initially in one eye, then in both. This may lead to it being misdiagnosed as either anterior ischemic optic neuropathy or optic neuritis. Imaging tests like CT scans or MRI scans will often show enlargement and enhancement of the optic chiasm and involvement of intracranial nerves. As with other gliomas, a biopsy is the only way to confirm this diagnosis.

Unfortunately, neither surgery nor radiotherapy can significantly improve the outlook for this condition. However, in rare cases, combining these treatments with chemotherapy may slightly increase survival by a few months.

What else can Optic Nerve Glioma be?

Optic nerve gliomas can usually be identified correctly using MRI scans because they have distinct characteristics. Another condition, optic nerve sheath meningiomas, can sometimes be confused with optic nerve gliomas since they occur in the same place, but they do appear differently on MRI scans, and are not commonly seen in children. Thus, doctors should also think about other conditions that could look similar, such as:

• Meningioma
• Rhabdomyosarcoma
• Orbital lymphoma
• Benign lymphoproliferative lesions
• Neuroblastoma
• Epithelial tumors
• Inflammatory lesions
• Infectious lesions
• Metastasis of tumors from outside the eye

Surgical Treatment of Optic Nerve Glioma

When discussing the role of surgery in medicine, it often comes into play when a patient is experiencing worsening symptoms or in specific scenarios where a tumor is negatively affecting key areas of the body. For instance, if a patient is experiencing progressive loss of vision, severe swelling in the eye socket, heightened pressure in the skull, or when a tumor is posing a risk to the optic nerve, surgery may be considered. An “optic nerve glioma” is a type of tumor that doesn’t often spread or affect both eyes. Here, surgery can help reduce swelling and ease pain around the eye.

In cases where eye sight has already been impaired, the tumor can be removed. This is typically done through an orbital approach, in an effort to keep the eye and all the muscles around it intact, improving how it looks after the procedure. But it’s important to note that if surgery happens before vision loss, it could also lead to loss of vision.

The outcome of surgery can vary depending on the exact location of the tumor:

For gliomas (a type of tumor) confined only to the optic nerve, about 17% of patients may experience a return or worsening of the tumor if the tumor was not fully removed or if no treatment was provided. Among these patients, a small percentage (12%) may pass away due to the tumor spreading to the brain. However, the overall outlook for maintaining vision is positive with over 90% of patients having stable vision over time.

Fully removing the optic nerve gliomas through surgery, with or without additional radiotherapy treatment, can reduce the chance of death to nearly none. But it is important to remember that surgery does carry its own risk of vision loss. For tumors that have extended beyond the optic nerve and caused vision loss, surgery helps prevent further spread of the tumor and reduces the chance of death.

Gliomas that extend to the optic chiasm exhibit similar features as those confined to the eye’s optic nerve. If these tumors are left untreated for a period of 10 years, the mortality rate can be as high as 17%. The mortality rate can increase if the tumor starts invading surrounding tissues like the hypothalamus or third ventricle. Removing a part of the tumor might result in a high rate of the tumor returning or progressing (64%). Despite this, 80% of cases remain stable without treatment. Radiotherapy can be used to slow down the tumor’s growth in the chiasm without the risk of vision loss associated with surgery.

If gliomas extend to the optic chiasm and invade the hypothalamus, they become more dangerous. The risk of mortality in patients with these tumors goes up beyond 50% over a period of 15 years. Although radiotherapy and chemotherapy can help reduce the mortality rate, the recurrence or progression still occurs in about half of the cases.

It’s important to remember that surgery always carries potential risks. In this scenario, about 6% of people may pass away due to the surgery. Other complications can include diminished vision, hormonal imbalances, and problems with the hypothalamus function, which controls key functions such as blood pressure, body temperature, fluid/electrolyte balance, and body weight.

What to expect with Optic Nerve Glioma

Gliomas, or tumors, in the optic pathway in patients with Neurofibromatosis Type 1 (NF1- a genetic disorder that causes tumors to form on nerve tissue) generally have better chances of recovery. However, these chances can be influenced by factors like the method of patient selection and the tumor’s location. Many of these tumors might not grow or cause any symptoms throughout a patient’s life. Frequently, these tumors are discovered by accident in patients with NF1 but tend to cause symptoms in other cases.

The position of the NF1-associated gliomas more commonly is pre-chiasmatic, meaning before the point where the optic nerves cross (chiasm). A study suggests that the growth rates for NF1 and sporadic (occasional, not regular) tumors are comparable. However, patients with bilateral chiasmatic or post-chiasmatic (after the optic nerve crossing) sporadic tumors were the only ones to face increased mortality due to the tumor’s development.

However, according to a comprehensive review of related literature, tumor recurrence or growth takes place in 38% of all optic pathway glioma cases, despite various treatment methods, including observation. After an average of 11 years of follow-up, the mortality rate linked to the tumor is 36%. Approximately 55% of patients either maintain stable vision or show improvement, while 45% suffer progressive vision loss. Spontaneous shrinkage of optic gliomas is rare but has been documented in some cases. The possibility of optic pathway gliomas turning malignant (cancerous), although exceedingly rare, has also been reported.

Sadly, all patients with malignant optic nerve gliomas usually lose their vision within months of the tumor’s discovery. The mortality rate in these cases is 100%, with an average survival period of less than 1 year.

Possible Complications When Diagnosed with Optic Nerve Glioma

Surgical complications can lead to problems like worsened eyesight, hormonal deficiencies, and irregularities in the brain’s functions. Certain treatments, like vinorelbine or vinblastine therapy, also carry risks. These risks can include allergic reactions, stomach problems, harm to the ears, kidneys, or nerves, lowered blood cell counts (in cases where platinum-based chemotherapy is used), and an increased chance of getting secondary leukemia, particularly with certain drugs like CCNU and procarbazine. The use of a drug called Vincristine can cause damage to peripheral nerves, lower sodium levels in the body, and hair loss. Bevacizumab can lead to high blood pressure, tiredness, high levels of protein in urine, and bleeding.

Common Side Effects:

• Worsened eyesight
• Hormonal deficiencies
• Allergic reactions
• Stomach problems
• Harm to the ears, kidneys, or nerves
• Lowered blood cell count
• Increased chance of secondary leukemia
• Damage to peripheral nerves
• High blood pressure
• Tiredness
• High protein levels in urine
• Bleeding

Drugs that inhibit MEK, a type of enzyme, can cause skin conditions. However, they might also lead to severe eye-related issues, like optic nerve damage, swollen veins in the retina, inflammation inside the eye, separation of the sensory layer of the retina from the back of the eye, and retinopathy related to the MEK inhibitor. These effects are generally rare and can often be reversed, especially in children.

Following radiotherapy, patients might suffer from hormonal disturbances. For instance, around 72% of patients treated with cranial radiation may develop deficiencies in hormones controlled by the central part of the brain, with growth hormone and TSH shortages being the most common. About 20% of patients might experience deficiencies in ACTH, delayed puberty, or a general shortage of hormones produced by the pituitary gland. Obesity and diabetes insipidus could also result from radiotherapy. Early detection and treatment with external hormone supplements can help prevent severe developmental issues.