Continuing Education Activity

Compressive optic neuropathy can be caused by intrinsic or extrinsic compression anywhere along the optic nerve. In addition to damage by compression, optic nerve damage can occur as a result of demyelination, ischemia, metabolic, and traumatic insult. The most common sign is slow progressive monocular visual loss, sometimes associated with headaches. This activity reviews the evaluation and management of compressive optic neuropathy and highlights the role of the healthcare team in the care of patients with this condition.

Objectives:

• Identify the etiology of compressive optic neuropathy.
• Explain the evaluation of compressive optic neuropathy.
• Review the management options available for compressive optic neuropathy.
• Summarize the importance of improving care coordination amongst the interprofessional team to enhance the delivery of care for patients with compressive optic neuropathy.

Introduction

Any intrinsic or extrinsic compression anywhere along the optic nerve can produce compressive optic neuropathy (CON). Other than damage by compression, optic nerve damage can occur as a result of demyelination, ischemia, metabolic, and traumatic insult.[1] The most common sign is a slow progressive monocular visual loss, sometimes associated with headaches. Bilateral visual loss can result from midline lesions (pituitary adenoma, craniopharyngioma, meningioma, giant aneurysms) or bilateral orbital lesions (thyroid disease, sarcoidosis). It is essential to correctly identify the cause of the CON as the differential diagnosis is broad, and management varies accordingly.

The optic nerve has over 1 million nerve fibers.[2][3] This quantity of fibers demonstrates the complexity and importance that the visual system has had in our evolution. The visual pathway starts in the retina and ends in the visual cortex at the occipital lobe. The retina consists of two functional parts: the optic part and the non-visual retina. The optic part of the retina consists of the neural and pigmented layer. In contrast, the non-visual retina is an extension of the pigmented layer and ends in the ciliary and iridial parts of the retina.

The optic nerve begins in the lamina cribrosa of the sclera and exits the orbit through the optic canal. As it leaves the orbit, it is engulfed with an extension of the cranial dura and subarachnoid layer, which forms the optic nerve sheath. The axons of the ganglion cells project as the optic nerve and decussate in the optic chiasm and continue as the optic tract which courses to the lateral geniculate ganglion, which then projects to the primary visual cortex as the optic radiations. The optic nerve averages 50 mm in length (1 mm intraocular segment, 25 mm intraorbital segment, 9 mm intracanalicular segment, and 16 mm intracranial segment).

Etiology

CON can be produced by an extrinsic or intrinsic lesion, causing a mass effect anywhere along the optic nerve.[4] Rarely, an intrinsic lesion of the optic nerve (optic nerve glioma) can cause a slow compression damaging its axons. Many disorders can compress the optic nerve and can be categorized as follows:

1. Infectious
   • Aspergilloma[3][5]
2. Inflammatory
   • Idiopathic orbital inflammation-pseudotumor[6]
   • Sarcoidosis[7]
   • Thyroid orbitopathy-Graves disease[8][9]
   • IgG4 pachymeningitis[10][11][12][13]
3. Vascular
   • Aneurysm[14]
   • Carotid-cavernous fistula[15]
   • Lymphangioma[16][17]
   • Orbital varix[18][19]
   • Ectatic internal carotid artery[20][21]
4. Traumatic
   • Hematoma[22][23]
   • Fracture[24]
5. Neoplastic
   • Hemangioma[4][25]
   • Schwannoma[26]
   • Meningioma[27][28]
   • Glioma (Neurofibromatosis Type 1)[29]
   • Lymphoma[30]
   • Sarcoma[31]
   • Metastatic[32]
   • Pituitary adenoma[33]
   • Craniopharyngioma[34]
   • Dermoid[35]
6. Bone tumors/lesion
   • Fibrous dysplasia[36][37]
   • Paget's disease[38]
   • Osteoma[39]
   • Osteopertrosis[40][41]
   • Hyperostosis[27]
   • Langerhans cell histiocytosis[42]
7. Other
   • Mucocele[43][44][45]
   • Granulomatous meningitis[46]

Epidemiology

Overall estimates from reported cases are 4 cases per 100,000 individuals per year. Gender, race, ethnicity, and age vary depending on the specific etiology.

Given that etiologies causing CON are ample, estimates of incidence vary with each etiology.

• Thyroid orbitopathy in Graves disease has an incidence of 16 cases per 100,000 in females and 2.9 per 100,000 in males.[47][48]
• Craniopharyngioma has an incidence of 0.5 to 2 cases per 100,0000 persons per year.[49]
• Fibrous dysplasia has an incidence of 1 in 5,000 to 10,000 persons.[50]
• Orbital hemangiomas have a prevalence of 8%-10% of benign tumors in the pediatric age group with a female predominance 5 to 1.[51][52]
• Pituitary adenoma has a frequency of 10.5%, but they only produce visual symptoms when they are large and compress the optic nerve or the chiasm.[53]
• Optic gliomas usually affect children and account for 3% to 5% of childhood tumors.[54]
• Cerebral aneurysm near the optic nerve has a prevalence of 3%.[55][56]

Pathophysiology

The optic nerve is part of the central nervous system (CNS). The mammalian CNS lacks the ability for regeneration and axonal growth. When the optic nerve is exposed to axonal damage, glial scars are formed that limits the diffusion of growth factors.[1] Inhibitory proteins of myelin like Nogo and myelin-associated glycoprotein, low expression of growth factors, and lack of laminin are also some factors that hinder the ability for re-growth.[57] The more proximal the damage is to the eye, the quicker the apoptosis of retinal ganglion cells will be. Apoptosis will lead to a cascade of p53 that will result in further cell death.

A CON can occur by compressing the vascular supply and causing ischemia to the nerve or directly causing mass effect upon the axons, thereby impairing axonal transport and signal transmission. The areas most susceptible to compression are where the nerve passes through small bone structures like the orbital apex and optic canal.

Optic nerve compression seen in exophthalmos secondary to thyroid disease occurs due to the enlargement of extraocular muscles due to the proliferation of fibroblasts, increased extracellular matrix, and adipocyte proliferation and differentiation.[8][9]

History and Physical

Patients with CON usually present with chronic progressive vision loss. It can be in one or both eyes. They can present with headaches, nausea, vomiting, diplopia, dyschromatopsia, exophthalmos, afferent pupillary defect, photophobia, red-eye, or unexplained weight loss. Sudden or rapid visual loss are rare except for traumatic cases. These cases usually have a blunt trauma or a penetrating injury. The nerve can be injured at any part, but the orbital apex and the optic canal are the most susceptible areas to damage.

It is imperative to obtain a good history and physical exam to help narrow the broad differential diagnosis.

• Vision loss: Symmetric or asymmetric
• Slow versus rapid onset
• Family history of cancer
• History of radiation
• Cardiovascular risk factors: hypertension, peripheral vascular disease, tobacco use
• Metabolic disease
• Autoimmune history

Physical Exam

• Snellen chart: Visual acuity
• Funduscopic exam
• Slit-lamp examination: Evaluate retina, retinal arteries and veins, cornea, fovea, optic cup
• Visual field test: Help differentiate central vs. peripheral visual loss
• Ishihara’s test: Evaluate if a color deficit is present
• Tonometry: Evaluate intraocular pressure
• Extraocular eye movements
• Proptosis

Evaluation

A full neurological examination followed by a complete ophthalmological evaluation should be performed. The exam will give a baseline visual acuity and monitor progression or improvement.

The eye with optic nerve compression will have reduced visual acuity. It can also show a deficiency in color vision (dyschromatopsia), which can be evaluated by using the Ishihara test plate. Proptosis or resistance to manual pressure, suggest an intraorbital lesion. Ocular motility abnormalities are checked. The optic disc can be atrophic or edematous but can also appear healthy. Optociliary shunt vessels can be seen due to obstruction in the venous return.

Laboratory studies include complete blood count, comprehensive metabolic panel, lipid panel, thyroid-stimulating hormone, T3, T4, luteinizing hormone, anti-thyroid antibodies, thyroid releasing hormone, follicle-stimulating hormone, prolactin, adrenocorticotropin hormone, insulin growth factor-1, cortisol, bone-specific alkaline phosphatase, and prostate-specific antigen. The angiotensin-converting-enzyme is usually elevated in more than half of the patients with active sarcoidosis.

Brain and orbit magnetic resonance imaging will show in detail the optic nerves, parasellar area, and orbital contents. Fat suppression images are needed to demonstrate enhancing lesions inside the orbit. Lesions involving the orbital bones should be examined using a computed tomographic (CT) scan of the head and orbit. It will demonstrate orbital fractures and concomitant injuries in traumatic cases. Ultrasonography can be used for intraorbital biopsy of anterior lesions.

Treatment / Management

The first step in management is to treat the underlying condition. Corticosteroids are beneficial for inflammation (sarcoidosis) and thyroid disease CON. For these conditions, withdrawal of the steroid treatment can cause acute deterioration of vision. Surgical orbital decompression can help CON caused by thyroid ophthalmoplegia.[58][59][60] For tumors intimately attached to the optic nerve, like optic nerve meningiomas, surgery can cause further loss of vision. Radiation therapy is beneficial for aggressive recurrent tumors and those in areas adjacent to cranial nerves and eloquent brain. It can also be used for surgically difficult to reach tumors like the cavernous sinus. Radiation can cause irreversible optic nerve damage; therefore, it has to be used judiciously.

In traumatic cases, conservative treatment is appropriate in patients with mild deficits as spontaneous improvement is possible. Steroids have no benefit for trauma. Surgery is used for patients with radiological evidence of compression.[23][61] Direct compression of the optic nerve by bone fragments or a subperiosteal hematoma is usually treated surgically.[61][62] However, surgery carries the risk of complications such as postoperative cerebrospinal fluid leak and meningitis.[63]

Differential Diagnosis

• Glaucoma[33]
• Ischemic optic neuropathy[64]
• Retinal vein occlusion
• Multiple sclerosis
• Uveitis

When evaluating for the specific etiology, the following common disorders have to be ruled out as their management differs:

• Pituitary tumors
• Schwannoma
• Meningioma
• Aneurysm
• Arteriovenous malformation
• Lymphoma
• Sarcomas
• Metastasis
• Glioma
• Trauma
• Sarcoidosis

Prognosis

The prognosis of CON depends on the pathophysiology (vascular insufficiency or axonal damage) and the time between presentation and treatment.

The recovery of visual symptoms is usually correlated with the length of time to decompress. The consensus in the literature is that the earlier the decompression, the better the outcome. Complete visual recovery has been seen as early as one week.[14] Slow progressive vision improvements have also been reported. More than half of the patients improve irrespective of the pre-operative visual status.[26] Early decompression is recommended, but good results can still be obtained even if decompression is performed delayed.[26]

It is important to emphasize that prognosis of visual recovery varies given the etiology causing the optic nerve compression. For tumoral etiologies, negative predictive factors for visual improvement are the severity of visual loss, disc atrophy, recurrent tumor resection, an extension to the cavernous sinus, hard consistency of the tumor, absence of arachnoid plane, extensive tumor resection, and longer duration of visual loss. Overall, 60% of patients with tumors will experience some improvement after optic nerve decompression.[65]

Complications

Complications of CON include papilledema, blurry vision, afferent pupillary defect, diplopia, nausea, vomiting, permanent vision loss, impaired extraocular movement, and impaired ability to perform activities of daily living due to impaired vision.[66]

Treatment with decompressive surgery may lead to complications such as hemorrhage, infections, complete vision loss, prolonged intubation, coma, and death.

Consultations

• Neurosurgeon
• Neuro-opthalmologist
• Radiation-oncologist
• Endocrinologist
• Neuroradiologist

Deterrence and Patient Education

When vision is significantly affected, the patient needs to be educated to use safety glasses to protect the unaffected eye. All patients who developed CON should attend their regular ophthalmologist care visits to evaluate for visual improvement or deterioration.

As the etiologies of CON are multiple, the patient needs a complete evaluation by an interprofessional team to reach the cause and get urgent treatment to improve the outcome.

Early decompression is recommended, but good results can still be obtained even if decompression is delayed. Patients should see an ophthalmologist as soon as they have symptoms. More than half of the patients improve irrespective of the pre-operative visual status.[26][65]

For tumoral etiologies, 60% of patients will experience some improvement after optic nerve decompression.

Enhancing Healthcare Team Outcomes

While the ophthalmologist is almost always involved in the care of patients with CON, it is essential to consult with an interprofessional team of specialists that include a neurosurgeon, neuro-ophthalmologist, neurologist, and endocrinologist. The nurses will assist with the education of the patient and family. In the postoperative period for eye care, the pharmacist will ensure that the patient is on adequate eye pharmacotherapy. The neuroradiologist plays a vital role in determining the cause. Many lesions have specific radiologic features that can distinguish from other differential diagnoses.