Compressive optic neuropathy (CON) is caused by injury to the optic nerve by an extrinsic lesion.
The primary function of the optic nerve is to transmit visual information from the retina to the brain. The optic nerve contains the axons from the retinal ganglion cells and extends posteriorly from the globe, through the orbit and optic canal, to reach the optic chiasm. At the chiasm, contralateral nasal fibers decussate and join uncrossed temporal fibers to become the optic tracts. The optic nerve consists of more than a million nerve fibers.[1] The total length of the optic nerve averages 50 mm: 1 mm for the intraocular segment, 25 mm for the intraorbital segment, 9 mm for the intracanalicular segment, and 16 mm for the intracranial segment.[2] An injury to the optic nerve anywhere along this pathway by an extrinsic lesion is termed compressive optic neuropathy.
Any lesion that produces associated mass effect can cause CON, including infectious (eg, aspergilloma), inflammatory (eg, inflammatory pseudotumor), vascular (eg, aneurysm), traumatic (eg, fracture, hematoma), and neoplastic (eg, meningioma, glioma) etiologies. The optic nerve is particularly vulnerable to injury by a compressive force where it is adjacent to bone or in a small confined space (eg, orbital apex, optic canal).[3]
The clinical hallmarks of a compressive optic neuropathy include slowly progressive vision loss, reduced visual acuity and/or visual field, dyschromatopsia, a relative afferent pupillary defect, and eventual optic atrophy. Initially, the optic disc may be swollen or normal (retrobulbar optic neuropathy). Up to 75% of patients with intracranial tumors present with a headache.[3]
Clinicians should consider compressive optic neuropathy in the differential diagnoses of unexplained optic neuropathy, including atypical glaucoma. The initial evaluation should include a neuroimaging study, preferably MRI of the brain and orbits with and without contrast with fat suppression to evaluate for a compressive lesion.
The management of compressive optic neuropathy depends on the etiology. The surgical approach can be difficult, given the proximity of anterior visual pathway compressive lesions to critical neurovascular structures in the orbit and intracranial space.
Optic nerve compression by an extrinsic lesion has been postulated to cause atrophy of ganglion cell axons either through ischemia or mechanical disruption of axonal transport. Rarely, an intrinsic lesion of the optic nerve (ie, optic nerve glioma) can cause damage to the individual axons due to slow compression of the fascicles within the tumor.
Compressive optic neuropathy can affect individuals of any age, sex, race, or ethnicity.
Frequency
United States
Compressive optic neuropathy (CON) is relatively rare, with an estimated incidence of about 4 cases per 100,000 individuals per year.
Mortality/Morbidity
Compressive optic neuropathy (CON) can lead to permanent vision loss, particularly if optic atrophy is evident at the time of diagnosis. However, with certain conditions such as Graves orbitopathy and pituitary adenomas, significant visual recovery may occur after surgical intervention.[4]
Tumors compressing the optic nerve in the intracranial space may cause additional neurologic morbidity (eg, endocrine dysfunction, cranial nerve palsies, papilledema, stroke).
Tumors within the orbit that cause CON may be associated with proptosis, ptosis, or diplopia.[5]
Trauma can also cause CON. Spheno-orbital or optic canal bone fractures and retrobulbar or optic nerve sheath blood within the orbit can compress the optic nerve and lead to acute vision loss.[6]
Patients with compressive optic neuropathy (CON) typically present with slowly progressive or chronic vision loss in one or both eyes. Bilateral cases can result from midline lesions (eg, pituitary adenoma, craniopharyngioma, meningioma) or from bilateral lesions (eg, thyroid eye disease).
Patients may complain of blurred vision, dimness of vision, or an inability to read with the affected eye. Peripheral vision loss, including nerve fiber layer defects, junctional visual field loss, or bitemporal hemianopsia, can result from compressive lesions of the anterior visual pathway. The duration of the vision loss may be difficult to determine; if optic atrophy is already present, the axonal injury occurred at least 6 weeks prior to presentation.
CON may be found incidentally during a routine eye examination or refraction when a patient is documented to have unexplained visual acuity loss. Another common presentation is in patients who are referred for an evaluation after a failed driving test.
Rarely, patients with CON will have sudden visual loss due to an intralesional hemorrhage (eg, pituitary apoplexy). These patients can present with the complaint of “worst headache of my life.”
The patient or the patient's relatives may note the development of proptosis or exophthalmos.
In rare cases, patients may complain of a transient loss of vision. This clinical scenario is typically caused by an orbital apex tumor, and the vision loss occurs only in certain positions of gaze (ie, gaze-evoked amaurosis). This presentation for CON is thought to be related to either direct pressure on the optic nerve or a temporary interruption of the blood supply by the tumor in certain positions of gaze.[3]
Sudden or rapidly progressive vision loss due to CON is rare, but trauma would be the main inciting factor in these circumstances. History reveals either blunt or penetrating injury. Trauma can occur along any portion of the optic nerve; however, the intracanalicular portion of the optic nerve is especially susceptible to indirect traumatic forces. Stress forces from trauma transmitted to the skull cause injury to the intracanalicular segment in particular because it is tightly adherent to the periosteum in this location.[6]
In general, an 8-point eye examination should be performed in every patient undergoing ophthalmological evaluation. This examination includes an assessment of visual acuity, pupils, extra-ocular motility and alignment, intraocular pressure, confrontational visual fields/perimetry, external examination, slit-lamp examination, and funduscopic examination. Further workup for CON should include a full neurological examination, including testing the function of all cranial nerves.[7]
The findings of CON in terms of (1) central visual acuity, (2) color vision, (3) pupillary function, and/or (4) visual field (ie, perimetry) are discussed below. Depending on the location of the lesion, additional clinical findings may include proptosis, strabismus, eyelid malposition, anosmia, facial numbness, or pituitary dysfunction.[3]
Optic nerve function
Visual acuity
Visual acuity is typically reduced in the affected eye, although the deficit may be moderate. Mass lesions in the orbit compressing the globe may result in a hyperopic shift.
Color vision
Dyschromatopsia commonly occurs in CON. The Ishihara test plate is a simple method to assess color vision in the office setting. Other testing methods for dyschromatopsia include pseudoisochromatic color plates and Farnsworth-Munsell test.[8]
Desaturation of color hue: When a bright color (eg, red) is viewed by each eye individually, the patient will describe the color to be less vivid or washed-out in the eye with CON.
Pupils
Because CON is typically a unilateral process, examination of the pupils could reveal a relative afferent pupillary defect on the affected side (ie, Marcus Gunn pupil). However, a relative afferent pupillary defect may not be seen if the contralateral optic nerve or retina has been damaged by an unrelated condition (eg, previous trauma).[3]
Visual field examination
As the ganglion cell axons within the optic nerve travel toward the chiasm, the inferior and superior topographic organization from the optic disc is preserved, but the fibers serving central vision move toward the interior of the optic nerve. This arrangement of fibers within the optic nerve produces the characteristic visual field defects associated with CON.
The majority of fibers within the optic nerve are concerned with central vision. Therefore, CON almost always causes a central scotoma, usually with some peripheral constriction. Altitudinal or arcuate visual field defects mimicking glaucoma may be seen in some cases. The location of the lesion does not always correspond with the topographic location of the visual field defect; for example, a superior orbital mass may not always cause an inferior visual field defect. Enlargement of the blind spot may be noted when optic disc edema is present.
When compression of the optic nerve occurs near its junction with the optic chiasm, perimetry may demonstrate a central scotoma in one eye and a temporal visual field defect in the other eye. This combination of visual field findings suggests intracranial localization at the anterior aspect of the chiasm (ie, junctional scotoma). Tumors at the optic chiasm, commonly pituitary adenomas, often cause a bitemporal hemianopsia that respects the vertical midline.[3]
Additional clinical findings
Proptosis
Proptosis is defined as pathologic, forward displacement of the globe in the orbit.
Formal assessment of proptosis: The distance from the lateral canthal rim to the corneal surface is measured with a Hertel exophthalmometer. Proptosis can also be assessed qualitatively by comparing the projection of the two globes with the observer positioned above the patient's forehead.[9]
If more than 2 mm of proptosis exists, a space-occupying lesion of the orbit is suspected.
Slowly progressive proptosis is often undetected by patients and their families.
Extraocular motility
Ocular motility abnormalities may occur if cranial nerve three, four, or six is involved, either through mechanical factors or direct compression of cranial nerves at the superior orbital fissure.[3] However, ocular motility may be normal if the orbital mass is moderate in size and the growth rate is slow.
Relative resistance to retropulsion of the globe: Pressing on the globes through the closed lids may reveal an asymmetric resistance to retropulsion, suggesting the presence of a space-occupying lesion in the orbit.
Dilated fundus examination
Funduscopic examination may reveal an optic disc that appears normal, edematous, or atrophic.
Disc edema is typically seen with orbital processes. Optic disc edema in CON is thought to occur from a mechanical blockage of axonal transport by the tumor or mass lesion. In clinical practice, chronic, unilateral optic disc edema is much more likely to be related to optic nerve compression than papilledema, which is almost always a bilateral process, although occasionally it is asymmetric.
If axonal damage has been present for longer than 6 weeks, optic atrophy can be detected clinically as a variable degree of optic disc pallor.
When CON causes optic atrophy, occasionally it is accompanied by optic disc "cupping". It is not known why some cases of CON are associated with an enlargement of the optic disc cup, but clinicians should be aware that rare cases of low-tension glaucoma may be due to a compressive lesion.[10]
The combination of ipsilateral optic atrophy and contralateral disc edema is known as the Foster Kennedy syndrome. This clinical picture results from compression of one optic nerve and papilledema involving the other optic nerve from an intracranial lesion (eg, meningioma).[11]
Fundus examination images are shown below.
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A 72-year-old man with a moderate decrease in vision in the left eye (20/20 right, 20/25 left). Fundus examination revealed a normal right optic nerve....
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Same patient as in image above of a 72-year-old man with a moderate decrease in vision in the left eye (20/20 right, 20/25 left). Fundus examination r....
Vascular abnormalities of the optic disc
CON may cause the appearance of optociliary shunt vessels, which are collateral channels connecting the retinal circulation to the choroidal circulation. These vessels become dilated when the venous return within the optic nerve becomes obstructed by a compressive force. Blood is then shunted to the choroidal circulation where it exits through the vortex veins.
The four most common causes of optic disc shunt vessels include retinal vein occlusion, optic nerve sheath meningioma, optic nerve glioma, and chronic papilledema.
The triad of optic atrophy, optociliary shunt veins (optochoroidal collaterals), and progressive visual loss was initially described in patients with optic nerve sheath meningioma (ie, Hoyt-Spencer triad).[12]
Orbital tumors compressing the globe may result in choroidal folds. The folds or striae can occur within the macula or adjacent to the optic disc.
Workup in cases of compressive optic neuropathy should begin with a history and physical examination, followed by laboratory studies and imaging studies.
Blood tests can be helpful in the diagnosis of compressive optic neuropathy. However, the serologic workup should be guided by the history and clinical presentation.[15]
If thyroid ophthalmopathy is suspected, blood tests for thyroid function, including TSH, serum T4 and T3, thyroid-stimulating immunoglobulins, and anti-thyroid antibodies should be performed.
An elevated angiotensin-converting enzyme level may be seen in 52%-90% of patients with active sarcoidosis.[16]
Since prostate cancer can metastasize to the brain and orbit, an elevated prostate specific antigen (PSA) level may be helpful in male patients with suspected bony orbital metastases and optic nerve compression.[17]
Insulin-like growth factor 1 (IGF-1), prolactin, luteinizing hormone (LH), follicle-stimulating hormone (FSH), thyrotropin-releasing hormone (TRH) and alpha subunit, cortisol, and thyroxine (T4) can be obtained to assess a pituitary tumor.
Bony tumors or protrusions of the orbit can lead to CON.[18] Alkaline phosphatase levels would be elevated in Paget disease of bone; an elevated bone-specific alkaline phosphatase (BSAP) has 84% sensitivity.[19]
Whenever there is clinical suspicion of compressive optic neuropathy (CON), a neuroimaging study is indicated to determine the presence and location of the responsible lesion. Given the high sensitivity and specificity of modern neuroimaging, a negative scan finding essentially reduces the possibility of CON as the cause of vision loss.
In most cases of CON, magnetic resonance imaging (MRI) is the imaging modality of choice because of the excellent soft-tissue resolution of the anterior visual pathway and parasellar area. Typically an orbit and brain MRI with and without contrast is ordered to evaluate a patient for CON. Abnormalities within the peri-optical spaces are more consistent with meningiomas, whereas a global increase in the size of the optic nerve is in favor of a glioma. Example MRIs are shown below.
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Axial MRI taken 3 weeks after the onset of distorted vision in the right eye; visual acuity is reduced to counting fingers at 1 ft. Evidence of optic ....
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MRI of same patient as in the image above taken 4 months later. Patient responded well to IV Solu-Medrol, but symptoms returned when steroids were red....
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Neuroimaging study (MRI of brain and orbits) revealed an extensive meningioma involving the left orbital apex (arrow).
Computed tomography (CT) scanning offers excellent visualization of the bony anatomy and is particularly useful to evaluate the intraconal space of the orbit. However, for imaging the orbital apex and optic canal, MRI is preferred over CT due to the absence of signal interference from adjacent bone seen on tomography.
Ultrasonography may be useful to document the presence of anterior orbital lesions but offers limited penetration into the deep orbit. However, in certain clinical situations, ultrasonography may be used to image patients quickly in the office in order to determine whether CT or MRI is warranted.
If the source of CON is a tumor, staging is an important aspect of the evaluation. The tumor, nodes, and metastasis (TNM) system is most commonly used to stage tumors. Tumor (T) is the size of the mass. Nodes (N) is the measure of lymph node involvement. Metastases (M) is the measure of tumor extension to different parts of the body. Taken together, the TNM system is used to evaluate the stage of the tumor.[21] Secondary tumors in the orbit due to metastases suggest an advanced stage of the primary tumor.
Treatment of compressive optic neuropathy should be aimed at the underlying cause. Treatment can be separated into medical management and surgery.
A favorable response to treatment with corticosteroids should not be considered as confirmation of a diagnosis until good quality MRIs and CT scans are obtained.
A practical approach for those cases in which the MRI and/or CT scan strongly indicates a meningioma (both intraorbital and intracanalicular) is to monitor the patient with serial visual acuity measurements and field testing. If visual loss progresses, consider treatment with radiation, and, if growth continues, surgery may be considered with or without embolization of feeder vessels to the tumor.
Decisions for surgical interventions to address vision loss should be made based on careful examination. Realistic expectations regarding the probability of improvement need to be discussed with the patient.
Corticosteroids may be useful in compressive optic neuropathy caused by inflammation (e.g. sarcoid) and thyroid ophthalmopathy. Radiation can also be considered for thyroid eye disease or some anterior visual pathway tumors (eg, meningioma).[22, 23]
Treatment of compressive optic neuropathy is aimed at managing the underlying cause. Consider surgical excision or decompression as a treatment option when visual failure results from optic nerve compression by a tumor.[4] Apical optic nerve tumors (eg, cavernous hemangioma) may require an orbitocranial approach.[24]
Surgical orbital decompression may be necessary for compressive optic neuropathy of thyroid eye disease.
If the tumor is intimately involved with the optic nerve, as often is the case with nerve sheath meningiomas, surgical removal often results in further loss of vision. This is thought to be due to a compromise of the shared blood supply.
If the cause of CON is trauma (eg, sheath or retrobulbar hematoma), surgical decompression may be necessary. Steroids can be used preoperative, intraoperatively, or postoperatively.[6]
Surgery to remove orbital tumors compressing the optic nerve is frequently associated with injury to the surrounding structures, including third, fourth, and/or sixth cranial nerves, which may result in paralytic strabismus and ptosis.
Surgery to remove lesions that are intimately involved with the nerve sheath (eg, meningiomas, schwannomas) often results in further loss of vision or blindness, and primary radiation therapy may be indicated.
Long-term monitoring is indicated for patients who are found to have chronic CON. Patients should seek regular care with their ophthalmologist, as well as the appropriate specialist.
Many cases of compressive optic neuropathy (eg, thyroid ophthalmopathy, orbital pseudotumor, lymphoma, sarcoid) will improve at least transiently with steroid treatment. Intravenous steroids may hasten visual recovery. It may be difficult to withdraw steroid treatment from such patients without deterioration of vision.
Biological agents and immune mediators that target specific aspects of disease pathogenesis may have a role in inflammatory and autoimmune processes causing compressive optic neuropathy. However, the efficacy of these drugs has not been well studied.[22]
See Thyroid Ophthalmopathy for details of medical treatment.
Andrew G Lee, MD, Chair, Department of Ophthalmology, Blanton Eye Institute, Houston Methodist Hospital; Clinical Professor, Associate Program Director, Department of Ophthalmology and Visual Sciences, University of Texas Medical Branch School of Medicine; Clinical Professor, Department of Surgery, Division of Head and Neck Surgery, University of Texas MD Anderson Cancer Center; Professor of Ophthalmology, Neurology, and Neurological Surgery, Weill Medical College of Cornell University; Clinical Associate Professor, University of Buffalo, State University of New York School of Medicine
Disclosure: Received ownership interest from Credential Protection for other.
Ashwini Kini, MD, FRCS, Clinical Fellow in Neuro-Ophthalmology, Department of Ophthalmology, Houston Methodist Hospital
Disclosure: Nothing to disclose.
Specialty Editors
Simon K Law, MD, PharmD, Clinical Professor of Health Sciences, Department of Ophthalmology, Jules Stein Eye Institute, University of California, Los Angeles, David Geffen School of Medicine
Disclosure: Nothing to disclose.
Chief Editor
Hampton Roy, Sr, MD, Associate Clinical Professor, Department of Ophthalmology, University of Arkansas for Medical Sciences
Disclosure: Nothing to disclose.
Additional Contributors
Diana Katherine Lee, Georgetown University School of Medicine
Disclosure: Nothing to disclose.
Edsel Ing, MD, MPH, FRCSC, Associate Professor, Department of Ophthalmology and Vision Sciences, University of Toronto Faculty of Medicine; Active Staff, Michael Garron Hospital (Toronto East Health Network); Consulting Staff, Hospital for Sick Children and Sunnybrook Hospital, Canada
Disclosure: Nothing to disclose.
Jonathan W Kim, MD, Director of Oculoplastic and Orbital Surgery, Co-director of Ocular Oncology Service, Co-director of Neuro-ophthalmology Service, Department of Ophthalmology, Stanford Medical Center
Disclosure: Nothing to disclose.
Talmadge (Ted) Cooper, MD, Clinical Associate Professor, Department of Ophthalmology, Stanford University School of Medicine
Disclosure: Nothing to disclose.
Acknowledgements
Brian R Younge, MD Professor of Ophthalmology, Mayo Clinic School of Medicine
Brian R Younge, MD is a member of the following medical societies: American Medical Association, American Ophthalmological Society, and North American Neuro-Ophthalmology Society
Elwahed SA, Mustafa O. Norms of Optic Nerve Length on MR Imaging for Adults Sudanese. IOSR Journal of Dental and Medical Sciences (IOSR-JDMS). 2018. 17(7):35-9.
Miller NR, Newman NJ, Biousse V. Walsh and Hoyt's Clinical Neuro-Ophthalmology. 6th ed. Lippincott, Williams & Wilkins; 2004.
Schiefer U, Wilhelm H, Hart W. Neuro-ophthalmic presentations of orbital disease. Clinical Neuro-Ophthalmology: A Practical Guide. Wien & New York: Springer; 2007.
American Academy of Ophthalmology. The 8-Point Eye Exam. Available at https://www.aao.org/young-ophthalmologists/yo-info/article/how-to-conduct-eight-point-ophthalmology-exam. May 24, 2016; Accessed: April 20, 2019.
Allen RC. Hertel Measurement, Hertel Exophthalmometer. University of Iowa Carver College of Medicine. Available at https://webeye.ophth.uiowa.edu/eyeforum/atlas-video/hertel-measurement-hertel-exophthalmometer.htm. January 12, 2017; Accessed: April 20, 2019.
Vilensky J, Robertson W, Suarez-Quian C. The Clinical Anatomy of the Cranial Nerves: The Nerves of "On Olympus Towering Top". Ames, Iowa: Wiley-Blackwell; 2015.
A 72-year-old man with a moderate decrease in vision in the left eye (20/20 right, 20/25 left). Fundus examination revealed a normal right optic nerve.
Same patient as in image above of a 72-year-old man with a moderate decrease in vision in the left eye (20/20 right, 20/25 left). Fundus examination revealed an atrophic left optic nerve.
Axial MRI taken 3 weeks after the onset of distorted vision in the right eye; visual acuity is reduced to counting fingers at 1 ft. Evidence of optic nerve compression is not seen; disease in the sphenoid sinus is reported.
MRI of same patient as in the image above taken 4 months later. Patient responded well to IV Solu-Medrol, but symptoms returned when steroids were reduced. Large mass compressing the right optic nerve is seen. Biopsy revealed lymphoma.
Neuroimaging study (MRI of brain and orbits) revealed an extensive meningioma involving the left orbital apex (arrow).
Axial MRI taken 3 weeks after the onset of distorted vision in the right eye; visual acuity is reduced to counting fingers at 1 ft. Evidence of optic nerve compression is not seen; disease in the sphenoid sinus is reported.
MRI of same patient as in the image above taken 4 months later. Patient responded well to IV Solu-Medrol, but symptoms returned when steroids were reduced. Large mass compressing the right optic nerve is seen. Biopsy revealed lymphoma.
A 72-year-old man with a moderate decrease in vision in the left eye (20/20 right, 20/25 left). Fundus examination revealed a normal right optic nerve.
Same patient as in image above of a 72-year-old man with a moderate decrease in vision in the left eye (20/20 right, 20/25 left). Fundus examination revealed an atrophic left optic nerve.
Neuroimaging study (MRI of brain and orbits) revealed an extensive meningioma involving the left orbital apex (arrow).
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