Ocular Diseases

All patients who complain of decreased vision need an ophthalmologic evaluation. Even patients with known disorders that can potentially affect vision deserve a thorough ophthalmic examination if their vision changes. For example, in a patient known to have an optic nerve sheath meningioma, unrelated retinal detachment may develop. Anterior segment and retinal disorders are not always obvious on a cursory eye examination and may mimic optic nerve or intracranial disease.²² A few selected ocular disorders that may be confused with neurological vision loss are discussed in this section.

Anterior Segment Disorders

Tear film disorders, such as dry eye syndrome, commonly cause transient visual blurring in one or both eyes that may range in duration from seconds to hours. Patients may also complain of eye pain. Tear dysfunction is common in women older than 40 years and may be associated with collagen vascular disease, medications, or systemic disorders such as sarcoidosis. In certain patients in whom an ocular surface disorder is suspected, a trial of artificial tears may be indicated before starting an extensive neuroophthalmic evaluation.

Cataract typically causes a gradual onset of blurred (rather than dim) vision or monocular diplopia. Cataract is often evident in the red reflex with the ophthalmoscope. Additional typical findings include a normal or diffusely depressed visual field (cataracts do not cause focal visual field defects), a myopic shift in refraction, and the lack of an RAPD.

Retinal Abnormalities

Macular diseases cause central scotomas or metamorphopsia. Ocular coherence tomography (Fig. 13-E5) is a relatively new noninvasive tool for imaging the macula that has simplified the diagnosis of macular disease, although intravenous fluorescein angiography is still often required. Age-related macular degeneration is a common cause of painless central vision loss in patients older than 50 years; typically, macular pigment changes, whitish macular drusen, or blood is evident with the ophthalmoscope, but the findings may be subtle. Central serous retinopathy causes central scotomas in younger patients (and is often confused with optic neuritis). Epiretinal membranes tend to cause metamorphopsia rather than discrete scotomas and are not always evident on ophthalmoscopy. Macular holes can decrease visual acuity and cause tiny central visual field defects so small that the foveal threshold may be the only abnormal point with automated perimetry. Cystoid macular edema can occur in association with diabetes, uveitis, and retinitis pigmentosa and cause central vision loss. Most of the time, retinal trauma is obvious from the history and fundus examination, but permanent subtle changes from trauma can occur.

FIGURE 13-E5 Ocular coherence tomography. This powerful ocular imaging technique takes advantage of the relative transparency of the retina to produce cross-sectional images of the macula. A, Normal contour of the fovea. Note the normal “dimple” at the foveola and stratified architecture of the retina. B, Cystoid macular edema (CME). The normal structure of the fovea is disrupted with fluid-filled cysts in patients with CME, a situation not uncommon after cataract surgery. The CME is blatantly obvious in this study, but it is often very difficult to identify and diagnose with ophthalmoscopy alone.

Branch retinal artery occlusion causes acute vision loss and focal visual field defects that can be similar to those associated with optic nerve disorders.^23,24 Acutely, the fundus examination reveals a whitish yellow opaque area of edematous ischemic retina; frequently, emboli can be seen in the retinal arterioles (Fig. 13-E6).^25,26 However, the retinal edema typically clears in days to weeks, with only subtle changes in the caliber of the affected retinal arteriole remaining. Similarly, the retinal edema and “cherry-red spot” from central retinal artery occlusion quickly vanishes but leaves retinal arteriolar narrowing and mild diffuse optic nerve pallor (Fig. 13-E7).

FIGURE 13-E6 Hollenhorst’s plaque. A white, glistening cholesterol embolus can be seen in a typical location, lodged at the bifurcation of a retinal arteriole. These flat crystalline emboli, not necessarily occlusive, commonly accompany the sticky, lumen-filling, occlusive platelet-fibrin emboli originating from large-vessel atherosclerotic disease.

FIGURE 13-E7 Cherry-red spot from central retinal artery occlusion. Occlusion of the central retinal artery causes ischemia and opacification of the nerve fiber layer. This cream-colored edematous nerve fiber layer is most evident where the nerve fiber layer is thickest, in and around the macular area. Because of the anatomic peculiarities of the foveola, no axons can swell and thus obscure the normal red color of the uninvolved choroidal circulation, thereby giving rise to the infamous “cherry-red spot.”

Central retinal vein occlusion²⁷ and branch retinal vein occlusion²⁸ cause marked retinal hemorrhages that are impressive and difficult to miss initially (Fig. 13-E8). Sometimes, venous collateral vessels on the optic disc (opticociliary shunts), tortuous retinal veins, and slight disc pallor remain and mimic the findings of an optic nerve sheath meningioma.

FIGURE 13-E8 Central retinal vein occlusion. The characteristic appearance of central retinal vein occlusion is striking: flame-shaped hemorrhages (within the nerve fiber layer of the retina) are seen throughout the posterior pole along with engorged retinal veins and optic disc edema.

Retinitis pigmentosa is typically associated with pigmented “bone spicules” along vessels in the retinal periphery, optic disc pallor, arteriolar narrowing, and vitreous cells. Perimetry may reveal the classic “ring scotoma” seen in the predominantly rod varieties or central scotomas when the cones are primarily affected. Findings on electroretinography are usually abnormal before retinal changes are evident.

Cancer-associated retinopathy (CAR) is a paraneoplastic syndrome in which autoantibodies are directed against components of the retina; it is usually associated with small cell carcinoma or other visceral malignancies.^29–31 The classic triad consists of photosensitivity, ring scotomatous visual field loss, and attenuated retinal arterioles.³² The electroretinogram is typically abnormal, and CAR antibodies may be detected in serum.^33,34 A CAR-like syndrome can also occur with melanoma (melanoma-associated retinopathy) and in the setting of systemic autoimmune disorders.³⁵

Papilledema

Elevated intracranial pressure from any cause can be transmitted to the optic nerve head and usually results in bilateral optic disc swelling. There are many causes of optic disc swelling, but the term papilledema refers specifically to the bilateral disc swelling associated with elevated intracranial pressure (Fig. 13-5). The optic disc may be markedly elevated, with hemorrhages of the nerve head and surrounding retina. Usually, there is no visual loss acutely, except for enlargement of the physiologic blind spot from elevation and compression of the peripapillary retina. If acute central visual loss is present, a different diagnosis such as bilateral optic neuritis or bilateral AION (i.e., giant cell arteritis) is more likely. Chronic papilledema can cause loss of the peripheral visual field, with central vision affected only very late in its course.³⁶ The presence of bilateral optic disc edema requires immediate investigation, starting with a blood pressure measurement to evaluate the possibility of malignant hypertension and neuroimaging to rule out an intracranial mass or other abnormality. Normal findings on neuroimaging in the presence of elevated intracranial pressure suggest IIH, also called pseudotumor cerebri.³⁷ IIH typically occurs in obese women between puberty and menopause.³⁸ Men, as well as women who are not overweight, frequently harbor identifiable causes of elevated intracranial hypertension (such as an occult dural arteriovenous malformation, dural venous sinus occlusion, sleep apnea, and other conditions) and should not be considered to have IIH until an exhaustive clinical investigation confirms that there is no identifiable cause. IIH occurs in children, but the same careful scrutiny just noted should be applied to this group as well.³⁹

FIGURE 13-5 Papilledema in a 19-year-old obese woman with idiopathic intracranial hypertension. Results on magnetic resonance imaging were normal, and lumbar puncture showed an opening pressure of 380 mm H₂O. A and B, Optic nerves. Bilateral, diffuse optic disc edema is identified. C and D, Visual fields. With the exception of enlargement of the physiologic blind spot, visual field defects are uncommon acutely. This patient demonstrates enlargement of the blind spots and small inferior nasal steps bilaterally, findings suggestive of chronicity. E, Clinical course. Patients frequently notice transient visual obscurations, which are brief episodes (lasting 1 to 5 seconds) of monocular or binocular visual blackout often associated with postural changes. Chronic disc edema can lead to progressive peripheral visual field loss.

It is important to understand that all patients with papilledema or known intracranial hypertension must be monitored by an ophthalmologist with serial optic disc evaluations (and photographs) and visual fields. The vision loss with papilledema can be insidious and unappreciated by the patient initially, with severe peripheral visual field loss even in the presence of excellent visual acuity.⁴⁰

Anterior Ischemic Optic Neuropathy

AION is characterized by sudden, painless loss of vision associated with unilateral optic disc swelling in patients 45 years or older. An infarct of the optic nerve head occurs as a result of occlusion of one or more of the posterior ciliary arteries.⁴¹ These vessels originate from the ophthalmic artery in the orbit, enter the globe around the optic nerve, and supply the peripapillary choroid and optic nerve head. AION may occur as a sequela of generalized atherosclerotic disease (i.e., nonarteritic AION)⁴² or be secondary to vasculitis, most commonly giant cell arteritis (i.e., arteritic AION).⁴³

The most common form of AION is nonarteritic and it is manifested as isolated monocular vision loss. The disc edema and resulting pallor are typically confined to the upper or lower portion of the nerve, with a corresponding altitudinal visual field defect (Fig. 13-6). The visual field defect tends to be permanent, although minimal improvement may occur over time. No treatment has been shown to be effective.

FIGURE 13-6 Anterior ischemic optic neuropathy. A 59-year-old man with systemic hypertension was evaluated because of acute, painless visual loss in his left eye. A, Optic nerve. The left optic nerve demonstrates disc edema, more prominent superiorly than inferiorly. B, The uninvolved right optic nerve shows a small central cup. This disorder tends to affect patients with small, cupless optic nerves. C, Six weeks after the onset of symptoms, the optic disc edema has resolved, with pallor of the superior pole of the optic nerve head being apparent. D, Visual field. Although altitudinal visual field defects are common (shown here), virtually any optic nerve–related field defect can be found in patients with ischemic optic neuropathy. E, Clinical course. Visual loss is sudden and usually painless. It is often noticed on awakening and may progress initially with stepwise deterioration.

The precipitating mechanisms of this multifactorial event are not fully understood.⁴⁴ The architecture of the optic disc is an important factor because affected discs are almost always small and cupless. Patients with nonarteritic AION may have systemic vascular diseases such as systemic hypertension (40%) or diabetes mellitus (20%) or systemic manifestations of atherosclerotic disease such as angina pectoris, previous myocardial infarction, intermittent claudication, or a history of stroke.^45,46 Hypercholesterolemia is associated with nonarteritic AION in patients 50 years or younger.⁴⁷ Unilateral or bilateral nonarteritic AION can occur in predisposed patients with hypotensive episodes in the setting of surgery (including spinal cord surgery with induced hypotension) or trauma. The prognosis for vision is not good in this situation, even with prompt correction of hypotension, hypovolemia, and hypoperfusion.⁴⁸

There is no proven, effective treatment of nonarteritic AION. Optic nerve sheath fenestration, once considered a potential surgical treatment in the past, was formally studied and shown to be ineffective, possibly even harmful.^49,50

Thirty percent to 50% of patients have an event in the second eye, usually years later. Most clinicians advocate the daily use of aspirin because it may theoretically decrease the risk for an event in the contralateral eye.⁵¹ As with all functionally monocular patients, care should be taken to protect the unaffected eye from trauma with shatterproof polycarbonate lens eyeglasses.

In all cases of AION, it is vital to determine whether there is any evidence of an arteritic cause (e.g., giant cell arteritis). Untreated giant cell arteritis can cause rapid, sequential, or simultaneous blindness in both eyes. For this reason, the erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) level should be determined for all patients older than 55 years who have AION. If giant cell arteritis is suspected because of an elevated ESR or CRP, or both, or because of symptoms such as headache, scalp and temple tenderness, myalgias, arthralgias, low-grade fever, anemia, malaise, weight loss, anorexia, or jaw claudication,⁵² oral or intravenous steroid treatment should be instituted immediately.⁵³ In acute cases, the patient may benefit from high-dose intravenous steroids. Biopsy of the temporal artery should follow within days of steroid therapy.^54,55 In arteritic AION, the visual loss is usually profound, and the optic nerve is often diffusely swollen and pale (Fig. 13-E9).

FIGURE 13-E9 Arteritic anterior ischemic optic neuropathy from giant cell arteritis (GCA). An 82-year-old man had sudden, profound vision loss in his right eye. This was preceded by 2 days of brief episodes of transient vision loss in the affected eye lasting seconds. The erythrocyte sedimentation rate (ESR) was 12. Despite the normal ESR and denial of headache, GCA was strongly suspected given the patient’s systemic complaint of “tender cords” on his scalp, jaw claudication, and weight loss. Temporal artery biopsy was performed and demonstrated fracture of the internal elastic lamina and the presence of giant cells. A, The patient’s thickened, tender, pulseless temporal arteries are evident. It is important to note that this sign is not always as apparent as in this patient. Patients with GCA may not demonstrate such prominent findings. Additionally, patients without GCA may have visibly thickened temporal arteries from arteriosclerosis. B, The optic disc is very pale, with diffuse edema.

Optic Neuritis

Optic neuritis is typically manifested as unilateral visual loss (often described as a skim, scum, blur, haze, cloud, dimness, or washed-out view) in young adults (15 to 45 years old), with women outnumbering men 5 to 1. The vision worsens progressively over a period of several days and is almost always accompanied by retrobulbar pain that is made worse with eye movement (Fig. 13-7). After 1 or 2 weeks, vision begins to recover slowly. In most cases, vision gradually improves over a period of 3 to 12 months, and in more than 80% of patients, recovery is nearly complete.⁵⁶ Optic neuritis is caused by demyelination of the optic nerve. Because optic neuritis is commonly associated with multiple sclerosis (MS),^57–59 it is no surprise that patients may report other past or present neurological symptoms.

FIGURE 13-7 Optic neuritis. A 34-year-old healthy man experienced a decline in vision in his left eye (to count fingers at 3 ft) over a 4-day period along with retrobulbar pain with eye movement. Ten days after the onset of symptoms, he began to improve. Four months later, the patient had 20/20 vision in his affected eye with a normal visual field. A, Disc appearance. This patient demonstrates diffuse disc edema, which is seen in only a third of patients with optic neuritis. The remaining two thirds have a normal disc on evaluation. As the disc edema resolves, optic disc pallor generally appears. B, Visual fields. Although central scotomas are common in patients with optic neuritis, any type of optic nerve visual field defect can be seen, including general depression of the visual field, altitudinal visual field defects, and arcuate scotomas. This visual field shows a centrocecal scotoma combined with an inferior nasal step and nonspecific superior field loss. C, Clinical course. Vision generally decreases over a week or so, with slow recovery over a period of weeks to months. The patient may recover nearly normal visual acuity and visual fields.

The optic disc initially appears normal in two thirds of adults with optic neuritis.⁶⁰ An RAPD provides objective evidence of the visual loss. In addition to optic neuritis, compressive optic neuropathy, giant cell arteritis, carcinomatous meningitis, optic nerve trauma, and radiation-induced optic neuropathy can also cause acute monocular visual loss with relatively normal-appearing optic discs initially. In older patients, it may be difficult to distinguish optic neuritis with a swollen disc from AION.

The Optic Neuritis Treatment Trial (ONTT) was a multicenter national study that addressed the efficacy of steroid treatment in patients with optic neuritis. The ONTT randomized 458 patients with optic neuritis into three treatment groups: no treatment (i.e., placebo tablets), moderate-dose oral prednisone, and high-dose intravenous methylprednisolone for 3 days (followed by an 11-day taper of oral prednisone).⁶¹ The outcomes of the study and resultant treatment recommendations are as follows:

Many clinicians have modified the original high-dose intravenous regimen (250 mg every 6 hours for 3 days) to make it practical for home intravenous therapy, with 500 mg methylprednisolone administered twice each day or even 1000 mg once daily for 3 to 5 days.⁶¹

In a high percentage of women with optic neuritis and a lower percentage of men, clinically definite MS is eventually diagnosed in their lifetimes, although some studies did not find a gender predilection.⁶² The probability is greatly increased (50% to 80%) when white matter changes are seen on MRI.^58,59

The discussion regarding long-term treatment options for patients with optic neuritis who are at risk for MS is complex. The Controlled High-Risk Subjects Avonex Multiple Sclerosis Prevention Study (CHAMPS) was one of the first to suggest that patients with isolated optic neuritis (no other neurological symptoms) and white matter lesions on MRI may benefit from initiation of interferon beta-1a. Other clinical studies have added additional information (and complexity) to treatment decisions for potential MS in patients with optic neutitis.⁶³

Optic neuritis can occur in response to a viral illness or immunization or may be idiopathic, with clinical findings and a course identical to the optic neuritis associated with MS but without systemic symptoms ever being manifested.

Compressive and Infiltrative Optic Neuropathies

Compression of the optic nerve in the orbit, in the optic canal, or intracranially usually causes slow, progressive loss of vision (Fig. 13-8).^64–68 Common compressive optic neuropathies include optic nerve sheath meningioma and orbital Graves’ disease, although any mass lesion adjacent to the optic nerve in the orbit, in the optic canal, or intracranially can be implicated (Fig. 13-E10).

FIGURE 13-8 Compressive optic neuropathy. A 30-year-old woman complained of slow, painless, progressive visual loss in her right eye. An optic nerve sheath meningioma was identified by magnetic resonance imaging and computed tomography. A, Optic nerve. Depending on the location of compression, compressive optic neuropathies may be manifested as disc edema, as illustrated here, or as progressive optic disc pallor without edema. B, Visual field. Optic nerve compression may cause peripheral or central visual field defects. In this patient, three quadrants were involved, as well as depression of her central vision. C, Six months later, this patient’s disc edema has partially resolved, but the optic disc pallor remains. D, Imaging. Magnetic resonance imaging (coronal view) of the orbit reveals a well-circumscribed orbital optic nerve sheath meningioma (arrow). E, Clinical course. Slow, progressive visual loss over a period of weeks to months is common.

FIGURE 13-E10 Optic nerve compression. A 72-year-old woman was evaluated because of a slow, relentlessly progressive decline in vision in her left eye. A, The left optic nerve was diffusely pale. The right optic disc was the typical disc at risk for anterior ischemic optic neuropathy (AION). B, Neuroimaging was performed because the patient’s history of slow visual loss was not compatible with the signs and symptoms of AION. The scan showed a mass, and a subsequent cerebral angiogram (pictured here) revealed a carotid-ophthalmic artery aneurysm (arrow).

Meningiomas of the optic nerve sheath represent only 5% of all orbital tumors, but because of their anatomic proximity to the optic nerve, they are more likely than other orbital tumors to cause optic nerve compression and loss of vision. Optic nerve sheath meningiomas commonly occur in women (female-to-male ratio of 3:1) in their fourth decade. Optic atrophy and visual loss with opticociliary collateral vessels on the optic disc are characteristic of optic nerve sheath meningiomas.^64,69 Meningiomas can also arise from the intracranial dura and compress the intracranial optic nerve or the chiasm. Sphenoid wing meningiomas frequently have both intraorbital and intracranial components.

Surgical excision of an optic nerve sheath meningioma is indicated only when the tumor is confined to the orbit and the eye is blind because surgical excision of the meningioma invariably strips the vascular supply of the optic nerve and results in blindness. The decision to excise a tumor when intracranial extension is present is complex and depends on whether there is a threat to the contralateral optic nerve or chiasm; the size, location, and growth of the tumor; and the remaining sight in the affected eye. Steroids have only a short-term effect but are often used during radiation therapy.

Observation may be a reasonable initial treatment. The natural history of optic nerve sheath meningiomas is highly variable. They may remain static for many years, or they may progress relatively rapidly. Sequential neuroimaging plus careful monitoring of optic nerve function (sequential visual fields, visual acuity, contrast sensitivity testing, color vision testing, RAPD measurement, and other indicators of optic nerve function) in patients with an optic nerve sheath meningioma is vital because it provides a guide for management. Conformal radiation therapy is emerging as the most viable treatment option.^70–73

Optic nerve gliomas usually occur in childhood (75% before 20 years of age) and are manifested as proptosis, visual loss, strabismus, or nystagmus.⁷⁴ About half of optic nerve gliomas arise in the orbital portion of the optic nerve; the remainder arise intracranially. Fifty percent of patients with optic nerve gliomas have neurofibromatosis type 1 (NF1). Fifteen percent of patients with NF1 harbor an optic nerve glioma. These tumors are pilocytic astrocytomas (juvenile type) with a benign cytologic appearance. They enlarge very slowly or may appear inactive.⁷⁵ Spontaneous regression of even large, symptomatic optic gliomas can occur, both in patients with and in patients without NF1.⁷⁶ By contrast, malignant gliomas of the anterior visual pathway that arise in adulthood behave very differently and rapidly lead to blindness and death.^77,78

Neuroimaging of childhood gliomas typically reveals a fusiform swelling of the optic nerve or chiasm, or both.⁷⁹ Involvement of the chiasm may be associated with endocrine dysfunction and hypothalamic involvement. Children with optic nerve or chiasmal glioma should undergo endocrine evaluation, as well as a thorough search for systemic signs of neurofibromatosis. Most clinicians favor a conservative watch-and-wait approach given the usual static course in children,⁷⁵ but surgical resection may be considered in exceptional patients with a blind eye and disfiguring proptosis. The indications for and effectiveness of radiation treatment and chemotherapy for these tumors are controversial and unresolved.

The optic nerve and disc may be directly infiltrated in lymphoproliferative^80–82 or granulomatous (sarcoidosis)^83–87 disorders. Leukemic infiltration with visual loss may respond to urgent radiation treatment (Fig. 13-9).

FIGURE 13-9 A and B, Infiltrative optic neuropathy. A 17-year-old boy with acute lymphocytic leukemia thought to be in remission experienced sudden loss of vision in his right eye. Marked, pallid edema infiltrating both optic nerves is identified, with hemorrhages present on the left. After an emergency evaluation confirmed the diagnosis, immediate radiotherapy of the optic nerves was instituted.

Infectious agents can affect the optic nerve by direct infiltration, by inciting a local inflammatory response or autoimmune attack on the optic nerve (Fig. 13-E11), by local mass effect from an infectious focus, or by compromise of the vascular supply by vasospasm or vascular occlusion from the products of an inflammatory response. Many agents have been implicated, but syphilis can affect the visual pathway in so many and varied ways that it should always be included in the differential diagnosis of otherwise unexplained optic neuropathy.

FIGURE 13-E11 Cat-scratch neuroretinitis. A 10-year-old girl had a febrile illness several weeks after exposure to a kitten. Three weeks after the systemic symptoms had subsided, the patient had vision loss in her left eye. A, The visual field revealed a dense central scotoma. B, The optic disc showed diffuse edema with a focal elevation of the optic disc that has the appearance of an optic disc granuloma. The optic disc edema is accompanied by white edema residues in the inner macula that line up radially in Henle’s layer, forming a star. Vitreous cells were also present. Several deep, white, choroidal patches were seen in the retinal periphery of both eyes. A serologic titer (indirect fluorescent antibody) for Bartonella henselae was positive, thus implicating cat-scratch disease neuroretinitis. The patient improved dramatically over a 3-month period, with visual acuity improving from 20/400 to 20/30. This patient was not treated with systemic antibiotics because her acute systemic illness had resolved, but many clinicians will treat cat-scratch disease neuroretinitis with a course of ciprofloxacin, doxycycline, or other antibiotics.

Optic Disc Drusen and Other Anomalies

About 1% of the population may have elevated optic discs as a result of optic nerve head drusen (Fig. 13-10).⁸⁸ In this condition, hyaline material is present in the substance of the optic disc and elevates the axons as they enter the optic nerve head. The rock-like, irregular yellow material is often exposed in older patients.⁸⁹ This condition is bilateral in 70% of patients. Peripheral visual field defects may occur, but optic disc drusen typically do not decrease visual acuity.

FIGURE 13-10 Disc drusen neuropathy. A 60-year-old woman noticed a stepwise decline in the vision of each eye over the previous year. Optic nerve head drusen were implicated as the cause of her visual loss after an extensive evaluation showed no evidence of other causes. A, Optic nerves. In older patients, optic nerve head drusen are often visible as chunks of rock candy–like material poking through the axons of the optic nerve head, as seen in this patient’s left optic disc. The right optic disc also showed drusen. B, Visual fields. This patient’s left visual field demonstrates an inferior nasal step (the right visual field was similar). C, Clinical course. Acute, episodic, stepwise decline in the visual field may occur. Transient visual obscurations have also been reported with this entity.

In young patients, optic disc drusen may be situated deep in the substance of the optic nerve and not be visible with the ophthalmoscope. The elevated appearance of these discs with “buried” drusen can be confused with true optic disc edema. Features that help distinguish these anomalous discs from pathologic optic disc swelling include a “crowded” appearance with no central cup, irregularly scalloped disc margins, anomalous branching of the central retinal artery with many vessels crossing the disc margin, and lack of change over time (Fig. 13-11).

FIGURE 13-11 A and B, Congenitally anomalous optic nerves. An asymptomatic 4-year-old boy was referred after a routine ophthalmic examination showed possible disc edema. Five years later, the appearance of the optic disc is identical to that in the initial photographs. As the appearance of this patient’s optic disc demonstrates, anomalous optic nerves are frequently “crowded,” with no central cup identified. Many vessels cross the disc margin, and many of these optic nerves harbor buried optic disc drusen.

Eyes with a long axial length (i.e., high myopia or nearsightedness) may have an oblique insertion of the nerve into the globe with an apparent elevation of the nasal rim of the disc and an excavation of the temporal aspect: a “tilted” disc. Depression of the retina just temporal to the disc (nasal to the fovea) can cause “refractive” bilateral temporal visual field defects that may simulate chiasmatic lesions.

Toxic and Nutritional Optic Neuropathies

Slow, insidious loss of central vision, often manifested as bilateral central or centrocecal scotoma, suggests a toxic (i.e., medication or poison) or nutritional cause. Frequently, pallor of the temporal aspect of the optic nerve is present, although the nerve may initially appear normal. The combination of alcohol abuse and poor diet may result in central visual loss. Vitamin supplementation (especially folic acid and thiamine) may dramatically improve these visual deficits. Nutritional and substance abuse consultation may also be needed. Notable toxic substances causing optic neuropathies include ethambutol (slowly progressive central vision loss and disc pallor) and amiodarone (bilateral vision loss and optic disc edema).

Hereditary Optic Neuropathies

A variety of hereditary optic neuropathies may be manifested as part of a neurological syndrome or appear as isolated findings. Kjer’s dominant optic atrophy causes relatively mild to moderate central visual loss that may not be noticed until vision-screening examinations at school. The optic discs usually show bilateral temporal pallor, but they may appear relatively normal at the onset of symptoms. The inheritance pattern may not be obvious in the family history because incomplete penetrance is common.⁹⁰

Leber’s hereditary optic neuropathy causes rapid, sequential loss of central vision in young men and occasionally in women. Although the disc swelling is rarely impressive, the optic nerves often display fine peripapillary telangiectasia, which gives way to pallor after loss of vision. This disorder is inherited through at least three known mitochondrial DNA mutations and is therefore passed from (usually asymptomatic) women to their children.⁹¹

Traumatic Optic Neuropathy

Traumatic optic neuropathy may be caused by direct trauma to the optic nerve from foreign bodies or bone fragments or by indirect trauma, with visual loss resulting from force transmitted to the optic canal by blunt trauma to the brow without fracture.^92,93 The optic disc may appear normal acutely, but pallor inevitably follows in 4 to 8 weeks. High-dose intravenous steroids⁹⁴ and surgical decompression of the optic canal⁹⁵ have been advocated for the management of acute traumatic optic neuropathy in the past, but the efficacy and safety of these treatments have been questioned.⁹⁶ Retinal detachment, penetrating injuries, and other globe injury must be sought in all cases of visual loss from trauma.⁹⁷

The Chiasm

At the chiasm, axons representing each half of the visual space are routed to their respective optic tracts. Because axons from the nasal hemiretina of each eye decussate, defects in the temporal visual fields of both eyes (“bitemporal hemianopia”) result from lesions that affect the central portion of the chiasm (Fig. 13-12). However, chiasmal injury usually arises from mass lesions that do not attack with pinpoint accuracy; the visual fields may reflect damage primarily to one or both optic nerves (optic nerve–related visual field defect), the body of the chiasm (bitemporal field defects), the optic tract (incongruous homonymous field defects), or a combination of these three patterns of visual field loss.⁹⁸ Mass lesions arising from the sellar and parasellar region that affect the chiasm include pituitary tumors, meningiomas, craniopharyngiomas, Rathke’s cleft cysts, and occasionally, giant aneurysms. The chiasm is located about 1 cm above the sella; thus, tumors arising in the sella (such as pituitary macroadenomas) must be relatively large to compress the chiasm and affect vision. These large pituitary macroadenomas are generally nonsecreting, given that patients with secreting adenomas usually seek medical help for their endocrine dysfunction before the tumor is large enough to compress the chiasm. The prognosis for improvement in visual fields and visual acuity is good (>80%) after transsphenoidal surgery for pituitary adenomas.⁹⁹ Rarely, “herniation” of the chiasm into an empty or surgically manipulated sella may affect the body of the chiasm.¹⁰⁰ In addition to mass lesions, conditions that commonly affect the optic nerve are also potential causes of chiasmal dysfunction: demyelination, gliomas, infiltration, vasculitis (Fig. 13-13), and trauma.¹⁰¹

FIGURE 13-12 Chiasmatic compression. A 40-year-old woman noticed a gradual decline in the vision of her right eye over a 6-month period. A and B, Optic nerves. Pallor of the right optic disc is evident. Mild pallor of the left optic disc is suspected. C and D, Visual fields. Marked temporal and central field loss can be seen in the right visual field. The asymptomatic left eye had superotemporal visual field loss, which suggested a lesion affecting the chiasm. E, Neuroimaging. Magnetic resonance imaging demonstrates a large, enhancing mass in the region of the optic chiasm. Pathologic examination of the surgical specimen confirmed a meningioma.

FIGURE 13-13 Chiasmatic radiation vasculitis. A 35-year-old woman underwent surgical resection and subsequent irradiation for a right temporal lobe glioma. She experienced acute visual loss 2 years after radiation therapy. A diagnosis of radiation neuropathy was made after an extensive evaluation had ruled out other causes. A, Neuroimaging. Magnetic resonance imaging with gadolinium shows enhancement of the right hemichiasm (arrow) involving the right optic nerve and right optic tract. B, Visual fields. The patient had no light perception (NLP) in her right eye (right optic nerve lesion), with only her nasal field remaining in the left eye (right optic tract lesion).

Lesions affecting the chiasm almost never cause optic disc swelling but rather result in retrograde axonal atrophy, which with time will result in visible optic disc pallor and loss of nerve fiber layers (Fig. 13-14). An RAPD is often present with chiasmal disease, depending on the density and asymmetry of the visual field loss in each of the two eyes. The RAPD will be present in the eye with the greatest visual field loss, not necessarily the eye with the worst visual acuity.

FIGURE 13-14 Chiasmatic trauma. A healthy 7-year-old boy sustained a closed head injury in an automobile accident. A, Goldmann visual fields show complete bitemporal hemifield defects. B, With time, bilateral “bow-tie” atrophy developed as a result of loss of axons from the nasal hemiretinae (corresponding to the temporal hemifields).

Before modern neuroimaging, visual field testing played a central role in the diagnosis of sellar tumors, with visual field defects identified by perimetry providing neuroanatomic localization. Although the presence and location of tumors in this region can be identified precisely with MRI and computed tomography, visual field testing still plays an important role in the diagnosis and follow-up assessment of patients. Neuroimaging provides a structural assessment, which may be difficult to interpret in some cases because of postoperative changes. Visual field testing complements neuroimaging by providing a functional means of monitoring patients over time to evaluate for recurrence of tumor.

Retrochiasmal Visual Pathways

Lesions of the visual system posterior to the chiasm affect homonymous portions of the visual fields in both eyes. Optic tract lesions are caused by the same processes that affect the chiasm. Of 21 patients with tract lesions, 17 were due to tumor or aneurysm.¹⁰² Tract lesions produce relatively incongruous homonymous visual field defects and often produce a specific pattern of optic disc pallor (bow-tie atrophy in the eye with temporal visual field loss, loss of the superior and inferior nerve fiber layer in the eye with nasal field loss). Optic tract lesions may also produce an RAPD because pupillomotor fibers travel in the optic tract before exiting at the brachium of the superior colliculus.^100,103,104 Tract lesions are therefore characterized by contralateral incongruous homonymous visual field defects (Fig. 13-E12) and a small RAPD and optic disc pallor (frequently bow-tie or band atrophy¹⁰⁵) in the eye contralateral to the lesion.¹⁰³

FIGURE 13-E12 Optic tract lesion. A 69-year-old man noted a slow decline in vision that he attributed to his left eye. The left eye demonstrated optic disc pallor and a relative afferent pupillary defect suggestive of left optic neuropathy. However, Humphrey threshold perimetry showed a left incongruous homonymous visual field defect (pictured), thus implicating a right optic tract lesion. Neuroimaging demonstrated a suprasellar mass elevating the left optic tract and chiasm.

Axons in the optic tract synapse in the lateral geniculate nuclei. From there, superior retrogeniculate fibers travel directly through the parietal lobe to the occipital cortex and synapse superior to the calcarine fissure. Parietal lesions cause homonymous defects that are denser inferiorly. Inferior fibers take a more indirect route and sweep around the temporal horn of the ventricular system (i.e., Meyer’s loop) and through the temporal lobe to neurons in the inferior occipital cortex (see Fig. 13-4). Lesions in the temporal lobe produce homonymous visual field defects that are denser in the superior quadrants (Fig. 13-15). Such superior visual field defects may be created iatrogenically when pallidotomy is performed for Parkinson’s disease or temporal lobectomy is performed for seizures.¹⁰⁶

FIGURE 13-15 Temporal lobe arteriovenous malformation. A, A right temporal lobe arteriovenous malformation is identified by magnetic resonance imaging. B, Visual fields demonstrate a left homonymous superior visual field defect.

From the chiasm posteriorly, corresponding axons move closer together as they converge on a single point in the occipital cortex; the more posterior the lesion, the more precise the homonymous defects approximate each other (i.e., greater congruity).¹⁰⁷ Occipital lesions tend to be highly congruous (Figs. 13-16, 13-17, and Fig. 13-E13). Complete homonymous visual field defects are said to be nonlocalizing because they can be caused by lesions anywhere from the optic tract to the occipital lobe (Fig. 13-E14). A homonymous hemianopic visual field defect from a unilateral retrochiasmal lesion does not cause decreased visual acuity. However, bilateral retrochiasmal lesions (e.g., bilateral occipital infarcts) can profoundly affect vision in both eyes despite normal findings on ophthalmoscopy and normal pupillary responses (Fig. 13-E15).

FIGURE 13-16 Checkerboard visual fields. A 60-year-old man noticed a visual deficit after cerebral angiography. His left (A) and right (B) visual fields demonstrate a right inferior homonymous quadrantic defect and a left superior homonymous quadrantic defect. Magnetic resonance imaging confirmed that this is the result of left superior and right inferior occipital lobe infarcts.

FIGURE 13-17 Occipital arteriovenous malformation. A, Sagittal and coronal magnetic resonance images demonstrate an occipital arteriovenous malformation near the surface of the occipital cortex. B, Goldmann perimetry demonstrates the corresponding small, but highly congruous homonymous paracentral visual field defects.

FIGURE 13-E13 Occipital lobe arteriovenous malformation (AVM). A 28-year-old woman had visual loss attributed to a what she called a stroke 5 years earlier. A, Humphrey perimetry shows highly congruous right homonymous visual field defects suggestive of an occipital lobe lesion. B, Encephalomalacia of the left occipital tip is evident on magnetic resonance imaging (large arrow), with flow voids (small arrow) suggestive of an AVM (subsequently confirmed by angiography).

FIGURE 13-E14 Nonlocalizing complete homonymous hemianopia. A 77-year-old man complained of loss of vision in his “left eye.” A, Humphrey perimetry depicts the complete left homonymous hemianopic defect that was evident with confrontation perimetry. Such complete homonymous defects are said to be nonlocalizing because the degree of congruity cannot be assessed. B, Computed tomography demonstrated a subacute infarction (arrows) in the distribution of the right posterior cerebral artery.

FIGURE 13-E15 Bilateral occipital lobe lesions. A 61-year-old woman gradually lost vision in both eyes because of a meningeal hemangiopericytoma involving both occipital lobes. The patient’s therapy included surgery, chemotherapy, and radiation therapy. Visual acuity fell to counting fingers only despite normal fundus examination results. A, Magnetic resonance imaging shows bilateral enhancing occipital lobe lesions. B, Humphrey automated perimetry demonstrates highly congruous bilateral homonymous visual field defects. Unlike unilateral retrochiasmal lesions, bilateral lesions can affect visual acuity.

Abducens Nerve (Cranial Nerve VI)

In patients with left abducens paresis, there may be no misalignment of right gaze because the left lateral rectus muscle is relaxed in this field of gaze. However, in left gaze, the left lateral rectus muscle cannot fully pull the left eye out, and an esotropia is evident. To avoid diplopia, the patient may assume a posture with the head turned to the left. Examination of the function of cranial nerve VI is performed by having the patient look in far right and far left gaze (Fig. 13-19, Video 13-1). Trauma is a common cause of abducens palsy in all age groups (see Table 13-2). Acute, painful abducens paresis in a patient 45 years or older who has hypertension or diabetes suggests an ischemic cranial mononeuropathy. Recovery over a period of 2 to 6 months is the rule. In young patients, abducens palsies may occur as a postviral syndrome, but the clinician must remain alert for the possibility of tumor. Elevation of intracranial pressure can affect the function of one or both sixth cranial nerves (see Table 13-3).

FIGURE 13-19 Abducens palsy in a 20-year-old woman with a traumatic left sixth cranial nerve palsy. Ocular versions are relatively normal on right gaze, but the marked weakness of the left lateral rectus muscle is evident on left gaze.

VIDEO 13-1

Left sixth cranial nerve palsy. This patient has normal gaze to the right but demonstrates an inability to adduct the left eye (demonstrated by having the patient look to the left).

Trochlear Nerve (Cranial Nerve IV)

The trochlear nerve innervates only the superior oblique muscle, but this muscle has a complex action. Because of its redirection at the trochlea and attachment to the globe, the superior oblique muscle intorts, depresses, and abducts the eye. When the globe is adducted, however, the angle of the muscle’s insertion minimizes all actions except pure depression. This fact simplifies clinical evaluation of the superior oblique muscle; the clinician looks at how well the right eye can move down in left gaze and how well the left eye moves down in right gaze (Fig. 13-20, Video 13-2). The vital role of the superior oblique muscle in ocular cyclotorsion explains why patients with trochlear palsy often describe diplopia with one image tilted.

FIGURE 13-20 Superior oblique (trochlear nerve) palsy. This composite of the nine diagnostic positions of gaze demonstrates a left superior oblique palsy. The greatest deviation occurs when the patient looks down and to the right (asterisk). In this adducted position, the left superior oblique becomes the major depressor of the left eye, and its weakness is identified as a left hypertropia.

VIDEO 13-2

Left fourth cranial nerve palsy. A superior oblique palsy is often very subtle clinically, and cranial nerve IV is the most difficult of the ocular motor nerves to evaluate clinically. This patient has normal gaze to the right and left, but even upgaze and downgaze appear normal. The left fourth nerve palsy is evident only by observing that the left eye does not look down as far as the right eye when the left eye is adducted (patient looking down and to the right). This is best appreciated when compared with gaze directed down and to the left, which shows normal alignment.

Trauma is a common cause of trochlear palsy (also called superior oblique palsy). “Decompensation” of congenital fourth cranial nerve palsies is also common but difficult to diagnose convincingly. Neoplasm must be excluded when other causes are not evident (see Tables 13-2 and 13-4).^111,112

Oculomotor Nerve (Cranial Nerve III)

The oculomotor nerve is complex. It innervates all the extraocular muscles (including the levator palpebrae), except for the lateral rectus and superior oblique muscles. It also carries parasympathetic efferent fibers to the pupillary sphincter and ciliary muscle through the ciliary ganglion. Complete third cranial nerve palsy produces an eye that is turned down and out (because of remaining function of the superior oblique and lateral rectus muscles) and a dilated pupil with ptosis (Video 13-3). Partial or incomplete paresis may present a more confusing picture (Fig. 13-21). The pupillary fibers run superficially in the nerve and are preferentially affected by compression, such as from a posterior communicating artery aneurysm or brainstem herniation. Ischemic cranial mononeuropathy of the vasa nervosum of the third nerve generally shows relative pupillary sparing, with the pupil being less affected than motility. Evaluation of the pupil plays a major role in clinical decision making.^113,114 Oculomotor palsy occurring after relatively minor trauma may be the initial sign of a basal intracranial tumor or posterior communicating artery aneurysm.¹¹³ Other causes are outlined in Tables 13-2 and 13-5.

FIGURE 13-21 Oculomotor nerve palsy. In this patient, injury to the left third cranial nerve resulted from closed head trauma. Although motility is only partially affected, the left pupil is fixed and dilated (A). In the primary position, a left ptosis (with compensatory right lid retraction) is seen, with the left eye in a “down-and-out” position (A and B). The affected eye does not adduct (C), elevate (D), or depress (E) well. Notice that abduction (abducens nerve) is intact (F).

VIDEO 13-3

Right third cranial nerve (oculomotor) palsy. This patient has complete ptosis of the right upper lid. With the eyelid lifted, the palsied right eye appears “down and out” because the only extraocular muscles still working are unopposed: the lateral rectus (abducts the eye) and the superior oblique (depresses the eye). Right gaze is intact, but the patient cannot fully adduct, elevate, or depress the right eye. The end of this clip shows anisocoria in bright light as a result of a deficiency in pupillary constriction of the right eye. Thus, this patient has a complete external third nerve palsy with relative pupillary involvement. Pupillary involvement increases the probability of a compressive third nerve lesion (i.e., aneurysm), but it can also occur in patients with ischemic third nerve palsy (as in this case).

Regeneration after disruption of the axons of the oculomotor nerve may result in misdirection and produce clinical signs of aberrant regeneration: pupillary constriction¹¹⁵ or lid elevation with attempted adduction or paradoxical motility.¹¹⁶ Aberrant regeneration never occurs with an ischemic (diabetic) mononeuropathy and always implies that the nerve has been injured in such a way that the myelin sheath and perineurium have been broached (i.e., aneurysm, tumor, or trauma).¹¹⁷ Aberrant regeneration may rarely occur without an antecedent acute third cranial nerve palsy. This is called primary aberrant regeneration and occurs as a result of slow-growing cavernous sinus masses, such as a meningioma or aneurysm.

Determining the Abnormal Pupil

The first and most important step in examining the pupils is to determine whether the larger or the smaller one is abnormal. If a problem exists in the parasympathetic system on one side, that pupil will be larger. In this setting, the difference in pupillary size is most apparent in bright light because that pupil does not constrict well. With a sympathetic outflow deficit, the difference in pupillary size is greatest in the dark, thereby implicating the smaller pupil. Simple, or physiologic, anisocoria is common, with a small difference in pupillary size (generally less than 0.5 mm) remaining constant in light and dark.

The Abnormally Large Pupil

When the larger pupil is abnormal, the most important concerns are oculomotor nerve compression, Adie’s pupil, or pharmacologic mydriasis. Pupillary dilation in isolation, without any other sign of oculomotor nerve dysfunction, is unlikely to be caused by an oculomotor palsy. An Adie “tonic” pupil is generally manifested as unilateral mydriasis with the pupillary response to near focus being far better than the response to light; this light-near dissociation is also seen in “blind” eyes and bilaterally in patients with neurosyphilis or the dorsal midbrain syndrome. Redilation and relaxed accommodation occur very slowly after convergence and near focus, thus the designation as a tonic pupil. This condition is the result of an insult to the ciliary ganglion, with subsequent aberrant regeneration of pupillary and accommodative fibers. Irregular reinnervation of the iris sphincter segments is seen as sector palsies or vermiform movements on slit-lamp examination. Supersensitivity of the pupillary sphincter can be identified with dilute pilocarpine testing (Fig. 13-22).¹¹⁹

FIGURE 13-22 Adie’s pupil. A, Anisocoria that was most noticeable in bright light developed in a 56-year-old asymptomatic individual. B, Clinical suspicion of a left Adie pupil was confirmed with 0.125% pilocarpine. Thirty minutes after drops were placed in both eyes, left pupillary sphincter supersensitivity was evident.

Pharmacologic mydriasis can occur in many settings: contact with jimsonweed, contamination from a scopolamine patch (used for motion sickness) or other medications, or purposeful administration of mydriatic agents. Weak pilocarpine (0.1%) readily constricts the pupil as a result of neurogenic mydriasis but is ineffective if topical parasympathetic blocking drugs (e.g., atropine) or other causes are responsible for the mydriasis.

The Abnormally Small Pupil

When the smaller pupil is abnormal, an oculosympathetic paresis (e.g., Horner’s syndrome) must be considered. Relative miosis and a slight ptosis (1 to 2 mm) may result from interruption of the oculosympathetic pathway anywhere along the three-neuron chain: from the hypothalamus to the ciliospinal center of Budge-Waller (C8-T1), across the lung apex to the superior cervical ganglion, or from the superior cervical ganglion by means of the carotid plexus sympathetic nerves to the pupillary dilator. Postganglionic interruption (at or distal to the superior cervical ganglion) is commonly benign or idiopathic, but preganglionic or central oculosympathetic pareses are associated with malignancy in about half the cases.¹¹⁸ Pharmacologic testing with topical cocaine and apraclonidine is useful in confirming an oculosympathetic paresis (Fig. 13-23).^120,121 Hydroxyamphetamine, previously used to aid in localizing the level of an oculosympathetic paresis, is no longer available.

FIGURE 13-23 Horner’s syndrome in a 37-year-old man with a history of right-sided cluster headaches being evaluated for right oculosympathetic paresis. A, Right ptosis and miosis. B, Forty minutes after bilateral instillation of 10% cocaine eyedrops, the left pupil dilates, but the right does not, thus confirming the diagnosis of oculosympathetic paresis. Paredrine (hydroxyamphetamine hydrobromide) testing (not shown) gave a similar result, which implicated the third-order neuron (postganglionic) lesion.

Dorsal Midbrain Syndrome

Lesions in the region of the pretectum and posterior commissure frequently produce characteristic signs. Dorsal midbrain syndrome (also known as Parinaud’s syndrome or mesencephalic syndrome) consists of vertical gaze deficiencies, convergence spasm or paresis, bilateral mid-dilated pupils with light-near dissociation (poor reaction to light and good reaction to near), and convergence-retraction nystagmus. The nystagmus is unique to this syndrome and consists of rapid convergence with retraction of the globes on attempted upgaze. This result is most evident with an optokinetic stimulus moving downward because the fast upward component induces this finding (Video 13-4). Common causes include pinealomas, aneurysms of the vein of Galen, and noncommunicating hydrocephalus with distention of the third ventricle and the anterior aqueduct of Sylvius. This syndrome may also occur with stroke as one of the “top of the basilar” syndromes.¹²²

VIDEO 13-4

Dorsal midbrain (Paranaud’s) syndrome. Three video segments illustrate the findings in dorsal midbrain syndrome. 1. The patient demonstrates a convergence movement of the eyes in attempted upgaze (repeated upward saccades are stimulated by an optokinetic nystagmus (OKN) drum slowly rotating downward before the patient). 2. The pupil reacts somewhat to bright light but more briskly to a near stimulus. 3. This view across the nose shows that the eyes are actually retracting into the orbit in addition to converging on attempted upgaze: convergence-retraction nystagmus.

Ocular Myasthenia Gravis

Ocular myasthenia gravis can mimic a neuropathy of cranial nerves III (except pupil involvement), IV, or VI, alone or in any combination, but it is often manifested as elusive diplopia or ptosis that is not easily categorized.^123,124 Ocular symptoms are generally apparent before other systemic signs and symptoms, and in some patients, the disorder is confined to the ocular muscles.^124,125 Because this disorder of the neuromuscular junction causes apparent fatigue of muscular function, patients frequently report worsening symptoms (i.e., increasing ptosis or diplopia) as the day progresses and relief after a nap or rest. The orbicularis oculi is often involved and weak. This weakness may be demonstrated by having patients forcefully close their eyes against resistance. The diagnosis is sometimes difficult to make because the results of edrophonium chloride (Tensilon) testing, serum acetylcholine receptor antibody assay, repetitive electromyographic nerve stimulation, or trials of pyridostigmine bromide (Mestinon) may be unremarkable or equivocal. Single-fiber electromyography has the greatest sensitivity and specificity but is technically difficult. Correctly diagnosing this disease early in its course saves the patient a long and often expensive evaluation.

Orbital Graves’ Disease

Because the signs and symptoms of orbital Graves’ disease frequently occur in patients with normal thyroid function, normal results of thyroid function tests do not rule out the disease. Although associated with thyroid malfunction, the orbital disorder seems to run its own course, independent of success in treating the endocrine manifestations. Orbital Graves’ disease is manifested in three ways: restrictive strabismus, proptosis with external eye disease, and compressive optic neuropathy. The disturbed motility pattern can be manifested as diplopia without an evident cause. Because the inferior and medial rectus muscles are generally involved first, the eyes are usually turned in (i.e., esodeviation) and down (i.e., hypodeviation).¹¹¹ Contrary to popular belief, significant muscle involvement can occur without any external manifestations. Strabismus surgery is contraindicated during the active phases of the disease, but prism correction in the spectacles is occasionally helpful.

Compressive optic neuropathy can also occur without fanfare and should always be included in the differential diagnosis of optic nerve pallor (or disc edema), despite a lack of obvious external signs. Optic nerve compression results from crowding of the orbital apex by enlarged extraocular muscles. Treatment usually consists of a trial of steroids for a defined period, followed by surgical decompression of the orbit or irradiation if the signs and symptoms persist.¹²⁶

Enlargement and inflammation of the extraocular muscles can push the globe forward and cause exophthalmos. Orbital Graves’ disease is the most common cause of unilateral or bilateral exophthalmos in adults. True upper eyelid retraction also occurs and exaggerates the exophthalmic appearance by exposing white sclera above the superior limbus. For these and other reasons, exposure and dry eye problems can become serious, both functionally and cosmetically. Occasionally, eyelid relaxation surgery is indicated to protect the cornea.