Orbital Disease and Neuro-Ophthalmology
Todd A. Goodglick
Matthew D. Kay
Joel S. Glaser
David T. Tse
Warren J. Chang
PART I: AN OVERVIEW
The orbit is to neuro-ophthalmology what Yankee stadium is for New York baseball fans. It may not be where all of the action takes place but it is certainly where the neuro-ophthalmologist enjoys the home field advantage. That diseases of the orbit fall within the purview of neuro-ophthalmology should come as no surprise, given its concern with the neural connections of ocular and visual function. Optimally this scope includes the diagnosis as well as the management, both medical and surgical, of these diseases. The orbit shares bony partitions with the sinuses medially and inferiorly, the anterior cranial fossa above, the superior orbital fissure and cavernous sinus at the orbital apex, and the sphenoid complex and middle cranial fossa posteriorly (Figs. 14.1 and 14.2). Symptoms and signs of diseases from each area overlap, and multiple medical subspecialties therefore encounter patients with potential orbital and thus ophthalmic problems. Moreover, there are congenital, inflammatory, infectious, neoplastic, vascular, and traumatic processes that bridge the orbital-sinus-cranial interface. An ophthalmologist dealing with orbital problems must therefore have some knowledge of these other fields of medicine, not to mention good relationships with colleagues in these areas with whom to collaborate. Clinically, orbital diseases that cause visual or ocular complaints can be confused and misdiagnosed as intracranial problems. For example, while proptosis is a common indicator of orbital masses, passive orbital congestion with exophthalmos is also a sign of arteriovenous fistula, intracranial obstruction of venous flow, or of tumor growth in the middle cranial fossa or paranasal sinuses.
This chapter introduces orbital diseases and emphasizes the central role of the neuro-ophthalmologist in their diagnosis and management. Although various specialists commonly deal with problems of the orbit, the utility of a consultation for an eye exam can be overlooked to the detriment of patient care. Orbital lesions causing diplopia are discussed at length in Chapter 12. Neither the specifics of orbitocranial anatomy (Figs. 14.1 and 14.2) nor an exhaustive commentary on all orbital diseases is included, but common surgical approaches are discussed in Part II of this chapter. The reader is referred to the several excellent anatomic atlases available, and especially to Rootman’s1 Diseases of the Orbit.
 FIG. 14.1 A: Relative dimensions of orbital and adnexal structures. B: Bones of the orbital floor, from above. Note relationship of ethmoidal sinus complex medially and sphenoid wing posteriorly. (Rootman J. Diseases of the Orbit. Philadelphia, PA: JB Lippincott; 1988.) |
 FIG. 14.2 A: Front view of orbital bones constituting rims and posteromedial structures. B: Anterosuperior view of orbital roof8 (i.e., anterior cranial fossa) and middle cranial fossa9,11 at posterior aspect of orbit. C: Bony details of medial orbital wall and posterior relationships at orbitocranial junction. (All numbers refer to accompanying table.) (Rootman J. Diseases of the Orbit. Philadelphia, PA: JB Lippincott; 1988.) |
HISTORY-TAKING
As with other fields of clinical medicine, accuracy in diagnosis and appropriateness of management depend on an orderly protocol that begins with taking an accurate and careful history (Table 14.1). Review of the personal medical history is an essential part of the assessment of orbital and neuro-ophthalmologic problems. For example, failure to uncover a past history or even a family history of thyroid disease is to ignore a substantial clue to the single most common cause of uni- or bilateral proptosis. Likewise, the presence or absence of vision loss in a patient with orbital congestion and ophthalmoplegia helps to localize an apical from a cavernous sinus lesion. A history of poorly controlled diabetes might suggest the possibility of an opportunistic fungus such as those causing mucormycosis. Clearly, any previous cancer history is suspect, although metastases constitute only 3% to 7% of all biopsied orbital masses2 (nasopharyngeal and sinus neoplasms accounting for 23% of secondary orbital masses in the British Columbia series3). A history of cranial or facial trauma likewise must be assessed, but is usually not subtle.
In addition, to family history a complete review of systems is important and frequently of diagnostic value. It is recognized, for instance, that optic glioma is a relatively frequent manifestation of neurofibromatosis (see Volume 2, Chapter 5). Therefore, in a child with unexplained chronic proptosis, the occurrence of skin lesions (birthmarks, skin lumps, or tumors), seizures, or central nervous system (CNS) masses in blood relatives is critical information. Ideally, such family members should be examined or further details obtained. Dysthyroidism also has a distinct familial predilection.
A carefully noted history of rapidly progressive proptosis in a child (Fig. 14.3) should be considered an orbital emergency, with the clinician’s responsibility being to rule out a life-threatening tumor such as rhabdomyosarcoma or metastatic neuroblastoma. A similar picture may evolve with acute orbital congestion associated especially with ethmoidal or maxillary sinusitis, in children with or without fever.4,5 In contrast, in an adult, with the exception of metastatic tumors, most orbital neoplasms produce insidiously progressive exophthalmos. Inflammatory orbital “pseudotumor”6 is the only common cause of relatively abrupt, usually painful, proptosis with diplopia in the otherwise well adult. Myositis occurs in children or adults.7 The acute phase of Graves’ disease may mimic other orbital congestive syndromes (see below), but usually this most common orbitopathy is subacute or chronic and characterized by achiness and pressure rather than significant pain (Fig. 14.4). In contrast, intermittent painful proptosis, at times accompanied by spontaneous subconjunctival hemorrhage or lid ecchymoses, is practically pathognomonic of lymphangiomas8 or, with a history of postural variability indicating a possible venous varix. Presentation can occur over a wide age spectrum, with severe coughing or prolonged retching, or during protracted obstetrical labor, pressure in intraorbital veins may be momentarily raised to the point of rupture with formation of a usually painful retrobulbar hematoma.9,10 These Valsalva orbital hemorrhages usually resolve spontaneously.
TABLE 14-1 History-Taking in Orbit Disease | ||||||||||||||||||||||||||||||||||||||||||||||||||
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 FIG. 14.3 Acute proptosis in childhood. Top: A 5-year-old boy with 6-day history of massive firm swelling in upper lid and downward displacement of globe by rhabdomyosarcoma occupying orbital roof. Bottom: A 7-year-old boy with 3-day course of painful red swelling and complete ptosis of right lid; orbital cellulitis secondary to ethmoiditis resolved quickly on antibiotic therapy. |
 FIG. 14.4 A: Graves’ disease with unilateral right lid retraction. B: Lid lag on downward gaze. C: Patient shows more profound bilateral “stare,” proptosis, and edema of four lids. |
In situations where the duration of proptosis is not clear, review of antecedent photographs (driver’s license, family snapshots, etc.) may be extremely helpful. The clinician should be aware that proptosis may be suddenly discovered rather than actually occurring rapidly, so that the evidence provided by review of previous photographs is helpful in dating true onset. Such photographs may be scrutinized with the illumination and magnification provided by the 20 diopter (D) lens.
Insidiously progressive orbital masses that produce axial (straightforward) displacement of the globe tend not to produce diplopia until they have progressed significantly. Diseases that have a propensity for infiltration of extraocular muscles such as myositis,7,11 and the restrictive myopathy of Graves’ disease regularly results in diplopia early in their course. As a rule of thumb, pathology such as masses located superiorly in the orbit commonly produce deficits in upward gaze, nasal masses produce adduction deficits, and temporal masses produce abduction deficits. Orbital fractures can result in a variety of patterns of diplopia. Under ideal conditions, these physical observations should be confirmed by enhanced computed tomography (CT) or magnetic resonance imaging (MRI); standardized ultrasonography may be a useful and complementary diagnostic tool when available if an inflammatory process is considered.
Problems with vision can be due to direct compression of the orbital portion of the optic nerve or its circulation by both intra- and extraconal as well as extraorbital pathology but, as with neural structures elsewhere, if the progression is insidious, remarkable chronicity and growth can be seen with preserved and normal nerve function. Retrobulbar masses that indent the posterior pole of the globe may induce relative hyperopia, requiring additional plus lenses to improve acuity. Transient blurring of vision in extremes of gaze, especially abduction or noted during reading,12 can be produced by any orbital mass, including dysthyroidism. This phenomenon may be related to compression of the optic nerve as it is dynamically stretched over a mass, compressed by contracting muscles, as the posterior wall of the globe becomes deformed, or as vascular flow is compromised (or combinations of these mechanical effects) and can even result in gaze evoked amaurosis.
Proptosis with true orbital pain (as opposed to ocular irritation or foreign body sensation) is relatively rare, with the following exceptions: acute orbital inflammation, metastases, elevated venous pressure due to arteriovenous fistulas or malformations; acute thrombosis of venous varices; and acute thrombosis of enlarged orbital veins associated with arteriovenous fistulas or vascular malformations. Orbital and eye pain may also be a symptom associated with the ophthalmoplegia of an orbital apex and/or cavernous sinus syndrome (see Chapter 12), or can be referred pain from meningeal based pathology. Atta et al.13 have elaborated a syndrome of venous stasis orbitopathy, composed of proptosis, ophthalmoplegia, and injected conjunctival vessels, of vascular (arteriovenous fistulas) and nonvascular etiologies. These authors note the usefulness of standardized echography, especially with measurement of extraocular muscle diameters, to distinguish fistulas from mass lesions.
ORBITAL EXAMINATION
The ophthalmologist is secure in his ability to directly visualize the anterior and posterior segments of the globe, but the orbit is seemingly less amenable to direct observation. Nonetheless, an office evaluation of the orbit is not as limited as one might think with the appreciation of the standard eye examination as a sensitive and quantitative orbital and neurologic assessment. In addition to standard evaluation of visual function, pupils and ocular motility, the comprehensive eye exam yields observations regarding disruption of normal orbital anatomy and function as outlined in Table 14.2. Even in an era of excellent imaging modalities, the eye exam remains indispensable in evaluating any disease involving or approaching the orbit because it quantitates function.
TABLE 14-2 Orbit: Physical Examination | ||||||||||||||||||||||||||||||||||||||||||
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Preliminary observations of the face, eyes, and eyelids should be made during history-taking, before the patient’s attention is called to the actual examination and before sympathomimetic agents are instilled for pupil dilation (Fig. 14.4; see also Volume 2, Chapter 3, Fig. 3.11); some patients will stare only during intense concentration or conscious effort to cooperate. Facial asymmetry should be identified even when dismissed as congenital or physiologic. Temporalis bulging can be the only sign of a sphenoid wing meningioma, and assessment of facial bone structure may lead to a diagnosis of dysostotic conditions or simple facial hypoplasia associated with congenital superior oblique palsies.
Anomalies of lid position and movement need not be bilateral. Ptosis is quite rare in Graves’ disease, but is fairly common with inflammatory pseudotumor. Lateral ptosis may result from orbital inflammation of the lacrimal gland (dacryoadenitis) or from a plexiform neurofibroma of the lid. Ptosis, in the absence of pain or other congestive orbital signs, should always bring to mind the possibility of myasthenia. Unilateral ptosis may account for contralateral lid retraction; thus, a patient with right partial ptosis may show relative retraction of the left upper lid, due to increased effort in an attempt to overcome the ptosis (Hering’s law of equivalent innervation is applicable to the two levator palpebrae).14 If the eye with ptosis is occluded, or the lid mechanically raised, the opposite retracted lid will assume a normal position in such cases as opposed to pathologic cases of lid retraction. The differential diagnosis of lid retraction is:
Graves’ ophthalmopathy
Aberrant third nerve regeneration
Unilateral ptosis, with contralateral overaction of levator palpebrae (e.g., myasthenia)
Collier’s sign of dorsal midbrain (Parinaud) syndrome— bilateral
Hyperkalemic periodic paralysis
Congenital ptosis with retraction of the lid noted on downgaze
Mechanical or cicatricial changes
 FIG. 14.5 Conjunctival signs of Graves’ congestive orbitopathy. A: Characteristic fleshy hypertrophy of insertion of right lateral rectus (large arrows). Note localized chemosis of left caruncle (small arrow). B: Hypertrophy of insertion of medial rectus with hypervascularity of the vessels overlying the horizontal recti insertions (arrows). |
Lid swelling regularly results from the congestive edema of Graves’ disease, but also typically occurs in preseptal or orbital cellulitis, inflammatory pseudotumor, arteriovenous fistulas, and even with acute viral conjunctivitis. Most lid edema is accentuated by sleep, during which time the head is maintained in a relatively dependent position. Palpation of a discrete mass in the lids is exceedingly helpful, since potential biopsy is facilitated. The hue of the edema can be diagnostic ranging from the intense erythema of an infectious process to the boggy violacious faint erythema of an inflammatory process to the more purple ecchymotic appearance of an orbital hemorrhage, lymphangioma, or neuroblastoma.
Veins may be visible within the thin lid tissues, either passively dilated by diffusely increased orbital pressure or engorged by arterialization of orbital and adnexal vessels fed by arteriovenous communications. In the latter case, audible bruits and palpable thrills are evidence of turbulent, increased blood flow.
Abnormalities of the conjunctiva may serve as clues to orbital diagnosis. Generalized edema (chemosis) is too nonspecific a finding to be very helpful, as any retrobulbar mass may produce chronic or intermittent chemosis, presumably by interfering with venous drainage in the orbit. In Graves’ ophthalmopathy, the vessels overlying the insertions of especially the medial and lateral recti muscles are commonly enlarged, and indeed the muscle insertions themselves may be visibly hypertrophied (Fig. 14.5). These conjunctival signs are exceedingly useful in identifying Graves’ orbitopathy and should be sought in cases of unexplained proptosis and/or diplopia. Engorgement of ocular surface vessels takes on a more or less specific pattern or tortuosity and a corkscrew configuration in the presence of arteriovenous fistula (see Volume 2, Chapter 17, Fig. 17.14).
Diffuse or focal hyperemia of deeper scleral and episcleral vessels (especially in the superior lateral quadrant of the globe) is seen in anterior scleritis (episcleritis), or as an anterior component of posterior scleritis that accompanies the painful ophthalmoplegia syndrome of idiopathic orbital inflammation (Fig. 14.6).
Proptosis should be palpated and looked for both straight on and looking up at the patient from below (Fig. 14.7). The position of the globes relative to the orbital rims is subject to considerable individual and racial variations. Not the least problem is accuracy and reproducibility of measurements as obtained by a number of exophthalmometric techniques, of which the Hertel exophthalmometer is the most common, and probably the most accurate (Fig. 14.8). In a study of 681 normal adults ranging in age from 18 to 91 years, mean normal protrusion values were 15.4 mm in white women, 16.5 mm in white men, 17.8 mm in black women, and 18.5 mm in black men; upper limits of normal were 20.1, 21.7, 23.0, and 24.7 mm, respectively.15 No normal individual showed more than 2 mm of asymmetry.
 FIG. 14.6 A and B: A 60-year-old woman with painful swelling of left lids, abduction defect, and episcleral vascular suffusion. Results of ultrasonography were typical for idiopathic inflammation with thickened sclera. C: Second event involved right globe, as acute episcleritis. No underlying systemic disorder was found; both episodes were relieved dramatically with a course of oral corticosteroid therapy. |
 FIG. 14.7 Subtle degrees of proptosis detected by viewing the relative position of the lids and lashes as seen from over the brows (top). By placing the thumbs against the orbital rims, relative position of corneas may be assessed (bottom); also, with gentle pressure, relative resistance to retropulsation of the globes is determined. |
 FIG. 14.8 Exophthalmometry with Hertel instrument. White arrow indicates cornea of left eye as viewed through right-angle prism. Black arrow indicates mires fixed at 18 mm. Open arrow indicates baseline gauge. Note position of footplates placed against lateral orbital rims. |
Thus, there is presently no precise reproducible technique for quantitating proptosis, as minor deviations in positioning of exophthalmometers at the lateral orbital rim result in variations in readings.16 Even imaging studies have failed to provide a practical solution for this problem.
Some situations give the appearance of proptosis when the globes are in fact less asymmetric, such as unilateral lid retraction, wherein the involved eye appears larger; unilateral mild ptosis, wherein the contralateral eye appears larger due to an elevated lid height and asymmetry of facial bones including orbital rims; and unilateral enophthalmos,17 wherein the normal contralateral eye appears prominent in comparison (Fig. 14.9). The differential diagnosis of enophthalmos is included in Table 14.3.
 FIG. 14.9 Enophthalmos. A: A 56-year-old woman with right enophthalmos and fixation of the globe, and proptosis of the left eye. B: Bilateral orbital metastases of scirrhous breast carcinoma were disclosed by CT scan. Patient was referred for right proptosis but actually had left enophthalmos caused by simple senile atrophy of orbital fat pad, without history of facial trauma; note sunken superior lid sulcus on left (C), and relative position of left globe and lids, as viewed from below (D). |
TABLE 14-3 Causes of Enophthalmos | |||||||||
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In a small number of patients, differences in the axial lengths of the globes may account for relative unilateral proptosis. This situation is resolved by finding differences in the amount of myopia.
There is little evidence to support the claim that a complete third nerve palsy results in sufficient relaxation of the muscle cone to produce detectable proptosis.
Pulsation of the globe is encountered most commonly with acquired carotid-cavernous fistulas, and rarely in other conditions.18 Causes of pulsation are listed in Table 14.4.
Biomicroscopical examination usually reveals even minimal pulsation, best seen during measurement of intraocular tension by Goldmann applanation tonometry. Cotton-swab sticks may be placed tangentially across the corneal apices, such that transmitted pulsations are amplified by the length of the swab (Fig. 14.10).
TABLE 14-4 Causes of Globe Pulsation | |||||||
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 FIG. 14.10 To detect pulsation, cotton-tipped applicators are placed tangentially across closed lids. Pulsation is transmitted and amplified by length of stick (arrows). |
Exploration of the orbital rim by fingertip palpation (Fig. 14.11) may reveal masses lying in the tissues of the lids and also in the anterior portions of the orbit. Palpation of the orbital and facial bones is mandatory in assessing a patient with facial trauma looking for bony stepoffs or instability from a fracture.
Auscultation of the globe and face is an occasionally useful maneuver to confirm the presence of vascular bruits, as encountered in acquired arteriovenous fistulas or congenital vascular malformations. Bruits may be more intense over zygoma or mastoid bones, where the diaphragm of the stethoscope is more effective than the bell, with which the globe itself is better auscultated (Fig. 14.12). Symmetrical cranial or ocular bruits are commonly present in normal children and therefore must be evaluated with caution.
 FIG. 14.11 A and B: Fingertip exploration 360°; palpation for anterior aspect of orbital mass. |
Forced expiration against resistance (Valsalva maneuver) raises venous pressure in the neck, face, and head, such that orbital masses with significant draining veins will increase in volume, evidenced by transient increase in proptosis (Fig. 14.13). This phenomenon is typically demonstrable in the presence of congenital venous varices or arteriovenous malformations, but may also be seen with acquired carotid-cavernous fistula or with primary or secondary bony defects that permit transmission of intracranial pressure to orbital contents. Crying infants with such lesions may show this sign spontaneously or with head-hanging.
Where accompanying physical signs are absent or minimal, the single most useful technique in distinguishing nonrestrictive ophthalmoplegia (e.g., cranial nerve palsies, myasthenia, chronic progressive external ophthalmoplegia) from a restrictive myopathy (e.g., Graves’ ophthalmopathy) is the forced (passive) duction test. In 1967, Stephens and Reinecke19 reported a method for quantitation of the forced duction test, but no standardized accessible and practical instrument is currently available. There are various techniques to test for mechanical resistance to rotation of the globe, but typically this can be assessed in an examination chair with topical anesthetic applied with a cotton swab to the muscle insertion after which the muscle can be grabbed with a forceps or pushed with a cotton swab. The forced duction test will be positive, that is, there will be resistance to mechanical rotation of the globe, in the following situations: Graves’ restrictive myopathy, inflammatory pseudotumor (myositis), infiltrating carcinoma, and incarceration of extraocular muscles and their surrounding soft tissue attachments that herniate into orbital wall fractures. Because of secondary fibrotic contractures of extraocular muscles, on rare occasions the forced duction test will be positive in the chronic fixed form of ocular myasthenia, in advanced chronic external ophthalmoplegia, with extremely long-standing sixth or third nerve palsies, and the syndrome of Congenital Fibrosis of the Extraocular Muscles. A restrictive myopathy also may occur in long-standing postcataract diplopia.
 FIG. 14.12 Auscultation of globe and face. Top: Stethoscope bell used to auscultate globe and orbit; note that contralateral eye fixates finger to minimize lid movement. Middle: Stethoscope diaphragm was used to auscultate zygoma. Bottom: Stethoscope diaphragm used to auscultate temple. Vascular bruits may also be best heard at the mastoid. |
In situations where the globe is mechanically restricted (again, Graves’ disease is typical) intraocular tension may be elevated, or pressure may inordinately rise on attempted upward gaze.20,21 However, it must be recognized that intraocular pressure increases linearly with vertical excursions of the globe, changes of as much as 7 mm Hg being recorded in normal subjects.22 Indeed, this phenomenon in normal subjects brings into question the validity of this procedure as an adjunct in the diagnosis of Graves’ orbitopathy.23 Carotid cavernous or dural arterial fistulas also typically elevate intraocular tension by raising episcleral venous drainage pressure.
 FIG. 14.13 A 46-year-old woman with recurrent right orbital pain. A: Minimal right proptosis detected by observing position of lids and lashes (arrows) from above the brow. B: Increasing right proptosis during Valsalva maneuver (arrows). Orbital venography demonstrated typical venous varix. |
The ocular fundus may be altered by any retrobulbar mass in the following ways: indentations of the posterior wall of the globe produces chorioretinal striae (Fig. 14.14), while compression at the equator of the globe and beyond results in a more diffuse flattening, best appreciated by indirect ophthalmoscopy, and accentuated by rotation of the eye toward the quadrant(s) of the orbit occupied by the tumor; dilation and tortuosity of retinal veins (venous hemorrhages or occlusions suggest relatively high pressures, as encountered with arteriovenous fistulas); retinal arterial occlusions, especially in orbital phycomycoses such as mucormycosis; edema or frank elevation of the optic nerve head; optic atrophy in chronic compression; optociliary shunt vessels of the disk, especially with perioptic meningioma; and retinal detachment or choroidal suffusion with inflammatory lesions or scleritis. De La Paz and Boniuk24 have extensively reviewed the fundus manifestations of orbital disease.
Optic disc swelling (Table 14.5) does not necessarily suggest actual infiltration of the nerve or its meninges, this fundus finding being rather nonspecific and observed potentially with any increase in retrobulbar mass. Indeed, in orbital context, disc edema is seen most commonly with Graves’ orbitopathy. On rare occasions, optic gliomas produce a picture of disc swelling with or without venous occlusion, and perioptic meningiomas may be characterized by a clinical triad of slowly progressive visual loss, pallor admixed with disk swelling, and papillary retinociliary venous shunts (see Chapter 5, Part II).
 FIG. 14.14 Chorioretinal striae through fovea caused by retrobulbar mass, which in this case was an hemangioma. |
DIAGNOSTIC CONSIDERATIONS
After history-taking and thorough physical examination as outlined in the preceding sections, the clinician should be able to make at least a tentative but rational diagnosis, even before special diagnostic studies are undertaken. Excluding congenital dysostoses, malformations and cysts, and traumatic fractures and hematomas, which rarely cause diagnostic dilemmas, all orbital disease may in essence be classified into only four common types: (1) Graves’ ophthalmopathy, (2) idiopathic inflammations, (3) vascular malformations and fistulas, and (4) true neoplasms. Large series of patients with orbital disorders show variable specific incidence rates, depending on referral patterns and age groups. Graves’ orbitopathy may be underestimated since many clinicians do not regularly refer uncomplicated cases; the same is true for trauma and congenital anomalies (Table 14.6).
TABLE 14-6 Causes of Orbital Disease | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Graves’ Disease
Graves’ congestive orbitopathy is the single most common orbital disorder, with annual incidence rates ranging from 12 to 20 per 100,000 population, and with higher prevalence rates (42%) among Caucasian (European) groups than in Asians (8%). The age-specific incidence rates are greatest among middle-aged patients, and are approximately four times higher in women than in men. In patients with hyperthyroidism, ophthalmopathy is evident in 25% to 50%, but severe complications evolve in just 3% to 5%. Several studies have linked tobacco smoking to increased severity of Graves’ orbitopathy,25 possibly related to alterations in immunoregulatory cell function induced by smoking, and increased synthesis of glycosaminoglycans by orbital fibroblasts. Accordingly, patients with Grave’s orbitopathy should be strongly encouraged to quit smoking and should be informed of the potentially more severe nature of the clinical course in patients who smoke.
Thyroid eye disease (TED) is usually associated with hyperthyroidism, and less frequently with Hashimoto’s thyroiditis, euthyroid states, thyroid carcinoma, or primary hyperthyroidism. About 80% of patients will develop signs of ophthalmopathy either during the year before or the year after a diagnosis of thyroid malfunction.26 Delayed onset of TED many years and even decades after the onset and treatment of clinical dysthyroidism may exceptionally occur. Tallstedt et al.27 demonstrated a 2- to 3-fold increase in risk of developing orbitopathy when the thyroid disease was managed with radioactive iodine treatment as opposed to surgical or medical treatment; this effect may be related to the release of thyroid antigens and to subsequent enhancement of autoimmune response directed toward antigens shared by the thyroid and the orbit. Evolution of ophthalmopathy after radioiodine therapy is often transient and may be ameliorated by the administration of prednisone.25,28
The principal signs are lid retraction and edema, proptosis, and diplopia. If congestive signs are slight, the ocular motor defects are regularly misdiagnosed, and unsuitable studies for intracranial disease ensue. Eye movement defects with Graves’ disease are discussed in detail in Volume 2, Chapter 12. Infrequently Graves’ disease presents in an acute inflammatory form that mimics orbital cellulitis or idiopathic pseudotumor, including pain, lid swelling with ptosis, diplopia, and infrequently visual loss.29 Proptosis and restrictive myopathy also may occur in children with hyperthyroidism.30
Obscured by the more obvious external congestive signs and by symptoms of diplopia, the complication of compressive optic neuropathy may be overlooked. Although its incidence is said to be less than 5% among patients with typical thyroid disease, Graves’ optic neuropathy is a treatable cause of potentially disabling visual loss (see also Volume 2, Chapter 5, Part II). Congestive symptoms always precede visual loss, which is usually gradual in onset and bilateral in most patients, but may occasionally be acute and asymmetrical. Presenting acuities are poorer than 20/60 in 50% of cases; central scotomas, at times combined with arcuate field depression, are the predominant visual field defects. Congestive signs are usually of moderate intensity without severe proptosis or exposure keratopathy. Bilateral and symmetrical ductional restriction is the most commonly associated motility disturbance. Oral corticosteroids are often effective in restoring visual function, but steroid-unresponsive neuropathy may be improved promptly by orbital irradiation or surgical decompression.31,32 The medical management of Graves’ disease is complex and demands a comprehensive approach, often requiring a variety of medical, surgical, (see below) and radiotherapeutic interventions.33,34
It is worth noting that Graves’ ophthalmopathy frequently presents or worsens weeks to months after radioactive iodine ablative therapy, and that concomitant corticosteroid therapy may ameliorate this effect.25,28 Radioactive iodine ablation is by no means therefore contraindicated in the presence of mild or moderate orbitopathy. Char35 has reviewed the immune mechanisms by which intrathyroidal clonally restricted B-cells secrete autoantibodies, with extraocular muscle and orbital tissues, including fibroblasts, acting as antigenic targets; fibroblasts in turn produce glycosaminoglycan that binds water, increasing orbital connective tissue volume. Prednisone and orbital irradiation, in variable combinations, are all applicable forms of therapy. Indeed, in the Mayo Clinic experience36 of therapies for Graves’ ophthalmopathy, only 20% of patients required one or more surgical procedures; 7 of 120 patients (6%) developed optic neuropathy.
Inflammations
Orbital inflammatory disease may take several distinct forms. Acute orbital cellulitis is defined as infectious inflammation of soft tissues posterior to the orbital septum, characterized by distension and hyperemia of the lids and conjunctiva, pain, proptosis, and limitation of eye movements. Although contiguous spread of sinus infections into the orbit were previously a frequent and potentially life-threatening complication, this situation is now relatively rare given the widespread availability of antibiotics. However, in children and young adults, orbital cellulitis is still associated with ethmoidal and maxillary sinusitis. Principal predisposing risk factors include ocular or adnexal surgical procedures (lid, strabismus, or retinal operations), facial or orbital trauma, especially with retained orbital foreign bodies, dacryocystitis or other periorbital infections, insect bite envenomization, diabetes, and immunosuppressive states. Those bacterial agents commonly responsible for sinusitis (predominantly Streptococcus pneumoniae, Staphylococcus aureus, and less frequently Haemophilus influenzae), not surprisingly are implicated in orbital cellulitis.37 Rapidly progressive rhabdomyosarcoma may present a clinical picture of pseudocellulitis in children (see Fig. 14.3). This life-threatening emergency demands emergent biopsy followed by chemotherapy and orbital irradiation. CT scanning or MRI is mandatory, not only to disclose sinus disease, but also to determine the presence of meningitis, cavernous sinus thrombosis, or orbital abscess formation, which requires surgical drainage. Most associated abscesses occur in the medial orbit adjacent to the ethmoidal sinuses, with spread of infection via communicating veins (septic thrombophlebitis) or across the thin lamina papyracea. Chronic mucoceles may also be associated with cellulitis or abscess formation.
Rhinoorbital mucormycosis (genera Mucor, Absidia, or Rhizopus) is a catastrophic form of often fulminant, necrotizing orbital infection, most likely to occur in patients in ketoacidosis or immunosuppressed by chemotherapy, AIDS, or hemodialysis. Such infection is extremely rare in healthy individuals. A chronic form of rhinocerebral mucormycosis is well described,38 and is associated with carotid artery and cavernous sinus thrombosis. Rapid confirmation by nasopharyngeal mucosal aspiration and biopsy is essential. Wide debridement and amphotericin B infusion may be life-saving, and hyperbaric oxygen has been advocated.39 Aspergillosis may also cause an indolent or acute orbital cellulitis (see also Volume 2, Chapter 12).
Allergic fungal sinusitis is a relatively uncommon form of chronic paranasal mycosis in immunocompetent individuals. This entity can involve the orbit without direct invasion or dire outcome, and is most frequently, but not exclusively, attributed to Aspergillus. Signs include nasal obstruction, focal pain, proptosis, diplopia, optic neuropathy, and facial deformity. Inflamed sinus mucosa shows hyperintense signal characteristics on both T1- and T2-weighted MRI, but isointense signal of sinus cavities, with involvement of multiple sinuses; peripheral eosinophilia and elevated total immunoglobulin E, as well as fungus-specific IgE and IgG, help establish the diagnosis.40 In the differential spectrum are included invasive fungal sinusitis, orbital inflammatory pseudotumor, metastatic carcinoma, lymphoma, Wegener’s granulomatosis, and systemic vasculitis.
Idiopathic orbital inflammation (orbital pseudotumor) is a frequent cause of acute, subacute, or chronic painful ophthalmoplegia, accompanied by variable orbital signs. This clinical term encompasses noninfectious processes that mimic cellulitis, Graves’ disease, or neoplasm; thus, the term orbital pseudotumor. Inflammation may be diffuse, or localized to the posterior scleral coat (posterior scleritis), to single or multiple extraocular muscles (orbital myositis; see Volume 2, Chapter 12), to the lacrimal gland (dacryoadenitis), or to the meninges surrounding the intraorbital optic nerve (perioptic neuritis). Alternatively, orbital pseudotumor may present as a soft tissue mass. Signs and symptoms are determined by location and include severe to mild orbital ache, diplopia, lid swelling with ptosis, conjunctival chemosis, episcleral injection, proptosis, and ductional defects. Uveitis, uveal effusion, and optic neuropathy are rare, but account for visual loss.
There is an emerging literature on a sclerosing form of orbital pseudotumor associated with IgG4-related disease in which there may also be systemic involvement of multiple organs including the pancreas, kidneys, retroperitoneum, and prostate among other sites.41,42,43,44 Not only can this condition mimic lymphoma,45 there are cases of lymphoma arising in IgG4-related chronic sclerosing dacryoadenitis.46,47,48 Steroid therapy is currently the mainstay of treatment of this evolving entity, although alternative immunosuppressive therapies such as monoclonal antibodies may be useful particularly in the not infrequent circumstance of steroid resistance.49
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