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Acquired Binocular Horizontal Diplopia

1999; Elsevier BV; Volume: 74; Issue: 9 Linguagem: Inglês

10.4065/74.9.907

1942-5546

Paul W. Brazis, Andrew G. Lee,

Vestibular and auditory disorders

Binocular horizontal diplopia is an important symptom that may foretell or help localize and characterize various neurologic and neuromuscular disorders. An appropriate evaluation requires a careful and complete neuro-ophthal-mic history and examination. This review focuses on the differential diagnosis of binocular horizontal diplopia. Binocular horizontal diplopia is an important symptom that may foretell or help localize and characterize various neurologic and neuromuscular disorders. An appropriate evaluation requires a careful and complete neuro-ophthal-mic history and examination. This review focuses on the differential diagnosis of binocular horizontal diplopia. Binocular horizontal diplopia is usually due to disease processes affecting the medial or lateral rectus muscles or the innervation of these muscles (including ocular motor cranial nerves and neuromuscular junction) or to processes affecting fusion or convergence and divergence mechanisms. By definition, patients with horizontal diplopia complain that the 2 images are side by side. The separation of images may vary or remain unchanged at far-or near-fixation. For example, the image separation due to a left abducens nerve palsy is typically worse at distance than at near and worse on left gaze. Distinguishing between monocular and binocular diplopia is imperative because these 2 disorders have different diagnostic implications. Horizontal diplopia is binocular if it disappears with either eye closed; this suggests that the underlying problem is due to ocular misalignment. Monocular diplopia persists with 1 eye closed, is not due to ocular misalignment, and is usually due to local eye disease or refractive error. Monocular diplopia often clears when a pinhole is placed over the involved eye. Although monocular diplopia may be annoying and anxiety provoking, its implications are essentially ocular, and thus it is of interest only to ophthalmologists. A phoria is a latent ocular misalignment that is kept in check by fusion. Fusion is the process of merging images from each eye into a single perception. Sensory fusion is the cortical integration of 2 images, whereas motor fusion represents the corrective movements of the eyes required to maintain eye alignment on a specific target. Breakdown of fusion due to fatigue, stress, illness, etc may allow a preexisting phoria to become an intermittent or manifest tropia. Esophorias and esotropias (ETs) are medial deviations; exophorias and exotropias (XTs) are lateral deviations. The degree of eye deviation may be approximately equal in all directions of gaze (comitant) or may vary in different positions of gaze (incomitant). Horizontal deviations due to childhood strabismus are typically comitant, whereas most of the acquired deviations are incomitant. Ductions (each eye moving separately) and versions (both eyes moving conjugately) must always be assessed. In the assessment of a normal eye excursion, an imaginary vertical line through the lower lacrimal punctum should coincide with a boundary line between the inner third and outer two thirds of the cornea. If more cornea is hidden, adduction is excessive; if more cornea and some sciera are visible, adduction is limited. If abduction is normal, the corneal limbus should touch the outer canthus. If the limbus passes that point and some of the cornea is hidden, abduction is excessive; if some of the sciera remains visible, abduction is limited.1von Noorden GK Binocular Vision and Ocular Motiliry: Theory and Management of Strabismus. 5th ed. Mosby, St Louis, Mo1996Google Scholar In this report, we summarize the causes of acquired horizontal diplopia from a neuro-ophthalmologic perspective (Table 1). Etiologic factors of binocular horizontal diplopia are divided into disorders causing ET and disorders causing XT (Table 1). Congenital and childhood strabismus syndromes (Table 2) are mentioned superficially. A thorough and excellent discussion of childhood strabismus syndromes was recently published.1von Noorden GK Binocular Vision and Ocular Motiliry: Theory and Management of Strabismus. 5th ed. Mosby, St Louis, Mo1996Google ScholarTable 1Causes of Acquired Binocular Horizontal Diplopia Causes ofesotropia Childhood strabismus syndromes (see Table 2)Change of angle of preexisting childhood strabismus or loss of suppression scotomaDecompensation of a long-standing esophoriaConsecutive esotropia (after strabismus surgery)Optical (eg, optical center change in glasses, overminus in accommodative esophoria)Sensory esotropia (usually not associated with diplopia)Disorders of muscle and restrictive syndromes Orbital myositis (orbital pseudotumor)Thyroid eye diseaseMyasthenia gravisMedial orbital wall fracturePostsurgical esotropiaIsolated weakness of lateral rectus muscleMuscle traumaProgressive external ophthalmoplegia syndromesOther orbital disease processes Disorders of cranial nerves Sixth nerve palsyOcular neuromyotonia Central disorders Cyclic esotropiaPeriodic alternating esotropiaDivergence insufficiency or paralysisAcute acquired comitant esotropiaSpasm of the near reflexMidbrain pseudo-sixth nerve palsyThalamic esotropiaAcquired motor fusion deficiencyHemifield slide phenomenaCauses ofexotropia Childhood strabismus syndromes (see Table 2)Change of angle of preexisting childhood strabismus or loss of suppression scotomaDecompensation of a long-standing exophoriaConsecutive exotropia (after strabismus surgery)Optical factorsSensory exotropia (usually not associated with diplopia)Disorders of the muscle Orbital myositis (orbital pseudotumor)Thyroid eye disease (uncommon)Myasthenia gravisMedial orbital wall fracturePostsurgical exotropiaIsolated weakness of medial rectus muscleMuscle traumaProgressive external ophthalmoplegia syndromesOther orbital disease processes Disorders of cranial nerves Third nerve palsyOcular neuromyotonia Central disorders Acquired motor fusion deficiencyInternuclear ophthalmoplegia (INO) (wall-eyed monocular INO syndrome and wall-eyed bilateral INO syndrome) and the one-and-a-half syndrome (paralytic pontine exotropia)Vitamin E deficiency (eg, abetalipoproteinemia)Convergence insufficiency and paralysisHemifield slide phenomena Open table in a new tab Table 2Classification of Childhood Strabismus Syndromes*Modified from von Noorden' with permission. Esodeviations Comitant esodeviation Accommodative esotropia RefractiveNonrefractiveHypoaccommodativePartially accommodative esotropia Nonaccommodative esotropia Infantile (onset, birth to 6 mo)Acquired (includes esotropia with myopia, cyclic esotropia, and some cases of divergence insufficiency) MicrotropiaNystagmus blockage syndromeNoncomitant esodeviation A- and V-pattern esotropiaDuane retraction syndrome type 1 and 3Congenital mechanical-restrictive esodeviations (eg, congenital fibrosis) Secondary esodeviation Sensory esotropiaConsecutive esotropia (after strabismus surgery)Exodeviations PrimaryDuane syndrome type 2Restrictive-congenital fibrosisSecondary Sensory exotropiaConsecutive exotropia (after strabismus surgery)* Modified from von Noorden' with permission. Open table in a new tab Childhood strabismus syndromes will be discussed briefly because they may be confused with acquired causes of ET and XT. Most childhood ETs are comitant and manifest with cross-eyes or amblyopia when the child is young. Childhood comitant ETs may be due to hyperopia, impaired accommodation, or convergence. Noncomitant childhood ETs include A-pattern and V-pattern esodeviations, in which the esodeviation is worse on upward gaze and downward gaze, respectively; retraction syndromes (see subsequent discussion); and mechanical-restrictive esodeviation due to congenital fibrosis of the medial rectus muscle. Some patients with congenital nystagmus are able to decrease the amplitude or frequency of their nystagmus by convergence (nystagmus blockage syndrome), and thus an ET develops. Occasionally, adults with a long-standing, essentially asymptomatic esophoria may have diplopia due to decompensation. This decompensation of a long-standing esophoria may occur after head trauma, with changing refractive needs, with systemic illnesses, when the patient takes drugs that depress the central nervous system (eg, alcohol or sedatives), or for unclear reasons. A thorough history and examination often reveal supportive evidence for a longstanding strabismus, including a history of childhood strabismus or patching, head turn, and horizontal comitance. Childhood XT is less frequent than childhood ET. The XT may be intermittent or persistent, and sometimes adults with exophoria or intermittent XT may have diplopia due to an inability to compensate adequately for the eye misalignment (decompensation of exophoria). The Duane retraction syndrome is characterized by a narrowing of the palpebral fissure and globe retraction on adduction. Three types have been described.2DeRespinis PA Caputo AR Wagner RS Guo S Duane's retraction syndrome [published correction appears in Surr Ophthalmol. 1996;40:423].Surv Ophthalmol. 1993; 38: 257-288Abstract Full Text PDF PubMed Scopus (172) Google Scholar In type 1, abduction is limited, but adduction is normal or only slightly limited. Some patients have impaired adduction but normal or slightly limited abduction (type 2), whereas others have pronounced impairment of both adduction and abduction (type 3).3Huber A Elcclrophysiology of the retraction syndrome.Br J Ophthalmat. 1974; 58: 293-300Crossref PubMed Scopus (236) Google Scholar Eye deviation may or may not be present in primary position, but if present, ET is usually present in patients with type 1 and type 3, while XT is more frequent in those with type 2. Although many patients adopt a head turn to maintain single binocular vision, they rarely complain of spontaneous diplopia. When asked, they realize they have diplopia and state that they recognize 2 images when their eyes are misaligned. With all 3 types, there may be a vertical deviation of the adducting eye, which takes the form of upshoots and downshoots. Although the Duane retraction syndrome is predominantly congenital and is thought to be due to anomalous innervation of the lateral rectus muscle by the inferior division of the oculomotor nerve,2DeRespinis PA Caputo AR Wagner RS Guo S Duane's retraction syndrome [published correction appears in Surr Ophthalmol. 1996;40:423].Surv Ophthalmol. 1993; 38: 257-288Abstract Full Text PDF PubMed Scopus (172) Google Scholar an acquired Duane-like syndrome has been described in patients with pontine glioma, in those with rheumatoid arthritis, after trigeminal rhizotomy, and after removal of an orbital cavernous hemangioma by lateral orbitotomy.4Otradovcc J Obraz Duanova retrakcniko syndromu u nadoru mozkového kmene.Cesk Oftalmol. 1968; 24: 90-95PubMed Google Scholar, 5Smith JL Damast M Acquired retraction syndrome after sixth nerve palsy.Br J Ophthalmol. 1973; 57: 110-114Crossref PubMed Scopus (9) Google Scholar, 6Sood GC Srinath BS Krishnamurthy G Acquired Duane's retraction syndrome following Kronlein's operation.Eye Ear Nose Throat Mon. 1975; 54: 308-310PubMed Google Scholar, 7Baker RS Robertson Jr, WC Acquired Duane's retraction syndrome in a patient with rheumatoid arthritis.Ann Ophthalmol. 1980; 12: 269-272Google Scholar Consecutive ET refers to esodeviation that occurs iatrogenically after surgical overcorrection of an exo-deviation (patients in whom an exodeviation is surgically undercorrected may still have diplopia postoperatively). Similarly, consecutive XT results from surgical over-correction of ET or may arise spontaneously in a previously esotropic patient, especially in association with poor vision in the deviating eye (sensory XT). Sensory deviations including ET or XT result from reduced visual acuity in 1 eye. Such patients do not complain of diplopia because of the visual loss. Loss of fusion in cases of visual loss allows a preexisting phoria to manifest. Sidikaro and von Noorden8Sidikaro Y von Noorden GK Observations in sensory heterotropia.J Pediatr Ophthalmol Strabismus. 1982; 19: 12-19PubMed Google Scholar described 121 patients with sensory heterotropias and noted that ET and XT occurred with almost equal frequency when the onset of visual impairment occurred at birth or between birth and 5 years. Sensory XT, however, predominates in older children and adults.8Sidikaro Y von Noorden GK Observations in sensory heterotropia.J Pediatr Ophthalmol Strabismus. 1982; 19: 12-19PubMed Google Scholar Orbital Myositis.—Orbital myositis (idiopathic orbital inflammation or orbital pseudotumor) is a clinicopatho-logic entity with the following diagnostic criteria: (1) a unilateral orbital mass lesion, clinically manifesting with signs of mass effect, inflammation, or infiltration; (2) neuroimaging showing a focal or diffuse inflammatory lesion; (3) histopathology demonstrating a fibroinflammatory lesion; and (4) investigations eliminating identifiable local or systemic causes.9Mombaerts I Goldschmeding R Schlingemann RO Koomneef L What is orbital pseudolumor?.Surv Ophthalmol. 1996; 41: 66-78Abstract Full Text PDF PubMed Scopus (223) Google Scholar When the inflammatory process is confined to 1 or multiple extraocular muscles, the process is referred to as orbital myositis, although some investigators believe that orbital pseudotumor and orbital myositis may be distinct clinicotherapeutic entities.10Mombaerts I Koomneef L Current status in the treatment of orbital myositis.Ophthalmology. 1997; 104: 402-408Abstract Full Text PDF PubMed Scopus (113) Google Scholar Patients have acute or subacute orbital pain and diplopia. Findings include conjunctival chemosis and injection, ptosis, and proptosis. The process may be unilateral or bilateral and usually resolves with corticosteroid therapy.10Mombaerts I Koomneef L Current status in the treatment of orbital myositis.Ophthalmology. 1997; 104: 402-408Abstract Full Text PDF PubMed Scopus (113) Google Scholar The illness is often monophasic, but episodes may recur. Characteristics associated with recurrences include male gender, lack of proptosis, eyelid retraction, horizontal extraocular muscle involvement, multiple or bilateral extraocular muscle involvement, muscle tendon sparing on neuroimaging, and lack of response to corticosteroids or nonsteroidal anti-inflammatory agents.11Mannor GE Rose GE Moseley IF Wright JE Outcome of orbital myositis: clinical features associated with recurrence.Ophthalmology. 1997; 104: 409-413Abstract Full Text PDF PubMed Scopus (91) Google Scholar Neuroimaging in patients with orbital myositis reveals enlarged, irregular muscles usually with tendinous insertion involvement. The differential diagnosis includes thyroid eye disease, orbital cellulitis (including orbital aspergillosis or mucormycosis infection), sarcoidosis, Erdheim-Chester disease, low-flow dural-cavernous sinus fistula, lymphoid hyperplasia, lymphoma, Hodgkin disease, orbital muscle metastasis, Wegener granulomatosis, and other vasculitides. Pathological studies of orbital myositis reveal an inflammatory infiltrate composed mainly of small well-differentiated mature lymphocytes, admixed with plasma cells, in a diffuse or multifocal pattern. The muscle fibers are swollen and separated by edema and fibrosis, with loss of normal striations and degeneration of muscle fibers.9Mombaerts I Goldschmeding R Schlingemann RO Koomneef L What is orbital pseudolumor?.Surv Ophthalmol. 1996; 41: 66-78Abstract Full Text PDF PubMed Scopus (223) Google Scholar Other atypical histopathologic patterns, such as extensive sclerosis, true vasculitis, granulomatous inflammation, and tissue eosinophilia, can be used for subclassification of orbital pseudotumor.9Mombaerts I Goldschmeding R Schlingemann RO Koomneef L What is orbital pseudolumor?.Surv Ophthalmol. 1996; 41: 66-78Abstract Full Text PDF PubMed Scopus (223) Google Scholar Thyroid Eye Disease.—Thyroid eye disease (thyroid orbitopathy, thyroid ophthalmopathy, or Graves disease) is characterized clinically by eyelid retraction, eyelid lag in downward gaze, exophthalmos, diplopia (due to extraocular muscle inflammation or fibrosis), potential visual loss due to compressive optic neuropathy or corneal damage, and signs and symptoms of orbital congestion.12Bartley GB Gorman CA Diagnostic criteria for Graves' ophthalmopathy.Am J Ophthalmol. 1995; 119: 792-795Abstract Full Text PDF PubMed Scopus (284) Google Scholar, 13Bartley GB The epidemiologic characteristics and clinical course of ophthalmopathy associated with autoimmune thyroid disease in Olmsled County, Minnesota.Trans Am Ophthalmol Soc. 1994; 92: 477-588PubMed Google Scholar, 14Bartley GB Fatourechi V Kadrmas EF et al.The incidence of Graves' ophthalmopathy in Olmsted County, Minnesota.Am J Ophthalmol. 1995; 120: 511-517Abstract Full Text PDF PubMed Scopus (132) Google Scholar, 15Bartley GB Fatourechi V Kadrmas EF et al.Clinical features of Graves' ophthalmopathy in an incidence cohort.Am J Ophthalmol. 1996; 121: 284-290Abstract Full Text PDF PubMed Scopus (324) Google Scholar, 16Bartley GB Fatourechi V Kadrmas EF et al.Chronology of Graves' ophthalmopathy in an incidence cohort.Am J Ophthalmol. 1996; 121: 426-434Abstract Full Text PDF PubMed Scopus (102) Google Scholar Patients may develop ophthalmopathy even in the absence of clinical or laboratory evidence of thyroid disease or after correction of hyperthyroidism. The ophthalmopathy of thyroid disease is an autoimmune process with a progressive but self-limited variable course extending over 1 to 3 years. In adults, it is a common cause of acquired diplopia or exophthalmos. The clinical spectrum of ophthalmopathy ranges from minor eye symptoms and signs to severe, disabling vision-threatening problems. Thyroid ophthalmopathy is present if eyelid retraction occurs in association with objective evidence of thyroid dysfunction or abnormal regulation, exophthalmos, optic nerve dysfunction, or ex-traocular muscle involvement. Eyelid retraction is the most common ophthalmic feature of autoimmune thyroid disease, being present either unilaterally or bilaterally in more than 90% of patients at some point in the clinical course. Exophthalmos of 1 or both eyes affects approximately 60% of patients, restrictive extraocular myopathy is apparent in about 40%, and optic nerve dysfunction occurs in either 1 or both eyes in 6%.12Bartley GB Gorman CA Diagnostic criteria for Graves' ophthalmopathy.Am J Ophthalmol. 1995; 119: 792-795Abstract Full Text PDF PubMed Scopus (284) Google Scholar, 13Bartley GB The epidemiologic characteristics and clinical course of ophthalmopathy associated with autoimmune thyroid disease in Olmsled County, Minnesota.Trans Am Ophthalmol Soc. 1994; 92: 477-588PubMed Google Scholar, 14Bartley GB Fatourechi V Kadrmas EF et al.The incidence of Graves' ophthalmopathy in Olmsted County, Minnesota.Am J Ophthalmol. 1995; 120: 511-517Abstract Full Text PDF PubMed Scopus (132) Google Scholar, 15Bartley GB Fatourechi V Kadrmas EF et al.Clinical features of Graves' ophthalmopathy in an incidence cohort.Am J Ophthalmol. 1996; 121: 284-290Abstract Full Text PDF PubMed Scopus (324) Google Scholar, 16Bartley GB Fatourechi V Kadrmas EF et al.Chronology of Graves' ophthalmopathy in an incidence cohort.Am J Ophthalmol. 1996; 121: 426-434Abstract Full Text PDF PubMed Scopus (102) Google Scholar The restrictive extraocular muscle involvement may be confirmed by impaired ocular motility during the forced duction test. The extraocular muscles predominantly affected include the inferior, medial, and superior rectus muscles; because the process causes muscle tightness or restriction, the diplopia is worse in the direction opposite that of the involved muscle(s) action. Thus, hypertropia and ET are common in patients with thyroid eye disease, but XT is unusual because the lateral rectus muscle is usually not involved substantially. In fact, if a patient with thyroid eye disease is noted to have XT, superimposed my-asthenia gravis (MG) should be considered because the risk of MG is increased in patients with thyroid eye disease.'17Vargas ME Warren FA Kupersmith MJ Exotropia as a sign of myasthenia gravis in dysdhyroit ophthalmopathy.Br J Ophthalmol. 1993; 77: 822-823Crossref PubMed Scopus (27) Google Scholar Neuroimaging (computed tomography or magnetic resonance imaging) of the orbits often reveals smooth enlargement of multiple extraocular muscles, frequently bilaterally, with the muscle tendinous insertions tending to be spared. Thyroid ophthalmopathy may be asymmetric between the 2 orbits clinically and on neuroimaging, and the disease process often undergoes spontaneous exacerbations and remissions. The disorder often begins with an acute, active inflammatory phase, lasting 6 to 18 months, which is mediated by lymphocytic and fibroblastic infiltration into orbital tissues. The acute phase is followed by a chronic phase, characterized by hypertrophy and fibrosis of the extraocular muscles, lacrimal glands, and orbital fat.18Lee AG Brazis PW Therapeutic neuro-ophthalmology.Curr Neur. 1997; 17: 265-292Google Scholar Thyroid eye disease and orbital myositis may resemble each other clinically. The differential diagnostic features are outlined in Table 3.Table 3Clinical Differential Diagnosis of Orbital Myositis and Thyroid Eye DiseaseOrbital myositisThyroid eye diseasePreponderance same in males and femalesFemale preponderanceAcute or subacute onsetGradual onsetOften severe orbital painPainless or foreign body sensation unless cornea damaged from exposureMotility problems earlyMotility problems lateLimited ductions in the field of action of the involved muscle (paretic)Limited ductions usually to side opposite the involved muscle (restrictive)No eyelid lag or retractionEyelid lag and retractionNeuroimaging of orbitNeuroimaging of orbit Enlarged muscles irregular Enlarged muscles often smooth Tendinous insertion usually involved Tendinous insertions tend to be spared Unilateral abnormalities when clinically unilateral Often bilateral muscle involvement even if clinically unilateral Open table in a new tab Myasthenia Gravis.—Myasthenia gravis is a chronic disorder of neuromuscular transmission characterized clinically by varying weakness and fatigue of voluntary muscles. This disease is caused by an acquired autoimmunity to the motor endplate and is associated with antibodies that block or cause increased degradation of acetylcholine receptors (AchRs). Ocular MG, a variant of MG, clinically involves only the extraocular, levator palpebrae superioris, or orbicularis oculi muscles. Approximately 48% to 53% of patients with MG will have solely ocular symptoms at onset, and ocular symptoms remain in 49% of these patients. Increased duration of pure ocular MG is associated with a decreased risk of late generalization, with only 15% of observed generalizations occurring after more than 2 years of purely ocular symptoms.19Bever Jr, CT Aquino AV Penn AS Lovelace RE Rowland LP Prognosis of ocular myasthenia.Ann Neurol. 1983; 14: 516-519Crossref PubMed Scopus (196) Google Scholar The diagnosis of MG should be considered in all patients with ptosis or ocular motor weakness without pupillary involvement.20Weinberg DA Lesser RL Vollmer TL Ocular myasthenia: a protean disorder.Surv Ophthalmol. 1994; 39: 169-210Abstract Full Text PDF PubMed Scopus (66) Google Scholar Weakness and fatigue confined to the extraocular muscles or eyelids combined with orbicularis oculi paresis are symptoms especially suggestive of this diagnosis. Clinical involvement of the pupil, eye pain or headaches, visual loss, or involvement of sensation essentially negate this diagnosis. MG may cause hypertropia, ET, or XT and can mimic many neurogenic conditions, including abducens nerve palsies, gaze abnormalities, and internuclear ophthalmoplegia (INO) (see subsequent discussion). Therefore, in any patient with an abnormality of horizontal gaze (eg, sixth nerve palsy), MG should be considered. Fatigability and variability of clinical findings are characteristic of MG. The diagnosis is made by demonstrating fatigability of the eyelids or eye muscles. Positive results on a Tensilon test and AchR antibody studies may help to confirm the diagnosis. Of note, AchR antibodies are positive in 80% to 95% of patients with generalized MG and in 34% to 56% of patients with ocular MG.19Bever Jr, CT Aquino AV Penn AS Lovelace RE Rowland LP Prognosis of ocular myasthenia.Ann Neurol. 1983; 14: 516-519Crossref PubMed Scopus (196) Google Scholar, 21Evoli A Tonali P Bartoccioni E Lo Monaco M Ocular myasthenia: diagnostic and therapeutic problems.Acta Neurol Scand. 1988; 77: 31-35Crossref PubMed Scopus (106) Google Scholar, 22Oosterhuis HJ Long-term effects of treatment in 374 patients with myasthenia gravis.Monogr Allergy. 1988; 25: 75-85PubMed Google Scholar, 23Limburg PC The TH Hummel-Tappel E Oosterhuis HJ Anti-acetylcholine receptor antibodies in myasthenia gravis, part 1: relation to clinical parameters in 250 patients.J Neurol Sei. 1983; 58: 357-370Abstract Full Text PDF PubMed Scopus (156) Google Scholar, 24Seybold ME Myasthenia gravis: a clinical and basic science review.JAMA. 1983; 250: 2516-2521Crossref PubMed Scopus (58) Google Scholar, 25Vincent A Newsom-Davis J Acetylcholine receptor antibody as a diagnostic test for myasthenia gravis: results in 153 validated cases and 2967 diagnostic assays.J Neurol Neurosurg Psychiatry. 1985; 48: 1246-1252Crossref PubMed Scopus (405) Google Scholar, 26Bartoccioni E Sauderi F Evoli A Provenzano C Flamini G Ocular myasthenia gravis: two different diseases.Lancet. 1986; 1: 1038-1039Abstract PubMed Scopus (11) Google Scholar, 27Drachman DB de Silva S Ramsay D Pestronk A Humoral pathogenesis of myasthenia gravis.Ann N Y Acad Sci. 1987; 505: 90-105Crossref PubMed Scopus (95) Google Scholar, 28Howard Jr, FM Lennon VA Finley J Matsumoto J Elveback LR Clinical correlations of antibodies that bind, block, or modulate human acetylcholine receptors in myasthenia gravis.Ann NY Acad Sei. 1987; 505: 526-538Crossref PubMed Scopus (191) Google Scholar, 29Newsom-Davis J Willcox N Schluep M et al.Immunological heterogeneity and cellular mechanisms in myasthenia gravis.JAMA NY Acad Sei. 1987; 505: 12-26Crossref PubMed Scopus (56) Google Scholar, 30Morel E Vemet-der Garabedian B Eymard B Raimond F Bustarrcl FA Bach JF Binding and blocking antibodies to the human acetylcholine receptor: are they selected in various myasthenia gravis forms?.Immunol Res. 1988; 7: 212-217Crossref PubMed Scopus (12) Google Scholar, 31Soliven BC Lange DJ Penn AS et al.Seronegative myasthenia gravis.Neurology. 1988; 38: 514-517Crossref PubMed Google Scholar, 32Oh SJ Kim DE Kumoglu R Bradley RJ Dwyer D Diagnostic sensitivity of the laboratory tests in myasthenia gravis.Muscle Nerve. 1992; 15: 720-724Crossref PubMed Scopus (175) Google Scholar Testing for AchR binding, blocking, and modulating antibodies increases the assay yield in patients with generalized MG and ocular MG. Thus, approximately one half of patients with MG that is confined to the ocular muscles will have negative AchR antibodies. Fractures of the Medial Orbital Wall and Postsurgi-cal ET and XT.—Orbital trauma may result in horizontal diplopia because of a fracture of the medial orbital wall in isolation or accompanied by a fracture of the orbital floor or other orbital bones.1von Noorden GK Binocular Vision and Ocular Motiliry: Theory and Management of Strabismus. 5th ed. Mosby, St Louis, Mo1996Google Scholar, 33Whyte DK Blowout fractures of the orbil.Br J Ophthalmol. 1968; 52: 721-728PubMed Google Scholar, 34Dodick JM Galin MA Kwitko M Medial wall fracture of the orbit.Can J Ophthalmol. 1969; 4: 377-378PubMed Google Scholar, 35Duane TD Schatz NJ Caputo AR Pseudo-Duane's retraction syndrome.Trans Am Ophthalmol Soc. 1977; 74: 122-132Google Scholar, 36Eitzcn JP Elsas FJ Strabismus following endoscopic intranasal sinus surgery.J Pediatr Ophthalmol Strabismus. 1991; 28: 168-170PubMed Google Scholar Incarceration of the medial rectus muscles may lead to ET with impaired abduction or XT with impaired adduction. Medial orbital wall injury may occur iatrogenically during endoscopie transnasal sinus surgery.1von Noorden GK Binocular Vision and Ocular Motiliry: Theory and Management of Strabismus. 5th ed. Mosby, St Louis, Mo1996Google Scholar, 36Eitzcn JP Elsas FJ Strabismus following endoscopic intranasal sinus surgery.J Pediatr Ophthalmol Strabismus. 1991; 28: 168-170PubMed Google Scholar In addition, medial or lateral orbital surgery (eg, optic nerve sheath fenestration) may directly injure the medial or lateral rectus muscles, an outcome resulting in initial muscle paresis, sometimes followed by scarring and restrictive ET or XT, respectively. Other ocular surgeries (eg, pterygium surgery, scleral buckle, and glaucoma setons) may also result in horizontal diplopia. Isolated Weakness of the Medial or Lateral Rectus Muscles.—Isolated medial rectus paresis is rare and results in XT because of unopposed action of the lateral rectus muscle. The XT is worse on gaze to the opposite side and is associated with impaired adduction on the side of the weak muscle. Impaired monocular adduction is more often noted, however, with INO (see subsequent discussion) than isolated medial rectus palsy because of a partial third nerve palsy. Isolated medial rectus muscle paresis may occur with MG, orbital myositis, muscle trauma, or orbital disease. Lesions of the oculomotor nerve cause medial rectus paresis but not in isolation. Bec