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Major Review

Orbital Myositis: A Comprehensive Review and Reclassification

McNab, Alan A. DMedSc, FRANZCO*,†

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Ophthalmic Plastic and Reconstructive Surgery: March/April 2020 - Volume 36 - Issue 2 - p 109-117
doi: 10.1097/IOP.0000000000001429
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Orbital myositis (OM) is relatively rare but is the next most common cause of extraocular muscle (EOM) disease after thyroid-associated orbitopathy (TAO).1,2 It typically presents as idiopathic acute onset, painful diplopia in young adult females, with inflammation of a single EOM, and usually responds to a course of oral corticosteroids. However, there are many atypical cases. These include chronic and recurrent idiopathic OM, those not responding to corticosteroids, and cases occurring in the setting of systemic inflammatory, autoimmune, and infective conditions, and in response to drugs.

Thyroid-associated orbitopathy is by far the commonest cause of inflammation of EOM, but this review specifically does not address TAO, and summarizes the current state of knowledge of all other forms of OM.


There is no agreed nomenclature or classification system to describe OM. Some case reports and reviews use the term “ocular myositis.”3 Schoser4 suggested using the terms “limited oligosymptomatic ocular myositis” and “severe exophthalmic ocular myositis” to differentiate typical from atypical OM. However, many cases do not fit this simple classification. There is also no agreement on how to describe OM that occurs in the setting of specific inflammatory or autoimmune conditions.

Orbital myositis bears many similarities to uveitis. It is an inflammatory condition, often idiopathic, but also often occurring in the setting of specific autoimmune, inflammatory, and infective conditions. There have been efforts to standardize nomenclature in uveitis.5 This common language assists researchers to define conditions and their response to treatment, and in reporting and comparing their research.6

Using the Standardized Uveitis Nomenclature, and evaluating patients with a thorough history, ophthalmic examination, and targeted investigations, led one tertiary uveitis center to reclassify 52/179 (29.0%) patients with idiopathic uveitis and give them a specific diagnosis.7 Orbital myositis would benefit from a similar systematized approach. After presenting a review of all forms of OM, the author proposes a classification system that might serve as a basis for a clearer understanding of OM and also serve as a framework for future research.


Idiopathic acute OM is an uncommon disease but the commonest form of OM. There is acute onset orbital pain, exacerbated by eye movement, with diplopia, often some eyelid swelling, ptosis, and conjunctival chemosis.8 There may be injection over the insertion of the affected muscle. The muscle may be paretic, restricted, or both. On imaging (CT or MRI), there is usually enhancing fusiform enlargement of the muscle belly, often with involvement of the muscle tendon.

Females are more affected, in a ratio of 2:1.8,9 While any age can be affected (range 3–84 years in one meta-analysis), the majority are young adults (mean, 37 years; median, 34).8

Most have a single affected muscle (68% of 75 cases in the series by Siatkowski et al9), with 2 affected muscles in 22%, 3 or more in 10%, and only 1 with bilateral involvement. The relative frequency of involvement of each EOM is listed in Table 1 and differs from that observed in TAO.

Frequency of 208 extraocular muscles affected by orbital myositis9

Ocular motility varies between patients and over the course of the disease. A few may have normal motility but with pain in the direction of action of the muscle. Siatkowski et al9 noted normal motility for several days, followed by a paretic phase (average, 13 days), then a combined paretic and restrictive phase (mean, 22 days), and finally a restrictive phase lasting 19 days on average. Not all follow this pattern, and many pass straight from a paretic phase to normal function with treatment. Early treatment may prevent later fibrosis and restrictive strabismus. Others have observed differing patterns of motility disturbance at presentation, with pure paresis (20.5%), mixed paretic and restrictive (34.1%), and pure restrictive patterns (45.5%) seen in a large cohort of 44 Chinese patients.10 An extended period of restrictive movement suggests fibrosis in the muscle, and recovery may be incomplete.

Oblique Muscle Myositis.

Orbital myositis of the oblique muscles is relatively uncommon. There are reports of isolated superior11–13 or inferior oblique myositis,14 or both together.15 When the inferior oblique is affected, there is usually marked inferior conjunctival chemosis.16

Levator Palpebrae Superioris Myositis.

There are several cases of isolated levator palpebrae superioris myositis reported,17–21 with acute onset painful ptosis (paresis), reduced levator muscle function, and sometimes eyelid lag on down gaze (restriction). Four acute adult cases responded well to steroids,17–20 but 3 children had a chronic course with poor response to treatment.21

Recurrent OM.

Typical acute idiopathic OM usually responds (68% of 75 cases reported by Siatkowski et al9) within days or weeks to a course of oral corticosteroids. However, recurrence on weaning treatment, or months or years after the episode, is relatively common. Siatkowski et al9 reported recurrences in 15% of 75 patients within 6 months. Mombaerts and Koornneef22 however found that 9 of her 16 cases (56%) had 1 or more recurrence with a disease-free interval of 4.1 months (range, 0.5–17 months). Six of 26 cases of OM reviewed by Mannor et al23 developed recurrent disease. Clinical features associated with recurrence were male gender, multiple EOM involvement, and lack of response to corticosteroids.

Chronic OM.

Chronic OM usually occurs in patients with a poor response to corticosteroids, raising concerns about the diagnosis. A biopsy should be obtained to exclude other pathologies. Many patients with a chronic course will have an underlying systemic disease and may require steroid-sparing or biologic agents.24


Many single case reports or small series describe an association between systemic inflammatory or autoimmune diseases and OM (Table 2). The commonest are immunoglobulin G4–related ophthalmic disease (IgG4-ROD) and inflammatory bowel disease (IBD). Siatkowski et al9 found 4/75 (5.3%) cases with associated diseases (2 IBD, 1 systemic lupus erythematosus [SLE], and 1 relapsing polychondritis),9 Mombaerts and Koornneef22 reported 3/16 (18.8%) (IBD, psoriasis, and Human Leukocyte Antigen – B27 spondyloarthritis), and Patrinely et al54 reported 3/15 (20%) (IBD 1 case, and sarcoidosis in 2). Weinstein et al28 had 3/12 cases (25%) with associated diseases (IBD, SLE, and rheumatoid arthritis), and Yan and Wu10 reported 6/44 (1 SLE, 2 “lumbar rheumatism,” and 3 a preceding upper respiratory tract infection).

Autoimmune and inflammatory conditions associated with orbital myositis (with number of reported cases)

The demographic and clinical features of OM occurring in association with other diseases often differ from that seen in idiopathic acute OM. The data of all cases where there have been 4 or more reported in association with the particular condition are summarized in Table 3. The 4 granulomatosis with polyangiitis (GPA or Wegener granulomatosis) cases had insufficient published data to include in the Table 2.

Demographic and clinical details of OM in the setting of systemic inflammatory and autoimmune disease (idiopathic OM is listed at the top of the table for comparison purposes)

IgG4-Related Ophthalmic Disease.

IgG4-related disease commonly affects the orbit (IgG4-ROD),120,121 and EOM involvement in IgG4-ROD is relatively common (15–37% of IgG4-ROD).25–27 Multiple muscles are usually involved, and in just over half, bilateral EOM disease is seen. Extraocular muscle disease is always seen with other manifestations of IgG4-ROD, commonly infra-orbital nerve enlargement, paranasal sinus disease, and lacrimal gland disease.122 Despite the EOMs being enlarged, usually in a fusiform pattern, patients almost never have pain with eye movement, and eye movements are relatively normal. One study reporting strabismus in IgG4-ROD with EOM disease found that half the patients had normal movements with orthophoria, and half had small-angle tropias.123

Fibrosis does not appear to occur within EOMs to a sufficient degree to lead to restrictive strabismus. The relative lack of motility disturbance and the presence of other features of IgG4-ROD easily differentiates this condition from most other forms of OM.

Inflammatory Bowel Disease.

In 31 reported cases of OM with IBD (27 with Crohn disease and 4 with ulcerative colitis), the pattern of muscle involvement has differed from that seen with idiopathic acute OM.11,24,28–53 Inflammatory bowel disease–associated OM affected single muscles in only 32.2% (68% in idiopathic acute OM) and occurred bilaterally in 45.2% of cases (1.3% in idiopathic acute OM). Recurrent OM was also common in the IBD group (30%). In 6 cases, symptoms of OM preceded the onset of symptoms of IBD, sometimes by as much as 1 to 2 years.24,30,44,45,53

Several cases with IBD have had EOM biopsies. In 3 cases, a nonspecific infiltration of T-lymphocytes was reported,38,53 with some necrosis in one case53 and suppurative granulomatous inflammation in another.40

Most patients were managed with corticosteroids, but 10/23 (43.5%) required additional immunosuppression: infliximab,24,46,48 adalimumab,45,49 azathioprine,48,53 methotrexate, mycophenolate,53 and cyclophosphamide.42 This suggests that OM in IBD is more severe and more resistant to corticosteroids than idiopathic OM.


When orbital sarcoidosis has primarily affected EOM,54–67 bilateral involvement (69%) of multiple muscles (77%) has been common. In 14/16 with clinical details, 10 (71%) had painless diplopia and/or swelling. Sarcoidosis of other sites was known or found in 8/13 cases, and 5/13 had no evidence of sarcoidosis elsewhere on investigation. In 3 cases, lacrimal gland sarcoidosis was also present, and in 2 cases, disease spread from EOM in adjacent orbital fat.

In 11/13 (84.6%), sarcoidosis was diagnosed on EOM biopsy, and 2 had confirmation from biopsies elsewhere. Where treatment was reported, all responded well to corticosteroids.

Systemic and Discoid Lupus Erythematosus.

Of 10 reported cases of OM occurring in patients with SLE (8)9,10,28,68–72 or discoid lupus erythematosus (2),73,74 clinical details have been reported in 8 (6 SLE, 2 discoid lupus erythematosus). Six of 8 (75%) have been bilateral, and 75% were acute in onset. Half were on treatment for SLE when presenting with OM, and one was known to have discoid lupus erythematosus. One patient’s OM was their first presentation of SLE.71

Giant-Cell Myocarditis.

The association of OM with giant-cell myocarditis is rare but important because giant-cell myocarditis carries a high morbidity and mortality.124 There have been 8 reported cases of OM associated with giant-cell myocarditis75–82 and 1 case of fulminant lymphocytic myocarditis.83 Importantly, 7/9 cases of OM have presented before the onset of cardiac symptoms (range, 1 month to 3 years; median, 2 months). Two presented simultaneously with cardiac symptoms.

All 9 cases have had subacute OM with multiple muscles affected, bilaterally in 8/9 (89%), and in 7/9 (78%), pain has been a feature. Three have developed muscle disease elsewhere (bulbar,75,76 proximal limb,75,76 diaphragm83). Five of 9 cases have had EOM biopsies (2 postmortem) and have shown nonspecific lymphocytic infiltrate in all cases, histiocytic infiltrate in 2, and giant cells in only 1.

Presenting cardiac features included cardiac failure and ventricular tachycardia. Four of 9 patients died of cardiac failure, 3 needed cardiac transplant, and only 2 settled with immunosuppression.

Giant-cell myocarditis is associated with many autoimmune conditions,124 and in the 9 patients with OM and giant-cell myocarditis, 2 had vitiligo,77,78 and 1 rheumatoid arthritis.82

Poststreptococcal Pharyngitis.

After infection with group-A streptococci, inflammatory syndromes including rheumatic fever, reactive arthritis, and glomerulonephritis may occur. Uveitis uncommonly can occur,125 as may OM, with 9 cases confirmed by elevated antistreptolysin titers or positive throat cultures.84–88 Orbital myositis has also been reported after upper respiratory tract infections and flu-like illnesses without confirmation of infection by streptococci.10,22,28,126–128 Eight of these reports were from published series of OM, with 1/6,127 1/12,28 1/6,128 2/16,22 and 3/4410 patients reported to have had a preceding upper respiratory tract infection or flu-like illness (in total 8/84 [9.5%] with this association).

All cases in the confirmed poststreptococcal group have been single muscle OM, and orbital symptoms occurred between 2 and 6 weeks after the streptococcal infection. One patient also had a migratory arthritis.

Rheumatoid Arthritis.

The 5 women with rheumatoid arthritis all had established rheumatoid arthritis when their OM developed.18,89–92 Two developed OM while on the tumor necrosis factor inhibitor etanercept.91,92

Eosinophilic GPA (or Churg Strauss Syndrome).

All patients in this group had bilateral OM with multiple muscles affected,93–96 but only one reported mild pain.94

Behçet Disease.

All 5 cases presented with single muscle painful OM,24,97–100 with 1 later becoming multiple and bilateral.24 One patient’s OM was their first presentation of Behçet’s.98 Two patients required infliximab24 or cyclophosphamide for control of OM.

GPA (or Wegener Granulomatosis).

Patients with GPA frequently manifest orbital disease, with inflammatory masses often involving EOM, but rarely EOM disease can occur alone. Ismailova et al101 reported the clinical features of 74 GPA patients with orbital disease, dividing them into 3 patterns: an orbital mass without lacrimal gland involvement (60.8%), lacrimal gland involvement (35.1%), and EOM myositis (only 4.1%). In a case of superior oblique OM in a patient with GPA, the disease subsequently infiltrated the orbit more widely.102


Orbital myositis has been reported in a variety of infective conditions (Table 4). The commonest of these is herpes zoster ophthalmicus.

Infective diseases associated with orbital myositis

Herpes Zoster Ophthalmicus.

Orbital inflammation uncommonly occurs with herpes zoster ophthalmicus, including inflammation of EOMs. Twenty-three cases have been reported of OM in the setting of herpes zoster ophthalmicus,15,129–141 16 in females (69.6%), with an age range of 13 to 84 years (mean, 61.8; median, 66 years). Eight of 23 (34.8%) have had clinical and imaging features of OM from 1 to 9 days (most 2–3 days) prior to the development of the vesicular rash. More commonly, the OM has presented a few days after the rash, but 2 cases have developed OM a month later.

On MRI, inflammation of other orbital structures is often seen, including optic nerve sheath, orbital apex tissues, and lacrimal gland. Most cases show swelling in multiple or all EOMs, with only 4/23 (17.4%) having a single affected EOM. Treatment has usually been with a combination of antivirals (acyclovir) and oral steroids.

A case of acute single muscle OM after primary varicella zoster virus infection (chicken pox) has been published.151

Lyme Disease.

In 8 cases of OM in Lyme disease, half have been male, with ages ranging from 5 to 68 years (mean, 39; median, 46).142–148 All were acute onset and unilateral, with half affecting a single muscle, and half 2 or more. Pain was a feature in 5, and 1 had recurrent episodes.


The commonest parasitic infestation affecting EOMs is cysticercosis. It is common in areas of poor sanitation. If the orbit is affected, 80% of cases involve EOM.153 The involved EOM is often grossly enlarged with a cystic area within it seen on CT scan or B-scan ultrasonography. Treatment is with albendazole and corticosteroids.


Several medications have been associated with OM in various forms (Table 5). The commonest have been relatively new monoclonal antibodies (ipilimumab and other immune checkpoint inhibitors [ICIs], and the anti–cluster of differentiation-52 alemtuzumab) and bisphosphonates.

Orbital myositis caused by drug reactions

Ipilimumab and Other ICIs.

Immune checkpoint inhibitors are used to treat systemic malignancies, especially metastatic melanoma, and target 1 of 3 ligands: cytotoxic T-lymphocyte antigen-4 (ipilimumab), programmed (cell) death protein 1 (pembrolizumab, nivolumab), and programmed (cell) death ligand-1 (programmed [cell] death ligand-1, atezolizumab, avelumab, durvalumab). They activate T-cells, which attack malignant cells, but also upregulate the immune system with frequent autoimmune-like side effects, including uveitis, dry eye, myasthenia gravis, and sclerokeratitis.180 The commonest orbital manifestation is a TAO-like reaction, but other patterns of myositis have been described.

Of 17 cases reported,154–164 12 have presented with features similar to acute onset TAO, which has been bilateral in all but 1 case.156 Thyroid function (reported in 6 cases) was normal in 4, overactive in 1, and underactive in 1 patient who also had hypophysitis.162 Abnormal thyroid antibodies were documented in only 2 cases154,155 and were normal in 8. One patient with preexisting-treated Graves disease developed a TAO-like reaction after starting treatment with a programmed (cell) death protein 1 inhibitor.164

The clinical features of the TAO-like presentation have differed from typical TAO. The onset has been acute and has followed infusion of the ICI within 1 or several days, but not always after the first infusion. Inflammation has often been severe with marked conjunctival chemosis and limited eye movements. Usually, most or all the EOMs have been involved. One patient has had optic neuropathy which responded well to medical treatment.158 Many patients have had ptosis rather than eyelid retraction. Response to withholding the drug and giving corticosteroids has often been rapid and complete or near complete.

Three cases have described complete ophthalmoplegia and ptosis in response to ICIs.161–163 In 1 case, the EOMs were not enlarged, and the patient also developed severe cardiac and skeletal myositis which proved fatal.163 Single muscle OM has been described in only 2 patients after receiving ICIs.160,161


Alemtuzumab is an anti-cluster of differentiation-52 monoclonal antibody, which depletes circulating B- and T-lymphocytes and is used most commonly in the treatment of relapsing-remitting multiple sclerosis but also in hematologic disorders. Autoimmune disorders complicate treatment in nearly 50% of patients. Thyroid dysfunction, the commonest, occurred in 34% of patients having alemtuzumab in 1 trial, with 22% developing Graves hyperthyroidism, 7% hypothyroidism, and 4% subacute thyroiditis.165

Fourteen cases of TAO after alemtuzumab have been reported.166–169 The largest series reported one center’s experience with 162 patients treated with alemtuzumab for multiple sclerosis, of whom 71 (44%) developed thyroid dysfunction (62 [87%] of these were Graves disease).169 Ten patients of 62 (16%) developed TAO which ranged from mild to severe sight-threatening disease. All had elevated thyroid stimulating hormone receptor antibodies, and all were managed medically.


Bisphosphonates inhibit bone resorption by reducing osteoclast function and are used in the treatment of osteoporosis, osteolytic bone tumors and metastases, and Paget disease. Orbital inflammation is increasingly recognized as a side effect. Among cases of orbital inflammation, OM has been reported.

Of 11 cases with OM featuring in the presentation, 6 have been female.170–175 Bilateral OM has occurred in 6 cases, and only 3 have had isolated single muscle OM without features of inflammation beyond EOM.175 All other cases have had multiple muscles affected, with painful eye movements and diplopia in most. Acute onset of symptoms occurs within 0 to 28 days of exposure to the drug. Zoledronate has been the commonest inciting cause, being responsible for 22 of 29 cases of orbital inflammation summarized by Pirbhai et al.174

Treatment has been with corticosteroids, intravenously and/or orally, and response has usually been rapid and complete.


Statins (3-hydroxy-3-methylglutaryl-co-enzyme A reductase inhibitors) are very widely prescribed drugs used to reduce cholesterol levels. Generalized skeletal myopathy occurs in 1% to 5% of patients in clinical trials and 10% to 15% in observational studies.176 There is a single case report of OM with supportive orbital imaging in a 45-year-old man on simvastatin.176 The OM settled on withdrawal of the drug and recurred with rechallenge. This same article reported documented adverse drug reactions to statins of diplopia in 361 cases, proptosis in 8, and ophthalmoplegia in 83, suggesting that OM is much commoner than the lack of publications would suggest.

In 2008, Fraunfelder and Richards177 published a article documenting 256 cases of ptosis, diplopia, and ophthalmoplegia in patients taking satins, many of whom had dechallenge and rechallenge to confirm the relationship between drug and adverse effect. Orbital imaging was not reported. They surmised that the most plausible mechanism of action was myositis of the EOMs and levator muscles.


Enlargement of EOMs presumably due to inflammation has been described as a paraneoplastic phenomenon in a small number of cases (Table 6).181–188 In all cases, the OM has been bilateral and affected most or all EOMs. One case in a patient with breast cancer had bilateral superior rectus involvement only.181

Paraneoplastic orbital myositis: reported cases

In the most cases, the OM resolved or improved significantly, and quite rapidly, with removal of the primary lesion, sometimes with the addition of oral corticosteroids. In the case of OM in association with high-grade non-Hodgkin lymphoma, there were associated neurologic abnormalities, and these and the OM improved with immunosuppression.187 This patient had an EOM biopsy showing destruction of myofibers and granulomatous inflammation.


Orbital myositis shares many features with uveitis. Extraocular muscle is a target for an inflammatory response in many autoimmune, inflammatory, and infective conditions, but a large proportion remains “idiopathic.” In the past, there has been no attempt to classify OM in a systematic way. Based on the above review of all forms of OM, the author would propose a relatively simple but comprehensive classification, which is detailed in Table 7. This could serve as the basis for future reports, discussions, and research, with a potentially agreed common language to describe the various forms of OM.

A proposed classification of orbital myositis

A careful and systematic approach to any patient presenting with features of OM will more likely identify an underlying or associated disease or cause and reduce the proportion labeled as idiopathic. A full medical history to detect possible associated or underlying causes of OM and a full drug history are mandatory. Orbital imaging should be obtained, and a contrast-enhanced MRI is more useful than CT. Involvement of other structures such as lacrimal gland (TAO, sarcoidosis, GPA, IgG4-ROD), orbital nerves (IgG4-ROD), and paranasal sinuses (IgG4-ROD, GPA) should be looked for.

Targeted investigations aimed at possible underlying or associated inflammatory or autoimmune conditions should be performed. If a patient has atypical features, then strong consideration should be given to obtaining a biopsy of affected EOM.

Patients should be warned of possible future recurrent disease or the development of associated systemic medical conditions.

With this approach, OM will likely be less often an idiopathic disease.


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