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Original Investigations

Sarcoid Orbital Myopathy

Clinical Presentation and Outcomes

Vahdani, Kaveh M.D., F.R.C.Ophth.; Rose, Geoffrey E. D.Sc., F.R.C.Ophth.

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Ophthalmic Plastic and Reconstructive Surgery: January/February 2020 - Volume 36 - Issue 1 - p 61-66
doi: 10.1097/IOP.0000000000001462
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Abstract

Sarcoidosis, an idiopathic multisystem disorder characterized by noncaseating granuloma formation, commonly affects the lungs, skin, lymph nodes, and eyes.1,2 While uveal inflammation is the commonest ocular manifestation, adnexal and orbital disease can occur—with a predilection for lacrimal gland involvement.1 Although rare, abnormal eye movements may result from infiltration of the cranial nerves innervating the extraocular muscles (EOM)1 or due to actual muscle disease.3–15

We report the clinical manifestations, ocular and systemic associations, radiological features, and treatment outcome for patients presenting with sarcoid-like granulomatous disease involving the EOM.

METHODS

Patients seen between 1990 and 2016 with a diagnosis of sarcoid orbital myopathy were identified from the orbital database at Moorfields Eye Hospital, and the demographic and clinical features derived from a retrospective review of clinical case-notes. Cases without recorded orbital imaging at the time of presentation were excluded from the study.

A diagnosis of systemic sarcoidosis was based on 2 or more characteristics: clinical presentation, compatible chest X-ray findings (hilar lymphadenopathy, reticulo-nodular shadowing, and/or fibrosis), pulmonary function tests, elevated serum angiotensin-converting enzyme, or confirmatory biopsy. Based on investigation at the time of referral, our patients either had known systemic disease (Group I) or had a new diagnosis of sarcoidosis based on systemic investigation and/or orbital biopsy (Group II).

Data analysis was performed using SPSS v.24 (IBM Chicago, IL, U.S.A.); all tests were two-tailed, and an α-risk of 0.05 was considered clinically significant. Categorical variables were compared using Fisher exact test, and continuous variables with unpaired Student t-test.

The study was IRB approved (MEH #164) and adhered to the tenets of the Declaration of Helsinki.

RESULTS

Orbital imaging and records were available for 53 patients with sarcoid-like granulomatous orbitopathy and 20 (15 females; 75%) had EOM involvement. In Group I patients, 5 of 8 had orbital biopsy and 3 of 8 had prior extra-orbital biopsy; in Group II, 9 of 12 had orbital biopsy and 3 had compatible orbital imaging with characteristic chest X-ray and systemic findings (Table 1).

TABLE 1
TABLE 1:
Clinical characteristics, treatment, and outcome for each of 20 patients with sarcoidosis affecting the extraocular muscles—8 with known systemic sarcoidosis (cases 1–8), and 12 with a new diagnosis after orbital presentation

Group I patients were a decade younger at orbital diagnosis, but the difference was not statistically significant. Likewise, although the proportion of Afro-Caribbean patients in both groups was much higher than the prevalence of 2.9% in the United Kingdom,16 there was no bias of race (p = 0.33) or gender (p = 1.0) between the 2 groups (Table 2). The incidence of symptoms and signs in the 2 groups was not significantly different, the commonest being eyelid swelling or lump (19 patients; 95%), reduced motility with diplopia (12/20; 60%), or ache (8/20; 40%) (Table 2). Disease was unilateral in 16 of 20 cases, with 1.8 mm average relative exophthalmos (median 1 mm; range 0–7 mm)—this being similar in the 2 groups (p = 0.18) (Table 2). Again, although there was some variation in the incidence of prior uveitis (Table 2), patterns of systemic involvement (Table 2), proportion with raised serum angiotensin-converting enzyme, or absolute values of serum angiotensin-converting enzyme (Table 3), these were not significantly different between the 2 groups: only the proportion with multiple system involvement was significantly different (p = 0.03), with 88% in Group I and 33% in Group II (Table 2). Chest X-rays were available for review in 10 patients, with 9 being abnormal and 7 of 9 typical for sarcoid—hilar lymphadenopathy being the commonest change in both groups (Table 3). Chest CT and lysozyme results were not available for these patients.

TABLE 2
TABLE 2:
Group characteristics for 20 patients with sarcoidosis affecting the extraocular muscles
TABLE 3
TABLE 3:
Systemic investigations for 20 patients with sarcoidosis involving the extraocular muscles

Extraocular muscle involvement was typically either diffuse muscular swelling (a single muscle in 25% of each of the Groups; Table 3), or enlarged muscle(s) contiguous with an orbital mass (Fig.). The superior rectus/levator complex was most commonly affected (58% in Group II), the superior oblique only rarely (none in Group I), and there was no evident bias between the 2 groups (Table 3). Most patients had lacrimal gland (70%) and fat involvement (95%) (Table 3).

Management and Outcome.

Four patients were on oral corticosteroids prior to orbital presentation (2 in each group) and 16 received oral prednisolone after orbital diagnosis—14 commencing steroids (6/6 in Group I, 8/10 in Group II) and 2 continuing previous steroids (both in Group I). The steroids were required for <3 months in 6 of 16 patients (38%: 2/8 in Group I; 4/8 in Group II), but the remaining 10 of 16 received them for a mean period of 29.9 months (median 22.5; range 7–70). The duration of steroid treatment was not significantly different in the 2 groups—32.8 months in Group I and 25.5 months in Group II (p = 0.68). Five (25%) patients—3 of 8 in Group I and 2 of 12 in Group II—needed secondary immunosuppression for an average of 56 months (median 34; range 2–191); these including mycophenolate (3 patients), methotrexate (3), hydroxychloroquine (3), cyclosporine (1), azathioprine (1), and interferon (1) (Table 1).

Clinical improvement was noted in 13 of 20 (65%) patients, the results being similar in the 2 groups (p = 1.0) (Table 1). Visual functions were largely unchanged, apart from 2 patients who lost 3 or more Snellen lines—one with severe glaucomatous optic atrophy (in whom the extensive orbital disease improved on steroids) and another who was lost to follow up before completion of investigations. The overall average follow up was 56 months (median 41; range 1–315), with no significant difference between the 2 groups (p = 0.59 for 15 patients with >6 months follow up) (Table 1). Disease recurrence occurred in 6 patients (3/8 in Group I, 3/12 in Group II) at an average interval of 12.5 months after diagnosis (median 10; range 1–31 months) and recurrences were treated by restarting or increasing steroids (4 patients), or addition of second-line immunosuppressants in 2 patients (Table 1).

DISCUSSION

Although biopsy-proven systemic sarcoid myopathy occurs in over a half of patients,2 extraocular sarcoid myopathy is rare and confined to <20 case reports—with only 14 having imaging evidence of EOM enlargement, and 12 of 14 having no prior history of sarcoidosis (Table 4).3–15 Two patients were receiving treatment for presumed euthyroid thyroid eye disease,14 and 1 presented 18 years after treatment.11 As in our study, most (64%) patients were females, typically presenting in the fifth decade, and with a notably high proportion (40%) of Afro-Caribbean patients. Likewise, as in our study, the commonest presentations were with reduced eye movements and diplopia, eyelid swelling or proptosis, and with or without pain. Bilateral disease was commoner in the published literature, but the predominance of multiple muscle involvement was similar to our findings—4 reported patients having bilateral diffuse enlargement of multiple EOM (Table 4). Serum angiotensin-converting enzyme was elevated in 29% of our patients compared with 40% in the existing reports (Table 4).

TABLE 4
TABLE 4:
Summary of publications reporting sarcoidosis extraocular myopathy

Most of our patients had fusiform muscular enlargement with tendinous involvement (especially the superior rectus/levator complex), although some had thickened muscles alongside diffuse involvement of fat or lacrimal gland. Previous reports have shown similar changes with, only rarely, nodular muscle enlargement.10

Most patients with sarcoid orbital myopathy are reported to respond well to systemic corticosteroids and only a minority require second-line immunosuppression or low dose orbital radiotherapy.11,12,14 Except for 4 patients in whom the condition was observed (without progression), all of our patients received oral steroids with most showing clinical improvement; however, about a third developed recurrent disease after an average interval of a year, 3 patients after cessation of oral steroids, and another 3 while on low-dose (1–5 mg prednisolone) maintenance therapy.

In summary, sarcoid orbital myopathy is rare and mainly affects the levator muscle and the superior and lateral recti—possibly due to neighboring dacryoadenitis being extremely common. Most patients will settle with systemic corticosteroids, a quarter need second-line immunosuppressants, and one-third will have relapse.

Patterns of extraocular muscle involvement in sarcoidosis: A and B, (Case 3) A 41-year old Caucasian female with known systemic sarcoidosis presented with right eyelid swelling, proptosis, and reduced motility; imaging shows fusiform enlargement of the right medial, lateral, and inferior recti. C and D, (Case 13) A 54-year-old Afro-Caribbean female, without known disease, presented with involvement of the right inferior rectus and oblique muscles in a diffuse inferotemporal mass. E, (Case 11) Infiltration and thickening of three recti (medial, lateral, superior), and the right levator and superior oblique muscles in a 46-year-old Caucasian female with newly presenting sarcoid orbital myopathy. F, (Case 20) A 78-year-old Caucasian female presented with right dacryoadenitis and painful limitation of supraduction; imaging shows right hypoglobus due to the enlarged gland with thickening of the neighboring superior rectus/levator complex.

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