Grand Rounds Shivani V. Reddy, M.D. University of Louisville Department of Ophthalmology and Visual Sciences

Patient Presentation CC: Left Eye Pain CC: Left Eye Pain HPI: 31 y/o WF presents to the ER with 5 days of pain/pressure OS. She describes the pain as 8/10, deep and stabbing in quality with gradual worsening over the 5 day period. Denies blurry vision, photophobia or foreign body sensation. HPI: 31 y/o WF presents to the ER with 5 days of pain/pressure OS. She describes the pain as 8/10, deep and stabbing in quality with gradual worsening over the 5 day period. Denies blurry vision, photophobia or foreign body sensation.

History POHx: episode of OD pain 7 months prior - CT orbits with OD superior rectus, lateral rectus and - CT orbits with OD superior rectus, lateral rectus and lacrimal gland enlargement lacrimal gland enlargement - resolved with Prednisone 60 mg PO Q.day x 2 weeks - resolved with Prednisone 60 mg PO Q.day x 2 weeks myopia myopia PMHx: migraines, anxiety FAMHx: no known thyroid or autoimmune diseases ROS: URI which she recovered from 3 weeks prior MEDS: benadryl, protonix, flexaril, depakote ALLERGIES: lortab, toradol, sulfa antibiotics

Exam VA TP P 20/20 20/ no RAPD EOM: -1 restriction in all gazes with pain OS no diplopia MRD 1: 4mm OU no lid lag no proptosis OS 4→3

Exam OD OS LIDS/LASHES WNL WNL CONJ WNL WNL CORNEA WNL, no staining WNL, no staining IRIS WNL WNL LENS WNL WNL FUNDUS EXAM: c/d: 0.3 with sharp rim OU MVP wnl OU PHYSICAL EXAM: no cervical/submandibular LAD

CT SCAN Enlargement of superior oblique muscle OS, no lacrimal gland involvement

Summary DDx:  Thyroid Eye Disease  Autoimmune Disease  Orbital malignancy  Infectious (orbital cellulitis)  NSOI 32 y/o WF presents with 5 days of OS pain worsened on EOM with minor movement restriction in all gazes. Ant segment and fundus exam WNL. CT scan shows swelling of superior oblique muscle. She had a similar episode OD previously that resolved upon treatment with corticosteroids

Laboratory Workup -ESR WNL ANA negative -CRP WNL ACE WNL -CBC WNL Thyroid Function Tests -Free T4 WNL -T3 WNL -TSH WNL -TSI negative -T-Perox negative

Summary DDx:  Thyroid Eye Disease  Autoimmune Disease  Orbital malignancy  Infectious (orbital cellulitis)  NSOI 32 y/o WF presents with 5 days of OS pain worsened on EOM with minor movement restriction in all gazes. Ant segment and fundus exam WNL. CT scan shows swelling of superior oblique muscle. She had a similar episode OD previously that resolved upon treatment with corticosteroids. Negative Workup

Treatment  Started on oral Prednisone 1mg/kg with ranitidine 3 day follow-up  Pain and EOM restriction resolved  Started on slow taper  No recurrences as of 2 weeks ago per telephone follow-up

Nonspecific Orbital Inflammation (NSOI)  Also known as:  Inflammatory orbital pseudotumor  Idiopathic orbital inflammatory syndrome  Benign process characterized by polymorphous lymphoid infiltrate +/- fibrosis of varying degrees  No known local or systemic cause  Diagnosis of exclusion  Controversial pathogenesis, likely cell mediated

NSOI  typically unilateral in adults, but upto 1/3 bilateral in  children  5 main locations in order of frequency:  Lacrimal gland (darcryoadenitis)  Extraocular muscles (myositis)  50% with tendon involvement  Anterior orbit  +/- tenons involvement (ring sign)  Orbital apex  Diffuse  Sclerosing subtype with marked orbital fibrosis

NSOI  Variable presentation depending on location  Most typical feature is deep-rooted boring retro-orbital pain  Other common features  EOM restriction +/- pain  Proptosis  Conjunctival Inflammation  Chemosis  Upper eyelid erythema  Children commonly present with uvietis, disc edema and eosinophilia

NSOI  Lab findings:  Elevated ESR  CBC with eosinophilia  + ANA levels  Mild CSF pleocytosis  Histological Findings  Pleomorphic cellular infiltrate with lymphocytes, plasma cells and eosinophils, later stages with fibrotic changes  Sclerosing subtype shows very little inflammation

NSOI Dacryoadenitis with marked inflammation and expansion along the lateral orbital wall. Diffuse gland enlargement with blurring of margins

NSOI Extraocular muscle inflammation with tubular enlargement 2/2 tendon involvement medial rectus > superior muscle complex > lateral rectus > inferior rectus

NSOI Diffuse orbital involvement showing fat enhancement (asterix’s)

Diagnosis  Based on a combination of clinical symptoms, labs and imaging  Biopsy if - diagnosis uncertain, atypical presentation, poor response to initial medical treatment

Treatment  Mild cases  Observation  NSAIDS + PPI  Moderate - Severe Cases  Corticosteroids are mainstay of therapy at 1mg/kg dosing  Slow taper to ensure complete suppression of inflammation  Refractory Cases & Sclerosing Variant  Immunomodulator therapy  Cyclosporine, cyclophosphamide, methotrexate  Low dose radiation

Response/Prognosis  78% with +ve initial response BUT only 37% cured, 52% disease recurrence  Patients with optic neuropathy 2/2 compression showed 95% response rate  Sclerosing subtype tends to show less of a treatment response  Per 2007 review of 56 published biopsy proven NSOI cases  34% have complete resolution  43% with partial resolution  23% refractory

Ophthal Plast Reconstr Surg 2013;29:286–289) Prospective, noncomparitive interventional case series 47 patients with acute idiopathic orbital inflammation Dacryoadenitis – 31 Myositis – 12 Diffuse – 4 cases Patients injected with 2-4 ml betamethasone suspension through a 22 gauge needle into the inflamed gland, around the inflamed muscle and periocularly in diffuse cases After injection, NSAIDS + topical steroid treatment for 2 weeks F/U was weekly x 1 month, every 3 months x 1 year, then yearly

Dacryoadenitis – 31 cases (4 recurrent) 25 cases 2ml suspension, 6 cases 4ml suspension Mean age 26.4 years, F>M (24:7) Complete response weeks No recurrences/complications Myositis - 12 cases (1 recurrent) 2ml suspension Mean age 27.4 years, M>F (9:3) Complete response weeks 1 recurrence 14 months post with LR inflammation- resolved after inj#2 No other recurrences/complications Diffuse Inflammation – 4 cases (2 recurrent) 4 ml suspension Mean age 29.2 years, all men Complete response weeks 1 recurrence 9 months post, resolved after inj #2 No other recurrences/complications

THANK YOU

References  BCSC Section 4. Ophhtalmic Pathology and Intraocular tumors  BCSC Section 8. Orbit, Eyelids and Lacrimal System  Ding ZX, Lip G, Chong V. Idiopathic orbital pseudotumor. Clinical Radiology 2011;66:  Kapur R, Sepahdari AR, Mafee MF, et al. MR imaging of orbital inflammatory syndrome, orbital cellulitis, and orbital lymphoid lesions: the role of diffusion- weighted imaging. AJNR Am J Neuroradiol 2009;30:64-70  Mombaerts I, Schingmann RO, Goldschmeding R, et al. Are systemic corticosteroids useful in the management of orbital pseudotumors? Ophthalmol. 1996;103:  Ahn Yuen SJ, Rubin PAD. Idiopathic Orbital Inflammation Distribution, Clinical Features, and Treatment Outcome. Arch Ophthalmol. 2003;121:  Swamy BN, McCluskey P, Nemet A, Crouch R, Martin P, Benger R, Ghabriel R, Wakefield D. Idiopathic orbital inflammatory syndrome: Clinical features and treatment outcomes. Br J Ophthalmol 2007;91: