The enucleated right eye contained a diffuse chronic inflammatory infiltrate in the choroid including epithelioid histiocytes forming noncaseating granulomas (A), and it also contained Dalen-Fuchs nodules (B) (hematoxylin-eosin, original magnification ×100).
A chronic, low-grade inflammation including flare and posterior synechiae persisted in the left eye when oral prednisone was tapered.
Kim J, Jeroudi A, Angeles-Han ST, Grossniklaus HE, Yeh S. Adalimumab for Pediatric Sympathetic Ophthalmia. JAMA Ophthalmol. 2014;132(8):1022-1024. doi:10.1001/jamaophthalmol.2014.426
Copyright 2014 American Medical Association. All Rights Reserved. Applicable FARS/DFARS Restrictions Apply to Government Use.
Sympathetic ophthalmia (SO) is an autoimmune, bilateral, granulomatous panuveitis occurring after accidental or surgical trauma to the eye.1 Systemic corticosteroids are first-line therapy for SO, with immunomodulatory therapy used for corticosteroid-sparing immunosuppression and chronic, refractory cases. Biological response modifiers are a class of therapeutics that target specific cytokines mediating inflammation, and tumor necrosis factor α (TNF-α)–antagonist biological response modifiers have shown promise for uveitis.2 Herein, we report the first use, to our knowledge, of adalimumab for refractory pediatric SO leading to resolution of inflammation.
A young girl had accidental trauma to the right eye resulting in corneoscleral laceration, which was repaired the day of trauma. Postoperative visual acuity was hand motions OD. Two weeks later, increasing inflammation concerning for endophthalmitis prompted intravitreal antibiotic injection and subsequent pars plana vitrectomy with lensectomy. Visual acuity became no light perception OD postoperatively.
Nine weeks after her initial injury, the patient began experiencing photophobia and redness of her uninjured left eye. Visual acuity was 20/20 OS. Examination of the left eye under anesthesia showed anterior and posterior segment inflammation with white peripheral chorioretinal deposits concerning for SO. Treatment with topical prednisolone acetate, 1%, and oral prednisone, 60 mg/d, was started. Enucleation of the right eye was performed 11 weeks after the initial injury, with histopathologic findings consistent with SO (Figure 1). The patient was referred to our service for further management.
On our initial examination, visual acuity was 20/25 OS and intraocular pressure was 36 mm Hg OS with rare anterior chamber cell and trace flare. Ophthalmoscopic examination showed 1+ vitreous cell without choroidal lesions. The patient developed weight gain and cushingoid habitus with oral prednisone. Treatment with topical timolol maleate, 0.5%, was started for elevated intraocular pressure.
Oral prednisone was tapered to 10 mg/d over a 12-week period in conjunction with initiating subcutaneous injection of 10 mg of methotrexate sodium weekly. Despite dose escalation of methotrexate sodium to 25 mg by subcutaneous injection weekly over the following 9 months, the patient continued to have low-grade anterior chamber inflammation, developed posterior synechiae (Figure 2), and experienced flares up to 3+ anterior chamber cell when tapering oral prednisone below 10 mg/d.
Subcutaneous injection of 20 mg of adalimumab every 2 weeks was initiated after a negative purified protein derivative reading, and within 3 months inflammation completely resolved with discontinuation of oral prednisone, prednisolone, and timolol. After 6 months of stability while receiving adalimumab, methotrexate was tapered and discontinued over 6 months.
After 18 months of receiving adalimumab, visual acuity was 20/25 OS with no evidence of recurrent inflammation, posterior synechiae, or fundus abnormalities.
Sympathetic ophthalmia is presumed to be an autoimmune, T-cell–mediated response to melanocyte self-antigens exposed during surgery or trauma. A cytokine-profiling study in an animal model resembling SO showed upregulation of TNF-α levels associated with photoreceptor damage.3 As TNF-α potentiates T-cell–mediated immunity, TNF-α antagonist therapy may provide a targeted approach for anti-inflammatory therapy.2
Gupta et al4 reported a case of pediatric SO refractive to multiple immunosuppressants that was treated with intravenous infliximab, a chimeric murine/human monoclonal antibody targeting TNF-α, with prolonged control of inflammation achieved with infliximab alone. An adult case of SO refractory to multiple immunosuppressants achieved inflammation resolution with addition of adalimumab, a recombinant human monoclonal anti–TNF-α antibody given subcutaneously.5 In a series of 131 patients with refractory uveitis, addition of adalimumab reduced immunosuppressive load by 50% in 85% of patients.6
To our knowledge, this is the first report of the use of TNF-α blocker adalimumab leading to resolution of inflammation in refractory pediatric SO. Addition of adalimumab led to long-term control with discontinuation of all other immunosuppressants for our patient. Although experience is limited to case reports, adalimumab could be considered for refractory SO and potentially other ocular autoimmune conditions in which TNF-α is thought to play a role in pathogenesis.
Corresponding Author: Steven Yeh, MD, Emory Eye Center, Department of Ophthalmology, Emory University School of Medicine, 1365B Clifton Rd NE, Atlanta, GA 30322 (firstname.lastname@example.org).
Published Online: July 10, 2014. doi:10.1001/jamaophthalmol.2014.426.
Author Contributions: Mr Kim and Dr Yeh had full access to all of the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis.
Study concept and design: Jeroudi, Yeh.
Acquisition, analysis, or interpretation of data: Kim, Angeles-Han, Grossniklaus, Yeh.
Drafting of the manuscript: Kim, Jeroudi, Yeh.
Critical revision of the manuscript for important intellectual content: Jeroudi, Angeles-Han, Grossniklaus, Yeh.
Obtained funding: Yeh.
Administrative, technical, or material support: Grossniklaus, Yeh.
Study supervision: Angeles-Han, Yeh.
Conflict of Interest Disclosures: None reported.
Funding/Support: This work was supported in part by an unrestricted departmental grant to the Emory Eye Center from Research to Prevent Blindness, Core Grant for Vision Research P30 EY006360 from the National Eye Institute, and the Knights Templar Educational Foundation of Georgia (Drs Angeles-Han and Yeh). Dr Angeles-Han was supported by grant K23 EY021760 from the National Eye Institute.
Role of the Sponsor: The funders had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; and decision to submit the manuscript for publication.
Disclaimer: The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.