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Research Letters |

Successful Treatment of Refractory Sympathetic Ophthalmia in a Child With Infliximab FREE

Seema R. Gupta, MD; Isabella T. Phan, MD; Eric B. Suhler, MD, MPH
[+] Author Affiliations

Author Affiliations: Department of Ophthalmology, Casey Eye Institute, Oregon Health and Science University (Drs Gupta, Phan, and Suhler) and Portland Veterans Affairs Medical Center (Dr Suhler), Portland.


Arch Ophthalmol. 2011;129(2):250-252. doi:10.1001/archophthalmol.2010.358.
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Sympathetic ophthalmia (SO) is a bilateral granulomatous panuveitis following accidental or surgical trauma to 1 eye. Systemic corticosteroid therapy is first-line therapy, but immunosuppressive agents are commonly required for longer-term treatment. There is scant literature on the treatment of SO in children and none using modern therapy with biological response modifiers. We report a case of SO in a child treated successfully with infliximab after having failed therapy with methotrexate, cyclosporine, mycophenolate mofetil, and daclizumab.

A 7-year-old boy was struck in the right eye by a toy arrow. The injury was repaired the same day with pars plana vitrectomy and lensectomy, corneal wound and retinal detachment repair, and intraocular foreign body removal. Seven days later, repeated vitrectomy was needed for endophthalmitis with subsequent visual acuity of no light perception. Enucleation of the damaged eye was not elected at the time. Six weeks after the injury, the patient visited his referring ophthalmologist with bilateral eye pain. Examination revealed visual acuity of 20/20 OS and 4+ cells in the anterior chamber, with reported normal retinal examination results. He began treatment with oral prednisone, 60 mg/d; topical prednisolone acetate in the left eye hourly; neomycin sulfate, polymyxin B sulfate, and dexamethasone (Maxitrol) ointment in the left eye at bedtime; and scopolamine hydrobromide in the left eye twice daily. He was referred to our uveitis clinic, where he was seen 9 days later. At his initial visit to our clinic, visual acuity was no light perception OD and 20/50 OS. The right anterior segment was grossly malformed with no posterior view, while the left eye examination revealed 1+ cells in the anterior chamber. Posterior segment examination of the left eye revealed 1+ vitreal cells and haze, a normal optic nerve, and a whitish, pale retinal appearance diffusely throughout the posterior pole, with numerous midperipheral elevated, edematous choroidal infiltrates consistent with Dalen-Fuchs nodules. Fluorescein angiography demonstrated serous macular detachment and active chorioretinitis (Figure 1A and B).

Place holder to copy figure label and caption
Figure 1.

Fluorescein angiograms at presentation depicting active chorioretinitis coalescing into central serous retinal detachment. A, Early phase. B, Late phase. C, Late phase 2 weeks after initiation of therapy.

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The patient was treated with pulse intravenous methylprednisolone sodium succinate (Solu-Medrol), 650 mg/d (30 mg/kg), for 3 days followed by oral prednisone, 50 mg/d, cyclosporine, 60 mg twice daily (5.2 mg/kg), and methotrexate, 12.5 mg every week. The patient's family elected expeditious enucleation of the right eye, with histopathologic examination of the enucleated eye showing prominent choroidal granulomatous inflammation consistent with SO (Figure 2). The aforementioned regimen led to initial improvement, with all chorioretinal lesions gaining an atrophic appearance (Figure 1C and Figure 3). However, on steroid tapering to 40 mg of prednisone daily over 4 weeks, a recurrence of panuveitis required a repeated course of pulse methylprednisolone followed by oral prednisone, 50 mg/d, cyclosporine, 80 mg twice daily (6.5 mg/kg), and methotrexate, 12.5 mg every week. A second attempt to taper corticosteroids led to a third flare 4 months later, which occurred a week after treatment with oral prednisone was discontinued. This required a third round of pulse intravenous methylprednisolone followed by oral prednisone, 60 mg/d, cyclosporine, 100 mg twice daily, and substitution of mycophenolate mofetil, 600 mg twice daily, for methotrexate. His cyclosporine dose subsequently was reduced to 75 mg twice daily owing to elevation of the creatinine level. A third attempt to taper his prednisone dosage to 15 mg/d over the next 2 months led to another recurrence, requiring an oral steroid increase to 30 mg/d and initiation of treatment with intravenous daclizumab, 2 mg/kg every 2 weeks, with continuation of treatment with mycophenolate and cyclosporine; however, inflammation recurred 3 months later when the patient reached a prednisone dosage of 7.5 mg/d. At this time, treatment with daclizumab was stopped and treatment with infliximab was started at a dosage of 10 mg/kg every 4 weeks, with the prednisone dosage increased to 30 mg/d and the dosages of mycophenolate and cyclosporine maintained.

Place holder to copy figure label and caption
Figure 2.

Histopathologic examination reveals a Dalen-Fuchs nodule consisting of a chronic inflammatory infiltrate of lymphocytes and epithelioid cells between the retinal pigment epithelium and the Bruch membrane. Note the marked thickening of the choroid by a lymphocytic infiltrate (hematoxylin-eosin, original magnification ×20).

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Figure 3.

Peripheral atrophic-appearing Dalen-Fuchs nodules after initial treatment with corticosteroids and immunosuppression.

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Two weeks after starting treatment with infliximab, the patient's inflammation was well controlled. We were able to successfully taper the prednisone dosage to 5 mg/d within 5 months of starting treatment with infliximab, with subsequent discontinuation of treatment with cyclosporine, prednisone, and mycophenolate 13, 17, and 24 months, respectively, after starting treatment with infliximab. At the last follow-up 26 months after starting treatment with infliximab, his visual acuity was 20/30 −1/+1 with continued quiescence.

To our knowledge, this is the first reported case of the use of infliximab, or any biological response modifier, in pediatric SO. Infliximab has been shown in previous studies to be an effective immunosuppressant for the treatment of refractory uveitis in adults and children.14 Elevated ocular and systemic levels of tumor necrosis factor have been found in patients and the retinas of enucleated eyes with SO,5 and tumor necrosis factor may contribute to photoreceptor damage leading to vision loss in SO.6

Our patient had been refractory to combination therapy with methotrexate and cyclosporine as well as combination therapy with mycophenolate, cyclosporine and daclizumab. Initiation of infliximab therapy led to a durable remission for more than 2 years and allowed a good visual outcome. Therefore, we suggest that infliximab therapy should be considered in cases of pediatric SO that are refractory to conventional therapy.

Correspondence: Dr Suhler, Casey Eye Institute, 3375 SW Terwilliger Blvd, Portland, OR 97239 (suhlere@ohsu.edu).

Financial Disclosure: None reported.

Funding/Support: This work was supported by an unrestricted grant from Research to Prevent Blindness to the Casey Eye Institute and by the Department of Veterans Affairs (Dr Suhler).

Suhler  EBSmith  JRGiles  TR  et al.  Infliximab therapy for refractory uveitis: 2-year results of a prospective trial. Arch Ophthalmol 2009;127 (6) 819- 822
PubMed
Gallagher  MQuinones  KCervantes-Castañeda  RAYilmaz  TFoster  CS Biological response modifier therapy for refractory childhood uveitis. Br J Ophthalmol 2007;91 (10) 1341- 1344
PubMed Link to Article
Saurenmann  RKLevin  AVRose  JB  et al.  Tumour necrosis factor alpha inhibitors in the treatment of childhood uveitis. Rheumatology (Oxford) 2006;45 (8) 982- 989
PubMed Link to Article
Kahn  PWeiss  MImundo  LFLevy  DM Favorable response to high-dose infliximab for refractory childhood uveitis. Ophthalmology 2006;113 (5) 860- 864, e2
PubMed Link to Article
Palexas  GNSussman  GWelsh  NH Ocular and systemic determination of IL-1 beta and tumour necrosis factor in a patient with ocular inflammation. Scand J Immunol Suppl 1992;11173- 175
PubMed Link to Article
Parikh  JGSaraswathy  SRao  NA Photoreceptor oxidative damage in sympathetic ophthalmia. Am J Ophthalmol 2008;146 (6) 866- 875, e2
PubMed Link to Article

Figures

Place holder to copy figure label and caption
Figure 1.

Fluorescein angiograms at presentation depicting active chorioretinitis coalescing into central serous retinal detachment. A, Early phase. B, Late phase. C, Late phase 2 weeks after initiation of therapy.

Graphic Jump Location
Place holder to copy figure label and caption
Figure 2.

Histopathologic examination reveals a Dalen-Fuchs nodule consisting of a chronic inflammatory infiltrate of lymphocytes and epithelioid cells between the retinal pigment epithelium and the Bruch membrane. Note the marked thickening of the choroid by a lymphocytic infiltrate (hematoxylin-eosin, original magnification ×20).

Graphic Jump Location
Place holder to copy figure label and caption
Figure 3.

Peripheral atrophic-appearing Dalen-Fuchs nodules after initial treatment with corticosteroids and immunosuppression.

Graphic Jump Location

Tables

References

Suhler  EBSmith  JRGiles  TR  et al.  Infliximab therapy for refractory uveitis: 2-year results of a prospective trial. Arch Ophthalmol 2009;127 (6) 819- 822
PubMed
Gallagher  MQuinones  KCervantes-Castañeda  RAYilmaz  TFoster  CS Biological response modifier therapy for refractory childhood uveitis. Br J Ophthalmol 2007;91 (10) 1341- 1344
PubMed Link to Article
Saurenmann  RKLevin  AVRose  JB  et al.  Tumour necrosis factor alpha inhibitors in the treatment of childhood uveitis. Rheumatology (Oxford) 2006;45 (8) 982- 989
PubMed Link to Article
Kahn  PWeiss  MImundo  LFLevy  DM Favorable response to high-dose infliximab for refractory childhood uveitis. Ophthalmology 2006;113 (5) 860- 864, e2
PubMed Link to Article
Palexas  GNSussman  GWelsh  NH Ocular and systemic determination of IL-1 beta and tumour necrosis factor in a patient with ocular inflammation. Scand J Immunol Suppl 1992;11173- 175
PubMed Link to Article
Parikh  JGSaraswathy  SRao  NA Photoreceptor oxidative damage in sympathetic ophthalmia. Am J Ophthalmol 2008;146 (6) 866- 875, e2
PubMed Link to Article

Correspondence

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