0
We're unable to sign you in at this time. Please try again in a few minutes.
Retry
We were able to sign you in, but your subscription(s) could not be found. Please try again in a few minutes.
Retry
There may be a problem with your account. Please contact the AMA Service Center to resolve this issue.
Contact the AMA Service Center:
Telephone: 1 (800) 262-2350 or 1 (312) 670-7827  *   Email: subscriptions@jamanetwork.com
Error Message ......
Research Letters |

Infliximab Therapy for Aggressive Mooren Ulceration FREE

Valerie P. J. Saw, FRANZCO; Neil Cornelius, FCOphth(SA); Alan D. Salama, PhD, FRCP; Charles Pusey, PhD, FRCP; Susan L. Lightman, PhD, FRCOphth
Arch Ophthalmol. 2008;126(5):734-735. doi:10.1001/archopht.126.5.734.
Text Size: A A A
Published online

Mooren ulceration is an uncommon corneal autoimmune disease that can lead to blindness. We describe a patient with aggressive disease in whom inflammatory control was only achieved after infusion of a tumor necrosis factor α antagonist, infliximab.

A 37-year-old Nigerian man with a 14-year history of bilateral Mooren ulceration had a right corneal perforation and a desmetocele in his severely damaged left eye (Figure, A and B). Snellen visual acuity was 6/60 OD, improving to 6/36 OD with pinhole, and hand movements OS. Systemic cyclosporine at a dosage of 5 mg/kg/d and prednisolone tapering from 1 mg/kg/d and ceasing after 8 weeks were given, with 2% cyclosporine eyedrops and ofloxacin eyedrops both 3 times daily to the right eye. The right corneal perforation healed with glue and a therapeutic contact lens. However, the desmetocele in the left eye perforated during an inflammatory episode 2 months later, so mycophenolate mofetil (CellCept; Hoffman-La Roche Inc, Nutley, New Jersey) at a dosage of 1 g twice daily was added, a 12-mm corneoscleral lamellar tectonic graft and cataract extraction were carried out, and Baerveldt tube surgery was performed for intractably elevated intraocular pressure.

Place holder to copy figure label and caption
Figure.

Bilateral Mooren ulceration. A, Right eye at the initial visit with active ulceration. B, Left eye at the initial visit with a desmetocele and advanced disease. C, Right eye with new infiltrates at the 1-o’clock position and iris prolapse at the site of perforation, under a bandage contact lens. D, Left eye following corneoscleral graft with active guttering superotemporally and a central persistent epithelial defect. E, Right eye with quiescent disease 5 months after commencing infliximab therapy and conjunctival resection. F, Left eye with quiescent disease 5 months after commencing infliximab therapy.

Graphic Jump Location

After 4 months of quiescence, the disease again reactivated with new infiltrates and melts resulting in a flat chamber in the right eye and new guttering in the periphery of the left corneoscleral graft (Figure, C and D). Cyclophosphamide treatment at a dosage of 100 mg/d was commenced with another course of oral prednisolone, and mycophenolate treatment was stopped. Three weeks later, the patient developed microscopic hematuria and bloody stools, so cyclophosphamide treatment had to be discontinued. Stool cultures were negative for parasites. The infiltrates and melts in the right eye continued to be active, so infliximab at a dosage of 5 mg/kg was added, combined with oral cyclosporine. The inflammation in both eyes responded rapidly to this treatment, with gradual return of the inflammation in the 2-week interval between infusions. The patient received 3 infusions over 6 weeks. A right conjunctival recession and cautery procedure was carried out after another perforation, which sealed spontaneously under a bandage lens, and mycophenolate was again added to the immunosuppressive regimen.

Following this, both corneas healed and the eyes became white, so the infliximab infusions were reduced to 6 weekly. At the last visit, 5 months after commencing infliximab treatment, the disease appears to be quiet (Figure, E and F). Snellen visual acuity is currently 6/60 OD, improving to 6/18 OD with a scleral contact lens. Unfortunately, the patient has no vision in the left eye due to the uncontrolled glaucoma. Infliximab infusions are currently being continued at decreasing intervals.

This case demonstrates how difficult Mooren ulceration can be to treat, given both the delay in onset of action and adverse effects of conventional immunosuppressive therapy. The pathogenesis of Mooren ulceration is uncertain but may involve an immune response to a corneal stromal protein (corneal antigen), which is identical to calgranulin C released by neutrophils during the host defense response to helminths.1 Infiltration of lymphocytes, macrophages, and Langerhans cells has been observed in the conjunctiva adjacent to Mooren ulceration.2

Tumor necrosis factor α is an important cytokine in the establishment and maintenance of inflammation in many autoimmune diseases, and the success of tumor necrosis factor α antagonists in immune-mediated rheumatic diseases has led to its off-label use in ocular inflammatory disease.3 Apart from inhibition of tumor necrosis factor α, infliximab also appears to induce regulatory T cells in rheumatoid arthritis4 and to induce T-cell apoptosis in Crohn disease,5 both of which might be relevant in ocular inflammation.

To our knowledge, effective treatment with tumor necrosis factor α antagonists has not previously been described in Mooren ulceration. This article shows that addition of infliximab may be useful when rapid control of inflammation is desirable and/or when conventional immunosuppressive therapy is not tolerated or effective.

Correspondence: Dr Saw, Moorfields Eye Hospital, 162 City Rd, London EC1V 2PD, England (v.saw@ucl.ac.uk).

Financial Disclosure: None reported.

Gottsch  JDLi  QAshraf  FO'Brien  TPStark  WJLiu  SH Cytokine-induced calgranulin C expression in keratocytes. Clin Immunol 1999;91 (1) 34- 40
PubMed Link to Article
Kafkala  CChoi  JZafirakis  P  et al.  Mooren ulcer: an immunopathologic study. Cornea 2006;25 (6) 667- 673
PubMed Link to Article
Hale  SLightman  S Anti-TNF therapies in the management of acute and chronic uveitis. Cytokine 2006;33 (4) 231- 237
PubMed Link to Article
Nadkarni  SMauri  CEhrenstein  MR Anti-TNF-alpha therapy induces a distinct regulatory T cell population in patients with rheumatoid arthritis via TGF-beta. J Exp Med 2007;204 (1) 33- 39
PubMed Link to Article
Sieper  JVan Den  BJ Diverse effects of infliximab and etanercept on T lymphocytes. Semin Arthritis Rheum 2005;34 (5) ((suppl 1)) 23- 27
PubMed Link to Article

Figures

Place holder to copy figure label and caption
Figure.

Bilateral Mooren ulceration. A, Right eye at the initial visit with active ulceration. B, Left eye at the initial visit with a desmetocele and advanced disease. C, Right eye with new infiltrates at the 1-o’clock position and iris prolapse at the site of perforation, under a bandage contact lens. D, Left eye following corneoscleral graft with active guttering superotemporally and a central persistent epithelial defect. E, Right eye with quiescent disease 5 months after commencing infliximab therapy and conjunctival resection. F, Left eye with quiescent disease 5 months after commencing infliximab therapy.

Graphic Jump Location

Tables

References

Gottsch  JDLi  QAshraf  FO'Brien  TPStark  WJLiu  SH Cytokine-induced calgranulin C expression in keratocytes. Clin Immunol 1999;91 (1) 34- 40
PubMed Link to Article
Kafkala  CChoi  JZafirakis  P  et al.  Mooren ulcer: an immunopathologic study. Cornea 2006;25 (6) 667- 673
PubMed Link to Article
Hale  SLightman  S Anti-TNF therapies in the management of acute and chronic uveitis. Cytokine 2006;33 (4) 231- 237
PubMed Link to Article
Nadkarni  SMauri  CEhrenstein  MR Anti-TNF-alpha therapy induces a distinct regulatory T cell population in patients with rheumatoid arthritis via TGF-beta. J Exp Med 2007;204 (1) 33- 39
PubMed Link to Article
Sieper  JVan Den  BJ Diverse effects of infliximab and etanercept on T lymphocytes. Semin Arthritis Rheum 2005;34 (5) ((suppl 1)) 23- 27
PubMed Link to Article

Correspondence

CME
Also Meets CME requirements for:
Browse CME for all U.S. States
Accreditation Information
The American Medical Association is accredited by the Accreditation Council for Continuing Medical Education to provide continuing medical education for physicians. The AMA designates this journal-based CME activity for a maximum of 1 AMA PRA Category 1 CreditTM per course. Physicians should claim only the credit commensurate with the extent of their participation in the activity. Physicians who complete the CME course and score at least 80% correct on the quiz are eligible for AMA PRA Category 1 CreditTM.
Note: You must get at least of the answers correct to pass this quiz.
Please click the checkbox indicating that you have read the full article in order to submit your answers.
Your answers have been saved for later.
You have not filled in all the answers to complete this quiz
The following questions were not answered:
Sorry, you have unsuccessfully completed this CME quiz with a score of
The following questions were not answered correctly:
Commitment to Change (optional):
Indicate what change(s) you will implement in your practice, if any, based on this CME course.
Your quiz results:
The filled radio buttons indicate your responses. The preferred responses are highlighted
For CME Course: A Proposed Model for Initial Assessment and Management of Acute Heart Failure Syndromes
Indicate what changes(s) you will implement in your practice, if any, based on this CME course.

Multimedia

Some tools below are only available to our subscribers or users with an online account.

807 Views
4 Citations
×

Related Content

Customize your page view by dragging & repositioning the boxes below.

Articles Related By Topic
Related Collections
PubMed Articles
Multifocal and refractory pyoderma gangrenosum: Possible role of cocaine abuse. Australas J Dermatol Published online Jun 2, 2016;
Mucosal Healing of Pediatric Simple Ulcer Treated with Infliximab and Methotrexate. J Pediatr Gastroenterol Nutr Published online Feb 15, 2016;
Jobs
JAMAevidence.com

The Rational Clinical Examination: Evidence-Based Clinical Diagnosis
Diabetes, Foot Ulcer

The Rational Clinical Examination: Evidence-Based Clinical Diagnosis
Original Article: Does This Patient With Diabetes Have Osteomyelitis of the Lower Extremity?