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Peripheral Ulcerative Keratitis Treatment & Management

  • Author: Ellen N Yu-Keh, MD; Chief Editor: Hampton Roy, Sr, MD  more...
Updated: May 13, 2016

Medical Care

Local treatment of peripheral ulcerative keratitis (PUK) is aimed at preventing or reducing corneal damage. Systemic therapy is aimed at controlling the underlying disease. A goal is reepithelialization of the epithelial defect to halt progressive corneal ulceration.

Surgical care may be combined with adjunctive local therapy with topical 1% medroxyprogesterone (which inhibits collagenase synthesis) or topical 20% N -acetylcysteine (a competitive inhibitor of collagenase). Lubricating drops, gels, and ointments and antibiotic drops or ointments can be helpful in aiding reepithelialization.

Topical steroid use is not recommended and should be used with caution in the treatment of patients with PUK associated with systemic disease because it may aggravate corneal melt due to collagen synthesis inhibition. However, some physicians would recommend its use only if the extent of corneal involvement is less than two quadrants and/or if stromal thickness is not less than 50%.[30]

Systemic collagenase inhibitors (tetracycline 250-mg tab qid or doxycycline 100-mg tab bid) may help slow the progression.

Some physicians recommend oral vitamin C given at 500 mg four times a day to facilitate corneal healing.[30]

There is limited experience in the use of topical cyclosporine[31] and topical tacrolimus.[32] Topical cyclosporine combined with lamellar keratoplasty (see Surgical Care) was noted to improve the healing rate in Mooren ulcer.[33] However, an underlying systemic vasculitis is not addressed with this route of treatment.

Many studies have documented that patients with PUK who have associated systemic diseases have recurrences following localized temporizing treatment unless they are given adequate systemic immunosuppressive therapy. To address the underlying problem, both systemic steroid and cytotoxic immunosuppressive medications have been used, alone or in combination, and are effective at controlling ocular and systemic inflammation. Immunosuppressive agents have been indicated for management of the following:

  • PUK associated with potentially lethal systemic vasculitic syndromes, such as PAN, RA, SLE, RP, WG, PSS, Sjögren syndrome, allergic angiitis of Churg-Strauss, and giant cell arteritis
  • PUK associated with necrotizing scleritis with vasculitis based on histopathologic analysis
  • Bilateral and/or progressive Mooren ulcer
  • PUK unresponsive to aggressive conventional medical and surgical therapy

Cyclophosphamide is the drug of choice for almost all PUK associated with a connective tissue disorder. The intravenous route has been used with success in PUK associated with rheumatoid arthritis.[34] Methotrexate (MTX), azathioprine, cyclosporine A, and chlorambucil have been found to be effective.[8] High-dose oral prednisone may be started, while the chemotherapeutic agents take effect after 4-6 weeks. When local or systemic infectious causes are suspected, therapy must be aimed at eliminating the infectious organism using the appropriate antibiotic medications based on clinical presentation or culture.

The use of the tumor necrosis factor alpha (TNF-alpha) antagonist infliximab has been reported to be effective in rheumatoid arthritis-associated PUK cases refractory to the above conventional immunomodulatory therapy.[35, 36] For its use in treating PUK in Crohn disease, see Pham et al.[37]

Rituximab, a chimeric monoclonal antibody directed against the CD20 protein found in B cells, has been used in treatment-resistant PUK in WG[38] and RA.[39]


Surgical Care

Tissue adhesives, such as cyanoacrylate glue, are recommended for use in impending perforation and perforation size smaller than 1-2 mm.[6] Adhesive application follows keratectomy and conjunctival resection to remove sources of collagenase, cytokines, and inflammatory cells from the ulcerated cornea, temporarily preventing further stromal loss.

Peripheral ulcerative keratitis in the right eye o Peripheral ulcerative keratitis in the right eye of a patient with rheumatoid arthritis. Glue has been placed.

Application of a bandage contact lens prevents discomfort and dislodging of the adhesive.[6]

Amniotic membrane transplantation has been used in the management of Mooren ulcer.[40] Amniotic membranes have properties that promote rapid healing and reduce inflammation by sequestering inflammatory cells infiltrating the ocular surface.[41, 42] However, they may have a limited role in treating eyes with severe ischemia (eg, rheumatoid arthritis).[43] .

In severe cases of peripheral ulcerative keratitis (PUK) associated with membranous endothelial exudation, anterior chamber washout may be combined with amniotic membrane transplantation.[44]

Tectonic procedures, including lamellar keratoplasty, penetrating keratoplasty, and corneoscleral patch grafts, are performed as needed to maintain the integrity of the globe when corneoscleral perforation is imminent or has occurred.

The corneoscleral rim of donor grafts have been used in partial lamellar keratoplasty and may be an alternative in areas where donor corneas are scarce.[45]

Visual results of corneal transplantation may be disappointing. However, corneal clarity may be maintained with good visual outcomes when accompanied by aggressive systemic anti-inflammatory therapy in selected patients.[13]



Referral to an appropriate specialist may be necessary. In patients with connective tissue diseases, comanagement with a rheumatologist is necessary to address the systemic disease. Pulmonary, nephrology, cardiac, hematology, and infectious disease consults may be necessary depending on the patient's symptoms and laboratory findings. Regular consultation with an oncologist may be necessary for those patients who are receiving chemotherapy.



Decreased visual acuity and systemic disorders may be limiting factors.

Contributor Information and Disclosures

Ellen N Yu-Keh, MD Consulting Staff, Department of Ophthalmology, St Luke's Medical Center, Quezon City, Philippines

Ellen N Yu-Keh, MD is a member of the following medical societies: Philippine Medical Association

Disclosure: Nothing to disclose.


C Stephen Foster, MD, FACS, FACR, FAAO, FARVO Clinical Professor of Ophthalmology, Harvard Medical School; Consulting Staff, Department of Ophthalmology, Massachusetts Eye and Ear Infirmary; Founder and President, Ocular Immunology and Uveitis Foundation, Massachusetts Eye Research and Surgery Institution

C Stephen Foster, MD, FACS, FACR, FAAO, FARVO is a member of the following medical societies: Alpha Omega Alpha, American Academy of Ophthalmology, American Association of Immunologists, American College of Rheumatology, American College of Surgeons, American Federation for Clinical Research, American Medical Association, American Society for Microbiology, American Uveitis Society, Association for Research in Vision and Ophthalmology, Massachusetts Medical Society, Royal Society of Medicine, Sigma Xi

Disclosure: Nothing to disclose.

Specialty Editor Board

Francisco Talavera, PharmD, PhD Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Received salary from Medscape for employment. for: Medscape.

Christopher J Rapuano, MD Professor, Department of Ophthalmology, Jefferson Medical College of Thomas Jefferson University; Director of the Cornea Service, Co-Director of Refractive Surgery Department, Wills Eye Hospital

Christopher J Rapuano, MD is a member of the following medical societies: American Academy of Ophthalmology, American Ophthalmological Society, American Society of Cataract and Refractive Surgery, Contact Lens Association of Ophthalmologists, International Society of Refractive Surgery, Cornea Society, Eye Bank Association of America

Disclosure: Serve(d) as a director, officer, partner, employee, advisor, consultant or trustee for: Cornea Society, Allergan, Bausch & Lomb, Bio-Tissue, Shire, TearScience, TearLab<br/>Serve(d) as a speaker or a member of a speakers bureau for: Allergan, Bausch & Lomb, Bio-Tissue, TearScience.

Chief Editor

Hampton Roy, Sr, MD Associate Clinical Professor, Department of Ophthalmology, University of Arkansas for Medical Sciences

Hampton Roy, Sr, MD is a member of the following medical societies: American Academy of Ophthalmology, American College of Surgeons, Pan-American Association of Ophthalmology

Disclosure: Nothing to disclose.

Additional Contributors

Fernando H Murillo-Lopez, MD Senior Surgeon, Unidad Privada de Oftalmologia CEMES

Fernando H Murillo-Lopez, MD is a member of the following medical societies: American Academy of Ophthalmology

Disclosure: Nothing to disclose.


The authors and editors of Medscape Reference gratefully acknowledge the contributions of previous author, Lijing Yao, MD, to the development and writing of this article.

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Peripheral ulcerative keratitis in the right eye of a patient with rheumatoid arthritis. Glue has been placed.
Same patient as in previous image, 1 year posttreatment.
Left eye of same patient as in previous images. Note the corneal thinning and scarring.
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