Peripheral Ulcerative Keratitis 

  • Author: Ellen N Yu, MD; Chief Editor: Hampton Roy Sr, MD   more...
 
Updated: Jan 11, 2012
 

Background

Peripheral corneal ulceration is a potentially devastating disorder consisting of a crescent-shaped destructive inflammation at the margin of corneal stroma that is associated with an epithelial defect, presence of stromal inflammatory cells, and progressive stromal degradation and thinning. Commonly referred to as peripheral ulcerative keratitis (PUK), it can quickly produce progressive necrosis of the corneal stroma, leading to perforation and blindness.[1]

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Pathophysiology

The peripheral cornea has distinct morphologic and immunologic characteristics that predispose it to inflammatory reactions. Unlike the avascular central cornea, the peripheral cornea is closer to limbal conjunctiva and derives part of its nutrient supply from the limbal capillary arcade, a source of immunocompetent cells, for example, macrophages, Langerhans cells, lymphocytes, and plasma cells.[2, 3] Any inflammatory stimulus in the peripheral cornea that is caused by invasion of microbial organisms (bacteria, virus, fungi, and parasites), immune complex deposition (in systemic immune diseases), trauma, malignancy, or dermatologic conditions may produce local and systemic immune responses, resulting in neutrophil recruitment and complement activation (both classic and alternative pathways) in both tissue and vessels.[2]

Activated complement components can increase vascular permeability and further generate chemotactic factors for neutrophils (eg, C3a, C5a). Neutrophils, in turn, infiltrate the peripheral cornea and release proteolytic and collagenolytic enzymes, reactive oxygen metabolites, and proinflammatory substances (eg, platelet-activating factor, leukotrienes, prostaglandins), causing dissolution and degradation of the corneal stroma.[4, 5] In addition, the inflamed limbal conjunctiva itself is capable of producing collagenase, which contributes to stromal degradation.[6]

Systemic diseases that may cause immune complex deposition at the peripheral cornea and PUK include such collagen vascular diseases as rheumatoid arthritis (RA), Wegener granulomatosis (WG), polyarteritis nodosa (PAN), relapsing polychondritis (RP), and systemic lupus erythematosus (SLE). Infectious conditions, whether systemic (eg, hepatitis, syphilis) or local (eg, herpes simplex keratitis, fungal keratitis), and noninfectious local disorders (eg, Mooren ulcer, marginal keratitis) also may cause PUK.

In summary, the major pathophysiologic mechanism of PUK is a result of degradation and tissue necrosis of corneal stroma produced by degradative enzymes, which are released primarily by neutrophils attracted into the area by diverse stimuli.

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Epidemiology

Frequency

United States

PUK is uncommon. RA has been reported as the most common collagen vascular disorder that causes PUK, accounting for 34% of noninfectious PUK.[6, 7, 8] PUK may be the initial manifestation of WG and PAN. PUK is rare in patients with RP; only 2 of 112 patients with RP were reported to develop PUK in a clinical review study.[9] PUK has also been reported to be associated with SLE, although this is uncommon.[3, 10] Mooren ulcer is a rare local autoimmune disease associated with PUK, with only 287 cases reported in the world literature, although some of these cases may have been the presenting manifestation of an occult systemic disease rather than true Mooren ulcer.[11]

Mortality/Morbidity

PUK produces great morbidity from the pain and resultant visual disability. It can be a harbinger of death if the underlying disease is not diagnosed and successfully treated.

Race

No good data are available on racial predilection for PUK.

Sex

Since PUK is more common in people with collagen vascular disorders (especially RA), it is more common in females than in males. However, PUK caused by Mooren ulcer is more common in males than in females.[11, 12]

Age

Age varies and is dependent on the associated systemic or local disorder.

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Proceed to Clinical Presentation
 
 
Contributor Information and Disclosures
Author

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

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

Disclosure: Nothing to disclose.

Coauthor(s)

C Stephen Foster, MD, FACS, FACR, FAAO  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 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, and Sigma Xi

Disclosure: Nothing to disclose.

Specialty Editor Board

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.

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

Disclosure: Medscape Salary Employment

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 Institute

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

Disclosure: Allergan Honoraria Speaking and teaching; Allergan Consulting fee Consulting; Alcon Honoraria Speaking and teaching; RPS Ownership interest Other; EyeGate Pharma Consulting fee Consulting; Bausch & Lomb Honoraria Speaking and teaching; Bausch & Lomb Consulting; Merck Honoraria Speaking and teaching

Lance L Brown, OD, MD  Ophthalmologist, Affiliated With Freeman Hospital and St John's Hospital, Regional Eye Center, Joplin, Missouri

Disclosure: Nothing to disclose.

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, and Pan-American Association of Ophthalmology

Disclosure: Nothing to disclose.

Additional Contributors

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.

References

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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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