Corneal Ulcer

No Results

No Results


The term “corneal ulcer” is often used interchangeably with “bacterial keratitis,” although, in practice, these are two different entities. Bacterial keratitis denotes a bacterial infection of the eye that causes inflammation and, potentially, ulceration of the cornea, whereas corneal ulcer describes a loss of corneal tissue due to many possible causes. Although acute corneal ulcers in emergency settings are most likely infectious in etiology, other sterile causes of ulceration exist.

This article specifically addresses sterile corneal ulcers associated with autoinflammatory diseases.

The most common autoimmune pathologies with ocular manifestations include rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), connective-tissue disorders (Sjögren syndrome, scleroderma, relapsing polychondritis), and vasculitis (granulomatosis with polyangiitis [GPA], polyarteritis nodosa, and, rarely, Behcet disease). Patients with ocular manifestations of autoinflammatory diseases often have keratoconjunctivitis sicca (dry eye syndrome), which can cause corneal ulceration. Less frequently, the autoinflammatory process can also directly attack the cornea, causing peripheral ulcerative keratitis (PUK), a condition that demands aggressive treatment.

Some cases of corneal ulcer may also be idiopathic; these are referred to as Mooren ulcers. These noninfectious ulcerations touch the peripheral cornea and have been classified into 2 clinical types. One is a milder, unilateral, less progressive form of the disease generally seen in elderly patients that responds well to therapy. The second type is a much more aggressive, frequently bilateral, relentless disease usually seen in younger patients that is poorly responsive to any therapy and often leads to corneal destruction. Increasing evidence has shown an autoimmune basis for this pathology. [1, 2]

Of note, patients with a poor corneal surface are at increased risk of corneal infection, especially those with systemic diseases in whom keratoconjunctivitis sicca (dry eye syndrome) is also often present.

The pathogenesis of corneal ulcers associated with autoinflammatory diseases is not clear. Possibilities include immunologic responses to unknown antigens and genetic susceptibility, such as genetic predisposition to the development of defective suppressor T-lymphocyte function, production of autoantibodies (eg, antinuclear antibodies), and activation of the complement pathway.

Peripheral ulcerative keratitis (PUK) is a rare manifestation of RA characterized by a progressive thinning of the peripheral cornea secondary to release of collagenases and proteases by neutrophils and/or macrophages and complement activation in the region of the limbal vasculature and avascular cornea. This leads to keratolysis, with or without ulceration. [3]

Genetic and environmental factors are associated with SLE. In a genetically susceptible individual, certain environmental stimuli, such as a viral infection or contact with certain drugs, induce alterations in DNA, immunoregulatory networks, or both, with resultant formation of autoantibodies, including antinuclear antibody (ANA).

The pathogenesis of polyarteritis nodosa is not clear, but, in some patients, it may be related to hepatitis B antigen–associated immune complex disease or other immune complexes.

Mooren ulcers are, by definition, idiopathic in origin. However, increasing evidence suggests that Mooren ulcer is, in fact, an autoimmune disease that exclusively targets the corneal stroma and is triggered by environmental factors in genetically susceptible individuals. [4] Associations have also been reported among Mooren ulcer, helminthiasis, [5] and ocular injuries. [6] Of note, this pathology has been previously associated with hepatitis C, [7] but more recent studies have failed to support this relationship. [8, 9]

A 2014 study involving 70 patients showed that ulcerative keratitis generally affected older, predominantly female patients, about two-thirds of whom had RA. [10]

The prevalence of ulcerative keratitis in patients with RA was 1.4% in a retrospective study of 589 patients. [11]

Development of a corneal ulcer associated with a connective tissue disease or a vasculitis carries a poor prognosis.

Patients who have RA with scleritis and a corneal melt die within 5 years without aggressive treatment. This type of corneal ulcer may lead to corneal thinning and perforation in the perilimbal region or paracentrally.

Wegener granulomatosis has no ethnic predilection.

RA primarily affects middle-aged females.

Scleroderma is 3-4 times more common in women than in men.

Polyarteritis nodosa is 2.5 times more likely to affect males than females.

No sexual predilection exists with Wegener granulomatosis.

Corneal ulcer associated with autoinflammatory diseases does not affect children. Except for the malignant form of Mooren ulcer, patients with this pathology are usually older than 30 years.

Wegener granulomatosis can affect all age groups.

Scleroderma usually starts in individuals aged 30-50 years.

Polyarteritis nodosa is more frequent in middle-aged males.

RA is the most common immune condition associated with corneal ulceration. [12] The development of extra-articular features of RA has been associated with increased morbidity and mortality. [13] In RA, peripheral ulcerative keratitis commonly manifests later in the disease process rather than at disease onset, suggesting that the disease is worsening. Several early studies demonstrated an increased mortality rate among patients with RA-associated scleritis or corneal ulcers. [14, 15] A more recent study also confirmed a higher mortality rate among patients with RA who had severe corneal ulcers requiring corneal transplantation, compared with ulcer-free patients with RA. [16] However, early initiation of aggressive systemic anti-inflammatory therapy has been shown to reduce the severity and morbidity of ulcerative keratitis. [10]

Shinomiya K, Ueta M, Sotozono C, Inatomi T, Yokoi N, Koizumi N, et al. Immunohistochemical analysis of inflammatory limbal conjunctiva adjacent to Mooren’s ulcer. Br J Ophthalmol. 2013 Mar. 97 (3):362-6. [Medline].

Kafkala C, Choi J, Zafirakis P, Baltatzis S, Livir-Rallatos C, Rojas B, et al. Mooren ulcer: an immunopathologic study. Cornea. 2006 Jul. 25 (6):667-73. [Medline].

Hardy S, Hashemi K, Catanese M, Candil M, Zufferey P, Gabison E, et al. Necrotising Scleritis and Peripheral Ulcerative Keratitis Associated with Rheumatoid Arthritis Treated with Rituximab. Klin Monbl Augenheilkd. 2017 Apr. 234 (4):567-570. [Medline].

Lee HJ, Kim MK, Wee WR, Oh JY. Interplay of Immune Cells in Mooren Ulcer. Cornea. 2015 Sep. 34 (9):1164-7. [Medline].

Zelefsky JR, Srinivasan M, Kundu A, Lietman T, Whitcher JP, Wang K, et al. Hookworm infestation as a risk factor for Mooren’s ulcer in South India. Ophthalmology. 2007 Mar. 114 (3):450-3. [Medline].

Srinivasan M, Zegans ME, Zelefsky JR, Kundu A, Lietman T, Whitcher JP, et al. Clinical characteristics of Mooren’s ulcer in South India. Br J Ophthalmol. 2007 May. 91 (5):570-5. [Medline].

Wilson SE, Lee WM, Murakami C, Weng J, Moninger GA. Mooren-type hepatitis C virus-associated corneal ulceration. Ophthalmology. 1994 Apr. 101(4):736-45. [Medline].

Jain AK, Sukhija J, Saini JS, Chawla Y, Dhiman RK. Hepatitis C virus-associated keratitis. Eye (Lond). 2004 Feb. 18 (2):131-4. [Medline].

Wang QS, Yuan J, Zhou SY, Chen JQ. Chronic hepatitis C virus infection is not associated with Mooren’s ulcer. Eye (Lond). 2008 May. 22 (5):697-700. [Medline].

Knox Cartwright NE, Tole DM, Georgoudis P, Cook SD. Peripheral ulcerative keratitis and corneal melt: a 10-year single center review with historical comparison. Cornea. 2014 Jan. 33 (1):27-31. [Medline].

Dong Y, Zhang Y, Xie L, Ren J. Risk Factors, Clinical Features, and Treatment Outcomes of Recurrent Mooren Ulcers in China. Cornea. 2017 Feb. 36 (2):202-209. [Medline].

Sainz de la Maza M, Foster CS, Jabbur NS, Baltatzis S. Ocular characteristics and disease associations in scleritis-associated peripheral keratopathy. Arch Ophthalmol. 2002 Jan. 120 (1):15-9. [Medline].

Turesson C, Jacobsson L, Bergström U. Extra-articular rheumatoid arthritis: prevalence and mortality. Rheumatology (Oxford). 1999 Jul. 38 (7):668-74. [Medline].

McGavin DD, Williamson J, Forrester JV, Foulds WS, Buchanan WW, Dick WC, et al. Episcleritis and scleritis. A study of their clinical manifestations and association with rheumatoid arthritis. Br J Ophthalmol. 1976 Mar. 60 (3):192-226. [Medline].

Foster CS, Forstot SL, Wilson LA. Mortality rate in rheumatoid arthritis patients developing necrotizing scleritis or peripheral ulcerative keratitis. Effects of systemic immunosuppression. Ophthalmology. 1984 Oct. 91 (10):1253-63. [Medline].

Stylianides A, Jones MN, Stewart RM, Murphy CC, Goodson NJ, Kaye SB. Rheumatoid arthritis-associated corneal ulceration: mortality and graft survival. Ophthalmology. 2013 Apr. 120 (4):682-6. [Medline].

Ladas JG, Mondino BJ. Systemic disorders associated with peripheral corneal ulceration. Curr Opin Ophthalmol. 2000 Dec. 11 (6):468-71. [Medline].

Murray PI, Rauz S. The eye and inflammatory rheumatic diseases: The eye and rheumatoid arthritis, ankylosing spondylitis, psoriatic arthritis. Best Pract Res Clin Rheumatol. 2016 Oct. 30 (5):802-825. [Medline].

Ahmed M, Niffenegger JH, Jakobiec FA, Ben-Arie-Weintrob Y, Gion N, Androudi S, et al. Diagnosis of limited ophthalmic Wegener granulomatosis: distinctive pathologic features with ANCA test confirmation. Int Ophthalmol. 2008 Feb. 28 (1):35-46. [Medline].

Harthan JS, Reeder RE. Peripheral ulcerative keratitis in association with sarcoidosis. Cont Lens Anterior Eye. 2013 Dec. 36 (6):313-7. [Medline].

Silpa-archa S, Lee JJ, Foster CS. Ocular manifestations in systemic lupus erythematosus. Br J Ophthalmol. 2016 Jan. 100 (1):135-41. [Medline].

Levitt AE, McManus KT, McClellan AL, Davis JL, Goldhardt R, Galor A. Ocular Inflammation in the Setting of Concomitant Systemic Autoimmune Conditions in an Older Male Population. Cornea. 2015 Jul. 34 (7):762-7. [Medline].

Siracuse-Lee D, Saffra N. Peripheral ulcerative keratitis in sarcoidosis: a case report. Cornea. 2006 Jun. 25 (5):618-20. [Medline].

Ji YS, Yoon KC. A rare case of peripheral ulcerative keratitis associated with Behçet’s disease. Int Ophthalmol. 2014 Aug. 34 (4):979-81. [Medline].

Lai THT, Far N, Young AL, Jhanji V. Rapid corneal thinning and perforated ulcerative keratitis in a patient with relapsing polychondritis. Eye Vis (Lond). 2017. 4:8. [Medline].

Paroli MP, Pinca M, Speranza S, Marino M, Pivetti-Pezzi P. Paracentral corneal melting in a patient with Vogt-Koyanagi-Harada’s syndrome, psoriasis, and Hashimoto’s thyroiditis. Ocul Immunol Inflamm. 2003 Dec. 11(4):309-13. [Medline].

Wei DW, Pagnoux C, Chan CC. Peripheral Ulcerative Keratitis Secondary to Chronic Hepatitis B Infection. Cornea. 2017 Apr. 36 (4):515-517. [Medline].

Asai T, Nakagami T, Mochizuki M. Three cases of corneal melting after instillation of a new nonsteroidal anti-inflammatory drug. Cornea. 2006 Feb. 25 (2):224-7. [Medline].

Flach AJ. Corneal melts associated with topically applied nonsteroidal anti-inflammatory drugs. Trans Am Ophthalmol Soc. 2001. 99:205-10; discussion 210-2. [Medline].

Guidera AC, Luchs JI, Udell IJ. Keratitis, ulceration, and perforation associated with topical nonsteroidal anti-inflammatory drugs. Ophthalmology. 2001 May. 108(5):936-44. [Medline].

Lambiase A, Bonini S, Aloe L, et al. Anti-inflammatory and healing properties of nerve growth factor in immune corneal ulcers with stromal melting. Arch Ophthalmol. 2000 Oct. 118(10):1446-9. [Medline].

Troumani Y, Beral L, Glatre F, Finke E, David T. [One case of corneal melting after instillation of bromfenac 0.09%]. J Fr Ophtalmol. 2014 Oct. 37 (8):e125-7. [Medline].

Schechter BA, Rand WJ, Nagler RS. Corneal melt after amniotic membrane transplant. Cornea. 2005 Jan. 24(1):106-7. [Medline].

Bouhout S, Robert MC, Deli S, Harissi-Dagher M. Corneal Melt after Boston Keratoprosthesis: Clinical Presentation, Management, Outcomes and Risk Factor Analysis. Ocul Immunol Inflamm. 2017 Jan 12. 1-7. [Medline].

Yazici AT, Kara N, Yüksel K, Altinkaynak H, Baz O, Bozkurt E, et al. The biomechanical properties of the cornea in patients with systemic lupus erythematosus. Eye (Lond). 2011 Aug. 25(8):1005-9. [Medline]. [Full Text].

Kalsow CM, Ching SS, Plotnik RD. Cellular Infiltrate in Rheumatoid Arthritis-associated Paracentral Corneal Ulceration. Ocul Immunol Inflamm. 2016 Aug 11. 1-6. [Medline].

Gomes BA, Santhiago MR, Jorge PA, Kara-José N, Moraes HV Jr, Kara-Junior N. Corneal involvement in systemic inflammatory diseases. Eye Contact Lens. 2015 May. 41 (3):141-4. [Medline].

Lambiase A, Rama P, Bonini S, et al. Topical treatment with nerve growth factor for corneal neurotrophic ulcers. N Engl J Med. 1998 Apr 23. 338(17):1174-80. [Medline].

Manni L, Rocco ML, Bianchi P, Soligo M, Guaragna M, Barbaro SP, et al. Nerve growth factor: basic studies and possible therapeutic applications. Growth Factors. 2013 Aug. 31 (4):115-22. [Medline].

Korsten P, Bahlmann D, Patschan SA. Rapid healing of peripheral ulcerative keratitis in rheumatoid arthritis with prednisone, methotrexate and adalimumab combination therapy. Rheumatology (Oxford). 2017 Feb 14. [Medline].

Ebrahimiadib N, Modjtahedi BS, Roohipoor R, Anesi SD, Foster CS. Successful Treatment Strategies in Granulomatosis With Polyangiitis-Associated Peripheral Ulcerative Keratitis. Cornea. 2016 Nov. 35 (11):1459-1465. [Medline].

Guindolet D, Reynaud C, Clavel G, Belangé G, Benmahmed M, Doan S, et al. Management of severe and refractory Mooren’s ulcers with rituximab. Br J Ophthalmol. 2017 Apr. 101 (4):418-422. [Medline].

Vanathi M, Sharma N, Titiyal JS. Tectonic grafts for corneal thinning and perforations. Cornea. 2002 Nov. 21(8):792-7. [Medline].

Al Motowa S, Al Zobidi M. Amniotic Membrane Transplant with a Special Technique (Motowa’s Sandwich Technique) in Mooren’s Ulcer. Middle East Afr J Ophthalmol. 2015 Jul-Sep. 22 (3):386-8. [Medline].

Krysik K, Dobrowolski D, Lyssek-Boron A, Jankowska-Szmul J, Wylegala EA. Differences in Surgical Management of Corneal Perforations, Measured over Six Years. J Ophthalmol. 2017. 2017:1582532. [Medline].

Rush SW, Rush RB. Outcomes of Infectious versus Sterile Perforated Corneal Ulcers after Therapeutic Penetrating Keratoplasty in the United States. J Ophthalmol. 2016. 2016:6284595. [Medline].

Hochberg MC. Updating the American College of Rheumatology revised criteria for the classification of systemic lupus erythematosus. Arthritis Rheum. 1997 Sep. 40(9):1725. [Medline].

Watanabe R, Ishii T, Yoshida M, Takada N, Yokokura S, Shirota Y, et al. Ulcerative keratitis in patients with rheumatoid arthritis in the modern biologic era: a series of eight cases and literature review. Int J Rheum Dis. 2015 Jul 14. [Medline].

Jean Deschênes, MD, FRCSC Professor, Research Associate, Director, Uveitis Program, Department of Ophthalmology, McGill University Faculty of Medicine; Senior Ophthalmologist, Clinical Director, Department of Ophthalmology, Royal Victoria Hospital, Canada

Jean Deschênes, MD, FRCSC is a member of the following medical societies: American Academy of Ophthalmology, Association for Research in Vision and Ophthalmology, Canadian Medical Association, Canadian Ophthalmological Society, International Ocular Inflammation Society, Quebec Medical Association

Disclosure: Nothing to disclose.

Susan Ruyu Qi  University of Montreal Faculty of Medicine, Canada

Disclosure: Nothing to disclose.

Simon K Law, MD, PharmD Clinical Professor of Health Sciences, Department of Ophthalmology, Jules Stein Eye Institute, University of California, Los Angeles, David Geffen School of Medicine

Simon K Law, MD, PharmD is a member of the following medical societies: American Academy of Ophthalmology, Association for Research in Vision and Ophthalmology, American Glaucoma Society

Disclosure: Nothing to disclose.

J James Rowsey, MD Former Director of Corneal Services, St Luke’s Cataract and Laser Institute

J James Rowsey, MD is a member of the following medical societies: American Academy of Ophthalmology, American Association for the Advancement of Science, American Medical Association, Association for Research in Vision and Ophthalmology, Florida Medical Association, Sigma Xi, Southern Medical Association, Pan-American Association of Ophthalmology

Disclosure: Nothing to disclose.

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.

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.

Kilbourn Gordon, III, MD, FACEP Urgent Care Physician

Kilbourn Gordon, III, MD, FACEP is a member of the following medical societies: American Academy of Ophthalmology, Wilderness Medical Society

Disclosure: Nothing to disclose.

Corneal Ulcer

Research & References of Corneal Ulcer|A&C Accounting And Tax Services