Medscape is available in 5 Language Editions – Choose your Edition here.


Central Sterile Corneal Ulceration Clinical Presentation

  • Author: Saadia Zohra Farooqui, MBBS; Chief Editor: Hampton Roy, Sr, MD  more...
Updated: Jun 27, 2016


In diagnosing this condition, differentiating between infectious and noninfectious etiologies is crucial. Since the clinical management of any corneal ulcer is dependent on its etiology, obtaining all of the salient factors (eg, endogenous, exogenous, local) is important. Therapies for sterile persistent ulcerations should be considered only after adequately addressing infectious and systemic factors.

Key points to assess in obtaining the history of a patient with a corneal ulcer include the following: 

  • Prior ocular history - Prior ocular and adnexal surgery, recurrent episodes or infections (eg, herpes), and corneal dystrophy
  • Past medical history - Immune status, collagen vascular diseases, systemic infections, diabetes, malnutrition, alcoholism, and chronic debilitating diseases
  • History of trauma - Foreign bodies and their origin (eg, soil, vegetation, water), chemical splashes, and lid lacerations
  • Contact lens use - Type, frequency, duration, overnight use, and hygiene
  • Medications - Ocular and otherwise
  • History of present illness - Duration, ocular symptoms (eg, degree of pain vs clinical impression), and chronicity
  • Social history - Patient from an area endemic for certain infectious processes, nutritional status, and any alcohol abuse

The etiology of a sterile ulcer is often multifactorial; in this setting, identifying the coconspirators in this process is important. A thorough evaluation to identify potential factors, including medications (medicamentosa), impaired corneal sensation (neurotrophic), exposure (eg, lagophthalmos), and reduced tear production (sicca), is necessary in most cases of persistent noninfectious ulceration.



The physical examination should begin with a gestalt impression of the entire patient, with attention to the following: 

  • General health of the patient - Skin lesions, skeletal abnormalities, mental status, degree of discomfort,  hearing aids, scars, and limitations to ambulation that may indicate a systemic illness
  • Local ocular adnexa and related organs - Eyelids, lacrimal system, blink rate, scars, mucous membranes (eg, lips/mouth, conjunctiva), orbit, symmetry, and evidence of inflammation or infection 
  • Palpation - If indicated for orbital resiliency (thyroid/exposure), lymphadenopathy, and lacrimal or other adnexal masses
  • Observation - Lagophthalmos and blink rate
  • Assessment of vital signs of the eye - Visual function, corneal sensation, tonometry, pupil function, and motility of the eye (Corneal sensation should be checked prior to tonometry.) 

On slit lamp examination of the cornea, note the appearance of and evaluate the following: 

  • Conjunctiva, sclera, and lids - Erythema, pattern of injection (ciliary flush, diffuse or deep), perilimbal nodules, discharge, lid closure, lid margin disease, and flipped upper lid to exclude foreign body and floppy eyelid syndrome 
  • Tear film - Degree, symmetry, regularity, and presence of debris
  • Epithelium - Location of epithelial defect (localized or diffuse), regularity, and microcysts
  • Stroma - Thinning and presence/pattern of infiltrates (eg, ring, feathery, radial)
  • Endothelium - Keratic precipitates
  • Anterior chamber - Hypopyon and inflammation
  • Corneal sensation
  • Symmetry between the eyes
  • Fluorescein examination
  • Dilated examination 


A thorough history and physical examination should allow a clinician to narrow down the differential diagnosis.

Infectious causes (which need to be ruled out first) include the following: 

  • Bacterial (focal infiltrate)
  • Fungal (vegetable matter, eg, branch; appearance of satellite lesions; feathery borders to infiltrate; chronic)
  • Acanthamoeba (contact lens wear, tap water, soil, severe pain out of proportion to the appearance, radial keratitis, ring ulcer) 
  • Herpes simplex virus (history, dendrites, decreased sensation, disciform keratitis, increased intraocular pressure)
  • Herpes zoster virus (vesicles over dermatome; pseudodendrites, no true terminal bulbs; decreased sensation; increased intraocular pressure) 
  • Contact lens related (infectious or noninfectious)

Noninfectious causes include the following: 

  • Chemical burns, including alkali/acid burn (check pH)
  • Thermal/radiation burns (history)
  • Sicca (filaments, Sjögren syndrome)
  • Neurotrophic (decreased sensation, may have minimal pain, rolled edges, oval, lower one half of cornea, may be quite thin, herpes zoster virus/herpes simplex virus, postsurgery, fifth-nerve palsy, chemical burns, abuse of topical anesthetics, neurotrophic keratitis, diabetes mellitus, multiple sclerosis) [19]
  • Exposure (lagophthalmos, lid abnormalities, inadequate blink, facial palsy, proptosis, thyroid disease)
  • Medicamentosa (drops)
  • Atopic (history, follicles/papillae)
  • Vitamin A deficiency (primary deficiency due to prolonged dietary deprivation; secondary deficiency due to diseases that interfere with fat absorption and storage, eg, celiac disease, cystic fibrosis, cholestasis) 
  • Basement membrane abnormalities (microcysts, evidence of map-dot-fingerprint or anterior stromal dystrophies, history of trauma, other dystrophy) 
  • Factitious

Immune-related causes (usually peripheral) include the following: 

  • Wegener granulomatosis
  • Rheumatoid arthritis
  • Other collagen vascular diseases (indicated from history and associated systemic findings)
Contributor Information and Disclosures

Saadia Zohra Farooqui, MBBS Senior Resident, Singapore National Eye Centre, Singapore General Hospital, Singapore

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.

Joseph JK Ma, MD Assistant Professor, Department of Ophthalmology, University of Toronto Faculty of Medicine, Canada

Joseph JK Ma, MD is a member of the following medical societies: American Academy of Ophthalmology

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.

  1. Wentworth JS, Paterson CA, Gray RD. Effect of a metalloproteinase inhibitor on established corneal ulcers after an alkali burn. Invest Ophthalmol Vis Sci. 1992 Jun. 33(7):2174-9. [Medline].

  2. Gabison EE, Mourah S, Steinfels E, et al. Differential expression of extracellular matrix metalloproteinase inducer (CD147) in normal and ulcerated corneas: role in epithelio-stromal interactions and matrix metalloproteinase induction. Am J Pathol. 2005 Jan. 166(1):209-19. [Medline].

  3. Ralph RA. Tetracyclines and the treatment of corneal stromal ulceration: a review. Cornea. May 2000. 19(3):274-7. [Medline].

  4. Shimmura S, Igarashi R, Yaguchi H, et al. Lecithin-bound superoxide dismutase in the treatment of noninfectious corneal ulcers. Am J Ophthalmol. 2003 May. 135(5):613-9. [Medline].

  5. Tripathi BK, Stepp MA, Gao CY, et al. The Cdk5 inhibitor olomoucine promotes corneal debridement wound closure in vivo. Mol Vis. 2008 Mar 17. 14:542-9. [Medline].

  6. Amjadi S, Mai K, McCluskey P, Wakefield D. The role of lumican in ocular disease. ISRN Ophthalmol. Jul 2013. 2013:632302. [Medline].

  7. Sigelman S, Friedenwald JS. Mitotic and wound-healing activities of the corneal epithelium; effect of sensory denervation. AMA Arch Ophthalmol. 1954 Jul. 52(1):46-57. [Medline].

  8. Nakamura M, Chikama T, Nishida T. Synergistic effect with Phe-Gly-Leu-Met-NH2 of the C-terminal of substance P and insulin-like growth factor-1 on epithelial wound healing of rabbit cornea. Br J Pharmacol. 1999 May. 127(2):489-97. [Medline].

  9. Yanai R, Nishida T, Chikama T, Morishige N, Yamada N, Sonoda KH. Potential New Modes of Treatment of Neurotrophic Keratopathy. Cornea. Nov 2015. 34 Suppl 11:S121-7. [Medline].

  10. Bonini S, Lambiase A, Rama P, et al. Topical treatment with nerve growth factor for neurotrophic keratitis. Ophthalmology. 2000 Jul. 107(7):1347-51; discussion 1351-2. [Medline].

  11. Dohlman CH, Slansky HH, Laibson PR, et al. Artificial corneal epithelium in acute alkali burns. Ann Ophthalmol. 1969. 112.

  12. Kenyon KR, Berman M, Rose J, et al. Prevention of stromal ulceration in the alkali-burned rabbit cornea by glued-on contact lens. Evidence for the role of polymorphonuclear leukocytes in collagen degradation. Invest Ophthalmol Vis Sci. 1979 Jun. 18(6):570-87. [Medline].

  13. Nubile M, Dua HS, Lanzini M, Ciancaglini M, Calienno R, Said DG, et al. In vivo analysis of stromal integration of multilayer amniotic membrane transplantation in corneal ulcers. Am J Ophthalmol. 2011 May. 151(5):809-822.e1. [Medline].

  14. Soni NG, Jeng BH. Blood-derived topical therapy for ocular surface diseases. Br J Ophthalmol. Jan 2016. 100(1):22-7. [Medline].

  15. Saika S, Miyamoto T, Yamanaka O, et al. Therapeutic effect of topical administration of SN50, an inhibitor of nuclear factor-kappaB, in treatment of corneal alkali burns in mice. Am J Pathol. 2005 May. 166(5):1393-403. [Medline].

  16. Sosne G, Qiu P, Christopherson PL, et al. Thymosin beta 4 suppression of corneal NFkappaB: a potential anti-inflammatory pathway. Exp Eye Res. 2007 Apr. 84(4):663-9. [Medline].

  17. Saika S, Yamanaka O, Okada Y, et al. Effect of overexpression of PPARgamma on the healing process of corneal alkali burn in mice. Am J Physiol Cell Physiol. 2007 Jul. 293(1):C75-86. [Medline].

  18. Stevenson W1, Sadrai Z, Hua J, Kodati S, Huang JF, Chauhan SK, et al. Effects of topical Janus kinase inhibition on ocular surface inflammation and immunity. Cornea. Feb 2014. 33(2):177-83. [Medline].

  19. Ioannidis AS, Zagora SL, Wechsler AW. A non-healing corneal ulcer as the presenting feature of type 1 diabetes mellitus: a case report. J Med Case Reports. 2011 Nov 4. 5(1):539. [Medline].

  20. Yoon KC, You IC, Im SK, et al. Application of umbilical cord serum eyedrops for the treatment of neurotrophic keratitis. Ophthalmology. 2007 Sep. 114(9):1637-42. [Medline].

  21. Alio JL, Abad M, Artola A, et al. Use of autologous platelet-rich plasma in the treatment of dormant corneal ulcers. Ophthalmology. 2007 Jul. 114(7):1286-1293.e1. [Medline].

  22. Albert DM, Jakobiec FA, eds. Principles and Practice of Ophthalmology. 2nd ed. Boston: WB Saunders Co; 2000.

  23. Dua HS, Gomes JA, Singh A. Corneal epithelial wound healing. Br J Ophthalmol. 1994 May. 78(5):401-8. [Medline].

  24. Geerling G, Joussen AM, Daniels JT, et al. Matrix metalloproteinases in sterile corneal melts. Ann N Y Acad Sci. 1999 Jun 30. 878:571-4. [Medline].

  25. Gipson IK, Inatomi T. Extracellular matrix and growth factors in corneal wound healing. Curr Opin Ophthalmol. 1995 Aug. 6(4):3-10. [Medline].

  26. He J, Bazan NG, Bazan HE. Alkali-induced corneal stromal melting prevention by a novel platelet-activating factor receptor antagonist. Arch Ophthalmol. 2006 Jan. 124(1):70-8. [Medline].

  27. Imanishi J, Kamiyama K, Iguchi I, et al. Growth factors: importance in wound healing and maintenance of transparency of the cornea. Prog Retin Eye Res. 2000 Jan. 19(1):113-29. [Medline].

  28. Kaufman HE, et al, eds. The Cornea. 2nd ed. Boston: Butterworth-Heinemann; 1998.

  29. Nagano T, Nakamura M, Nakata K, et al. Effects of substance P and IGF-1 in corneal epithelial barrier function and wound healing in a rat model of neurotrophic keratopathy. Invest Ophthalmol Vis Sci. 2003 Sep. 44(9):3810-5. [Medline].

  30. Watanabe M, Yano W, Kondo S, et al. Up-regulation of urokinase-type plasminogen activator in corneal epithelial cells induced by wounding. Invest Ophthalmol Vis Sci. 2003 Aug. 44(8):3332-8. [Medline].

  31. Wilson SE, Liu JJ, Mohan RR. Stromal-epithelial interactions in the cornea. Prog Retin Eye Res. 1999 May. 18(3):293-309. [Medline].

All material on this website is protected by copyright, Copyright © 1994-2016 by WebMD LLC. This website also contains material copyrighted by 3rd parties.