Central Sterile Corneal Ulceration Treatment & Management
- Author: Saadia Zohra Farooqui, MBBS; Chief Editor: Hampton Roy, Sr, MD more...
Individual treatment should be tailored toward the coconspirators that are identified by the history and physical examination. Again, the importance of first excluding infectious etiologies is paramount. Once identified, each contributing factor needs to be treated appropriately. All toxic drops should be eliminated if medicamentosa is suspected. Lagophthalmos should be treated with copious lubrication, with taping for variable amounts of time, beginning with sleeping hours. Tarsorrhaphy is indicated if previous method fails. Patients with sicca need copious lubrication and punctal plugs. Evaluate these patients for systemic rheumatologic disease if suspected by clinical history or examination. If immune disease is suspected, systemic immunomodulatory therapy may be necessary.
Treatment modalities are as follows:
- Antibiotics are used to treat the ulcer or as a prophylactic but do encourage resistant microbial strains. Long-term use with certain antibiotics may cause medicamentosa, epitheliopathy, and crystal deposits.
- Immunomodulatory medications (eg, cyclophosphamide, cyclosporine, methotrexate, azathioprine) are indicated if necessary. Topical cyclosporine A drops are being evaluated in clinical trials.
- Lubrication (eg, artificial tears) is recommended, but preservatives should be avoided.
- For chemical burns, corticosteroids (ie, prednisone) are useful for reducing surface inflammation; however, after 10-14 days, collagen synthesis becomes important in the repair process. Prednisone may alter the balance of collagen synthesis versus degradation. Although they have weaker anti-inflammatory properties, progestational steroids (eg, medroxyprogesterone) demonstrate less suppression of collagen synthesis (wound repair).
- Medroxyprogesterone (eg, Provera)
- Oral tetracycline or minocycline can be combined with topical tetracycline preparations or with other therapeutic modalities, such as topical antibiotics, cycloplegics, ocular hypotensives, sodium citrate, ascorbic acid, and acetylcysteine.
- Use of vitamin A is investigational. Initial trials demonstrated clinical efficacy that was not replicated subsequently.
- Although investigational, fibronectin has been shown to improve epithelialization in vitro; however, clinical trials did not demonstrate efficacy.
- Use of ascorbic acid/citrate for burns only is investigational.
- Serum derived tears are under investigation.
- Cell proliferation and trophic factors (eg, KGF, EGF, NGF) are investigational.
- Recombinant human tumor necrosis factor receptor Fc fusion protein (etanercept) can be used in progressive disease or in cases that are unresponsive to traditional therapies.
- PAF receptor antagonists are under investigation.
- Topical administration of NGF is under investigation.
- Topical application of lecithinated SOD analog (PC-SOD) has proven to be beneficial.
- Metalloproteinase inhibitors include the following:
- Synthetic thiols
- Sodium and calcium EDTA
- Punctal occlusion includes plugs/cautery.
- A primary barrier method (eg, therapeutic soft contact lenses, scleral lenses, glued on contact lens) should be created and used.
- Tissue adhesives are best for impending or actual perforations that are 1 mm or smaller in size. They may be removed or allowed to extrude spontaneously after 6-8 weeks when a fibrovascular scar has formed and eliminated the risk of stromal ulceration.
- Amniotic membrane transplantation (alone or with ex vivo expansion or limbal stem cell transplantation)
- Conjunctival flap/graft or Tenon-plasty (for reestablishment of limbal vascularization in alkali burns)
- Tarsorrhaphy (temporary vs permanent lateral)
- Corneal transplant (lamellar or penetrating) or tectonic graft (temporizing measure until graft bed is vascularized and arrests further ulceration)
- Mucous membrane grafting
See Medical Care for possible surgical treatments
See the list below:
- Corneal specialists
- Neurologist or neuro-ophthalmologist for probable CNS neurotrophic etiology
Complications include corneal scarring, neovascularization, decreased vision, central corneal perforation, and endophthalmitis. Other possible complications include cataract, glaucoma, and blindness.
Patients should wear eye protection to prevent injury to the cornea, especially if the cornea is thin.
Prognosis depends on the severity of the condition and the patient response to therapy, in addition to associated local and systemic factors.
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].
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].
Ralph RA. Tetracyclines and the treatment of corneal stromal ulceration: a review. Cornea. May 2000. 19(3):274-7. [Medline].
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].
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].
Amjadi S, Mai K, McCluskey P, Wakefield D. The role of lumican in ocular disease. ISRN Ophthalmol. Jul 2013. 2013:632302. [Medline].
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].
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].
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].
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].
Dohlman CH, Slansky HH, Laibson PR, et al. Artificial corneal epithelium in acute alkali burns. Ann Ophthalmol. 1969. 112.
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].
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].
Soni NG, Jeng BH. Blood-derived topical therapy for ocular surface diseases. Br J Ophthalmol. Jan 2016. 100(1):22-7. [Medline].
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].
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].
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].
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].
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].
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].
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].
Albert DM, Jakobiec FA, eds. Principles and Practice of Ophthalmology. 2nd ed. Boston: WB Saunders Co; 2000.
Dua HS, Gomes JA, Singh A. Corneal epithelial wound healing. Br J Ophthalmol. 1994 May. 78(5):401-8. [Medline].
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].
Gipson IK, Inatomi T. Extracellular matrix and growth factors in corneal wound healing. Curr Opin Ophthalmol. 1995 Aug. 6(4):3-10. [Medline].
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].
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].
Kaufman HE, et al, eds. The Cornea. 2nd ed. Boston: Butterworth-Heinemann; 1998.
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].
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].
Wilson SE, Liu JJ, Mohan RR. Stromal-epithelial interactions in the cornea. Prog Retin Eye Res. 1999 May. 18(3):293-309. [Medline].