Postoperative Corneal Melt Medication
- Author: Arun Verma, MD; Chief Editor: Hampton Roy Sr, MD more...
Medication Summary
The goal of pharmacotherapy is to reduce morbidity and to prevent complications. Tissue adhesives can be used with small perforations or descemetoceles with impending perforation.
Tissue adhesives
Class Summary
These agents may be applied under topical anesthesia at the slit lamp. The glue may induce significant inflammation and may be uncomfortable for the patient. They may adhere inadequately, may serve to harbor organisms once polymerized, and often are effective only in small perforations that can be dried readily. These substances polymerize rapidly when in contact with water. The favored adhesive for ocular surgery appears to be isobutyl-2-cyanoacrylate. Patients with progressive corneal melting secondary to ulcerative disease and patients with frank corneal perforations have been successfully treated with these cyanoacrylate adhesives.
The tissue adhesives most commonly used in the United States are cyanoacrylates, usually isobutyl or higher alkyl compounds. None of these are approved for ophthalmic use by the Food and Drug Administration, but N -butyl cyanoacrylate is under evaluation at this time.
N-butyl cyanoacrylate (Nexacryl)
Sterile, nontoxic, biocompatible, hemostatic, and bacteria static. A monomer, but when it comes in contact with moisture it is converted into a polymer. Inert material that solidifies within less than 5-10 seconds. Solidifies rapidly in alkaline media but slowly in acidic media. Does not get absorbed into the blood stream. Bacteria free and unaffected by many other bacteria.
Iso amyl-2 cyanoacrylate is a thickened monomer. Allows rapid wound closure with minimal scarring, reduced risk of subsequent infection, less traumatic, more efficient, precise, and safe.
The cyanoacrylate adhesive may be useful for covering ulcers and sealing perforations, because it can be applied over an ulcer bed and covered with a therapeutic soft contact lens. If glue displaces spontaneously from cornea in a few weeks, it can be reapplied to achieve continued stromal protection.
Various techniques have been described for the use of tissue adhesives; all require debridement of necrotic tissue and epithelium surrounding perforation, drying of area to which glue is to be applied, and application of least amount of glue that can cover the defect. Drying of defect can be carried out with cellulose sponges, and air or viscoelastic may be placed behind the perforation to separate tissue and reduce fluid present. The glue itself may be applied to a small plastic disk and then placed over the perforation, applied directly from the tip of a fine needle attached to a tuberculin syringe, or applied with a specially made applicator. The glue may come off and need to be reapplied, at times repeatedly. Usually, because of the rough surface of polymerized glue, a bandage soft contact lens is placed on the eye after the glue has polymerized.
Topical collagenase inhibitors
Class Summary
Mucolytic agent acetylcysteine has been advocated by some authors because they have shown to inhibit the lytic effect of collagenase in presence of, as well as in absence of, corticosteroids. Corneal melting, when it occurs, usually does not occur until after the fifth day following corneal surgery. Thus, it is reasonable to use corticosteroids to suppress the inflammatory response and prevent scarring for at least the first 5-7 days. The exact value of anticollagenase agents such as acetylcysteine has not been proven. Cysteine also inhibits collagenase and is more readily available as acetylcysteine, 10-20% concentration (Mucomyst). Another collagenase inhibitor is penicillamine. The use of collagenase inhibitors as adjunctive therapy in the treatment of progressive corneal melting has been disappointing.
Both disodium edetic acid and acetylcysteine have been used to inhibit collagenase activity, particularly in Pseudomonas corneal infections. These agents should be started if postoperative melting is observed.
Disodium ethylenediaminetetraacetic acid (EDTA) (Endrate) and calcium disodium EDTA (Calcium Disodium Versenate) inhibit collagenase through chelation. Evidence of local effective doses is not available, but 0.2 M irritation has been documented.
Among the many synthetic inhibitors of collagenase is Galardin. This agent appears to prevent the corneal ulceration of alkali injury by diminishing the release from PMNs of matrix metalloproteinases (MMPs) that digest capillary walls to allow extravasation of the PMNs. Any decrease in the number of locally extravasated PMNs decreases the potential pool of MMPs at the site of injury. Galardin further reduces inflammation by preventing release of tumor necrosis factor-a (TNF-a), a cytokine that activates PMNs, from producer cells such as macrophages and activated T cells. Galardin also may block MMPs released from inflammatory cells, corneal fibroblasts, and epithelial cells. It has been tried in cases of postoperative corneal melts.
Other synthetic inhibitors of MMPs include mercaptan (thiol)-containing compounds resembling the drug captopril, which inhibits the metalloproteinase angiotensin-converting enzyme in the treatment of heart failure and hypertension. One of the MMP inhibitors derived in this manner, HSCH2 CH[CH2 CH(CH3)2]CO-Phe-Ala-NH2 (SIMP), is effective in inhibiting corneal ulceration.
The alpha2-macroglobulin of serum is a powerful inhibitor of collagenase and the other MMPs. Alpha1-antitrypsin is considerably less effective against collagenase, but it too has been documented to prevent corneal ulceration after ocular chemical injuries. Blood is drawn into dry, sterile containers containing no anticoagulants clots and yields serum that can be separated and refrigerated until needed. If autologous blood is available, its therapeutic use need not be delayed by testing for human immunodeficiency virus or hepatitis. Gentamicin sulfate sufficient to achieve a concentration of 0.003% can be added to the serum before its administration by drops or by continuous perfusion.
N-acetylcysteine (Mucomyst 10-20%),
Topical collagenase inhibitor that may be beneficial in some patients. Formulated from commercially available Mucomyst, diluted to a 5% or 10% solution with artificial tears, and is applied 4-6 times/d. The 10% acetylcysteine drops can be given several times daily. Mucolytic action of this agent sometimes clears the ulcer. Not harmful to the globe or adnexum and obviously should be tried in pediatric age group before subjecting a child to a general anesthetic.
Ask the pharmacist to supply the acetylcysteine in a dark dropper bottle because of its instability in light.
Adequate lubrication with preservative-free tear and ointment supplements is important. Guidelines for solution have been used safely.
Corticosteroids
Class Summary
Adequate lubrication with preservative-free tear and ointment supplements such as corticosteroids are very important. Corticosteroids modify the body's immune response to diverse stimuli.
Prednisone (Deltasone, Orasone, Sterapred)
Immunosuppressant for treatment of autoimmune disorders; may decrease inflammation by reversing increased capillary permeability and suppressing PMN activity.
Immunosuppressive agents
Class Summary
Used for unresponsive severe corneal inflammatory disease or to prevent postoperative corneal melting syndromes in susceptible cases. Immunosuppressive medication may be beneficial. A more direct strategy in immuno intervention involves inhibition of various effector cells. Targeting effector cell products such as cytokines or their receptors has been effective.
Systemic and topical administration has been investigated regarding corneal graft rejection, intermediate and posterior uveitis, and noninfectious, immune-related corneal ulcers and postoperative corneal melts.
Topical CsA is of use in corneal graft rejection and prevention of postoperative corneal melts. A marginal corneal ulceration related to autoimmune disease can be improved through the use of topical and systemic CsA.
Cyclosporine (Sandimmune, Neoral)
Specific modulator of T-cell function and an agent that depresses cell-mediated immune responses by inhibiting helper T-cell function. Has been used to treat a variety of forms of uveitis, often with good results. Binds to cyclophilin, an intracellular protein, which in turn prevents formation of interleukin 2 and the subsequent recruitment of activated T cells. Oral CsA and topical CsA (0.05%) can be used in melting stromal ulcers. It may be a good alternative mode of achieving ocular immunosuppression. Topical CsA has been shown to prevent postoperative corneal melts and to reduce the incidence of graft rejections in patients at high risk. A marginal corneal ulceration related to autoimmune disease can be improved through the use of topical and systemic CsA.
Cyclosporine has about 30% bioavailability, but there is marked interindividual variability. Cyclosporine specifically inhibits T-lymphocyte function with minimal activity against B cells. Maximum suppression of T-lymphocyte proliferation requires that the drug be present during the first 24 h of antigenic exposure.
Oral cyclosporine has been used, with apparent efficacy, to treat corneal melting syndromes such as Mooren ulcer and that associated with Wegener granulomatosis.
The use of systemic cyclosporine significantly improves the results of surgery.
Antibiotics
Class Summary
Therapy must be comprehensive and cover all likely pathogens in the context of this clinical setting.
Doxycycline (Vibramycin, Doryx, Bio-Tab, Vibra-Tabs)
Inhibits protein synthesis and thus bacterial growth by binding to 30S and possibly 50S ribosomal subunits of susceptible bacteria.
Cottinger, AJ, Berkley, RP, Nordan IT, et al. Bacterial corneal ulcers following keratorefractive surgery. In: A retrospective study of 14163 procedures. Paper presented at: Ocular Microbiology Immunology Group Meeting. San Francisco, CA; September 28, 1985.
Greiner MA, Li JY, Mannis MJ. Longer-term vision outcomes and complications with the Boston type 1 keratoprosthesis at the University of California, Davis. Ophthalmology. Aug 2011;118(8):1543-50. [Medline].
Yang HK, Kline OR Jr. Corneal melting with intraocular lenses. Arch Ophthalmol. Aug 1982;100(8):1272-4. [Medline].
Gelender H. Descemetocele after intraocular lens implantation. Arch Ophthalmol. Jan 1982;100(1):72-6. [Medline].
Insler MS, Boutros G, Boulware DW. Corneal ulceration following cataract surgery in patients with rheumatoid arthritis. J Am Intraocul Implant Soc. Nov 1985;11(6):594-7. [Medline].
Utine CA, Tzu JH, Akpek EK. Lamellar keratoplasty using gamma-irradiated corneal lenticules. Am J Ophthalmol. Jan 2011;151(1):170-174.e1. [Medline].
Barletta JP, Angella G, Balch KC, Dimova HG, Stern GA, Moser MT, et al. Inhibition of pseudomonal ulceration in rabbit corneas by a synthetic matrix metalloproteinase inhibitor. Invest Ophthalmol Vis Sci. Jan 1996;37(1):20-8. [Medline].
Barletta JP, Balch KC, Dimova, et al. Inhibition of Pseudomonas corneal ulcers by a synthetic matrix metalloprotease inhibitor Galardin (GM[6001]). Invest Ophthalmol Vis Sci. 1993;34:1058.
Benson WE, Diamond JG, Tasman W. Intraocular irrigating solutions for pars plana vitrectomy. A prospective, randomized, double-blind study. Arch Ophthalmol. Jun 1981;99(6):1013-5. [Medline].
Bernauer W, Ficker LA, Watson PG, Dart JK. The management of corneal perforations associated with rheumatoid arthritis. An analysis of 32 eyes. Ophthalmology. Sep 1995;102(9):1325-37. [Medline].
Binder PS, Baumgartner SD, Fogle JA. Histopathology of a case of epikeratophakia (aphakic epikeratoplasty). Arch Ophthalmol. Sep 1985;103(9):1357-63. [Medline].
Binder PS, Zavala EY. Why do some epikeratoplasties fail?. Arch Ophthalmol. Jan 1987;105(1):63-9. [Medline].
Cameron ME. Preventable complications of pterygium excision with beta-irradiation. Br J Ophthalmol. Jan 1972;56(1):52-6. [Medline].
Castillo A, Diaz-Valle D, Gutierrez AR, Toledano N, Romero F. Peripheral melt of flap after laser in situ keratomileusis. J Refract Surg. Jan-Feb 1998;14(1):61-3. [Medline].
Chung H, Tolentino FI, Cajita VN, Acosta J, Refojo MF. Reevaluation of corneal complications after closed vitrectomy. Arch Ophthalmol. Jul 1988;106(7):916-9. [Medline].
Clewes AR, Tunn EJ, Kaye S, Bucknall RC. Use of intravenous cyclophosphamide in the prevention of corneal melt: justified or not?. Rheumatology (Oxford). Feb 2005;44(2):257-8. [Medline].
Dougherty PJ, Hardten DR, Lindstrom RL. Corneoscleral melt after pterygium surgery using a single intraoperative application of mitomycin-C. Cornea. Sep 1996;15(5):537-40. [Medline].
Dua HS, Saini JS, Azuara-Blanco A, Gupta P. Limbal stem cell deficiency: concept, aetiology, clinical presentation, diagnosis and management. Indian J Ophthalmol. Jun 2000;48(2):83-92. [Medline].
Edelhauser HF, Hine JE, Pederson H, Van Horn DL, Schultz RO. The effect of phenylephrine on the cornea. Arch Ophthalmol. May 1979;97(5):937-47. [Medline].
Ewing-Chow DA, Romanchuk KG, Gilmour GR, Underhill JH, Climenhaga DB. Corneal melting after pterygium removal followed by topical mitomycin C therapy. Can J Ophthalmol. Jun 1992;27(4):197-9. [Medline].
Farrell PL, Smith RE. Bacterial corneoscleritis complicating pterygium excision. Am J Ophthalmol. May 15 1989;107(5):515-7. [Medline].
Foulks GN, Thoft RA, Perry HD, Tolentino FI. Factors related to corneal epithelial complications after closed vitrectomy in diabetics. Arch Ophthalmol. Jun 1979;97(6):1076-8. [Medline].
Gelender H. Corneal melting syndrome. Arch Ophthalmol. Feb 1983;101(2):303. [Medline].
Gilliland GD, Hutton WL, Fuller DG. Retained intravitreal lens fragments after cataract surgery. Ophthalmology. Aug 1992;99(8):1263-7; discussion 1268-9. [Medline].
Grayson, M. Diseases of the Cornea. 2nd ed. St Louis: CV Mosby; 1983.
Gupta S, Basti S. Corneoscleral, ciliary body, and vitreoretinal toxicity after excessive instillation of mitomycin C. Am J Ophthalmol. Oct 15 1992;114(4):503-4. [Medline].
Hoffer KJ, Darin JJ, Pettit TH, Hofbauer JD, Elander R, Levenson JE. Three years experience with radial keratotomy. The UCLA study. Ophthalmology. Jun 1983;90(6):627-36. [Medline].
Hong C, Kitazawa Y, Tanishima T. Influence of argon laser treatment of glaucoma on corneal endothelium. Jpn J Ophthalmol. 1983;27(4):567-74. [Medline].
Lam DS, Leung AT, Wu JT, Fan DS, Cheng AC, Wang Z. Culture-negative ulcerative keratitis after laser in situ keratomileusis. J Cataract Refract Surg. Jul 1999;25(7):1004-8. [Medline].
Latina MA, Melamed S, March WF, Kass MA, Kolker AE. Gonioscopic ab interno laser sclerostomy. A pilot study in glaucoma patients. Ophthalmology. Nov 1992;99(11):1736-44. [Medline].
Leahey AB, Gottsch JD, Stark WJ. Clinical experience with N-butyl cyanoacrylate (Nexacryl) tissue adhesive. Ophthalmology. Feb 1993;100(2):173-80. [Medline].
Lemp MA. Cornea and sclera. Arch Ophthalmol. Aug 1974;92(2):158-70. [Medline].
Liu SM, Su J, Hemady RK. Corneal melting after avulsion of a Molteno shunt plate. J Glaucoma. Dec 1997;6(6):357-8. [Medline].
Mamalis N, Johnson MD, Haines JM, Teske MP, Olson RJ. Corneal-scleral melt in association with cataract surgery and intraocular lenses: a report of four cases. J Cataract Refract Surg. Jan 1990;16(1):108-15. [Medline].
Mandelbaum S, Waring GO 3rd, Forster RK, Culbertson WW, Rowsey JJ, Espinal ME. Late development of ulcerative keratitis in radial keratotomy scars. Arch Ophthalmol. Aug 1986;104(8):1156-60. [Medline].
Margherio RR, Cox MS Jr, Trese MT, Murphy PL, Johnson J, Minor LA. Removal of epimacular membranes. Ophthalmology. Aug 1985;92(8):1075-83. [Medline].
Margo CE, Polack FM, Hood CI. Aspergillus panophthalmitis complicating treatment of pterygium. Cornea. 1988;7(4):285-9. [Medline].
Morgan KS, Asbell PA, McDonald MB, May JG, Loupe DN, Kaufman HE. Preliminary visual results of pediatric epikeratophakia. Arch Ophthalmol. Oct 1983;101(10):1540-4. [Medline].
Nelson JD, Williams P, Lindstrom RL, Doughman DJ. Map-fingerprint-dot changes in the corneal epithelial basement membrane following radial keratotomy. Ophthalmology. Feb 1985;92(2):199-205. [Medline].
Ohashi Y, Matsuda M, Hosotani H, Tano Y, Ishimoto I, Fukuda M, et al. Aldose reductase inhibitor (CT-112) eyedrops for diabetic corneal epitheliopathy. Am J Ophthalmol. Mar 15 1988;105(3):233-8. [Medline].
Pflugfelder SC, Saulson R, Ullman S. Peripheral corneal ulceration in a patient with AIDS-related complex. Am J Ophthalmol. Nov 15 1987;104(5):542-3. [Medline].
Portnoy SL, Insler MS, Kaufman HE. Surgical management of corneal ulceration and perforation. Surv Ophthalmol. Jul-Aug 1989;34(1):47-58. [Medline].
Pérez-Santonja JJ, Bellot J, Claramonte P, Ismail MM, Alió JL. Laser in situ keratomileusis to correct high myopia. J Cataract Refract Surg. Apr 1997;23(3):372-85. [Medline].
Quillen DA, Rosenwasser GO. Aerosol application of cyanoacrylate adhesive. J Refract Corneal Surg. Mar-Apr 1994;10(2):149-50. [Medline].
Refojo MF, Dohlman CH, Ahmad B, Carroll JM, Allen JC. Evaluation of adhesives for corneal surgery. Arch Ophthalmol. Nov 1968;80(5):645-56. [Medline].
Rosenbery S. Corneal dellen following contact-lens wear. Am J Ophthalmol. Jun 1969;67(6):970. [Medline].
Roy FH. Ocular Differential Diagnosis. 4th ed. Philadelphia: Lea and Febiger; 1984.
Rubinfeld RS, Pfister RR, Stein RM, Foster CS, Martin NF, Stoleru S, et al. Serious complications of topical mitomycin-C after pterygium surgery. Ophthalmology. Nov 1992;99(11):1647-54. [Medline].
Schwartz DE. Corneal sensitivity in diabetics. Arch Ophthalmol. Mar 1974;91(3):174-8. [Medline].
Shivitz IA, Arrowsmith PN. Delayed keratitis after radial keratotomy. Arch Ophthalmol. Aug 1986;104(8):1153-5. [Medline].
Smith RE, Schanzlin DJ. Rheumatoid diseases. In: Smolin, Thoft, eds. The Cornea: Scientific Foundations and Clinical Practice. 2nd ed. Boston: Little, Brown & Co; 1997.
Smith SG, Lindstrom RL, Nelson JD, Weiss JL, Doughman DJ. Corneal ulcer-infiltrate associated with soft contact lens use following penetrating keratoplasty. Cornea. 1984;3(2):131-4. [Medline].
Soong HK, Quigley HA. Dellen associated with filtering blebs. Arch Ophthalmol. Mar 1983;101(3):385-7. [Medline].
Stern GA, Weitzenkorn D, Valenti J. Adherence of Pseudomonas aeruginosa to the mouse cornea. Epithelial v stromal adherence. Arch Ophthalmol. Dec 1982;100(12):1956-8. [Medline].
Swinger CA, Villasenor RA. Homoplastic keratomileusis for correction of myopia. J Refr Surg. 1985;1:219-23.
Townsend WM. Corneal melt after cataract surgery. Conjunctival flaps. In: The Cornea. New York: Churchill Livingstone; 1988:669.
Vitrectomy with silicone oil or perfluoropropane gas in eyes with severe proliferative vitreoretinopathy: results of a randomized clinical trial. Silicone Study Report 2. Arch Ophthalmol. Jun 1992;110(6):780-92. [Medline].
Vitrectomy with silicone oil or sulfur hexafluoride gas in eyes with severe proliferative vitreoretinopathy: results of a randomized clinical trial. Silicone Study Report 1. Arch Ophthalmol. Jun 1992;110(6):770-9. [Medline].
Waring GO 3rd, Lynn MJ, Gelender H, Laibson PR, Lindstrom RL, Myers WD, et al. Results of the prospective evaluation of radial keratotomy (PERK) study one year after surgery. Ophthalmology. Feb 1985;92(2):177-98, 307. [Medline].
Weiss JL, Williams P, Lindstrom RL, Doughman DJ. The use of tissue adhesive in corneal perforations. Ophthalmology. Jun 1983;90(6):610-5. [Medline].
Wilhelmus KR. Corneal edema following argon laser iridotomy. Ophthalmic Surg. Aug 1992;23(8):533-7. [Medline].
Wilhelmus KR, Hamburg S. Bacterial keratitis following radial keratotomy. Cornea. 1983;2:143-6.
Zabel RW, MacDonald IM, Mintsioulis G. Corneal endothelial decompensation after argon laser iridotomy. Can J Ophthalmol. Dec 1991;26(7):367-73. [Medline].
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