Postoperative Corneal Melt Medication

Updated: Aug 29, 2019
  • Author: Arun Verma, MD; Chief Editor: Hampton Roy, Sr, MD  more...
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Medication

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.

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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.

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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.

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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.

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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.

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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.

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