• Cornea/External Disease

    A penetrating corneal injury or defect requires urgent medical attention and can often be effectively managed in the office by application of a tissue adhesive product. Cyanoacrylate adhesives and fibrin glues are 2 options for the management of acute corneal perforations up to 3 mm in diameter or of severe corneal thinning caused by microbial keratitis, traumatic or post surgical wound leaks, chemical burns, neurotrophic keratitis, and rheumatologic or other non-infectious corneal melts. This article reviews the basic preparations and uses of tissue adhesives for treating corneal injury and evaluates the 2 primary adhesives available today: cyanoacrylates and fibrin glue. It must be noted that ophthalmic use of all commercially available tissue adhesive products is considered off-label.

    Cyanoacrylate Adhesives

    Several preparations of cyanoacrylate adhesives are available for clinical use today, but cyanoacrylates with moderate length alkyl side chains are preferred for corneal application (e.g., Histoacryl, Isodent, Indermil, and Nexacryl). Application of these adhesives can be performed with the patient sitting at the slit lamp microscope or lying supine under a microscope. A topical anesthetic is given, and an eyelid speculum is placed. A cotton tip applicator or Weck-cel sponge is used to dry the cornea and to gently debride the epithelium surrounding the defect. If a large diameter or gaping perforation is being treated, or if the anterior chamber is flat, an intercameral injection of viscoelastic solution or air can be considered to maintain the anterior chamber and to avoid glue adhesion to iris or lens.

    A small amount of cyanoacrylate glue is then placed onto a sterile plastic drape or the inside of sterile, glove wrapping paper and drawn into a 30-gauge needle on a tuberculin syringe. A tiny aliquot of glue is placed directly onto the cornea; the glue will polymerize, expand, and harden within seconds of application. The wound should be tested with a fluorescein strip for a Seidel leak, and a soft bandage contact lens should be placed. Ideally, the cyanoacrylate glue and bandage contact lens should be left in position until spontaneous sloughing occurs. Duration of glue adherence ranges from a few days to an average of more than 2 months. One advantage of cyanoacrylate glue is that it exhibits immediate bacteriostatic activity against Gram-positive organisms. The patient should also be provided with topical antimicrobial therapy that is tailored to an identified infectious organism or given as prophylaxis for as long as the contact lens and glue are in place.

    Stromal neovascularization is a prominent and anticipated feature of the corneal healing response in the presence of cyanoacrylate glue. Common complications from application of cyanoacrylates to the cornea include the need for reapplication of the glue, giant papillary conjunctivitis, and secondary glaucoma. Formation of irido-corneal synechiae due to inadvertent instillation of glue into the anterior chamber, posterior synechiae, and polymerization on to the corneal endothelium can also occur. Finally, secondary microbial infiltrates can develop, especially when the contact lens and glue are in place for greater than 6 weeks, so vigilance must be maintained.

    Fibrin Glue

    While tissue adhesives were first used in ocular surgery in the 1960s, the first commercially available preparation of fibrin sealant (Tisseel VH) was approved by the Food and Drug Administration (FDA) in 1998 for hemostasis. Subsequently, the use of Tisseel for treating corneal perforations was reported by Duchesne in 2001 (Cornea. 2001;20:230-232). Fibrin sealants are biologic, human, plasma-based glues which mix thrombin and fibrinogen to form activated fibrin glue. Although fibrin glues can be “homemade” by individual hospital laboratories, Tisseel VH remains the commercial product most often used for ophthalmic purposes.

    The Tisseel fibrin glue product comes in 4 labeled and color coded vials: (1) sealer protein concentrate (human), (2) fibrinolysis inhibitor solution (bovine), (3) thrombin (human), and (4) calcium chloride solution. The first two components are heated and combined to form the sealer protein solution, and the third and fourth components are heated and mixed to form the thrombin solution. Preparation time is approximately 20 minutes, and the solutions are stable for up to 4 hours after reconstitution. A specialized injector (Duploject system) provided by the manufacturer is suboptimal for the minute volumes of glue used for ophthalmic cases. The sealer protein and thrombin solutions should instead be drawn and maintained in separate, 3-cc syringes.

    Application of the glue should be performed with the patient supine using a microscope. Preparation of the eye is identical to the steps described for cyanoacrylate glue application above. The sealer protein and thrombin solutions are individually applied to the corneal defect through 27-gauge needles. The glue will set in about 30 seconds but should be allowed to stabilize for several minutes before performing Seidel testing and placement of a bandage contact lens. Amniotic membrane can also be secured in place by fibrin glue to support closure of the corneal wound.

    Cyanocrylate Adhesives versus Fibrin Glues: Indications and Advantages

    Cyanoacrylate induced corneal neovascularization was thought to potentiate healing of corneal perforations compared with fibrin sealants, which are less likely to promote a neovascular response. In contrast, Sharma et al, who performed a prospective, clinical trial in 41 eyes with corneal perforations up to 3 mm in diameter randomized to receive fibrin glue applications or N-butyl-2-cyanoacrylate, found that overall rates of healing were similar between the groups, but eyes receiving fibrin glue healed faster compared with eyes receiving cyanoacrylate glue (Ophthalmology. 2003;110:291-298). The need for glue reapplication was the same between both groups, even though the duration of cyanoacrylate adherence to the cornea was significantly longer (2-90 days) than fibrin glue adherence (2-14 days). The cyanoacrylate group also showed higher rates of deep stromal neovascularization and giant papillary conjunctivitis. An additional comprehensive review of cyanoacrylate and fibrin adhesives is present in papers by Chan and Bhatia.3,4

    In the outpatient clinic, however, cyanoacrylate glues are typically more accessible than fibrin glues, as they take less time to prepare, require less equipment, and cost less. The intrinsic, antibacterial effect of cyanoacrylates may also be beneficial in some cases, and cyanoacrylates carry no risk for transmission of blood-borne infectious diseases like fibrin glue. On the other hand, the significantly decreased toxicity and inflammatory potential of fibrin glue appears to be ideal for other anterior segment applications such as pterygium surgery with conjunctival autografts, amniotic membrane grafting, lamellar keratoplasty, and the securing of laser in situ keratomileusis (LASIK) surgery flaps to prevent epithelial ingrowth. Research in the field of ophthalmic tissue adhesives is ongoing, and the goal is to develop other, more effective sealants with greater tissue compatibility, clarity, and durability.

    References

    1. Duchesne B, Tahi, H Galand A. Use of human fibrin glue and amniotic membrane transplant in corneal perforation. Cornea. 2001;20:230-232.
    2. Sharma A, Kaur R, Kumar R, Kumar S, Gupta P, Pandav S, Patnaik B, Gupta A. Fibrin glue versus N-butyl-2-cyanoacrylate in corneal perforations. Ophthalmology. 2003;110:291-298
    3. Chan SM, Boisjoly H. Advances in the use of adhesives in ophthalmology. Curr Opin Ophthalmol. 2004;15:305-310.
    4. Bahtia S. Ocular surface sealants and adhesives. Ocul Surf. 2006;4:146-154.

    Author Disclosure

    The author states that she has no significant financial relationship with the manufacturer or provider of any product or service discussed in this article or with the manufacturer or provider of any competing product or service.