Ocular options in a sutureless future

Surgeons move toward bioadhesives, but these may require finessing.

By Parag A. Majmudar, MD

To achieve wound closure and tissue adhesion, surgeons have increasingly trended away from sutures and toward bioadhesives. For example, Dermabond (Ethicon) has all but replaced sutures for skin lacerations in the emergency room. In ophthalmology, sutures are still the gold standard for penetrating keratoplasty/corneal transplantation, but bioadhesives are taking on an increasing role for other applications.

While a number of adhesives are available to ophthalmologists, most are not specifically formulated for ophthalmic use. Although surgeons may use them in an off-label fashion, the adhesives may have certain characteristics, such as abrasiveness or toxicity, which make them unfavorable for ocular applications. The ideal ophthalmic adhesive would:

• Efficiently secure tissues

• Provide antimicrobial activity

• Have an extended duration of effect until natural healing processes can take over

• Degrade naturally over time

• Exert no toxicity

• Be well tolerated on the surface of the eye with respect to its mechanical properties.

Bioadhesives come in two forms: glues and sealants. Glue holds tissues together, whereas a sealant fills in gaps. Both options are gaining momentum with ophthalmic surgeons.

Cyanoacrylate

While not FDA approved for ocular use, cyanoacrylate has been used by corneal specialists as an adhesive for corneal perforations, actual or impending. Cyanoacrylate is a temporizing measure until a more definitive intervention can take place.

The key to using cyanoacrylate, just as with other glues and sealants, is to ensure a dry environment prior to application. Normally in liquid form, cyanoacrylate polymerizes (solidifies) on contact with tissue. If it encounters any liquid, premature polymerization may occur and prevent a good seal.

Most patients require a soft contact lens (therapeutic bandage) to limit foreign-body sensation, but a large mound of glue will cause the lens to move excessively. So, I recommend using a micropipette to deliver the cyanoacrylate to prevent excessive glue deposition on the corneal surface.

Fibrin-based glues

Cyanoacrylate is a synthetic molecule whereas fibrin is a naturally occurring compound. It is a major component in several biological glues available to surgeons. Even though these glues are not specifically approved for ophthalmic surgery, surgeons may use these products, such as Evicel (Ethicon), Tisseel (Baxter) and Artiss (Baxter), for applications such as securing amniotic membrane or conjunctival grafts to the ocular surface.

These bioadhesives could completely replace sutures in cases of severe corneal thinning or impending corneal perforation in which placing sutures might be impractical. As is often the case, fibrin-based glues can supplement sutures when securing conjunctival grafts in pterygium surgery. They could also allow the surgeon to reduce the number of sutures used or even permit the use of dissolvable sutures.

Fibrin-based glues are available as a two-component system: fibrin and thrombin. Earlier versions required some mixing of the subcomponents as well as warming for 10 to 15 minutes preoperatively, but the latest iterations are available “out of the box.” Typically, the product comes in separate fibrin and thrombin syringes, but a dual injector allows an equal amount of the fibrin and thrombin to be expressed from the dual injector simultaneously.

One drawback to this approach is that the two components congeal when united within the lumen of the syringe, making it difficult to re-apply the glue. To avoid this problem, many surgeons keep the two components separate. They apply a small amount of each to opposite sides of the tissues being joined, thus preventing early polymerization. This early application allows the surgeon to re-apply to the same area — or to other areas — during a subsequent portion of the operation.

Surgeons can use fibrin-based glues to seal LASIK flap edges in cases of recurrent epithelial ingrowth and in cases of flap trauma, where epithelial cell ingrowth into the interface can be visually significant. The application is similar to that used for pterygium surgery, except that the surgeon will apply a therapeutic bandage lens, which will remain for several days after the glue polymerizes. The glue acts as a barrier so that the epithelial cells will repopulate and migrate onto the surface of the cornea, without findimg their way into the interface through a fistula.

Amar Agarwal MS, FRCS, FRCOphth described a novel use for bioadhesives.¹ In a procedure now commonly referred to as a “glued IOL,” the surgeon secures an IOL to the sclera without using sutures; after externalizing both haptics through opposite scleral flaps, the surgeon tucks the tip of the haptic into a channel in the scleral flap bed. Then, the surgeon uses bioadhesives to seal the scleral flaps, obviating the need for sutures.

Fibrin-based bioadhesives do not polymerize as quickly as cyanoacrylate adhesives; typically the glue sets within 30 to 60 seconds once the fibrin and thrombin components mix, so the surgeon has time to place the adhesive and then arrange the tissues in the optimal orientation prior to the glue solidifying. In addition, the fibrin-based adhesives have a much smoother surface profile so that bare glue on the ocular surface does not excessively irritate the patient. In fact, in cases of conjunctival graft after pterygium surgery, the surgeon often places fibrin glue over the area of bare sclera/Tenon’s at the site of graft harvesting to allow for earlier re-epithelialization.

Fibrin-based glues, along with cyanoacrylate adhesives, remain on the ocular surface for up to several weeks and therefore are appropriate for more long-term bonding of tissues.

Resure

Resure (Ocular Therapeutix) sealant is the latest option in the armamentarium of ophthalmic surgeons. It differs from cyanoacrylate and fibrin-based adhesives in composition as well as its mechanism and duration of action. A derivative of Duraseal (Covidien), Resure, used for neurosurgery applications such as sealing cerebrospinal fluid leaks, is a hydrogel that is packaged as two separate components, polyethylene glycol and trilysine amine, which are mixed at the time of application.

The adhesive sets fairly quickly once mixed, so I recommend a “5-7-11” technique. The surgeon counts off the seconds while beginning to mix the two components in the provided kit; at five seconds, stop mixing and start applying by seven seconds in a paintbrush stroke until covering the wound area. By 11 seconds, this process should be completed and the applicator removed from the surface of the eye. The sealant’s blue color enhances visibility during the application process and fades over the first 24 to 48 hours.

Resure is indicated to close clear corneal incisions after cataract surgery and acts by filling in the gaps on the ocular surface rather than by binding two tissues together. Surgeons usually place the sealant only for the first several days — it is not meant for applications that require a longer contact time. Resure, like all other adhesives discussed, requires a fairly dry surface; therefore if there is an active wound leak, its activity may be reduced.

Adequate sealing of cataract wounds is, of course, of paramount importance in reducing the incidence of endophthalmitis. When applied correctly, Resure’, which has a rubbery consistency, does not irritate the patient and works very effectively in sealing a cataract wound. In fact, in the pivotal clinical trial, only 4.1% of cataract incisions sealed with Resure demonstrated leakage, vs. 34.1% of sutured incisions, after application of a calibrated force to the incision.² In addition, while sutures can certainly close the incision, Resure has the added benefit of “waterproofing” it, thereby preventing egress of aqueous or ingress of surface bacteria.

While sutures have the advantage of cost, Resure does not have to be removed as would a suture. In addition, some evidence shows that Resure results in less astigmatic change than sutures after cataract surgery and therefore may be a superior option for cases of toric or multifocal IOL implantation, in which unexpected astigmatism may reduce overall postoperative patient satisfaction.³

In the pipeline

Another class of molecules being developed for the ophthalmic adhesive space, biodendrimers, are compounds that have very favorable viscosity and solubility characteristics, which may allow for efficient sealing of ocular tissues. One such biodendrimer, OcuSeal (Beaver-Visitec International) has CE approval in Europe but is not yet FDA approved.

Future applications of sealant technology may include cases of corneal lacerations/trauma whereby the irregular nature of the laceration prevents sutures from postsurgical leakage repair. Glaucoma surgeons may be able to use adhesives in cases of filtration bleb leakage as well, although achieving a dry surface prior to application may at times be challenging.

In addition, research is in progress regarding the use of these adhesives as drug delivery systems. Antibiotics incorporated into sealants would have the added benefit of antimicrobial activity in addition to providing a barrier effect. Other pharmaceutical agents could also be incorporated for delivery to the ocular surface. A major issue would be ensuring that the sealant remain on the surface for a specified amount of time. In the future this characteristic may be engineered and customized based on the application intended. OM

REFERENCES

About the Author

Parag A. Majmudar, MD, is the president and chief medical officer of Chicago Cornea Consultants, Ltd., where he practices cataract, corneal and refractive surgery. He is an associate professor of ophthalmology at Rush University Medical Center and serves on the International Council of the International Society of Refractive Surgery, from which he recently received an ISRS Achievement Award. Dr. Majmudar has no financial interest in any product discussed.