Adhesives for Ophthalmic Use

Surgeons welcome the first wound sealant approved by the FDA for use in the eye.

BY TERRY KIM, MD

WITH DECREASING TOLERANCE FOR COMPLICATIONS of any kind and increasing expectations for high-quality refractive outcomes after our procedures, surgeons are suturing less and less. As a result, interest in using tissue adhesives to keep incisions sealed and protect the ocular surface so it can heal has been growing.

Cornea specialists have many potential uses for adhesives, including addressing corneal thinning, securing lamellar grafts and preventing recurrent epithelial ingrowth after LASIK. Cyanoacrylate and fibrin adhesives have been used off-label with some success. Cataract surgeons, too, have a substantial interest in adhesives as a way to guarantee the integrity of clear corneal incisions. Many published studies have shown the incisions are vulnerable to leakage and call into question whether they are truly self-sealing with stromal hydration alone.^1-3 Incompetent wounds allow fluid to travel in and out, which can lead to sight-threatening complications such as endophthalmitis, hypotony, corneal decompensation and epithelial downgrowth. Wound leaks can also compromise refractive outcomes as well by altering the effective positioning of the IOL.

The Optimal Ophthalmic Sealant

Tissue adhesives not designed specifically for use in the eye have been used off-label, but have several disadvantages in the ocular environment, including difficult application processes, unfavorable mechanical properties (stiffness and abrasiveness) and potential toxicity.

Adhesives ideal for ophthalmic use would have the following properties:

Secures the tissue in place

Persists long enough to allow incision to heal

Promotes the natural healing mechanism

Degrades as tissue is regenerated

Acts locally and safely

Induces minimal astigmatism

Provides microbial barrier to infection

Provides transparency

Has elastic mechanical properties

Has optimal rheological properties for delivery

Offers favorable solute diffusion properties.

Eye-specific Options

Polymer chemist Dr. Mark Grinstaff and I were fortunate to have the opportunity, via an NIH grant, to study some novel tissue adhesives that could be used specifically for ophthalmic applications. We looked at molecules called biodendrimers, which are very different from linear polymers like cyanoacrylate in terms of their shape, viscosity, solubility and reactivity. The biodendrimer adhesive was very effective as a wound sealant, which led to the development of a product called OcuSeal (Beaver-Visitec International) that is approved for use in Europe but not currently available in the United States.

We’ve finally reached an important step in the United States, however, with the ReSure Sealant (Ocular Therapeutix, Inc.), the first FDA-approved tissue sealant for ophthalmic use. ReSure Sealant is indicated for the intraoperative management of clear corneal incisions (CCIs) (up to 3.5 mm) with a demonstrated wound leak, for which a temporary dry surface can be achieved, in order to prevent postoperative fluid egress from such incisions following cataract surgery with IOL placement in adults. A synthetic hydrogel that contains a blue visualization aid to assist in application, ReSure serves as a soft and lubricious surface barrier. It gently sloughs off in the tears during corneal re-epithelialization, and hydrolysis occurs within approximately 7 days.

The pivotal trial that led to its approval by the FDA was robust, involving nearly 500 eyes undergoing clear corneal cataract surgery that were randomized to suture or sealant. Following cataract surgery with IOL implantation, 50% of the incisions leaked spontaneously.⁴ Those that did not were challenged using an Ocular Force Gauge (OFG). Patients were randomized into the study if a leak was observed with < 1.0 oz. of force. If no leak was observed, the patient was considered a screen failure. After application of ReSure or suture, the CCIs were challenged again with the OFG. If a leak was detected, the patient was a primary endpoint failure. Subjects were evaluated at 1 hour, and at 1, 3, 7, 14, 21 and 28 days after surgery. The primary endpoint was the proportion of eyes with wound leakage within the first 7 days of surgery. ReSure Sealant was superior to sutures, preventing wound leak in 95.9% of cases while sutures prevented wound leak in 65.9% of cases (Figure 1). In addition, there were significantly fewer device-related adverse events in the sealant group than in the suture group, 1.6% vs. 30.6%. No safety concerns were reported. Patients were comfortable overall, and 94.1% of the sealant cases were rated “easy” or “very easy” by the surgeons participating in the trial.⁴

FIGURE 1. In the clinical trial that led to its approval by the FDA, ReSure Sealant was superior to sutures for preventing wound leak following clear corneal cataract surgery.

Myriad of Potential Uses

The area of ophthalmic adhesives will continue to be an exciting one to watch. As the number of approved indications increases, not only cataract surgeons but also cornea, refractive, glaucoma, retina and oculoplastic surgeons will be able to benefit from the added protections these devices provide.

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