New thin-film adhesive for sealing full-thickness corneal incisions in rabbits

Abstract

Purpose: To compare the repair of penetrating corneal incisions in an in vivo rabbit model using a laser-activated thin-film adhesive, sutures, or self-seal.

Setting: The University of Sydney, Camperdown, Australia.

Design: Animal studies.

Methods: Under an operating microscope, 2.0 mm penetrating incisions were created in 162 right eyes. Incisions in one group were repaired with the adhesive, the second group received a single 10-0 nylon suture, and the third group was left to self-seal. Rabbits were killed humanely at predetermined timepoints over 2 weeks, and wound healing was assessed using burst pressure and immunohistological studies. A modified McDonald-Shadduck scoring was used to assess eyes.

Results: The mean burst pressure of the adhesive group was significantly higher than the sutured or self-sealed groups at all timepoints within the first 72 hours. At 0 hour, the burst pressure was 98.0 (±17.0) mm Hg, 30.6 (±2.1) mm Hg, and 3.8 (±0.6) mm Hg (P < .00001) for adhesive-treated (n = 5), sutured (n = 5), and self-sealed wounds (n = 5), respectively. These increased to 229.0 (±53.7) mm Hg, 12.4 (±2.9) mm Hg, and 27.3 (±4.0) mm Hg (P = .0011) at 72 hours. The modified McDonald-Shadduck score was significantly higher for eyes repaired using the adhesive than those sutured or left to self-seal for the first 72 hours. On histology and immunofluorescence, adhesive treatment demonstrated better wound approximation and higher myofibroblastic activation than the other groups.

Conclusions: The adhesive was efficacious in sealing penetrating corneal incisions and tolerated higher burst pressures than sutures or self-seal. The adhesive was biocompatible in rabbits, and incisions demonstrated a rapid gain in wound strength that sustained over the study period.

Figure 1.

The mean burst pressure tolerated by 2 mm penetrating corneal incisions closed using adhesive (green), suture (blue), or left to self-seal (red) over 336 hours (14 days) (A) and during the first 72 hours (3 days) (B).

Figure 2.

The trend of mean mMS score of eyes with 2 mm penetrating corneal incisions closed using adhesive (green), suture (blue), or self-seal (red) over 336 hours (14 days). mMS = modified McDonald-Shadduck

Figure 3.

Representative periodic acid-Schiff light microscopy of penetrating corneal incisions in rabbits treated with self-sealing (A, D), adhesive (B, E), or suture (C, F) at 24 hours (day 1, A-C) and 72 hours (day 3, D-F). Arrows in B demonstrate denuded corneal stroma after epithelial debridement. Arrows in E demonstrate regenerated corneal epithelia after mechanical debridement. In F, a maturing but thickened epithelial sheet anteriorly, and good approximation of stromal lamellae, posterior wound gape persists with fibrin plug. The presence of cystic spaces around suture material is marked (*).

Figure 4.

Representative periodic acid-Schiff light microscopy of penetrating corneal incisions in rabbits treated with self-sealing (G, J), adhesive (H, K), and suture (I, L) at 168 hours (day 7, G-I) and 336 hours (day 14, J-L). Arrows in H highlight the exaggerated epithelial plug that suggests wound dehiscence. In L, the incision axis is marked by a dashed line and suture material marked (*). There were irregularly thickened epithelial sheets, keratocyte accumulation along the incision track, and a strong inflammatory response within stroma, with stromal swelling and breakdown.

Figure 5.

Representative composite images of immunofluorescence microscopy with alpha smooth muscle actin (labeled red) and Hoechst nuclear dye (stained blue) of penetrating corneal incisions in rabbits treated with self-sealing (A, D), adhesive (B, E), and suture (C, F) at 24 hours (day 1, A-C) and 72 hours (day 3, D-F). Incision tracks were labeled using a fine dashed white line.

Figure 6.

Representative composite images of immunofluorescence microscopy with alpha smooth muscle actin (labeled red) and Hoechst nuclear dye (stained blue) of penetrating corneal incisions in rabbits treated with self-sealing (G, J), adhesive (H, K), and suture (I, L) at 168 hours (day 7, G-I) and 336 hours (day 14, J-L). Incision tracks were labeled using a fine dashed white line.