Effect of topical antiinflammatory drugs on mechanical behavior of rabbit cornea

Abstract

Background: A variety of antiinflammatory therapies are employed to promote corneal wound healing. The effects of steroidal and nonsteroidal antiinflammatory drugs on the biomechanical properties of rabbit cornea were investigated over time using tensile tests.

Methods: Full-thickness incisions were made and used to analyze the effects of dexamethasone sodium phosphate 0.1% and diclofenac sodium 0.1% on corneal biomechanical properties during wound healing at 7, 14 and 21 days after surgery.

Results: The full-thickness incision deeply modified all of the mechanical properties. At 3 weeks after incision, regardless of the drug therapy, the tensile modulus was about 70% of the value for the intact cornea.

Conclusions: Topical treatment with dexamethasone was particularly effective during the first week after surgery; the second week after surgery, a similar result was observed in the corneas treated with diclofenac. Low doses of steroidal and nonsteroidal antiinflammatory drugs would seem to have the potential to improve biomechanical properties only during the early stage of the healing process of the cornea.

Fig. 1

(A) Histology of the rabbit cornea showing the tissues involved in the tensile test. (B) Scheme of the full-thickness central incision executed over a length of 7 mm and suturing positions according to the procedure described by Leibowitz et al (30). (C) Punching of cornea samples using rapid prototyped molds reproducing the curvature of the cornea to obtain “dog-bone” shaped microtensile test specimens according to ASTM D1708.

Fig. 2

Stress-strain curve for intact cornea loaded at a strain rate of 5 mm/min. The J-shaped or toe region, extending up to a strain of 0.30 mm/mm, suggests a relatively high flexibility at low strain levels. An almost linear region can be detected up to the break point. The error bars represent the standard deviation.

Fig. 3

Tensile modulus vs. strain for intact cornea loaded at a strain rate of 5 mm/min. The tensile modulus is derived from the slope of the stress-strain curve. In the initial toe region of the stress-strain curve, the tensile modulus is low, while it gradually increases with strain, reaching a maximum value at a strain level of 0.30 mm/mm (30%). The error bar represents the standard deviation.

Fig. 4

Tensile modulus of control, group A and group B. Column heights and error bars represent the mean values and standard deviations, respectively. Columns displaying different superscript letters are significantly different (p<0.05). Irrespective of the group sample, the tensile modulus significantly increases with time. After 1 week of treatment, the tensile modulus of corneas treated with steroidal drugs (group B) is significantly higher (p<0.05) than that of the control and group A. After 2 weeks, the difference is statistically significant only for the diclofenac-treated group (group A). No difference was observed among the samples after 3 weeks. Irrespective of the treated group sample, after 3 weeks of treatment, the tensile moduli are significantly lower than that of the intact cornea (reference group).

Fig. 5

Ultimate stress of control, group A and group B. Column height represents the mean value. Columns displaying different superscript letters are significantly different (p<0.05) – i.e., the difference between the mean values of 2 samples is not statistically significant if 1 or 2 letters are the same. After 1 week of treatment, the mean value of the ultimate stress of group A and group B is significantly higher (p<0.05) than that of control group. After 2 weeks of treatment, no significant difference can be observed between the group treated with dexamethasone (group B) and the control group. Instead, a statistically significant difference is found between group A (treated with diclofenac 0.1%) and control group. After 3 weeks of treatment, the strength of both group A and group B samples is significantly lower than that of the control group. Irrespective of the treated group sample, after 3 weeks of treatment, the strength values are significantly lower than that of the intact cornea (reference group).

Fig. 6

Ultimate strain of control, group A and group B. Column heights represent mean values, and error bars represent standard deviations. Columns displaying different superscript letters are significantly different (p<0.05) – i.e., the difference between the mean values of 2 samples is not statistically significant if 1 or 2 letters are the same. After 1 week of treatment, the ultimate strain of both groups A and B is significantly different than that of the control group (p<0.05). After 2 weeks of treatment, no difference is observed between diclofenac-treated (group A) and dexamethasone-treated (group B) groups, and a significant difference (p<0.05) is detected only between group B and control group. After 3 weeks of treatment, no difference is observed in the ultimate strain values among all groups. Irrespective of the treated group sample, the ultimate strain values are significantly lower than that of the intact cornea (reference group).