The effect of nerve growth factor on corneal nerve regeneration and dry eye after LASIK

Dry eye is the most common complication after refractive surgery, especially after laser in situ keratomileusis (LASIK), in which nerves may be cut when making the corneal flap. Nerve growth factor (NGF) has been demonstrated to stimulate corneal sensitivity and nerve regeneration and NGF has been suggested as a potential treatment for dry eye disease (DED). Hence, this study aimed to investigate the effect of NGF on corneal nerve regeneration, sensitivity and dry eye symptoms after LASIK, compared to hycosan and normal saline (NS) treatments. Thirty-eight New Zealand white rabbits that underwent LASIK procedures were randomly assigned to three groups. Each group underwent NGF, hycosan, and NS treatment. The nerve densities and the number of corneal sub-basal and superficial stromal nerves were measured with confocal microscopy, and the results were compared before surgery and at one month and three months postoperatively. Corneal sensitivity was assessed with an esthesiometer. The tear breakup time (TBUT) was recorded to check for signs of dry eye. The whole corneas of the experimental animals were excised at three months after the surgery for immunohistochemically analysis. After LASIK, treatment with NGF significantly accelerated the recovery of sub-basal and superficial stromal nerve densities and the numbers, compared to hycosan and NS treatments at one month and three months postoperatively (NGF vs. hycosan, P < 0.01 each; NGF vs. NS, P < 0.01 each). The recovery of corneal sensitivity was significantly enhanced in the NGF group compared to the hycosan or NS treatment groups after surgery (P < 0.05). Also, the TBUT data showed a statistically significant longer time in the NGF group at one month, and three months postoperatively (P < 0.05). Immunofluorescence analysis showed the nerve fiber quantity of the NGF group was larger than in the hycosan and NS groups. Taken together, the experimental results suggested that mNGF had an obvious effect on promoting corneal nerve repairing and the potential to improve dry eye in different periods following LASIK.