Alteration of the pattern of regenerative corneal subbasal nerves after laser in‐situ keratomileusis surgery

Abstract

Purpose Corneal nerves exhibit high plasticity, which allows successful reinnervation after nerve damage caused by laser in‐situ keratomileusis (LASIK) surgery. This study aimed to examine corneal subbasal nerve orientation during regeneration after LASIK. Methods This study involved 20 healthy, myopic subjects who had undergone bilateral Femto‐LASIK 12–16 months prior with a superior hinge position. The corneal subbasal nerve plexus at the central, mid‐temporal and mid‐superior cornea on the right eye were imaged using in vivo confocal microscopy. Global nerve fibre orientation (indicating the overall pattern) and variation of nerve fibre orientation (indicating the consistency of the orientation) was determined using customised MATLAB™ software (http://www.mathworks.com/products/matlab.html). Differences in nerve orientation variables between groups were examined using the Mann‐Whitney U test. Linear mixed models with Bonferroni adjustment were conducted to examine differences between corneal regions, and over time, after LASIK. Results There were no differences between post‐LASIK and control groups in global nerve orientation at any of the examined corneal regions. The post‐LASIK subjects had a greater variation of nerve orientation at the central (p = 0.007) and temporal (p = 0.049) cornea than the controls. There was a difference in global nerve fibre orientation between corneal regions (p < 0.001) in the controls but not in the post‐LASIK group. The variation of nerve fibre orientation was higher at the central, compared to the temporal and superior cornea after LASIK (p < 0.001), although there were no differences between corneal regions in controls. Conclusions Our results demonstrate that there was an increased variability in the corneal subbasal innervation patterns following LASIK when compared to controls.

Neurogenic dry eye associated with intravitreal injection of anti-VEGF agents

“…17 During femtosecond laser-assisted laser in situ keratomileusis (FS-LASIK), all the nerves along the entire circumference (except the hinge) of the flap are transected, leading to decreased corneal surface perception, reduced blink frequency, and reduced tear secretion. 18 Corneal nerve fibres were damaged after LASIK surgery, which inevitably decreased corneal sensitivity. 19 Considering corneal sensitivity, proper corneal nerve fibres are essential for normal sensitivity.…”

“…24 NGF has been reported to promote the repair of corneal nerve injury after LASIK, increase corneal stroma nerve branches and promote axonal lengthening. 18 Gong et al 25 found that the corneal sensitivity of rabbit eyes treated with NGF after LASIK was significantly improved and that the stability of the tear film was improved. VEGF is a nutritional factor of the corneal nerve and plays a role in mediating corneal nerve repair.…”

Neurophysiology of corneal neuropathic pain and emerging pharmacotherapeutics

“…Aberrant regeneration of corneal nerves could alter corneal neurophysiological responses and may be implicated in neuropathic pain. Aberrant regeneration has been studied in the cornea of people who have undergone refractive surgery such as LASIK (Chao et al., 2020). For instance, the corneal nerves in the sub‐basal layer did not wholly recover their preoperative pattern after LASIK, even 10 years later (Garcia‐Gonzalez et al., 2019).…”

“…Aberrant regeneration has been studied in the cornea of people who have undergone refractive surgery such as LASIK (Chao et al, 2020).…”

“…For instance, the corneal nerves in the sub‐basal layer did not wholly recover their preoperative pattern after LASIK, even 10 years later (Garcia‐Gonzalez et al., 2019). Also, studies have demonstrated increased alteration in the corneal nerve patterns following LASIK compared to controls (Chao et al., 2020). Apart from this corneal nerve morphological alterations, other investigations suggest a higher tear film substance P concentration accompanied by a corresponding change in corneal dendritic cell density after 12 months post‐LASIK (Chao et al., 2022).…”