Corneal Sub-Basal Nerve Plexus Regeneration Pattern following Implantable Collamer Lens Implantation for Myopia: A Prospective Longitudinal In Vivo Confocal Microscopy Study

Abstract

Implantable Collamer Lens (ICL) surgery has increasingly been adopted for myopia correction in recent decades. This study, employing in vivo confocal microscopy (IVCM), aimed to assess the impact of corneal incision during ICL surgery on the corneal sub-basal nerve plexus (SNP) and adjacent immune dendritiform cells (DCs). In this longitudinal study, eyes from 53 patients undergoing ICL surgery were assessed preoperatively and postoperatively over a twelve-month period. Quantification of seven SNP parameters was performed using ACCMetrics V.2 software. Ultimately, the final analysis was restricted to one eye from each of the 37 patients who completed a minimum of three months' postoperative follow-up. Preoperative investigations revealed a positive correlation of DC density with patient age and a negative association with corneal nerve fiber density (CNFD). Additionally, both DCs and CNFD were positively linked to spherical equivalent refraction (SER) and inversely related to axial length (AL). Intriguingly, preoperative DC density demonstrated an indirect relationship with both baseline and postoperative CNFD changes. Post-surgery, an initial surge in DC density was observed, which normalized subsequently. Meanwhile, parameters like CNFD, corneal nerve fiber length (CNFL), and corneal nerve fractal dimension (CNFrD) initially showed a decline following surgery. However, at one-year follow-up, CNFL and CNFrD displayed significant recovery, while CNFD did not return to its baseline level. This study thus delineates the regeneration pattern of SNP and alterations in DC density post-ICL surgery, highlighting that CNFD in the central cornea does not completely revert to preoperative levels within a year. Given these findings, practitioners are advised to exercise caution in older patients, those with high myopia, or elevated preoperative DCs who may undergo delayed SNP regeneration.

Keywords: Visian ICL V4c; corneal confocal microscopy; corneal sub-basal nerve plexus; implantable collamer lens; refractive surgery.

Figure 1

In vivo confocal microscopy images of dendritiform cells (DCs) before and one day after ICL surgery. In vivo confocal microscopy images of dendritiform cells (DCs) from the cornea of a 29-year-old female patient with high myopia, characterized by an axial length of 26.14 mm and a spherical equivalent refractive error (SER) of −7.875 diopters. (A) Pre-surgery: Image showing a median DC density of 25.25 ± 10.6 cells/mm², with individual cells indicated by arrows. (B) Post-surgery (first day): Increased DC density observed, with a count of 87.5 ± 21.6 cells/mm². Arrows mark the labeled DCs. Each panel represents a 400 µm × 400 µm area of the corneal layer, illustrating the changes in DC density as a response to surgical intervention.

Figure 2

Changes in dendritic cell density and corneal nerve fibers pre- and post-ICL surgery as detected by IVCM. (A) Dendritic cell (DC) density: the DC density increased on the first day post-surgery compared to baseline, with the difference becoming significant only between the first postoperative day and the third postoperative month. (B) Corneal nerve fiber density: there was a significant decrease in density following surgery, which remained below baseline levels even at 12 months post-surgery. (C) Corneal nerve branch density (CNBD) and (E) corneal total branch density (CTBD): both metrics experienced a minor decline post-surgery but returned to baseline by 12 months post-surgery. (D) Corneal nerve fiber length (CNFL): a marked decrease was observed after surgery, but values returned to baseline by the 12th postoperative month. (F) Corneal nerve fiber area (CNFA): one week post-surgery, the CNFA values were significantly lower than baseline. (G) Corneal nerve fiber width (CNFW): a significant reduction was evident by the first month post-surgery. (H) Corneal nerve fractal dimension (CNFrD): this metric showed a notable decrease post-surgery and failed to revert to baseline levels by 12 months post-surgery. All pre- and post-surgery evaluations employed repeated-measures ANOVA, further supplemented by post hoc analyses using Tukey’s HSD test. The data depicted in the graphs are expressed as the mean ± standard error of the mean (SEM). An asterisk (*) in the figure indicates a p-value of less than 0.05, signifying a statistically significant difference between the compared groups.

Figure 3

Changes in corneal nerve fiber density (CNFD) and corneal nerve fiber length (CNFL) in a 29-year-old female who underwent ICL (Implantable Collamer Lens) surgery. (A) Baseline (pre-surgery): prior to undergoing surgery, the CNFD and CNFL values were recorded at 37.498 ± 15.21 (total nerves/mm²) and 19.368 ± 11.20 (mm/mm²), respectively. (B) Postoperative month 12: by the end of the 12th month post-surgery, the CNFD and CNFL values were recorded at 24.998 ±12.11 (total nerves/mm²) and 14.336 ± 8.10 (mm/mm²), respectively.