Effect of high and low molecular weight sodium hyaluronic acid eye drops on corneal recovery after crosslinking in keratoconus patients

Abstract

Objective: To assess the impact of eye drops containing high molecular weight hyaluronic acid (HMW-HA) and low molecular weight hyaluronic acid (LMW-HA) on corneal nerve regeneration, dendritic cell (DC) density, corneal sensitivity (CS) and ocular surface parameters in patients with keratoconus following corneal crosslinking (CXL).

Methods and analysis: 63 eyes of 55 patients with keratoconus were randomised to receive eye drops containing HMW-HA (n: 20) for 12 months, LMW-HA (n: 23) for 12 months and polyvinyl alcohol (n: 20) until closure of the epithelial defect in the control group after CXL. Subbasal nerve plexus (SNP) was imaged with corneal confocal microscopy and quantified with ACCMetrics. DC density was calculated with Image J. Ocular Surface Disease Index (OSDI) questionnaire and non-invasive break-up time (NI-TBUT) were evaluated. All measurements were performed before CXL and 1, 3, 6 and 12 months postsurgery.

Results: At 6 months post-CXL, SNP reached to its preoperative. CS was higher in the HMW-HA groups compared with the other two groups in the 3rd and 6th month post-CXL. DC density was higher in the LMW-HA group compared with the HMW-HA group in the postoperative 3rd month. OSDI were higher in the control group compared with both the LMW-HA and HMW-HA groups at postoperative 3rd and 6th months. NI-TBUT was lower in the control group in the 6th and 12th months compared with the other groups.

Conclusions: The use of artificial tear drops containing HMW-HA may have a therapeutic effect to promote corneal nerve regrowth and support faster functional recovery after CXL.

Trial registration number: NCT06243991.

Keywords: Cornea; Ocular surface; Wound healing.

Figure 1. Comparison of subbasal nerve fibre parameters at follow-ups between groups. Mean values and SD are shown. *Kruskal-Wallis test, p values in bold are statistically significant. HMW-HA, high molecular weight hyaluronic acid; LMW-HA, low molecular weight hyaluronic acid.

Figure 2. Representative in vivo confocal microscopy images of subbasal nerve plexus before and after CXL. (A–E) Control group. (F–J) LMW-HA group. (K–O) HMW-HA group. Preoperative image of subbasal nerves before CXL (A, F, K). Postoperative images; 1 month (B, G, L), 3 months (C, H, M), 6 months (D, I, N) and 12 months (E, J, O) after CXL. CXL, corneal crosslinking; HMW-HA, high molecular weight hyaluronic acid; LMW-HA, low molecular weight hyaluronic acid.

Figure 3. Comparisons of dendritic cell density in groups at follow-ups. Median values and 95% CIs are shown. *Kruskal Wallis test, p values in bold are statistically significant. HMW-HA, high molecular weight hyaluronic acid; LMW-HA, low molecular weight hyaluronic acid.