The Effect Of High And Low Molecular Weight Sodium Hyaluronic Acid Eye Drops On Corneal Nerve Regeneration And Corneal Sensitivity After Crosslinking

Corneal crosslinking (CXL) induced by riboflavin and UVA, used to halt the progression of keratoconus induces acute morphologic and functional damage to the subbasal corneal nerve plexus (SNP). Hyaluronic acid (HA) has been proven to be one of the key players in the tissue regeneration process. Studies have shown that HA properties depend on its molecular size. HA in its high molecular weight form (HMW-HA) displays anti-inflammatory and neuroregenerative properties, as compared to, low molecular weight HA (LMW-HA). The aim of this study was to evaluate the effect of HMW-HA and LMW-HA eye drops on corneal nerve regeneration, corneal sensitivity after CXL and compare with the controls.

Marmara University School of Medicine Department of Ophthalmology, İstanbul, Turkey

Sixty-three eyes of 55 keratoconus patients were randomized to instill eye drops containing HMW-HA (n: 20) (Comfort Shield) for 6 months, LMW-HA (n:23) (Thealoz Duo) for 6 months and polyvinyl alcohol (n: 20) (Refresh) until the epithelial defect closure in the control group after CXL. SNP imaging was performed with corneal confocal microscopy (CCM, HRT III/RCM) preoperative, postoperative 1st, 3rd, and 6th months. ACCMetrics program (Manchester University, UK) was used to quantify corneal nerve fiber density (CNFD), corneal nerve fiber length (CNFL), corneal nerve fiber branching density (CNBD), corneal nerve fiber total branching density (CTBD) values. Corneal sensitivity was measured using the Cochet-Bonnet esthesiometer.

SNP parameters did not differ significantly between the groups before CXL. The SNP density was significantly reduced at one month post-operatively in all study groups (p<0.05). At postoperative month six, CNFD, CNBD, CNFL, and CTBD were restored to preoperative levels in the HMW-HA group, while they remained reduced in the LMW-HA and the control group (p<0.05). CNFD, CNBD, CNFL, and CTBD were higher in the HMW-HA group compared to the other two groups at the postoperative month six (p<0.05). Corneal sensitivity was significantly lower in control and LMW-HA groups at the postoperative 3rd months (p<0.05). No significant difference was observed between the postoperative 3rd values and the preoperative values in the HMW-HA group (p>0.05).

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.