High Molecular Weight Hyaluronan Promotes Corneal Nerve Growth in Severe Dry Eyes

Abstract

The purpose of this study was to investigate the effect of high molecular weight hyaluronan (HMWHA) eye drops on subbasal corneal nerves in patients suffering from severe dry eye disease (DED) and to evaluate the damage of subbasal corneal nerves associated with severe DED. Designed as an international, multicenter study, 16 patients with symptoms of at least an Ocular Surface Disease Index (OSDI) score of 33, and corneal fluorescein staining (CFS) of at least Oxford grade 3, were included and randomized into two study arms. The control group continued to use their individual optimum artificial tears over the study period of eight weeks; in the verum group, the artificial tears were substituted by eye drops containing 0.15% HMWHA. At the baseline visit, and after eight weeks, the subbasal nerve plexus of 16 patients were assessed by confocal laser scanning microscopy (CSLM). The images were submitted to a masked reading center for evaluation. Results showed a significant increase of total nerve fiber lengths (CNFL) in the HMWHA group (p = 0.030) when compared to the control group, where the total subbasal CNFL did not significantly change from baseline to week 8. We concluded that in severe DED patients, HMWHA from topically applied eye drops could cross the epithelial barrier and reach the subbasal nerve plexus, where it exercised a trophic effect.

Preparation and Evaluation of Bacterial Nanocellulose/Hyaluronic Acid Composite Artificial Cornea for Application of Corneal Transplantation

“…These results showed that the cells adhered and proliferated well on the surface of the sample. There was large amount of HA in the extracellular matrix of all cellular layers of the corneal epithelium, and these HA could maintain the ocular surface homeostasis . After BNC cross-linking of HA, the HA fixed on BNC could further promote the adhesion and proliferation of the corneal stromal cells.…”

Reflections on the Ocular Surface: Summary of the Presentations at the 4th Coronis Foundation Ophthalmic Symposium Debate: “A Multifactorial Approach to Ocular Surface Disorders” (August 31 2021)

“…Since the physical properties of HA (rheology, viscoelasticity and mucoadhesion) and its biological activity (via binding to hyaladherins) are highly dependent on its MW, comprehensive information on this biopolymer should be provided in studies evaluating not only the concentration but also, the average MW or the intrinsic viscosity, in order to adequately compare the results, especially in relation to the data in the literature. From the results of the HYLAN M study and of other animal studies [103,120], as well as from other studies in the literature, it can be concluded that HA eye drops with high and very high MWHA can provide a holistic approach to DED treatment, which at the same time addresses several of its complex interacting pathomechanisms [70,101,103,[121][122][123][124][125]. It has been proposed that eye drops containing specific HMWHA and vHMWHA should be referred to not only as a wetting agent or multiple-action tear substitute but also, as an ocular surface modulator that is capable of interacting with and influencing the ocular surface components [126].…”

“…Patients were randomized into a verum group treated with preservative-free 0.15% vHMWHA and a control group that continued to use their individual artificial tears. An eight-week treatment with vHMWHA provided significantly better symptomatic relief, with less discomfort and pain, and confocal laser scanning microscopy revealed a significant increase in total nerve fiber length of the subbasal nerve plexus in a subgroup of 16 patients [70].…”

“…In DED patients, a single drop 0.15% of high molecular weight sodium hyaluronan (HMWHA) solution significantly reduces the ocular surface irritation evoked by prolonged eye opening [41]. Moreover, after a one month treatment with 0.15% HMWHA, the intensity of ocular surface irritation during the interblink period falls significantly, remaining lower than in untreated patients even 12 h after the last application of HMWHA [70]. Hence, prolonged tear supplementation with 0.15% HMWHA in DED pa-tients produces a sustained decrease in ocular surface irritation, suggesting that the beneficial effect of this long-term treatment might not only be a consequence of improved TF dynamics but also, the result of a significant decrease in corneal sensory nerve excitability [52,71].…”

“…In addition to the functional effects of HA on corneal sensations, it was recently shown that topically applied HMWHA exerts positive trophic effects in individuals, corneal confocal microscopy demonstrating it promotes a regeneration of compromised nerves [70] (Fig. 11).…”