Cationic Emulsion-Based Artificial Tears as a Mimic of Functional Healthy Tear Film for Restoration of Ocular Surface Homeostasis in Dry Eye Disease

Abstract

Dry eye disease (DED) is a complex multifactorial disease that affects an increasing number of patients worldwide. Close to 30% of the population has experienced dry eye (DE) symptoms and presented with some signs of the disease during their lifetime. The significant heterogeneity in the medical background of patients with DEs and in their sensitivity to symptoms renders a clear understanding of DED complicated. It has become evident over the past few years that DED results from an impairment of the ocular surface homeostasis. Hence, a holistic treatment approach that concomitantly addresses the different mechanisms that result in the destabilization of the tear film (TF) and the ocular surface would be appropriate. The goal of the present review is to compile the different types of scientific evidence (from in silico modeling to clinical trials) that help explain the mechanism of action of cationic emulsion (CE)-based eye drop technology for the treatment of both the signs and the symptoms of DED. These CE-based artificial tear (AT) eye drops designed to mimic, from a functional point of view, a healthy TF contribute to the restoration of a healthy ocular surface environment and TF that leads to a better management of DE patients. The CE-based AT eye drops help restore the ocular surface homeostasis in patients who have unstable TF or no tears.

Keywords: artificial tear; cationic emulsion; dry eye; polar lipid; tear film lipid layer.

FIG. 1.

Comparison of the structure of a healthy tear film (A) and the CEs (B). CE, cationic emulsion; TFLL, tear film lipid layer.

FIG. 2.

Coarse-grain molecular dynamic simulations (side and bottom-up views of the lipid film) of the incorporation of CKC and poloxamer in lipid film with polar lipid deficiency. Non-polar lipids, pink; polar lipids, blue; CKC, red; Poloxamer, white and green (A). Brewster angle microscopy images of the excellent miscibility of mineral oil (B) with MGS, and (C) spreading of medium-chain triglyceride over MGS. (D) Specular microscopy images of TFLL before and after instillation of CE at the ocular surface; field of view is ∼3 cm² (adapted from Georgiev et al.). CKC, cetalkonium chloride; MGS, meibomian gland secretion.

FIG. 3.

Inflammatory cell counts in the cornea of rat treated with the CE ATs (adapted from Liang et al.). ATs, artificial tears.

FIG. 4.

Percentage of corneal clearing on treatment with the CE AT and HA-based eye drop in patients with mild-to-moderate DED with CFS scores up to 2 at study inclusion. CFS, corneal fluorescein staining; DED, dry eye disease; HA, hyaluronic acid.

FIG. 5.

(A, B) Corneal healing over time after the instillation of 1 drop of the CE AT in patients with severe DED (CFS ≥4 at the beginning of the study).

FIG. 6.

(A, B) Symptom improvement in a patient population with severe DED on treatment with the CE AT.

FIG. 7.

Schematic of the mechanisms of action of CEs in the management of signs and symptoms of DED.