Selective Pharmacologic Therapies for Dry Eye Disease Treatment: Efficacy, Tolerability, and Safety Data Review from Preclinical Studies and Pivotal Trials

Abstract

Keratoconjunctivitis sicca, also known as dry eye disease (DED), is a prevalent, multifactorial disease associated with compromised ocular lubrication, ocular surface inflammation and damage, and ocular symptoms. Several anti-inflammatory, topical ophthalmic therapies are available to treat clinical signs and symptoms of DED in the USA and Europe. Cyclosporine A (CsA)-based formulations include an ophthalmic emulsion of 0.05% CsA (CsA 0.05%), a cationic emulsion (CE) of CsA 0.1% (CsA CE), and an aqueous nanomicellar formulation of 0.09% CsA (OTX-101). Lifitegrast is a 5% ophthalmic solution of a lymphocyte function-associated antigen 1 antagonist that is believed to target T cell activation and recruitment to inhibit ocular inflammation. Here we provide a comprehensive review summarising preclinical studies and pivotal trial data for these treatments to provide a complete understanding of their efficacy and safety profile. Overall, data in the evaluated studies show a favourable risk-benefit profile for the use of targeted topical anti-inflammatory pharmacologic treatments in patients with DED. Pivotal trials for CsA 0.05%, CsA CE, OTX-101, and lifitegrast clearly demonstrate treatment efficacy compared to vehicle across treatments with no serious ocular treatment-emergent adverse events (TEAEs). Patients using ophthalmic treatments reported ocular TEAEs more frequently than those treated with vehicle; however, relatively few TEAEs led to treatment discontinuation. The specific signs and symptoms of DED that improve with treatment vary with the treatment prescribed. Long-term and direct comparative studies between treatments are needed to further understand treatment differences in efficacy and safety profiles.

Keywords: Cyclosporine A; Dry eye; Keratoconjunctivitis sicca; Lifitegrast; OTX-101; Ocular drug therapy; Ocular inflammation; Tear deficiency.

Fig. 1

Change from baseline in conjunctival staining score with a CsA 0.05%, b CsA CE, c OTX-101 0.09%, and d lifitegrast treatments. CsA 0.05% cyclosporine ophthalmic emulsion 0.05%, CsA CE 0.1% (1 mg/mL) cyclosporine A cationic emulsion, lifitegrast lifitegrast ophthalmic solution 5.0%, OTX-101 cyclosporine ophthalmic solution 0.09%, Ph phase, SD standard deviation, SE standard error

Fig. 2

Change from baseline in corneal staining score with a CsA 0.05%, b OTX-101 0.09%, and c lifitegrast treatments. CsA 0.05% cyclosporine ophthalmic emulsion 0.05%, lifitegrast lifitegrast ophthalmic solution 5.0%, OTX-101 cyclosporine ophthalmic solution 0.09%, Ph phase, SE standard error

Fig. 3

Change from baseline in Schirmer’s test score with a CsA 0.05%, b CsA CE, and c OTX-101 0.09%. *Worse eye analysis. CsA 0.05% cyclosporine ophthalmic emulsion 0.05%, CsA CE 0.1% (1 mg/mL) cyclosporine A cationic emulsion, NR not reported, OTX-101 cyclosporine ophthalmic solution 0.09%, Ph phase, SD standard deviation, SE standard error