Osmoprotectants, carboxymethylcellulose and hyaluronic acid multi-ingredient eye drop: a randomised controlled trial in moderate to severe dry eye

Abstract

PurposeTo assess the safety and efficacy of an eye drop combining osmoprotectants, carboxymethylcellulose and hyaluronic acid (O/CMC/HA) in reducing symptomatic, moderate to severe dry eye, compared with HA.MethodsIn this investigator-masked, randomised study, patients instilled 1–2 drops/eye of O/CMC/HA or HA (2–6 times/day) for 3 months. Primary endpoint: mean change in Global Ocular Staining Score (GOSS) from baseline at day 35. Noninferiority of O/CMC/HA was tested in the per-protocol population; if achieved, superiority was tested in the intent-to-treat population. Secondary efficacy endpoints: mean change from baseline in GOSS, Ocular Surface Disease Index (OSDI), Schirmer score, tear break-up time (TBUT), corneal/conjunctival staining, conjunctival hyperaemia, symptoms, and patient/investigator assessments.ResultsBaseline characteristics were comparable between groups (n=40 each). O/CMC/HA was noninferior (and not superior) to HA based on similar GOSS reductions from baseline at day 35 and month 3 in both groups (P=0.778, day 35, per-protocol population). Overall, O/CMC/HA and HA provided similar reductions in OSDI, Schirmer score, TBUT, corneal staining and hyperaemia from baseline at 35 days (P≥0.155). More patients reported less severe stinging/burning, sandiness/grittiness, and painful/sore eyes at month 3 with O/CMC/HA (P≤0.039), and more rated the dropper bottle easy to use (87.5%), compared with HA (46.2% P=0.002). Other patient and investigator assessments were similar between groups. O/CMC/HA and HA were well tolerated.ConclusionsO/CMC/HA is noninferior to HA in improving objective signs of dry eye, with potential advantages for subjective symptoms and patient acceptance.

Investigating the potential benefits of a new artificial tear formulation combining two polymers

“…The effectiveness of the CMC–HA combination at 0.5%/0.1% concentrations (Optive Fusion; Allergan plc, Dublin, Ireland) has been reported recently in two multicenter, randomized clinical trials involving patients with mild to severe dry eye. 39 , 40 The effects of this combination on dry eye symptoms that develop after cataract surgery have also been investigated in a randomized study. 41 Moreover, preservative-free and multidose preserved formulations with this combination of polymers have now become available.…”

Combination of hyaluronic acid, carmellose, and osmoprotectants for the treatment of dry eye disease

“…Recently, in a randomized, investigator-blinded prospective study, the efficacy and safety of the combination of osmoprotectants/CMC/HA were evaluated in terms of the reduction of symptoms in patients with moderate-to-severe DED, in comparison with a compound with 0.18% HA. 70 The results of this study showed that, with regard to the improvement of DED symptoms, the combined formulation of HA/CMC/osmoprotectants was not inferior to 0.18% HA. Also, compared with 0.18% HA, a higher percentage of patients reported a significantly lower amount of severe itching/burning, foreign body sensation (grittiness), and ocular pain/irritation after 3 months of treatment with the combination of osmoprotectants/CMC/HA.…”

“…Also, compared with 0.18% HA, a higher percentage of patients reported a significantly lower amount of severe itching/burning, foreign body sensation (grittiness), and ocular pain/irritation after 3 months of treatment with the combination of osmoprotectants/CMC/HA. 70 Furthermore, a lower number of patients presented ocular pain/irritation on day 35 of treatment in the group treated with the combination of osmoprotectants/CMC/HA in comparison with HA. 70 …”

Effect of 5-Oxo-2-Pyrrolidinecarboxylic Acid (PCA) as a New Topically Applied Agent for Dry Eye Syndrome Treatment

“…Artificial tears, generally based on water-retentive polymers such as carboxymethylcellulose and hyaluronic acid, replace and/or reproduce the natural tear film and control the inflammatory response [ 31 , 32 , 33 ]. An improvement of the efficacy of tear substitutes can be obtained with the addition of osmoprotective agents that contribute to the stabilization of the cell volume under hyperosmotic stress, limiting cellular apoptotic phenomena and inflammation processes [ 14 ].…”

“…A positive effect on cell viability in the presence of taurine supplementation was observed by Shioda et al [ 12 ] that was ascribed to a possible antioxidant activity or membrane stabilization effect of taurine, a well-known osmolyte substance [ 13 ]. Osmoprotective substances such as erythritol, l -carnitine, and glycerine in combination with carboxymethylcellulose were more efficient in controlling primary outcomes (e.g., tear osmolarity, Schirmer-I test scores) and were consequently able to reduce the cellular stress level at the ocular surface in humans [ 14 ]. In addition, the ability of trehalose to allow for the survival of cells in unfavourable conditions, such as those present in a hyperosmotic environment, was exploited for use in the development of eye drops.…”