Disease aetiology-based design of multifunctional microemulsion eye drops for moderate or severe dry eye: a randomized, quadruple-masked and active-controlled clinical trial

Abstract

Purpose: To assess the safety and efficacy of multi-ingredient sacha inchi microemulsion (SIME) eye drops designed to target (1) tear film instability, (2) tear hyperosmolarity, and (3) ocular surface damage and inflammation in moderate or severe dry eye.

Methods: This randomized, quadruple-masked, active-controlled parallel study in 64 adult patients comprised three parts. Part 1 (n = 3): one eye was treated with SIME for one day. Part 2 (n = 9): randomized eyes were treated with SIME and 0.2% hyaluronic acid (HA) control eye drops 3 times a day for 10 days. Part 3 (n = 26 + 26): randomized treatment was applied on both eyes 3 times a day for 30 days. OSDI change was tested for superiority of SIME over HA. Ocular assessments were performed at baseline and after the last dose.

Results: Both treatments were well tolerated without adverse device effects. Tear film break-up time (p = 0.0025) and ocular protection index (p = 0.0026; change vs. HA, p = 0.047) increased significantly with SIME after 30 days. Tear osmolarity decreased more in SIME than in the HA group and significantly with both eye drops in hyperosmolar subgroups. Corneal (p = 0.014) and nasal conjunctival staining (p = 0.043) were reduced with SIME in per-protocol patients (n = 24). Conjunctival (p = 0.001) and lid redness (p = 0.012) decreased with SIME in all patients (n = 26). Symptoms decreased by about 25 OSDI units with both treatments (p < 0.0001) and with nonsignificant difference between treatments.

Conclusions: Sacha inchi microemulsion (SIME) proved safe and efficacious in improving each aetiologic factor for dry eye as revealed through objective tests. Hyperosmolar stress dominating blink cycles must be disrupted by biophysical protection of the ocular surface to facilitate resolution of cellular damage and inflammation, and relief of ocular symptoms.

Keywords: fatty acids, omega-3; hyaluronic acid; lubricant eye drops; ophthalmic emulsion; osmolar concentration; protective agents; tears; trehalose.

Figure Fig. 1

Flow diagram of the study.

Figure Fig. 2

Tear film break‐up time (TBUT). A, Part 2 (n = 9); B, Part 3 (n = 26). Mean ± SD from ITT population. SIME, sacha inchi microemulsion eye drops; HA, hyaluronic acid control eye drops.

Figure Fig. 3

Ocular protection index (OPI). A, Part 2 (n = 9); B, Part 3 (n = 26). Mean ± SD from ITT population. Dash line marks OPI = 1.

Figure Fig. 4

Tear osmolarity. A, Part 2 (n = 9); B, Part 2 patients with tear hyperosmolarity (≥308 mOsm/l, dash line) at baseline (SIME , n = 5; HA, n = 3); C, Part 3 (n  = 26); D, Part 3 patients with tear hyperosmolarity (SIME, n  = 8; HA , n = 14). Mean ± SD from ITT population.

Figure Fig. 5

Signs of ocular surface damage. A, Corneal staining; B, temporal conjunctival staining; C, nasal conjunctival staining. Mean ± SD of the mean values of eyes (Oxford scale 0–5) in PP population of Part 3 (SIME, n = 24; HA, n = 25).

Figure Fig. 6

Signs of ocular surface inflammation. A, Conjunctival redness, B, lid redness. Mean ± SD of the mean values of eyes (IER scale 0–4) in safety/ITT data set population of Part 3 (n = 26).

Figure Fig. 7

Box–whisker plot of ocular surface disease index (OSDI). A, OSDI sum score; B–D, subscale scores of OSDI. The mean is marked with a diamond. Boxes represent interquartile ranges separated by the median; whiskers indicate the minimum and maximum values. All data are from ITT population of Part 3 (n = 26). ***p < 0.0001.