Alternative Therapies for Dry Eye Disease

Rhiya Mittal; Sneh Patel; Anat Galor


Curr Opin Ophthalmol. 2021;32(4):348-361. 

In This Article

Therapies for Ocular Surface Inflammation

Ocular inflammation is a major contributor to DED and can be seen in both ATD and ETD.[61] The source of ocular inflammation has been linked to T-cell activation and subsequent release of pro-inflammatory cytokines, especially IL-1, IL-6, IL-8, and TNF-α, in both humans and DED animal models.[62] Anti-inflammatory medications, including cyclosporine and lifitegrast, are mainstay treatments for DED. More recently, naturally occurring anti-inflammatory substances have been explored as alternative therapies in DED.

One such therapy is trehalose, a naturally occurring disaccharide with high resistance to environmental desiccative and oxidative stress. When suspended in solution and applied to the eyes, it decreases inflammation by activating the transcription factor EB, resulting in autophagosome activation and subsequent destruction of pro-inflammatory cytokines.[63] In an open-label study, 15 subjects with ETD (OSDI>18, TBUT<10, Schirmer>10) received trehalose/hyaluronate tear substitute (one drop/eye, 3×/day × 2 months). Symptoms and signs of DED improved including OSDI (38.7 ± 12.7 to 22.2 ± 2.9; P < 0.05), TBUT (6.2 ± 1.9 s to 8.6 ± 1.3 s; P < 0.05), and corneal staining (3.4 ± 0.5 to 1.23 ± 0.6; P < 0.05).[64] Another in vitro study demonstrated that trehalose had anti-inflammatory effects. This study examined corneal epithelial cells preincubated for one hour with 0%, 0.1%, 0.5%, 1.0%, 1.5%, 2.0%, 3.0%, or 5.0% trehalose NaCl solution and then exposed to a 450mOsm NaCl solution. Percentage of pro-inflammatory markers after desiccation was significantly lower in the 0.5%, 1.0%, and 1.5% trehalose groups compared to the control group. As compared to control cells, the 1.0% trehalose cells showed the greatest difference in markers (TNFα: 26.1 ± 9.6pg/mL trehalose vs 96.4 ± 12.6pg/mL control; IL-1β: 27.0 ± 8.9pg/mL trehalose vs 87.0 ± 10.8pg/mL control; IL-6: 4.5 ± 0.7ng/mL trehalose vs 7.6 ± 1.4ng/mL control; P < 0.05). Interestingly, higher trehalose concentrations (2.0–5.0%) lost these protective effects and inflammatory markers actually increased.[63] Though preliminary results are promising, randomized trials with a comparison group (placebo) are needed to examine the clinical value of trehalose in DED. This also applies to other anti-inflammatory natural products that have mostly been examined preclinically in animal models or in vitro. Other promising anti-inflammatory products for DED include Aster koraiensis extract,[65] polydatin,[66]Eurya japonica extract,[67] L-carnitine,[68] pterostilbene,[69] alpha-lipoic acid,[70] selenoprotein P,[71] vitamin B12,[68,72] carotenoids,[73] and anthocyanins.[74]

Overall, given the important role of inflammation in DED, there is interest in exploring the effects of naturally derived anti-inflammatory products in the disease, although these investigations are still in early stages.