Abstract
Purpose :
To determine the therapeutic effects of topical treatment with ALY688 ophthalmic solution in a rabbit model of dry eye. ALY688 is a peptide analogue of adiponectin demonstrated to have anti-inflammatory and regenerative actions on the ocular surface.
Methods :
Adult New Zealand White (NZW) Rabbits were dosed three times daily OU with either ALY688 0.4% Ophthalmic Solution (n=6) or vehicle control (n=6) for 14 days (Study Days -1 to 13). On Days 0 to 13, rabbits were dosed topically three times daily OU with 1% Atropine Sulfate Ophthalmic Solution (Akorn, Inc) 15 minutes before test article administration. Four additional rabbits received atropine only in both eyes. Corneal fluorescein staining (NEI scale), tear breakup time (TBUT), and tear volume evaluations (Schirmer strips) were assessed in a masked fashion at baseline and on Days 1, 3, 7, 10, and 13. Slit-lamp examinations were performed at baseline and on the final day of dosing (Day 13).
Results :
Atropine administration significantly decreased tear volume and tear break-up time, accompanied by increased corneal fluorescein staining compared to baseline. ALY688 administration alleviated all these effects, with statistically significant improvement over vehicle at multiple timepoints, and by overall integrated analyses (p<0.005). The peak difference in TBUT was measured at Day 7 (19.6±3.8 sec in ALY688 group vs. 8.5±0.9 sec in vehicle group, p=0.01), in corneal staining at Day 10 (1.7±0.4 in ALY688 group vs. 6.8±1.6 in vehicle group, p<0.01), and in tear volume on Day 13 (7.8±0.8 in ALY688 group vs. 4.7±0.6 in vehicle group, p=0.01). Anterior segment slit-lamp exams performed after 14 days of dosing with 0.4% ALY688 showed no abnormal findings or signs of irritation.
Conclusions :
ALY688 Ophthalmic Solution was highly effective at improving clinical dry eye signs (corneal staining, tear break up time, and tear volume) in an atropine-induced model of dry eye disease in NZW rabbits. Effects were noted as early as study Day 1, two days after initiation of ALY688 treatment. ALY688 was well tolerated and produced no signs of ocular irritation or anterior segment abnormalities. These results are consistent with previous studies showing similar beneficial effects in a mouse model of desiccative stress-induced dry eye. ALY688 is a promising novel treatment for dry eye disease.
This abstract was presented at the 2019 ARVO Annual Meeting, held in Vancouver, Canada, April 28 - May 2, 2019.