Study IRIS Pharma: evaluation of effectiveness of eye drop ML7 formulation in a rat modele of scopolamine-induced dry eye

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1. 1. Summary

Purpose:

The aim of the study was to evaluate the therapeutic potential of topical applied ML7 formulation in a rat model of scopolamine-induced dry eye.

Method:

Dry eye symptoms were induced in albino Lewis female rats by systemic scopolamine diffusion (20 mg/day) over 21 days. Rats were randomized into 4 groups. One group was not induced and not treated (naïve group). The other groups were induced and received either three instillations of ML7, or three instillations of Placebo per day (TID) from the day of induction to the end of the study on Day 21. Oral Cyclosporine A treatment
(25 mg/kg/day) from Day 0 to Day 21 was used as reference.

Tear production was measured using the phenol red thread test and corneal fluorescein staining was scored using the standardized National Eye Institute (NEI) grading system.

Results:

Scopolamine reduced tear production and increased corneal fluorescein staining after
7 days of induction and over a 3-week period.

3 rats were humanely euthanized, two in Placebo-treated group and one in Cyclosporine A-treated group because of edema and skin necrosis at the pump implantation sites.

Topical application of ML7 (TID) failed to improve tear production. The tear volumes were similar to those of the Placebo-treated group.

Topical application of ML7 (TID) reduced significantly corneal fluorescein staining after
7 days of treatment in comparison with the placebo treatment. After 21 days of treatment, the corneal staining was lower than in the vehicle group, however no statistical analysis could be performed at this time-point due to the number of animals left in the vehicle group (2 euthanized animals for ethical reason).

As expected, oral administration of Cyclosporine A improved tear production and reversed corneal staining by 3 weeks of treatment.

Conclusion:

Oral administration of Cyclosporine A improved tear production and reversed the corneal staining by 3 weeks of treatment and validated the assay.

Topical administration of ML7 was effective to reverse the corneal staining induced by the scopolamine on Day 7.

Link to the validated report:

N50F25612r2