# Prospective Comparative Study of Topical Tacrolimus and Sirolimus for the Treatment of Pigmentary Keratitis in Pug Dogs

## TL;DR

This study compares two eye drops, tacrolimus and sirolimus, for treating pigmentary keratitis in Pug dogs, finding tacrolimus more effective and safer.

## Contribution

The study provides the first prospective comparative evidence on the efficacy and safety of tacrolimus versus sirolimus for treating pigmentary keratitis in Pugs.

## Key findings

- Both tacrolimus and sirolimus improved tear-film parameters and reduced corneal pigmentation in Pugs.
- Tacrolimus showed superior efficacy in increasing tear production and promoting pigment regression compared to sirolimus.
- Sirolimus was associated with more frequent adverse effects, including corneal ulcers and irritation.

## Abstract

Pigmentary keratitis is a common eye condition in Pug dogs, in which dark pigment gradually spreads across the cornea, reducing comfort and eventually affecting vision. It is usually caused by chronic irritation, tear film instability, or the characteristic facial conformation of the breed. Because no fully effective treatment exists, managing this disease remains a challenge in veterinary practice. This study compared two topical immunomodulatory eye drops—tacrolimus and sirolimus—used to reduce inflammation and support tear production. Thirty-two Pugs received one of these treatments for six months, during which tear production, tear quality, and changes in corneal pigmentation were regularly assessed. Both treatments improved tear-film parameters, increased comfort, and reduced the amount of pigment on the corneal surface. However, tacrolimus produced clearer benefits, particularly in improving tear production and in creating a visible line of pigment regression. Some unwanted effects, including eye irritation and corneal ulcers, occurred more frequently in dogs treated with sirolimus. Overall, these findings suggest that tacrolimus may be the safer and more effective option for managing pigmentary keratitis in Pugs. This information may help veterinarians make better treatment decisions and improve the quality of life of affected dogs.

Pigmentary keratitis (PK) is a prevalent ocular surface disease in Pug dogs, yet comparative evidence on topical immunosuppressants remains limited. This prospective comparative clinical study evaluated the efficacy and safety of two agents with distinct mechanisms—tacrolimus, a calcineurin inhibitor, and sirolimus, an mTOR inhibitor—for the treatment of PK. Thirty-two Pugs (63 eyes) were randomly assigned to receive either 0.03% tacrolimus or 0.03% sirolimus three times daily for six months. Tear film quantity and quality were assessed using the Schirmer tear test, tear break-up time, and Ferning patterns, alongside serial clinical scoring of corneal pigmentation and ocular surface signs. Both treatments improved tear-film parameters, although only tacrolimus produced statistically significant increases in tear production and more frequent formation of a pigment-free “clear line,” indicating enhanced pigment regression. Pigment lightening and transparency recovery improved similarly in both groups. Adverse events—including blepharospasm, diffuse corneal oedema, and complicated ulcers—occurred more frequently in the sirolimus group, suggesting a comparatively less favorable short-term safety profile. Overall, both tacrolimus and sirolimus demonstrated therapeutic benefit in PK, although tacrolimus showed superior quantitative efficacy and better tolerability. Further long-term studies are warranted to clarify safety considerations and to optimize immunomodulatory strategies for this breed-specific condition. These findings suggest tacrolimus may be considered a first-line immunomodulatory therapy for PK in Pug dogs.