AUTHOR=Albarry Maan Abdullah , Parekh Mohit , Ferrari Stefano , Eltahir Heba Mahmoud , Shehata Ahmed M , Shaker Mohamed A , Elbadawy Hossein Mostafa 

TITLE=Incremental Concentrations of Tacrolimus Eye Drops as a Strategy for the Management of Severe Vernal Keratoconjunctivitis

JOURNAL=Frontiers in Pharmacology

VOLUME=Volume 13 - 2022

YEAR=2022

URL=https://www.frontiersin.org/journals/pharmacology/articles/10.3389/fphar.2022.798998

DOI=10.3389/fphar.2022.798998

ISSN=1663-9812

ABSTRACT=Purpose: To assess the effect of different concentrations of Tacrolimus eye suspension on the epithelium and stromal ‎keratocytes of human corneas and to investigate whether it can be safely used for severe cases of Vernal ‎Keratoconjunctivitis (VKC).‎
Methods: Tacrolimus eye suspension was prepared in a range of concentrations; 0.005%, 0.01%, 0.05%, 0.1% and ‎‎0.2%. Molecular analysis was performed ex vivo on human corneas (n=18) obtained from the eye bank. Transparency ‎and thickness of each cornea was measured while Live/Dead staining was performed using triple labeling assay. ‎Incremental concentration approach was then tested on 3 severe cases of VKC. ‎
Results: All tested Tacrolimus concentrations showed no significant changes in corneal thickness or transparency. In ‎corneas treated with 0.1%, rare scattered dead cells were observed, while the folds of corneal surfaces were mostly ‎viable, unlike concentrations higher than 0.1% and lower than 0.05%. Stromal cell densities were highest in 0.1% ‎Tacrolimus treatment condition. Incremental concentrations of Tacrolimus suspension was shown to significantly ‎improve VKC cases, where the concentration used for each case depended on the severity of the case. ‎
Conclusions: Topical administration of Tacrolimus was not toxic to human corneal cells at all tested concentrations ‎and the 0.1% concentration has shown the best viability of the corneal tissue. Tacrolimus eye suspension was shown ‎to be safe and effective for use in severe VKC and is proposed as a topical ocular immunosuppressant drug enabling ‎clinicians to incrementally increase the drug concentration in according to the clinical severity of the disease to ‎achieve the optimal therapeutic response.‎