[Influence of Aging on Severity and Anti-Inflammatory Treatment of Experimental Dry Eye Disease].

Aging is an important factor in dry-eye disease that has not been studied in the context of therapeutic measures. Aging-associated modifications of the ocular immune system implicate that anti-inflammatory therapies may act differently among younger individuals in terms of onset and effect of different substances. The goal of this study was to determine differences in clinical phenotype and topical anti-inflammatory therapy using a desiccating stress mouse model. An experimental dry-eye disease (desiccating stress model) was induced in 12-week and 12-month-old female BALB/c mice. Topical therapy included 0.05% cyclosporine/F4H5 (Novaliq), F4H5, 0.05% cyclosporine (Restasis, Allergan) and dexamethasone (Monodex, Thea Pharma) for 3 consecutive weeks. A control group received no therapy whatsoever. Readout parameters included tear secretion, corneal fluorescein staining at 5 timepoints and histological analysis of goblet cell count at the end of the experiments. The older mice demonstrated a significantly stronger dry eye phenotype than the younger mice. Following therapy, the older mice responded to topical anti-inflammatory therapy significantly later than the younger individuals. Regarding the different substances used, cyclosporine/F4H5 showed a significantly faster decrease in corneal fluoresceine staining after only 1 week of therapy in comparison to all other groups. This substance was also superior regarding tear secretion and goblet cell count in age matched groups and in comparison to younger mice. These experimental data support the implication that aging should be considered as an important factor in daily clinical practice. Furthermore, the differences found between substance classes, such as calcineurin antagonists and steroids, as well as different drug formulations, should be considered in future pre-clinical and clinical trials.