Purchase this article with an account.
Celine Olmiere, Anne-Laure Raveu, Christophe Baudouin; T1565, a new efficient and safe preservative free hydrocortisone. Invest. Ophthalmol. Vis. Sci. 2017;58(8):1079. doi: https://doi.org/.
Download citation file:
© ARVO (1962-2015); The Authors (2016-present)
There is a controversy on the use of long term dexamethasone in ophthalmology due to side effects, mainly intraocular pressure rise (IOP). The aim of this preclinical work was to evaluate the efficacy/risk balance of preservative free hydrocortisone. Modifications of IOP were examined after twice daily instillations of T1565 (preservative free hydrocortisone 0.335%), for 5 weeks in a rat model of glucocorticoid-induced ocular hypertension, in comparison to dexamethasone.
Twenty four albino rats (Sprague Dawley females) were divided into 2 treatment groups (n=12 per group) and twice daily instilled from Day 1 to Day 36 with T1565, or dexamethasone (dex). Everyday a general clinical examination was performed with weighing and IOP was measured each week. In parallel, an in vitro comparison of inflammatory marker mRNA was performed in two different in vitro models of dry eye, namely desiccative and hyperosmolar stresses, comparing dexamethasone 0.1% vs hydrocortisone 0.335%.
Animals treated with T1565 had a usual body weight gain variation during the course of the study whereas for dex-treated animals the body weight gain was repressed after 7 days, as expected.All animals were in good health and no particular signs were observed except an agitation of all the animals during IOP measurement. Animals treated with T1565 had a non-significant increase of the mean IOP until Day 15, and then a stabilization.Dex-treated animals showed as expected, an increase of the mean IOP until Day 39 with no sign of stabilization. Moreover, mean IOP at D36 was 9.5±1.6 mmHg vs 8.3±0.7 mmHg at baseline for animals treated with T1565 and 11.6±1.2 mmHg vs 7.7±0.5 mmHg at baseline for animals treated with dexamethasone.In vitro, with hydrocortisone a comparable decrease with dexamethasone was observed in hyperosmolar stress : decrease of CCL-2, and desiccative stress : decrease of IL-6, IL-8 and CCL-2.
This study shows the safety and efficacy of this new preservative-free hydrocortisone T1565. Twice daily instillations of a preservative-free hydrocortisone T1565 induced a slight IOP elevation after a 2-week dosing period followed by stabilization whilst dexamethasone treatment led to significant continuing IOP increase and drastically reduced body weight gain, as expected with this treatment. Furthermore, ocular inflammatory marker mRNA were reduced as efficiently as with dexamethasone.
This is an abstract that was submitted for the 2017 ARVO Annual Meeting, held in Baltimore, MD, May 7-11, 2017.
This PDF is available to Subscribers Only