June 2017
Volume 58, Issue 8
Open Access
ARVO Annual Meeting Abstract  |   June 2017
Effect of a low concentration of desonide disodium phosphate on inflammatory parameters in a model of endotoxin-induced uveitis
Author Affiliations & Notes
  • Francesco Giuliano
    Research and Preclinical Development, S.I.F.I. S.p.A., Lavinaio-Aci S. Antonio, CT, Italy
  • Valeria Vitale
    Research and Preclinical Development, S.I.F.I. S.p.A., Lavinaio-Aci S. Antonio, CT, Italy
  • Giuseppe De Pasquale
    Research and Preclinical Development, S.I.F.I. S.p.A., Lavinaio-Aci S. Antonio, CT, Italy
  • Maria Grazia Mazzone
    Business and Portfolio Development, S.I.F.I. S.p.A., Lavinaio-Aci S. Antonio, CT, Italy
  • Footnotes
    Commercial Relationships   Francesco Giuliano, S.I.F.I. S.p.A. (E); Valeria Vitale, S.I.F.I. S.p.A. (E); Giuseppe De Pasquale, S.I.F.I. S.p.A. (E); Maria Grazia Mazzone, S.I.F.I. S.p.A. (E)
  • Footnotes
    Support  None
Investigative Ophthalmology & Visual Science June 2017, Vol.58, 5180. doi:
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      Francesco Giuliano, Valeria Vitale, Giuseppe De Pasquale, Maria Grazia Mazzone; Effect of a low concentration of desonide disodium phosphate on inflammatory parameters in a model of endotoxin-induced uveitis. Invest. Ophthalmol. Vis. Sci. 2017;58(8):5180.

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      © ARVO (1962-2015); The Authors (2016-present)

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Abstract

Purpose : A viable approach to an effective, yet safer, use of glucocorticoids in mild/moderate ailments of the ocular surface may be represented by eyedrops containing low concentrations of this class of molecules. Thus, we set out to characterize the effects of three different concentrations of desonide disodium phosphate (DES) in a model of endotoxin (LPS)-induced uveitis seeking to identify the one that could spare intraocular structures while exerting antiinflammatory activity on the ocular surface.

Methods : NZW male rabbits (7-11 w) were anesthetized, injected intravitreally with 100 ng of LPS (055:B5) and treated topically with 55 µl of DES 0.25%, 0.025%, 0.0025% or vehicle (VHC) immediately after, and then at 3, 6, and 9 h following LPS injection. The corneal thickness was measured by pachimetry prior to injection and then 9 and 24 h later. Then, animals were suppressed and the aqueous humor (AH) withdrawn for total leukocytes and prostaglandin E2 (PGE2) determination. Data were gathered from at least 10 animals per group. Significant differences between groups were sought by one-way ANOVA.

Results : Nine and 24h following LPS injection, VHC animals showed an increase of corneal thickness by 9% and 11% over baseline values (359±16 µm), respectively. The corneal edema induced by LPS was inhibited by DES 0.25% and 0.025% on average by more than 70% (p<0.001) both at 9 and 24 h, while DES 0.0025% was found to lack any significant effect (p>0.05). Similarly, when compared to VHC animals, DES 0.0025% did not inhibit accumulation of leukocytes or PGE2 in AH, whereas DES 0.25% and 0.025% on average produced an inhibition of both parameters by more than 20% and 40%, respectively. However, only DES 0.25% did produce effects on accumulation of leukocytes and PGE2 attaining statistical significance (p<0.05).

Conclusions : Here we have shown that DES, a medium-potency glucocorticoid, administered at concentrations matching those used in clinical practice is effective in inhibiting inflammation in a rabbit model of LPS-induced uveitis. Most importantly, we have shown that DES 0.025%, a concentration 10-times lower than that used in clinical practice, retained a notable degree of activity that may well prove effective in treating or preventing inflammatory conditions of the ocular surface while sparing intraocular tissues from adverse effects.

This is an abstract that was submitted for the 2017 ARVO Annual Meeting, held in Baltimore, MD, May 7-11, 2017.

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