September 2016
Volume 57, Issue 12
Open Access
ARVO Annual Meeting Abstract  |   September 2016
Ocular tolerability assessment of PHMB (Polyhexanide) 0.8%, 0.25% and 0.08% ophthalmic solutions in rabbits.
Author Affiliations & Notes
  • Antonino Asero
    SIFI SPA, Lavinaio - Aci S. Antonio, Italy
  • Michela Salvador
    Research Toxicology Centre, Pomezia, Italy
  • Abraham Nyska
    Research Toxicology Centre, Pomezia, Italy
  • Silvana Venturella
    Research Toxicology Centre, Pomezia, Italy
  • Vincenzo Papa
    SIFI SPA, Lavinaio - Aci S. Antonio, Italy
  • Anna Rita Blanco
    SIFI SPA, Lavinaio - Aci S. Antonio, Italy
  • Footnotes
    Commercial Relationships   Antonino Asero, SIFI SpA (E); Michela Salvador, Research Toxicology Centre SPA (E); Abraham Nyska, Research Toxicology Centre SPA (E); Silvana Venturella, Research Toxicology Centre SPA (E); Vincenzo Papa, SIFI SpA (E); Anna Rita Blanco, SIFI SpA (E)
  • Footnotes
    Support  European Commission Grant n°305661
Investigative Ophthalmology & Visual Science September 2016, Vol.57, 5395. doi:
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      Antonino Asero, Michela Salvador, Abraham Nyska, Silvana Venturella, Vincenzo Papa, Anna Rita Blanco; Ocular tolerability assessment of PHMB (Polyhexanide) 0.8%, 0.25% and 0.08% ophthalmic solutions in rabbits.. Invest. Ophthalmol. Vis. Sci. 2016;57(12):5395.

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

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Abstract

Purpose : To establish the eye drops 0.08% PHMB as sufficiently safe in rabbits to be tested in Phase I clinical trials as potential orphan drug in the treatment of Acanthamoeba keratitis.

Methods : Forty-two New Zealand White rabbits (n=8/Groups 2 and 3; n=12/Groups 1 and 4) were instilled into the right eye with 50 µL of PHMB vehicle (Group 1), PHMB 0.08%, 0.25% and 0.8% eye drops (Groups 2, 3 and 4), 13 times a day at approximately 1 hour intervals from Day 1 to 7 (Week 1) and 7 times a day at approximately 2 hours intervals from Day 8 to 14 (Week 2). The left eye remained untreated. Two animals/sex of Groups 1 and 4, were sacrificed after 1 week of recovery. Ocular irritation assessment was performed daily, before first dosing, in all animals during the treatment and once daily during the recovery period. In addition, fluorescein staining of cornea, slit-lamp examination and ophthalmoscopy were performed at weekly intervals in all animals during the study. Macroscopic and microscopic examination of treated and untreated eyes were performed in all animals sacrificed at the end of the treatment.

Results : Slight conjunctival redness with slight/moderate discharge was noted in few animals treated with 0.08% and 0.25% PHMB eye drops (Groups 2-3). Recovery occurred in all animals after the treatment period. No treatment-related changes were observed in the eyes of animals of these groups after microscopic examination.
Only animals treated with 0.8% PHMB eye drops (Group 4) showed moderate/severe treatment-related effect with irreversible ocular toxicity during the follow-up period. The observed microscopic damages were from minimal to mild severity and consisted of combination of conjunctival/corneal oedema, necrosis, iris congestion and acute inflammation. However, even in Group 4, histopathological evaluations of the eye lens showed no degenerative changes. Moreover, for all tested PHMB solutions no indication of systemic effects were observed during the period of the study.

Conclusions : Two-week repeated instillation of 0.08% and 0.25% PHMB ophthalmic solutions in the rabbit eye did not show any relevant treatment-related effect. These results support our next plan to investigate with sufficient safety margin the PHMB 0.08% eye drops in Phase I clinical trials as a selected orphan drug for the treatment of Acanthamoeba keratitis.

This is an abstract that was submitted for the 2016 ARVO Annual Meeting, held in Seattle, Wash., May 1-5, 2016.

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