July 2019
Volume 60, Issue 9
Open Access
ARVO Annual Meeting Abstract  |   July 2019
Melatonin and agomelatine improved effects on the IOP
Author Affiliations & Notes
  • Dario Rusciano
    Scientific Department, Sooft Spa, Roma, Italy
  • Nicola Pescosolido
    Ophthalmology, University Policlinic, Rome, Italy
  • Salvatore Pezzino
    Scientific Department, Sooft Spa, Roma, Italy
  • Rosario Pignatello
    Drug Science, University of Catania, Catania, Italy
  • Roberta Corsaro
    Drug Science, University of Catania, Catania, Italy
  • Massimo Dal Monte
    University of Pisa, Pisa, Italy
  • Maurizio Cammalleri
    University of Pisa, Pisa, Italy
  • Paola Bagnoli
    University of Pisa, Pisa, Italy
  • Footnotes
    Commercial Relationships   Dario Rusciano, None; Nicola Pescosolido, None; Salvatore Pezzino, None; Rosario Pignatello, None; Roberta Corsaro, None; Massimo Dal Monte, None; Maurizio Cammalleri, None; Paola Bagnoli, None
  • Footnotes
    Support  None
Investigative Ophthalmology & Visual Science July 2019, Vol.60, 3786. doi:
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      Dario Rusciano, Nicola Pescosolido, Salvatore Pezzino, Rosario Pignatello, Roberta Corsaro, Massimo Dal Monte, Maurizio Cammalleri, Paola Bagnoli; Melatonin and agomelatine improved effects on the IOP. Invest. Ophthalmol. Vis. Sci. 2019;60(9):3786.

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

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Purpose : Aim of this study has been the evaluation of melatonin and agomelatine effects on the IOP of normal rats after administration of innovative topical formulations given as eye drops.

Methods : Different formulations of melatonin were obtained in buffered saline, in nanolipidic carriers (NLC) and in nanomicelles (NMC). Agomelatine and the mixture of melatonin and agomelatine was formulated in nanomicelles only. Eye drops of such formulations were instilled in the eyes of normal wistar rats, and their IOP measured by the use of an Icare® Tonolab at different time points. The concentration of melatonin in whole rat eyes was determined by HPLC/MS.

Results : All melatonin eye drops showed a significant IOP decreasing effect. The formulation in NMC gave better and longer lasting effects than the NLC formulation, which in turn was better than the formulation in saline. Agomelatine eye drops formulated in NMC also showed a concentration-dependent IOP lowering effect, which at the lower concentrations (0.01% and 0.1%) was comparable to melatonin (around 30% IOP maximum decrease). Agomelatine at 1% appeared more effective (50% of IOP maximum decrease) than the equivalent melatonin formulation (40% maximum decrease). Finally, the association of agomelatine and melatonin (each at 0.1%) showed a long-lasting (up until 8 hours) decrease, ranging between 40 and 30% of maximum decrease.

Conclusions : Melatonin and agomelatine are already known to have hypotonizing effects on the IOP when given by the oral (Pescosolido N et al. Ophthalmic Physiol Opt. 2015 Mar; 35:201-5) or the topical route (Martínez-Águila A et al. J Pharmacol Exp Ther. 2016; 357:293-9. Martínez-Águila A et al. Eur J Pharmacol. 2013; 701:213-7). Data here presented show that such effect can be improved when melatonin and agomelatine are formulated in nanomicelles, and given topically onto the eye. Interestingly, the mechanism by which they lower the IOP appears to enhance, or to be complementary to the mechanisms of the other anti-glaucoma drugs. Accordingly, the anecdotic observation on a single patient under Maximum Tolerated Medical Therapy (taking all 4 classes of antiglaucoma drugs) showed a consistent further reduction (around 25%) of the IOP when agomelatin and/or melatonin eye drops (a galenic formulation at 1% of each component, in buffered saline) were added to the MTMT treatment.

This abstract was presented at the 2019 ARVO Annual Meeting, held in Vancouver, Canada, April 28 - May 2, 2019.


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