High-precision piezo-ejection Ocular microdosing: Phase II Study on Local and Systemic Effects of Topical Phenylephrine

Abstract

Aim: Conventional eyedropper-delivered volumes (25–50 µl) exceed the eye's usual tear-film volume (7 µl) and precorneal reservoir capacity, risking overflow and ocular/systemic complications. Piezoelectric high-precision microdosing may circumvent these limitations. Results & methodology: In this masked, nonrandomized, cross-over study, subjects (n = 12) underwent pupil dilation with topical phenylephrine (PE) administered by 32-µl eyedropper (2.5% or 10% formulation) and 8-µl electronic microdosing (10% formulation). Microdosing with PE-10% achieved comparable peak dilation as 10% eyedropper-delivery and superior dilation to 2.5% eyedropper-delivery (p = 0.009) at 75 min. Microdosing significantly reduced 20-min plasma PE levels versus PE10% eyedropper; neither treatment altered heart rate/blood pressure. Eye irritation occurred significantly less frequently with microdosing than PE10% eyedrops. Conclusion: Piezo-ejection PE microdosing achieves comparable biological effect as eyedropper dosing; reduced systemic absorption may decrease risk of systemic side effects.

Keywords:

• adverse events
• microdosing
• ocular drug delivery
• ocular medication
• phenylephrine
• piezo-ejection system
• pupil dilation
• systemic absorption

Financial & competing interests disclosure

T Ianchulev, R Weinreb and J Tsai are consultants for Eyenovia Incorporated (FL, USA), the device manufacturer. T Ianchulev is named on the device patent application. J Tsai is a consultant for Aerie Pharmaceuticals (CA, USA), Inotek Pharmaceuticals (MA, USA), and Shire plc (Dublin, Ireland). L Pasquale is a speaker for Bausch & Lomb (NY, USA), and has received travel support from the Glaucoma Foundation-New York and research funding from the National Institutes of Health for work unrelated to the current study. S Lin is a consultant for Aerie Pharmaceuticals, Allergan plc, (Dublin, Ireland), Iridex Corporation (CA, USA), and Aleyegn Incorporated (CA, USA), and has received travel support and honoraria from Eyenovia. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

The authors thank M Silverman (Biomedical Publishing Solutions, FL, USA) for scientific writing and statistical analysis services. Silverman's fee was paid by Eyenovia.

Ethical conduct

The study protocol was reviewed and approved by the Institutional Review Board at Oculos Clinical Research LLC, which oversaw performance of the study at the Sall Research Medical Center, Artesia, CA, during October and November of 2016. Study performance complied with the tenets of the Declaration of Helsinki and the Health Insurance Portability and Accountability Act. All subjects provided written informed consent.