PROJECT SUMMARY
Tympanostomy tube otorrhea (TTO) is the most common complication after tympanostomy tube (TT)
placement in children. Despite the standard treatment using topical antibiotics, TTO is often persistent or
recurrent. Biofilms on TT are implicated to be the major cause of persistent and recurrent TTO. Antimicrobial
blue light (aBL), an innovative non-pharmacological approach, has recently attracted increasing attention due
to its prominent antimicrobial activity through photoexcitation of naturally occurring endogenous porphyrins in
bacteria to produce cytotoxic reactive oxygen species. In the preliminary study, we demonstrated that aBL was
effective in killing common TTO pathogens in experimental biofilms. The objective of this R21 proposal is to
develop a novel Optical Tympanostomy Tube (Optical-TT), which is made from a biocompatible light-scattering
optical material and emits aBL from the whole surface of tube, for prevention and treatment of TTO. To this
end, we propose two Specific Aims.
In Aim 1, we will perform in vitro studies to determine the efficacy of Optical-TT mediated by aBL in prevention
and eradication of experimental biofilms on Optical-TTs formed by representative TTO pathogens, including
Haemophilus influenzae, Staphylococcus aureus and Pseudomonas aeruginosa. For prevention of biofilms on
Optical-TTs, Optical-TTs will be "activated" using aBL within 30 min after bacterial inoculation; while for
eradication of biofilms, Optical-TTs will be "activated" using aBL after biofilms have matured on the tubes. The
bacterial load of biofilms on Optical-TTs will be determined by quantitative colony-forming units (CFU) counting
and qualitative scanning electron microscopic (SEM) imaging. The efficacy found with Optical-TT will be
compared with those of ciprofloxacin solution and silver oxide-impregnated Silicone TT.
In Aim 2, we will perform preclinical animal studies to determine the efficacy and safety of aBL-mediated
Optical-TT in prevention and treatment of experimental TTO in chinchillas. For prevention of TTO, Optical-TT
will be "activated" using aBL within 30 min after bacterial inoculation; while for treatment of TTO, Optical-TT will
be "activated" using aBL when TTO are visible via tympanometry and otomicroscopy. The bacterial load on
Optical-TTs and in the middle ear bullae will be determined by CFU counting and SEM imaging. The efficacy
found with aBL will be compared with that of ciprofloxacin/dexamethasone otic drops, which are the current
stand of care for TTO. As the safety study, the ototoxicity of Optical-TT to the auditory function will be
determined by measurement of auditory brain response and hair cell survival in the cochlea.
Collectively, successful completion of the Specific Aims outlined in this proposal will provide the preclinical
evidence required to determine the effectiveness and safety of aBL-mediated Optical-TT in prevention and
treatment of TTO. The studies will also demonstrate the functionality of a prototype system of Optical-TT.