title: Electronic enhancement of tear secretion.
abstract: OBJECTIVE
  To study electrical stimulation of the lacrimal gland and afferent nerves for enhanced tear secretion, as a potential treatment for dry eye disease. We investigate the response pathways and electrical parameters to safely maximize tear secretion.
  
  
  METHODS
  We evaluated the tear response to electrical stimulation of the lacrimal gland and afferent nerves in isofluorane-anesthetized rabbits. In acute studies, electrical stimulation was performed using bipolar platinum foil electrodes, implanted beneath the inferior lacrimal gland, and a monopolar electrode placed near the afferent ethmoid nerve. Wireless microstimulators with bipolar electrodes were implanted beneath the lacrimal gland for chronic studies. To identify the response pathways, we applied various pharmacological inhibitors. To optimize the stimulus, we measured tear secretion rate (Schirmer test) as a function of pulse amplitude (1.5-12 mA), duration (0.1-1 ms) and repetition rate (10-100 Hz).
  
  
  RESULTS
  Stimulation of the lacrimal gland increased tear secretion by engaging efferent parasympathetic nerves. Tearing increased with stimulation amplitude, pulse duration and repetition rate, up to 70 Hz. Stimulation with 3 mA, 500 μs pulses at 70 Hz provided a 4.5 mm (125%) increase in Schirmer score. Modulating duty cycle further increased tearing up to 57%, compared to continuous stimulation in chronically implanted animals (36%). Ethmoid (afferent) nerve stimulation increased tearing similar to gland stimulation (3.6 mm) via a reflex pathway. In animals with chronically implanted stimulators, a nearly 6 mm increase (57%) was achieved with 12-fold less charge density per pulse (0.06-0.3 μC mm(-2) with 170-680 μs pulses) than the damage threshold (3.5 μC mm(-2) with 1 ms pulses).
  
  
  CONCLUSIONS
  Electrical stimulation of the lacrimal gland or afferent nerves may be used as a treatment for dry eye disease. Clinical trials should validate this approach in patients with aqueous tear deficiency, and further optimize electrical parameters for maximum clinical efficacy.
authors.affiliation: Stanford University, Electrical Engineering, Stanford, CA, USA.
authors.forename: Mark
authors.initials: M
authors.lastname: Brinton
authors.forename: Jae Lim
authors.initials: JL
authors.lastname: Chung
authors.forename: Andrea
authors.initials: A
authors.lastname: Kossler
authors.forename: Koung Hoon
authors.initials: KH
authors.lastname: Kook
authors.forename: Jim
authors.initials: J
authors.lastname: Loudin
authors.forename: Manfred
authors.initials: M
authors.lastname: Franke
authors.forename: Daniel
authors.initials: D
authors.lastname: Palanker
mesh_terms: D000344:Afferent Pathways / Q000502:physiology*; D000818:Animals; D015352:Dry Eye Syndromes / Q000503:physiopathology / Q000628:therapy; D004599:Electric Stimulation Therapy / Q000009:adverse effects / Q000379:methods*; D005131:Eye Injuries / Q000209:etiology / Q000473:pathology; D007765:Lacrimal Apparatus / Q000293:injuries / Q000294:innervation* / Q000378:metabolism*; D010525:Peripheral Nerves / Q000502:physiology; D011817:Rabbits; D013666:Tears / Q000378:metabolism*; D016896:Treatment Outcome