title: Toxicity of insulin administered chronically to human eye in vivo.
abstract: Insulin administered in eyedrop from with a surfactant agent has been shown to be clinically effective in treating diabetes in animal models. Concentrations of insulin as high as 100 U/ml in saline were shown to produce no detectable clinical toxicity to human eyes in single-dose administration. We sought to investigate the local toxicity of insulin in human eyes during long-term, multidose administration. A prospective, randomized, placebo controlled, double-masked study was conducted involving eight healthy volunteers. Subjects were given 50 microliters sterile saline containing 100 U/ml crystalline porcine insulin randomized to one eye and 50 microliters placebo (sterile saline) to the fellow eye administered twice daily for 8 weeks. Subjective ocular irritation and visual acuity and objective assessment of the eyelids, conjunctiva, cornea, anterior chamber, crystalline lens, pupil size, and intraocular pressure were evaluated. Blood D-glucose levels were monitored to assess glycemic levels. There was no statistically significant difference (p > 0.05) observed between insulin-treated and placebo-treated eyes. Eyedrops containing insulin were subjectively as comfortable and objectively as clinically innocuous as sterile saline alone. The results of this study demonstrate that insulin (100 U/ml) in saline is nontoxic to the human eye after long-term, multi-dose exposure. Topical administration of insulin combined with an absorption-promoting agent may be a practical and feasible alternative to multiple daily subcutaneous injections or implanted pump devices currently used in the long-term treatment of diabetes mellitus if a nonirritating absorption-promoting agent can be identified.(ABSTRACT TRUNCATED AT 250 WORDS)
authors.affiliation: Department of Optometry, School of Optometry, University of Alabama at Birmingham.
authors.forename: J D
authors.initials: JD
authors.lastname: Bartlett
authors.forename: T G
authors.initials: TG
authors.lastname: Slusser
authors.forename: A
authors.initials: A
authors.lastname: Turner-Henson
authors.forename: K P
authors.initials: KP
authors.lastname: Singh
authors.forename: J A
authors.initials: JA
authors.lastname: Atchison
authors.forename: D J
authors.initials: DJ
authors.lastname: Pillion
mesh_terms: D000328:Adult; D001786:Blood Glucose / Q000032:analysis; D004311:Double-Blind Method; D005123:Eye / Q000187:drug effects*; D005260:Female; D006801:Humans; D007328:Insulin / Q000008:administration & dosage* / Q000009:adverse effects; D007429:Intraocular Pressure / Q000187:drug effects; D008297:Male; D009883:Ophthalmic Solutions / Q000008:administration & dosage* / Q000009:adverse effects; D011446:Prospective Studies; D014792:Visual Acuity / Q000187:drug effects
chemical_list: D001786:Blood Glucose; D007328:Insulin; D009883:Ophthalmic Solutions