Precorneal residence time of artificial tears measured in dry eye subjects

Optom Vis Sci. 2008 Aug;85(8):725-31. doi: 10.1097/OPX.0b013e3181824de3.


Purpose: The purpose of this investigation was to measure the precorneal residence time of saline and five marketed artificial tears in dry eye subjects using fluorometry.

Methods: FITC-dextran, 70 kDa molecular weight, was admixed under sterile conditions (0.1% wt/vol) into buffered saline and the marketed artificial tear formulations of varying viscosity. Precorneal residence time (RT) was measured directly in 16 mild to moderate dry eye subjects, classified by sub-type, in a six-way cross-over, masked and randomized study. FITC-dextran tracer decay with a scanning fluorometer was used to estimate the gross RT (i.e., the time in minutes for the signal to return to baseline).

Results: All subjects were classified as having non-inflammatory meibomian gland dysfunction except one, who had a mixture of aqueous deficiency and meibomian gland dysfunction. In two separate determinations, the saline RTs were 19.1 +/- 7.4 and 17.6 +/- 8.2 min. The RTs for the formulations varied to some degree by viscosity, with two higher viscosity formulations demonstrating the longest RTs of 36 to 41 min, approximately twice that of saline (p < 0.001 for both 0.4% polyethylene glycol/0.3% propylene glycol, and 1.0% carboxymethylcellulose). An oil emulsion, low viscosity carboxymethylcellulose and moderate viscosity hydroxypropylmethylcellulose-containing formulation were not statistically different from saline (RTs of 18, 22 and 24 min, p values = 0.983, 0.818 and 0.099, respectively).

Conclusions: More than two-fold RT differences were found for the higher viscosity, more muco-adhesive formulations compared to saline. However, other formulations provided RTs close to saline, suggesting that RT is influenced by factors other than simple viscosity. Future studies should examine the interplay of spreading characteristics, pseudoplasticity and muco-adhesion relative to RT to determine the individual and cumulative effects on formulation retention.

Publication types

  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Cornea / metabolism*
  • Cross-Over Studies
  • Dextrans / pharmacokinetics
  • Diagnostic Techniques, Ophthalmological
  • Double-Blind Method
  • Dry Eye Syndromes / metabolism*
  • Female
  • Fluorescein-5-isothiocyanate / analogs & derivatives
  • Fluorescein-5-isothiocyanate / pharmacokinetics
  • Fluorescent Dyes / pharmacokinetics
  • Fluorophotometry
  • Humans
  • Male
  • Middle Aged
  • Ophthalmic Solutions / pharmacokinetics*
  • Prospective Studies
  • Time Factors
  • Viscosity


  • Dextrans
  • Fluorescent Dyes
  • Ophthalmic Solutions
  • fluorescein isothiocyanate dextran
  • Fluorescein-5-isothiocyanate