Comparison of lacrimation kinetics in dry eye patients and normals.

A 100 mm long and 5 mm wide filter paper strip enclosed in a transparent plastic sheath to prevent evaporation was used to determine the time dependence of wetting of the strip in the anesthetized eyes of dry eye patients and age-matched normals. Prior to the measurements, the paper strips were extracted by lipid solvents and marked at every millimeter length. Wetted length data were plotted against time and the resulting wetting curves were analyzed to obtain the time dependence of the tear secretion rate during lacrimation. Every eye studied exhibited an exponentially decaying tear secretion rate that could be characterized by three kinetic parameters per cycle: the initial and final tear secretion rates and the secretion decay coefficient. The eyes of the sicca patients showed a much simpler lacrimation pattern than did the controls: 60% of the dry eyes exhibited a one-cycle lacrimation pattern while only 5% of the normal group did so. The tear secretion kinetic parameters characterizing the lacrimation pattern reduced to one-cycle were compared. Both the dry eyes and the control eyes started to lacrimate at about the same high initial secretion rate. However, the lacrimation rate was found to decrease faster and to a lower final rate in dry eye patients as opposed to normal controls.

Colloid osmotic pressure of artificial tears.

While the total osmolality of the aqueous tears and tear substitutes has received much attention in the past few years, the colloidal osmolality or the oncotic pressure (which includes the Donnan effect), has received practically no attention except for one single foreign publication. The colloidal osmolality of tears is twentyfold less than that of the corneal stroma, which in turn is less than 1% of the total osmolality of an isotonic solution, i.e. the magnitude of the colloidal osmolality is only a few hundreths of a per cent of total osmolality. This may be the reason why its role was thought to be unimportant by many researchers. Despite its relatively small magnitude when compared to total osmotic pressure, the oncotic pressure has been shown to play a major role in the maintenance of the water balance of bodily tissues and has been used as a diagnostic parameter in alveolar edema. The same principle has been used to formulate a collyrium, Dehydrex, or dextran-containing storage media for excised corneas such as the Kaufman-McCarey medium that have a colloidal osmolality at least equal to that of deturgescent corneal stroma. Such formulations are able to dehydrate corneal stroma even in the total absence of epithelium. Dehydrex has been shown to have a beneficial effect on damaged epithelium and is thought to be the drug of choice for the treatment of recurrent epithelial erosion when other treatment modalities have failed. In the present study, the total osmolality and the oncotic pressure of several artificial tear preparations presently marketed was determined and compared with the oncotic pressure of tears and the corneal stroma. We have found that the oncotic pressure of HypoTears is nearly sixty times higher than that of the leading artificial tear, thus it is comparable to the oncotic pressure of Dehydrex. We believe that the favorable patient acceptance of HypoTears is more likely due to this unusually high oncotic pressure than to its hypoosmolality. Such an artificial tear formulation should be effective in ameliorating microcystic epithelial edema and in increasing impaired epithelial adhesion to the underlying tissue in the cornea.

Kinetics of lacrimal secretions in normal human subject.

A novel technique was used to study the time course of lacrimation in normal human subjects with and without the use of topical anesthetic. The Schirmer technique was modified to eliminate evaporation, to improve absorption capacity, and to allow the determination of the length of paper strip wetted as a function of time. By the use of a theoretical model, the wetting curve thus obtained could be analyzed and basic secretion parameters characteristic of lacrimation kinetics were obtained. Fourteen adult females and six adult males between the ages of 21 and 47 years were included in the study. All the eyes examined exhibited essentially the same type of tear secretion kinetics. Initially, the lacrimation occurred at a high rate which then exponentially diminished to a final, lower value. This exponential cycle of secretion pattern could occur repeatedly during the time of measurement and was not qualitatively altered by the use of topical anesthesia. In addition to time dependence of wetted length, we also determined the weight of the absorbed tears in the filter paper strips in order to obtain the average specific volume of wetting for each measurement. The specific volume of wetting is needed to convert wetting rates to secretion rates. Our results indicate that the novel method used may be developed into a sensitive but clinically applicable technique for determining lacrimation kinetics quantitatively in patients. The interrelationship between the kinetics parameters of tear secretion and the various types of lacrimal deficiencies remains to be determined.

Kinetics of capillary tear flow in the Schirmer strip.

The popular Schirmer test of tearing ability heretofore has never been analyzed kinetically and the interpretation of the results is usually based on implicit, often erroneous assumptions. We have analyzed the capillary flow of fluids in filter paper strips in vitro systems for the cases of unlimited supply and limited supply at constant rates, and in vivo using human subjects, who kinetically corresponded to limited supply having variable rates. The effects of evaporation, surface tension, viscosity, paper pore-size, and the wettability of the cellulose fibers in the paper were also studied. The results show that in the case of unlimited supply, the fluid absorption is kinetically identical to fluid uptake by a horizontal capillary. This implies that the paper strip can absorb fluids only at a certain maximum rate which decreases with time. At lower secretion rates, the rate of wetting length increase is linearly proportional to the secretion rate provided that evaporation is prevented. Evaporation increases with increased wetting length until a steady state is reached where the length of wetting remains constant in time. As long as the secretion rate remains below the maximum uptake rate of the paper strip, the paper and fluid characteristics have a negligible influence on the wetting rate thus the rate of wetting can provide quantitative information on the secretion rate. Wetting length versus time curves obtained in vivo can be best described mathematically by assuming that the initially high secretion rate exponentially decays to a lower, final value. From the data, the magnitude of the initial and final tear secretion rates as well as the secretion rate decay coefficient can be calculated. These physiologically relevant values quantitatively characterize the functioning of the lacrimal system and may have diagnostic value in detecting marginal lacrimal deficiencies and predicting poor contact lens tolerance.