Lachrymal Determinations: Methods and Updates on Biopharmaceutical and Clinical Applications

Abstract

This article displays different procedures used to collect lachrymal fluid and describes some of its applications. Sampling tears represents the main difficulty to produce precise and reproducible results. The direct sampling procedure consists in collecting tears with capillary tubes and has the drawback of demanding previous stimulation that induces major dilution. The indirect method does not require preliminary stimulation but has been held responsible for altering epithelium and promoting leakage from plasma. Schirmer strips and sponges are classically required. Applications are numerous in biopharmaceutical and clinical fields. The determination of endogenous components has great potentiality as a diagnostic tool, but the use of tear as a substitute of plasma does not present clinical relevance. Levels of drugs like immunosuppressive or antibiotic agents are determined in tears to verify that pharmacological concentrations are reached and frequency of administration is deduced from kinetic fitting.

An eye on the dog as the scientist's best friend for translational research in ophthalmology: Focus on the ocular surface

“…Several strategies can be used to overcome current obstacles with the tear volume; however, each come with its own set of drawbacks (listed in parentheses): (i) Sedate or anesthetize the animal to extend collection duration and obtain a larger volume (altered lacrimal functional unit and ocular surface homeostasis) 183,188,202,238,245-247 ; (ii) Pool tear samples from several subjects (reduced statistical power and loss of information regarding interindividual variability) 216,241,245 ; (iii) Induce reflex tearing with a stimulant-either physical (e.g., irritation to nasal mucosa or cornea), chemical (e.g., parenteral pilocarpine or ammonium fumes) or physiological (e.g., yawn or sneeze reflex)-thereby accelerating tear flow and shortening collection time (diluted tear sample, unable to control flow rates) 202,235,246,249 ; (iv) Instill fluid (e.g., saline) on the ocular surface immediately before tear collection, a process called "flush" or "washout" that yields a larger tear sample in a shorter amount of time (diluted tear sample, nonstandardized instilled volume, nonhomogenous mixing of fluid with tears). 193,229,235,[245][246][247]249 In particular, the diluting effect of reflex tearing or flush methods may drop the concentration of low-abundant compounds below the analytical limit of quantification, and potentially mask differences between groups due to reduced variance in tear composition. 229,250 A third limitation of microcapillary tubes is the technical difficulty associated with the collection method.…”

“…229,250 A third limitation of microcapillary tubes is the technical difficulty associated with the collection method. In fact, it is nearly impossible (or very challenging) to avoid reflex lacrimation in a consistent manner, even with cooperative patients and experienced personnel 230,231,235,249,251 ; for instance, capillary tear collection by Markoulli et al resulted in tear secretion that was approximately fourfold faster than basal tear flow in humans (4.6 vs. 1.2 µl/min, respectively). 122,235 Of note, sampling itself may act as a stimulant due to environmental factors (air movement, light) 251 and the stress/anxiety experienced by patients when capillary tubes are used.…”

Lens-care-solution-induced alterations in dynamic interfacial properties of human tear-lipid films

“…We have shown [18,33] that our sessile-bubble technique provides new essential information that is more representative and relevant to in vivo ocular lipid films than results obtained by studying monolayers. This is important because under ocular conditions tear lipids in the form of monolayers are typically not observed.…”

“…The concentration chosen for our experiments-a dilution of 1:10 (LCS to buffer solution)-is significantly lower than the initial dilution right after lens insertion. With basal tear secretion rate of 0.5-2.2 l/min [18], this concentration might be reached within a couple of hours after lens insertion. The effect of LCS concentration in aqueous phase has been checked with two other concentrations, one twice as high (1:5), and the other half of the used dilution (1:20).…”

Tear sample collection using cellulose acetate absorbent filters

“…, 1984; Jones et al. , 1997; Dumortier and Chaumeil, 2004). Glass capillaries are commonly used, but collect tears slowly and erratically, are not well accepted by patients and are not suited for children and special needs populations.…”