A mass and solute balance model for tear volume and osmolarity in the normal and the dry eye.

Tear hyperosmolarity is thought to play a key role in the mechanism of dry eye, a common symptomatic condition accompanied by visual disturbance, tear film instability, inflammation and damage to the ocular surface. We have constructed a model for the mass and solute balance of the tears, with parameter estimation based on extensive data from the literature which permits the influence of tear evaporation, lacrimal flux and blink rate on tear osmolarity to be explored. In particular the nature of compensatory events has been estimated in aqueous-deficient (ADDE) and evaporative (EDE) dry eye. The model reproduces observed osmolarities of the tear meniscus for the healthy eye and predicts a higher concentration in the tear film than meniscus in normal and dry eye states. The differential is small in the normal eye, but is significantly increased in dry eye, especially for the simultaneous presence of high meniscus concentration and low meniscus radius. This may influence the interpretation of osmolarity values obtained from meniscus samples since they need not fully reflect potential damage to the ocular surface caused by tear film hyperosmolarity. Interrogation of the model suggests that increases in blink rate may play a limited role in compensating for a rise in tear osmolarity in ADDE but that an increase in lacrimal flux, together with an increase in blink rate, may delay the development of hyperosmolarity in EDE. Nonetheless, it is predicted that tear osmolarity may rise to much higher levels in EDE than ADDE before the onset of tear film breakup, in the absence of events at the ocular surface which would independently compromise tear film stability. Differences in the predicted responses of the pre-ocular tears in ADDE compared to EDE or hybrid disease to defined conditions suggest that no single, empirically-accessible variable can act as a surrogate for tear film concentration and the potential for ocular surface damage. This emphasises the need to measure and integrate multiple diagnostic indicators to determine outcomes and prognosis. Modelling predictions in addition show that further studies concerning the possibility of a high lacrimal flux phenotype in EDE are likely to be profitable.

Surface tension in tears / Tensión superficial de la lágrima

No disponible

No disponible

Functional aspects of the tear film lipid layer.

The lipid layer is an essential component of the tear film, providing a smooth optical surface for the cornea and retarding evaporation from the eye. The meibomian lipids which compose it are well adapted for this purpose. They form a thin, smooth film whose thickness, and probably composition, influences the rate of evaporation. Their melting range ensures sufficient fluidity for delivery to the tear film from the lid margin reservoirs, while the film itself may exhibit a higher viscosity at the cooler temperature of the ocular surface. The factors governing lipid film formation during the blink are not fully understood, but one view is that the polar lipids, interacting with the aqueous sub-phase of the tear film, spread in advance of the non-polar components, which form the bulk of the film. The meibomian lipids stabilise the tear film by lowering its free energy; they carry water into the film during its formation and interact with lipid-binding proteins in the aqueous phase, such as tear lipocalin. The lipocalins, complexed with other tear components, may also contribute to the high, non-Newtonian viscosity of the tear film and its low surface tension, features which are essential for tear film stability. Formation of the lipid film is a complex process. Lipid is delivered to the tear film in the up-phase of the blink, more from the lower than the upper reservoir. The lipid layer comes to a stop well after completion of the blink and remains relatively immobile until it is compressed in the down-phase of the blink that follows. Then, it either retains its structure in a series of subsequent blinks, or is completely re-constituted after mixing with the reservoir lipids. Delivery of meibomian lipid to the marginal reservoirs is mainly the result of continuous secretion, under neural and hormonal control, supplemented by lid action. The reservoirs provide a hydrophobic barrier to tear overspill and to contamination by skin lipids which might destabilise the tear film. They probably also provide the chief route for meibomian lipid excretion.

The contribution of meibomian disease to dry eye.

The tear film lipid layer is the major barrier to evaporation from the ocular surface. A decrease in its thickness or functional integrity may cause evaporative dry eye (EDE). Obstructive meibomian gland dysfunction (MGD) is the most common cause of EDE and occurs as a primary disorder or secondary to acne rosacea, seborrheic or atopic dermatitis, and with cicatrizing conjunctival disorders, such as trachoma, erythema multiforme, and cicatricial pemphigoid. MGD may be an incidental finding in asymptomatic eyes, or it may be responsible for irritative lid symptoms in the absence of dry eye. MGD-dependent EDE is diagnosed on the basis of a defined degree of MGD in a symptomatic patient showing typical ocular surface damage in the absence of an aqueous tear deficiency. When MGD occurs in a background of aqueous tear deficiency (ATD), then an additional evaporative component may assumed, depending on the extent of meibomian obstruction. However, definitive criteria are not yet established. The clinical severity of dry eye is greatest when ATD and EDE occur together, particularly in Sjogren syndrome. A hypothesis is proposed to explain the steps leading to primary, simple MGD and subsequent EDE.

Tears in health and disease.

PURPOSE: A brief review of normal tear function and changes resulting from disease. METHODS: The factors contributing to normal tear physiological function are considered, and the effect of changes in composition, as reported in the literature, is surveyed, with emphasis on the physical performance of the tears. Major classes of tear tests which would reveal functional changes are listed. RESULTS: Where possible, changes of measurable functions in disease are described. Gaps in our current knowledge are indicated. CONCLUSIONS: Many techniques exist for examination and assessment of both normal and disease tears, but further development is needed to adapt some of these to clinical situations, and to make them more specific diagnostic tests.

Tear meniscus changes during cotton thread and Schirmer testing.

PURPOSE: To elucidate the effect of the cotton thread test (CT-T) and Schirmer test (S-T) on the tear reservoir by evaluating the radius of tear meniscus curvature. METHODS: The radii (R) of the central lower tear menisci were measured by a newly developed video meniscometer in 11 eyes of 11 normal volunteers (6 men, 5 women; mean age, 27.7 +/- 3.6 years [SD]) and 9 eyes of 9 patients with tear deficiency and severe dry eye in whom the puncta had been therapeutically occluded (9 women; mean age, 50.6 +/- 10.4 years). In this dry eye group, the absence of reflex tearing, coupled with the absence of lacrimal drainage due to punctal occlusion allowed more precise observation of the removal of tears from the meniscus. A 1-minute CT-T was performed, followed after an interval of 10 minutes by a 1-minute S-T. Tear meniscus curvature was documented before (R:(0)) and during the tests at 30 seconds (R(30)) and 60 seconds (R:(60)). RESULTS: In the normal group, respective R values (CT-T; S-T; mean +/- SD mm) were R(0) (0.26 +/- 0.11; 0.26 +/- 0. 07), R(30) (0.27 +/- 0.16; 0.20 +/- 0.13), and R(60) (0.29 +/- 0.15; 0.23 +/- 0.21); and in the dry eye group, respective R: values (CT-T; S-T) were R(0) (0.59 +/- 0.23; 0.51 +/- 0.19), R(30) (0.52 +/- 0.25; 0.22 +/- 0.09), and R(60) (0.51 +/- 0.19; 0.21 +/- 0.08). It was demonstrated in the dry eye group that R was diminished more by the S-T than by the CT-T in the time course of the measurement (P = 0.01). In the dry eye group alteration of R occurred within the first 30 seconds, and in this group significant correlation was found between R(0) and the S-T result (r = 0.67; P = 0.05), and between R(60)- R(0) and the S-T result (r = -0.81; P = 0.01). Also, there was a significant correlation between R(60)- R(0) and the S-T result in the normal group (r = 0.71; P = 0.02). There were no significant correlations between R(0) or R(60)- R(0) and the CT-T results in either group. CONCLUSIONS: These studies afford some insight into the dynamics of the Schirmer test, suggesting that wetting is influenced by the negative hydrostatic pressure within the tear meniscus. With the protocol used, no conclusion could be drawn about the relation between meniscus radius and wetting of the cotton thread.

Reflective meniscometry: a new field of dry eye assessment.

PURPOSE: To report a newly developed noninvasive method to measure the radius of tear meniscus curvature (reflective meniscometry) and its application to normal eyes, dry eyes, and other ocular surface conditions. METHODS: Two types of meniscometer--photographic and video--were devised. Both use tear meniscus as a concave mirror, and a specular reflex of an illuminated target at the meniscus was photographed or videotaped to obtain the radius of tear meniscus curvature. The photographic system was applied to 45 normal and 32 dry eyes; in the dry eyes, the radius of tear meniscus curvature was compared to the results of other dry eye examinations. The video system was used to examine meniscus formation on the ocular surface in patients with ocular surface irregularities. RESULTS: The radii of tear meniscus curvature were significantly lower in dry eyes (0.250 +/- 0.086 mm, mean +/- SD) than in normal eyes (0.365 +/- 0.153; p = 0.0003). There were significant correlations between the radius and fluorescein staining score (p = 0.0032) and the grading of interference colors on the precorneal oil film (p = 0.0125). Videomeniscometry demonstrated the tear meniscus to be very stable and proved to be useful in the study of menisci at the edge of rigid contact lenses and other menisci encountered in ocular surface disorders. CONCLUSIONS: Measurement of the radius of tear meniscus curvature may be useful in the diagnosis of dry eyes. Reflective meniscometry is expected to find wide applications in the analysis of tear meniscus in ocular surface disorders.

Components responsible for the surface tension of human tears.

PURPOSE: It was previously thought that the surface tension of tears was due to dissolved mucin, but it has recently been shown that very little mucin is present. The surface tensions of solutions of commercial mucin, lysozyme, lactoferrin or secretory IgA are all higher than that of tears. The influence of tear lipocalin and lipids remained to be tested. METHODS: Surface tension was determined by a micro-method on pooled intact stimulated human tears, and following extraction with lipid solvents. The extracted material was also added back, as was a variety of lipid standards (phospholipids, glycolipids, sterols, etc.). TLC and GLC were used in partial identification of the extract. Another lipocalin, bovine beta-lactoglobulin, was also tested alone and mixed with tear lipids, model lipids, or model tear proteins. RESULTS: Intact tears had a surface tension of 42-46 mN/m, but after lipid extraction this rose to 53-55.5 mN/m. Addition of lipids to the delipidised tear fluid gave a range of tensions from 42 to 49 mN/m, with the greatest effects shown by phospholipids (phosphatidylcholine, sphingomyelin), but full recovery was only achieved by using the extracted lipid material. Human meibomian oil was less effective. The GLC peak profile of the extract was markedly different from meibomian oil, and the TLC pattern was consistent with the presence of glycolipids. CONCLUSIONS: The surface tension of tears is due to a complex of tear lipocalin with a polar lipid fraction extractable from tears by lipid solvents and different from meibomian lipid. Lipocalin and this lipid fraction may be secreted together by the lacrimal gland.

Assessment of meibomian gland function in dry eye using meibometry.

OBJECTIVE: To study meibomian gland function in dry eyes using meibometry. METHODS: Forty-two patients with clinically diagnosed dry eye that was reclassified as meibomian gland dysfunction (MGD [n = 12]), aqueous-tear deficiency (AD [n = 10]), MGD combined with AD (n = 2), "incomplete" dry eye (n = 12), and non-dry eye (6 eyes) were compared with 41 healthy control subjects. The following 2 techniques of meibometry were applied: direct meibometry (DM) measuring lipid imprints using the Meibometer, and integrated meibometry (IM) using image-scanning and computer densitometry. Tear film lipid layer thickness was assessed using interference microscopy. RESULTS: Imprints were homogeneous for all subjects except those with MGD. Mean+/-SE readings on results of DM were 127.24+/-24.4 for MGD, 306.4+/-9.2 for AD, 248.6+/-13.2 for incomplete dry eye, and 268.5+/-6.3 for controls, showing lower values in the MGD group relative to all others (P<.001). Results of IM gave similar results (P<.001, P =.01, and P<.001, respectively). Lipid layers appeared lower for the MGD group than others. CONCLUSIONS: Compared with controls, lid lipid levels are reduced in patients with MGD, and increased in women with AD. Lipid layer thickness is increased in women with AD compared with patients with MGD. Both meibometric techniques may be useful for evaluating MGD. Although DM requires special equipment (the Meibometer), it provides a record of immediate diagnostic value. Although IM is less effective than DM, it offers visual documentation of the lipid imprint, which may itself be of diagnostic value, and uses equipment available in many laboratories.

Physical properties of stimulated and unstimulated tears.

It has long been assumed that unstimulated tears are more thoroughly equilibrated with epithelial secretions than stimulated tears, since they are in contact with tarsal, bulbar and corneal surfaces for longer. It was also believed from results with model solutions that soluble mucin is responsible for the observed surface tension and viscosity of tears. If longer contact means more mucin is dissolved in the aqueous tears, then the surface activity (surface tension lowered by mucin) and viscosity (raised by mucin) of tears should therefore be enhanced in unstimulated over stimulated tears. Pools of stimulated and minimally-stimulated tears were collected from a group of healthy adult volunteers by glass capillary. Viscosities were measured in the Contraves Low Shear 30 rheometer over the range of shear rates 0-130 sec-1. Surface tension was measured in the collection capillaries by a micro-technique, before and after refrigerated storage. Both surface tension and viscosity were determined for a variety of tear proteins and mucins. No significant difference was found between the viscosity/shear rate plots of stimulated and unstimulated tear samples. The viscosities of solutions of individual tear proteins were low, except for the combination of lysozyme and secretory IgA. Surface tensions were also similar in both cases, and unchanged by storage at room temperature or refrigeration, indicating no significant loss of surface-active material by adsorption on the capillary walls. Results with model mucin solutions gave a variety of results indicating either little surface activity or losses due to wall adsorption. Tear proteins, individually or in combination, did not lower surface tension to the level of tears. Tear viscosity seems not to depend on the level of dissolved mucins. This suggests either that a constant level of these is picked up even by short-term contact with ocular surfaces, or that viscosity arises from currently unknown materials which vary little with tear flow rate. This type of shear-dependent viscosity is most easily simulated in model solutions with polyionic linear macromolecules, including mucins. The contribution of individual proteins to overall viscosity is small, but combinations including lysozyme show tear-like characteristics, and may indicate that proteins whose concentration is relatively independent of tear flow rate combine with other tear components (possibly including mucins or lipids) to produce their full effect on tear viscosity. The surface tension results suggest that mucins are not of primary importance. Theories of tear film structure and performance need revision.

The meibomian glands and tear film lipids. Structure, function, and control.

Meibomian gland disease--and, in particular, obstructive meibomian gland disease--makes an important contribution to ocular surface disease, in the form of meibomian keratoconjunctivitis. With improved methods for the study of meibomian oil composition and function, we are moving closer to the possibility of distinguishing the contribution of meibomian deficiency, as opposed to inflammatory events, to this disorder. More importantly, where aqueous tear deficiency and meibomian gland disease coincide in patients with dry eye, we are closer to the possibility of distinguishing their relative contributions to the dry eye state. This has implications for future therapies.

An instrument for quantifying meibomian lipid on the lid margin: the Meibometer.

An instrument, the Meibometer, is described for estimating the casual level of meibomian lipid on the human eyelid margins, adapted from a commercially-available instrument used for measurement of skin surface lipid. A loop of plastic tape is pressed onto the everted lower lid margin to lift off a blot of lipid. The resultant change in light transmission of the tape is read by a photometer. Readings are not affected by side (R or L), time of day or lid surface temperature. After cleaning lipid from the lid margins with hexane, the rate of recovery per 10 blinks, as a percentage of the pre-cleaned level, was measured as 33.7 +/- 5.8 (mean +/- SE). This rate of delivery appears to provide enough lipid for complete resurfacing of the preocular tear film with every blink. Over short periods no detectable lipid was delivered in the absence of blinking.