The lipid layer and stability of the preocular tear film in newborns and infants

doi:10.1016/S0161-6420(03)00451-2

Ophthalmology

Volume 110, Issue 7, July 2003, Pages 1408-1411

https://doi.org/10.1016/S0161-6420(03)00451-2 Get rights and content

Abstract

Purpose

To measure the thickness of the precorneal lipid layer and the stability of the precorneal tear film in neonates and infants in the first 6 postnatal months.

Design

Prospective, observational case series.

Participants

One hundred ninety-eight neonates and infants in the newborn nursery.

Methods

The Keeler Tearscope Plus (Keeler Instruments Inc., Broomall, PA) was used to evaluate lipid layer thickness by interference fringe biomicroscopy and directly to measure noninvasive tear breakup time (NIBUT). The thickness was classified from level 1 (open meshwork—very thin) to level 9 (colored fringe pattern—very thick).

Main outcome measures

Noninvasive tear breakup time in seconds and classification level of lipid layer thickness.

Results

The mean lipid layer classification for all newborns was 8.3 ± 0.9, with no significant difference between genders. The thickest classifications (levels 8 and 9) were found in 83.3% of all infants. At 3 and 6 postnatal months, all infants studied had a lipid layer classification of 9. Mean NIBUT was 32.5 ± 5.2 seconds (range, 17.6–48.5 seconds) and was not significantly different whether stratified by race, postconceptional age, or birthweight. However, although NIBUT was longer in males at birth (35.1 ± 4.2 seconds versus 29.4 ± 4.5 seconds; P < 0.001), it was equal in both genders at 3 and 6 postnatal months.

Conclusions

In the first 6 postnatal months, the lipid layer of the tear film is much thicker than in adults. The NIBUT in newborns is prolonged compared with adult values. This thick lipid layer in infants provides stability that may help prevent the thin aqueous layer from evaporating.

Section snippets

Materials and methods

The Human Subjects Protection Committee of the Research and Education Institute at Harbor-UCLA Medical Center approved the protocol. Informed consent was obtained from parents or legal guardians of participating minors. The infants were securely wrapped in a swaddling cloth. The eyelids were separated with 2 cotton-tipped applicators. Great care was taken to apply the applicators only to the upper and lower rims of the orbit. No pressure was applied directly on the eye.

The lipid layer of the

Results

Of the 198 neonates studied, 98 were female. The mean birth weight was 3314 ± 543 g (range, 1890–5030 g). At examination, the mean postnatal age was 1.6 ± 1.2 days (range, 0–8 days), and the mean postconceptional age was 38.9 ± 1.8 weeks (range, 32.3–42.6 weeks).

The mean classification of the lipid pattern at birth was 8.3 ± 0.9. All newborns but one had a lipid layer classification exceeding level 5. The thickest classifications (levels 8 and 9) were found in 83.3% of the infants (Fig 2).

Nature of the lipid layer of the tear film

Most previous studies of the characteristics of the tear film of infants looked at the overall secretion of tears. Once Apt and Cullen6 established that newborns did indeed have tears, subsequent studies to characterize tears further generally investigated only the aqueous layer of the preocular tear film.

In 1994, however, Kaercher et al2 in Germany looked at the biophysical properties of the superficial lipid layer in children. Although they used the term infant in their title and text, the

Acknowledgements

The authors thank Nancy G. Berman, PhD, Harbor-UCLA Medical Center, who performed the extensive statistical analysis.

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Correlations between bulk and surface properties of meibomian lipids with alteration of wax-to-sterol esters content
2022, Chemistry and Physics of Lipids
In a recent study (Ewurum et al., 2021), wax (WE) and sterol esters (CE) from human meibum secretions (MGS) were separated and reconstituted with controlled WE/CE ratios (0%, 20%, 30%, 40%, 50%, 75% and 100% CE weight fractions). It was found that the alterations in the CE content of WE/CE mixtures modified the hydrocarbon chain conformation and packing of the mixture. A major question that emerges is whether the spectroscopic packing parameters determined for bulk meibum translate to a change in the performance of meibomian layers at the air/water interface, as it is the surface film functionality that is crucial for the performance of MGS at the ocular surface. The study of human meibum films with Langmuir surface balance was performed to access the surface properties at blink-like deformations of the film area. Surface pressure (π)-area (A) isocycles and stress relaxations were used to assess the layer’s reorganization during area cycling and dilatational elasticity, respectively. The morphology of the films was monitored by Brewster angle microscopy. It was found that the increased order and chain melting temperature of the bulk samples correlated with a raise in the maximum surface pressure attained at minimal surface area and in the transient dilatational modulus of the meibomian layers. Such correlations may allow for development of an improved understanding between the bulk and surface properties of human meibum and of other natural and synthetic tear lipid films.
Lipid conformational order and the etiology of cataract and dry eye
2021, Journal of Lipid Research
Lens and tear film lipids are as unique as the systems they reside in. The major lipid of the human lens is dihydrosphingomylein, found in quantity only in the lens. The lens contains a cholesterol to phospholipid molar ratio as high as 10:1, more than anywhere else in the body. Lens lipids contribute to maintaining lens clarity, and alterations in lens lipid composition due to age are likely to contribute to cataract. Lens lipid composition reflects adaptations to the unique characteristics of the lens: no turnover of lens lipids or proteins; the lowest amount of oxygen of any tissue; and contains almost no intracellular organelles. The tear film lipid layer (TFLL) is also unique. The TFLL is a thin (100 nm) layer of lipid on the surface of tears covering the cornea that contributes to tear film stability. The major lipids of the TFLL are wax esters and cholesterol esters that are not found in the lens. The hydrocarbon chains associated with the esters are longer than those found anywhere else in the body (as long as 32 carbons), and many are branched. Changes in the composition and structure of the 30,000 different moieties of TFLL contribute to the instability of tears. The focus of the current review is how spectroscopy has been used to elucidate the relationships between lipid composition, conformational order and function, and the etiology of cataract and dry eye.
Human meibum chain branching variability with age, gender and meibomian gland dysfunction
2019, Ocular Surface
Citation Excerpt :
A measure of tear film stability is the amount of time it takes for tears to break up following a blink (TBUT) [8]. On average, TBUT decreases with age from over 35 s in infants to ∼8 s in adults [9–13]. With meibomian gland dysfunction, TBUT has been found to be even shorter (below 5 s) and this leads to dry eye symptoms [14–17].
NMR spectroscopy was used to measure hydrocarbon chain branching variability in meibum with age, gender and Meibomian gland dysfuction (MGD). A cohort of 65 meibum donors without dry eye and 31 donors with MGD was studied. Heteronuclear 2D NMR was used to confirm CH₃ resonance assignments allowing us to positively identify 23 of the 27 proton resonances of cholesteryl ester and ¹H resonances due to straight chain, iso-branched and anteiso-branched hydrocarbons. Meibum from donors without dry eye contained 57 ± 1% straight-chains, 23 ± 1% iso-branched chains and 20 ± 1% anteiso-branched hydrocarbon chains. Compared with meibum from donors without dry eye, meibum from donors with MGD contained less, 50 ± 2% straight-chains, more, 32 ± 2% iso-branched chains and the same amount, 18.0 ± 0.07%, of anteiso-branched hydrocarbon chains. Meibum hydrocarbon chain branching did not change with age between 22 and 68 years of age, nor was it influenced by gender. Based on previous studies, one would expect anteiso-branched chains would contribute to lowering the phase transition temperature of meibum, decrease the elasticity of the tear film lipid layer and increase the molecular area and spreading of meibum on the surface of the eye. Although we speculate that the observed differences in iso-chain branching do not influence tear film stability or rheology, the speculation has yet to be tested.
Tear film analysis and evaluation of optical quality: A review of the literature (French translation of the article)
2019, Journal Francais d'Ophtalmologie
La sécheresse oculaire est une pathologie complexe et multifactorielle de la surface oculaire et des larmes. Elle est associée à des symptômes d’atteinte de la surface oculaire qui constituent l’un des motifs les plus fréquents de consultation en ophtalmologie. Malgré leur utilisation fréquente en pratique, les tests cliniques classiques pour évaluer le syndrome sec et les maladies de la surface oculaire–recherche des symptômes, temps de rupture du film lacrymal (BUT), évaluation des glandes de Meibomius, test à la fluorescéine, test de Schirmer–ont montré une reproductibilité et une fiabilité faibles. De plus, les symptômes subjectifs sont souvent peu ou mal corrélés aux signes objectifs. Le film lacrymal étant le premier système traversé par la lumière, la qualité optique de l’œil dépend fortement de l’homogénéité du film lacrymal. Des méthodes d’investigation variées ont été développées pour évaluer le film lacrymal tant sur le plan structural que fonctionnel : la topographie cornéenne, l’interférométrie, la mesure du ménisque de larmes, le taux d’évaporation, l’osmolarité lacrymale ou encore l’aberrométrie. Certaines sont facilement accessibles aux cliniciens alors que d’autres restent du domaine de la recherche clinique. L’ensemble de ces tests permettent néanmoins une meilleure compréhension de la physiopathologie du film lacrymal. Cette revue a pour but de donner un aperçu des tests existants et leur rôle dans l’évaluation de l’importance du film lacrymal sur la fonction visuelle.
Dry eye is a complex multifactorial disease of the ocular surface and tears. It is associated with ocular surface symptoms and is one of the most common causes for ophthalmologic consultation. Despite their frequent use in clinical practice, the usual tests to evaluate dry eye and ocular surface disease–history of symptoms, tear break-up time (TBUT), Meibomian gland evaluation, corneal fluorescein staining, Schirmer test–have shown low reproducibility and reliability. In addition, subjective symptoms are often weakly or poorly correlated with objective signs. Since the tear film is the first system through which light must pass, the optical quality of the eye is highly dependent on the homogeneity of the tear film. Various investigative methods have been developed to evaluate both the structural and functional quality of the tear film, such as corneal topography, interferometry, tear meniscus measurement, evaporation rate, tear osmolarity and even aberrometry. Some are easily accessible to clinicians, while others remain in the field of clinical research. All of these tests provide a better understanding of the pathophysiology of the tear film. This review hopes to provide an overview of the existing tests and their role in evaluating the significance of the tear film in visual function.
The ocular surface in children: A review of current knowledge and meta-analysis of tear film stability and tear secretion in children
2019, Ocular Surface
Citation Excerpt :
Nine of 10 studies conducted in children [4,19,33–37,40,41] assessed tear film stability while six of 10 studies in children assessed tear secretion [33–36,38,41]. Four of 5 studies [42–45] conducted in neonates assessed tear secretion but only one [39] measured tear film stability. Most study participants were derived from control groups to one of several paediatric health conditions including allergic conjunctivitis [19,36,37], diabetes [33,41], juvenile rheumatoid arthritis [34], chronic renal failure [35], premature babies [42–44] and glaucoma patients on topical therapy [38].
A review of ocular surface and meta-analysis of tear stability (tear break up time, TBUT) and tear secretion (Schirmer test) values in healthy children was conducted.
Articles published between 1996 and 2017 indexed on MEDLINE, PubMed, Embase, Scopus and Google Scholar were retrieved using defined search terms. Statistical analysis (including sensitivity analysis and meta-regression) was performed.
23 studies were summarised (5,291 participants; neonates (0–29 days), infants (1 month - 1 year) or children (1–18 years) and a meta-analysis conducted using 15 eligible studies (1,077 participants). The combined mean TBUT in children was 14.64 seconds (s) (95% CI, 11.64, 17.64) and 21.76 s (95% CI, 20.43, 23.09) for sodium fluorescein TBUT and non-invasive TBUT respectively (NIBUT). The combined mean NIBUT was 32.5 s (95% CI, 31.78–33.22) in neonates. The combined mean Schirmer I with and without anesthesia were 16.26 mm/5 min (95% CI, 13.17, 19.36) and 29.30 mm/5 min (95% CI, 27.65, 30.96) in children and 9.36 mm/5 min (95% CI, 6.54, 12.18) and 17.63 mm/5 min (95% CI, 12.03, 23.23) in neonates. Meta-regression showed a significantly lower TBUT in children from studies conducted in Asia (p = 0.004).
There is paucity of data on ocular surface variables in healthy children, making it difficult to draw valid comparisons with adult values.
Interobserver and intraobserver repeatability of lipid layer pattern evaluation by two experienced observers
2014, Contact Lens and Anterior Eye
Citation Excerpt :
This system is less specific than Guillon's classification, because it includes less categories [13]. Other authors have used a more sensitive classification scheme to that of Guillon including inter-categories [26,27]. Hence Isenberg et al. [26] reported the ten LLP grades: (1) lipid absent, (2) open meshwork, (3) detailed meshwork, (4) closed meshwork, (5) meshwork-wave combination, (6) wave, (7) wave-amorphous combination, (8) amorphous, (9) amorphous-colour combination and (10) colour.
The lipid layer plays a major role in limiting evaporation of the tear film. Based on interference phenomena, there is a test directed to lipid layer pattern (LLP) evaluation, but is affected by subjective interpretation of the patterns. The aim of this study is to compare the LLP evaluation between two experienced observers on a group of healthy patients. Furthermore, observers re-evaluated the same images to check their individual repeatability.
LLP was examined using a Tearscope-plus (Keeler, Windsor, UK) attached to a slit lamp. Tear film was recorded by a Topcon DV-3 digital camera video and LLP images were captured. This yielded 124 LLP images that were categorized (based on Guillon's scheme) by two expert observers in two sessions separated by one month. Interobserver repeatability and intraobserver repeatability between both sessions were studied by using Cohen's kappa coefficient.
Comparing LLP categorization between both observers, Cohen's kappa coefficient was 0.615 and 0.633 for first and second session, respectively. When comparing LLP categorization by the same observer between both sessions, Cohen's kappa coefficient was 0.770 and 0.812 for Observer 1 and Observer 2, respectively. These results indicate substantial correlation in all cases. The most frequent misinterpretations were between open and closed meshwork and Wave and closed meshwork patterns.
Although substantial correlation was found between categorizations of experienced observers, misinterpretation of the patterns may appear even in the same observer. Some misinterpretations between adjacent patterns could be palliated by including intermediate patterns between those categories.

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^☆

Manuscript no. 220085

Supported in part by National Center for Research Resources (GCRC grant no.: M01 RR00425, Bethesda, MD); the Sara Kolb Fund, Los Angeles, CA; the Kirchgessner Foundation, Los Angeles, CA; and Research to Prevent Blindness, Inc., New York, New York (Senior Scientific Investigator Award to SJI).

Dr. Guillon has a financial interest in the Tearscope Plus.

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The lipid layer and stability of the preocular tear film in newborns and infants☆

Abstract

Purpose

Design

Participants

Methods

Main outcome measures

Results

Conclusions

Section snippets

Materials and methods

Results

Nature of the lipid layer of the tear film

Acknowledgements

Am J Ophthalmol

Am J Ophthalmol

Ophthalmology

J Invest Dermatol

J Invest Dermatol

The development of tearing in preterm and term neonates

Arch Ophthalmol

Biophysical behaviour of the infant Meibomian lipid layer

Int Ophthalmol

An instrument for in vivo tear film interferometry

Optom Vis Sci

Preocular tear film characteristics of nonwearers and soft contact lens wearers

Optom Vis Sci

Clinical exploration of the lipid phase of the laryngeal film using Tearscope Plus

J Fr Ophtalmol

Newborns do secrete tears

JAMA

A compositional based model for the tear film lipid layer

Trans Am Ophthalmol Soc