Associations between Serial Intravitreal Injections and Dry Eye.

PURPOSE: To investigate the effects of serial intravitreal injections (IVIs) on the ocular surface and meibomian glands (MGs) in patients treated with anti-vascular endothelial growth factor (anti-VEGF) for neovascular age-related macular degeneration (nAMD). DESIGN: Retrospective, controlled, observational study. PARTICIPANTS: Patients with nAMD receiving unilateral IVIs with anti-VEGF agents. The fellow eye was used as control. METHODS: Tear film and ocular surface examinations were performed on a single occasion at a minimum of 4 weeks after IVI. A pre-IVI asepsis protocol with povidone-iodine (PVP-I) was applied. MAIN OUTCOME MEASURES: Upper and lower MG loss, tear meniscus height (TMH), bulbar redness (BR) score, noninvasive tear break-up time (NIBUT), tear film osmolarity (TOsm), Schirmer test, corneal staining, fluorescein tear film break-up time (TBUT), meibomian gland expressibility (ME), and meibum quality. RESULTS: Ninety patients with a mean age of 77.5 years (standard deviation [SD], 8.4; range 54-95) were included. The median number of IVIs in treated eyes was 19.5 (range, 2-132). Mean MG loss in the upper eyelid was 19.1% (SD, 11.3) in treated eyes and 25.5% (SD, 14.6) in untreated fellow eyes (P = 0.001). For the lower eyelid, median MG loss was 17.4% (interquartile range [IQR], 9.4-29.9) in treated eyes and 24.5% (IQR, 14.2-35.2) in fellow eyes (P < 0.001). Mean BR was 1.32 (SD, 0.46) in treated eyes versus 1.44 (SD, 0.45) in fellow eyes (P = 0.017). Median TMH was 0.36 mm (IQR, 0.28-0.52) in treated eyes and 0.32 mm (IQR, 0.24-0.49) in fellow eyes (P = 0.02). There were no differences between treated and fellow eyes regarding NIBUT, TOsm, Schirmer test, corneal staining, fluorescein TBUT, ME, or meibum quality. CONCLUSIONS: Repeated IVIs with anti-VEGF with preoperative PVP-I application was associated with reduced MG loss, increased tear volume, and reduced signs of inflammation compared with fellow nontreated eyes in patients with nAMD. This regimen may thus have a beneficial effect on the ocular surface. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found after the references.

Improving Stability of Tear Film Lipid Layer via Concerted Action of Two Drug Molecules: A Biophysical View.

The tear film at the ocular surface is covered by a thin layer of lipids. This oily phase stabilizes the film by decreasing its surface tension and improving its viscoelastic properties. Clinically, destabilization and rupture of the tear film are related to dry eye disease and are accompanied by changes in the quality and quantity of tear film lipids. In dry eye, eye drops containing oil-in-water emulsions are used for the supplementation of lipids and surface-active components to the tear film. We explore in detail the biophysical aspects of interactions of specific surface-active compounds, cetalkonium chloride and poloxamer 188, which are present in oil-in-water emulsions, with tear lipids. The aim is to better understand the macroscopically observed eye drops-tear film interactions by rationalizing them at the molecular level. To this end, we employ a multi-scale approach combining experiments on human meibomian lipid extracts, measurements using synthetic lipid films, and in silico molecular dynamics simulations. By combining these methods, we demonstrate that the studied compounds specifically interact with the tear lipid film enhancing its structure, surfactant properties, and elasticity. The observed effects are cooperative and can be further modulated by material packing at the tear-air interface.

Loss of ß Epithelial Sodium Channel Function in Meibomian Glands Produces Pseudohypoaldosteronism 1-Like Ocular Disease in Mice.

Human subjects with pseudohypoaldosteronism-1 because of loss-of-function mutations in epithelial sodium channel (ENaC) subunits exhibit meibomian gland (MG) dysfunction. A conditional ßENaC MG knockout (KO) mouse model was generated to elucidate the pathogenesis of absent ENaC function in the MG and associated ocular surface disease. ßENaC MG KO mice exhibited a striking age-dependent, female-predominant MG dysfunction phenotype, with white toothpaste-like secretions observed obstructing MG orifices at 7 weeks of age. There were compensatory increases in tear production but higher tear sodium and indexes of mucin concentration in ßENaC MG KO mice. Histologically, MG acinar atrophy was observed with ductal enlargement and ductal epithelial hyperstratification. Inflammatory cell infiltration was observed in both MG and conjunctiva of ßENaC MG KO mice. In older ßENaC MG KO mice (5 to 11 months), significant ocular surface pathologies were noted, including corneal opacification, ulceration, neovascularization, and ectasia. Inflammation in MG and conjunctiva was confirmed by increased cytokine gene and protein expression and positive Ly-6B.2 immunostaining. Cell proliferation assays revealed lower proliferation rates of MG cells derived from ßENaC MG KO than control mice, suggesting that ßENaC plays a role in cell renewal of mouse MG. Loss of ßENaC function resulted in MG disease and severe ocular surface damage that phenocopied aspects of human pseudohypoaldosteronism-1 MG disease and was sex dependent.

Evaluation of Long-Term Silicone Hydrogel Use on Ocular Surface Inflammation and Tear Function in Patients With and Without Meibomian Gland Dysfunction.

OBJECTIVES: To determine whether silicone hydrogel (SH) contact lens (CL) use, with or without meibomian gland dysfunction (MGD), promotes ocular surface inflammation. METHODS: Subjects wearing SH-CL for at least 6 months who also had coexisting MGD (group 1, n=20), SH-CL users who did not have MGD (group 2, n=20), patients who had MGD but did not use CL (group 3, n=20), and healthy CL-naive individuals with no known systemic or ocular diseases (group 4, n=20) were included in this cross-sectional, single-center study. All subjects underwent tear function tests consisting of tear break-up time (tBUT), ocular surface staining, Schirmer test, and the Ocular Surface Disease Index (OSDI) questionnaire, as well as determination of tear IL-1RA, IL-1ß, IL-2, IL-2R, IL-4, IL-5, IL-6, IL-7, IL-8, IL-10, IL-12, IL-13, IL-15, IL-17, IFN-α, IFN-γ, TNF-α, granulocyte-macrophage colony-stimulating factor, IP-10, monokine induced by gamma interferon, RANTES, eotaxin, MIP-1α, MIP-1ß, and MCP-1 levels using Luminex multicytokine immunobead assay. Intergroup comparisons were made using one-way analysis of variance or Kruskal-Wallis test. RESULTS: The tBUT was lower (P=0.048) and ocular surface staining (P=0.032) as well as OSDI scores (P=0.001) were higher in group 1 but not in groups 2 or 3 when compared with those in the control group. Tear cytokine levels were similar across all groups. None of the tear cytokine levels were elevated in CL wearers (groups 1 and 2) or those with MGD (groups 1 and 3) as compared to those in control subjects. CONCLUSION: Silicone hydrogel contact lens use with concomitant MGD is not associated with cytokine-driven ocular surface inflammation but may impact tear function leading to dry eye symptoms.

Meibomian Gland Dysfunction in Primary and Secondary Sjögren Syndrome.

PURPOSE: We hypothesized that women with primary (pSS) and secondary Sjögren syndrome (sSS; with systemic lupus erythematosus [SLE] or rheumatoid arthritis [RA]) have meibomian gland dysfunction (MGD). We sought to test our hypothesis. METHODS: Subjects with pSS, sSS + SLE, sSS + RA, and non-SS-related MGD were recruited from the Sjögren's Syndrome Foundation or outpatient clinics at Tufts University School of Dental Medicine or Brigham and Women's Hospital. The control population was recruited from the Greater Boston area. After providing written informed consent, the subjects underwent an eye examination and/or completed two questionnaires that assess symptoms of dry eye disease (DED). RESULTS: Our results demonstrate that pSS and sSS patients have MGD. These subjects had meibomian gland orifice metaplasia, an increased number of occluded meibomian gland orifices, and a reduced quality of meibomian gland secretions. Further, patients with pSS, sSS + SLE, sSS + RA, and MGD had significant alterations in their tear film, lid margin, cornea, and conjunctiva. Symptoms of DED were increased ∼10-fold in all pSS, sSS, and MGD groups relative to controls. CONCLUSIONS: Our findings support our hypothesis and show that individuals with pSS, sSS + SLE, and sSS + RA have MGD. In addition, our study indicates that patients with pSS and sSS have both aqueous-deficient and evaporative DED.

Noninvasive ocular surface analyzer as an adjunct in diagnosis and estimating prevalence of meibomian gland dysfunction: Hospital-based comparative study.

Purpose: To assess the role of noninvasive ocular surface analyzer (OSA) in workup of meibomian gland dysfunction (MGD) and to estimate hospital-based prevalence of MGD using this objective device. Methods: The study recruited 113 consecutive participants attending the ophthalmology outpatient department of a tertiary care hospital. All participants were administered a symptom questionnaire. Participants underwent a comprehensive ocular examination, including slit-lamp biomicroscopy and meibomian gland expression. Lipid layer thickness (LLT), noninvasive tear breakup time (NIBUT), tear meniscus height (TMH), and meibomian gland loss (MGL) were assessed using OSA. The presence of either or both reduced/absent meibum secretion and cloudy to toothpaste-like secretion was diagnosed as MGD. Results: Prevalence of total MGD was 57.52% (95% confidence interval [95% CI]: 48.3%-66.8%) and that of symptomatic MGD was 42.5% (95% CI: 33.2%-51.7%). Prevalence of total and symptomatic MGD was highest in those aged ≥50 years (P < 0.001 and P = 0.004, respectively). Computer vision syndrome increased the odds of symptomatic MGD (odds ratio [OR]: 4.3). NIBUT and MGL significantly differed in MGD and non-MGD groups (P = 0.023 and P < 0.001, respectively). LLT significantly differed between asymptomatic and symptomatic cases (P = 0.033). MGL >25% increased the odds of having MGD (OR: 19.1). Significant negative correlations were observed between MGL and NIBUT (P = 0.04) and between MGL and LLT (P = 0.02). MGL demonstrated the highest diagnostic accuracy for MGD (AUC = 0.827, sensitivity = 75.4%, specificity = 85.4%, cut-off value: ≥26%). Conclusion: MGD is a common disorder in adults attending the ophthalmology outpatient services of a tertiary eye care hospital. Incorporating noninvasive OSA in clinical practice can aid in rapid and reliable measurements of MGD-related parameters.

Immuno Tomography (IT) and Imaging Mass Cytometry (IMC) for constructing spatially resolved, multiplexed 3D IMC data sets.

PURPOSE: We have previously used Immuno Tomography (IT) to identify label-retaining stem cell populations in the cornea and meibomian gland. While this method provides the unique ability to quantify stem cell populations comprised of 1-4 cells, the number of antigens that can be sequentially used to characterize these unique cells is limited by antigen stability after antibody stripping and re-probing. To address this deficiency, we have evaluated the capability of Imaging Mass Cytometry™ (IMC™) to generate multiplexed images using metal-conjugated antibodies to label IT plastic sections and generate 3-dimensional IMC data sets (3D IMC). METHODS: K5-H2B-GFP mice, 56 days after doxycycline chase, were sacrificed and eyelid tissue processed for IT. A total of 400 serial, plastic sections, 2 µm thick, were then probed using metal-tagged antibodies specific for sox 9, collagen type I, E-cadherin, Ki67, GFP, αSMA, vimentin, and DNA intercalator. Multiplexed images were then generated using an Imaging Mass Cytometry system (Fluidigm®), and 3D reconstructions were assembled. RESULTS: All 8 metal-labeled tags were detected and their images were successfully assembled into 3D IMC data sets. GFP-labeled nuclei were identified within the meibomian glands in comparable numbers to those previously reported for slow-cycling meibomian gland stem cells. CONCLUSIONS: These findings demonstrate that IMC can be used on plastic sections to generate multiplexed, 3D data sets that can be reconstructed to show the spatial localization of meibomian gland stem cells. We propose that 3D IMC might prove valuable in more fully characterizing stem cell populations in different tissues.

Meibomian Gland Dysfunction in a Hospital-Based Population in Central India.

PURPOSE: To estimate the prevalence of meibomian gland dysfunction (MGD) in a hospital-based population in India. METHODS: This cross-sectional study screened 3410 subjects ≥20 years or older attending the outpatient department by systematic random sampling. The patients were subjected to a comprehensive eye examination, Ocular Surface Disease Index questionnaire, fluorescein tear film breakup time, Schirmer I test, lissamine green stain, lid margin changes, and meibomian gland expression. MGD was diagnosed when 1 or both of the following was present in at least 1 eye: reduced or absent meibum secretion and cloudy to inspissated toothpaste-like secretion on digital pressure over the eyelids. RESULTS: The study included 570 subjects with a mean age of 49.3 ± 16.2 (20-84) years. MGD was diagnosed in 317 (55.61%) subjects, of whom 272 (47.7%) had only MGD and 45 (7.9%) had coexisting MGD and aqueous tear deficiency. The age-adjusted prevalence rate of MGD was 48.4% (95% confidence interval: 43.9-52.1). This rate increased significantly with age (P < 0.001) in both men (P < 0.001) and women (P < 0.001). The crude and age-adjusted prevalence of symptomatic MGD (Ocular Surface Disease Index score ≥13) was 26.1% (71/272) and 32.9% (95% confidence interval: 27.4-38.6), respectively. The prevalence of symptomatic MGD significantly declined with increasing age (P = 0.003), and this was reflected in both men (P = 0.013) and women (P = 0.179) but was not statistically significant in the latter. CONCLUSIONS: The prevalence of MGD was higher in Indian subjects than that previously reported. Although the total MGD prevalence increased with age, the prevalence of symptomatic MGD decreased. Asymptomatic MGD was more common than symptomatic MGD.

Cyclic Change of Fatty Acid Composition in Meibum During the Menstrual Cycle.

Purpose: To evaluate the fatty acid (FA) composition in the meibum of pre- and postmenopausal women and age-matched men. Methods: This prospective study involved 24 healthy subjects; six premenopausal women in their 30s with a regular menstrual cycle (young-female [yF] group), six postmenopausal women in their 60s (elderly-female [eF] group), and 12 age-matched men (i.e., young-male [yM] and elderly-male [eM] groups, respectively). The menstrual cycle was divided into six phases (phase I-VI). Meibum was obtained from the meibomian gland orifices via a Daviel spoon, and its FA composition was then analyzed via gas chromatography mass spectrometry (GC-MS). Principal component analysis (PCA) was performed on the GC-MS results. Results: The mean FA composition of all subjects was 40% saturated FAs (SFA) and 60% unsaturated FAs (UFAs). The PCA results of all groups indicated two categories (PC1 [77.5%] and PC2 [12.4%]); one consisting of yF-group samples of mainly phase II and III and the other consisting of the yF-group samples of the rest of the cycle, as well as from eF-group, yM-group, and eM-group samples. Each group had a distinctive nature. The FAs that most contributed to PC1 were C14:0, C16:0, and C18:0 in a positive correlation, and C18:1n9 in a negative correlation. Conclusions: FA composition noticeably changes during the menstrual cycle and is somewhat affected by sex and age. The ratio of SFAs (C16:0, C18:0) to mono-UFAs (C18:1n9) in the FA composition might have an impact on the lipid quality of meibum, thus suggesting alteration of its melting temperature and viscosity.

Direct Visualization of Continuous Meibum Secretion From the Orifices of Meibomian Glands to the Tear Film.

PURPOSE: To present a new method to directly visualize meibum secretion on the tear film from meibomian gland orifices and show that meibum is continuously secreted between blinking. METHODS: Eighteen patients with dry eye syndrome and 17 healthy subjects were included in the study. We used the Lipiscanner to evaluate the tear film lipid layer. The lipid layer was classified into thick, normal, and thin lipid layer. The lipid layer on the lower tear meniscus of the right eye was observed after a drop of saline solution was applied to the eye. We recorded continuous meibum secretion onto the tear meniscus surface. We calculated the rate of continuous meibum secretion by analyzing videos. Noncontact meibography was performed for meibomian glands in the lower eyelid. The quality of meibum from the 5 orifices at the same area was then scored. RESULTS: The mean continuous meibum secretion rate was 2.7 pL/s in the healthy group and 8.0 pL/s in the dry eye group. The rates were 1.3, 6.7, and 9.4 pL/s in the thin, normal, and thick tear film lipid layer group, respectively. They were 3.4, 3.4, 10.7, and 18.1 pL/s in grade 0, 1, 2, and 3 meibomian gland dropout groups, respectively. The rates were 0.00, 4.7, 10.1, 2.0, and 0.7 pL/s in the normal meibum, yellow without increased viscosity, yellow with increased viscosity, toothpaste, and no meibum groups, respectively. CONCLUSIONS: We showed how to visualize meibum being secreted into the tear film from the meibomian gland orifices, and we were able to observe the continuous secretion of meibum between blinks.

Meibomian Gland Dysfunction Model in Hairless Mice Fed a Special Diet With Limited Lipid Content.

PURPOSE: A novel meibomian gland dysfunction (MGD) model was developed to facilitate understanding of the pathophysiology of MGD and to evaluate treatment with azithromycin ophthalmic solution (azithromycin). MGD was induced in HR-1 hairless mice by feeding them a special diet with limited lipid content (HR-AD). METHODS: Male HR-1 hairless mice were fed an HR-AD diet for 16 weeks. Development of MGD was assessed by histopathology at 4-week intervals. The lid margin was observed by slit-lamp examination. After cessation of the HR-AD diet, the mice were fed a normal diet to restore normal eye conditions. Expression of cytokeratin 6 was determined by immunostaining. We evaluated the effects of topically applied azithromycin on the plugged orifice in this model. RESULTS: After mice were fed the HR-AD diet, histopathology analysis showed hyperkeratinization of the ductal epithelium in the meibomian gland. Ductal hyperkeratinization resulted in the loss of acini, followed by atrophy of the gland. Slit-lamp examination revealed a markedly plugged orifice, telangiectasia, and a toothpaste-like meibum compared with that of a normal eyelid. Cessation of feeding with HR-AD ameliorated both the MGD signs and the expression of cytokeratin 6, restoring the tissue to a histologically normal state. Azithromycin treatment significantly decreased the number of plugged orifices and ameliorated atrophy, as revealed by histopathologic analysis. CONCLUSIONS: We developed a novel model that mimics human MGD signs in HR-1 hairless mice fed an HR-AD diet. Azithromycin treatment led to therapeutic improvement in this model. This MGD model could be useful for the evaluation of drug candidates for MGD.

Incomplete response to artificial tears is associated with features of neuropathic ocular pain.

AIMS: Artificial tears are first-line therapy for patients with dry eye symptoms. It is not known, however, which patient factors associate with a positive response to therapy. The purpose of this study was to evaluate whether certain ocular and systemic findings are associated with a differential subjective response to artificial tears. METHODS: Cross-sectional study of 118 individuals reporting artificial tears use (hypromellose 0.4%) to treat dry eye-associated ocular pain. An evaluation was performed to assess dry eye symptoms (via the dry eye questionnaire 5 and ocular surface disease index), ocular and systemic (non-ocular) pain complaints and ocular signs (tear osmolarity, tear breakup time, corneal staining, Schirmer testing with anaesthesia, and eyelid and meibomian gland assessment). The main outcome measures were factors associated with differential subjective response to artificial tears. RESULTS: By self-report, 23 patients reported no improvement, 73 partial improvement and 22 complete improvement in ocular pain with artificial tears. Patients who reported no or partial improvement in pain with artificial tears reported higher levels of hot-burning ocular pain and sensitivity to wind compared with those with complete improvement. Patients were also asked to rate the intensity of systemic pain elsewhere in the body (other than the eye). Patients who reported no or incomplete improvement with artificial tears had higher systemic pain scores compared with those with complete improvement. CONCLUSIONS: Both ocular and systemic (non-ocular) pain complaints are associated with a differential subjective response to artificial tears.

Diffuse lamellar keratitis: evaluation of etiology, histopathologic findings, and clinical implications in an experimental animal model.

PURPOSE: To induce diffuse lamellar keratitis (DLK) and investigate the potential causative agents in an animal model. SETTING: Magill Research Center for Vision Correction, Storm Eye Institute, Medical University of South Carolina, Charleston, South Carolina, USA. METHODS: In 70 eyes of 35 Dutch Belted rabbits, a corneal flap was cut and the interface randomly exposed to 1 of 7 substances: Pseudomonas aeruginosa endotoxin, 1 of 2 Staphylococcus aureus exotoxins, meibomian gland secretion, povidone-iodine 10%, Palmolive Ultra soap, and Klenzyme soap. Slitlamp examinations were performed 1, 3, 5, and 7 days postoperatively. The DLK was staged from 1 to 4. On day 7, the rabbits were killed and the eyes enucleated and processed for histopathologic examination. RESULTS: At the end of the study, 54 eyes (46 exposed, 8 control) were available for evaluation. The 8 eyes studied concurrently in the control group remained clear and did not show interface inflammation. Thirty-one of 46 eyes (67%) treated with the various test substances developed DLK. The highest DLK rates were found with the cleaning soap Palmolive Ultra (100%; P =.022) and P. aeruginosa lipopolysaccharide endotoxin (90%; P =.026). CONCLUSIONS: Interface inflammation was consistently induced in the animal model. All 7 agents caused DLK in at least some eyes. The histopathologic evaluation showed the morphologic profile of the marked inflammatory cellular reaction that occurred in almost all the specimens.

Interactions of Meibomian gland secretion with polar lipids in Langmuir monolayers.

The surface interactions of Meibomian gland secretion (MGS) with polar lipid (PL), Egg Sphingomyelin (SM) or Dipalmitoylphosphatidylcholine (DPPC), are studied in mixed pseudo-binary films formed at the air/water interface of Langmuir surface balance. The behavior of the mixed films during slow quasi-equilibrium compression and during fast dynamic compression-decompression is registered by measurements of surface pressure and surface potential, and by monitoring film morphology with Brewster Angle Microscopy (BAM). Quasi-equilibrium compression isotherms are used to calculate the excess Gibbs and Helmholtz energy of mixing between MGS and PLs and thus to evaluate the interactions between the lipid compounds at the interface. The effects of PLs on the mixed film's elastic moduli of area compressibility, morphology and capability to attain high surface pressures are also examined. PLs interact with MGS with different strength and in different manner: MGS-SM interaction is weak and might lead to interfacial disaggregation of the thick meibium domains when SM is in excess, while MGS-DPPC interaction is strong and results in the formation of thick lipid aggregates. Both PLs increase the mixed films reciprocal compressibility and capability to achieve higher surface pressures. The results demonstrate that in vitro studies of the surface interactions between MGS and PLs might be beneficial in the selection of PLs for artificial tear formulations and for examination on molecular scale of the possible role of PLs at the ocular surface.

[Abnormal property of meibomian secretion and dry eye syndrome].

PURPOSE: To study the relationship between meibomian secretion and dry eye. METHODS: To observe 68 outpatients (136 eyes) consecutively. Routine check up included vision, anterior segment and fundus, scoring of tear break up time (BUT), Schirmer I test and rose bengal staining (rb). Recorded the property of meibomian secretion. Defined the dry eye as mild and severe. RESULTS: Meibomian secretion was sorted as egg-white-like secretion (n=28), milk-yellowish secretion (n=26), granular secretion (n=30) and toothpaste-like secretion (n=52). The result declared that BUT and rb scoring stepped up consecutively in the above secretions, that was higher in toothpaste-like secretion than in other groups (all P < 0.01). Schirmer I scoring was below 1 in all groups, and there was no difference in the groups. Fifty-four eyes (40%) met the criteria of dry eye syndrome. The incidence of dry eye stepped up in groups as egg-white-like secretion (2/28) 7.1%, milk-yellowish secretion (4/26) 15%, granular secretion (8/30) 27% and toothpaste-like secretion (40/52) 77%. The incidence was higher in granular secretion than in egg-white-like secretion (P < 0.05), while the incidence was higher in toothpaste-like secretion than in any of other 3 groups (P < 0.01). There was no severe dry eye in egg-white-like secretion and milk-yellowish secretion, while dry eye was found in 2 out of 8 in granular secretion, and in 19 out of 40 in toothpaste-like secretion. Incidence of severe dry eye was found higher in toothpaste-like secretion than in non toothpaste-like secretion (P < 0.05). CONCLUSION: Abnormal meibomian secretion affects the stability of ocular surface. The patients with toothpaste-like secretion are prone to dry eye and tend to have a worse dry eye than other secretion groups.

Lipid deposition on hydrogel contact lenses: how history can help us today.

The tear film is a complex fluid that is precisely maintained and which is essential to the health of the ocular surface. One of the major components of the tear film is lipid, which is produced by the meibomian glands and serves many important functions on the ocular surface. It is estimated that there are more than 45 individual lipids within the tear film, which vary greatly in their structure and properties. The composition of the lipid within the tear film has an enormous influence on the stability of the tear film, with a subsequent impact on the occurrence of dry eye and the ultimate success of contact lens wear. The purpose of this review article is to describe the composition of the tear film lipids and their interaction with contact lens materials, with a particular emphasis on how the chemistry of novel silicone hydrogel materials has resulted in clinicians needing to understand the deposition of lipids onto contact lenses and how they may best manage this complication.

Spoilage of hydrogel contact lenses by lipid deposits. Tear-film potassium depression, fat, protein, and alcohol consumption.

"Jelly-bump" deposits, which are composed mainly of lipids, on high water content, extended-wear hydrogel lenses, are a clinically significant problem of unknown etiology. The authors explored the effect of nutrition on the frequency of deposition of these jelly bumps. Forty-three patients were included in this masked case-control study from five contact lens practices in North America. Thirty patients were lipid-depositor cases and 13 were controls. Tear specimens were drawn and analyzed for potassium by atomic-absorption spectrophotometry. Detailed dietary histories were conducted and diet nutrient composition was computed. Patients with diminished tear-potassium concentrations have an increased risk of jelly-bump deposition. Elevated intake of protein, alcohol, and cholesterol also appeared to be correlated significantly with increased jelly-bump deposition. The authors found that diabetics and the use of diuretics, anticholinergics, sympathomimetics, were associated with tear-film potassium depletion and lipid deposit formation.

Biophysical characteristics of the Meibomian lipid layer under in vitro conditions.

The biophysical behaviour of the Meibomian gland secretion was tested under in vitro conditions. Thereby, simultaneous recording of surface pressure and surface potential was performed. The Meibomian lipid layer was compared with other surface-active components like polyvinylalcohol and polyvinylpyrrolidone. On the other hand, Eledoisin was tested as an example for a surface-inactive substance. An attempt was made to describe the biophysical interaction between a given artificial tear substitute and the Meibomian lipid layer. With respect to the surface potential Dipalmitoyl-phosphatidyl-choline was established as an analogue for Meibomian gland secretion. Fluorescence measurements in the presence of a cyanine dye (1 N,N'dioctadecyloxacarbocyanine) were used as a method to localize the site of the characteristic potential change. From the fluorescence spectra under compression we conclude that the molecular change takes place at the lipid-subphase interface of the Meibomian lipid layer.

The instilled fluid dynamics and surface chemistry of polymers in the preocular tear film.

Using slit lamp fluorophotometry it was demonstrated that the rate of drainage of a vehicle placed in the eye increased with increasing volume and that polymer solutions increased the thickness of the precorneal tear film (PTF). By increasing the viscosity of the delivery vehicle, (e.g., a hydroxypropylmethylcellulose polymer solutions), the PTF retention of fluorescein could be increased. The increased retention was shown to be due to an increase in the tear reservoir volume provided by the more viscous solutions. The PTF retention of fluorescein in a polyvinyl alcohol (PVA) vehicle was not as viscosity dependent, although PVA did seem to produce greater initial PTF fluorescence. This suggested that PVA initially produced a thicker PTF. The PTF retention of fluorescein by five commercial solutions did not have any relation to their wetting properties. The only good correlation with fluorescein retention in the PTF measured, seemed to be the ability of different polymer solutions to stabilize a thick layer of water as measured by the spontaneous spreading of polymer molecules at the air/liquid interface on wet glass surfaces. This model was designed to simulate tear film spreading in vivo. The results suggest that different polymer solutions may produce thicker PTF's than normal by virtue of their ability to drag water with them as they spread over the ocular surface with each blink. Mechanisms by which polymer solutions may increase the thickness of the PTF are discussed.