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OBJECTIVES: This study evaluated whether swimming goggle wear contributes to meibomian gland (MG) atrophy or functional change. METHODS: Subjects included minimal goggle wear experience (normal subjects) and maximal goggle wear experience (competitive swimmers). Principal outcome measures were meiboscore and percent MG area remaining percent gland area remaining [PGAR]). Clinical tests included symptoms, tear meniscus height, lipid layer thickness, fluorescein tear breakup time, corneal and conjunctival staining, lower lid margin signs, gland secretion quality, Schirmer I, and meibography. RESULTS: Forty-two age-matched, and sex-matched subjects completed the study (25 normal subjects and 17 goggle-wearing swimmers). Tear breakup time was significantly shorter in goggle wearers (P=0.016, Mann-Whitney U). Differences in meibography, symptoms, and other clinical dry eye workup parameters were not statistically significant (all P values >0.05). Regression analysis indicated that sex, tear breakup time, and meiboscore statistically impacted PGAR. CONCLUSIONS: There was no apparent difference in MG morphology and function between goggle-wearing swimmers and nongoggle-wearing control subjects in this study sample. Although swimming goggles have been documented as having adverse effects on the periorbital tissues, mechanical forces from long-term swimming goggle wear may not impact MG morphology or function. The tarsal plate likely plays a protective role for the MGs from external mechanical friction from swimming goggles.
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Dispositivos de Proteção dos Olhos , Glândulas Tarsais , Biometria , Humanos , Projetos Piloto , NataçãoRESUMO
OBJECTIVES: The aim of this study was to develop and evaluate, using psychometric approaches, a meibomian gland dysfunction (MGD)-specific questionnaire in noncontact lens wearers. METHODS: The MGD subjects were recruited and classified as the MGD dry eye subtype based on accepted tests (e.g., Schein symptom survey, tear breakup time, corneal and conjunctival staining, abnormal meibum or meibomian gland atrophy, and a normal Schirmer test). The MGD questionnaire items were drawn from published and anecdotal sources. The preliminary instrument contained 24 items targeting the frequency and intensity of 12 symptoms. Rasch analysis was used for psychometric evaluation of the survey items. RESULTS: Sixty nine MGD subjects completed the survey and clinical testing. Sample severity levels were as follows: none subclinical, 10 minimal, 43 mild, 16 moderate, and none severe. Three iterations of analysis, eliminating INFIT and OUTFIT scores <, and >3.0, and using subject responses reduced the final questionnaire to seven question pairs. Final analysis for the remaining 14 items demonstrated an excellent fit to the Rasch model (e.g., for persons, INFIT MNSQ=0.97; ZSTD=-0.2; OUTFIT MNSQ=0.96; ZSTD=-0.2; item fit statistics were similar). Construct validity also seems good (e.g., correlation to Schein and change with treatment). CONCLUSIONS: The MGD-specific instrument is a valid quantitative measure of the symptoms stemming from MGD sufferers. Further research is necessary to determine whether diagnostic efficacy is sufficient to differentiate the MGD dry eye subtype in an independent sample of normals and both major dry eye subtypes exhibiting a broad severity range.
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Síndromes do Olho Seco/fisiopatologia , Glândulas Tarsais/fisiopatologia , Psicometria/métodos , Qualidade de Vida , Inquéritos e Questionários , Lágrimas/metabolismo , Progressão da Doença , Síndromes do Olho Seco/metabolismo , Óculos , Feminino , Seguimentos , Humanos , Masculino , Glândulas Tarsais/metabolismo , Pessoa de Meia-Idade , Estudos Prospectivos , Lágrimas/químicaRESUMO
OBJECTIVES: To quantify tear elimination rate (ER) underneath silicone hydrogel (Si-Hy) and scleral gas permeable (GP) contact lenses (CLs). METHODS: Subjects successfully using either well-fitting soft Si-Hy CLs or scleral GP CLs were recruited. Most scleral GP CL wearers had irregular corneas (e.g., keratoconus). An objective fluorometer measured decay of fluorescein isothiocyanate dextran dye signal (70 kD MW) from which the tear ER in %/min was calculated. For GP scleral lenses, the ER was determined for both the initial settling period and the 30- to 60-min period, and without lenses. All ERs were calculated from 5 to 30 min to avoid reflex tearing effects. RESULTS: Fourteen soft Si-Hy CL and 12 scleral GP CL wearers completed the study. The ER for the scleral GP CL wearers averaged 0.57 (±0.6) %/min for the 0- to 30-min and 0.42 (±0.5) %/min for the 30- to 60-min period (P=0.515). Non-CL wear tear ER in these same subjects averaged 34.17 (±15.9) %/min and was significantly different versus both scleral GP wear periods (both P values <0.001). The ER for the soft Si-Hy CL wearers, 5 to 30 min, averaged 6.09 (±2.8) %/min. CONCLUSIONS: Our data demonstrate significantly less ER in well-fit scleral GP CL wearers compared with soft Si-Hy CL wearers for both the settling and longer wear periods (both P values <0.001). Moreover, slightly greater tear exchange was observed during the scleral GP CL settling period than later, which may reflect a change over time in tear vault thickness.
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Lentes de Contato Hidrofílicas , Esclera/metabolismo , Lágrimas/metabolismo , Adulto , Lentes de Contato Hidrofílicas/efeitos adversos , Dextranos/administração & dosagem , Feminino , Fluoresceína-5-Isotiocianato/administração & dosagem , Fluoresceína-5-Isotiocianato/análogos & derivados , Humanos , Hidrogel de Polietilenoglicol-Dimetacrilato , Masculino , Silicones , Adulto JovemRESUMO
PURPOSE: This study evaluated the validity and diagnostic efficacy of a modified Schein dry eye questionnaire and compared it to the Ocular Surface Disease Index (OSDI). METHODS: The original Schein survey was modified to allow numerical scoring on a 0 to 24 scale and evaluated in prospective studies in normal and dry eye subjects. Receiver operating characteristic (ROC) analysis for test efficacy in aqueous deficient dry eye (ADDE) and evaporative dry eye (EDE) related to meibomian gland dysfunction was determined. RESULTS: Dry eye subtype, age and gender were statistically significant in explaining variation in modified Schein scores (n = 377; general linear model; all P values < 0.006) whereas for Ocular Surface Disease Index (OSDI) only age and gender were significant, but not dry eye subtype. The modified Schein ROC curve had an area under the curve (AUC) of 0.693 (95% confidence interval [CI], 0.635-0.753), with cutpoint of 7.5 (sensitivity of 0.75, specificity of 0.55). Similarly, the OSDI had an AUC of 0.685 (95% CI, 0.610-0.760), at a cutpoint of 10.4 (sensitivity of 0.75, specificity of 0.55). Modified Schein and OSDI correlated well (Pearson r = 0.81; P < 0.001). Symptom change for the modified Schein with artificial tear treatment was significant in EDE subjects (Dunnet's tests, P value < 0.001). CONCLUSIONS: The modified Schein questionnaire is rapid to administer and score and compares well with the OSDI for test efficacy. Moreover, it differentiates normals from ADDE and EDE subtypes and is responsive to dry eye treatment. These attributes make the modified Schein survey an attractive dry eye symptom characterization instrument. TRANSLATIONAL RELEVANCE: The modified Schein symptom survey, validated against clinical diagnosis and an existing survey, provides a new, efficacious diagnostic and treatment monitoring instrument in dry eye disease.
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Síndromes do Olho Seco , Disfunção da Glândula Tarsal , Síndromes do Olho Seco/diagnóstico , Humanos , Estudos Prospectivos , Inquéritos e Questionários , LágrimasRESUMO
OBJECTIVES: To determine the efficacy of widely available subtype clinical tests to characterize evaporative dry eye disease (EDED) related to meibomian gland dysfunction (MGD) compared to normal and to validate those clinical cut points in an independent sample. METHODS: A diagnostic accuracy study (52 subjects), an investigator-masked study, was followed by a larger independent sample (364 subjects) analysis to confirm efficacy in normal and EDED subjects. All subjects were 18 years of age and older and were classified using a battery of clinical tests for dry eye that included symptoms, tear meniscus height, tear stability, ocular staining, evaporative-specific tests, and the Schirmer I test. RESULTS: Normal (nondry eye; n = 26) and EDED (n = 26) subjects completed the efficacy study. The global tests of tear breakup time, staining, and symptoms all produced AUCs ≥ 0.70, representing acceptable discrimination. EDED-specific tests of eyelid marginal signs, gland secretion quality, and gland loss did not demonstrate acceptable test efficacy or differences between normal and EDED subjects. In a larger, independent sample of normal and EDED subjects, gland secretion quality and eyelid marginal score achieved acceptable diagnostic levels: AUCs of 0.789 (CI: 0.734-0.844) and 0.729 (CI: 0.648-0.810), respectively, but not lipid interferometry grade or lower eyelid gland dropout estimated using meiboscopy. CONCLUSIONS: Meibomian gland secretion quality is an efficient and useful functional indicator in EDED and should be incorporated into core outcome sets for this dry eye subtype.
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PURPOSE: The purpose of this work was to gather preliminary data in normals and dry eye subjects, using a new, non-invasive imaging platform to measure the thickness of pre-corneal tear film. METHODS: Human subjects were screened for dry eye and classified as dry or normal. Tear film thickness over the inferior paracentral cornea was measured using laser illumination and a complementary metal-oxide-semiconductor (CMOS) camera. A previously developed mathematical model was used to calculate the thickness of the tear film by applying the principle of spatial auto-correlation function (ACF). RESULTS: Mean tear film thickness values (±SD) were 3.05 µm (0.20) and 2.48 µm (0.32) on the initial visit for normals (n=18) and dry eye subjects (n=22), respectively, and were significantly different (p<0.001, 2-sample t-test). Repeatability was good between visit 1 and 2 for normals (intraclass correlation coefficient [ICC]=0.935) and dry eye subjects (ICC=0.950). Tear film thickness increased above baseline for the dry eye subjects following viscous drop instillation and remained significantly elevated for up to approximately 32 min (n=20; p<0.05 until 32 min; general linear mixed model and Dunnett's tests). CONCLUSIONS: This technique for imaging the ocular surface appears to provide tear thickness values in agreement with other non-invasive methods. Moreover, the technique can differentiate between normal and dry eye patient types.
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Córnea/diagnóstico por imagem , Imageamento Tridimensional , Lágrimas/fisiologia , Xeroftalmia/diagnóstico por imagem , Adolescente , Adulto , Piscadela , Estudos de Casos e Controles , Córnea/efeitos dos fármacos , Córnea/fisiopatologia , Feminino , Fluoresceína/análise , Humanos , Imageamento Tridimensional/instrumentação , Imageamento Tridimensional/métodos , Lasers , Masculino , Computação Matemática , Microscopia de Fluorescência , Soluções Oftálmicas/administração & dosagem , Radiografia , Reprodutibilidade dos Testes , Lágrimas/efeitos dos fármacos , Xeroftalmia/diagnóstico , Xeroftalmia/fisiopatologia , Adulto JovemRESUMO
PURPOSE: The purpose of this investigation was to examine the relationship between the visual effect (VE) and residence time (RT) of artificial tears (ATs) in dry eye subjects. METHODS: The VEs and RTs were measured after administration of 25 µl of an AT into the inferior fornix of 18 dry eye subjects. The VE was investigated by measuring contrast sensitivity before and after AT administration. The return to baseline sensitivity (RTBS) was taken as the time it took to return to within 1 SD of baseline contrast sensitivity. RT was measured using fluorescent formulations and a scanning fluorometer. RESULTS: No correlation was found between RTBS and RT for a low viscosity (saline-F) and a medium viscosity AT (CMC-F; p>0.05). There was a moderate correlation for a higher viscosity AT (PEG-F; p=0.03). For all solutions, RT was significantly longer than RTBS (p<0.001). There was a significant difference in RTBS between saline-F and PEG-F (p=0.002) but not between saline-F and CMC-F (p=0.87). There was a significant difference in RT between saline-F and both PEG-F and CMC-F (p<0.001 and p=0.018, respectively). CONCLUSIONS: No correlation was found between RTBS and RT for saline-F or CMC-F (moderate correlation for PEG-F). These ATs are present on the eye for a significantly longer time than their adverse affect on vision. An ideal AT would result in minimal if any initial blur on instillation while remaining in the eye for an extended period of time.
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Sensibilidades de Contraste/efeitos dos fármacos , Síndromes do Olho Seco/tratamento farmacológico , Síndromes do Olho Seco/fisiopatologia , Soluções Oftálmicas/administração & dosagem , Soluções Oftálmicas/farmacocinética , Adulto , Idoso , Estudos Cross-Over , Dextranos , Método Duplo-Cego , Feminino , Fluoresceína-5-Isotiocianato/análogos & derivados , Humanos , Instilação de Medicamentos , Masculino , Pessoa de Meia-Idade , Soluções Oftálmicas/efeitos adversos , Soluções Oftálmicas/química , Estudos Prospectivos , Fatores de Tempo , ViscosidadeRESUMO
PURPOSE: The purpose of this study was to characterize the natural history of meibomian gland morphogenesis in the mouse. METHODS: Embryonic (E) and post natal (P) C57Bl/6 mouse pups were obtained at E18.5, P0, P1, P3, P5, P8, P15, and P60. Eyelids were fixed and processed for en bloc staining with Phalloidin/DAPI to identify gland morphogenesis, or frozen for immunohistochemistry staining with Oil red O (ORO) to identify lipid and antibodies specific against peroxisome proliferator-activated receptor gamma (PPARgamma) to identify meibocyte differentiation. Samples were then evaluated using a Zeiss 510 Meta laser scanning confocal microscope or Nikon epi-fluorescent microscope. Tissues from adult mice (2 month-old) were also collected for western blotting. RESULTS: Meibomian gland morphogenesis was first detected at E18.5 with the formation of an epithelial placode within the fused eyelid margin. Invagination of the epithelium into the eyelid was detected at P0. From P1 to P3 there was continued extension of the epithelium into the eyelid. ORO and PPARgamma staining was first detected at P3, localized to the central core of the epithelial cord thus forming the presumptive ductal lumen. Ductal branching was first detected at P5 associated with acinar differentiation identified by ORO and PPARgamma staining. Adult meibomian glands were observed by P15. Western blotting of meibomian gland proteins identified a 50 kDa and a 72 kDa band that stained with antibodies specific to PPARgamma. CONCLUSIONS: We have demonstrated that meibomian gland development bears distinct similarities to hair development with the formation of an epithelial placode and expression of PPARgamma co-incident with lipid synthesis and meibocyte differentiation.
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Glândulas Tarsais/embriologia , Morfogênese , Animais , Diferenciação Celular , Núcleo Celular/metabolismo , Lipídeos/biossíntese , Glândulas Tarsais/citologia , Glândulas Tarsais/metabolismo , Camundongos , Camundongos Endogâmicos C57BL , Microscopia Confocal , PPAR gama/metabolismoRESUMO
PURPOSE: To examine the effects of volume and method on fluorescein tear breakup time (TBUT) values and to evaluate test efficacy in an independent sample free of selection bias. METHODS: Subjects were assessed using a battery of dry eye tests (DETs). Efficacy study: Subjects were randomized to the DET, standard strip, and liquid NaFl on separate days. A masked examiner measured TBUTs from video recordings. Verification study: Subjects were investigated for efficacy using volumes of 5.0 and 2.0 µL mL of NaFl for TBUT. RESULTS: Efficacy study: 46 subjects completed the study. Log-transformed TBUTs were significantly different, normal subjects versus dry subjects, for all 3 methods (all P values < 0.001). Area under the curves (AUCs), cut-points, sensitivity, and specificity were 1) DET: 0.873, 4.4 seconds, 0.97, and 0.67, respectively; 2) 2.0 mL: 0.901, 3.22 seconds, 0.90, and 0.87, respectively; and 3) standard strip: 0.912, 3.42 seconds, 0.97, and 0.80, respectively. Verification study: Data splitting analysis for the 2.0 µL data (n = 174 dry subjects and 97 normal subjects) generated an AUC of 0.917 and a cut-point of 6.05 seconds for a sensitivity of 0.87 and a specificity of 0.81. The 5.0 µL sample yielded an AUC of 0.940, with a sensitivity and specificity of 0.92 and 0.83, respectively, at a cut-point of 5.5 seconds. CONCLUSIONS: Little difference in TBUT was found using the 3 clinical methods with video recordings. Analysis using liquid NaFl suggests that the TBUT test has excellent diagnostic accuracy and that a cut-point of 5.3 to 6.0 seconds is the optimum to differentiate normals from persons with dry eye.
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Síndromes do Olho Seco/diagnóstico , Fluoresceína/farmacologia , Lágrimas/metabolismo , Síndromes do Olho Seco/metabolismo , Feminino , Corantes Fluorescentes/farmacologia , Humanos , Masculino , Pessoa de Meia-Idade , Curva ROC , Gravação em VídeoRESUMO
The purpose of this study was to characterize the age-related changes of the mouse meibomian gland. Eyelids from adult C57Bl/6 mice at 2, 6, 12 and 24 months of age were stained with specific antibodies against peroxisome proliferator activated receptor gamma (PPARgamma) to identify differentiating meibocytes, Oil Red O (ORO) to identify lipid, Ki67 nuclear antigen to identify cycling cells, B-lymphocyte-induced maturation protein-1 (Blimp1) to identify potential stem cells and CD45 to identify immune cells. Meibomian glands from younger mice (2 and 6 months) showed cytoplasmic and perinuclear staining with anti-PPARgamma antibodies with abundant ORO staining of small, intracellular lipid droplets. Meibomian glands from older mice (12 and 24 months) showed only nuclear PPARgamma localization with less ORO staining and significantly reduced acinar tissue (p < 0.04). Acini of older mice also showed significantly reduced (p < 0.004) numbers of Ki67 stained nuclei. While Blimp1 appeared to diffusely stain the superficial ductal epithelium, isolated cells were occasionally stained within the meibomian gland duct and acini of older mice that also stained with CD45 antibodies, suggesting the presence of infiltrating plasmacytoid cells. These findings suggest that there is altered PPARgamma receptor signaling in older mice that may underlie changes in cell cycle entry/proliferation, lipid synthesis and gland atrophy during aging. These results are consistent with the hypothesis that mouse meibomian glands undergo age-related changes similar to those identified in humans and may be used as a model for age-related meibomian gland dysfunction.
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Envelhecimento/fisiologia , Glândulas Tarsais/fisiologia , Envelhecimento/imunologia , Envelhecimento/metabolismo , Envelhecimento/patologia , Animais , Diferenciação Celular/fisiologia , Núcleo Celular/metabolismo , Proliferação de Células , Citoplasma/metabolismo , Proteínas do Olho/metabolismo , Antígenos Comuns de Leucócito/metabolismo , Lipogênese/fisiologia , Glândulas Tarsais/citologia , Glândulas Tarsais/imunologia , Camundongos , PPAR gama/metabolismo , Fator 1 de Ligação ao Domínio I Regulador Positivo , Fatores de Transcrição/metabolismoRESUMO
PURPOSE: This study examined whether hyperspectral stimulated Raman scattering (hsSRS) microscopy can detect differences in meibum lipid to protein composition of normal and evaporative dry eye subjects with meibomian gland dysfunction. METHODS: Subjects were evaluated for tear breakup time (TBUT), staining, meibum expression and gland dropout. Expressed meibum was analyzed using SRS vibrational signatures in the CH stretching region (2800-3050â¯cm-1). Vertex component analysis and K-means clustering were used to group the spectral signatures into four fractions containing high lipid (G1) to high protein (G4). RESULTS: Thirty-three subjects could be statistically analyzed using pooled meibum (13 with stable tear films (TBUTsâ¯>â¯10â¯s) and 20 with unstable tear films (TBUTsâ¯≤â¯10â¯s). Significant differences in meibum from subjects with unstable vs. stable TBUTs were found for the G1 fraction (medians 0.164 and 0.020, respectively; pâ¯=â¯0.012) and the G2 fraction (medians 0.244 and 0.272, respectively; pâ¯=â¯0.045). No differences were observed for the G3 and G4 fractions. Single orifice samples were not significantly different vs. pooled samples from the fellow eye, and eyelid sector samples (nasal, central and temporal) G2:G3 fractional components were not significantly different (pâ¯=â¯0.449). Spearman analysis suggested a significant inverse correlation between G1 fraction and TBUT (Râ¯=â¯-0.351; pâ¯=â¯0.045). CONCLUSIONS: hsSRS microscopy allows compositional analysis of expressed meibum from humans which correlated to changes in TBUT. These findings support the hypothesis that hsSRS may be useful in classifying meibum quality and evaluating the effects of therapy.
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Doenças Palpebrais/metabolismo , Aprendizado de Máquina , Glândulas Tarsais/metabolismo , Microscopia Óptica não Linear/métodos , Lágrimas/metabolismo , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Doenças Palpebrais/diagnóstico , Feminino , Humanos , Metabolismo dos Lipídeos , Masculino , Glândulas Tarsais/diagnóstico por imagem , Pessoa de Meia-Idade , Reprodutibilidade dos Testes , Adulto JovemRESUMO
PURPOSE: It was the purpose of this investigation to examine both retention time (RT) and retention of effect of two ophthalmic formulations in the same dry eye subjects. METHODS: This was a randomized, subject-masked cross-over study. Dry eye subjects, characterized by sub-type, were recruited. For direct RT measurement, fluorescein isothiocyanate (FITC)-dextran, 70 kDa molecular weight, was admixed at 0.1% wt/vol concentration into buffered saline (active control) and a viscous marketed artificial tear formulations (test formulation). RT in minutes was estimated directly as the return to baseline intrinsic fluorescence with an objective scanning fluorometer. Retention of effect was measured with a xeroscope as non-invasive breakup time (NIBUT) and by use of a numerical rating scale for comfort. RESULTS: Eleven subjects, with most being classified as having non-inflammatory meibomian gland dysfunction, completed the study. The RTs averaged 17.7 (+/-10.0) and 26.8 (+/-16.5) minutes for the saline and test formulations, respectively. The averages for NIBUT were 8.73 (+/-6.1) and 19.5 (+/-4.9) minutes, for saline and the test formulations, respectively. Return to baseline for the numerical rating scale comfort averages were 9.91 (+/-4.1) and 20.21 (+/-6.4) minutes for the saline and test formulations, respectively. When residence time was subtracted from the retention of effect measures, no statistical significance was found for the polymeric solution (vs. comfort, p = 0.153; vs. NIBUT, p = 0.109). However, statistical differences were found for direct retention compared against comfort (p = 0.01) and NIBUT (p = 0.004) for buffered saline. CONCLUSIONS: It seems that these two retention of effect measures are much shorter than RT measured directly. Future work should aim to confirm these findings in additional dry eye sub-types and in those with more severe disease manifestations.
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Síndromes do Olho Seco/metabolismo , Soluções Oftálmicas/farmacocinética , Administração Tópica , Adulto , Estudos Cross-Over , Dextranos/farmacocinética , Feminino , Fluoresceína-5-Isotiocianato/análogos & derivados , Fluoresceína-5-Isotiocianato/farmacocinética , Corantes Fluorescentes/farmacocinética , Fluorofotometria , Humanos , Concentração de Íons de Hidrogênio , Masculino , Pessoa de Meia-Idade , Preparações Farmacêuticas , Estudos Prospectivos , Método Simples-Cego , ViscosidadeRESUMO
PURPOSE: The purpose of these investigations was to develop an improved method for measuring precorneal residence time (RT) and to demonstrate its efficacy with novel formulations. METHODS: A biomicroscope was adapted for use as a clinical fluorometer. Using a nonpenetrating fluorescent probe (FITC-dextran, 70,000-73,000 molecular weight [MW]), RT was estimated as the time to return to baseline (gross RT) and from parameters derived from least-squares regression fits to the decay data (area under the curve [AUC], elimination rate, and time for 50% of the signal to be eliminated [T(50)]). One rabbit and two human studies were conducted. The studies were randomized, double-masked, and controlled. Repeatability in humans was examined in 15 subjects (six determinations per subject, n = 90 total). RESULTS: The FITC-dextran tracer did not penetrate into corneal tissue. The rabbit gross RTs were 14.5, 15.0, and 16.0 minutes for three low-viscosity solutions (eta = 2.7-7.7 mPa/sec) and 22.5 minutes for a more viscous solution (eta = 357 mPa/sec). For a high-viscosity (eta approximately equal 30,000 mPa/sec) gel in humans, the method demonstrated approximately a twofold increase in gross RT and AUC compared with buffered saline. Repeatability of the method appeared acceptable, with intersubject variability the most significant factor affecting precision. CONCLUSIONS: The new method is safe and convenient and offers comprehensive RT data. Furthermore, it appears to differentiate among formulations. However, as with other tear-influenced parameters, there is significant variability. Thus, sufficient sample sizes are necessary for meaningful comparative investigations.
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Córnea/metabolismo , Dextranos/farmacocinética , Técnicas de Diagnóstico Oftalmológico , Fluoresceína-5-Isotiocianato/farmacocinética , Corantes Fluorescentes/farmacocinética , Adulto , Animais , Área Sob a Curva , Método Duplo-Cego , Feminino , Fluoresceína-5-Isotiocianato/análogos & derivados , Fluorofotometria , Géis , Meia-Vida , Humanos , Masculino , Pessoa de Meia-Idade , Coelhos , Reprodutibilidade dos Testes , ViscosidadeRESUMO
OBJECTIVE: To identify age-related changes in human meibomian glands that may be associated with meibomian gland dysfunction (MGD). METHODS: Excess eyelid tissue from 36 patients (age range, 18-95 years, 19 female, 17 male) who underwent canthoplasty procedures were used. Dermatologic history, age, and presence of MGD were recorded. Samples were frozen, sectioned, and stained with specific antibodies against peroxisome proliferator-activated receptor γ (PPARγ) to identify meibocyte differentiation, Ki67 nuclear antigen to identify cycling cells, and CD45 to identify inflammatory cell infiltration. RESULTS: Staining for PPARγ showed cytoplasmic and nuclear localization in the 2 youngest subjects (ages, 18 and 44 years). Older individuals (>60 years) showed predominantly nuclear staining, with cytoplasmic staining limited to the basal acinar cells in 17 of 31 subjects. The number of Ki67 positively stained basal cells were significantly elevated in the younger compared with older subjects based on linear regression analysis (r(2) = 0.35; P < .001). There was also a significant correlation between MG expression grade and CD45 cell infiltration (r = 0.414; P = .05). CONCLUSIONS: These results indicate that aging human meibomian glands show decreased meibocyte differentiation and cell cycling that is associated with the development of MGD. Findings also suggest that altered PPARγ signaling may lead to acinar atrophy and development of an age-related hyposecretory MGD. CLINICAL RELEVANCE: Meibomian gland dysfunction and evaporative dry eye are common age-related eyelid disorders. Understanding the underlying mechanism of MGD may lead to the development of novel therapeutic strategies to treat this disease.
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Envelhecimento/fisiologia , Doenças Palpebrais/metabolismo , Glândulas Tarsais/metabolismo , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Diferenciação Celular , Proliferação de Células , Doenças Palpebrais/patologia , Feminino , Técnica Indireta de Fluorescência para Anticorpo , Humanos , Antígeno Ki-67/metabolismo , Antígenos Comuns de Leucócito/metabolismo , Masculino , Glândulas Tarsais/patologia , Pessoa de Meia-Idade , PPAR gama/metabolismoRESUMO
PURPOSE: The study purpose was to evaluate corneal barrier function and staining relative to potential bioincompatibilities. METHODS: This was a randomized double-masked study (n = 25 subjects). Three lens material-care solution combinations were tested: (1) lotrafilcon B/polyhexamethylene biguanide (PHMB)-based multipurpose (MPS) solution (MPS-1); (2) lotrafilcon B/polyquaternium-1 and myristamidopropyl dimethylamine-based solution (MPS-2); and (3) lotrafilcon B and another PHMB-based solution (MPS-3). Saline served as the control. New lenses were soaked in the preserved solutions or saline and then worn for 2 hours before corneal measurements. Barrier function was characterized by the fluorescein penetration rate, corneal amount, both measured with an objective scanning fluorometer. The dye penetration rate ratio, test to control; amount ratio, test to control, and corneal staining were evaluated. RESULTS: The mean rate ratios (± SD) for the combinations were 2.98 (± 3.04), 1.23 (± 1.01), and 1.83 (± 1.77) for MPS-1, MPS-2, and MPS-3 solutions, respectively. Significant ratio differences were found across regimens (P = 0.007); for MPS-1 compared with baseline (P = 0.031) and for MPS-1 compared with MPS-2 (P = 0.007). The statistical results for staining were similar. CONCLUSIONS: Use of an objective quantitative physiological method suggests that significant differences in lens solution bioincompatibilities occur that mirror corneal staining data relative to corneal compromise.
Assuntos
Soluções para Lentes de Contato/efeitos adversos , Lentes de Contato Hidrofílicas , Epitélio Corneano/efeitos dos fármacos , Hidrogéis , Silicones , Adulto , Biguanidas/efeitos adversos , Estudos Cross-Over , Método Duplo-Cego , Epitélio Corneano/metabolismo , Feminino , Fluoresceína/metabolismo , Fluorofotometria , Humanos , Masculino , Teste de Materiais , Permeabilidade , Polímeros/efeitos adversos , Propilaminas/efeitos adversos , Erros de Refração/terapia , Coloração e Rotulagem , Adulto JovemRESUMO
PURPOSE: The purpose of this investigation was to measure the precorneal residence time of saline and five marketed artificial tears in dry eye subjects using fluorometry. METHODS: FITC-dextran, 70 kDa molecular weight, was admixed under sterile conditions (0.1% wt/vol) into buffered saline and the marketed artificial tear formulations of varying viscosity. Precorneal residence time (RT) was measured directly in 16 mild to moderate dry eye subjects, classified by sub-type, in a six-way cross-over, masked and randomized study. FITC-dextran tracer decay with a scanning fluorometer was used to estimate the gross RT (i.e., the time in minutes for the signal to return to baseline). RESULTS: All subjects were classified as having non-inflammatory meibomian gland dysfunction except one, who had a mixture of aqueous deficiency and meibomian gland dysfunction. In two separate determinations, the saline RTs were 19.1 +/- 7.4 and 17.6 +/- 8.2 min. The RTs for the formulations varied to some degree by viscosity, with two higher viscosity formulations demonstrating the longest RTs of 36 to 41 min, approximately twice that of saline (p < 0.001 for both 0.4% polyethylene glycol/0.3% propylene glycol, and 1.0% carboxymethylcellulose). An oil emulsion, low viscosity carboxymethylcellulose and moderate viscosity hydroxypropylmethylcellulose-containing formulation were not statistically different from saline (RTs of 18, 22 and 24 min, p values = 0.983, 0.818 and 0.099, respectively). CONCLUSIONS: More than two-fold RT differences were found for the higher viscosity, more muco-adhesive formulations compared to saline. However, other formulations provided RTs close to saline, suggesting that RT is influenced by factors other than simple viscosity. Future studies should examine the interplay of spreading characteristics, pseudoplasticity and muco-adhesion relative to RT to determine the individual and cumulative effects on formulation retention.
Assuntos
Córnea/metabolismo , Síndromes do Olho Seco/metabolismo , Soluções Oftálmicas/farmacocinética , Adulto , Idoso , Estudos Cross-Over , Dextranos/farmacocinética , Técnicas de Diagnóstico Oftalmológico , Método Duplo-Cego , Feminino , Fluoresceína-5-Isotiocianato/análogos & derivados , Fluoresceína-5-Isotiocianato/farmacocinética , Corantes Fluorescentes/farmacocinética , Fluorofotometria , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Fatores de Tempo , ViscosidadeRESUMO
PURPOSE: Use of polyhexanide based multipurpose solutions (MPSs) for contact lens disinfection has been linked to low-grade corneal staining. In vitro data suggest that carboxymethylcellulose (CMC) may neutralize polyhexanides. The purpose of this investigation was to determine whether a pre-application drop of CMC reduces polyhexanide staining in vivo. METHODS: Thirty adapted soft contact lens (SCL) wearers participated in this investigator-masked, randomized, two-way cross-over study. Subjects wore a new Group II lens (alphafilcon A, 66% water) daily for 4 weeks and disinfected lenses using a MPS containing 0.0001% polyaminopropyl biguanide. A lens lubricant containing either CMC or povidone as the primary viscolyzer was applied to the lens each day before lens wear. Biomicroscopic signs and symptomatology were assessed. The difference in scores, 0 to 4 weeks and the difference between lubricants were analyzed. RESULTS: The cumulative fluorescein staining scores for combined eyes demonstrated a significant increase over time (e.g., cumulative staining score; p=0.004 and p<0.001 for CMC and povidone, respectively, matched pairs t-test, two-tailed), suggesting that for both lubricants the staining worsened with wear. This effect was expected and likely driven by the MPS. However, the mean cumulative staining scores for CMC and povidone were 2.8 and 2.6 out of 20 possible at baseline, increasing to 4.9 and 7.1 at 4 weeks, respectively. The increases were significantly different (p=0.003, matched pairs t-test, two-tailed) suggesting a greater increase in corneal staining for the povidone lubricant. The symptom scores were not significantly different, 0 to 4 weeks by regimen or between preinstillation drops. CONCLUSIONS: These results suggest that a CMC-containing preapplication drop can reduce corneal staining resulting from disinfection with a polyhexanide MPS. This result is consistent with a proposed mechanism for CMC to neutralize cationic disinfectants and may offer clinicians another means to reduce this type of corneal staining.