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Ocular surface mucosa is the first-line ocular tissue to be exposed to environmental stress. We evaluated tear functions and keratoconjunctival epithelial alterations after sidestream cigarette smoke (SCS) exposure and tried to clarify the role of the transcription factor nuclear factor erythroid 2-related factor 2 (Nfe2l2, also known as Nrf2), on the ocular surface. In wild-type and Nrf2(-/-) mice, tear volume did not change after SCS exposure. Tear film breakup time (tear stability) in Nrf2(-/-) mice was significantly shorter than that in wild-type mice after SCS exposure. Vital staining scores, including fluorescein and Rose Bengal staining, showed significantly higher values in Nrf2(-/-) mice than in wild-type mice after SCS exposure. Excessive oxidative stress accumulation was detected in Nrf2(-/-) mice after SCS exposure using immunohistochemical analysis. Immunohistochemical analysis also revealed decreased mucin 1 (Muc1) and Muc5ac staining in Nrf2(-/-) mice after SCS exposure. mRNA expression levels of Muc1, Muc4, and Muc5ac and of SAM-pointed domain epithelial-specific transcription factor in Nrf2(-/-) mice were lower than those in wild-type mice after SCS exposure. Mean tear IL-6 concentrations increased significantly in Nrf2(-/-) mice after SCS exposure. In conclusion, SCS exposure induced decreased tear stability, ocular surface damage, and altered conjunctival phenotype in Nrf2(-/-) mice. Nrf2 could play an important role in protection of the ocular surface against SCS exposure., (Copyright © 2015 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.)

Background: Skin prick tests are widely used to determine sensitivity in allergic diseases. There is limited information about the natural history of skin sensitization tests and factors that affect them. It was aimed to determine the changes in skin test results and the factors affecting the reactivity of skin tests after a period of approximately four years in children with allergic disease., Methods: SPT of 170 patients among 2485 children with asthma and/or allergic rhinitis and/or atopic dermatitis, who underwent SPT between 2005 and 2007, were repeated after an interval of at least 3 years., Results: The mean age was 10.7 ± 3.1 (5-18) years and 70% of the patients were male. In total 66 (39.0% of the study population) had a different skin tests result in follow-up. Alterations: loss of sensitivity in 18 (11%) patients, the formation of a new sensitivity in 37 (22%) patients, and 11 (6%) both gained and lost sensitization. The presence of atopy in the family, the presence of allergic rhinitis and IgE elevation significantly predicted the incidence of new sensitization. The presence of sensitization to multiple allergens significantly predicted the incidence of loss of sensitization., Conclusions: It is found that there was an alteration of sensitization in 4/10 children at the end of the average 4-year period. The presence of family atopy, the presence of allergic rhinitis and serum total IgE elevation were risk factors for the development of new sensitization. On the other hand sensitization to multiple allergens was risk factors for the loss of sensitization.

Purpose: To investigate the differences of functional visual acuity (FVA) and high order aberrations (HOAs) in relation to tinted and clear hydrogel soft contact lens (SCL) wear., Methods: A prospective comparative study was performed in 16 eyes of 16 healthy volunteers. Dynamic visual acuity (using a FVA measurement system) and higher-order aberrations (using a wavefront sensor) were compared in subjects wearing two types of soft contact lenses: 1-day Acuvue(®) (Vistakon, Jacksonville, FL) clear and the 1-day Acuvue(®) Define(TM) (Vistakon, Jacksonville, FL) tinted lens. The blink rates were recorded during FVA testing. The correlation between the difference of HOAs and differences in FVA values was analyzed., Results: The mean LogMAR FVA scores with clear and tinted SCLs were 0.07 ± 0.13 and 0.14 ± 0.17 (P<0.05). The mean blink frequencies with clear and tinted SCL wear were 18.4 ± 8.3 and 25.3 ± 4.7 blinks/min (P<0.05). Both 3rd-order aberrations and total HOAs showed statistically significant differences between the two types of soft contact lenses for 6mm pupil measurements (P<0.05). A significant positive linear correlation was observed between ΔHOAs and ΔLogMAR FVA for 6mm pupil measurements (R=0.53, P=0.04)., Conclusions: Tinted contact lens wear appears to induce a reduction in optical quality. Functional visual acuity measurement is a useful procedure to study the changes of visual performance and quality in tinted contact lens wear., (Copyright © 2013 British Contact Lens Association. Published by Elsevier Ltd. All rights reserved.)

The aim of the present study was to investigate the diagnostic significance of visualization of periesophageal fat pad in ultrasonography or computed tomography for sliding hiatal hernias. Forty-six controls and 21 esophageal hiatal hernia patients were compared in terms of sonographic and tomographic esophageal diameters. We suggest that absence of periesophageal fat pad sign in ultrasonography or computerized tomography is a noteworthy finding that calls for further investigation for the diagnosis of sliding hiatal hernias., (© 2013.)

Purpose: To clarify meibomian gland (MG) alterations in atopic keratoconjunctivitis (AKC) patients and compare the findings with obstructive MG dysfunction (MGD) patients and control subjects using in vivo confocal microscopy (CM)., Design: Prospective, controlled, single-center study., Participants: Twelve AKC patients (10 males, 2 females; mean age, 31.0±16.5 years), 12 obstructive MGD patients (7 males, 5 females; mean age, 37.6±5.6 years), and 26 control subjects (13 males, 13 females; mean age, 32.9±5.7 years) were recruited. No significant age or gender differences were observed between the 3 groups., Methods: All subjects underwent assessment of tear evaporation rate from the ocular surface (TEROS), slit-lamp examinations, tear break-up time (BUT) measurements, vital staining, Schirmer test I, meibography, MG expressibility, and CM examination of the MG (HRTII-RCM). Statistical analysis was performed using the Mann-Whitney test., Main Outcome Measures: The MG acinar unit density, inflammatory cell density, MG acinar unit longest diameter, MG acinar unit shortest diameter, and MG acinar unit area as observed by in vivo CM, MG drop-out, MG expressibility grading, tear stability, tear evaporation, and vital staining scores., Results: The TEROS values, mean BUT, vital staining scores, MG expressibility, and MG dropout grades were significantly worse in AKC patients compared with those in obstructive MGD patients and controls (P<0.05). The mean values of the CM parameters in AKC patients were significantly worse than those observed in the obstructive MGD patients and controls (P<0.001)., Conclusions: Changes in MG in AKC patients seem to be more severe than in patients with obstructive MGD and controls. In vivo CM is a noninvasive, efficient tool in the assessment of MG status and ocular surface disease in AKC., (Copyright © 2012 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.)

An imbalance between free radical generation and radical scavenging antioxidant systems results in oxidative stress, which has been associated with cell injury observed in many age-related diseases. The superoxide dismutase (SOD) family is a major antioxidant system, and deficiency of Cu,Zn-superoxide dismutase-1 (Sod1) in mice leads to many different phenotypes that resemble accelerated aging. In this study we examined the morphologic features and the secretory functions of the lacrimal glands in Sod1(-/-) mice. Lacrimal glands showed atrophy of acinar units; fibrosis; infiltration with CD4(+) T cells, monocytes, and neutrophils; increased staining with both 4-hydroxy-2-nonenal and 8-hydroxy-2'-deoxyguanosine; increases in apoptotic cells; and the presence of the epithelial-mesenchymal transition in senescent Sod1(-/-) mice. Electron microscopy findings revealed evidence of epithelial-mesenchymal transition, presence of swollen and degenerated mitochondria, and the presence of apoptotic cell death in the lacrimal glands of senescent Sod1(-/-) mice. These alterations were also associated with the accumulation of secretory vesicles in acinar epithelial cells, decreased production of both stimulated and nonstimulated tears, and a decline in total protein secretion from the lacrimal glands. Our results suggest that Sod1(-/-) mice may be a good model system in which to study the mechanism of reactive oxygen species-mediated lacrimal gland alterations., (Copyright © 2012 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.)

Objective: To estimate the prevalence and risk factors of dry eye disease (DED) in a rural setting in Japan., Design: Cross-sectional study., Participants: We included 3294 subjects, aged ≥ 40 years who were in the residential registry for Koumi town., Intervention: Subjects in a rural mountain area, Koumi town, completed questionnaires designed to detect dry eye diagnosis and risk factors., Main Outcome Measures: Clinically diagnosed DED was defined as the presence of a previous clinical diagnosis of DED by ophthalmologists or severe symptoms of DED (both dryness and irritation constantly or often). Current symptoms of DED and possible risk factors such as age, gender, educational history, smoking history, alcohol drinking history, height and weight, visual display terminal (VDT) use, and contact lens (CL) wear, and past/current history of certain common systemic diseases were the main outcome measures. We used logistic regression analysis to examine associations between DED and other demographic factors., Results: Of the 3294 eligible residents, 2791 residents (85%) completed the questionnaire. The percentage of women with a composite outcome of clinically diagnosed DED or severe symptoms (21.6%; 95% confidence interval [CI], 19.5-23.9) was higher than that of men (12.5%; 95% CI, 10.7-14.5; P<0.001). A low body mass index (BMI; odds ratio [OR], 2.07; 95% CI, 0.98-4.39), CL use (OR, 3.84; 95% CI, 1.46-10.10), and hypertension (HT) (OR, 1.39; 95% CI, 0.94-2.06) were risk factors for DED in men. Use of a VDT (OR, 2.33; 95% CI, 1.12-4.85), CL use (OR, 3.61; 95% CI, 2.13-6.10), and myocardial infarction or angina were the risk factors (OR, 2.64; 95% CI, 1.51-4.62), whereas high BMI was a preventive factor (OR, 0.69; 95% CI, 0.48-1.01) for DED in women., Conclusions: Among a Japanese cohort, DED leading to a clinical diagnosis or severe symptoms is prevalent. Use of CLs was a common dry eye risk factor in both genders. The condition is more prevalent in men with low BMI, HT, and in women with myocardial infarction or angina and VDT use. Relevant measures directed against the modifiable risks may provide a positive impact on public health and quality of life of Japanese., Financial Disclosure(s): The authors have no proprietary or commercial interest in any materials discussed in this article., (Copyright © 2011 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.)

Purpose: To prospectively investigate the effects of 2 week senofilcon A contact lens (CL) daily wear on the functional visual acuity (VA), ocular surface and tear film., Methods: Seventeen right eyes of 17 senofilcon A CL wearers without any ocular or systemic diseases were examined before and 2 weeks after lens wear. Visual acuity measurements, tear evaporation rate, ELISA for tear cytokines, strip meniscometry, tear lipid layer interferometry, tear film break-up time (BUT), in vivo confocal microscopy, corneal sensitivity, ocular surface vital staining, Schirmer I test and brush cytology for MUC5AC mRNA expression were performed before and after CL wear., Results: The best corrected Landolt VA, functional VA parameters, the mean lipid layer interferometry grades, tear evaporation rates, Schirmer test values, vital staining scores and in vivo confocal microscopy parameters did not show any significant differences after 2 weeks of CL wear. The tear film BUT showed a significant decrease together with a significant down regulation of MUC5 AC mRNA expression after CL wear. A statistically significant elevation in the mean tear interleukin (IL)-6 concentration was also observed after 2 weeks of CL wear., Conclusions: Two week senofilcon A daily CL wear seems to be associated with tear instability, a decrease in MUC5AC expression, and elevation of IL-6 in tears without significant alterations in epithelial damage scores or in the morphology or density of in vivo keratoconjunctival cells and nerves. Alterations associated with long term wear and patients with dry eye disease need to be studied in future trials., (Copyright © 2010 British Contact Lens Association. Published by Elsevier Ltd. All rights reserved.)

Purpose: To investigate the applicability of tear meniscus height (TMH) measurement using Visante optical coherence tomography (OCT) in the diagnosis of dry eye disease., Design: Prospective, controlled, single-center study., Participants: Twenty-four right eyes of 24 patients (6 males, 18 females; mean age, 63.14±13.4 years) with definite dry eye according to the Japanese dry eye diagnostic criteria and 27 right eyes of 27 control subjects (12 males, 15 females; mean age, 56.04±14.22 years) were recruited., Methods: All subjects underwent slit-lamp TMH measurement, OCT upper and lower TMH measurements, tear film breakup time (BUT) measurements, vital stainings, and Schirmer test. The results were compared between the 2 groups by Mann-Whitney test., Main Outcome Measures: The correlation between the clinical findings of slit-lamp TMH, strip meniscometry examination, tear functions, vital staining scores, and the OCT upper and lower TMH parameters were tested by Spearman's correlation test. Receiver operating characteristic (ROC) curve technique was used to evaluate the sensitivity, specificity and cutoff values of OCT TMH examination in the diagnosis of dry eye., Results: The OCT upper and lower TMH values, slit-lamp TMH, strip meniscometry, tear film BUT, and vital staining scores were significantly lower in the dry eye patients compared with controls (P<0.001). A significant correlation between the OCT upper and lower TMH measurements as well as slit-lamp TMH, strip meniscometry, tear functions, vital staining scores, and the Schirmer test was found. The ROC curve technique analysis of the OCT lower TMH showed that, when the cutoff value was set at <0.30 mm, the sensitivity and specificity of the testing were 67% and 81%, respectively., Conclusions: The Visante OCT is a quick, noninvasive method for assessing the TMH, with acceptable sensitivity, specificity, and repeatability, and may have potential applications for the diagnosis and evaluation of dry eye disease., (Copyright © 2010 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.)

Purpose: To evaluate the efficacy, sensitivity and specificity of confocal microscopy (CM) parameters: meibomian gland (MG) acinar longest diameter (MGALD), MG acinar shortest diameter (MGASD), inflammatory cell density (ICD), and MG acinar unit density (MGAUD) in the diagnosis of MG dysfunction (MGD)., Design: Prospective, controlled, single-center study., Participants: Twenty MGD patients (9 males, 11 females; mean age, 63.5+/-16.5 years) and 26 age- and gender-matched control subjects (13 males, 13 females; mean age, 53.2+/-15.7 years) were recruited., Methods: All subjects underwent slit-lamp examinations, tear film break-up time (BUT) measurements, assessment of tear evaporation rate from the ocular surface (TEROS), vital stainings, Schirmer test, meibography, MG expressibility, and CM of the MG. Data were compared between the 2 groups using the Mann-Whitney and chi-square tests., Main Outcome Measures: The correlation between the clinical findings of tear functions, vital staining scores, and the 4 CM parameters were tested by Spearman's correlation coefficient by rank test. Receiver operating characteristic curve technique was used to evaluate the sensitivity, specificity, and cutoff values of CM parameters., Results: The mean tear film BUT, vital staining scores, TEROS values, MG expressibility, and MG dropout grades by meibography were significantly worse in MGD patients compared with controls (P<0.001). The mean values of the MGALD, MGASD, ICD, and MGAUD in MGD patients were significantly worse than those observed in the controls with CM. All CM parameters showed a strong, significant correlation with tear functions, ocular surface vital stainings, MG expressibility, and MG dropout grades. The cutoff values for MGALD, MGASD, ICD, and MGAUD in the diagnosis of MGD were 65 microm, 25 microm, 300 cells/mm2, and 70 glands/mm2, respectively. The sensitivity and specificity values of these parameters under these cutoff values were 90% and 81% for MGALD, 86% and 96% for MGASD, 100% and 100% for ICD, 81% and 81% for MGAUD., Conclusions: Confocal microscopy has the potential to diagnose the simple MGD with high sensitivity and specificity. The CM-based diagnostic parameters correlated significantly and strongly with the status of the ocular surface disease., Financial Disclosure(s): The authors have no proprietary or commercial interest in any of the materials discussed in this article., (Copyright 2010 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.)

Background: Differential expression of chemokine genes were investigated in various types of ocular surface cells., Methods: Primary cultures of human corneal epithelial cells (n = 3), corneal fibroblasts (n = 2), conjunctival epithelial cells (n = 2) and conjunctival fibroblasts (n = 2) were established and incubated with or without interleukin (IL)-4 (30ng/ml) and tumor necrosis factor (TNF)-alpha(30ng/ml) for 24 hours. Gene transcription levels of 33 chemokines and production of 4 chemokines were analyzed., Results: After stimulation, chemokine expression increased for 18 of 33 coded chemokine gene transcripts. In stimulated conjunctival and corneal cells, CC chemokine genes increased in fibroblasts (expression of 6 out of 8 genes), while CXC chemokine genes increased in both epithelial cells (expression of 4 out of 9 genes in conjunctival epithelial cells and 7 out of 9 genes in corneal epithelial cells) and in fibroblasts (expression of 8 out of 9 genes in conjunctival and corneal fibroblasts). Except for MCP-1, gene transcription levels for most CC chemokines were inducible and, except for IP-10 and I-TAC, most CXC chemokines were constitutively expressed. Corneal epithelial cell and fibroblast production patterns for eotaxin-1, MCP-1 and IP-10 were comparable to the mRNA expression pattern., Conclusions: Corneal and conjunctival fibroblasts exhibited marked increases in the expression of chemokines upon stimulation with TNF-alpha and IL-4, suggesting that fibroblasts may be one of the primary sources of chemokines in allergic conjunctival diseases. Therefore, regulation of chemokine production from these cells may be an effective strategy for treating such diseases.

Biosorption of Pb(II) ions from aqueous solutions was studied in a batch system by using Candida albicans. The optimum conditions of biosorption were determined by investigating the initial metal ion concentration, contact time, temperature, biosorbent dose and pH. The extent of metal ion removed increased with increasing contact time, initial metal ion concentration and temperature. Biosorption equilibrium time was observed in 30min. The Freundlich and Langmuir adsorption models were used for the mathematical description of biosorption equilibrium and isotherm constants were also evaluated. The maximum biosorption capacity of Pb(II) on C. albicans was determined as 828.50+/-1.05, 831.26+/-1.30 and 833.33+/-1.12mgg(-1), respectively, at different temperatures (25, 35 and 45 degrees C). Biosorption showed pseudo second-order rate kinetics at different initial concentration of Pb(II) and different temperatures. The activation energy of the biosorption (Ea) was estimated as 59.04kJmol(-1) from Arrhenius equation. Using the equilibrium constant value obtained at different temperatures, the thermodynamic properties of the biosorption (DeltaG degrees , DeltaH degrees and DeltaS degrees ) were also determined. The results showed that biosorption of Pb(II) ions on C. albicans were endothermic and spontaneous. The optimum initial pH for Pb(II) was determined as pH 5.0. FTIR spectral analysis of Pb(II) adsorbed and unadsorbed C. albicans biomass was also discussed.

Objective: To determine the prevalence of dry eye disease (DED) and risk factors among young and middle-aged Japanese office workers using visual display terminals (VDTs)., Design: Cross-sectional prevalence survey., Participants: Four thousand three hundred ninety-three Japanese young and middle-aged office workers using VDTs., Intervention: Office workers completed questionnaires sent by e-mail designed to detect dry eye diagnosis and risk factors., Main Outcome Measures: Clinically diagnosed DED was defined as the presence of a previous clinical diagnosis of DED by dry eye specialists or severe symptoms of DED (both dryness and irritation constantly or often). Current symptoms of DED and possible risk factors such as age, duration of VDT use, type of VDT work, environmental factors, presence of systemic diseases, systemic medicine use, smoking history, and contact lens (CL) use were the main outcome measures. We used logistic regression to examine associations between DED and other demographic factors., Results: Of the 4393 office workers, 3549 (80.1%) completed the questionnaire. Clinically diagnosed DED was present in 266 (10.1%) of 2640 male subjects and in 195 (21.5%) of 909 female subjects. Severe symptoms of DED were observed in 711 male and in 436 female participants. More than 4 hours of VDT use was associated with an increased risk of DED (odds ratio [OR], 1.68; 95% confidence interval [CI], 1.40-2.02). In addition, CL use (OR, 3.91; 95% CI, 3.37-4.53) increased the risk of severe dry eye symptoms., Conclusions: Dry eye disease leading to a clinical diagnosis or severe symptoms is prevalent among young and middle-aged Japanese office workers. The condition is more prevalent among females, CL wearers, and prolonged VDT users. Relevant measures directed against the modifiable risks could provide a positive impact on public health and quality of life of office workers., Financial Disclosure(s): The authors have no proprietary or commercial interest in any materials discussed in this article.

Objective: To elucidate the morphologic alterations of the cornea in atopic keratoconjunctivitis (AKC) using confocal microscopy (Heidelberg Retina Tomograph II-Rostock Cornea Module: HRT-II RCM)., Design: Prospective comparative study., Participants: We studied 21 right eyes of 21 AKC patients (11 males, 10 females; mean age, 26.3 years) as well as 19 right eyes of 19 normal subjects (12 males, 7 females; mean age, 28.4 years)., Methods: All subjects underwent corneal sensitivity measurements, Schirmer test, tear film break-up time, fluorescein and Rose Bengal stainings, and HRT-II confocal laser scanning microscopy of the central cornea., Main Outcome Measures: The epithelial and endothelial cell densities of the central cornea, the density of subbasal long nerve fibers (LNFs) and total nerve branches (NBs) of the subbasal nerve plexus were calculated. The morphologic characteristics of the corneal nerves were studied. Correlation between nerve density, tear functions, and ocular surface examination parameters were investigated., Results: The corneal sensitivity, tear stability and vital staining scores were significantly worse in eyes with AKC (P<0.01). Eyes with AKC showed a significantly lower density of basal epithelial cells, LNFs, and NBs compared with normal eyes. Nerve fiber abnormalities such as increased tortuosity, bifurcation abnormality, sharp deflections, and thickening of stromal nerves, as well as several inflammatory cells in close proximity of the subbasal and stromal nerve fibers were observed., Conclusions: The corneal disease in AKC was associated with significant alterations of the basal epithelium, and subbasal and stromal corneal nerves, which related to the changes in tear functions and corneal sensitivity. Confocal scanning laser microscopy was useful to study the pathological in vivo corneal changes in AKC.

The present work proposes the use of Bacillus subtilis immobilized on Amberlite XAD-4 as new biosorbent in trace metal determination. The procedure is based on the biosorption of Cu and Cd ions on a column of Amberlite XAD-4 resin loaded with dried, dead bacterial components prior to their determination by flame AAS. Various parameters such as pH, amount of adsorbent, eluent type and volume, flow rate of solution and matrix interference effect on the retention of the metal ions have been studied. The optimum pH values of quantitative sorption for Cu and Cd were found to be 7.0 and 7.5, respectively. These metal ions can be desorbed with 1M HCl (recovery, 96-100%). The sorption capacity of the resin was 0.0297 and 0.035 mmol g(-1) for Cu(2+) and Cd(2+), respectively. The tolerance limit of some electrolytes were also studied. This procedure was applied to Cu(2+) and Cd(2+) determination in aqueous solutions, including river and well water systems. In order to evaluate the accuracy of the proposed procedure, the certified reference materials, NRCC-SLRS-4 Riverine water and LGC7162 Strawberry leaves were analyzed.

Purpose: To evaluate and grade the extent and severity of chronic ocular manifestations in Stevens-Johnson syndrome (SJS)., Design: Prospective multicenter case series., Participants: We enrolled 73 patients (138 eyes) with SJS seen between April 2003 and March 2005 at 3 tertiary referral centers., Methods: Patients with a confirmed history of SJS and chronic ocular complications that persisted for at least 1 year from the onset of SJS were included. Their detailed medical history and ophthalmic examination results were recorded on an itemized data collection form. Complications were categorized as corneal, conjunctival, and eyelid complications, and 13 components were evaluated and graded on a scale from 0 to 3 according to their severity., Main Outcome Measures: These were broadly classified as corneal (superficial punctate keratopathy, epithelial defect, loss of the palisades of Vogt, conjunctivalization, neovascularization, opacification, keratinization), conjunctival (hyperemia, symblepharon formation), and eyelid (trichiasis, mucocutaneous junction involvement, meibomian gland involvement, punctal damage) complications., Results: The most severely affected complication components were loss of the palisades of Vogt (114 eyes; 82.6%) and meibomian gland involvement (102 eyes; 73.9%). Visual acuity in 74 of the 138 eyes (53.6%) was worse than 20/200. The severity of corneal, conjunctival, and eyelid complications was significantly correlated with visual loss. All 13 complications were correlated significantly with logarithm of the minimum angle of resolution (logMAR) visual acuity; the correlation coefficient (R) ranged from 0.359 to 0.810 (P<0.0001); for corneal epithelial defects, R was 0.169 (P = 0.0473). Eyes with a higher total score for the 3 complication categories had poorer vision (R = 0.806; P<0.0001). Multivariate regression analysis showed that corneal neovascularization, opacification, keratinization, and cataracts significantly affected logMAR visual acuity (P<0.0001, P<0.0001, P = 0.0142, P = 0.0375, respectively)., Conclusions: The authors describe a new method for grading the extent and severity of ocular involvement in patients with SJS and demonstrate that the severity of ocular involvement is correlated significantly with the final visual outcome. This new grading system provides a more objective method for evaluating SJS patients and may be adapted for use in other cicatricial ocular surface diseases.

The tear film, composed of the lipid, aqueous and mucin layers, has many functions including defending the ocular surface. The tear film covering the ocular surface presents a mechanical and antimicrobial barrier and ensures an optical refractive surface. The lipid component originates from the meibomian glands of the tarsus and forms the superficial layer of the tear film. The aqueous component contains electrolytes, water, and a large variety of proteins, peptides and glycoproteins, and is primarily secreted by the lacrimal gland. Mucins are glycoproteins expressed by epithelial tissues of mucous surfaces. They protect tissues by functioning as antioxidants, providing lubrication, and inhibiting bacterial adherence. Quantitatively and qualitatively, its composition must be maintained within the fairly narrow limits to maintain a healthy and functional visual system. Abnormalities of the tear film, affecting the constituents or the volume, can rapidly result in serious dysfunction of the eyelids and conjunctiva and ultimately affect the transparency of the cornea. Many ocular surface tests have been developed for the clinical diagnosis of dry eye syndromes. This paper provides an overview on laboratory methods for the analysis of the tear film. Understanding the components of the tear film will aid in the treatment of dry eye syndromes and the ocular surface diseases.

Objective: To investigate whether peripheral corneal neovascularization in bullous keratopathy (BK) is due to conjunctivalization, a sign of limbal stem cell deficiency., Design: Observational case-control study., Participants: Sixteen BK patients., Methods: Patients were divided into 2 groups: BK without peripheral neovascularization [NV(-) group; 5 patients, 5 eyes] and BK with neovascularization [NV(+) group; 11 patients, 13 eyes]. Evidence of conjunctivalization was evaluated by periodic acid-Schiff staining of impression cytology samples from the peripheral vascularized cornea. The 2 groups' durations of disease also were compared. Penetrating keratoplasty (PK) was performed in all 16 cases, and the 2 groups' durations of reepithelialization after PK were compared., Main Outcome Measures: Presence of goblet cells using impression cytology, duration of BK, and duration of postoperative reepithelialization., Results: Goblet cells were found on the peripheral corneal surface in all eyes in the NV(+) group. However, all eyes in the NV(-) group were negative for goblet cells (P<0.0001). Duration of disease was 14.4+/-5.4 months in the NV(-) group and 66.2+/-65.5 months in the NV(+) group (P = 0.030). Duration of postoperative epithelialization was 6.2+/-2.2 days in the NV(-) group and 28.8+/-36.5 days in the NV(+) group (P = 0.046)., Conclusion: Conjunctivalization of the peripheral cornea and delayed postoperative epithelialization in BK patients with NV suggest the presence of limbal stem cell deficiency in such patients. Patients with long-standing disease were found to be more prone to neovascularization. For this reason, early surgery may lead to a better surgical outcome.

Purpose: To investigate the effect of periocular warming on accommodation amplitude and near vision after prolonged near work in visual display terminal (VDT) workers in an office setting., Design: Prospective interventional observational case series., Participants: Ten healthy Japanese male volunteers (mean age, 39.3+/-2 years [range, 36-43]) with a best distance corrected visual acuity (VA) of >20/20 who performed near work for 7 hours were included in the study., Main Outcome Measures: The differences of subjective and objective accommodations, near acuity, and pupil diameters were compared and studied in 2 experimental settings with and without periocular warming., Methods: Two experiments were performed on each subject on 2 different days. In one experiment, the subjects wore an eye mask and closed their eyelids for 10 minutes after 7 hours of VDT work (lid closure [LC] group). In the other experiment, the subjects applied warming sheets (WSs) to their eyelids and the periocular region and wore masks for 10 minutes again after 7 hours of VDT work (WS group). Visual display terminal work was performed under the same settings on both days. Subjective and objective accommodations, near vision, and pupil diameters were measured immediately before and immediately after the resting or warming procedure and again 90 minutes after the resting or warming procedures., Results: Fifty percent of eyes had an increase in the accommodation amplitude of at least 0.5 diopters immediately after application of the WSs. Forty percent of eyes still maintained the accommodation amplitude level at 90 minutes. The mean near logarithm of the minimum angle of resolution VA immediately after application of WSs and at 90 minutes significantly improved relative to the near acuity values after simple eyelid closure., Conclusion: Periocular warming was found to be associated with increases in subjective and objective accommodations, with a concomitant improvement in near VA. Periocular warming with disposable WSs is a simple and effective method of increasing near work-related ergonomy.

Objective: To evaluate the effect of autologous serum application for epithelial disorders in neurotrophic keratopathy (NK)., Design: Retrospective, noncomparative case series., Participants: Fourteen eyes of 11 patients with NK seen at Tokyo Dental College, Ichikawa General Hospital, Department of Ophthalmology, were studied., Intervention: Twenty percent topical autologous serum eye drops were applied 5 to 10 times daily until resolution of the NK. Patients underwent routine ophthalmic examinations, including slit-lamp examination, corneal fluorescein dye testing, Cochet-Bonnet corneal sensitivity (Luneau, France), and best-corrected visual acuity (BCVA) measurements before and at the end of the treatment. Moreover, serum samples from 10 healthy volunteers were studied for the levels of substance P (SP), insulinlike growth factor (IGF-1), and nerve growth factor (NGF) by using radioimmunoassay and enzyme-linked immunosorbent assay techniques. Tear samples from 3 healthy subjects also were analyzed for NGF and IGF-1 levels by the same techniques., Main Outcome Measures: The changes in corneal disease state, corneal sensitivity, and BCVA with treatment were evaluated. The levels of neural healing factors like SP, IGF-1, and NGF in serum as well as NGF and IGF-1 in tears of healthy subjects also were examined., Results: The epithelial disorders healed completely in all eyes within 6 to 32 days (mean, 17.1+/-8.0 days), with a decrease in corneal scarring. The mean pretreatment corneal sensitivity was 11.8+/-11.6 mm, which increased to 30.0+/-22.9 mm after treatment at the last follow-up. Five eyes attained normal corneal sensitivity with treatment. The BCVA improved by >2 Landolt lines in 78.6% of the eyes. The mean concentrations of SP in diluted and undiluted serum were 31.4+/-8.4 pg/ml and 157.0+/-42.1 pg/ml, respectively. The mean respective concentrations of IGF-1 in diluted and undiluted serum were 31.4+/-14.8 ng/ml and 157.0+/-73.9 ng/ml. The mean concentrations for NGF were 93.6+/-63.5 pg/ml and 468.3+/-317.4 pg/ml in serum samples with and without dilution, respectively. The mean concentration of NGF in tears was found to be 54 pg/ml. Insulinlike growth factor 1 was not detected in tears in this study., Conclusions: Autologous serum harbors neurotrophic factors. Autologous serum treatment may provide neural healers to the compromised ocular surface and seems promising for the restoration of the ocular surface epithelial integrity in patients with NK.

Objective: To describe the ocular surface and tear function findings in premature and term babies., Design: Prospective, case-control study., Participants: Forty-eight eyes of 24 premature babies seen at the Department of Ophthalmology of Uludag University School of Medicine, Bursa, Turkey, from March 2002 through September 2002 and 50 eyes of 25 healthy term babies were studied., Intervention: The subjects underwent routine ophthalmic examinations; corneal sensitivity measurements; Schirmer test with anesthesia, with and without nasal stimulation; primary Jones test; fluorescein staining of the ocular surface; and conjunctival impression cytology., Main Outcome Measures: Premature and term babies were compared for corneal sensitivity, lacrimal drainage system patency, tear function and ocular surface staining parameters, goblet cell density, and squamous metaplasia grade. The relation of these parameters to the status of the ocular surface was also investigated., Results: Mean corneal sensitivity scores were 45+/-5.0 mm and 55+/-4.5 mm in the premature and term babies, respectively (P<0.001). Premature babies had a mean corneal fluorescein staining score of 1.5+/-0.25 points, compared with 0.22+/-0.28 points in the term babies (P<0.001). The mean Schirmer test scores without and with stimulation were 1.5+/-2.5 mm and 4.15+/-2.5 mm in the premature babies, respectively, compared with 15+/-3.5 mm and 18.75+/-4.5 mm in the term babies. The intragroup and intergroup Schirmer test scores were statistically significant (P<0.001). The primary Jones test was positive in 20.8% of the eyes in the premature babies, whereas it was positive in 84% of eyes in the term babies. The premature babies with positive primary Jones test results all had corneal epithelial defects or severe superficial punctuate keratopathy. Mean conjunctival impression cytology squamous metaplasia scores were 1.86+/-1.2 in the premature babies and 0.86+/-0.47 in the term babies (P<0.001). Mean goblet cell densities were 393+/-484 cells/mm(2) and 739+/-503 cells/mm(2) in the premature and term babies, respectively (P<0.001)., Conclusion: Decreased corneal sensitivity, reduced tearing, and lacrimal drainage patency are important determinants of ocular surface disease in premature infants. Premature newborns with low Schirmer test scores and a patent lacrimal system may experience corneal and conjunctival epithelial problems and should be carefully checked for the presence of dry eye complications.

Purpose: To evaluate the effect of lacrimal punctal occlusion in the management of the ocular surface disease in chronic Stevens-Johnson syndrome., Design: Retrospective noncomparative case series., Participants: Thirty-one eyes of 18 patients with chronic Stevens-Johnson syndrome seen at the Department of Ophthalmology of the Tokyo Dental College were studied., Intervention: Patients' lacrimal puncta were occluded by cauterization or with punctal plugs., Main Outcome Measures: The effect of lacrimal punctal occlusion was evaluated by changes in subjective symptoms, best-corrected visual acuity (VA), Schirmer test, tear clearance test, and ocular surface double vital staining before and after punctal occlusion., Results: After lacrimal punctal occlusion, symptomatic improvement was observed in 19 eyes (61.3%). The mean logarithmic VA showed significant improvement from -0.64+/-0.87 to -0.52+/-0.86 (P<0.05). The Schirmer I test results before punctal occlusion yielded a mean score of 7.4+/-8.7 mm, which changed to 10.2+/-8.3 mm after punctal occlusion. The mean preocclusion and postocclusion tear clearance values were 7.5+/-6.6 times and 4.9+/-4.8 times, respectively. The Rose Bengal staining score decreased from 4.7+/-2.8 to 2.7+/-2.2 points (P<0.05), and the fluorescein staining score decreased from 5.0+/-2.3 to 2.2+/-2.5 points (P<0.05), respectively., Conclusions: Concurrent improvements in subjective symptoms, vital staining scores, and VA point to the favorable effects of lacrimal punctal occlusion for the ocular surface health in chronic Stevens-Johnson syndrome.

Purpose: To describe the ocular surface disorder in patients with keratoconus., Design: A prospective, case-controlled study., Participants: Seventy-five eyes of 38 patients with keratoconus seen at Uludag University School of Medicine, Department of Ophthalmology, from March 2000 through April 2001, and 80 eyes of 40 normal control subjects were studied., Intervention: The subjects underwent routine ophthalmic examinations, corneal sensitivity measurements, Schirmer test, tear film breakup time (BUT), fluorescein and rose bengal staining of the ocular surface, and conjunctival impression cytology., Main Outcome Measures: Patients and control subjects were compared for corneal sensitivity, tear function, ocular surface staining parameters, goblet cell density, and squamous metaplasia grade. The relation of these parameters to the severity of keratoconus progression was also investigated., Results: The mean corneal sensitivity was significantly lower in keratoconus patients compared with control subjects (P < 0.001). The BUT values were also significantly lower in the keratoconus group. Patients with keratoconus had significantly higher fluorescein and rose bengal staining scores (P < 0.001). Corneal sensitivity and tear function changes seemed to get worse with advanced stages of keratoconus. Impression cytology showed goblet cell loss and conjunctival squamous metaplasia, both of which again related to the extent of progression of keratoconus., Conclusions: The ocular surface disease in keratoconus is characterized by disorder of tear quality, squamous metaplasia, and goblet cell loss, all of which seem to relate to the extent of keratoconus progression.

Purpose: To study the changes in ocular surface findings with recurrence after phototherapeutic keratectomy (PTK) in patients with Avellino and granular dystrophy., Design: Observational case series., Participants: Five eyes of five patients with recurrent granular/Avellino corneal dystrophy after PTK seen at Kobe Kaisei Hospital were studied., Intervention: The patients underwent routine ophthalmic examinations, corneal sensitivity measurements, tear film breakup time (BUT), Schirmer test, tear film lipid layer interferometry, and conjunctival impression cytology., Main Outcome Measures: The alterations of clinical features, tear function, and conjunctival impression cytology parameters with a recurrence after PTK were investigated., Results: The average pre-PTK corneal sensitivity and tear film breakup time were low in all five patients. Tear film lipid layer interferometry grade and conjunctival squamous metaplasia displayed higher grades before PTK. All of these parameters improved gradually after PTK and were maintained until a recurrence, which was associated with further worsening of the corneal sensitivity, tear function, and impression cytology parameters., Conclusions: Although PTK improves the ocular surface health in granular/Avellino corneal dystrophies, recurrence of the initial dystrophy is associated with decline of the ocular surface health parameters. Our findings also suggest that corneal epithelium is most probably involved in the recurrence of the disease process in Avellino/granular corneal dystrophy.

Purpose: To describe the ocular surface disorder in patients with diabetes., Design: A prospective, case-controlled study., Participants: Eighty-eight eyes of 50 noninsulin-dependent diabetes mellitus patients seen at the Department of Ophthalmology, Kobe University School of Medicine, from September 1998 through February 1999, and 40 eyes of 20 healthy control individuals were studied., Intervention: All subjects underwent routine ophthalmic examinations, corneal sensitivity measurements, Schirmer test, tear film break-up time (BUT) analysis, and conjunctival impression cytologic analysis., Main Outcome Measures: Patients and control subjects were compared for corneal sensitivity, tear function parameters, goblet cell density, and squamous metaplasia grade. The relation of diabetic peripheral neuropathy, metabolic control, duration of disease, and status of retinopathy to the ocular surface disorder was also noted., Results: The mean corneal sensitivity was significantly lower in diabetic patients, diabetic patients with peripheral neuropathy, and poorly controlled diabetes compared with control subjects (P < 0.001). The BUT and Schirmer test values were also significantly lower in the diabetic group, in patients with peripheral neuropathy and poor metabolic control. Impression cytologic analysis showed goblet cell loss and conjunctival squamous metaplasia, both of which again related to peripheral neuropathy, poor diabetic control, and decreased corneal sensitivity. The examined parameters did not relate to duration of disease or status of diabetic retinopathy., Conclusions: The ocular surface disease in diabetes is characterized by a disorder of tear quantity and quality, squamous metaplasia, and goblet cell loss, all of which seem to evolve in close proximity to the status of metabolic control and peripheral neuropathy.

Purpose: To study the ocular surface disorder in patients with Avellino, granular, and lattice dystrophy, band keratopathy, and corneal leukoma before and after excimer laser phototherapeutic keratectomy., Design: A prospective case-controlled study., Participants: A total of 45 eyes of 33 patients with superficial corneal opacities seen at Kobe Kaisei Hospital, Department of Ophthalmology, and 40 eyes of 20 normal control subjects were studied., Intervention: The subjects underwent routine ophthalmic examinations, corneal sensitivity measurements, tear film break up time (BUT), Schirmer test, tear film lipid layer interferometry, and conjunctival impression cytology., Main Outcome Measures: The patients and the control subjects were compared for prephototherapeutic keratectomy (PTK) tear function parameters, tear film lipid layer interferometry grade, goblet cell density, and conjunctival squamous metaplasia grade. Alterations of these parameters within 3 months after PTK were also looked for., Results: The average pre-PTK corneal sensitivity and tear film break up time were lower in patients compared with control subjects before PTK. Tear film lipid layer interferometry grade and conjunctival squamous metaplasia grades were higher in the patients than the controls before PTK. All these parameters improved gradually and significantly after PTK. Goblet cell density was significantly lower in the patients compared with controls before PTK. Schirmer test results and goblet cell density did not show any significant alterations after PTK., Conclusions: Concurrent improvements in corneal sensitivity, tear film break up time, lipid layer interference grades, and conjunctival squamous metaplasia grades all point to the favorable effects of PTK on the ocular surface by improving the stability of the tear film and ocular surface health through attainment of a regular corneal surface and probably inducing qualitatively/quantitatively better mucin production by a healthier epithelium after PTK.

Purpose: This study aimed to describe the ocular surface disorder in patients with atopic dermatitis (AD)., Design: A prospective case-controlled study., Participants: A total of 44 patients with active AD seen at Kobe University School of Medicine, Department of Ophthalmology, during 1994 through 1996 and 22 normal control subjects were studied., Intervention: The subjects underwent routine ophthalmic examinations, tear film break-up time (BUT), Schirmer test, and conjunctival impression cytology., Main Outcome Measures: Patients and control subjects were compared for tear function parameters, goblet cell density, and conjunctival squamous metaplasia grade. The relation of duration and recurrences of AD to the ocular surface disorder also was looked for., Results: The duration of atopic disease ranged from 18 to 32 years (mean, 22.8 years). The average for exacerbations was 4.5 times. Chronic allergic conjunctivitis with superficial punctate keratitis was the most frequent clinical presentation. The BUT and Schirmer test values were significantly lower in patients with AD compared with those of the control subjects. Impression cytology showed goblet cell loss and conjunctival squamous metaplasia, both of which related to the number of recurrences of AD rather than the duration of disease. Facial atopy and allergic keratoconjunctivitis (AKC) related to the metaplasia of the ocular surface (P < 0.001). Patients with reduced goblet cell density also showed low BUT levels (P < 0.001)., Conclusion: Ocular surface disorder of AD characterized by goblet cell loss and conjunctival squamous metaplasia seemed to evolve independently of the duration of disease but worsen with increased number of flare-ups. Direct epithelial damage by the allergic reaction, disorder of tear quality, and quantity may be important in the genesis of the atopic ocular surface disease.