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The 2017 consensus report of the Asia Dry Eye Society (ADES) on the definition and diagnosis of dry eyes described dry eye disease as "Dry eye is a multifactorial disease characterized by unstable tear film causing a variety of symptoms and/or visual impairment, potentially accompanied by ocular surface damage." The report emphasized the instability of tear film and the importance of visual dysfunction in association with dry eyes, highlighting the importance of the evaluation of tear film stability. This report also discussed the concept of tear film-oriented therapy, which stemmed from the definition, and which is centered on provision of insufficient components in each tear film layer and ocular surface epithelium. The current ADES report proposes a simple classification of dry eyes based on the concept of tear film-oriented diagnosis and suggests that there are three types of dry eye: aqueous-deficient, decreased wettability, and increased evaporation. It is suggested that these three types respectively coincide with the problems of each layer: aqueous, membrane-associated mucins, and lipid/secretory mucin. Although each component cannot be quantitatively evaluated with the current technology, a practical diagnosis based on the patterns of fluorescein breakup is recommended. The Asia Dry Eye Society classification report suggests that for a practical use of the definition, diagnostic criteria and classification system should be integrated and be simple to use. The classification system proposed by ADES is a straightforward tool and simple to use, only through use of fluorescein, which is available even to non-dry eye specialists, and which is believed to contribute to an effective diagnosis and treatment of dry eyes.

Background: To determine whether quality of life (QOL) and health utility are affected to the same extent among dry eye (DE) patients with short tear film break-up time dry eye (TBUT-DE) with minimal clinical signs were as severe as aqueous-deficient dry eye (ADDE)., Methods: A multicenter cross-sectional study was conducted among DE patients who visited one of 10 eye clinics in Japan. Among the 463 registered patients, this study involved 449 patients with DE who were aged 20 years or older. Ophthalmic examination findings were assessed, including tear film break-up time (TBUT), Schirmer I value, and keratoconjunctival staining score. QOL was evaluated with the Dry Eye-Related Quality-of-Life Score (DEQS; 0 [best], 100 [worst]) and health utility (1 [total health], 0 [worst]) with the Health Utilities Index Mark 3 (HUI-3); scores were stratified by DE subgroup., Results: Median (interquartile range) of DEQS and HUI-3 scores across all participants were 21.7 (10.0-40.0) and 0.82 (0.69-0.91), respectively. Median (interquartile range) DEQS and HUI-3 scores in the ADDE group were 23.3 (10.0-40.0) and 0.79 (0.69-0.88), respectively; those in the short TBUT-DE group were 23.3 (13.3-38.3) and 0.82 (0.74-0.92), respectively. There were no significant between-group differences in questionnaire scores. Among the ophthalmic examination findings, a weak significant correlation between TBUT, corneal staining score and keratoconjunctival staining score to DEQS; TBUT and Schirmer test values to HUI-3, were seen., Conclusions: The burden of short TBUT-DE on QOL as assessed by the DEQS and HUI-3 was as severe as that in ADDE. Our findings suggest that clinicians should be aware of the impact of short TBUT-DE on patients QOL and utility values., Trial Registration: University Hospital Medical Information Network (registration no. UMIN 000015890). Registered 10th December 2014, retrospectively registered.

Purpose: To evaluate the effect of meibomian gland dysfunction (MGD) and friction-related disease (FRD) on the severity of dry eye disease (DED)., Design: Cross-sectional observational study., Participants: This study enrolled 449 patients with DED (63 men and 386 women; mean age, 62.6±15.7 years [range, 21-90 years]) for analysis., Methods: Subjective symptoms, the ocular surface, tear function, and the presence of MGD and FRD (superior limbic keratoconjunctivitis, conjunctivochalasis, and lid wiper epitheliopathy) were investigated., Main Outcome Measures: Schirmer value, tear film breakup time (TBUT), and keratoconjunctival score., Results: We classified the participants into aqueous-deficient dry eye (ADDE; n = 231 [51.4%]) and short TBUT dry eye subtype (TBUT-DE; n = 109 [24.3%]) subgroups. The TBUT was shorter in patients with MGD than in those without MGD, whereas other ocular signs showed no difference (TBUT: MGD present, 1.97±1.02 seconds; MGD absent, 2.94±1.63 seconds [P < 0.001]; ADDE/MGD present, 1.94±1.08 seconds; ADDE/MGD absent, 2.77±1.61 seconds [P < 0.001]; short TBUT-DE/MGD present, 2.07±0.97 seconds; short TBUT-DE/MGD absent, 2.94±1.23 seconds [P = 0.01]). The ADDE patients with FRD showed a worse TBUT than ADDE patients without FRD (TBUT: ADDE/FRD present, 2.08±1.39 seconds; ADDE/FRD absent, 2.92±1.54 seconds; P < 0.001)., Conclusions: This study showed associations between MGD, FRD, or both and ocular signs in DED. In the presence of MGD, FRD, or both, TBUT was significantly shortened regardless of the dry eye status or subtype., (Copyright © 2018 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.)

Introduction: The aim of this study was to investigate the clinical characteristics and practice pattern of patients with dry eye disease (DED) in eye clinics across Japan., Methods: A multi-center, cross-sectional study was conducted among patients with DED who visited eye clinics in Japan. Subjective symptoms, patient's background, ocular surface features, and tear function were evaluated. Main outcome measures were tear break-up time (TBUT), Schirmer I value, kerato-conjunctival staining score, and dry eye symptom questionnaire score., Results: Initially, 463 subjects were enrolled, and 449 cases (63 male and 386 female; mean age, 62.6 ± 15.7 years) were included in the final analysis. Overall, 94.9% of patients had a shortened TBUT (≤5 s), and 54.6% had an aqueous tear deficiency (Schirmer I value ≤5 mm). The most prevalent subtype of dry eye was aqueous-deficient dry eye, which was present in 35.0% of all patients, followed by short-BUT-type dry eye, which was seen in 26.7%., Conclusion: The two most common DED subtypes were aqueous-deficient and short-BUT-type dry eye. Shortened TBUT is the most common feature of dry eye, regardless of subtype. The current treatment choice mainly consisted of hyaluronic acid, two novel mucin secretagogues, diquafosol and rebamipide, and steroidal eye drops., Trial Registration: University Hospital Medical Information Network: UMIN (registries no. UMIN 000015890)., Funding: Japan Dry Eye Society, Tokyo, Japan, and Santen Pharmaceutical Co., Ltd., Osaka, Japan.

For the last 20 years, a great amount of evidence has accumulated through epidemiological studies that most of the dry eye disease encountered in daily life, especially in video display terminal (VDT) workers, involves short tear film breakup time (TFBUT) type dry eye, a category characterized by severe symptoms but minimal clinical signs other than short TFBUT. An unstable tear film also affects the visual function, possibly due to the increase of higher order aberrations. Based on the change in the understanding of the types, symptoms, and signs of dry eye disease, the Asia Dry Eye Society agreed to the following definition of dry eye: "Dry eye is a multifactorial disease characterized by unstable tear film causing a variety of symptoms and/or visual impairment, potentially accompanied by ocular surface damage." The definition stresses instability of the tear film as well as the importance of visual impairment, highlighting an essential role for TFBUT assessment. This paper discusses the concept of Tear Film Oriented Therapy (TFOT), which evolved from the definition of dry eye, emphasizing the importance of a stable tear film., (Copyright © 2016 The Author(s). Published by Elsevier Inc. All rights reserved.)

Tear fluids are a mixture of secretions derived from lacrimal glands, accessory lacrimal glands, conjunctiva, and meibomian glands. Compositional changes to tears occur in the normal state and during ocular surface disease, such as dry eye conditions. We have investigated compositional changes to tears after topical application of ophthalmic solutions, with regard to tear-specific proteins (secretory immunoglobulin A, lactoferrin, lipocalin-1, and lysozyme) and ocular surface mucin in normal and dry eye conditions using high-performance liquid chromatography. After application of saline solution (0.9% sodium chloride) in normal subjects, transient but significant decreases in all tear components were observed. The recovery of protein concentrations took up to 30 minutes and lasted longer when the saline solution was applied more frequently. When applying ophthalmic solutions, a balance between washout and dilutional effects should be considered in addition to the therapeutic effect. Investigation of the effect of diquafosol solution (3%) in normal subjects revealed a significant increase in sialic acid concentration, a marker of ocular mucin, at 5 minutes after application, whereas a significant decrease was observed with saline. This result indicates the accelerated secretion of mucin from ocular tissues induced by diquafosol. A clinical study to determine the efficacy of diquafosol in patients with dry eye revealed improvements in tear breakup time, keratoconjunctival staining scores, and Schirmer test score, accompanied by an increase in sialic acid concentration in tears. Investigating normal and dry eye conditions through tear analysis may clarify the pathophysiology of dry eye conditions and support the efficacy of treatments.

Purpose: To evaluate the efficacy of topical application of 3% diquafosol tetrasodium solution for the treatment of soft contact lens (SCL) wearers with dryness. In addition to clinical tests and subjective symptoms, we assessed the fluorescence intensity of wheat germ agglutinin conjugate of fluorescein (F-WGA) used as a marker of membrane-associated mucins and sialic acid concentration in tear fluids as a marker of secreted mucins., Methods: Twelve SCL wearers with dryness symptoms were treated with diquafosol for 4 weeks. Clinical tests included the tear film break-up time (BUT), corneal and conjunctival fluorescein staining scores, and Schirmer values. Subjective symptoms were evaluated by the Dry Eye-Related Quality-of-Life Score (DEQS). Fluorescence intensities in the central cornea were measured by fluorophotometry at 5 minutes after a 5% F-WGA solution was applied to the eye. The tears collected by the Schirmer test strips were analyzed by high-performance liquid chromatography (HPLC), and the concentrations of sialic acid; total protein; and the four major tear proteins secretory IgA, lactoferrin, lipocalin-1, and lysozyme proteins were measured., Results: Comparing the results before and after diquafosol treatment, BUT (p < 0.01), kerato-conjunctival staining score (p < 0.05), corneal staining score (p < 0.05), and DEQS score (p < 0.01) showed statistically significant improvements. The F-WGA fluorescence intensities (p < 0.0001) significantly increased after treatment, whereas the concentrations of sialic acid and tear proteins remained unchanged., Conclusions: Topical application of diquafosol solution to the SCL wearers with dryness improved biomarker of membrane-associated mucins, BUT, staining of cornea and conjunctiva, and subjective symptoms.

Purpose: Unstable tear film characterized by shorting of tear break-up time (BUT) is associated with discomfort and dryness in contact lens wearers. The glycocalyx is thought to be crucial in maintaining the wettability and lubrication of the ocular surface. We evaluated the ocular surface glycocalyx in soft contact lens (SCL) wearers using a fluorescein-labeled wheat germ agglutinin (F-WGA) as a marker to demonstrate the ocular surface glycoconjugates in vivo., Methods: Twenty experienced SCL wearers and 20 healthy volunteers with no history of CL wearing (controls) were enrolled in the study. After applying a 5% F-WGA solution to the eyes of study individuals, fluorescent intensities in their respective central corneas were measured by fluorophotometry. The relationship between F-WGA intensity in the corneal surface and clinical parameters associated with contact lens wear were analyzed., Results: F-WGA fluorescence intensity in the SCL group was 418.5 ± 103.3, which was significantly lower than that of the controls (825.0 ± 179.8; p < 0.0001, Mann-Whitney test). F-WGA fluorescence intensity was not correlated with Schirmer's test values or age, whereas a statistically significant correlation between F-WGA fluorescence intensity and tear film BUT was observed (r = 0.77, p < 0.0001). The decrease in F-WGA fluorescence intensity could be reversed by discontinuation of SCL use., Conclusion: Reduction and/or compositional alteration of ocular surface glycocalyx may be one of the causative factors of SCL-induced eye dryness.

Purpose: To evaluate the clinical efficacy of 3% diquafosol sodium ophthalmic solution for dry eye, and to analyze the concentration of tear proteins and mucin-like substances after the treatment., Methods: Fifty eyes of 25 patients with dry eye syndrome were prospectively enrolled. The patients were treated with diquafosol solution at a dose of 1 drop in each eye 6 times daily for 4 weeks. The parameters of clinical efficacy were tear osmolarity, tear breakup time (BUT), fluorescein staining scores for the cornea and conjunctiva, Schirmer test values, and subjective symptoms evaluated using the ocular surface disease index (OSDI). Tears collected with Schirmer test strips were analyzed by high-performance liquid chromatography, and the concentrations of the total protein and the 4 major tear proteins, namely, secretory IgA, lactoferrin, lipocalin-1, lysozyme, and N-acetyl-neuraminic acid (Neu5Ac), were measured. Neu5Ac is a major sialic acid, a marker of secretory mucins., Results: The BUT, keratoconjunctival staining scores, and Schirmer test values were improved with statistical significance after the treatment with diquafosol solution, while changes in the other parameters, including tear osmolarity, corneal staining scores, and OSDI scores were not significant. The Neu5Ac concentration was significantly increased, which was not accompanied by changes in tear proteins., Conclusions: Topical application of diquafosol significantly improved the clinical parameters of the BUT, keratoconjunctival staining scores, and Schirmer test values and was accompanied by increased sialic acid content in the tears of patients with dry eye.

Purpose: This study was performed to assess the impact of dry eye on patients' quality of life (QOL) and to analyze the association between subjective symptoms and ocular surface findings of dry eye., Methods: The study population consisted of 158 patients with dry eye aged 20 years or older who visited any of the 15 medical care facilities enrolled in the study. The backgrounds and ocular findings of the patients were investigated, and their QOL was evaluated with the Japanese version of the 25-item National Eye Institute Visual Functioning Questionnaire (VFQ-25) and of the Medical Outcomes Study (MOS) 8-item Short-Form Health Survey (SF-8) to examine the association between subjective symptoms and ocular surface findings., Results: Of the patients enrolled, 15 were men and 143 were women, and their average age was 62.5 +/- 12.6 years. Sixty patients (38.0%) had comorbid Sjögren syndrome (SS). The results of Schirmer testing, fluorescein staining, and rose bengal staining for SS patients were significantly worse than those for the non-SS patients, but the VFQ-25 and SF-8 scores were not significantly different between the SS and non-SS patients. In the ocular surface findings, a weak association between the fluorescein staining scores and general vision scores, a subscale of the VFQ-25, was found. However, the ocular surface findings and VFQ-25/SF-8 results in the simple correlation analysis as well as in the multiple linear regression analysis showed no significant associations., Conclusions: Ocular surface findings and QOL scores of patients with dry eye appear to disagree. Therefore, it is necessary to address subjective symptoms and QOL scores in addition to examination findings when evaluating dry eye.

Purpose: To describe a method of quantifying the tear meniscus height (TMH) and using these values to diagnose patients with dry eye., Methods: Thirty-eight eyes of 19 healthy subjects and 14 patients diagnosed with dry eye were studied. Each eye received 2 microL of 1% fluorescein-sodium solution in the conjunctival sac, and digital photographs were taken of the external surface of the eye with a fundus camera. The tear meniscus was extracted from the digitalized image and used to measure the TMH with NIH image software. The correlation between the mean TMH and Schirmer test values or cotton-thread test values was evaluated., Results: The means of the upper and lower TMH in healthy subjects were 0.22 +/- 0.06 and 0.24 +/- 0.08 mm, respectively. The comparable values in patients with dry eye were 0.17 +/- 0.04 and 0.17 +/- 0.07 mm (upper TMS, P = 0.01; lower TMH, P = 0.04; unpaired t test). A significant correlation was found between the TMH and Schirmer test values (r = 0.72, P = 0.01) but not with cotton-thread test values., Conclusions: Fluorescein photographs of the eye can be used to quantify the upper and lower TMH separately and simultaneously without specialized equipment. This technique can be used for the diagnosis of dry eye.

Purpose: The pathophysiology of nasolacrimal duct obstruction (NLDO) may involve quantitative as well as qualitative changes in tears. We measured tear protein concentrations in patients with primary acquired NLDO and compared them with the tear proteins in healthy individuals and patients with dry eye disease. Study Design: Case–control study. Methods: Twenty-four patients diagnosed with primary acquired NLDO who underwent endoscopic lacrimal passage intubation were included in the study. Tear fluid was collected with Schirmer's test strips three times: before intubation, after intubation while the nasolacrimal tube was in place, and after extubation. At the same time, 24 age-matched normal controls and 24 patients with dry eye were selected from subjects whose tears were collected during the same study period. We measured the following components of tear fluid: total protein, lactoferrin, albumin, and interleukin 6 (IL-6) levels. Results: Total proteins and albumin levels in tears of the NLDO group were significantly lower than those of the control group (P < 0.001 and P = 0.014, respectively, Mann–Whitney U test). Total proteins, albumin, and lactoferrin levels were significantly increased after extubation of nasolacrimal tube (P < 0.001, P = 0.004, and P = 0.029, respectively, Wilcoxon matched-pairs signed-rank test). There were no statistically significant differences in total protein, albumin, lactoferrin and IL-6 levels between patients with NLDO after lacrimal passage extubation and controls. Conclusions: Our study shows distinct differences in protein composition of tear fluid in NLDO eyes and demonstrates that these can be normalized by nasolacrimal tube placement. [ABSTRACT FROM AUTHOR]

Background: This study was performed to estimate the annual direct cost incurred by dry eye patients, which includes expenses for treatment and drugs, as well as the cost of punctal plugs. Methods: The study group consisted of 118 dry eye patients aged 20 years or older who visited any of the 15 medical care facilities that participated in this prospective cohort dry eye study. We estimated annual direct costs from outpatient medical records and survey questionnaires obtained from patients. Results: Of the total patients enrolled, 10 were men and 108 women, and their average age was 64.1 ± 11.2 years. The number of hospital visits made by patients was 5.8 ± 3.6 per year. Among those who used ophthalmic solutions, the numbers of bottles used per year were as follows: 32.1 ± 20.8 bottles of hyaluronic acid ophthalmic solution (87 patients), 53.1 ± 42.2 bottles of artificial tears (40 patients), and 33.2 ± 23.2 bottles of over-the-counter eyedrops (15 patients). In patients with punctal plugs, 4.1 ± 3.9 plugs were used annually. The annual drug cost was 32,000 ± 21,675 Japanese yen (323 ± 219 US dollars). The clinical cost was 16,318 ± 9961 Japanese yen (165 ± 101 US dollars). The total direct costs including punctal plug treatment amounted to 52,467 ± 38,052 Japanese yen (530 ± 384 US dollars). Conclusion: Although treatment modalities for dry eye in Japan were different from those in the US and in European countries, the direct cost of dry eye patients in Japan was comparable with that reported in those countries. Considering the high prevalence of dry eye, the direct cost of this chronic condition may be significant. [ABSTRACT FROM AUTHOR]

(1) Background: To evaluate the characteristics of fluorescein breakup patterns (FBUPs) among patients with dry eye disease (DED) and efficacy of FBUPs as a diagnostic test for DED subgroups. (2) Methods: The study enrolled 449 patients with DED. FBUPs were categorized as follows: area break (AB), line break (LB), spot break (SB), dimple break (DB), and random break (RB). Schirmer value, fluorescein breakup time (FBUT), keratoconjunctival score, DED subgroups and subjective symptoms were examined. (3) Results: LB patients presented with short FBUT and high keratoconjunctival score. AB patients presented with short FBUT, high cornea and keratoconjunctival scores. SB patients were young with short FBUT. DB patients exhibited low keratoconjunctival score. RB patients were young, with long FBUT and low keratoconjunctival scores. Among DED subgroups, LB and AB constituted 74.7% of aqueous-deficiency dry eye (ADDE). SB and DB constituted 42.4% of short FBUT dry eye (short FBUT-DE). Post-test probabilities and positive likelihood ratios for ADDE were 58.7% and 1.63, respectively; those for short FBUT-DE were 46.3% and 2.02, respectively. Patients with SB and AB exhibited significantly severe subjective symptoms than other FBUPs. (4) Conclusions: FBUPs are associated with both objective findings and symptoms of DED and may be a clinical tool for identification of DED subgroups. [ABSTRACT FROM AUTHOR]

We investigated the association between dry eye disease and systemic comorbidities, including dry eye subtype, quality of life (QOL) and health utility among patients with dry eye disease. This cross-sectional, observational study enrolled 449 patients with dry eye disease (386 females; mean age, 62.6 ± 15.7 [range, 21–90] years). Ophthalmic examination findings included tear film break-up time (TBUT), Schirmer I value and keratoconjunctival staining score. QOL and health utility were evaluated using the Dry Eye-Related Quality-of-Life Score (DEQS) and Human Utility Index Mark 3 (HUI-3), respectively. Background information, including systemic comorbidities, was obtained. Prevalence of systemic comorbidities was 48.8% (219/449). No significant difference occurred between DEQS and systemic comorbidity. However, patients with dry eye disease and systemic comorbidities (depression and insomnia) exhibited significantly worse ocular surface parameters, particularly regarding TBUT, than those without. Dry eye disease with insomnia or depression comorbidity significantly correlated with friction-related diseases (including conjunctivochalasis or lid wiper epitheliopathy). A high prevalence of several systemic comorbidities occurred in patients with dry eye disease. This study shows an association between ocular signs and systemic comorbidities, particularly depression and insomnia. Ophthalmologists should be aware of patients' systemic comorbidities in the diagnosis and management of dry eye disease. [ABSTRACT FROM AUTHOR]