Chika Shigeyasu

Impact of dry eye on work productivity

Background The purpose of this study was to evaluate the impact of dry eye on work productivity of office workers, especially in terms of presenteeism. Methods A total of 396 individuals aged ≥20 years (258 men and 138 women, mean age 43.4 ± 13.0 years) were recruited through an online survey. Data from 355 responders who did not have missing values were included in the analysis. They were classified into the following four groups according to the diagnostic status and subjective symptoms of dry eye: a definite dry eye group; a marginal dry eye group; a self-reported dry eye group; and a control group. The impact of dry eye on work productivity was evaluated using the Japanese version of the Work Limitations Questionnaire. The cost of work productivity loss associated with dry eye and the economic benefits of providing treatment for dry eye were also assessed. Results The degree of work performance loss was 5.65% in the definite dry eye group, 4.37% in the marginal dry eye group, 6.06% in the self-reported dry eye group, and 4.27% in the control group. Productivity in the self-reported dry eye group was significantly lower than that in the control group (P < 0.05). The annual cost of work productivity loss associated with dry eye was estimated to be USD 741 per person. Conclusion Dry eye impairs work performance among office workers, which may lead to a substantial loss to industry. Management of symptoms of dry eye by providing treatment may contribute to improvement in work productivity.

Diquafosol Tetrasodium Increases the Concentration of Mucin-like Substances in Tears of Healthy Human Subjects

Abstract Purpose: This study was undertaken to determine the effect of topical application of diquafosol tetrasodium on proteins and mucin-like substances from tears of clinically healthy subjects. Methods: Tears were collected from both the eyes of 10 healthy volunteers. Diquafosol tetrasodium solution (3%) was applied once to the right eye and 0.9% sodium chloride solution (saline) once to the left eye. Tear samples were collected by Schirmer test strips before application and 5, 15, 30 and 60 min after application. Sialic acid, a marker of mucin-like substances, and major tear proteins including secretory IgA, lactoferrin, lipocalin-1, and lysozyme were measured by high performance liquid chromatography. Results: Levels of total protein, sIgA and lysozyme were transiently decreased in both groups but returned to baseline levels within 15 min after application. The concentration of lactoferrin and lipocalin-1 did not change significantly in both groups. Sialic acid in tears was significantly decreased 5 min after saline application, but significantly increased 5 min after diquafosol application. No significant difference in sialic acid was seen after 15 min in both groups. Conclusions: Topical application of saline and diquafosol resulted in transient decrease of tear proteins possibly due to wash out or dilution effects. In contrast, diquafosol application significantly increased sialic acid, although the effect was transient. This suggests diquafosol stimulates the secretion of mucins from ocular tissues of healthy human subjects.

Annual direct cost of dry eye in Japan

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.

Clinical features of anterior segment dysgenesis associated with congenital corneal opacities.

Purpose: Anterior segment dysgenesis is one of the main causes of congenital corneal opacities. In this study, we investigated the clinical features and visual outcomes of patients with anterior segment dysgenesis in a large number of cases. Methods: The medical records of patients with congenital corneal opacities in relation to anterior segment dysgenesis seen in the National Center for Child Health and Development, Japan, between April 2002 and October 2009, were retrospectively studied. Results: Records of 220 eyes of 139 patients were reviewed. Mean follow-up period was 5 years. Clinical diagnoses were Peters anomaly (72.7%), anterior staphyloma (11.4%), Rieger anomaly (7.7%), sclerocornea (6.4%), and others (1.8%). Visual acuity was measured in 61 patients. The best-corrected visual acuity in the better eye of bilaterally involved patients was 20/60 to 20/1000 (low vision according to the International Classification of Diseases, Ninth Revision, Clinical Modification) in 43.2% and less than 20/1000 (legally blind) in 24.3%. Fundus examination was performed in 82 eyes, and disorders were seen in 12 (12 of 82; 14.6%). Systemic abnormalities were present in 35 patients (35 of 139; 25.2%); a family history was present in 5 patients (5 of 139; 3.6%). Of the 160 eyes of 109 patients with Peters anomaly, 51 patients (51 of 109; 46.8%) had bilateral Peters anomaly, 30 (30 of 109; 27.5%) had fellow eyes that were normal, and 28 (28 of 109, 25.7%) showed other abnormal ocular findings in the fellow eye. Conclusions: Anterior segment dysgenesis shows diverse clinical features, various severities of corneal opacities, and visual outcomes. Further understanding of the disease as an abnormality during embryogenesis and neural crest cell differentiations may be required.

Keratomycosis caused by Aspergillus viridinutans: an Aspergillus fumigatus-resembling mold presenting distinct clinical and antifungal susceptibility patterns

We report here a case of fungal keratitis caused by Aspergillus viridinutans, a member of the genus which was found to have clinical and antifungal susceptibility characteristics distinct from the species it most closely resembles, Aspergillus fumigatus. A 26-year-old woman presented with contact lens-associated keratitis, the etiologic agent of which was initially slow growing and found to be resistant to amphotericin B and voriconazole. Therapeutic keratoplasty was performed and an isolate from a corneal scraping was identified as A. viridinutans through partial DNA sequencing of the β-tubulin gene, along with its slow growth 42°C. In contrast with A. fumigatus, A. viridinutans proved to be resistant to a wider variety of antifungal agents. To the best of our knowledge, this is the first case of keratitis caused by A. viridinutans. Clinical isolates of the genus Aspergillus include rarely encountered species such as A. viridinutans. These species may show clinical manifestations distinct from those of A. fumigatus, including clinical resistance to amphotericin B and voriconazole and relatively low susceptibility to other antifungal agents.

Ocular surface reconstruction after exposure to high concentrations of antiseptic solutions.

Purpose: To report the clinical course in accidental exposure of the cornea to antiseptic solutions in 3 cases. Methods: Observational case series. Exposure to 20% chlorhexidine gluconate solution was observed in 2 cases and to 10% benzalkonium chloride solution in 1 case. Results: Not only superficial damage but also toxicity to corneal endothelial cells leading to corneal edema was observed in all 3 cases. Epithelial transplantation was performed: autologous cultivated limbal epithelial transplantation (auto-CLET), conjunctivolimbal autograft (CLAU), or living-related cultivated limbal epithelial transplantation (lr-CLET). A stable ocular surface was achieved, although exposure to high concentrations of antiseptic solutions caused severe anterior chamber inflammation; cataract and glaucoma developed in 2 cases, requiring further surgical treatment. Conclusions: Exposure to high concentrations of antiseptics causes both ocular surface and intraocular damage. Epithelial transplantation enables restoration of a stable ocular surface. However, management of intraocular consequences, including secondary glaucoma and corneal endothelial damage, still remains a challenge in the prognosis of such cases.

Diquafosol for Soft Contact Lens Dryness: Clinical Evaluation and Tear Analysis.

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.

Fluorophotometric Analysis of the Ocular Surface Glycocalyx in Soft Contact Lens Wearers

Abstract 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.

Evaluation of the frequency of ophthalmic solution application: washout effects of topical saline application on tear components.

Abstract Purpose: To determine and compare the effects of single and frequent topical applications of saline solution on tear protein concentration in clinically normal subjects. Materials and methods: Tears were collected from both eyes of 11 normal volunteers using Schirmer’s strips. Saline solution (0.9% sodium chloride) was applied once in the right eye and five times with an interval of 1 min each in the left eye. Tears were collected before and 5, 15, 30 and 60 min after application of the solution. Total tear protein concentration in the samples was measured by the Bradford method and major tear protein concentration (secretory immunoglobulin A, lactoferrin, lipocalin-1, lysozyme and sialic acid) was measured using a high-performance liquid chromatography assay. Results: A significant decrease was observed in the concentration of total tear protein, major tear proteins and sialic acid after topical application of saline solution. This decrease was attributed to the washout and dilution effect. A low protein concentration persisted longer with more frequent application of the solution. The concentration of secretory immunoglobulin A and sialic acid concentration recovered slowly compared with that of other proteins. Conclusions: Even a single application of saline solution resulted in significant changes in major tear protein and sialic acid concentration in the tears of normal subjects. Differences in the recovery of tear protein concentration may be related to the process of protein production and secretion. A balance between normal tear function and the therapeutic effects of ophthalmic solutions should be considered when deciding the frequency of application, particularly in patients with dry eye.

Abnormal Corneal Lesions Induced by Trastuzumab Emtansine: An Antibody-Drug Conjugate for Breast Cancer.

Purpose: To report a case of atypical corneal lesions presumably induced by trastuzumab emtansine, an antibody–drug conjugate that is designed to selectively deliver cytotoxic agents to human epidermal growth factor receptor 2 (HER2)–positive breast cancer cells. Case: A 64-year-old Japanese woman developed bilateral corneal epithelial abnormalities that originated from the limbus. The corneal lesions covered the superior area in the right eye and both superior and inferior areas including the visual axis in the left eye. The patient had advanced ductal carcinoma of the left breast and had been receiving anticancer treatment with trastuzumab emtansine for 15 months. After switching the chemotherapy from trastuzumab emtansine monotherapy to the combination of docetaxel, trastuzumab, and pertuzumab, the abnormal corneal lesions showed gradual improvement. Conclusions: As corneal epithelial cells express human epidermal growth factor receptor 2 under normal conditions, such cells may also be targeted by trastuzumab emtansine and lead to corneal epithelial lesions.