Published papers

Purpose To investigate tear function and prevalence of dry eye disease (DED) in visual display terminal (VDT) users. Design Cross-sectional study. Methods Six hundred and seventy-two young and middle-aged Japanese office workers who used VDT completed questionnaires and underwent dry eye testing. We estimated the prevalence of DED using logistic regression analysis to examine associations between DED and possible risk factors. The ocular surface feature, prevalence of DED, and risk factors were evaluated. Results Of the 672 workers, 561 (83.5%, mean age: 43.3 ± 9.1 years) completed the questionnaire. The percentage of women with a composite outcome of definite DED or probable DED was 76.5%, which was higher than that among men (60.2%; odds ratio [OR] = 2.00; 95% confidence interval [CI], 1.29-3.10, P =.002). Workers over 30 years of age had a higher risk of DED (OR = 2.22; 95% CI, 1.06-4.66), as did workers using a VDT >8 hours per day (OR = 1.94; 95% CI, 1.22-3.09). Average Schirmer value was 18.7 ± 11.7 mm and tear break-up time (TBUT) was 4.0 ± 2.5 seconds (78.6% of study participants had TBUT ≤5 seconds). Conclusions DED is prevalent among young to middle-aged Japanese VDT users. Ophthalmic findings revealed short TBUT and corneal staining accompanied by normal Schirmer test values. Increased risk for DED was noted for women aged over 30 years and prolonged VDT use. Measures to modify the adverse impact of VDT use on the ocular surface may provide a positive impact on public health and quality of life for office workers using VDTs.

PURPOSE: To evaluate surgically induced changes in corneal, internal, and ocular higher-order aberrations (HOAs) after phakic intraocular lens (PIOL) implantation and compare them between two PIOLs with different pupillary diameters. METHODS: Twenty-three eyes with an Artisan PIOL (Ophtec BV, Groningen, The Netherlands) (Artisan group) and 30 eyes with an Artiflex PIOL (Ophtec BV) (Artiflex group) were retrospectively evaluated. The corneal, internal, and ocular HOAs and refractive data were recorded preoperatively and 6 months postoperatively. The root mean squares (RMSs) of the total HOAs from the third- to sixth-order Zernike coefficients were calculated. The RMSs of the third- and fourth-order coefficients represented coma-like aberrations (S3) and spherical-like aberrations (S4), respectively. The main outcome measures were the differences in the parameters among the groups with different pupillary diameters. RESULTS: The mean postoperative spherical equivalents decreased from -11.84 ± 4.90 to -0.16 ± 0.40 diopters and -9.78 ± 3.20 to -0.09 ± 0.26 diopters in the Artisan and Artiflex groups, respectively. With the 4- and 5-mm pupillary diameters, the postoperative internal and ocular spherical aberrations (Z40) were significantly lower in the Artiflex group than in the Artisan group (4 mm, P = .002, .024; 5 mm, P = .004, .022, respectively). With the 6-mm pupillary diameter, there were no significant postoperative differences in any parameter measured between groups; both groups had positive spherical aberration values. CONCLUSIONS: The postoperative ocular spherical aberrations were positive after Artisan and Artiflex implantation. The postoperative ocular spherical aberration was greater in the Artisan group, possibly due to differences in the SAs of both PIOLs. Copyright © SLACK Incorporated.

The morbidity of ocular diseases, including macular degeneration, diabetic retinopathy, and dry eye disease, has been gradually increasing worldwide. Because these diseases develop from age-associated ocular dysfunctions, interventions against the aging process itself may be a promising strategy for their management. Among the several approaches to interrupt aging processes, calorie restriction (CR) has been shown to recover and/or slow age-related functional declines in various organs, including the eye. Here, we review interventions against the aging process as potential therapeutic approaches to age-related ocular diseases. The effects of CR and CR mimetics in animal models of age-related eye diseases are explored. Furthermore, we discuss the possibilities of expanding this research to prospective studies to elucidate the molecular mechanisms by which CR and/or CR mimetics preserve ocular functions. © 2013 The Authors.

Purpose. To investigate the expression pattern of claudins in human corneal endothelium, and to evaluate the functional role of the claudin-10b subtype. Methods. Corneal endothelium with Descemet's membrane and the corneal epithelium were stripped from donor human corneal stroma. Reverse transcription-polymerase chain reaction (RT-PCR) was performed to evaluate the claudin subtypes expressed in corneal endothelium, stroma, and epithelium. Immunohistochemistry was performed to confirm the expression of claudin subtypes in corneal endothelium, and the expression pattern was compared to that of corneal epithelium. Finally, transendothelial resistance (TER), short-circuit current (SCC), and potential difference (PD) were measured in human corneal endothelial cell line B4G12 cells with or without claudin-10 small interfering RNA (siRNA) transfection by Ussing chamber system. Results. Transcripts for claudin-1, -2, -3, -4, -7, -10b, -11, -15, -22, -23, and -24 were identified in corneal endothelium sample by RT-PCR. Immunohistochemistry confirmed the expression of claudin-1, -2, -4, -7, -10, -11 -15, -22, and -23 in corneal endothelium. In corneal stroma, claudin-1, -2, -3, -4, -5, -6, -7, -8, -10b, -11, -12, -14, -15, -22, -23, and -24 were identified by RTPCR. In corneal epithelium, claudin-1, -3, -4, -7, -11, -14, and -23 were identified by immunohistochemistry and RT-PCR. Downregulation of claudin-10b by siRNA resulted in the decrease of SCC and PD, but not TER, in B4G12 cells. Conclusions. The expression pattern of claudin-10b+/claudin-14- was specific in corneal endothelium among the three corneal layers. Claudin-10b may play an important role in the tight junction of corneal endothelium. © 2013 The Association for Research in Vision and Ophthalmology, Inc.

PURPOSE: To design a mathematical model that can predict the relationship between the ganglion cell complex (GCC) thickness and visual field sensitivity (VFS) in glaucoma patients.DESIGN: Retrospective cross-sectional case series.METHOD: Within 3 months from VFS measurements by the Humphrey field analyzer 10-2 program, 83 eyes underwent macular GCC thickness measurements by spectral-domain optical coherence tomography (SD-OCT). Data were used to construct a multiple logistic model that depicted the relationship between the explanatory variables (GCC thickness, age, sex, and spherical equivalent of refractive errors) determined by a regression analysis and the mean VFS corresponding to the SD-OCT scanned area. Analyses were performed in half or 8 segmented local areas as well as in whole scanned areas. A simple logistic model that included GCC thickness as the single explanatory variable was also constructed. The ability of the logistic models to depict the real GCC thickness/VFS in SAP distribution was analyzed by the χ2 test of goodness-of-fit. The significance of the model effect was analyzed by analysis of variance (ANOVA).RESULTS: Scatter plots between the GCC thickness and the mean VFS showed sigmoid curves. The χ2 test of goodness-of-fit revealed that the multiple logistic models showed a good fit for the real GCC thickness/VFS distribution in all areas except the nasal-inferior-outer area. ANOVA revealed that all of the multiple logistic models significantly predicted the VFS based on the explanatory variables. Although simple logistic models also exhibited significant VFS predictability based on the GCC thickness, the model effect was less than that observed for the multiple logistic models.CONCLUSIONS: The currently proposed logistic models are useful methods for depicting relationships between the explanatory variables, including the GCC thickness, and the mean VFS in glaucoma patients.

Background: To elucidate the biological effects of blocking fluorescent light on the retina using specific blocking materials. Methods: Seven- to 8-week-old BALB/c mice were divided into three groups and placed in one of the three boxes: one blocked ultraviolet and violet wavelengths of light (violet blockade), one blocked ultraviolet, violet, blue and some other visible wavelengths (blue-plus blockade), and one allowed most visible light to pass through (control). They were then exposed to a white fluorescent lamp for 1h at 5.65E-05mW/cm2/s. After treatment, the electroretinogram, retinal outer nuclear layer thickness and retinal outer segment length were measured. In addition, retinal apoptotic cells were quantified by TdT-mediated dUTP nick-end labelling assay and c-Fos messenger RNA, and protein levels were measured by real-time reverse-transcription polymerase chain reaction and immunoblot analyses, respectively. Results: The blue-plus blockade group retained a significantly better electroretinogram response following light exposure than the control or violet blockade groups. The blue-plus blockade group also exhibited greater outer nuclear layer thickness and greater outer-segment length, and fewer apoptotic cells after light exposure than the other groups. The c-Fos messenger RNA and protein levels were substantially reduced in the blue-plus blockade group and reduced to a lesser extent in the violet blockade group. Conclusions: The blockade of blue plus additional visible wavelengths of light was most effective in protecting the retina from light-induced damage. The blockade of violet light alone was also effective in reducing intracellular molecular responses, but these effects were not sufficient for attenuating retinal degeneration. © 2014 Royal Australian and New Zealand College of Ophthalmologists.

Purpose: To report that spontaneous postkeratoplasty wound dehiscence or gaps caused by suture removal may occur years after penetrating and deep lamellar keratoplasty. Methods: We retrospectively reviewed the medical records of 667 keratoplasty patients (890 eyes). This study included 8 eyes of 8 patients (3 men and 5 women) aged 64 to 86 years who suffered from spontaneous wound dehiscence or gaps caused by suture removal. We examined their clinical backgrounds such as surgical procedure, reason for suture removal, and time interval between keratoplasty and suture removal. Results: The surgical procedures included 6 penetrating keratoplasties and 2 deep anterior lamellar keratoplasties. The most common reason for suture removal was high corneal astigmatism. Time interval between keratoplasty and suture removal was 15.9 ± 7.7 months (7-26 months). Three patients underwent suture removal from 6 months to 1 year after keratoplasty, 3 patients from 1 to 2 years, and 2 patients after more than 2 years. Conclusions: Whenever postoperative keratoplasty suture is removed, it is important to consider that wound dehiscence or gaps may occur without incidence of trauma.

Purpose. To assess the association of dry eye disease (DED) with physical activity and sedentary behavior. Methods. The cross-sectional survey conducted included Japanese office workers who use visual display terminals (n = 672). DED was assessed according to the Japanese Dry Eye Diagnostic Criteria, and participants were categorized into "definite DED," "probable DED," or "non-DED" groups based on the results of DED examinations. Physical activity and sedentary behavior of participants were assessed using the International Physical Activity Questionnaire (IPAQ), and physical activity level was calculated in metabolic equivalent units per week (MET, min/week). Participants were classified as having a high, moderate, or low level of physical activity. Results. Participants with abnormal tear break-up time (BUT) (≤5 s) were involved in sedentary behavior for significantly longer duration than those with normal BUT (P = 0. 035). Non-DED participants (14.5%) tended to have higher levels of physical activity than definite DED participants (2.5%). Participants with definite DED had significantly lower MET scores than those with non-DED (P = 0. 025). Conclusions. Our findings suggest that a lower level of physical activity and sedentary behavior are associated with DED; however, longitudinal/intervention studies with large groups of participants are needed to validate these findings.

Aim. To find predictive and indicative markers of risk for development of retinopathy of prematurity (ROP) and its progression to the stage requiring laser treatment, in premature infants whose gestational age (GA) was under 33 weeks. Methods. We retrospectively reviewed medical records of 197 premature infants born in 2005-2010 whose G A < 33 weeks and underwent eye screening at Keio University Hospital. The association between candidate risk factors and development or progression of ROP was assessed. Results. Among the 182 eligible infants (median GA, 29.1 weeks; median birth weight (BW), 1028 g), 84 (46%) developed any stage of ROP, of which 45 (25%) required laser treatment. Multivariate analysis using a stepwise method showed that GA (P = 0.002; 95% confidence interval (CI), 0.508-0.858), BW (P < 0.001; 95% CI, 0.994-0.998), and lower maternal age (P = 0.032; 95% CI, 0.819-0.991) were the risk factors for ROP development and GA (P < 0.001; 95% CI, 0.387-0.609) and lower maternal age (P = 0.012; 95% CI, 0.795-0.973) were for laser treatment. The odds ratio of requiring laser treatment was 3.3 when the maternal age was <33 years. Conclusion. ROP was more likely to be developed and progressed in infants born from younger mother and low GA. © 2014 Atsuro Uchida et al.

The microfabrication and measurements of organic materials have significant potential for industrial and medical applications. In particular, in the medical field, a non-invasive method of measuring the distribution of certain substances contained in organic materials has been strongly demanded. Introducing a fluorescence analysis system to a confocal system would be useful for the characterisation of materials while maintaining space resolution. In this study, we focused on age-related macular degeneration (AMD) as an example, and investigated the possibility of the visualisation of fluorescence spectra. We measured the fluorescence spectrum in photoreceptor cells that were separated from the macular of eyes obtained from an eye-bank, using a microslicer. Mixed spectra of lutein and zeaxanthin, which are not affected by other organisations of eye have been measured. We also evaluated the densities of lutein and zeaxanthin in photoreceptor cells from the spectrum. As a result, the mixing ratio of lutein to zeaxanthin was estimated to be 3.78:6.22. The results showed good agreement with the results of high-performance liquid chromatography (HPLC). The approach presented here can serve as a useful framework for measuring the densities of lutein and zeaxanthin in photoreceptor cells.Copyright © 2014 Inderscience Enterprises Ltd.

Objective. To characterize the epidemiology of Sjögren's syndrome (SS), including prevalence, disease type, extra-glandular involvement, satisfaction of diagnostic criteria sets, and treatment used in Japan. Methods. The Research Team for Autoimmune Diseases, the Research Program for Intractable Disease by the Ministry of Health, Labor and Welfare conducted primary and secondary surveys on epidemiology of SS in 2011. The primary survey covered 4,729 out of 14,095 Japan-wide Hospital Departments to investigate the prevalence of SS. The secondary survey encompassed 214 Hospital Departments that agreed to the survey, to characterize disease type, extra-glandular involvement, satisfaction of diagnostic criteria sets, and treatments. Results. The number of patients with SS in Japan estimated by the primary survey was 68,483. The secondary survey involving data collected from 2,195 SS patients from 98 Hospital Departments showed that the mean age of patients was 60.8 ± 15.2 years, male/female ratio was 1/17.4, primary/secondary SS was about 60%/40% and glandular/extra-glandular form in primary SS was about 70%/25%. The satisfaction rate was 53.8% for the 1999 revised Japanese Ministry of Health criteria for the diagnosis of SS, 47.7% for the 2002 American-European Consensus Group classification criteria for SS and 49.6% for 2012 American College of Rheumatology classification criteria for SS. Corticosteroids were used by 752 of 2,195 patients (34%), immunosuppressants by 358 patients (16%), biologics by 68 patients (3%) and secretagogues by 695 patients (32%). Conclusion. The surveys provided valuable information on the epidemiology of SS including prevalence, disease type, extra-glandular involvement, satisfaction of diagnostic criteria sets and treatments used today in Japan. © 2014 Japan College of Rheumatology.

Purpose: To evaluate the accuracy of intraocular lens (IOL) power calculations using ray tracing software in eyes after myopic laser in situ keratomileusis (LASIK). Methods: Twenty-four eyes of 17 cataract patients who underwent phacoemulsification and IOL implantation after myopic LASIK were analyzed retrospectively. The IOL power calculation was performed using OKULIX ray tracing software. The axial length was measured using the IOLMaster and keratometry data using TMS2N. The accuracy of the IOL power calculation using OKULIX was compared with those using the Camellin-Calossi, Shammas-PL, Haigis-L formulas and the double-K SRK/T formula using 43.5 diopters (D) for the Kpre. Results: The mean values of the arithmetic and absolute prediction errors were 0.63 ± 0.85 and 0.80 ± 0.68 D, respectively. The arithmetic prediction error by OKULIX was a significant hyperopic shift of the distribution of the postoperative refractive errors compared to the Camellin-Calossi, Shammas-PL and Haigis-L formulas (P < 0.05), and the absolute prediction error showed no significant difference with other formulas. The prediction errors using OKULIX were within ±0.5 D in 10 eyes (41.7 %) and within ±1.0 D in 18 eyes (75.0 %). The percentages of eyes within ±1.0 D using OKULIX were comparable to those obtained using the Camellin-Calossi, the Shammas-PL formulas and the double-K SRK/T formula using 43.5 D for the Kpre, and significantly (P < 0.05) higher than that obtained using the Haigis-L formula. Conclusions: IOL power calculations using OKULIX provided predictable outcomes in eyes that had undergone a previous myopic LASIK. © 2014 Japanese Ophthalmological Society.

IMPORTANCE There are limited reports on the relationship between mucin 5AC (MUC5AC) concentrations in tears, working hours, and the frequency of ocular symptoms in visual display terminal (VDT) users. This investigation evaluated these relationships among patients with dry eye disease (DED) and individuals serving as controls. OBJECTIVE To determine the relationship between MUC5AC concentration in the tears of VDT users based on the diagnosis of DED and frequency of ocular symptoms. DESIGN, SETTING, AND PARTICIPANTS An institutional, cross-sectional studywas conducted. Participants included 96 young and middle-Aged Japanese office workers. Both eyes of 96 volunteers (60 men and 36 women) were studied. Participants working in a company that used VDTs completed questionnaires about their working hours and the frequency of ocular symptoms. Dry eye disease was diagnosed as definite or probable, or it was not present. Tear fluid was collected from the inferior fornix after instillation of 50 μL of sterilized saline. The MUC5AC concentration was normalized to tear protein content and expressed as MUC5AC (nanograms) per tear protein (milligrams). The differences in MUC5AC concentration between DED Groups, between VDT working hours (short, intermediate, and long), and between symptomatic and asymptomatic Groups were evaluated with 95%CIs based on nonparametric Hodges-Lehmann determination. MAIN OUTCOMES AND MEASURES Ocular surface evaluation, prevalence of DED, and MUC5AC concentration. RESULTS The prevalence of definite and probable DED was 9%(n = 9) and 57%(n = 55), respectively. The mean MUC5AC concentration was lower in the tears of VDT users with definite DED than in those with no DED (P = .02; Hodges-Lehmann estimator, -2.17; 95%CI, -4.67 to -0.30). The mean MUC5AC concentration in tears was lower in the Group that worked longer hours than in the Group that worked shorter hours (P = .049; estimated difference, -1.65; 95%CI, -3.12 to 0.00). Furthermore, MUC5AC concentration was lower in participants with symptomatic eye strain than in asymptomatic individuals (P = .001; estimated difference, -1.71; 95%CI, -2.86 to -0.63). CONCLUSIONS AND RELEVANCE The data obtained in the present study suggest that office workers with prolonged VDT use, as well as those with an increased frequency of eye strain, have a low MUC5AC concentration in their tears. Furthermore, MUC5AC concentration in the tears of patients with DED may be lower than that in individuals without DED. Copyright 2014 American Medical Association. All rights reserved.

Purpose: To evaluate the postoperative outcome of toric intraocular lens (TIOL) implantation for cataract patients with high corneal astigmatism. Methods: This retrospective study included 24 eyes of 22 patients with high corneal astigmatism exceeded-1.50 D who underwent cataract surgery and implantation of TIOL (SN6AT6:12 eyes, SN6AT7:8 eyes, SN6AT8:3 eyes, SN6AT9:1 eye). The mean age of all cases was 68.1 years. Visual acuity, corneal astigmatism, subjective refraction, and rotation error were recorded preoperatively and 1 month postoperatively. Results: The uncorrected and correted distance visual acuities and subjective refraction were significantly (p<0.001) improved after TIOL implantation. There was no significant difference in corneal astigmatism between preoperatively and postoperatively. The mean rotation error was 2.8°. Conclusion: TIOL was effective for cataract patients with high corneal astigmatism.

The authors report the characteristics of fundus autofluorescence (FAF) images in a patient with galactosialidosis who presented with a macular cherry-red spot ophthalmoscopically. The cherry-red spot in the macula was hyperreflective in the FAF images. Optical coherence tomography (OCT) revealed an abnormally hyperreflective region in the retinal ganglion cell layer; however, the boundary between hyperreflective and normal regions was not clear. The findings indicate that FAF may be a more useful method to detect macular lesions than conventional funduscopic examination and OCT imaging in patients with lysosomal storage diseases presenting with a macular cherry-red spot.

Background/aims: To study the initial characteristics and response to intravitreal ranibizumab (IVR) treatment of age-related macular degeneration (AMD). Methods: We reviewed the clinical records of 141 eyes in 141 AMD patients who received monthly IVR for 3 months and thereafter pro re nata (PRN) injections for 9 months as the first treatment for AMD. Patients whose best corrected visual acuity (BCVA) worsened at month 12, and those with increased exudative fundus findings after IVR or an increased central retinal thickness of more than 100 μm at month 12, were considered to be non-responders as judged by BCVA and fundus findings, respectively. Non-responders' initial characteristics were analysed using logistic regression models. Results: 14.9% of eyes were non-responders as judged by BCVA, and 17.0% were non-responders as judged by fundus findings. Initial fibrovascular pigment epithelial detachment (PED) (OR 22.9, 95% CI 2.61 to 201) and serous PED (OR 4.12, 95% CI 1.08 to 15.8) were associated with non-response as judged by BCVA. Initial fibrovascular PED (OR 33.5, 95% CI 2.95 to 381) and type 1 choroidal neovascularization (OR 6.46, 95% CI 1.39 to 30.0) were associated with non-response, as judged by fundus findings. Conclusions: Although most AMD responded to IVR, non-responders had initial clinical characteristics that might be informative for managing their treatment.

While corneal endothelial damage in its most advanced stage results in bullous keratopathy where corneal transplantation is needed, there is no severity grading for corneal endothelial damage. The Japanese Corneal Society formed a working group to establish a severity grading for corneal endothelial damage. The following are the proposed severity grading criteria. Normal: Corneal endothelial cell (CEC) density is 2000 cells/mm2 or more. Grade 1: CEC density between 1000 and 2000 cells/ mm2. The corneal endothelium is below the normal physiological condition. Grade 2: CEC density between 500 and 1000 cells/ mm2. The transparency of the corneal endothelium is endangered. Even slight damage can induce bullous keratopathy. Grade 3: CEC density below 500 cells/mm2 but no corneal edema is observed. Grade 4: Bullous keratopathy. The cornea is opaque with edema.

Dry eye disease (DED) is defined as a multifactorial disease of the tears and ocular surface that results in symptoms of discomfort, visual disturbance, and tear-film instability, with potential damage to the ocular surface. It is thought to be associated with reduced quality of life (QOL). The aim of the present study was to investigate the effects of DED on health-related QOL in Japanese university sedentary office workers who are daily users of visual display terminal. In this study, 163 university staff (99 male and 64 female), aged 23-69 years, served as study subjects. Subjects were asked to answer the following three questions. (1) How often do your eyes feel dry? (2) How often do your eyes feel irritated? (3) Have you ever been diagnosed by a clinician as having dry eye syndrome? Sixty-eight subjects who answered "constantly," "often", or "sometimes" to both questions 1 and 2 were classified as the DED Group, and the remaining 95 were defined as the Non-DED Group. QOL was assessed by the SF-36 questionnaire, which consisted of 36 items to produce three summary scores, namely, mental, physical, and role/social component summary scores. For males, the DED Group had significantly lower scores than the Non-DED Group for mental component summary (MCS) (P = 0.005). In multiple regression analysis, MCS scores were adversely related to DED in males (P = 0.015). DED was associated with worsened QOL. DED should be regarded as a factor that can lead to deterioration of mental health.

PURPOSE: To investigate the relationship between the early signs of age-related macular degeneration (AMD) and the risk of developing exudative AMD (typical AMD or polypoidal choroidal vasculopathy [PCV]) in the fellow eye of Japanese patients with unilateral exudative AMD, focusing particularly on eyes with only pigmentary abnormality. METHODS: This study is a retrospective observational consecutive case series. We retrospectively reviewed the medical charts of patients who revisited the AMD clinic from 2010 to 2011 and confirmed 129 cases with unilateral exudative AMD at their first visit (baseline). The non-affected eyes at baseline (the second eye) were categorized by the presence of early signs of AMD. The incidence of exudative AMD (typical AMD or PCV) in the fellow eye was confirmed by fluorescein and indocyanine green angiography. RESULTS: Of the 129 patients, 14 (10.9%) developed exudative AMD in the fellow eye (median follow-up, 3.2 years; n = 7 typical AMD and n = 7 PCV). Eyes with both pigmentary abnormalities and large drusen were more likely to develop typical AMD (age- and sex-adjusted odds ratio = 9.46, 95% confidence interval = 1.05 to 85.0), whereas pigmentary abnormalities without large drusen were associated with PCV (age- and sex-adjusted odds ratio = 15.9, 95% confidence interval = 1.8 to 140.5). CONCLUSIONS: There was a difference in the association between early signs of AMD and incident development of either typical AMD or PCV. Further research is warranted to determine whether pigmentary abnormalities alone may be an important risk factor for PCV in Asians. Copyright © 2014 American Academy of Optometry.