Published papers

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.

We report the case of a 32-year-old male patient who presented with conjunctival redness after multiple bilateral eye-whitening surgeries. Slit-lamp examination revealed scleral melting, avascular areas, and demarcation lines in both eyes. Considering the treatment history and the clinical findings of the patient, we conclude that the removal of the conjunctiva and Tenon’s layer and use of mitomycin C is not desirable for a healthy ocular surface.

Purpose: To evaluate the efficacy and safety of autologous serum (AS) eye drops combined with punctal plugs (PPs) in patients with Sjögren syndrome (SS)-related dry eye. Methods: A retrospective clinical study was performed in patients with dry eye caused by SS. We evaluated the Schirmer test value, tear breakup time (tBUT), and fluorescein and Rose Bengal (RB) staining scores at baseline, 3 months, 6 months, 1 year, and >1 year after treatment. The dry eye indexes were also evaluated in 2 subgroups, which determined by the using of PPs, including the AS + PP group and AS only group. Results: A total of 56 eyes of 28 patients were investigated with a mean follow-up of 42.3 ± 26.1 months. After the application of AS eye drops, the Schirmer test showed no significant changes. The tBUT (2.7 ± 1.9 seconds) was significantly improved at each time point (3.9 ± 3.1, 4.5 ± 3.1, 3.7 ± 2.5, and 5.1 ± 4.0; P < 0.01), fluorescein staining (4.3 ± 2.8) was significantly improved at each time point (2.2 ± 2.2, 1.9 ± 1.9, 1.8 ± 1.6, and 1.8 ± 1.8; P < 0.01), and RB (2.6 ± 3.0) staining was significantly improved from 6-month treatment (1.5 ± 1.9, 1.9 ± 1.9, and 1.4 ± 1.8; P < 0.05, 0.01, and 0.01, respectively). When combined with PPs, the tBUT and RB staining scores were found to be significantly improved in the AS + PP group compared with those of the AS only group. Conclusions: Long-term application of AS eye drops was found to be an effective and apparently safe treatment for SS dry eye. Furthermore, PPs in combination with AS eye drops were considered to have an additive effect on SS dry eye. ©

Purpose: To evaluate whether the amount of meibum and its viscosity change after intraductal meibomian gland probing in patients with refractory obstructive meibomian gland dysfunction (o-MGD). Methods: Six lid margins of 3 patients with refractory o-MGD underwent intraductal meibomian gland probing. Meibum and the clinical outcome were evaluated before the procedure and at a 1-month postoperative visit. Meibum was quantified with a Meibometer, and its viscosity (Shimazaki grade) was assessed simultaneously. The tear film condition was evaluated by lipid layer interferometry (DR1, Kowa, Nagoya, Japan), and meibomian gland loss was analyzed by noncontact infrared meibography. Lid margin findings, tear break-up time, fluorescein score, and ocular symptoms were also assessed. Results: At the postoperative visits, all cases showed improvements in meibum lipid levels (446-1376, 757-802, and 396-571 meibometer units) and meibum viscosity (grade 3-0, 3-1, and 3-2). Two cases showed an improvement in tear break-up time (2-5 and 0-6 seconds). No morphological changes in the meibomian gland were observed in any cases. Conclusions: Intraductal meibomian gland probing seems to improve meibomian gland lipid levels, and it may be a good treatment option for cases of o-MGD that are resistant to conventional treatment.

Purpose To investigate the phenotype and predisposing factors of a granular corneal dystrophy type 2 transgenic mouse model. Methods Human TGFBI cDNA with R124H mutation was used to make a transgenic mouse expressing human protein (TGFBIR124H mouse). Reverse transcription PCR (RT-PCR) was performed to analyze TGFBIR124H expression. A total of 226 mice including 23 homozygotes, 106 heterozygotes and 97 wild-type mice were examined for phenotype. Affected mice were also examined by histology, immunohistochemistry and electron microcopy. Results RT-PCR confirmed the expression of TGFBIR124H in transgenic mice. Corneal opacity defined as granular and lattice deposits was observed in 45.0% of homozygotes, 19.4% of heterozygotes. The incidence of corneal opacity was significantly higher in homozygotes than in heterozygotes (p = 0.02). Histology of affected mice was similar to histology of human disease. Lesions were Congo red and Masson Trichrome positive, and were observed as a deposit of amorphous material by electron microscopy. Subepithelial stroma was also stained with thioflavin T and LC3, a marker of autophagy activation. The incidence of corneal opacity was higher in aged mice in each group. Homozygotes were not necessarily more severe than heterozygotes, which deffers from human cases. Conclusions We established a granular corneal dystrophy type 2 mouse model caused by R124H mutation of human TGFBI. Although the phenotype of this mouse model is not equivalent to that in humans, further studies using this model may help elucidate the pathophysiology of this disease.

Purpose: To investigate the relationship between visual function and the risks of falling and injurious falls in subjects with primary open angle glaucoma (POAG) Methods: Questionnaires were conducted in 365 POAG patients to assess history of falls and falls with injury and general patient health. Structural equation modeling (SEM) was used to investigate the relationship between visual function, as measured by a patient's binocular integrated visual field and visual acuity (VA), general health and the risks of falling and injurious falls. Results: Among the 365 subjects, 55 subjects experienced falls in the past year. A significant difference was observed in worse-eye VA between the faller and non-faller groups (p = 0.03). SEM of fallers obtained a Root Mean Square Error of Approximation (RMSEA) of 0.035 and a Comparative Fit Index (CFI) of 0.99. The 95% confidence intervals (CI) of regression coefficients from this model suggested better VA and worse VA were significant risk factors for falling. Among the 55 fallers, 22 subjects experienced an associated injury. There was a significant difference in gender between the non-injurious and injurious faller groups (p = 0.002). SEM of injurious fallers obtained a RMSEA of 0.074 and a CFI of 0.97. In this SEM model, the 95% CI of regression coefficients suggested gender and average total deviation values in the lower peripheral visual field were significant risk factors for an injurious fall. Conclusions: This study suggests that worse-eye and better-eye VAs are associated with falls. Furthermore, patients with inferior visual field loss and females were found to be at greater risk of injurious falls.

Purpose: We aimed to explore the prevalence of probable sleep and mood disorders in eye clinic visitors. Methods: This was a cross-sectional study. The participants were outpatients at six eye clinics from January through March, 2014. Outpatients were invited to complete a questionnaire containing the Pittsburgh Sleep Quality Index (PSQI) and Hospital Anxiety and Depression Scale (HADS). A final diagnosis was made, and patients were classified into six diagnostic groups. The main outcome measures were the scores of the PSQI and HADS among the diagnostic groups. Results: A total 1,000 outpatients participated, and 730 patients (mean age 59.5±19.0 years; 487 females) were analyzed after exclusion of children and patients diagnosed with healthy eyes, acute injury, or unilateral pseudophakia. The mean PSQI and HADS scores across all patients were 5.3±3.1 and 9.2±6.2, respectively. For the diagnostic groups, the mean PSQI and HADS scores, respectively, were 5.7±3.3 and 10.2±6.0 for dry eye (n=247), 5.4±3.2 and 9.2±5.7 for bilateral cataracts (n=159), 5.3±3.3 and 8.0±5.3 for bilateral pseudophakia (n=99), and, 5.0±3.1 and 9.8±6.6 for glaucoma (n=109). Overall, 37.3% of patients were poor sleepers (PSQI $6), and 45.5% had possible mood disorders (HADS $10). Stepwise regression analysis revealed that the PSQI and HADS scores were significantly correlated with both age (P,0.05) and the presence of dry eye (P,0.05). Conclusion: The prevalence of sleep and mood disorders was significantly higher in patients with dry eye. The present results suggest consultation-liaison psychiatry services may be beneficial among eye disease patients.

Objectives: To examine the effect of a dietary supplement containing bilberry extract (BE) on eye fatigue induced by acute video display terminal (VDT) loads.Design and setting: A prospective, randomized, double-blind, placebo-controlled study was performed from August 2012 to February 2013 in the Medical Corporation Jico-kai Yagi Hospital, and the Shinyokohama Shinoharaguchi Orthopedic Surgery and Dermatology Clinic, in Japan.Participants: Two hundred eighty-one office workers aged 20–40 years that used VDTs were screened by critical flicker fusion (CFF) and near point accommodation (NPA).Intervention: The participants were randomized to either a BE (480 mg/day) or placebo (vehicle) group, and took allocated capsule, daily, for 8 weeks.Measurements: The CFF, NPA, contrast visual acuity, functional visual acuity, keratoconjunctival epithelial damage, and fluorescein tear film break-up time were examined, and 18 subjective symptoms of eye fatigue were evaluated by questionnaire. Adverse events were reported via medical interviews. Data were collected both before and after VDT load at baseline, and 4, and 8 weeks after daily supplementation with either BE or placebo.Results: Of 281 participants screened, 88 having relatively lower levels of CFF and NPA were enrolled in the study. Of these, 37 control and 43 BE group subjects completed the study. The VDT load-induced reduction in CFF was alleviated after 8 weeks of BE supplementation (95% confidence interval, 0.10–1.60; p=0.023), in contrast to placebo supplementation, while NPA variation was not. Of the subjective symptoms of eye fatigue, VDT load-induced ocular fatigue sensation, ocular pain, eye heaviness, uncomfortable sensation, and foreign body sensation were mitigated more in the BE group than in the control group, at week 8 (p<0.05). There were no severe adverse events in either group.Conclusions: BE supplementation improved some of the objective and subjective parameters of eye fatigue induced by VDT loads.

Purpose To compare tear film parameters as well as meibomian gland morphologic features and function among patients with meibomian gland dysfunction (MGD), those with non-Sjögren syndrome aqueous-deficient dry eye (non-SS ADDE), those with non-SS ADDE and MGD, and normal subjects. Design Multicenter, cross-sectional, observational case series. Participants Forty-one eyes of 41 patients (all women; mean age ± standard deviation, 62.1±9.9 years) with non-SS ADDE, 70 eyes of 70 patients (all women; 66.0±8.7 years) with MGD, 17 eyes of 17 patients (all women; 72.4±7.8 years) with non-SS ADDE and MGD, and 70 eyes of 70 normal control subjects (all women; 65.0±7.1 years). Methods Ocular symptoms were scored from 0 to 14 and lid margin abnormalities from 0 to 4 according to their respective number. Meibomian gland changes were scored from 0 to 6 (meiboscore) on the basis of noncontact meibography findings, and meibum was graded from 0 to 3 depending on its volume and quality. Conjunctival and corneal epithelial damage were scored from 0 to 9 (fluorescein score). Tear film break-up time (TBUT) was measured as an index of tear film stability, and tear fluid production was evaluated with Schirmer's test. Main Outcome Measures Ocular symptom score, lid margin abnormality score, meiboscore, meibum grade, fluorescein score, TBUT, and Schirmer's test value. Results The ocular symptom score did not differ significantly between the MGD and non-SS ADDE groups (P = 0.762). The lid margin abnormality score, meiboscore, and meibum grade were significantly higher in the MGD group than in the non-SS ADDE group (P = 0.0012, P < 0.0001, and P < 0.0001, respectively). The fluorescein score, TBUT, and Schirmer's test value were significantly worse in the non-SS ADDE group than in the MGD group (P < 0.0001, P = 0.0061, and P < 0.0001, respectively). The meiboscore correlated significantly with Schirmer's test value only in the MGD group (ρ = 0.508, P = 8.3×10-6). Conclusions An increase in tear fluid production likely compensates for loss of meibomian glands in individuals with MGD.

Purpose To evaluate the validity of a dry eye (DE) screening method in visual display terminal (VDT) workers using functional visual acuity (VA) measurement combined with a symptoms questionnaire, and to make recommendations regarding practical use of the screening. Methods This prospective cross-sectional study included 369 young and middle-age office workers, who use VDTs. Subjects completed two types of DE questionnaires and underwent DE testing and functional VA measurement. Subjects were assigned to DE and non-DE groups. Sensitivity and specificity of the DE prediction value were assessed. According to the probability distribution of DE and non-DE calculated by the discriminant analysis formula, we classified subjects into three categories based on the most appropriate cut-off levels. Positive predictive value (PPV) and negative predictive value (NPV) of the DE prediction value were also assessed. Results Of 369 subjects, 218 and 151 subjects were assigned to the DE and non-DE groups, respectively. Sensitivity and specificity were 93.1% and 43.7%, respectively. Based on the probability prediction, the cut-off levels were defined as probability prediction ≥85%, 45%≤ probability prediction <85% and probability prediction <45%. Subjects with a probability prediction ≥85% were defined positive (N=130), while those with values <45% were defined as negative (N=73). The PPV and NPV were 83.8% and 80.8%, respectively. Conclusions Acceptable PPV and NPV were obtained by setting three discriminate categories. This improved version of the DE screening method may be acceptable for practical use in VDT workers.

A decrease in lacrimal gland secretory function is closely related to aging and leads to an increased prevalence of dry eye syndrome. Since calorie restriction (CR) is considered to prevent functional decline of various organs due to aging, we hypothesized that CR could prevent age-related lacrimal dysfunction. Six-month-old male Fischer 344 rats were randomly divided into ad libitum (AL) and CR (-35%) groups. After 6. months of CR, tear function was examined under conscious state. After euthanasia, lacrimal glands were subjected to histological examination, tear protein secretion stimulation test with Carbachol, and assessment of oxidative stress with 8-hydroxy-2 deoxyguanosine (8-OHdG) and 4-hydroxynonenal (HNE) antibodies. CR significantly improved tear volume and tended to increase tear protein secretion volume after stimulation with Carbachol compared to AL. The acinar unit density was significantly higher in the CR rats compared to AL rats. Lacrimal glands in the CR rats showed a lesser degree of interstitial fibrosis. CR reduced the concentration of 8-OHdG and the extent of staining with HNE in the lacrimal gland, compared to AL. Furthermore, our electron microscopic observations showed that mitochondrial structure of the lacrimal gland obtained from the middle-aged CR rats was preserved in comparison to the AL rats. Collectively, these results demonstrate for the first time that CR may attenuate oxidative stress related damage in the lacrimal gland with preservation of lacrimal gland functions. Although molecular mechanism(s) by which CR maintains lacrimal gland function remains to be resolved, CR might provide a novel therapeutic strategy for treating dry eye syndrome. © 2010 Elsevier Inc.

We evaluated ocular surface alterations in allogeneic hematopoietic stem cell transplantation (HSCT) recipients with or without chronic GVHD-related dry eye in a prospective study. Fifty eyes of 25 post-HSCT patients and 28 eyes of 14 age-matched healthy controls were included. Meibomian gland (MG) obstruction, tear evaporation rate, corneal sensitivity (CS), Schirmer test-I, tear break-up time (BUT) and ocular surface vital staining were examined. Conjunctival impression and brush cytology specimens were collected to evaluate the goblet cell density (GCD) and the inflammatory cell numbers. Obvious MG obstruction, decreased CS and enhanced tear evaporation rate were found in post-HSCT patients compared with normal controls. In addition, decreased conjunctival GCD, increased conjunctival squamous metaplasia and inflammatory cells were noted in cGVHD-related dry eyes compared with normal controls and post-HSCT without dry eye subjects. Furthermore, the conjunctival inflammatory cells were significantly higher in severe dry eyes compared with mild dry eyes (P=0.03). We found comprehensive ocular surface alteration in post-HSCT patients, regardless of whether they had cGVHD-related dry eye or not. The results suggest that the extent of inflammatory process seems to have a pivotal role in the outcome of the cGVHD-related dry eye. © 2010 Macmillan Publishers Limited All rights reserved.

Purpose : To report two cases who had received LASIK previously and who underwent cataract surgery with implantation of multifocal intraocular lens (IOL). Cases and Findings : Both were males aged 47 and 55 years respectively. LASIK had been performed 6 years and 2 years before respectively. Both cases were diagnosed with cataract in the right eye. Corrected visual acuity was 1.2 and 0.7 respectively. The affected eye was treated by cataract surgery and implantation of diffractive multifocal IOL. After surgery, near and far visual acuity with the naked eye was 1.2 and 1.0 in one case and 1.0 each in the other. Both patients expressed satisfaction with the outcome. Contrast sensitivity was at the lower limit of normal range in both cases. Conclusion : These two cases illustrate that refractive error and impaired visual function may result following implantation of multifocal IOL after LASIK. We advocate due explanation to obtain informed consent in such cases.

Purpose: To evaluate the predictability of total postoperative spherical aberration after aspheric intraocular lens (IOL) implantation using preoperative corneal spherical aberration. Setting: Keio University Hospital, Tokyo, Japan. Methods: Corneal and ocular higher-order aberrations (HOAs) were analyzed preoperatively and postoperatively in eyes having cataract extraction with aspheric IOL implantation. The predicted postoperative total spherical aberration Z(4,0) was calculated by adding the preoperative corneal spherical aberration and the labeled spherical aberration of the IOL. The prediction error of the postoperative total spherical aberration was calculated by subtracting the predicted postoperative total spherical aberration from the postoperative total spherical aberration. Surgically induced corneal spherical aberration was calculated by subtracting the postoperative from the preoperative corneal spherical aberration. Results: There were no statistically significant differences between preoperative and postoperative corneal spherical aberration, 3rd-order aberration, or HOAs. The prediction error of the postoperative total spherical aberration was within ±0.05 μm in 9 (24.3%) of the 37 eyes evaluated and within ±0.10 μm in 18 eyes (48.6%). Statistically significantly correlations were found between the surgically induced corneal spherical aberration and prediction error of postoperative total spherical aberration, the preoperative corneal spherical aberration and surgically induced corneal spherical aberration, and the preoperative corneal spherical aberration and prediction error of postoperative total spherical aberration. Conclusions: Predictability of postoperative ocular spherical aberration after cataract surgery with aspheric IOL implantation was insufficient because of the surgically induced corneal spherical aberration. Considering surgically induced corneal spherical aberration could improve the predictability of postoperative ocular spherical aberration. Financial Disclosure: No author has a financial or proprietary interest in any material or method mentioned. © 2010 ASCRS and ESCRS.