記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：SPRINGER JAPAN KK  

To determine the morphological characteristics of the cornea in eyes with posterior corneal vesicles (PCV) determined by in vivo confocal microscopy (IVCM). In addition, to compare the morphological characteristics of the corneas of eyes with PCV to those of eyes with posterior polymorphous corneal dystrophy (PPCD).
Three males and three females aged 17-75 years who were diagnosed with PCV by slit-lamp biomicroscopic findings were studied. The slit-lamp findings, specular microscopic images, corneal endothelial cell densities (CDs), central corneal thickness, and IVCM images were evaluated. Three cases that had been diagnosed with PPCD were also evaluated, and the findings were compared to those in eyes with PCV.
All six cases of PCV had unilateral lesions of Descemet's membrane and the corneal endothelium. Slit-lamp biomicroscopy showed broad, band-shaped lesions in five cases and multiple vesicle lesions in one case of PCV. The IVCM images of the six cases had a common appearance of the corneal endothelial cells in the affected areas showing iso-reflective nuclei and low reflective cell membranes as seen in normal corneal endothelial cells. The CDs in the affected eyes were about one-half of those of the not affected eyes. The IVCM images of the corneas of patients with PPCD showed polymorphic cells with hyperreflective nuclei, which are characteristics of epithelial cells.
The IVCM images demonstrated that the corneal endothelial cells of patients with PCV have normal morphology. These findings indicate that PCV is a distinct clinical entity different from PPCD.

DOI： 10.1007/s10384-016-0473-x

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DOI： 10.1097/ICO.0000000000000997

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DOI： 10.1097/ICO.0000000000000993

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DOI： 10.1097/GOX.0000000000001063

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：SPRINGER JAPAN KK  

To describe a characteristic form of the corona sign and its clinical relevance to the degree of corneal endothelial decompensation and investigate the underlying mechanism using a rabbit model.
These observational cases include 31 patients undergoing penetrating keratoplasty (PKP) and 15 patients undergoing Descemet stripping automated endothelial keratoplasty (DSAEK) with special attention to the circumferentially developed corneal epithelial edema. We also conducted a laboratory observation of horizontal water flow in the rabbit cornea.
We consistently observed the corona sign at the superior periphery during the initial stage of corneal endothelial decompensation after PKP. With progressive corneal endothelial cellular loss, the epithelial edema gradually expanded circumferentially in the periphery. The endothelial cellular density associated with the corona sign significantly (P < 0.01) decreased compared with that without the sign. The endothelial cellular density decreased significantly (P < 0.05) in cases with a circumferential corona sign compared with a superior corona sign. After DSAEK, however, the corneal epithelial edema subsided from the center but persisted peripherally as a corona sign in all cases. By 3 months postoperatively, the epithelial edema was confined to the superior periphery along with uneventful corneal endothelial healing. Rabbit experiments showed that total corneal endothelial decompensation decreased the horizontal intracorneal water migration (Inoue-Ohashi phenomenon) in the corneal periphery and induced peripheral corneal edema.
The slit-lamp microscopic findings of the corona-like epithelial edema in the peripheral cornea are associated with the stage of corneal endothelial function. To support this, the developmental mechanism of the corona sign was demonstrated experimentally.

DOI： 10.1007/s10384-016-0459-8

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：MEDICAL ASSOC NIPPON MEDICAL SCH  

Purpose: To report our findings in a case of childhood refractory interstitial keratitis successfully treated with 0.1% topical tacrolimus.
Methods: A 12-year-old boy presented with a 3-year history of interstitial keratitis. For the recurrent interstitial keratitis he had been treated with topical and systemic acyclovir, steroids, and topical cyclosporine for 3 years. Our examinations revealed severe stromal infiltrates and neovascularization. Treatment was changed from topical 0.5% cyclosporine to topical 0.1% tacrolimus combined with topical acyclovir and betamethasone.
Results: After 2 weeks of treatment with topical tacrolimus, the degree of stromal infiltrates decreased. Although the improvements were slow, the stromal infiltrates resolved somewhat, and neovascularization and topical acyclovir and betamethasone were tapered and stopped in 18 months. Since then, the patient has not shown any recurrence for 9 months without medication.
Conclusion: Our findings indicate that topical tacrolimus should be considered for treating refractory interstitial keratitis in children.

DOI： 10.1272/jnms.83.31

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：TAYLOR & FRANCIS INC  

Objectives: To determine whether eyelid pressure is involved in the development of lid-wiper epitheliopathy (LWE).
Methods: Study 1: The eyelid pressure was measured with a blepharo-tensiometer, and the degree of LWE was assessed in 79 eyes of 43 non-contact lens (CL) wearers. Study 2: The movements of the eyelids and displacement of the eyes during spontaneous blinking were photographed with a high-speed camera. The eyelid pressure was also measured in 34 normal eyes of 19 non-CL wearers who were not part of Study 1.
Results: Study 1: Upper-LWE was detected in 24 of 79 eyes (30.4%), and no significant difference was detected in the eyelid pressure between any grade of upper-LWE. Lower-LWE was detected in 41 of 79 eyes (51.9%), and the eyelid pressure (27.9 +/- 2.8 mmHg) in eyes with grade 3 LWE was significantly higher than that with grade 0 LWE (19.7 +/- 1.3 mmHg; p < 0.05). Study 2: The lower eyelid pressure was significantly correlated with the length of the horizontal movement of the lower eyelids (p < 0.05) and also with the degree of posterior movement of the eye globe (p < 0.05).
Conclusions: The higher pressure from the eyelid may be one of the causes for the development of lower-LWE.

DOI： 10.3109/02713683.2015.1009636

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：ROYAL SOC CHEMISTRY  

Quantitative proteomic approaches using selected reaction monitoring (SRM) are currently limited by the difficulty in the preparation of reference standards. In this study, we demonstrat the high-throughput production of a reference peptide library using a wheat germ cell-free synthesis system to develop a large-scale SRM assay for targeted proteomics.

DOI： 10.1039/c6mb00209a

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：HINDAWI LTD  

Purpose. To quantify changes in anterior segment (AS) parameters after laser peripheral iridotomy (LPI) using AS-optical coherence tomography (OCT) of iris bombe. Method. AS images of eight eyes were captured before and after iris bombe and more than 2 weeks after LPI (post-LPI) using AS-OCT. We compared the following AS parameters: anterior chamber depth (ACD), anterior chamber volume (ACV), iris curvature (IC), iris thickness at 500 mu m from the scleral spur (IT-1) in the middle between the iris root and pupillary margin (IT-2) and 500 mu m from the pupillary margin (IT-3) to the anterior chamber angle (ACA) (angle opening distance [AOD750]), and trabecular iris space area. Results. Mean IT-1 and IT-3, but not IT-2, were lower after iris bombe (IT-1, P = 0.001; IT-2, P = 0.081; and IT-3, P = 0.001). There were no significant differences between ACD at pre-LPI and before iris bombe (P = 0.096). The mean ACV and AOD750 of iris bombe increased at post-LPI (ACV, P < 0.01, and AOD750, P < 0.05). The mean IT-1, IT-2, and IT-3 increased at post-LPI (all, P <= 0.01). IC decreased at post-LPI (P < 0.001), and ACD at post-LPI did not change. Conclusions. The iris extends and becomes thinner during iris bombe. LPI during bombe decreases the IC and increases the ACV and ACA.

DOI： 10.1155/2016/8496201

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：LIPPINCOTT WILLIAMS & WILKINS  

Objective: To characterize the clinical profile of patients with recurrent subconjunctival hemorrhages (SCHs) and evaluate the effect of conjunctivochalasis (CCh) surgery on disease recurrences.
Methods: Three hundred and sixty-two patients with SCHs (mean age, 56.416.0 years) were enrolled in this multicenter epidemiologic study. The severity of CCh, lifestyle at the time of SCH onset, and the frequency of previous SCHs were compared. Thirty-eight patients with 2 or more episodes of SCHs (mean age, 68.28.9 years) underwent surgery for CCh. The effectiveness of surgery was evaluated by comparing the frequency of SCH preoperatively and postoperatively.
Results: Patients with three or more recurrent SCHs showed a significantly (P=0.003) higher grade of CCh and tended to be engaged in activities that require visual concentration, such as watching a visual display terminal, knitting, reading, and driving. More than 80% of eyes that underwent surgery to CCh showed no recurrence of the hemorrhages, and the frequency of SCH significantly (P<0.0001) decreased postoperatively.
Conclusions: Moderate or severe CCh and activities that may cause dry eye can be considered to be risk factors for recurrent SCHs. Surgery to treat CCh is a useful option for patients with frequent recurrences of SCHs.

DOI： 10.1097/ICL.0000000000000139

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：ELSEVIER SCIENCE INC  

PURPOSE: To determine the relationship between eyelid pressure during blinking and the fluorescein staining of the cornea and conjunctiva in dry eye patients.
DESIGN: Cross-sectional prospective study.
METHODS: The pressure of the upper and lower eyelids was measured with a specially designed blepahrotensiometer in 130 eyes of 65 dry eye patients (D group) and in 58 eyes of 31 normal controls (N group). The correlations between the location and degree of ocular surface staining scores and the eyelid pressure were calculated for the D group.
RESULTS: The pressures of the upper and lower eyelids were significantly higher in the D group than in the N group (upper P <.0001, lower P = .0040). The lower eyelid pressure was significantly correlated with the ocular surface staining scores for the inferior cornea (r = 0.19, P = .0307) and conjunctiva (r = 0.19, P = .0252).
CONCLUSIONS: The significant correlation between the eyelid pressure and the ocular surface staining suggests that mechanical friction on the ocular surface by the eyelids may be one of the factors that affects the fluorescein staining of the inferior ocular surface. (C) 2015 by Elsevier Inc. All rights reserved.

DOI： 10.1016/j.ajo.2015.06.028

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：LIPPINCOTT WILLIAMS & WILKINS  

Objective:
Miraflow is a cleaner for soft contact lens which contains 20% isopropyl alcohol. The purpose of this study was to determine the activity against Acanthamoeba trophozoites and cysts for Miraflow. In addition, to determine the activity of combined Miraflow and multipurpose solutions (MPSs) against Acanthamoeba cysts.
Methods:
Two simulated-use studies were conducted. The significance in the log reduction in the number of trophozoites and cysts of A. castellanii strains ATCC 50514 and ATCC 50370 or A. polyphaga ATCC 30461 after exposure to Miraflow alone was determined by the Spearman-Karber method. To examine the activity against Acanthamoeba of combined Miraflow and an MPS, the log reduction in the number of cysts after a 1-min exposure to Miraflow followed by a 4-hr exposure to MPS (ReNu fresh) was also determined.
Results:
Short-time exposure of 30 sec to Miraflow demonstrated activity against the Acanthamoeba trophozoites. However, a 1-min treatment was only relatively effective (1.1 log reduction) against the cysts of A. castellanii ATCC 50514, but no statistically significant reduction was observed for the cysts of the other 2 strains. The combined use with Miraflow and MPS demonstrated activity against the cysts, and a 3.0, 1.0, or 1.5 log reduction in the numbers was obtained for A. castellanii ATCC 50514, A. castellanii ATCC 50370, and A. polyphaga ATCC 30461, respectively.
Conclusions:
Exposure to combined Miraflow and MPS resulted in reductions in the number of Acanthamoeba cysts.

DOI： 10.1097/ICL.0000000000000112

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD  

Interactions between stromal and epithelial cells play important roles in the development, homeostasis, and pathological conditions of the cornea. Soluble cytokines are critical factors in stromal epithelial interactions, and growth factors secreted from corneal stromal cells contribute to the regulation of proliferation and differentiation of corneal epithelial cells (CECs). However, the manner in which the expression of growth factors is regulated in stromal cells has not been completely determined. To study stromal epithelial cell interactions, we used an organotypic culture model. Human or rabbit CECs (HCECs or RCECs) were cultured on amniotic membranes placed on human corneal fibroblasts (HCFs) embedded in a collagen gel. The properties of the organotypic culture were examined by hematoxylin -eosin staining and immunofluorescence. In the organotypic culture, HCECs or RCECs were stratified into two-three layers after five days and five-seven layers after nine days. However, stratification was not observed when the HCECs were seeded on a collagen gel without fibroblasts. K3/K12 were expressed on day 9. The HCF-embedded collagen gels were collected on days 3, 5, or 9 after seeding the RCECs, and mRNA expression of growth factors FGF7, HGF, NGF, EGF, TGF-alpha, SCF, TGF-beta 1, TGF-beta 2, and TGF-beta 3 were quantified by real-time PCR. mRNA expression of the growth factors in HCFs cultured with RCECs were compared with those cultured without RCECs, as well as in monolayer cultures. mRNA expression of TGF-alpha was markedly increased in HCFs cultured with RCECs. However, mRNA expression of the TGF-beta family was suppressed in HCFs cultured with RCECs. Principal component analysis revealed that mRNA expression of the growth factors in HCFs were generally similar when they were cultured with RCECs. In organotypic cultures, the morphological changes in the CECs and the expression patterns of the growth factors in the stromal cells clearly demonstrated stromal-epithelial cell interactions, and the results suggest that stromal cells and epithelial cells may act in concert in the cornea. (C) 2015 Elsevier Ltd. All rights reserved.

DOI： 10.1016/j.exer.2015.02.009

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：BMJ PUBLISHING GROUP  

Aims The purpose of this study is to elucidate the clinical manifestations and the current treatment status of cytomegalovirus (CMV) endotheliitis via a large case series obtained from a national survey conducted in Japan.
Methods The Japan Corneal Endotheliitis Study Group proposed diagnostic criteria for CMV endotheliitis based on a viral examination by PCR of aqueous humour, in combination with clinical manifestations. A national survey was then retrospectively conducted among 1160 members of the Japan Cornea Society. The study reviewed the patient profiles, clinical manifestations, and treatment modalities of individuals who met the diagnostic criteria for CMV endotheliitis.
Results The study included 109 eyes of 106 patients. Mean patient age was 66.9 +/- 10.9 years (85 males (80.2%), 21 females (19.8%)). Patients were commonly diagnosed with anterior uveitis and ocular hypertension prior to confirmation of CMV endotheliitis. Coin-shaped lesions were observed in 70.6%, and linear keratic precipitates in 8.3% of the patients, respectively. 95% of cases were treated with anti-CMV drugs.
Conclusions CMV endotheliitis is most common in middle-aged and elderly men. CMV endotheliitis should be suspected when patients present with corneal endotheliitis involving coin-shaped lesions accompanied by anterior uveitis and ocular hypertension.

DOI： 10.1136/bjophthalmol-2013-304625

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：ASSOC RESEARCH VISION OPHTHALMOLOGY INC  

PURPOSE. To test our hypothesis about whether there is water migration in the horizontal corneal plane and investigate its developmental mechanism.
METHODS. A fluorescein solution was intrastromally injected into normal and edematous corneas of rabbits, and the movement of the fluorescein solution was observed and recorded over time.
RESULTS. In normal corneas, the water flow was characterized by a swirling movement from the center to the periphery in the stroma. The fluorescein solution ultimately spread and occupied the entire cornea, indicating horizontal intracorneal swirling of water. In contrast, when the corneal endothelia were injured by intracameral injection of a preservative to create corneal edema, no water migration occurred, suggesting that the integrity of the corneal endothelial function is essential for water migration. The water migration stopped with injection of a sodium-potassium pump inhibitor, indicating that the enzyme is necessary for physiologic water migration in the cornea. With recovery of corneal endothelial function, the water migration began, and focal edema remained in the periphery with no water migration in this edematous area.
CONCLUSIONS. We report for the first time the presence of horizontal water migration in the cornea in a swirling pattern (i. e., intracorneal swirling migration of water, generated by the pump function in the corneal endothelial cells), which may supplement the conventional concept of development of corneal edema in the vertical plane. This dynamic water circulatory system may be involved in increasing the efficiency of the water transfer in the entire cornea.

DOI： 10.1167/iovs.14-14762

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：WILEY-BLACKWELL  

PurposeTo investigate the changes in the tear flow velocities caused by ageing.
MethodsNinety-nine subjects (41 men, mean age 48.320.7years) were recruited from the Department of Ophthalmology of the Ehime University Hospital. None of the subjects had serious abnormalities of the external surface of the eye. The Krehbiel flow of tears was determined by 40-m polymethylmethacrylate (PMMA) beads suspended in a fluorescein sodium solution (PPF). The movement of the beads was video recorded through a slit-lamp during normal blinking. The flow of the beads was determined with a Motion analyzer((R))software (KEYENCE Co., Osaka, Japan). The velocity of the beads in young age, 20-40years, middle age, 41-60years and old age, 61years, groups was determined.
ResultsThe equation describing the velocity (mm/second) of the PMMA particles as a function of age in the lower tear meniscus measured in the direction of the lacrimal punctum was Y=2.49-0.04X, where Y=velocity and X=age (r(2)=0.214; p<0.0001). For the upper meniscus, the equation was Y=4.83-0.05X (r(2)=0.195, p<0.0001). The average velocity was 0.70 +/- 1.66mm/second in the lower and 2.16 +/- 1.93mm/second in the upper tear meniscus (p<0.0001). The particle velocity decreased significantly with increasing age, but no significant difference between the male and female groups except for the lower tear meniscus when all subjects were analysed.
ConclusionThe PPF technique is a simple method of examining Krehbiel flow of tears and may be used for evaluating functional nasolacrimal duct obstruction quantitatively.

DOI： 10.1111/aos.12444

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：ASSOC RESEARCH VISION OPHTHALMOLOGY INC  

PURPOSE. To investigate the differing characteristics of limbal niche cells (LNCs) and limbal stromal cells (LSCs) in the maintenance of limbal epithelial stem/progenitor cells in the cornea.
METHODS. Limbal niche cells were obtained from direct dissection of the human corneal limbus, and LSCs were obtained from explant cultures of limbal stromal tissues under the same culture conditions. The resulting cultures were examined for their ability to support the growth of limbal stem/progenitor cells in colony-forming capacity, stratified epithelial cell sheet formation, maintenance of limbal epithelial stem/progenitor cell characteristics, and gene expression levels of factors that supported the limbal epithelial stem/progenitor cells.
RESULTS. The colony-forming efficiency of limbal epithelial stem/progenitor cells in the LNC group (6.57 +/- 1.54%) was significantly higher than that in the LSC group (1.43 +/- 0.47%). The epithelial cell sheets in the LNC group stratified into four or five layers compared with two or three stratified layers in the LSC group. Staining of both the colonies and the epithelial cell sheets in the LNC group showed a higher intensity of the limbal stem cell marker Delta Np63 than in the LSC group. Moreover, reverse transcription polymerase chain reaction analysis revealed that compared with the common expression of EGF and so on, the LNCs showed a higher expression level of E-cadherin and a lower expression level of neurotrophin-3 (NT3) than the LSCs.
CONCLUSIONS. LNCs have a different role compared to LSCs in their ability to support epithelial stem/progenitor cells and epithelial cellular sheet formation.

DOI： 10.1167/iovs-13-13698

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：WILEY-BLACKWELL  

Purpose
To describe a new method of measuring early phase tear clearance by anterior segment optical coherence tomography (AS-OCT).
Methods
Sixty normal subjects were divided into a young group (30 subjects; 29.6 +/- 7.2years) and an elder group (30 subjects; 71.4 +/- 10.8years). AS-OCT (CASIA SS-1000, Tomey, Japan) with customized software was used to record the tear meniscus at the centre of the lower eyelid. Five microlitres of lukewarm saline solution was dropped into the lower conjunctival sac, and an image of the tear meniscus was obtained immediately and again 30seconds after natural blinking. The tear meniscus height (TMH) and tear meniscus area (TMA) were measured in the AS-OCT images, and the percentage decrease in the TMH and TMA was used as a measure of the tear clearance. Correlations between tear clearance and clinical features including degree of conjunctivochalasis, degree of protrusion of inferior lacrimal punctum, distance of lacrimal punctum from the Marx line and fluorescein clearance rates were also determined in another healthy population consisting of 30 subjects.
Results
The OCT tear clearance rate was 35.2 +/- 11% for TMH and 28.1 +/- 12.4% for TMA in the young group, and 12.4 +/- 7.3% and 6.2 +/- 9.1%, respectively in the elder group. The differences were significant for both the TMH (p=0.017) and the TMA (p=0.024). The OCT-determined tear clearance was positively correlated with the fluorescein clearance rate, and negatively correlated with the distance between the lacrimal punctum and Marx line, degree of conjunctivochalasis and degree of lacrimal punctum protrusion.
Conclusion
AS-OCT can be used as a rapid, non-invasive and quantitative method of determining the early phase tear clearance rate in a normal healthy population.

DOI： 10.1111/aos.12260

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：KARGER  

Purpose: To evaluate ocular surface temperature in assessing the efficacy of anti-allergic eye drops. Methods: Thirteen asymptomatic patients (24.7 +/- 2.8 years) with proven seasonal allergic conjunctivitis due to cedar pollen were studied. A 0.025% levocabastine ophthalmic suspension was instilled in one eye (levocabastine eye) and artificial tears in the other eye (artificial tear eye) in a masked fashion 10 min prior to a conjunctival allergen challenge (CAC). Then, a drop of cedar pollen solution was dropped into the conjunctival sac to induce the allergic reaction. The surface temperature of the inferior bulbar conjunctiva was measured before and 30 min after the CAC with a newly developed non-contact ocular surface thermographer (OST). The degree of conjunctival injection and chemosis was also determined by slitlamp biomicroscopy. The changes in the symptoms were evaluated by a questionnaire. Results: After the CAC, the temperature increased by 0.67 +/- 0.10 degrees C in the artificial tear eyes but by only 0.21 +/- 0.06 degrees C in the levocabastine eyes (p < 0.05). The score for conjunctival injection was 1.38 +/- 0.24 and the chemosis score was 0.85 +/- 0.25 for the artificial tear eyes and 0.62 +/- 0.27 and 0.08 +/- 0.08 in the levocabastine eyes (p < 0.01). The temperature increase was significantly correlated with the conjunctival injection scores (r = 0.63; p < 0.001). Conclusion: The significant correlation of the conjunctival surface temperature with the severity of the conjunctival allergic reaction indicates that the temperature measured by the OST can be used to objectively evaluate the efficacy of topical anti-allergic agents. (C) 2014 S. Karger AG, Basel

DOI： 10.1159/000357105

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：BioMed Central Ltd.  

Background: Beauveria bassiana is an entomopathogenic fungus and is a rare cause of keratitis. We present a case of fungal keratitis caused by B. bassiana that was diagnosed by in vivo confocal microscopy and in vitro corneal cultures. In addition, we determined the temperature- and drug-sensitivities of the isolated strain of B. bassiana. Case presentation: A 59-year-old Japanese man with a 2-month history of keratitis was examined by slit-lamp biomicroscopy, in vivo confocal microscopy, and histology and cultures of corneal scrapings. The corneal scrapings were used to determine the minimal inhibitory concentrations of different antifungal drugs and also to determine the temperature-sensitivity. In vivo confocal microscopy and histological examinations showed filamentous fungal keratitis. The characteristics of the fungal growth indicated that the keratitis was caused by B. bassiana. The keratitis responded poorly to systemic and topical voriconazole and to natamycin ointment. However, it was resolved after changing the natamycin to micafungin combined with surgical debridement. The isolated strain was sensitive to itraconazole, miconazole, micafungin, voriconazole, and resistant to flucytosine and fluconazole. It was moderately sensitive to amphotericin B, and natamycin. After 7 days in culture, the isolate grew small white colonies at 25°C, very small colonies at 35°C and 37°C. Conclusion: The drug-sensitivity and temperature-sensitivity profiles of B. bassiana should be helpful in the treatment of B. bassiana keratitis. Therapeutic surgery may be helpful for mycotic keratitis poorly responsive to medical therapy alone.

DOI： 10.1186/1756-0500-7-677

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：LIPPINCOTT WILLIAMS & WILKINS  

Purpose: To compare 3 ocular lubricants containing sodium hyaluronate (SH), carboxymethylcellulose (CMC), and hydroxypropyl methylcellulose (HPMC) for their ability to enhance water retention and to protect human corneal epithelial cells (HCECs) from dehydration.Methods: Experiments were performed using 0.1% and 0.3% solutions of the 3 lubricants diluted in Milli-Q water for the water retention assays and in DMEM/F12 culture medium for the cell viability assays. Five milliliters of each of the lubricants was dropped onto a filter paper, and the paper was kept in an open container at 25 degrees C and a humidity of 36% to 38%. The weight of the paper was measured hourly for 4 hours. In the second set of experiment, cultured HCECs were exposed to the test lubricants for 60 minutes, and the lubricants were removed. Cells were then exposed to room air for up to 60 minutes. Cells were then incubated with a vital dye, and the absorption of the reduced form of the dye was measured. The cell survival rate was compared for the 3 lubricants.Results: Filter papers moistened with both 0.1% and 0.3% SH were significantly heavier than those moistened with CMC and HPMC at all time points. The survival rate of HCECs was significantly higher at most times with 0.1% and 0.3% SH than with CMC and HPMC solutions. The effects of CMC were not significantly different from those of HPMC.Conclusions: These findings indicate that SH is significantly better for water retention and protection of HCECs from dehydration than HPMC and CMC.

DOI： 10.1097/ICO.0b013e31829cfd44

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：BIOMED CENTRAL LTD  

Background: To develop a side-view imaging technique for observing the dynamic behavior of posterior chamber structures (PCSs) in porcine eyes which mimics closed-eye cataract surgery in humans.
Methods: Enucleated porcine eyes were placed into liquid nitrogen for 5 seconds and immediately bisected at about a 45-degree angle to the equatorial plane. The anterior portion was attached firmly to a glass slide with superglue and sprinkled with wheat flour. Phacoemulsification and aspiration (PEA) was performed as in humans on 10 consecutive porcine eyes. The movements of the PCSs were monitored through the glass slide with a high-resolution video camera set below the cut surface of the eye. The intraocular pressure (IOP) was monitored during the surgery. The highest IOP, operation time, and volume of irrigation fluid of 10 whole eyes were compared to that obtained from the bisected eyes glued to a glass slide. In a second set of experiments, the strength of the seal between the bisected eye and the glass slide was tested in three sets of eyes: 1) frozen eye fixed with superglue with wheat flour for 3 min; 2) frozen eye fixed with superglue for 3 min; and 3) non-frozen eye fixed with superglue for 30 min. The highest IOP that led to a disruption of the seal was compared among the three groups.
Results: PEA was successfully performed on 9 of 10 (90%) eyes with the movements of the PCSs clearly observed. The average maximum intraocular pressure of the 9 bisected eyes was 55.8 +/- 4.7 mmHg and that for the 10 unbisected eyes was 55.3 +/- 5.0 mmHg (P = 0.650). The frozen eye fixed with superglue in combination with wheat flour (Group 1) had the strongest sealing strength with an average IOP at the breaking point of 117.3 +/- 36.2 mmHg.
Conclusions: Our side-view imaging technique can be used to evaluate the changes of the PCSs during intraocular surgery and for surgical training of new residents.

DOI： 10.1186/1471-2415-13-47

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

Purpose: We report a patient who, based on the clinical manifestations, was originally diagnosed as having Chandler's syndrome and later developed varicella-zoster virus (VZV) DNA-positive anterior uveitis. Methods: The patient with Chandler's syndrome who manifested anterior uveitis underwent a complete ophthalmologic examination. Polymerase chain reaction (PCR) was used to amplify the viral DNA in the aqueous humor to determine the cause of the intraocular inflammation. Results: Slit-lamp biomicroscopy showed focal iris atrophy and peripheral anterior synechiae (PAS)
specular microscopy of the corneal endothelium disclosed the hammered-silver appearance. Based on these clinical findings, we diagnosed this patient as having Chandler's syndrome. During the follow-up period, however, the inflammatory cells suddenly appeared in the anterior chamber with formation of keratic precipitates and an increased intraocular pressure (IOP). VZV DNA was displayed in the aqueous humor by PCR. Based upon the diagnosis of VZV anterior uveitis, corticosteroids and acyclovir were given topically and systemically. The inflammation subsided with these medications
however, trabeculectomy was finally needed to control the IOP due to PAS progression. Conclusion: The coincidence of VZV anterior uveitis with Chandler's syndrome may constitute an implication for the possible viral etiology of iridocorneal endothelial syndrome. © 2013 S. Karger AG, Basel.

DOI： 10.1159/000357239

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1016/j.exer.2012.11.018

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：ELSEVIER SCIENCE INC  

PURPOSE: To determine whether polymorphisms in the Toll-like receptor 4 (TLR4) gene are associated with primary open-angle glaucoma (POAG), normal-tension glaucoma (NTG), and exfoliation glaucoma (XFG) in Japanese individuals.
DESIGN: Genetic association study.
METHODS: SETTING: Multicenter study. STUDY POPULATION: One hundred eighty-four unrelated Japanese patients with POAG, 365 unrelated patients with NTG, and 109 unrelated patients with XFG from 5 hospitals. PROCEDURES: Genomic DNA was extracted from leukocytes of the peripheral blood, and 8 polymorphisms in the TLR4 genes were amplified by polymerase chain reaction (PCR) and directly sequenced. Allele and genotype frequencies and the inferred haplotypes were estimated. MAIN OUTCOME MEASURES: Differences in allele and genotype frequencies and haplotypes between subjects with POAG, NTG, and XFG.
RESULTS: The allele frequency of rs2149356 of the TLR4 gene in the POAG, NTG, and XFG groups was the most significantly different from that of the control group (minor allele frequency 0.446, 0.395, 0.404, vs 0.308; P = .000058, P = .0030, and P = .015). The allele frequencies of the 5 TLR4 SNPs were higher in all of the glaucoma groups than that in the control group. The statistics of genotypes of TLR4 were approximately the same for all allele frequencies. The haplotypic frequencies with Tag SNPs studied earlier showed that only POAG was statistically significant. Other haplotypes, such as rs10759930, rs1927914, rs1927911, and rs2149356, had higher statistical significance (overall P = .00078 in POAG, overall P = .018 in NTG, and overall P = .014 in XFG).
CONCLUSIONS: This study demonstrated that TLR4 polymorphisms are associated with NTG in the Japanese, and they also play a role in the pathogenesis of POAG and XFG. (Am J Ophthalmol 2012;154:825-832. (C) 2012 by Elsevier Inc. All rights reserved.)

DOI： 10.1016/j.ajo.2012.03.050

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：ASSOC RESEARCH VISION OPHTHALMOLOGY INC  

PURPOSE. To evaluate the disinfectant effect of methylene blue (MB)-mediated photodynamic therapy (PDT) on a pathogenic strain of Acanthamoeba.
METHODS. Acanthamoeba castellanii (ATCC 50370) used in this study were treated under one of four experimental conditions: light irradiation and incubation in MB (L+M+), light irradiation and incubation in physiologic solution (L+M-), incubation in MB only (L-M+), and incubation in physiologic solution (L-M-). M+trophozoites were incubated in either 0.25 or 0.5 mM MB for 10 minutes. L+organisms were irradiated for 30 minutes following incubation in solution. A halogen lamp (660 +/- 10 nm) with a maximum output of 6 mW/cm(2) was used as the PDT light source. After treatment, antiacanthamoeba activity was evaluated by checking the respiratory activity of the amoeba with 5-cyano-2,3-tetrazolium chloride (CTC) staining. We also determined whether the effect of PDT with MB had been retained or augmented when it was performed in combination with conventional antiamoebic agents.
RESULTS. MB-PDT suppressed the respiratory activity of trophozoites in an MB-concentration-dependent manner at total light doses of 10.8 J/cm(2). The respiratory activity of each group as a percentage of that of L-M- is as follows: L+M+ 11.6% (0.5 mM), 60.9% (0.25 mM); L-M+ 116.5% (0.5 mM), 105.5% (0.25 mM); L+M- 107.6%; and L-M- 106.3%. (L+M+ versus L-M- P < 0.05). MB-PDT had a synergistic effect when used in combination with polyhexamethylene biguanide (PHMB) or amphotericin B, but not with voriconazole.
CONCLUSIONS. MB-PDT is effective against Acanthamoeba in vitro and has synergistic effects with PHMB and amphotericin B. (Invest Ophthalmol Vis Sci. 2012;53:6305-6313) DOI:10.1167/iovs.12-9828

DOI： 10.1167/iovs.12-9828

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：LIPPINCOTT WILLIAMS & WILKINS  

Purpose: To assess a newly developed eyelid pressure measurement system called a blepharo-tensiometer that uses a tactile pressure sensor.
Methods: The tactile sensor was 10 mm in diameter and approximately 0.4 mm thick. The sensor was covered with silicon rubber and was placed between a soft contact lens on the cornea and the inner surface of the eyelid. Under these conditions, the sensor measured the pressure of the eyelid on the ocular surface. The pressure of the upper and lower eyelids were measured separately while the eyelids were closed for at least 5 seconds in 34 eyes of 34 normal volunteers. To determine the reliability of the blepharo-tensiometer, the pressures of the upper and lower eyelids were measured on 3 separate days in both eyes of 12 normal volunteers. The correlation between the age and the eyelid pressure was calculated.
Results: The intraclass correlation coefficients for the 3 measurements ranged from 0.675 to 0.911 for the upper eyelid and 0.663 to 0.925 for the lower eyelid. The mean eyelid pressure was 16.95 +/- 6.08 mm Hg for the upper lid and 16.11 +/- 7.27 mm Hg for the lower lid. The eyelid pressure decreased with increasing age, and both the upper and lower eyelid pressures were significantly and negatively correlated with age (upper eyelid pressures, P < 0.0001;lower eyelid pressures, P=0.000432). No complication was detected after the measurements in all of the subjects.
Conclusions: Our blepahro-tensiometer can obtain repeatable measurements of the eyelid pressure and can be used to evaluate the pressure of the eyelids on the ocular surface in normal and diseased eyes

DOI： 10.1097/ICL.0b013e318268610a

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：MOLECULAR VISION  

Purpose: To study the roles played by stem cell factor (SCF) and SCF receptor c-kit in wound healing of corneal epithelial cells.
Methods: A 2 mm corneal epithelial wound was made in control (WBB6F1(+/+)), SCF (Sl/Sl(d))-, and c-kit (W/W-v) mutant mice, and the speed of wound healing, 5-bromo-2'-deoxyuridine (BrdU) incorporation, and scanning electron microscopic (SEM) morphology of the corneas were examined. The incorporation of BrdU and the degree of cell attachment in cultured mouse corneal epithelial cells (MCECs) isolated from WBB6F1(+/+), Sl/Sl(d), and W/W-v mice were examined. Cultured immortalized human corneal epithelial cells (HCECs) were examined by a cell attachment assay after their exposure to anti-SCF antibodies, tyrosine kinase inhibitor (genistein), and competitive Arg-Gly-Asp (RGD) peptide, as well as on cultures treated with extracellular matrix.
Results: The speed of corneal wound healing was slower in Sl/Sl(d) and W/W-v mice than in controls (p<0.01) and the speed of healing in Sl/Sl(d) mice recovered after topical application of SCF (8 ng/ml). No significant difference was found in the BrdU incorporation assay either in vivo or in vitro. Loosened epithelial cells were detected at wound margins in W/W-v mice by SEM. The cell attachment rate was increased by 157% in cells from WBB6F1(+/+) and 252% in Sl/Sl(d) MCECs by recombinant mouse SCF; however, no significant difference was found in W/W-v MCECs. Anti-SCF antibodies (Ab), genistein, and RGD peptide reduced the percentage of attached HCECs. Anti-SCF Ab inhibited the attachment of HCECs on fibronectin, laminin, or type IV collagen coated dishes.
Conclusions: These findings indicate that the SCF/c-kit system may play a role in corneal wound healing through epithelial cell attachment.

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：ELSEVIER SCIENCE INC  

Objective: To evaluate the diagnostic value of real-time polymerase chain reaction (PCR) for detecting Acanthamoeba in eyes diagnosed with Acanthamoeba keratitis (AK) by conventional tests. In addition, to determine the preoperative prognosis-determining factors in eyes with AK.
Design: Retrospective, cross-sectional study.
Participants: A total of 104 eyes of 103 patients who were diagnosed with AK or with bacterial or bacteria-associated keratitis (BK) by conventional tests.
Methods: Twenty-nine eyes with AK and 75 eyes with BK were evaluated for Acanthamoeba and bacterial DNA by real-time PCR. The Acanthamoeba copy numbers, bacterial load, and clinical parameters in the patients with AK were assessed for those significantly associated with poor outcome, that is, final visual acuity of <20/50 or requiring keratoplasty, by logistic regression analysis.
Main Outcome Measures: Acanthamoeba DNA copy number, bacterial DNA copy number, and odds ratio (OR) for poor prognosis.
Results: The detection of amoebic DNA was 50 times more sensitive by real-time PCR than by conventional cyst counting. The Acanthamoeba copy numbers at the first visit (mean: 4.7x10(5)+/- 3.2x10(5) copies) were significantly correlated with the AK stage, and both were significant risk factors for a poor outcome. The Acanthamoeba DNA copy numbers at the first visit and AK stage had a significantly high risk for poor outcome (OR of Acanthamoeba DNA copy per logarithm of copy numbers: 3.48, 95% confidence interval [CI], 1.04-111.63, P<0.05; OR of AK stage: 2.8 per stage increase, 95% CI, 1.07-7.30, P<0.05, after adjustment of age). In the AK cases with poor outcome, the amoebic DNA was not reduced by more than 90% after 1 month of treatment. The weak amoebic reduction was significantly associated with advanced AK stages or previous use of steroids. Bacterial 16S rDNA was detected in 53.6% of the eyes with AK, but it was not associated with any risk for refractoriness.
Conclusions: Real-time PCR was effective in detecting and managing AK. The Acanthamoeba copy number and AK stage at the first visit were significantly associated with poor outcome.
Financial Disclosure(s): The author(s) have no proprietary or commercial interest in any materials discussed in this article. Ophthalmology 2012;119:1111-1119 (C) 2012 by the American Academy of Ophthalmology.

DOI： 10.1016/j.ophtha.2011.12.023

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：BIOMED CENTRAL LTD  

Background: Bullous keratopathy (BK), a severe sight-threatening disorder can have a variety of etiologies such as prophylactic laser iridotomy, intraocular surgery, trauma, and other ocular disorders. However, there are cases of unknown origins, among which a unique clinical entity namely pseudoexfoliation syndrome (PEX) is having increased importance.
Case presentation: In this case note, we report the clinical features and in vivo confocal microscopic and pathological findings of two BK cases of unknown cause.
Conclusions: Our findings suggest that the BK was caused by the corneal endotheliopathy of PEX, a common disease that could affect up to 30% of people over 60 years old and is more prevalent than we have believed.

DOI： 10.1186/1471-2415-12-17

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：MOLECULAR VISION  

Purpose: To investigate the contactin-associated protein-like 2 (CNTNAP2) gene for single-nucleotide polymorphisms (SNPs) in Japanese patients with the exfoliation syndrome (XFS).
Methods: One hundred and eight unrelated Japanese patients with the XFS, and 199 normal controls were studied. Genomic DNA was extracted from the leukocytes of the peripheral blood, and 8 SNPs, rs826802, rs1404699, rs7803992, rs700308, rs4725736, rs2107856, rs2141388, and rs6970064, were amplified by polymerase chain reaction (PCR), directly sequenced, and genotyped.
Results: The allele frequencies of rs1404699 (p=8.57XE-3, odds ratio (OR)=1.59, 95% confidential intervals (CI); 1,12-2.24) and rs7803992 (p=5.43XE-4, OR=1.86, 95% CI; 1.31-2.65) were statistically significantly different between XFS and controls. In addition, there were significant differences in these genotype frequencies (p=0.0197 and 1.75XE-3). The allele and the genotype frequencies of rs2107856 and rs2141388, which were statistically significant SNPs in an earlier study, were not significantly different.
Conclusions: The variants, rs1404699 and rs7803992, of CNTNAP2 should be associated with XFS in the Japanese population.

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：AMER SOC MICROBIOLOGY  

The usefulness of 5-cyano-2,3-ditolyl-tetrazolium chloride (CTC) staining to determine the respiratory activity of Acanthamoeba was evaluated in this study. Acanthamoeba trophozoites and cysts have a red fluorescence after staining with CTC. To determine the effectiveness of CTC staining as a CTC biocidal assay for Acanthamoeba, the trophozoites and cysts of Acanthamoeba castellanii (ATCC 5037) were treated with serial concentrations of disinfectant solutions, namely, polyhexamethylene biguanide (PHMB) and commercial soft contact lens (SCL) disinfectant solutions. The treated Acanthamoeba organisms were stained with CTC, and their respiratory activity was determined by the intensity of fluorescence in a fluorescence microplate reader. The survival rates of the same samples were determined by a culture-dependent biocidal assay using the Spearman-Karber method. Our results showed that the respiratory activities determined by the CTC biocidal assay and the survival rates determined by the culture-dependent biocidal assay for Acanthamoeba trophozoites and cysts decreased in a dose-dependent way after PHMB treatments, and the results were significantly correlated (r = 0.83 and P < 0.01 for trophozoites; r = 0.60 and P < 0.01 for cysts; Spearman rank correlation test). The respiratory activities in the trophozoites and cysts treated with SCL disinfectant solutions were significantly correlated with the survival rate (r = 0.70 and P < 0.01 for trophozoites; r = 0.64 and P < 0.01 for cysts; Spearman rank correlation test). The significant correlation of the results indicated that the CTC biocidal assay can be used as an alternative method to a culture-dependent biocidal assay. The CTC biocidal assay is a rapid and simple method to test the effectiveness of disinfectant solutions against Acanthamoeba trophozoites and cysts.

DOI： 10.1128/JCM.06461-11

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：ASSOC RESEARCH VISION OPHTHALMOLOGY INC  

PURPOSE. To investigate the role played by epiregulin in corneal epithelial wound healing in vivo in epiregulin-knockout (KO) mice and cultured mouse corneal epithelial cells (MCECs).
METHODS. A 2-mm diameter central epithelial wound was created in epiregulin-KO and wild-type (WT) mouse corneas. The size of the unhealed area and the epithelial cell proliferation and migration were examined. Myeloperoxidase assay was performed to determine the number of polymorphonuclear (PMN) cells infiltrating corneal stroma. Real-time PCR was used to determine expression of the mRNA of inflammatory cytokines in the corneal epithelial cells. Expression of chemokine (C-X-C motif) ligand 2 (CXCL2) response to IL-1 beta was examined in MCECs with or without recombinant mouse epiregulin. Repetitive injuries were created to determine the effect of inflammation in healing in epiregulin-KO mice.
RESULTS. After a single injury, corneal epithelial wound healing and cell migration and proliferation were unimpaired. However, corneal opacities and a larger number of infiltrating PMN cells were observed in epiregulin-KO mice. Expression levels of IL-1 beta, IL-6, CXCL1, and CXCL2 were higher in epiregulin-KO than in WT corneal epithelia cells. The addition of epiregulin significantly reduced the expression of CXCL2 in response to IL-1 beta in MCECs. In response to repetitive injuries, a significant delay in healing and more severe opacities were observed in epiregulin-KO mice than in WT mice.
CONCLUSIONS. Our results indicate that during wound healing, epiregulin may regulate the expression of cytokines and chemokines to reduce an excessive accumulation of PMN cells, which will cause corneal opacity and persistent epithelial defects. (Invest Ophthalmol Vis Sci. 2012;53:2414-2423) DOI:10.1167/iovs.11-8869

DOI： 10.1167/iovs.11-8869

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：LIPPINCOTT WILLIAMS & WILKINS  

Purpose: To determine the density of corneal stromal cells in wearers of soft contact lenses (SCLs) and rigid gas-permeable (RGP) contact lenses (CLs).
Methods: The keratocyte density (KD) was measured at different depths of the stroma by confocal microscopy. In study 1, 32 wearers of rigid gas-permeable (RGP) lenses and 30 wearers of SCLs were studied. Forty volunteers with no history of CL wear were studied as controls. In study 2, 16 volunteers with no history of CL wear were divided into 2 groups; 7 subjects wore RGP lenses (oxygen transmissibility, Dk/L, 35) and 9 subjects wore SCLs (Dk/L, 34). All subjects were asked to wear the CLs daily for 6 months.
Results: In study 1, the KDs in the anterior stroma (AST) and the posterior stroma (PST) of the cornea were significantly lower in the RGP lens group than in the control group. The KD in the SCL group was significantly lower at all depths of the cornea than that of the control group. In study 2, the KD in the AST of the RGP lens group was significantly lower after 1 month of CL wear. The KD in the AST and PST of the SCL group was decreased significantly at 1 month, and all layers were decreased by 10% to 20% 6 months after wearing CLs. At 5 weeks after discontinuation of SCL wear, the KD in all layers was not significantly different from that at the baseline.
Conclusions: The change in the KD was greater in CL wearers than in volunteers with no history of CL wear and also greater in SCL wearers than in RGP lens wearers. Analysis of the KD by confocal microscopy may be a useful method for evaluating the effect of CL wear.

DOI： 10.1097/ICO.0b013e31821b71ff

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：ASSOC RESEARCH VISION OPHTHALMOLOGY INC  

PURPOSE. To devise a mathematical disease classification model for eyes with primary guttata cornea, on the bases of endothelial loss trajectory and probability of advanced disease. METHODS. A series of 1971 patients (3281 eyes), some with and some without guttata corneas, undergoing specular microscopy were retrospectively reviewed. The eyes were classified into four stages; stage 0, without guttae; 1, guttata cornea without edema; 2, mild Fuchs' corneal dystrophy (FCD); and 3, severe FCD, according to clinical records, and patient age and corneal endothelial cell density (ECD) were plotted. Nonparametric density smoothing was used to create a contour map, and a best-fit curve for ECD loss was calculated. The relation between ECD decrease rate and the stages were evaluated. RESULTS. Endothelial decrease rate in stage 0 was 0.44%/year, which was compatible with that of normal eyes reported in previous studies. Decrease rates of stages 1, 2, and 3 were 0.81%, 2.65%, and 3.08%/year, respectively. The age-ECD loss curves of 1.40%/year (ECO(1.4)) and 2.00%/year (ECO(2.0)) further divided stage 1 into three subgroups; stage 1a, asymptomatic guttata cornea; 1b, borderline guttata cornea; and 1c, pre-FCD. The ECO(2.0) cutoff line differentiated eyes with FCD from those without edema with a sensitivity and specificity of >90%. Stage 1c eyes were below ECO(2.0) and had a decrease rate as high as FCD. CONCLUSIONS. This mathematical model can be used to predict the prognosis of patients with primary guttata cornea. (Invest Ophthalmol Vis Sci. 2011;52:7888-7893) DOI:10.1167/iovs.11-8040

DOI： 10.1167/iovs.11-8040

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：MARY ANN LIEBERT INC  

Purpose: To determine the characteristics of the keratitis due to Colletotrichum gloeosporioides.
Methods: The medical records of 3 cases of fungal keratitis caused by C. gloeosporioides were reviewed to determine the clinical characteristics. The minimal inhibitory concentrations of different antifungal drugs for all 3 isolates were determined. All 3 isolates were grown on Sabouraud dextrose agar at 25 degrees C, 35 degrees C, and 37 degrees C to determine the temperature-sensitive growth.
Results: All 3 patients lived in the southwestern part of Japan and had an ocular trauma involving organic materials. The infectious foci were localized in the anterior stroma, and they did not extend deep into the stroma in all cases. The keratitis was treated with antifungal medications including topical voriconazole and natamycin eye ointment, and was resolved in 2-3 weeks. All of the isolated strains grew well at 25 degrees C but poorly at 35 degrees C and 37 degrees C. All isolated strains had similar drug-sensitivity profiles; they were sensitive to amphotericin B, itraconazole, miconazole, micafungin, and voriconazole, and relatively resistant to flucytosine, fluconazole, and natamycin.
Conclusions: All 3 cases of C. gloeosporioides keratitis had similar clinical features. The similarities in the drug-sensitivity profiles should be helpful in treating C. gloeosporioides keratitis.

DOI： 10.1089/jop.2011.0011

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記述言語：英語   出版者・発行元：WILEY-BLACKWELL  

DOI： 10.1111/j.1442-9071.2011.02547.x

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：SPRINGER JAPAN KK  

To investigate the relative efficacy of Japanese commercial soft contact lens disinfectant solutions against Acanthamoeba trophozoites and cysts.
Eight types of multipurpose solution (MPS), two types of hydrogen peroxide solution, and one povidone-iodine solution were evaluated to determine their effect against Acanthamoeba trophozoites and cysts (ATCC 50514). Acanthamoeba cysts were cultured in encystment medium for either 1 or 2 weeks (1 and 2-week-old cysts). The trophozoites and cysts were treated with each disinfectant solution for 0, 2, 4, 8, or 24 h. After performing four tenfold serial dilutions of each test solution, dilutions were cultured for 10 days. The number of surviving organisms was calculated using the trimmed Spearman-Karber method.
Among the MPS tested, only four were effective against trophozoites after treatment for 4 h, and none was effective against 2-week-old cysts. Hydrogen peroxide had a significant effect on trophozoites and 1-week-old cysts, but not on 2-week-old cysts. In contrast, povidone-iodine caused a 2.6 log reduction in 2-week-old cysts.
MPS were found to have limited efficacy against trophozoites and no efficacy against 2-week-old cysts. Only povidone-iodine had any efficacy against 2-week-old cysts.

DOI： 10.1007/s10384-011-0062-y

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：MARY ANN LIEBERT INC  

Purposec To report a case of necrotizing nocardial scleritis treated with surgical debridement and topical polyvinyl alcohol iodine (PAI) and antibiotics.
Case: A 78-year-old man underwent phacoemulsification with intraocular lens implantation in the left eye. He had an uncomplicated postoperative course for 2 months but then developed infectious scleritis. The patient received intensive antibiotics treatments; however, the lesion did not respond. Because of the poor response, Nocardia infection was suspected, and the lesion was repeatedly scraped and the patient was treated with systemic trimethoprim/sulfamethoxazole (TMP-SMX, 800 mg/day) and topical PAI (0.033%, 4 times/day). Cultures of the scrapings grew Nocardia. The treatment led to a complete resolution of the infection.
Conclusions: Necrotizing nocardial scleritis can be treated by surgical debridement and systemic TMP-SMX and topical PAI.

DOI： 10.1089/jop.2011.0043

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：ASSOC RESEARCH VISION OPHTHALMOLOGY INC  

PURPOSE. To compare the morphology of the anterior chamber angle (ACA) and iris in eyes with pseudoexfoliation (PEX) syndrome to that of their clinically unaffected fellow eyes and normal control eyes.
METHODS. Forty-two patients with unilateral PEX syndrome and 42 normal subjects were studied. Eyes were separated into those with PEX, their clinically unaffected fellow eyes, and normal eyes. The dark-light changes of the ACA and iris were documented by anterior segment optical coherence tomography (AS-OCT) video recordings. The nasal ACA parameters including the angle opening distance at 500 mu m (AOD500), the trabecular-iris space at 500 mu m (TISA500), and the trabeculariris angle at 500 mu m (TIA500); anterior chamber depth (ACD); iris-lens contact distance (ILCD), and iris configuration were analyzed with the built-in software and a customized program.
RESULTS. The ACA parameters were not significantly different among all three groups in the dark. The PEX eyes had significantly smaller ACA parameters than their fellow eyes and normal control eyes in the light. PEX eyes also had significantly shallower ACD, longer ILCD, and greater iris convexity (both in dark and light), and thinner iris (in dark) than their fellow eyes. The fellow eyes had significantly lower ACD both in the dark and light, and smaller angle opening distance at 500 mu m and ILCD in the light than normal controls. There were no significant differences in the iris area among the three groups.
CONCLUSIONS. Differences in the anterior segmental morphology are present between PEX and fellow eyes. These disparities may be related to the asymmetry in patients with the unilateral PEX syndrome. (Invest Ophthalmol Vis Sci. 2011;52:5679-5684) DOI:10.1167/iovs.11-7274

DOI： 10.1167/iovs.11-7274

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DOI： 10.1001/archophthalmol.2011.115

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：ELSEVIER SCIENCE INC  

PURPOSE: To evaluate the newly developed Ocular Surface Thermographer (TOMEY Corporation) for dry eye screening.
DESIGN: Prospective, controlled study.
METHODS: We studied 30 eyes of 30 patients diagnosed with dry eye (mean age standard deviation, 52.9 +/- 17.1 years) and 30 eyes of 30 normal subjects (42.7 +/- 17.0 years). The ocular surface temperature was measured immediately after eye opening and every second during 10 seconds of eye opening. The reliability of the measurements was determined by calculating intra-class correlation coefficients. Then, the correlations between the change in the ocular surface temperature and tear film break-up time, Schirmer I test values, and fluorescein staining scores were determined.
RESULTS: The measurements of the ocular surface temperature had a high degree of reliability. Immediately after eye opening, the temperature in the dry eye did not differ significantly from that in normal eyes in any of the 3 regions tested. The decrease in the ocular surface temperature in dry eyes was significantly greater than that in normal eyes (P<.001) at 10 seconds after eye opening. The decrease in the temperature of the cornea was correlated significantly with the tear film break-up time (r = -0.572; P<.001). When the changes in ocular surface temperature of the cornea were used as an index for dry eye, the sensitivity was 0.83 and the specificity was 0.80 after 10 seconds.
CONCLUSIONS: Measurements of the ocular surface temperature obtained with our newly developed Ocular Surface Thermographer after 10 seconds of eye opening may provide a simple, noninvasive screening test for dry eyes. (Am J Ophthalmol 2011;151:782-791. (C) 2011 by Elsevier Inc. All rights reserved.)

DOI： 10.1016/j.ajo.2010.10.033

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：ASSOC RESEARCH VISION OPHTHALMOLOGY INC  

PURPOSE. To measure the density of cells in different layers of the cornea and to determine Whether morphologic changes of the subbasal conical nerve plexus are present in eyes with the pseudoexfoliation (PEX) syndrome.
METHODS. Twenty-seven patients with unilateral PEX syndrome and 27 normal controls were investigated. All eyes underwent corneal sensitivity measurements with an esthesiometer and in vivo confocal microscopic study. Densities of the epithelial, stromal, and endothelial cells were measured. The density and tortuosity of the subbasal corneal nerve plexus were also evaluated.
RESULTS. Eyes with PEX syndrome had significantly lower cell densities in the basal epithelium (P = 0.003), anterior stroma (P = 0.007), intermediate stroma P = 0.009), posterior stroma (P = 0.012), and endothelium (P < 0.0001) than in the corresponding layers of normal eyes. PEX eyes also had lower subbasal nerve densities and greater tortuosity of the nerves than normal eyes. Fellow eyes of patients with PEX also had significantly lower densities of the basal epithelial and endothelial cells than the normal eyes. Conical sensitivity was significantly decreased in PEX eyes, and this was significantly correlated with the decrease of basal epithelial cell and subbasal nerve densities.
CONCLUSIONS. These results have shed light on understanding of the pathogenesis of decreased corneal sensitivity in eyes with PEX syndrome. PEX syndrome is probably a binocular condition for which keratopathy of the fellow eye also requires observation. (Invest Ophthalmol Vis Sci. 2011;52:1799-1761) DOI:10.1167/iovs.10-6098

DOI： 10.1167/iovs.10-6098

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：LIPPINCOTT WILLIAMS & WILKINS  

Purpose: To determine the effectiveness of laser confocal microscopy in detecting filamentous fungi in the cornea of patients with fungal keratitis (FK) and in evaluating the effectiveness of the treatment.
Methods: The corneas of 6 patients clinically diagnosed with FK were examined with the Heidelberg Retina Tomograph II-Rostock Cornea Module (HRT II-RCM). Three of these patients were also monitored periodically with the HRT II-RCM after antifungal treatment.
Results: The HRT II-RCM examination showed interlocking and branching, white, septated, hyphae-like lines in the cornea of all patients. All 6 patients had positive corneal smears and/or laboratory cultures. Three patients were monitored with HRT II-RCM after antifungal treatment. One patient, whose initial smear was negative, was diagnosed by HRT II-RCM before the positive culture results. In another case, the epithelial regeneration was impaired even 3 weeks after the initial treatment and HRT II-RCM revealed a mass of hyphae in the corneal ulcerated lesion. These findings indicated the necessity of surgical debridement. After the surgical debridement, the corneal epithelial defect was healed. HRT II-RCM was able to detect the morphological changes of hyphae after antifungal treatment and helped in the treatment modifications during the clinical course in all 3 patients.
Conclusions: These results indicate that HRT II-RCM can be used to diagnose FK and to monitor the effect of therapy on FK.

DOI： 10.1097/ICO.0b013e3181cd3c84

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：ASSOC RESEARCH VISION OPHTHALMOLOGY INC  

PURPOSE. To study the role played by HB-EGF in corneal epithelial wound healing.
METHODS. A 2-mm corneal epithelial wound was created in keratinocyte-specific, HB-EGF-deficient mice-HB(lox/lox):K-5Cre (HB(-/-))-and the speed of wound healing was compared with that in wild-type (WT) mice. Cultured confluent mouse corneal epithelial cells (MCECs) from WT and HB(-/-) mice were scraped, and the bare area was measured. The proliferation of MCECs was determined by BrdU incorporation. The degree of attachment of WT and HB(-/-) MCECs was also determined. The mRNA expression of EGF family and cell adhesion molecules was determined by real-time PCR.
RESULTS. Corneal epithelial wound healing was significantly delayed in HB(-/-) mice, and the expression of HB-EGF was detected at the leading edge of the wound in HB(lox/+):K5-Cre (HB(+/-)) mice by the presence of lacZ staining. The wound closure was significantly impaired in HB(-/-) MCECs and was improved by adding HB-EGF. The number of BrdU-positive MCECs of WT and HB(-/-) mice was not significantly different, and both increased to different degrees when HB-EGF was added. The adhesion of isolated HB(-/-) MCECs was lower than that of WT MCECs, but the degree of adhesion was restored by adding HB-EGF. The expression of epiregulin was upregulated in HB(-/-) MCECs, and alpha 6-and beta 1-integrin were upregulated by adding HB-EGF.
CONCLUSIONS. HB-EGF plays an important role in corneal epithelial cell healing by enhancing cellular attachment and part of cell proliferation. (Invest Ophthalmol Vis Sci. 2010;51:5630-5639) DOI:10.1167/iovs.10-5158

DOI： 10.1167/iovs.10-5158

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：LIPPINCOTT WILLIAMS & WILKINS  

Purpose: To determine the effectiveness of laser confocal microscopy in identifying Acanthamoeba cysts and trophozoites in the cornea of patients with Acanthamoeba keratitis (AK) and to evaluate its effectiveness in following AK after treatment.
Methods: The corneas of 9 patients clinically diagnosed with AK were monitored periodically with the Heidelberg Retina Tomograph II-Rostock Cornea Module (HRT II-RCM) to examine for Acanthamoeba cysts and trophozoites during the clinical course.
Results: Seven of 9 patients had positive corneal smears, and 5 of 9 patients had positive laboratory cultures. HRT II-RCM demonstrated the presence of highly reflective polygonal shadows with lower reflective borders in the cornea of all patients. In 1 patient, a highly reflective pleomorphic shadow with small less-reflective areas was detected inside the cell. The former finding resembled the image of Acanthamoeba cysts in culture as observed by HRT II-RCM, and the latter observation with that of Acanthamoeba trophozoites in culture. After treatment, the number of highly reflective inflammatory cells decreased and the number and morphology of the corneal epithelial cells with highly reflective nuclei recovered to normal levels.
Conclusion: These results indicate that in vivo laser confocal microscopy can be a useful method to make a diagnosis and to follow patients with AK.

DOI： 10.1097/ICO.0b013e3181ca36b6

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：ASSOC RESEARCH VISION OPHTHALMOLOGY INC  

PURPOSE. The Na+-/K+-dependent ATPase (Na, K-ATPase) expressed in the basolateral membrane of corneal endothelial cells plays an important role in the pump function of the corneal endothelium. The role of insulin in the regulation of Na, K-ATPase activity and pump function in corneal endothelial cells was investigated.
METHODS. Confluent monolayers of mouse corneal endothelial cells were exposed to insulin. ATPase activity was evaluated by spectrophotometric measurement of phosphate released from ATP with the use of ammonium molybdate; Na, K-ATPase activity was defined as the portion of total ATPase activity sensitive to ouabain. Pump function was measured with the use of a Ussing chamber; pump function attributable to Na, K-ATPase activity was defined as the portion of the total short-circuit current sensitive to ouabain. Western blot analysis and immunocytochemistry were performed to measure the expression of the Na, K-ATPase alpha(1)-subunit.
RESULTS. Insulin increased the Na, K-ATPase activity and pump function of cultured corneal endothelial cells. These effects were blocked by protein kinase C (PKC) inhibitors and protein phosphatases 1 and 2A inhibitor. Western blot analysis indicated that insulin decreased the ratio of the inactive Na, K-ATPase alpha(1)-subunit. Immunocytochemistry indicated that insulin increased the cell surface expression of the Na, K-ATPase alpha(1)-subunit.
CONCLUSIONS. These results suggest that insulin increases the Na, K-ATPase activity and pump function of cultured corneal endothelial cells. The effect of insulin is mediated by PKC and presumably results in the activation of PP1, 2A, or both, which are essential for activating Na, K-ATPase by alpha(1)-subunit dephosphorylation. (Invest Ophthalmol Vis Sci. 2010; 51:3935-3942) DOI: 10.1167/iovs.09-4027

DOI： 10.1167/iovs.09-4027

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：ASSOC RESEARCH VISION OPHTHALMOLOGY INC  

PURPOSE. The study hypothesis was that shear stress caused by abnormal aqueous flow is one of the causes of corneal endothelial cell loss after laser iridotomy (LI). The shear stress exerted on the corneal endothelial cells (CECs) in anterior chambers (ACs) of different depths was calculated by a computational fluid dynamics program. The effect of shear stress was also examined on human corneal endothelial cells (HCECs) grown on microscope slides.
METHODS. Three-dimensional models of the AC were constructed, with and without an LI window, and AC depths of 2.8, 1.8, 1.5, and 1.0 mm. The speed of aqueous streaming through the LI window was obtained from animal studies and used to calculate the shear stress exerted on the CECs. Cultured HCECs attached to glass slides were subjected to different magnitudes of shear stress by exposing the cells to different flow rates of the culture solution. The number of cells remaining attached to the slide under each condition was determined.
RESULTS. The shear stresses were 0.14, 0.31, 0.48, and 0.70 dyn/cm(2) for models with AC depths of 2.8, 1.8, 1.5, and 1.0 mm, respectively. When cultured HCECs were subjected to shear stress within the range calculated by the three-dimensional models, the number of cells remaining attached to the glass slide decreased as the magnitude and duration of the shear stress increased.
CONCLUSIONS. Shear stress exerted on CECs after LI may reach a magnitude high enough to cause cell damage and loss in eyes, especially in those with shallow anterior chambers. (Invest Ophthalmol Vis Sci. 2010; 51:1956-1964) DOI: 10.1167/iovs.09-4280

DOI： 10.1167/iovs.09-4280

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：MOLECULAR VISION  

Purpose: Toll-like receptor 4 (TLR4), a member of the TLR family, is an important pattern recognition molecule that plays a role in the host's innate immune responses to lipopolysaccharide (LPS), a component of gram-negative bacteria. Contact lens wear is one of the risk factors for bacterial keratitis. The purpose of this study was to determine whether hypoxia or contact lens wear alters the TLR4 signaling pathways in human corneal epithelial cells (HCECs).
Method: A simian virus 40-immortalized human corneal epithelial cell (SV40-HCEC) line was cultured under 20% O(2) or 2% O(2) and exposed to LPS. The expression of TLR4, interleukin-6 (IL-6), and IL-8 was determined using a real-time reverse transcription-polymerase chain reaction (RT-PCR), enzyme-linked immunosorbent assay ( ELISA), and immunoblotting. Immunoblotting was also used to determine whether the nuclear factor kappa B (NF kappa B) was activated in the SV40-HCEs. HCECs were obtained from 17 healthy volunteers and 18 hydrogel soft contact lens (SCL) wearers using impression cytology (IC), and the expression of the mRNA of TLR4 was determined using real-time RT-PCR.
Results: A reduction in the expression of the mRNA and protein of TLR4 was detected in SV40-HCECs cultured under hypoxic conditions. Hypoxia also attenuated both the LPS-induced expression of IL-6 and IL-8, and the activation of NF kappa B in SV40-HCECs. The expression of the mRNA of TLR4 was down-regulated in the HCECs of soft contact lens wearers.
Conclusions: These results indicate that hypoxia attenuates the TLR4 signaling pathway in HCECs, suggesting that the increase in the susceptibility to bacterial infections under hypoxic conditions may be related to the TLR4 signaling pathways.

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：MARY ANN LIEBERT INC  

Purpose: To report a case of fungal keratitis caused by Colletotrichum gloeosporioides, which is a rare pathogen in humans.
Methods: An 80-year-old woman developed fungal keratitis after having sustained a traumatic injury during field work. The patient was initially examined by slit-lamp biomicroscopy and the Heidelberg Retina Tomograph II-Rostock Cornea Module (HRT II-RCM). Corneal scrapings were collected and submitted for laboratory investigations.
Results: Many septate, hyphae-like interlocking and branching white lines were observed in the area of the infiltrate by HRT II-RCM. A tentative diagnosis of fungal keratitis was made, and the patient was treated with systemic and topical voriconazole and pimaricin ophthalmic ointment. The infectious focus resolved within 2 weeks, and there were no signs of a recurrence after 3 months of treatment with the antifungal agents. The culture of the corneal scraping grew C. gloeosporioides.
Conclusions: HRT II-RCM was useful in detecting filamentous fungi in the cornea. The treatment with voriconazole and pimaricin was effective in the treatment of C. gloeosporioides keratitis.

DOI： 10.1089/jop.2009.0069

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1089/jop.2009.0054

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：MOLECULAR VISION  

Purpose: To describe a new method of culturing mouse corneal epithelial cells (MCECs).
Methods: MCECs were isolated from C57/BL6 mouse corneas and cultured on type-I collagen-coated plastic dishes in low-calcium progenitor cell targeting medium (CnT-50). Expression of the mRNAs of N-terminal truncated isoform of p63 (DNp63), cytokeratin 12 (K12), and cytokeratin 14 (K14) were determined by reverse transcription-polymerase chain reaction (RT-PCR). To examine the differentiation capabilities, passage 3 (P3) MCECs at confluence were subcultured on amniotic membrane (AM) in a differentiation medium (CnT-30) until confluence. At confluence, 1 mM calcium was added and cultured for 4 more days. The expression of K12 in the stratified MCECs was analyzed by immunostaining.
Results: The MCECs cultured in CnT-50 proliferated until at least P10. The number of cells at confluency at P3 was 61.8 (SD +/- 9.4, n=5) times that at P0. MCECs cultured on AM in CnT-30 with addition of calcium were stratified up to two to three layers, and the stratified MCECs expressed K12. DNp63 mRNA was continuously expressed throughout the different passages, and K12 mRNA was detected in P0 cells and the stratified MCECs on AM.
Conclusions: Cultured MCECs maintain their proliferation and differentiation capabilities as well as their corneal epithelial cell characteristics. These results suggest that MCECs produced by this culturing method provide a useful experimental model which can enable further development of research of the corneal epithelium.

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：MOLECULAR VISION  

Purpose: The toll-like receptor 3 (TLR3) recognizes viral double-stranded RNA and its synthetic analog polyriboinosinic-polyribocytidylic acid (poly(I:C)), and the activation of TLR3 is known to induce the production of type I interferon (IFN) and inflammatory cytokines/chemokines. The purpose of this study was to determine the role played by innate responses to a herpes simplex virus 1 (HSV-1) infection of the corneal epithelial cells. In addition, we determined the effects of immunosuppressive drugs on the innate responses. Methods: Cultured human corneal epithelial cells (HCECs) were exposed to poly( I: C), and the expressions of the mRNAs of the cytokines/chemokines macrophage-inflammatory protein 1 alpha (MIP1-alpha), macrophage-inflammatory protein 1 beta (MIP1-beta), interleukin-6 (IL-6), interleukin-8 (IL-8), regulated on activation, normal T cell expressed and secreted (RANTES), Interferon-beta (IFN-beta), and TLR3 were determined using real-time reverse transcription-polymerase chain reaction (RT-PCR). The effects of dexamethasone (DEX, 10(-6) or 10(-5) M) and cyclosporine A (CsA, 10(-6) or 10(-5) M) on the expression of these cytokines and TLR3 were also determined using real-time RT-PCR. Levels of MIP1-alpha, MIP1-beta, IL-6, IL-8, RANTES, and IFN-beta were measured using the enzyme-linked immunosorbent assay (ELISA). The activation of nuclear factor kappa B (NF kappa B) and interferon regulatory factor 3 (IRF3) in HCECs was assessed by immunohistochemical staining. The effects of DEX and CsA on HCECs exposed to HSV-1 (McKrae strain) were also examined. Results: The expressions of MIP1-alpha, MIP1-beta, IL-6, IL-8, RANTES, IFN-beta, and TLR3 were up-regulated in HCECs exposed to poly(I:C). The poly(I:C)-induced expressions of IL-6 and IL-8 were down-regulated by both DEX and CsA, while the expressions of IFN-beta and TLR3 were suppressed by DEX alone. Similarly, the poly(I:C)-induced activation of NF kappa B was decreased by both DEX and CsA, and the activation of IRF3 was reduced by DEX alone. When HCECs were inoculated with HSV-1, DEX led to a decrease in the expression of IL6, IFN-beta, and TLR3, and an extension of plaque formation. Conclusion: These results indicate that DEX may increase the susceptibility of HCECs to viral infections by altering the TLR3 signaling pathways.

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DOI： 10.1001/archophthalmol.2008.594

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：THIEME MEDICAL PUBL INC  

This study demonstrated that endoscopic endonasal sinus surgery is a successful technique for reducing medial orbital blowout fractures and does not cause complications. Twenty-three patients with isolated medial blowout fractures that did not involve the inferior wall underwent reduction surgery using the endoscopic endonasal approach. Surgery was indicated if the patient experienced persistent diplopia, ocular motility limitation, or enophthalmos. Septoplasty and submucous resection of the inferior turbinate bone were performed to access the fracture site safely in 3 and 15 patients, respectively. The bone fragments entrapping the orbital content or adhesions between the orbital contents and the sinus mucosa were dissected carefully from the fracture site. An ophthalmologist used the eye traction test to verify improvement in ocular motility. A temporary Silastic sheet was applied in three patients, but no permanent supporting material was used in any patient. No surgical or late complications were seen. Preoperative symptoms were resolved in 22 of the 23 (95.5%) patients 6 months after surgery. We concluded that the endoscopic endonasal reduction based on endoscopic endonasal sinus surgery techniques is safe, accurate, and an appropriate surgical intervention for medial orbital blowout fractures.

DOI： 10.1055/s-0028-1112227

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：TAYLOR & FRANCIS INC  

Purpose: The Na+- and K+-dependent ATPase (Na,K-ATPase) expressed in the basolateral membrane of corneal endothelial cells plays an important role in the pump function of the corneal endothelium. We investigated the possible role of dexamethasone in the regulation of Na,K-ATPase activity and pump function in corneal endothelial cells. Methods: Confluent monolayers of mouse corneal endothelial cells were exposed to dexamethasone. ATPase activity of the cells was evaluated by spectrophotometric measurement of phosphate released from ATP with the use of ammonium molybdate, with Na,K-ATPase activity being defined as the portion of total ATPase activity sensitive to ouabain. Pump function of the cells was measured with the use of an Ussing chamber, with the pump function attributable to Na,K-ATPase activity being defined as the portion of the total short-circuit current sensitive to ouabain. Western blot analysis was examined to measure the expression of the Na,K-ATPase 1-subunit. Results: Dexamethasone (1 or 10 M) increased the Na,K-ATPase activity and pump function of the cultured cells. These effects of dexamethasone were blocked by cycloheximide, a protein synthesis inhibitor. Western blot analysis also indicated that dexamethasone increased the expression of the Na,K-ATPase 1-subunit, whereas it decreased the expression of the phospho-Na,K-ATPase 1-subunit. Conclusions: Our results suggest that dexamethasone stimulates Na,K-ATPase activity in mouse corneal endothelial cells. The effect of dexamethasone activation in these cells is mediated by Na,K-ATPase synthesis and increase in an enzymatic activity by dephosphorylation of Na,K-ATPase 1-subunits.

DOI： 10.1080/02713680902829624

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：MOSBY-ELSEVIER  

OBJECTIVE: To show the effectiveness of endoscopic reduction surgeries for delayed cases with blowout fractures, and to determine the cause of persisting diplopia based on surgical findings.
DESIGN: Retrospective study.
SETTING: Between 1997 and 2006, 114 patients with isolated blowout fractures underwent surgery. In 6 of 114 patients, there were delayed cases in which over 3 months had elapsed since the initial trauma. For persisting diplopia, surgeries were performed using an endoscopic endonasal approach.
RESULTS: Adhesion between the protruded periorbita and the paranasal sinus mucosa was remarkable in the delayed cases. Dissection of the adhesion and removal of the bone fragments were performed. The ocular motility improvement was confirmed by intraoperative eye traction tests. Postoperatively, diplopia disappeared in five patients.
CONCLUSION: Endoscopic reduction surgeries for delayed cases are available in the treatment of blowout fractures. The main cause of diplopia was determined to be the adhesion. (C) 2008 American Academy of Otolaryngology-Head and Neck Surgery Foundation. All rights reserved.

DOI： 10.1016/j.otohns.2007.10.037

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：ELSEVIER SCIENCE INC  

Purpose: To investigate clinical manifestations and response to antiviral therapy of 8 patients with cytomegalovirus (CMV)-induced corneal endotheliitis who were diagnosed and treated at 2 university hospitals in Japan.
Design: Retrospective, consecutive, multicenter case series.
Participants: Eight eyes of 8 patients diagnosed with active CMV corneal endotheliitis at Kyoto Prefectural University of Medicine and Ehime University School of Medicine. The diagnosis was made based on the detection by polymerase chain reaction assay of CMV, but not herpes simplex virus (HSV) and varicella zoster virus (VZV) DNA, in the aqueous humor from the affected eye.
Methods: Retrospective review of the clinical manifestations and responses to antiviral treatment.
Main Outcome Measures: Patient profiles, including duration of corneal endotheliitis, systemic disease, intraocular pressure, and clinical manifestation of anterior and posterior segments. The clinical response to systemic and topical antiviral treatment was evaluated by slit-lamp examination. Corneal endothelial density was examined by specular microscopy.
Results: The average observation period after CMV detection was 10.4 months (range, 2-24 months). None of the patients had systemic immunodeficiency. Corneal manifestations included linear keratic precipitates associated with multiple coin-shaped lesions and local corneal stromal edema. Of the 8 patients, 4 had undergone penetrating corneal transplantation. Systemic ganciclovir therapy was used in 7 patients, and in 1 patient, valacyclovir was administered, with the corneal endotheliitis responding quickly to the early administration of galovir. At the final examination, 6 eyes had a clear cornea, but 2 eyes had bullous keratopathy.
Conclusions: Besides HSV and VZV, CMV must be considered as an etiologic agent in patients with corneal endotheliitis. Cytomegalovirus corneal endotheliitis may be a newly identified clinical entity of reactivated CMV in the anterior chamber of individuals free of accompanying systemic symptoms.

DOI： 10.1016/j.ophtha.2007.04.053

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：LIPPINCOTT WILLIAMS & WILKINS  

Purpose. To compare the effects Of four commercially available multipurpose solutions (MPSs) on the structure and barrier function of corneal epithelial tight junctions. Methods. Human corneal epithelial cells were Cultured on collagen-coated slides and then exposed to MPS A (polyhexamethylene biguanide, macrogolglycerol hydroxystearate), MPS B (polyhexamethylene biguanide, poloxamine), MPS C (Alexidine, poloxamine), and MPS D (POLYQUAD, poloxamine) for 60 minutes. Tight junction integrity of the corneal epithelial cells was evaluated with ZO-1 (tight junction-related protein) labeling under laser confocal microscopy. To investigate the changes of ultrastructure in tight junctions of human corneal epithelial cells, an ultrathin cross-section of the cell on collagen membrane was also observed by transmission electron microscopy. For quantitative evaluation of barrier functions, transepithelial electrical resistance of the epithelial cell was measured 30, 60, and 120 minutes after MPS exposure by using a volt ohmmeter. Results. The control (i.e., without MPS treatment) and MPS A-treated epithelial cells showed a normal, continuous linear pattern in ZO-1 staining along with cell-cell junctions. However, epithelial cells treated with MPS B, MPS C, and MPS D showed discontinuous. disrupted line structures at cell-cell borders. This may correspond to a partial breakdown of epithelial tight junctions. Treatment of epithelial monolayers with MPS B, MPS C. and MPS D caused a time-dependent decrease in transepithelial electrical resistance, whereas there was no significant difference between the MPS A-treated group and the control group. Conclusions. These results Suggest the possibility that frequent use of a MPS with high cytotoxicity may lead to the breakdown of epithelial barrier functions and increase the risk of associated microbial infections in hydrogel lens wearers.

DOI： 10.1097/ICL.0b013e318073cbdb

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：MOLECULAR VISION  

Purpose: To investigate the effects of epiregulin, a newly identified member of the epidermal growth factor (EGF) family, on the proliferation of human corneal epithelial cells (HCECs).
Methods: The proliferation of HCECs was determined by cell counting and BrdU incorporation assays at specific times after exposure to different concentrations of human recombinant epiregulin (0 to 20 ng/ml). Immunohistochemical staining was used to localize epiregulin in cadaveric corneas. RT-PCR and real-time PCR were used to determine the expression levels of epiregulin in cultured and cadaveric HCECs. To examine the interaction between epiregulin and epidermal growth factor receptors (EGFRs), the phosphorylation of ErbB1 and ERK1/ERK2 (ERK1/2) was estimated by western blot analysis in the presence or absence of AG1478, a specific inhibitor of EGFR kinase activity. To search for cross-induction of epiregulin by other EGF family members, the expressions of EGF, heparin-binding epidermal growth factor-like growth factor (HB-EGF), amphiregulin (AR), and transforming growth factor-alpha (TGF-alpha) mRNA were determined by real-time PCR in the presence of 10 ng/ml of epiregulin. Conversely, the expression of epiregulin was also determined following the incubation of HCECs with 10 nM of either of EGF, HB-EGF, TGF-alpha, or AR.
Results: The mRNA of epiregulin was expressed in cultured HCECs and HCECs obtained from cadaveric eyes. Epiregulin was strongly detected in the limbal epithelium and basal epithelium of the peripheral cornea, but it was weakly detected in the central corneal epithelium. HCECs proliferated in the presence of epiregulin in a dose-dependent manner as detected by an increase in cell numbers or in BrdU incorporation. When HCECs were incubated with exogenous epiregulin, the expression of the mRNA of epiregulin was up-regulated as detected by real-time PCR, and the phosphorylation of ErbB1 and ERK1/2 was up-regulated in a dose-dependent manner as shown by Western blot analysis. These up-regulations were inhibited by AG1478, a specific inhibitor of EGFR kinase activity. Epiregulin increased the expression of HB-EGF and AR, while TGF-alpha, HB-EGF, AR, and EGF increased the expression of epiregulin in HCECs.
Conclusions: These findings indicate that epiregulin played an autocrine role in the proliferation of HCECs presumably through cross-induction with other EGF family members.

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DOI： 10.1097/ICO.0b013e31812f6b67

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：MOLECULAR VISION  

PURPOSE: To determine whether the promyelocytic leukemia zinc finger (PLZF) protein, a transcriptional repressor and negative regulator during cell cycling, plays a role in the proliferation of cultured human corneal endothelial cells (HCECs).
METHODS: The expressions of the mRNA and the protein of PLZF were determined by real-time PCR and western blot analysis, respectively. The changes in the expression of the PLZF gene of cultured HCECs were investigated at different times after cell-cell contacts were disrupted by incubation with EDTA. The cell proliferation rate was assessed with a real-time cell electronic sensing (RT-CES) system after cultured HCECs were infected with either PLZF or LacZ encoding adenovirus vector (Ad-PLZF or Ad-LacZ). The PLZF-regulating genes were analyzed by DNA microarray analysis in cultured HCECs infected with Ad-PLZF.
RESULTS: The expression of the mRNA of PLZF was first detected when the cultured HCECs became confluent, and the relative amount of PLZF mRNA continued to increase for up to 5 days as the cell-cell contacts were formed more firmly. On the other hand, the expression of the mRNA of PLZF decreased about 20 fold 3 h after EDTA exposure, and gradually returned to the original level as the cell-cell contacts were reformed at 72 h after the exposure. The assessment using the RT-CES system showed that the proliferation of cultured HCECs was inhibited for up to 72 h when infected by Ad-PLZF. DNA microarray analysis revealed that the transforming growth factor-beta stimulated clone 22 (TSC-22) gene was up-regulated by 2.32 fold when infected by Ad-PLZF.
CONCLUSIONS: These findings indicate that the expression of PLZF in HCECs is closely related to the formation of cell-cell contacts, and that PLZF may play a role in suppressing their proliferation.

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：ACADEMIC PRESS LTD ELSEVIER SCIENCE LTD  

Adipose differentiation-related protein (ADRP) is an intrinsic lipid storage protein found in lipid droplets of different type of cells. ADRP has been recognized to be a specific marker of lipid accumulation and a marker of differentiated adipocytes. The purpose of this study was to determine whether ADRP was present in the cells of the meibomian gland. The expression of the mRNA of ADRP was determined by RT-PCR and Northern blot analysis of the meibomian gland and other rat tissues. A newly generated polyclonal antibody against rat ADRP was used for Western blot analysis and immunohistochemical staining to determine whether ADRP was expressed in the rat meibomian gland. Meibomian gland acinar cells were isolated to determine when ADRP was expressed during cell differentiation in vitro. Northern blot analysis and Western analysis showed that ADRP was expressed in the meibomian gland. Immunoreactivity to ADRP was observed in the lobules of acinar cells in the meibomian gland, and was preferentially located adjacent the vacuolated cytoplasm. In culture, the meibocytes began to store lipid droplets in the cytoplasm as they became confluent, and the immunoreactivity for ADRP was found at the margins of the oil droplets. Our results suggest that ADRP can serve as a new marker for the identification of differentiated meibocytes containing lipid droplets, (c) 2007 Elsevier Ltd. All rights reserved.

DOI： 10.1016/j.exer.2006.12.007

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：ELSEVIER SCIENCE INC  

PURPOSE: To report confocal microscopic observations of characteristic corneal endothelial lesions in a patient with presumed cytomegalovirus (CMV) corneal endotheliitis.
DESIGN: Case report.
METHODS: A 77-year-old, immunocompetent man was admitted with corneal edema, keratic precipitates, and coin,shaped lesions in the right eye. Confocal microscopy was performed to examine the corneal endothelium. Polymerase chain reaction (PCR) was used to identify viral DNA in an aqueous humor sample.
RESULTS: CMV DNA was detected by PCR. Confocal microscopy showed large corneal endothelial cells with an area of high reflection in the nucleus surrounded by a halo of low reflection. This "owl's eye" morphology is characteristic of CMV infection. Topical and intra, venous ganciclovir treatment resulted in rapid resolution of the corneal precipitates and edema, followed by disappearance of the owl's eye morphology.
CONCLUSIONS: Confocal microscopy can detect the owl's eye morphology in the corneal endothelium of patients with presumed CMV corneal endotheliitis.

DOI： 10.1016/j.ajo.2006.11.026

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：LIPPINCOTT WILLIAMS & WILKINS  

Purpose: To report a case of acyclovir-resistant herpes simplex virus (HSV) keratitis after long-term, inconsistent use of topical acyclovir and fluorometholone.
Methods: A 70-year-old man with dendritic keratitis caused by an acyclovir-resistant HSV strain was examined. The 50% inhibitory concentration of different antiviral agents against the isolated virus and the DNA sequence of viral thymidine kinase were determined.
Results: The 50% inhibitory concentration of acyclovir and trifluorothymidine for the isolated HSV strain was 13.75 and 0.28 mu g/mL, respectively, indicating that the virus was resistant to acyclovir. DNA sequencing of the viral thymidine kinase revealed that this virus had a frameshift mutant with a G insertion in the 7Gs homopolymer. Topical trifluorothymidine was effective, and the epithelial lesion was completely resolved within 2 weeks.
Conclusion: A typical form of dendritic keratitis was caused by an acyclovir-resistant HSV with frameshift mutation in a 7Gs homopolymer region.

DOI： 10.1097/01.ico.0000240081.19635.db

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DOI： 10.1001/archopht.124.3.387

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：TAYLOR & FRANCIS INC  

Purpose : To investigate the role of angiotensin II (Ang II) receptor subtypes in subconjunctival injury. Methods : A wound-healing model was developed by subconjunctival blunt dissection in male wild-type, AT(1a) receptor-deficient (AT(1a)KO) and AT(2) receptor-deficient (AT(2)KO) mice. Collagen deposition and cell infiltration were evaluated histologically. Expression of collagen, matrix metalloproteinase (MMP), and tissue inhibitor of metalloproteinase-1 (TIMP-1) were determined by real-time PCR. Results : Subconjunctival injury increased the infiltration of inflammatory cells, collagen deposition in the subconjunctival space, and the expression of collagen type I and type III, TIMP-1 and MMP2. In AT(1a)KO mice, collagen deposition, cell infiltration, and expression of collagen and TIMP-1 were inhibited, but MMP2 expression was enhanced. In contrast, in AT(2)KO mice, the increase in collagen deposition, cell infiltration, and expression of collagen and TIMP-1 were further enhanced. Conclusions : These results indicate that AT(1a) and AT(2) receptor stimulation may in addition to other mechanisms be antagonistically involved in the wound-healing process after subconjunctival injury.

DOI： 10.1080/02713680500507200

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：TAYLOR & FRANCIS INC  

Purpose: To determine the role played by keratinocyte transglutaminase (TG1, TG(K)) in the abnormal keratinization of the cornea. Methods: Vitamin A-deficient rats were produced as a model of severe dry eyes, and the expression of the mRNA and the enzyme activity of TG1 were examined in the corneas. The envelope proteins and keratins of cornified cells were also examined immunohistochemically. Results: The expression and enzyme activity of TG1 mRNA on the ocular surface were significantly upregulated as the vitamin A deficiency developed. As the TG1 expression was upregulated, involucrin, loricrin, and keratin 10 began to be expressed on the epithelial cells of the cornea. Conclusions: Upregulation of TG1 expression followed by the appearance of the envelope proteins and keratin10 in cornified cells indicated that TG1 is involved in the abnormal keratinization of the cornea.

DOI： 10.1080/02713680591005940

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：AMER SOC NEURORADIOLOGY  

BACKGROUND AND PURPOSE: Selective neuronal death is a well-recognized histopathologic sequel to moderate ischemic brain damage. However, radiologic visualization of these changes has not been established, even with diffusion tensor imaging (DTI). We sought to determine whether DTI with b values >= 1900 s/mm(2) reveals occult diffusion abnormalities in patients with cerebral arterial occlusive disease.
METHODS: Six patients (five men, one woman; mean age standard deviation, 66 8 years) with unilateral internal carotid or middle cerebral arterial occlusive disease but not parenchymal T2 hyperintensity underwent 3T fast DTI with b <= 1300 s/mm(2) and slow DTI with b >= 1900 s/mm(2). We postprocessed mean diffusibility and fractional anisotropy (FA) images from the fast and slow DTI datasets. Standardized asymmetry indices (AIs) were used to identify regional asymmetries. Diagnostic accuracy among the DTI modalities was assessed by means of receiver operating characteristic analysis.
RESULTS: In hemispheres ipsilateral to occluded vessel, AIs were significantly elevated on fast mean-diffusibility images of white matter at the levels of the internal capsule (95% confidence interval [CI]: 1.00, 1.09; P = .045) and corona radiata (95% CI: 1.01, 1.12; P = .034). AIs were significantly decreased on slow FA images at the internal capsule (95% CI: 0.84, 0.98; P = .018) and white matter at the internal capsule level (95% CI: 0.92, 1.00, P = .043). The slow FA map had the highest accuracy (89.8%) for detecting the hemisphere ipsilateral to arterial occlusion.
CONCLUSION. Slow FA maps acquired by using DTI with high b values are useful for visualizing ischemic brain damage in apparently normal WM.

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：ASSOC RESEARCH VISION OPHTHALMOLOGY INC  

PURPOSE. To determine the association of the KL-6 epitope (sugar moiety) with MUC1 and its distribution on the ocular surface of human non-dry and dry eyes.
METHODS. The human ocular surface was examined immunohistochemically and immunoelectron microscopically using monoclonal antibody (mAb) KL-6, which recognize a carbohydrate epitope of MUC1. The expression patterns of KL-6 epitope in corneal and conjunctival cells were examined by impression cytology from 24 non-dry eye volunteers and 43 dry-eye patients.
RESULTS. In the cornea, bulbar conjunctiva, and limbus epithelium, mAb KL-6 reacted to the apical cell membrane of superficial cells and the intercellular space of superficial and wing cells. No immune reactivity of mAb KL-6 was observed in the basal plasma membrane of basal epithelial cells. Results of impression cytology indicated that the corneal epithelium of 13 of 24 non-dry eyes was weakly stained by mAb KL-6, whereas 42 of 43 dry eyes showed a mosaic pattern. In non dry eyes, 19 of 24 bulbar conjunctival epithelia expressed the KL-6 epitope in a honeycomb pattern. In mild (17/19) and moderate (17/17) dry eye conjunctiva, the KL-6 epitope showed a mosaic pattern. However, the expression of KL-6 epitope decreased in severe dry eyes, showing a mosaic pattern in three of seven patients and labeling a few cells weakly in four of seven patients.
CONCLUSIONS. These findings suggest that there is an upregulation of the sialylated KL-6 epitope of MUC1 by apical corneal and conjunctival cells in mild and moderate dry eyes. This upregulation may in part alleviate the consequences caused by goblet cell mucin dysfunction in dry eyes. It is noteworthy that the KL-6 epitope is downregulated in the conjunctiva of severe dry eyes, a phenomenon that may be explained in part by the malfunction of conjunctival epithelial cells.

DOI： 10.1167/iovs.03-0988

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：SWETS ZEITLINGER PUBLISHERS  

Purpose. To determine the expression and distribution of tissue transglutaminase (TG(c)) and extracellular matrix (ECM) proteins in rat cornea during epithelial wound healing.
Methods. Corneal epithelial defects were created in rat corneas, and TGc expression was examined by Northern blot analysis, in situ hybridization, and immunohistochemical staining after the injury. The presence of fibrinogen, laminin-1, nidogen/entactin, and type collagen was also determined immunohistochemically.
Results. TGc was expressed in normal corneas. During the early wound healing process, TGc mRNA expression was upregulated and TGc immunoreactivity was predominantly expressed in the migrating epithelial cells. ECM proteins were also expressed in a similar pattern as TGc.
Conclusions. The sites and time course of TGc expression indicate that TGc probably plays a role in maintaining the homeostasis of the cornea and in promoting epithelial wound healing. The simultaneous expression of TGc and ECM proteins suggests that the ECM proteins probably operate in concert with TGc in corneal wound healing.

DOI： 10.1076/ceyr.28.1.37.23493

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：ASSOC RESEARCH VISION OPHTHALMOLOGY INC  

PURPOSE. Lens epithelial cells (LECs) undergo epithelial-mesenchcymal transition (EMT) after injury and transform into myofibroblasts positive for alpha-smooth muscle actin (alphaSMA), an established marker of this process. Lumican is a keratan sulfate proteoglycan core protein. This study was conducted to examine whether human and mouse LECs express lumican after injury. To determine whether lumican may modulate EMT of LECs in response to injury or to exposure to transforming growth factor-beta2 (TGFbeta2), alphaSMA expression by the LECs was examined in lumican (Lum)-knockout mice in vivo and in organ culture.
METHODS. Human postoperative capsular specimens and healing, injured mouse lenses at various intervals were immunostained for lumican or alphaSMA. alphaSMA was also immunolocalized in healing, injured lenses of Lum-knockout mice. Finally, expression of lumican and alphaSMA was examined in lenses of Lum-knockout mice incubated with TGFbeta2.
RESULTS. Lumican was immunolocalized in matrix in human postoperative capsular opacification. Lumican and alphaSMA were upregulated in mouse LECs from 8 hours and day 5 after an injury, respectively. LECs accumulated adjacent to the capsular break were of epithelial shape in Lum(-/-) mice and fibroblast-like in Lum(+/-) mice during heating. alphaSMA expression by LECs was significantly delayed in Lum(-/-) mice, indicating that lumican may modulate injury-induced EMT in, LECs. TGFbeta2-induced EMT appeared to be suppressed in organ-cultured lenses of Lum(-/-) mice compared with those of Lum(+/+) mice.
CONCLUSIONS. Human capsular opacification contains lumican, and mouse LECs upregulate lumican and alphaSMA in response to injury. Loss of lumican perturbs EMT of mouse LECs.

DOI： 10.1167/iovs.02-1059

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© 2018 The Authors. Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association. The antitumor activity of activated CD8+ T cells in the tumor microenvironment seems to be limited due to their being metabolically unfit. This metabolic unfitness is closely associated with T-cell exhaustion and impairment of memory formation, which are barriers to successful antitumor adoptive immunotherapy. We therefore assessed the role of glutamine metabolism in the antitumor activity of CD8 + T cells using a tumor-inoculated mouse model. The adoptive transfer of tumor-specific CD8 + T cells cultured under glutamine-restricted (dGln) conditions or CD8 + T cells treated with specific inhibitors of glutamine metabolism efficiently eliminated tumors and led to better survival of tumor-inoculated mice than with cells cultured under control (Ctrl) conditions. The decreased expression of PD-1 and increased Ki67 positivity among tumor-infiltrating CD8 + T cells cultured under dGln conditions suggested that the inhibition of glutamine metabolism prevents CD8 + T-cell exhaustion in vivo. Furthermore, the transferred CD8 + T cells cultured under dGln conditions expanded more efficiently against secondary OVA stimulation than did CD8 + T cells under Ctrl conditions. We found that the expression of a pro-survival factor and memory T cell-related transcription factors was significantly higher in CD8 + T cells cultured under dGln conditions than in those cultured under Ctrl conditions. Given these findings, our study uncovered an important role of glutamine metabolism in the antitumor activity of CD8 + T cells. The novel adoptive transfer of tumor-specific CD8 + T cells cultured in glutamine-restricted conditions may be a promising approach to improve the efficacy of cell-based adoptive immunotherapy.

DOI： 10.1111/cas.13827

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記述言語：英語  

DOI： 10.1097/ICO.0000000000001723

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METHODS: The P. aeruginosa strains examined were parental strain PAO1 and isogenic mutant strain pvdE (ΔpvdE) defective in pyoverdine. Bacterial growth in vitro was determined by PAO1 and ΔpvdE optical densities in Luria-Bertani (LB) broth. PAO1 or ΔpvdE (10 colony-forming units/mL) was inoculated onto cultured human corneal epithelial cells (HCECs) for 1 hour. The monolayers were examined for bacterial adhesion and invasion. In addition, the corneas of C57BL/6 mice were infected with PAO1 or ΔpvdE. Corneal virulence was evaluated by determining clinical scores and bacterial counts during infection.RESULTS: The growth of PAO1 and ΔpvdE in LB broth was similar. Although adhesion of ΔpvdE onto HCECs was significantly increased compared with PAO1, the invasive capacity of ΔpvdE was significantly decreased. Clinical scores and bacterial numbers were significantly lower in ΔpvdE-infected eyes compared with PAO1-infected eyes at 6, 24, and 48 hours (P < 0.001). ΔpvdE was not detected in mouse corneas and did not induce corneal opacity at 6, 24, or 48 hours.CONCLUSIONS: ΔpvdE lost invasive ability toward HCECs. Moreover, ΔpvdE did not cause keratitis in vivo. Thus, pvdE pyoverdine synthesis has critical roles in proliferation and invasion on ocular surfaces and could be a target for prevention of P. aeruginosa keratitis.PURPOSE: Pseudomonas aeruginosa produces pyoverdine, encoded by the pvdE gene, for high-affinity iron uptake from transferrin and lactoferrin. This study investigated the contribution of pyoverdine to P. aeruginosa keratitis pathogenesis using in vitro and in vivo models.

DOI： 10.1097/ICO.0000000000001728

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© 2018 The Authors. PURPOSE. To determine whether an eyelid pressure measurement device, called a blepharo-tensiometer, can detect changes in the eyelid pressure in different types of ocular surface disorders. METHODS. First, the repeatability of the blepharo-tensiometer was determined by measuring the eyelid pressures on 3 separate days from healthy volunteers and calculating the intraclass correlation coefficients (ICCs). Second, to determine the ability of the blepharo-tensiometer to detect changes in the eyelid pressures in different types of ocular surface disorders, we compared the eyelid pressure of healthy eyes with dry eyes. Third, the correlations between the eyelid pressure and the location and magnitude of fluorescein staining of the ocular surface were analyzed. Fourth, the eyelid pressure in eyes with lid-wiper epitheliopathy (LWE) was measured. RESULTS. The ICCs ranged from 0.675 to 0.911 for the upper eyelid and 0.663 to 0.925 for the lower eyelid. The pressures of the upper and lower eyelids were significantly higher in dry eyes than in healthy eyes. The inferior ocular surface staining scores were strongly correlated with the lower eyelid pressure by multivariate analysis. The lower eyelid pressure was significantly correlated with the grade of the lower LWE. CONCLUSIONS. The blepahro-tensiometer can obtain repeatable measurements of the eyelid pressure and can be used to evaluate the pressure of the eyelids on the ocular surface in healthy and diseased eyes. The significant correlations between the eyelid pressure and the ocular surface staining suggests that the pressure on the ocular surface probably contributes to ocular surface disorders.

DOI： 10.1167/iovs.17-23586

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記述言語：英語  

© 2018 The Authors. Dry eye disease (DED) is one of the most common disease in the ophthalmic clinic, and the reasons DED patients visit ophthalmic clinics are symptoms such as stinging, burning, or scratchy sensations. The symptoms and visual disturbances of DED have a negative impact on the daily routines and social lives of the patients (i.e., their quality of life [QOL]). The presence of symptoms was required in the definition of DED by the National Eye Institute/ Industry Workshop in 1995; therefore, disease-specific questionnaires were essential for monitoring and managing patients with DED. Thereafter, many questionnaires have been developed to evaluate the specific symptoms of dry eyes. Although many questionnaires are available to assess the dry eye symptoms, it is essential that they provide valid answers and are easy to use to assess the effects of DED on the QOL. The Asia Dry Eye Society and Japan Dry Eye Society have proposed a new definition of DED that is a combination of symptoms and an unstable tear film, and information on these two factors is sufficient to make a definitive diagnosis of DED. Therefore, the assessments of the symptoms are fundamental in the diagnosis of DED.

DOI： 10.1167/iovs.18-24570

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© Copyright 2018, Mary Ann Liebert, Inc., publishers 2018. Purpose: The aim of this study was to analyze patient backgrounds, including activities of daily living (ADL) and living status, predisposing risk factors, causative agents, and severity with infectious keratitis in old (75 < 85 years of age) and very old (≥85 years of age) patients. Methods: We retrospectively reviewed 54 old patients who were hospitalized for infectious keratitis. The focus occupancy ratio (FOR) was defined as the total focus area/entire cornea area. Results: The mean patient age was 82.9 ± 5.6 years. There were 33 old and 21 very old patients. Dementia was found in 8 patients (14.8%), but the most common predisposing risk factor was post-keratoplasty (15 patients, 27.8%). However, 10 patients (18.5%) had unknown risk factors. In all, 16 patients (29.6%) had low ADL, including being bedridden or being unable to go outside without assistance, and 19 patients (35.2%) lived alone. Causative agents were detected in 31 patients (57.4%) and included bacteria in 22 patients and fungi in 9 patients. Seventeen patients (31.5%) had >25% focus size of the corneal area. The average FOR was 12.1% ± 14.1%, and the mean best-corrected visual acuity (BCVA) at the first and final visits was 1.88 ± 0.71 and 1.52 ± 1.03 logMAR, respectively. Multivariate analyses showed that age correlated with FOR and the final BCVA. Conclusions: Infectious keratitis in old and very old patients is likely to be severe due to low ADL and social environment. Ophthalmologists should take care to identify keratitis during its early stage in these patients.

DOI： 10.1089/jop.2018.0028

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記述言語：英語  

© 2018 Naito et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Purpose To compare the success rates of eye drop instillation in the sitting position and supine position among Japanese patients with ocular diseases (cataract, glaucoma, or retinal and vitreous diseases). Methods Patients who were hospitalized in Okayama University Hospital for eye surgery were studied. Instillation procedures of each patient in both the sitting and supine positions were recorded using a video camera at the time of instillation. We defined “success” when one drop fell accurately onto the ocular surface at the first attempt. Instillation of two or more drops, drops delivered to a site other than the eye surface, and touching the eyelashes, eyelids, or conjunctiva with the tip of the eye drop bottle were regarded as “failure”. We excluded patients with vision below counting finger. Results One-hundred and two patients (54 males and 58 females, aged 70.2 ± 12.3 years) with ocular disease who were hospitalized for surgery (cataract: 61.8%, glaucoma: 15.7%, retinal and vitreous diseases: 22.5%) were included in this prospective observational study. The mean duration of eye drop use was 3.1 ± 5.2 years. The success rate of eye drop instillation was significantly higher in the supine position than in the sitting position (64.7% vs. 50%, P = 0.0039). The mean age was significantly higher in the failure group than in the success group (74.0 ± 11.5 vs. 67.7 ± 12.4 years, P = 0.0085) for the sitting position, but not significantly different for the supine position (72.3 ± 12.9 vs. 70.1 ± 12.0 years, P = 0.3849). No significant differences in mean duration of drop use, mean corrected VA, and mean spherical equivalent refraction were observed between success and failure groups, for both sitting and supine positions. Conclusions In the present study, the success rate of eye drop instillation was significantly higher when applied in the supine position than in the sitting position.

DOI： 10.1371/journal.pone.0204363

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記述言語：日本語   出版者・発行元：全日本病院出版会  

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記述言語：英語   出版者・発行元：Taylor and Francis Ltd  

Objective: To determine the effect of botulinum toxin A (BTX-A) on the eyelid pressure in patients with benign essential blepharospasm (BEB). Methods: Twenty normal volunteers (10 men, 10 women
average age 59.7 ± 11.3 years) and 33 patients (12 men, 21 women
average age 61.1 ± 14.7 years) with BEB were studied. The upper and lower eyelid pressures were measured with a blepharo-tensiometer in the normal subjects (N group). The eyelid pressures and intraocular pressures (IOP) were measured before and after the BTX-A injections in the BEB patients (B group). Results: The mean eyelid pressure in the N group was 31.0 ± 6.8 mmHg for the upper eyelid and 29.9 ± 6.5 mmHg for the lower eyelid (P &gt
 0.05). The mean eyelid pressure in the B group before treatment was 35.3 ± 7.0 mmHg for the upper eyelid and 37.8 ± 6.6 mmHg for the lower eyelid. The eyelid pressure in the B group was significantly higher than in the N group for the upper and lower eyelids (both P &lt
 0.001). The eyelid pressure was significantly decreased after BTX-A treatment for the upper (29.9 ± 7.5 mmHg) and the lower (32.8 ± 7.0 mmHg) eyelids (both P &lt
 0.001). The mean IOP was 15.1 ± 2.9 mmHg before, and it significantly decreased to 14.5 ± 2.8 mmHg (P = 0.020) after the BTX-A injections. The IOP was significantly correlated with the lower eyelid pressure (P = 0.0435), but not with the upper eyelid pressure (P = 0.175). Conclusion: The eyelid pressure was higher in the patients with BEB. The eyelid pressure and the IOP were significantly reduced after the BTX-A injections. In addition, the IOPs were significantly correlated with the eyelid pressure of the lower eyelid.

DOI： 10.1080/02713683.2018.1464191

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記述言語：日本語   出版者・発行元：金原出版  

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記述言語：日本語   出版者・発行元：医学書院  

© 2018 Igaku-Shoin Ltd. All rights reserved. Purpose: To report changes in contrast sensitivity following surgery for involutional blepharoptosis by levator resection. Cases and Method: This prospective study was made on 40 eyes of 20 patients who received surgery for involutioal blepharoptosis during a 5-month period. The age averaged 72.8 ± 8.7 years. All the eyes received CO 2 -assisted resection of levator and Miiller muscle. Blepharoptosis was evaluated by means of margin reflex distance (MRD). Blepharoptosis was evaluated as mild when MRD was 1 mm or over and as severe when MRD was 0 mm over lower. Contrast sensitivity was evaluated regarding photopic and mesopic vision. Surgery was subjectively evaluated by questionnaire to the patients. Results: There were 20 eyes with mild MRD and 20 eyes with severe MRD before surgery. MRD improved significantly in both groups after surgery (p = 0.016, p = 0.007 respectively). There was no difference in uncorrected visual acuity after surgery. Contrast sensitivy remained unchanged after surgery in eyes with mild blepharoptosis. It increased in high spatial frequency for photopic and mesopic vision in eyes with severe blepharoptosis (p = 0.022, p = 0.018, respectively). The eye strain, evaluated by visual analog score (VAS), improved in eyes with mild and severe blepharoptosis. The improvement was more manifest in visual functions (p<0.05). Conclusion: Contrast sensitivity serves as indicator for improved visual function following surgery for involutional blepharoptosis.

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© 2018 Igaku-Shoin Ltd. All rights reserved. Purpose: To report the efficacy of DuoActive® ET on skin defect following lateral tarsal scrip procedure (LTSP) for cicatricial ectropion in a case of long-term treatment with glaucoma eyedrop. Case: A 76-year-old man was referred to us for cicatricial ectropion in the right lower eyelid. Findings and Clinical Course: This patient presented with severe ectropion of his right lower eyelid with conjunctivitis, plenty of discharge and apparent dermodesis of the inflammatory lid margin and skin. He had been using prostaglandin eyedrop for glaucoma for more than 15 years. The horizontal looseness of his lower eyelid was prominent and the lateral tarsal strip procedure was performed. The dermodesis of lid margin and skin was separated. Skin defect was noted around his lateral canthus and lower eyelid right after the surgery. DuoActive® ET was applied for wound healing. The skin healed in two weeks with good formation of lateral canthus and eyelid contour. Conclusion ; Prolonged application of prostaglandin eyedrop is a risk factor for cicatricial ectropion. DuoActive® ET was simple and effective for would healing in skin defect following eyelid surgery.

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記述言語：日本語   出版者・発行元：医学書院  

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記述言語：日本語   出版者・発行元：医学書院  

© 2018 Igaku-Shoin Ltd. All rights reserved. Purpose: To report changes in the shape of cornea and visual functions following surgery for blepharoptosis. Cases and Method: We reviewed 45 cases who received bilateral CO2 laser-assisted levator resection for involutional blepharoptosis in the past 2 years. The age averaged 73.8 ± 6.7 years. Before and after surgery, cases were evaluated regarding visual acuity, corneal astigmatism, total high-order aberration (HOA), coma, and spherical aberration. Area ratio was calculated from contrast sensitivity simulation using modulation transfer function (MTF). Results: Corneal astigmatism averaged l.$6±0.52D before surgery and 1.29±0.47D after surgery. The difference was significant (p = 0.013). After surgery, total HOA and coma aberration during phot- opia and coma aberration during mesopia decreased significantly. Area ratio increased significantly from presurgical value of 14.8 ±4.2% to postsurgical value of 18.6±4.5% (p = 0.019). Eye strain, as reported by patients, decreased regarding stiff shoulder, irritation and blurring (p<0.05 respectively). Conclusion: Surgery for blepharoptosis resulted in improved subjective and objective visual functions probably secondary to decreased corneal astigmatism. This finding seemed to be related to improvement in HOA and contrast sensitivity.

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記述言語：日本語   出版者・発行元：メディカル葵出版  

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© 2018 Newswood Limited. All rights reserved. BAD (Blink Associated Disorder) such as SLK (Superior Limbic Keratoconjunctivitis) or LWE (Lid Wiper Epitheliopathy) decreases QOL(Quality Of Life). Therefore, it is very important to investigate their cause. Then, FEA (Finite Element Analysis) was carried out for the friction developing on contact surfaces between an eyeball and an eyelid. As the calculated results, deformations and shearing stresses on the ocular surface and the eyelid’s one were shown. Finally, the relationship between the friction and BAD was discussed. As a result, BAD is thought to be caused by the friction occurred at blinking.

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Copyright © 2018 Yasuhito Ikegawa et al. Purpose. To compare the morphology of two types of vortex keratopathy: Amiodarone-induced keratopathy and the Fabry diseaseassociated keratopathy. Patients and Methods. Eight patients who were receiving oral amiodarone therapy and 3 patients with Fabry disease, a mother and her 2 daughters, were examined by slit-lamp biomicroscopy and in vivo confocal microscopy (IVCM) regularly. Results. Amiodarone-induced keratopathy developed in 7 of the 8 patients, and it was detected as early as 7 days by IVCM and 14 days by slit-lamp biomicroscopy. The in vivo confocal microscopic images showed a clustering of corneal epithelial cells with a highly reflective cytoplasm in both types of keratopathy. In the amiodarone-induced keratopathy, the highly reflective epithelial cells were first found at the center of the cornea and then spread to the periphery with increasing time on amiodarone. In Fabry disease, the highly reflective epithelial cells were consistently observed extending from the limbus to the central cornea. Conclusion. These findings suggest that the corneal epithelial cells most likely endocytose amiodarone from the tear film in the amiodarone-induced keratopathy. In Fabry disease, globotriaosylceramide deposits are taken up by the lysosomes of the limbal epithelial stem cells, and they differentiate and migrate to the center of the cornea to form the whorl pattern.

DOI： 10.1155/2018/5315137

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記述言語：日本語   出版者・発行元：一般社団法人 日本機械学会  

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記述言語：日本語   出版者・発行元：日本コンタクトレンズ学会誌編集部  

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記述言語：日本語   出版者・発行元：メディカル葵出版  

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記述言語：英語   出版者・発行元：PUBLIC LIBRARY SCIENCE  

Background
To investigate the success rate of eye drop instillation in glaucoma patients with visual field defect as well as non-glaucoma volunteers. Factors that may affect the success rate of eye drop instillation were also evaluated.
Design
A prospective, observational study.
Participants
Seventy-eight glaucoma patients and 85 non-glaucoma volunteers were recruited in this study.
Methods
Open angle glaucoma patients with visual field defect as well as non-glaucoma volunteers were asked to video record their procedures of eye drop instillation using a 5-mL plastic bottle of artificial tear solution. Success of eye drop instillation was judged on video based on the first one drop of solution successfully applied on the cornea, by two investigators.
Main outcome measures
Success rate of eye drop instillation in glaucoma patients and non-glaucoma volunteers. Factors related to success rate of eye drop instillation, such as visual field defect and clinical characteristics, were also analyzed using multivariable logistic regression.
Results
No significant deference in mean age was observed between two groups (glaucoma: 64.5 +/- 14.4 years, non-glaucoma: 60.9 +/- 14.1 years, P = 0.1156). Success rate of eye drop instillation was significantly lower (P = 0.0215) in glaucoma patients (30/78; 38.5%) than in non-glaucoma volunteers (48/85; 56.5%). The most frequent reason of instillation failure in glaucoma patients was touching the bulbar conjunctiva, cornea, eyelid or eyelashes with the tip of the bottle (29.5%). Multivariable logistic regression analysis identified lower corrected visual acuity (VA) (<= 1.0; odds ratio [OR] = 0.20, 95% confidence interval [CI] 0.04-0.93, P = 0.0411), lower mean deviation (MD) (< -12 dB; OR = 0.20, 95% CI 0.05-0.86, P = 0.0307) and visual field defect (VFD) in the inferior hemifield (OR = 0.11, 95% CI 0.02-0.34, P < 0.001) to be significantly related to instillation failure in glaucoma patients.
Conclusions
Success rate of eye drop instillation was significantly lower in glaucoma patients than in non-glaucoma volunteers. Corrected VA <= 1.0, MD < -12 dB and/or VFD in the inferior hemifield may be related to failure of eye drop instillation.

DOI： 10.1371/journal.pone.0185874

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記述言語：日本語   出版者・発行元：メディカル葵出版  

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記述言語：日本語   出版者・発行元：医歯薬出版  

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記述言語：日本語   出版者・発行元：メディカル葵出版  

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記述言語：日本語   出版者・発行元：金原出版  

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記述言語：日本語   出版者・発行元：眼科臨床紀要会  

Background - Conjunctival amyloidosis is a rare disease. Definitive diagnosis is made by histopathological findings. We report a case of conjunctival amyloidosis that was evaluated using in vivo confocal microscopy with the Heidelberg Retina Tomograph II Rostock Cornea Module (HRT- RCM). Case Report - A 37-year-old man visited Inouye Eye Clinic because of upper right eyelid thickening and discomfort on June 28th. 2007. He was referred to Ehime University Hospital on July 12th. 2011. because anti-inflammatory and antibacterial treatments were not effective. A yellow or pink hyperplastic lesion with hyperemia was observed in the upper right eyelid, and yellow elevated lesions were observed in both lower lids. We examined these lesions with HRT-RCM. The HRT-RCM images revealed mixed high and low reflective acellular areas that were clearly different from the normal conjunctival glandular structure. An excisional biopsy of conjunctival tissue from the upper right eyelid was submitted for pathology assessment. The histopathological findings revealed deposition of serum amyloid A. Because no amyloid deposition was detected in any other organs, the case was diagnosed as regional conjunctival amyloidosis. Conclusions ∗ HRT-RCM may be useful as a noninvasive adjunct for the diagnosis of conjunctival amyloidosis.

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記述言語：日本語   出版者・発行元：日本眼科学会  

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記述言語：日本語   出版者・発行元：日本コンタクトレンズ学会誌編集部  

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記述言語：日本語   出版者・発行元：公益社団法人 計測自動制御学会  

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記述言語：日本語   出版者・発行元：医学書院  

Purpose: To report the outcome of endoscopic nasolacrimal duct intubation as related to cultured microorganisms in nasolacrimal duct obstruction. Case and Method: This study was made on 74 sides of 64 patients who received endoscopic nasolacrimal duct intubation during 45 months through September 2014. The age ranged from 39 to 90 years, average 72 years. Discharge from lacrimal ducts was cultured before surgery. Patients were followed up for 6 months or longer after removal of lacrimal tube. Results: During the follow-up for an average of 10.8 months, nasolacrimal duct obstruction recurred in 16 out of 74 sides (21.6%). Overall rate of positive microbial growth was 58 out of 74 specimens (78.4 %). Rate of recurrence was higher when two or more species were involved (37.5 %) than when one or no species was involved (7.7% and 12.5% respectively). The difference was significant (p = 0.0141). Rate of recurrence was significantly higher when culture for Streptocococcus angiosus group was positive than in culture-negative cases (p = 0.0192). Conclusion: Outcome of endoscopic nasolacrimal duct intubation differed dependent on the species and number of causative microorganisms.

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記述言語：英語   掲載種別：速報，短報，研究ノート等（学術雑誌）   出版者・発行元：Elsevier Inc.  

DOI： 10.1016/j.ajo.2016.01.007

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記述言語：日本語   出版者・発行元：一般社団法人 日本機械学会  

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記述言語：日本語   出版者・発行元：メディカル葵出版  

CiNii Books

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記述言語：日本語   出版者・発行元：メディカル葵出版  

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記述言語：日本語   出版者・発行元：医学書院  

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記述言語：日本語   出版者・発行元：日本コンタクトレンズ学会誌編集部  

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記述言語：日本語   出版者・発行元：南江堂  

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記述言語：日本語   出版者・発行元：メディカル葵出版  

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記述言語：英語   出版者・発行元：LIPPINCOTT WILLIAMS & WILKINS  

Objective: To report lid-wiper epitheliopathy (LWE)-like staining at the lower eyelid margin (lower-LWE) and to determine the prevalence of LWE (upper-LWE) and lower-LWE in contact lens (CL) wearers and non-CL wearers.
Methods: Four hundred forty-three eyes of 229 non-CL wearers, 405 eyes of 208 soft CL wearers, and 135 eyes of 71 rigid gas permeable CL wearers were studied. Lissamine green and fluorescein (FL) staining were used to assess the degree of LWEs, tear break-up time (BUT), and cornea-conjunctival staining (FL-S). The correlations between the prevalence of LWEs and the other factors were evaluated.
Results: The prevalence of lower-LWE was significantly higher (39.5%) than upper-LWE in non-CL wearers (upper-LWE; 12.0%; P<0.001). The prevalence of both upper-and lower-LWE were significantly correlated with age and FL-S, but not sex and BUT, in non-CL wearers. The prevalence of both upper-and lower-LWE was significantly higher in younger than older subjects (P<0.001). Upper-and lower-LWE were detected in a higher percentage of CL wearers than in non-CL wearers (P<0.001).
Conclusion: Our results indicate that examination of the lower eyelid margin would be preferable to that of the upper eyelid margin in studies of LWE.

DOI： 10.1097/ICL.0000000000000040

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記述言語：日本語   出版者・発行元：日本眼科学会  

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記述言語：日本語   出版者・発行元：日本コンタクトレンズ学会誌編集部  

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記述言語：日本語  

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記述言語：日本語   出版者・発行元：メディカ出版  

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記述言語：日本語   出版者・発行元：メディカ出版  

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記述言語：日本語  

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記述言語：日本語  

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記述言語：日本語   出版者・発行元：日本コンタクトレンズ学会誌編集部  

CiNii Books

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記述言語：日本語   出版者・発行元：日本コンタクトレンズ学会誌編集部  

CiNii Books

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記述言語：日本語   出版者・発行元：メディカル葵出版  

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記述言語：日本語   出版者・発行元：メディカル葵出版  

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記述言語：日本語  

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記述言語：日本語   出版者・発行元：医学書院  

Purpose : To report the short-term effect of peroally administered pilocarpine for dry eye. Cases and Method : This prospective study was made on 30 eyes of 15 patients with dry eye and oral symptoms. The series comprised 2 males and 13 females. The age averaged 61.8 ±12.0 years. Each patient received 5 mg pilocarpine twice daily. Subjective and objective findings were evaluated 1 hour, 4 weeks, and 8 weeks after start of treatment. Oral symptoms were evaluated by visual analogue scale (VAS). Results : VAS and tear breakup time started to significantly improve one hour after treatment. Subjective ocular symptoms and findings by fluorescein staining of the cornea significantly improved after 4 weeks of treatment. There was no change in findings by Schirmer test throughout the studv for 8 weeks. Conclusion : Peroral pilocarpine promises to be of value for dry eye with oral symptoms.

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記述言語：日本語   出版者・発行元：医学書院  

Purpose: To report and evaluate the efficacy and indications of atelocollagen liquid punctum plugs (Keeptear̄ for dry eye symptoms. Cases and Method: This study was made on 30 eyes of 15 patients with dry eye symptoms. The age averaged 57±18 years. The lacrimal punctum was occluded by inserting Keeptear̄Cases were followed up for 8 weeks. Results: Ocular surface disease index (OSDI) improved after insertion. Objectively, treated eyes showed improved tear volume and keratoconjunctival fluorescein staining score. OSDI, tear volume and keratoconjunctival fluorescein staining score improved in eyes with Schirmer test of 6 mm or more and failed to improve with 5 mm or less. Conclusion: Insertion of Keeptear̄may be a useful therapeutic means for relatively mild dry eye symptoms.

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記述言語：日本語   出版者・発行元：日本眼科学会  

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記述言語：日本語   出版者・発行元：日本眼科学会  

To understand the current state of severe contact lens (CL)-associated microbial keratitis in Japan. The survey was conducted by the Japan Contact Lens Society and the Japanese Association for Ocular Infection in 224 facilities from April 2007 to March 2009. Patients who were diagnosed with CL-associated microbial keratitis and hospitalized for treatment were enrolled. Clinical characteristics of the keratitis, microbiologic findings and the status of CL hygiene were studied. A total of 350 patients were investigated, with an average age of 28.0 (9-90) years. Acanthamoeba was identified in 85 (24.3%) corneal specimens and Pseudomonus aeruginosa in 70 (20.0%) cases. One hundred ninety six (56.0%) patients were frequent replacement soft CL users. Extended wearing of daily-use CLs was found in 77 (22.0%) patients. Only 67 cases maintained good CL hygiene by daily rubbing-washing and the poor CL care situation was reviewed. The most frequently detected pathogenic microorganism was Acanthamoeba, followed by Pseudomonus aeruginosa. Our survey showed the importance of keeping good CL hygiene by proper lens care, and improvement of CL-related social regulations is urgently needed.

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記述言語：日本語   出版者・発行元：日本コンタクトレンズ学会誌編集部  

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記述言語：日本語   出版者・発行元：日本コンタクトレンズ学会誌編集部  

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記述言語：英語   掲載種別：速報，短報，研究ノート等（学術雑誌）  

DOI： 10.1136/bjo.2010.183814

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記述言語：日本語   出版者・発行元：日本眼科学会  

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記述言語：日本語   出版者・発行元：メディカル葵出版  

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PURPOSE: To investigate whether images obtained using DR-1, a tear specular microscope, can be applied to the evaluation of tear meniscus volume. METHODS: Of 94 eyes of 47 subjects examined, 66 eyes of 33 subjects were diagnosed with definite, suspected or absence of dry eye using the 2006 diagnostic criteria. Tear meniscus height values found using DR-1 meniscus height (DRMH, mm), slit lamp meniscus height (SLMH, low/medium/high), and fluorescein meniscus height (FLMH, mm) were compared. The reproducibility, sensitivity and specificity of DRMH values with regard to dry eye diagnosis were investigated. Changes in DRMH after insertion of lacrimal plugs and during soft contact lens (SCL) wear were also examined. RESULTS: DRMH was significantly correlated with SLMH (r = 0.737, Spearman rank correlation coefficient) and FLMH (r = 0.06, Bland-Altman analysis). DRMH values (mm) in the normal (0.29 +/- 0.05), suspected dry eye (0.19 +/- 0.07), and definitely dry eye groups (0.17 +/- 0.06) were significantly different (p < 0.001), and showed good reproducibility. At a cut-off value of 0.22 mm, the sensitivity of dry eye diagnosis was 84.1% and specificity was 90.9%. DRMH increased significantly after insertion of lacrimal plugs (p < 0.0001) and decreased significantly during SCL use (before vs. 60 minutes after SCL insertion, p < 0.05, before vs. 120 minutes after insertion, p < 0.001). CONCLUSION: DR-1 and specialized analysis software make simple and non-invasive evaluation of tear meniscus volume possible.

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記述言語：日本語   出版者・発行元：日本コンタクトレンズ学会誌編集部  

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記述言語：日本語   出版者・発行元：永井書店  

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記述言語：日本語   出版者・発行元：日本コンタクトレンズ学会誌編集部  

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記述言語：日本語   出版者・発行元：メディカル葵出版  

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記述言語：英語   出版者・発行元：B M J PUBLISHING GROUP  

Aims: To evaluate the usefulness of serial frozen sections of corneal scrapings stained with Fungiflora Y (FFY) to diagnose Acanthamoeba keratitis (AK).
Methods: Eight patients with suspected AK were studied. Serial frozen sections were made from part of the corneal epithelial scrapings and stained with FFY. The remaining corneal epithelial scrapings were submitted for laboratory culture.
Results: The FFY stained frozen sections were completed within an hour, and Acanthamoeba cysts were detected under a fluorescence microscope in all eight patients. The same sections were examined with a light microscope, and Acanthamoeba cysts were confirmed to be present from their morphological characteristics. Five of the eight patients had positive laboratory cultures for Acanthamoeba.
Conclusion: FFY staining of frozen sections of corneal scrapings is a rapid and reliable technique which can be used to make an early diagnosis of AK.

DOI： 10.1136/bjo.2009.158113

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記述言語：英語   出版者・発行元：株式会社メディカル葵出版  

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記述言語：英語   出版者・発行元：B M J PUBLISHING GROUP  

Aim: To determine whether thermography can be used to evaluate bleb function.
Methods: The surface temperatures of filtering blebs from 39 eyes of 33 post-trabeculectomy patients were measured using thermography. We introduced a new parameter: the temperature decrease in the filtering bleb (TDB) where TDB = (mean temperature of the temporal and nasal bulbar conjunctiva)-(temperature of the filtering bleb). The eyes were classified into good and poor intraocular pressure (IOP) control groups according to the patients' postoperative IOP. The morphological appearance of the filtering blebs were classified by slit-lamp images according to the Indiana Bleb Appearance Grading Scale. The differences in TDB were analysed statistically.
Results: Mean overall scores were as follows. The TDB were 0.54 (SD 0.20) degrees C and 0.21 (SD 0.18)degrees C for the good and poor IOP control groups, respectively. The difference between the TDB of the two IOP control groups was significant (p < 0.0001), but there was no significant relationship between morphological classification and TDB.
Conclusions: Thermographic measurements suggest that functional blebs have lower temperatures than nonfunctional blebs, and their morphological appearances are not affected by their temperature. Thermography may be useful for the evaluation of bleb function.

DOI： 10.1136/bjo.2008.152066

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記述言語：日本語   出版者・発行元：メディカル葵出版  

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記述言語：日本語  

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記述言語：日本語   出版者・発行元：日本眼科学会  

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PURPOSE: Lid-wiper epitheliopathy (LWE) is characterized by one part of the marginal conjunctiva of the upper eyelid being affected and is correlated with dry eye symptoms. This is a study of the clinical features of LWE. METHODS: Three hundred and sixty-four eyes of 182 patients with dry eye symptoms were studied. In all subjects the presence of LWE was determined by lissamine green staining followed by tests for dry eye. RESULTS: LWE was detected in 48 of 364 eyes (13.2%). One hundred thirty-four eyes were diagnosed with dry eye and LWE was detected in 25 of 134 eyes (18.7%). This rate was higher than that of non-dry eyes with LWE (23 of 230 eyes, 10.0%). Since LWE was detected at a high rate in contact lens (CL) wearers (22 of 37 eyes, 59.4%), LWE background factors in CL wearers and non-CL wearers were compared. Significantly higher fluorescein staining scores were detected in the LWE positive CL wearers compared to LWE negative CL wearers, whereas no significant differences were detected between the LWE positive and negative groups in any other dry eye examination. LWE-like lissamine green staining was detected on the lower eyelids in 122 eyes (33.0%). CONCLUSION: LWE was detected in more than 10% of patients with dry eye symptoms. Although LWE was detected in dry eye patients, no clear relationship was recognized between LWE and the presence of dry eye.

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記述言語：日本語   出版者・発行元：メディカル葵出版  

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記述言語：日本語   出版者・発行元：メディカル葵出版  

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記述言語：英語   出版者・発行元：メディカル葵出版  

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記述言語：日本語  

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記述言語：日本語  

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記述言語：日本語   出版者・発行元：メディカル葵出版  

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記述言語：日本語  

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記述言語：日本語   出版者・発行元：日本コンタクトレンズ学会誌編集部  

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記述言語：日本語   出版者・発行元：メディカル葵出版  

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We evaluated the analgesic effect of adhesive tape containing 60% lidocaine prior to retrobulbar anesthesia in 88 patients. We also evaluated the value of peroal 0.5 mg etiozolam in alleviating pain during retrobulbar anesthesia. The patients were allocated to one of four groups. One group received lidocaine tape. Another group received lidocaine tape and etiozolam. A third group received etiozolam only. A fourth group served as control. Use of lidocaine tape significantly reduced pain during needle puncture (p<0.01) but not during injection. Premedication with etiozolam failed to reduce pain during needle puncture or injection. The findings show that lidocaine tape reduces pain of needle puncture for retrobulbar anesthesia.

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記述言語：日本語   出版者・発行元：医学書院  

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記述言語：英語   出版者・発行元：AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC  

Lumican regulates collagenous matrix assembly as a keratan sulfate proteoglycan in the cornea and is also present in the connective tissues of other organs and embryonic corneal stroma as a glycoprotein. in normal unwounded cornea, lumican is expressed by stromal keratocytes. Our data show that injured mouse corneal epithelium ectopically and transiently expresses lumican during the early phase of wound healing, suggesting a potential lumican functionality unrelated to regulation of collagen fibrillogenesis, e.g. modulation of epithelial cell adhesion or migration. An anti-lumican antibody was found to retard corneal epithelial wound healing in cultured mouse eyes. Healing of a corneal epithelial injury in Lum(-/-) mice was significantly delayed compared with Lum(+/-) mice. These observations indicate that lumican expressed in injured epithelium may modulate cell behavior such as adhesion or migration, thus contributing to corneal epithelial wound healing.

DOI： 10.1074/jbc.275.4.2607

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記述言語：英語   出版者・発行元：ASSOC RESEARCH VISION OPHTHALMOLOGY INC  

PURPOSE. Keratin 12 (K12) is a cornea epithelial cell-specific intermediate filament component. To provide a better understanding of its expression, it is necessary to identify and characterize the promoter of Krt1.12 gene.
METHODS. The 2.5-kb DNA 5' to Krt1.12 gene was sequenced. K12 promoter-Rho-gal DNA constructs were prepared and used in vivo to transfect rabbit corneas, conjunctivas, and skin by particle-mediated gene transfer (Gene Gun). In vitro, the DNA constructs were transfected into cultured T-antigen-transformed rabbit corneal epithelial (RCE-T) cells and human fibrosarcoma HT-1080 fibroblasts with lipofectamine. The promoter activity was assessed by measuring beta-gal (beta-galactosidase) activity using histochemical staining with 5-Bromo-4-chloro-3-indolyl-beta-D-galactoside and enzyme assay with o-nitrophenyl beta-D-galactopyranoside.
RESULTS. There are four Pax-6 pair box binding elements found between -910 and -2000 bp 5'-flanking the transcription initiation site of the Krt1.12 gene. None of promoter constructs can be expressed by HT-1080 cells. Cotransfection of Pax-6 cDNA with K12 promoter-beta-gal constructs containing Pax-6 elements results in a fourfold increase of beta-gal activities in RCE-T cells but not HT-1080 fibroblasts. The data of in vivo transfection in the rabbit by Gene Gun indicate that reporter gene constructs containing 0.6-kb and longer DNA fragments 5'-flanking Krt1.12 gene are effectively expressed in corneal, but not conjunctival or epidermal epithelial cells.
CONCLUSIONS. The particle-mediated gene transfer is a suitable technique for in vivo delivery of transgenes to corneal epithelial cells. The 2.5-kb DNA fragment 5'-flanking Krt1.12 contains corneal epithelial cell-specific regulatory cis-DNA elements. Pax-6 is a positive transcription factor essential for keratin 12 expression.

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記述言語：英語   出版者・発行元：AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC  

Keratan sulfate proteoglycans (KSPGs) play a pivotal role in the development and maintenance of corneal transparency. Keratocan, lumican, and mimecan (osteoglycin) are the major KSPGs in vertebrate corneas. To provide a better understanding of the structure/function relationship of keratocan, we have cloned both the mouse keratocan gene and its cDNA. We have also examined its expression during embryonic development. The mouse keratocan gene spans approximately 6.5 kilobases of the mouse genome and contains three exons and two introns. Northern blotting and in situ hybridization were employed to examine keratocan gene expression during mouse development. Unlike lumican gene, which is expressed by many tissues other than cornea, keratocan mRNA is more selectively expressed in the corneal tissue of the adult mouse. During embryonic development, keratocan mRNA was first detected in periocular mesenchymal cells migrating toward developing corneas on embryonic day 13.5 (E13.5). Its expression was gradually restricted to corneal stromal cells on E14.5 similar to E18.5. Interestingly, keratocan mRNA can be detected in scleral cells of E15.5 embryos, but not in E18.5 embryos. In adult eyes, keratocan mRNA can be detected in corneal keratocytes, but not in scleral cells.

DOI： 10.1074/jbc.273.35.22584

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Purpose. Bsk (bare skin) is an autosomal dominant mutation linked to the Krt 1 (type 1 keratin) locus of mouse chromosome 11. The adult Bsk mouse manifests hair loss and corneal opacity. To identify and characterize the keratin genes involved in this mutation, we examined the hypothesis proposing that the Bsk mutation might involve a recombination event between cornea-specific (K12) and hair-specific (mHa 1, 2, 3 and 4) type I keratin genes. Methods. The Bsk phenotype was examined by histochemical analysis, using light and electron microscopy. RFLP was used for their genotyping, and possible keratin gene expression was examined by immunohistochemical staining, Western analysis, RT-PCR and Northern hybridization. Results. Northern hybridization, RT-PCR and Western blot analysis revealed that mHa 1, 2, 3 and 4 keratins are expressed in the skin, but not in cornea, whereas the expression of K12 is limited to the corneas of the Bsk mice. These data ruled out the hypothesis that Bsk phenotype results from a recombination event between K12 and mHa 1, 2, 3 and 4. Ultrastructural and biochemical analyses also indicated that Bsk does not involve negative dominant mutations of keratin 12, mHa 1, 2, 3 and 4, epidermal-specific keratin 10, or basal cell-specific keratin 14. Expression of an acidic 50 kD keratin, recognized by monoclonal antibody AK 2, was up-regulated in the injured corneas of normal mice as well as Bsk corneas. Conclusion. The gene linked to the Bsk mutation remains unknown. The pathological changes in the skin and corneas may be secondary to the loss of protecting hairs and lashes by an unknown mechanism.

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記述言語：英語   出版者・発行元：AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC  

Lumican is one of the major keratan sulfate proteoglycans (KSPG) in vertebrate corneas. We previously cloned the murine lumican cDNA. This study determines the structure of murine lumican gene (Lum) and its expression during mouse embryonic developments. The mouse lumican gene was isolated from a bacterial artificial chromosome mouse genomic DNA library and characterized by polymerase chain reaction and Southern hybridization. The lumican gene spans 6.9 kilobase pairs of mouse genome. The gene consists of three exons and two introns. Exon 1 constitutes 88 bases (b) of untranslated sequence. Exon 2 is 883 b and contains most of the coding sequence of lumican mRNA, and exon 3 has 152 b of coding sequence and 659 b of 3' noncoding sequence. The mouse lumican gene has a TATCA element, a presumptive TATA box, which locates 27 b 5'-upstream from the transcription initiation site, Northern hybridization and in situ hybridization indicate that ill early stages of embryonic development, day 7 post coitus the embryo expresses little or no lumican, Thereafter, different levels of lumican mRNA can be detected in various organ systems, such as cornea stroma, dermis, cartilage, heart, lung, and kidney. The cornea and heart are the two tissues that have the highest expression in adult. Immunoblotting studies found that KSPG core proteins became abundant in the cornea and sclera by postnatal day 10 but that sulfated KSPG could not be detected until after the eyes open. These results indicate that. lumican is widely distributed in most interstitial connective tissues, The modification of lumican with keratan sulfates in cornea is concurrent with eye opening and may contribute to corneal transparency.

DOI： 10.1074/jbc.272.48.30306

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記述言語：英語   出版者・発行元：LIPPINCOTT-RAVEN PUBL  

Purpose. Expression of the K3-K12 keratin pair characterizes the corneal epithelial differentiation. To elucidate the role of keratin 12 in the maintenance of corneal epithelium integrity, the authors bred mice deficient in keratin 12 by gene-targeting techniques.
Methods. One allele of murine Krt1.12 gene was ablated in the embryonic stem cell line, E14.1, by homologous recombination with a DNA construct in which the DNA element between intron 2 and exon 8 of the keratin 12 gene was replaced by a neogene. The homologous recombinant embryonic stem cells were injected to mouse blastocysts, and germ lines of chimeras were obtained, The corneas of heterozygous and homozygous mice were characterized by clinical observations using stereomicroscopy, histology with light and electron microscopy. Western immunoblot analysis, immunohistochemistry, in situ hybridization, and Northern hybridization.
Results. The heterozygous mice (+/-) one allele of the Krt1.12 gene appear normal and do not develop any clinical manifestations (e.g., corneal epithelial defects). Homozygous mice (-/-) develop normally and suffer mild corneal epithelial erosion, Their corneal epithelia are fragile and can be removed by gentle rubbing of the eyes or brushing with a Microsponge. The corneal epithelium of the homozygote (-/-) does not express keratin 12 as judged by immunohistochemistry, Western immunoblot analysis with epitope-specific anti-keratin 12 antibodies, Northern hybridization with P-32-labeled keratin 12 cDNA, and in situ hybridization with an anti-sense keratin 12 riboprobe. Light and electron microscopy revealed subtle abnormalities in the corneal epithelia of -/- mice (i.e., a decrease in number of cell layers) and cytolysis of superficial cells, but the number of hemidesmosomes and desmosomes are normal in basal and suprabasal cells. The number of keratin intermediate filaments in basal and suprabasal corneal epithelial cells in -/- mice decreases, and they appear as dense bundles. This morphology is similar to that of keratin intermediate filaments in epidermal epithelial cells but differs from that of normal corneal epithelial cells in which the keratins form fine filamentous networks. The superficial epithelial cells are devoid of keratin intermediate filaments and often detach from the corneal surface of -/- mice.
Conclusions. The presence of cornea-specific K3-K12 keratin pairs is essential for the maintenance of corneal epithelium integrity.

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Purpose. Bsk (bare skin) mouse is an autosomal dominant mutation linked to the Krt 1 locus (type 1 keratins) in mouse chromosome II. To identify and characterize the keratin genes involved in this mutation, we examined the expression of mHa (mouse hair keratin) 1,2,3 &4 and K12 in Bsk mice. Methods. Bsk mice were examined weekly for hair loss and corneal opacity. At different times animals were sacrificed. Genomic DNA were subjected to RFLP (restriction fragment length polymorphism) for mHa 1,2,3 &4 and K12 genes. Tissues were subjected to histological examination with light and electron microscopy, immunohistochemical, Western analysis with anti-mHa 3, anti-K12 and AE-1 antibodies and Northern hybridization with 32P labeled mHa 1,2,3 &4 and K12 cDNA. Total RNA were used in RT-PCR to detect the presence of mHa mRNAs in skins and corneas. Results. Bsk mice began to show hair loss about 6-8 weeks of age. Corneas developed opacity and epithelial defect at 2 months of age. Histology revealed severe inflammatory responses in skin and corneas when Bsk mice grew older. RFLP indicated that Bsk mice were classified in 3 genotypes with respect to the mHa 3 gene using BamHI. RT-PCR analysis indicated that 3′ end short form primer pairs detected mHa 3 mRNA in skin of Bsk mice, whereas 5′ end long form primer pairs didn't detect mHa 3 mRNA in skin of Bsk mice. Northern hybridization indicated that the expression of mHa 3 mRNA was observed in skins of 3 out of 14 Bsk mice and no expression in the eyes of mutants and wild type. Western analysis showed expression of mHa 3 in skin of 1 out of 3 Bsk mice and no expression in eyes of mutants and wild type. However there is a change in the expression of acidic keratins in Bsk skin and eye as detected by monoclonal antibody AE-1. Southern hybridization, RT-PCR analysis, Western analysis and Northern hybridization did not detect any abnormalities in mHa 1,2,4 and K12 genes. Conclusion. Our results revealed that the expression of mHa 3 is altered in the skin of Bsk mice. The Bsk mutation may involve the mouse mHa 3 gene.

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Purpose. Expression of K3/K12 keratin pair characterizes the cornea-type epithelial differentiations. To elucidate the role of keratin 12 in the maintenance of corneal epithelium integrity, we have created transgenic mice deficient in keratin 12 via gene target techniques. Methods. One allele of murine KrtI.12 gene was ablated in embryonic stem cells, ES14.1 via homologous recombination with a DNA construct in which the DNA elements of exons 2 through exon 7 of keratin 12 gene was replaced by a Neo-gene. The homologous recombinant ES cells were injected to mouse blastocysts and germ lines transgenic mice were obtained. The corneas of hemizygous and homozygous transgenic mice were characterized by clinical observations under stereo microscope, histology at light and eletron microscopy, immunohistochemistry, in situ hybridization, Northern hybridization and Western immunoblot analysis. Results. The hemizygous transgenic mice lacking one allele of Krt1.12 gene appear normal and do not develop any clinical manifestations, e.g., cornea epithetial defects. Homozygous transgenic mice lacking both alleles develop normally and suffer repetitive corneal epithelial defects. Histoligical examination did not reveal abnormality in corneal epithelium, i.e., number of cell layers, and hemidesmosomes and desmosome. The cornea epithelium does not express keratin 12 as judged by immunohistochemistry, Western immune blot analysis with epitope-specific anti-keratin 12 antibodies, and Northern hybridization with 32P-labeled keratin 12 cDNA and in situ hybridization with anti-sense keratin 12 riboprobe. Conclusion. The presence of cornea-specific K3/K12 keratin pair is essential for the maintenance of corneal epithelium integrity.

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記述言語：日本語   出版者・発行元：日本大腸肛門病学会  

大腸癌の基底膜や細胞外基質成分であるラミニン(LN),IV型コラーゲン(C-IV),フィブロネクチン(FN),III型コラーゲン(C-III)とその受容体,そしてマトリックスメタロプロテァーゼ(MMP)の局在と癌細胞の脈管侵襲や壁深達度との関連性について免疫組織化学法とRT-PCR法,in situ hybridization(ISH)法にて検討した.基底膜成分のC-IV,LN,C-IIIの局在が癌の進行とともに減少し,C-IV,LNでは癌がpmに浸潤すると,その局在は有意に減少し受容体に変化をみた.リンパ節転移を認める症例でLNのみが有意に減少していた(p<0.01).間質ではpm以上に浸潤した症例でFN,C-II,LNの増加と,リンパ節転移を有する症例でC-Nの有意な増加を認めた(P<0.05).RT-PCR法とISH法では,癌巣周囲の正常腺管と癌組織内の間質細胞にMMP-2とそのm-RNAの発現を認めた.以上の細胞生物学的知見は,癌細胞と基底膜,間質の相互作用の重要性を示唆していると思われた.

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記述言語：日本語   出版者・発行元：一般社団法人日本消化器外科学会  

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記述言語：日本語   出版者・発行元：一般社団法人日本消化器外科学会  

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記述言語：日本語   出版者・発行元：一般社団法人日本消化器外科学会  

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記述言語：日本語   出版者・発行元：一般社団法人日本消化器外科学会  

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