研究者詳細 - 坪田　一男

論文 - 坪田　一男

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Association of macular pigment optical density with serum concentration of oxidized low-density lipoprotein in healthy adults

Nagai Norihiro, Izumi-Nagai Kanako, Suzuki Misa, Shinoda Hajime, Koto Takashi, Uchida Atsuro, Mochimaru Hiroshi, Tomita Yohei, Miyake Seiji, Kobayashi Saori, Sasaki Mariko, Tsubota Kazuo, Ozawa Yoko

Retina 35 （ 4 ） 820 - 826 2015年04月

ISSN 0275-004X

Purpose: To analyze the association between macular pigment optical density (MPOD), which reflects lutein (L), zeaxanthin (Z), and meso-zeaxanthin (MZ) in the macula, and background characteristics. Methods: Fifty-five healthy adult volunteers were analyzed. Macular pigment optical density was measured using a heterochromatic flicker photometry technique, and serum concentrations of carotenoids and lipoproteins were by high-performance liquid chromatography and enzyme-linked immunosorbent assay, respectively. Dietary intake of nutrient was determined by a validated self-administered questionnaire on ingestion frequency. Results: Macular pigment optical density was positively correlated with serum concentrations of L and Z and dietary L intake and inversely correlated with serum oxidized low-density lipoprotein (LDL). Although MPOD decreased with age (95% confidence interval, -0.011 to -0.002; correlation coefficient, -0.269; P 0.007), serum L/Z and dietary L intake did not. In contrast, serum oxidized LDL was positively correlated with age (95% confidence interval, 0.69-2.34; correlation coefficient, 0.333; P 0.0004). After adjusting for age, sex, and oxidized LDL, serum L was positively correlated with MPOD (95% confidence interval, 0.88-1.69; P 0.000001). After adjusting for age, sex, and serum L, serum oxidized LDL was inversely correlated with MPOD (95% confidence interval, -0.002 to -0.0004; P 0.006). Conclusion: Macular pigment optical density was inversely correlated with serum oxidized LDL. Further study to know the impact of oxidized LDL on MPOD may be warranted.

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Driving self-restriction and motor vehicle collision occurrence in glaucoma

Ono Takeshi, Yuki Kenya, Awano-Tanabe Sachiko, Fukagawa Kazumi, Shimoyama Masaru, Ozawa Yoko, Ozeki Naoki, Shiba Daisuke, Tsubota Kazuo

Optometry and Vision Science 92 （ 3 ） 357 - 364 2015年03月

ISSN 1040-5488

Purpose. To confirm that subjects with primary open-angle glaucoma (POAG) who avoid driving in high-risk situations are less likely to be involved in motor vehicle collisions (MVCs) than those who do not. Methods. This study evaluated 252 consecutive Japanese aged between 40 and 85 years with POAG. All participants were requested to answer a questionnaire on their driving habits, including self-restriction in driving at night, in rain, in fog, on freeways, and lane changing, and history of MVCs. Those who reported restricting their driving in one or more ways constituted the self-restriction group, and those who reported no self-restriction made up the no-restriction group. The prevalence of MVCs and the crash rate (number of MVCs/10,000 km driven) were compared between the two groups. The association between prevalence of MVCs and the number of driving self-restrictions was also evaluated. Results. The association between driving self-restriction and MVCs was observed among the male subjects, not among the female subjects. Among the male subjects, the prevalence of MVCs was significantly higher in the no-restriction group than in the self-restriction group (no-restriction group, 33/107 = 30.8%; self-restriction group, 9/66 = 13.6%, p = 0.01). The crash rate was also significantly higher in the no-restriction group (no-restriction group, 1.4 T 0.8; self-restriction group, 0.4 T 0.3, average T SE, p = 0.01). No restriction was significantly associated with MVCs (multivariable-adjusted odds ratios, 2.43 [95% confidence interval, 1.03 to 5.73]). The number of driving self-restrictions was also associated with MVCs (multivariable- adjusted odds ratios, 0.41 [95% confidence interval, 0.18 to 0.99], per one increment of self-restriction). Conclusions. Driving self-restriction may be associated with a reduced prevalence of MVCs in men with POAG.

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The effect of Nrf2 knockout on ocular surface protection from acute tobacco smoke exposure

Kojima Takashi, Dogru Murat, Higuchi Akihiro, Nagata Taeko, Ibrahim Osama M A, Inaba Takaaki, Tsubota Kazuo

American Journal of Pathology 185 （ 3 ） 776 - 785 2015年03月

ISSN 0002-9440

Ocular surface mucosa is the first-line ocular tissue to be exposed to environmental stress. We evaluated tear functions and keratoconjunctival epithelial alterations after sidestream cigarette smoke (SCS) exposure and tried to clarify the role of the transcription factor nuclear factor erythroid 2-related factor 2 (Nfe2l2, also known as Nrf2), on the ocular surface. In wild-type and Nrf2^-/- mice, tear volume did not change after SCS exposure. Tear film breakup time (tear stability) in Nrf2^-/- mice was significantly shorter than that in wild-type mice after SCS exposure. Vital staining scores, including fluorescein and Rose Bengal staining, showed significantly higher values in Nrf2^-/- mice than in wild-type mice after SCS exposure. Excessive oxidative stress accumulation was detected in Nrf2^-/- mice after SCS exposure using immunohistochemical analysis. Immunohistochemical analysis also revealed decreased mucin 1 (Muc1) and Muc5ac staining in Nrf2^-/- mice after SCS exposure. mRNA expression levels of Muc1, Muc4, and Muc5ac and of SAM-pointed domain epithelial-specific transcription factor in Nrf2^-/- mice were lower than those in wild-type mice after SCS exposure. Mean tear IL-6 concentrations increased significantly in Nrf2^-/- mice after SCS exposure. In conclusion, SCS exposure induced decreased tear stability, ocular surface damage, and altered conjunctival phenotype in Nrf2^-/- mice. Nrf2 could play an important role in protection of the ocular surface against SCS exposure.

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Blue light-induced inflammatory marker expression in the retinal pigment epithelium-choroid of mice and the protective effect of a yellow intraocular lens material invivo

Narimatsu Toshio, Negishi Kazuno, Miyake Seiji, Hirasawa Manabu, Osada Hideto, Kurihara Toshihide, Tsubota Kazuo, Ozawa Yoko

Experimental Eye Research 132 48 - 51 2015年03月

ISSN 0014-4835

Oxidative stress in the retinal pigment epithelium (RPE) is a well-accepted pathogenic change in vision-threatening diseases such as age-related macular degeneration. One source of oxidative stress is excessive light exposure, which causes excessive activation of the visual cycle. Because short wavelength light (blue light) has more energy, it is reported to be more harmful to photoreceptor cells than the other wavelengths of light. However, the biological effect of blue light in the RPE of living animals and the protective effect of a yellow intraocular lens (IOL) material that blocks blue light is still obscure. Therefore, we compared the pathogenic effect in the RPE-choroid complexes of mice exposed to light in a box made of a clear or a yellow IOL material. We measured the level of reactive oxygen species (ROS) using 2', 7'-dichlorodihydrofluorescein diacetate, the mRNA levels of inflammatory cytokines and a macrophage marker by real-time polymerase chain reaction, and the protein level of monocyte chemotactic protein-1 (MCP-1) by ELISA. The ROS level after light exposure was suppressed in the RPE-choroids of light-exposed mice in the yellow IOL material box. In parallel, all the inflammatory cytokines that we measured and a macrophage marker were also suppressed in the RPE-choroids of light-exposed mice in the yellow IOL material box. Therefore, a yellow IOL material suppressed, and thus blue light exacerbated, the increase in the ROS level and inflammatory cytokine expression as well as macrophage recruitment in the RPE-choroid invivo after light exposure.

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Wickerhamomyces anomalus fungal keratitis responds to topical treatment with antifungal micafungin

Kamoshita Mamoru, Matsumoto Yukihiro, Nishimura Kazuko, Katono Yasuhiro, Murata Mitsuru, Ozawa Yoko, Shimmura Shigeto, Tsubota Kazuo

Journal of Infection and Chemotherapy 21 （ 2 ） 141 - 143 2015年02月

ISSN 1341-321X

We describe a 91-year-old woman who suffered from fungal keratitis after corneal transplantation. The causative organism was identified as Wickerhamomyces anomalus (formerly Pichia anomala or Hansenula anomala) on the basis of morphological characteristics and the sequence of the internal transcribed spacer region of the ribosomal RNA gene. The patient was successfully treated with topical micafungin (MCFG) only. We present the first report of a case of W.anomalus fungal keratitis that responded to topical treatment with the antifungal MCFG.

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Clinical and molecular characteristics of childhood-onset stargardt disease

Fujinami Kaoru, Zernant Jana, Chana Ravinder K., Wright Genevieve A., Tsunoda Kazushige, Ozawa Yoko, Tsubota Kazuo, Robson Anthony G., Holder Graham E., Allikmets Rando, Michaelides Michel, Moore Anthony T.

Ophthalmology 122 （ 2 ） 326 - 334 2015年02月

ISSN 0161-6420

Purpose To describe the clinical and molecular characteristics of patients with childhood-onset Stargardt disease (STGD). Design Retrospective case series. Participants Forty-two patients who were diagnosed with STGD in childhood at a single institution between January 2001 and January 2012. Methods A detailed history and a comprehensive ophthalmic examination were undertaken, including color fundus photography, autofluorescence imaging, spectral-domain optical coherence tomography (SD-OCT), and pattern and full-field electroretinograms. The entire coding region and splice sites of ABCA4 were screened using a next-generation, sequencing-based strategy. The molecular genetic findings of childhood-onset STGD patients were compared with those of adult-onset patients. Main Outcome Measures Clinical, imaging, electrophysiologic, and molecular genetic findings. Results The median ages of onset and the median age at baseline examination were 8.5 (range, 3-16) and 12.0 years (range, 7-16), respectively. The median baseline logarithm of the minimum angle of resolution visual acuity was 0.74. At baseline, 26 of 39 patients (67%) with available photographs had macular atrophy with macular/peripheral flecks; 11 (28%) had macular atrophy without flecks; 1 (2.5%) had numerous flecks without macular atrophy; and 1 (2.5%) had a normal fundus appearance. Flecks were not identified at baseline in 12 patients (31%). SD-OCT detected foveal outer retinal disruption in all 21 patients with available images. Electrophysiologic assessment demonstrated retinal dysfunction confined to the macula in 9 patients (36%), macular and generalized cone dysfunction in 1 subject (4%), and macular and generalized cone and rod dysfunction in 15 individuals (60%). At least 1 disease-causing ABCA4 variant was identified in 38 patients (90%), including 13 novel variants; ≥2 variants were identified in 34 patients (81%). Patients with childhood-onset STGD more frequently harbored 2 deleterious variants (18% vs 5%) compared with patients with adult-onset STGD. Conclusions Childhood-onset STGD is associated with severe visual loss, early morphologic changes, and often generalized retinal dysfunction, despite often having less severe fundus abnormalities on examination. One third of children do not have flecks at presentation. The relatively high proportion of deleterious ABCA4 variants supports the hypothesis that earlier onset disease is often owing to more severe variants in ABCA4 than those found in adult-onset disease.

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

Fukui Masaki, Yamada Masakazu, Akune Yoko, Shigeyasu Chika, Tsubota Kazuo

Current Eye Research 2015年01月

ISSN 0271-3683

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

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Abdominal breathing increases tear secretion in healthy women

Sano Kokoro, Kawashima Motoko, Ikeura Kazuhiro, Arita Reiko, Tsubota Kazuo

Ocular Surface 13 （ 1 ） 82 - 87 2015年01月

ISSN 1542-0124

Purpose To determine the relationship between abdominal breathing and tear meniscus volume in healthy women, we investigated the change in tear meniscus volume in two groups: normal breathing and abdominal breathing. Methods We used a crossover experimental model and examined 20 healthy women aged 20-54 years (mean ± SD, 32.7 ± 11.1 years). The participants were randomly assigned to one of two groups. During the first visit, the normal breathing group was subjected to normal breathing for 3 min, whereas the abdominal breathing group was subjected to abdominal breathing (4-second inhalation and 6-second exhalation) for 3 min. During the second visit, the protocols were swapped between the two groups. We estimated the R wave to R wave (R-R) interval, tear meniscus volume, salivary amylase activity, pulse, and blood pressure before and immediately after, 15 min after, and 30 min after completion of the breathing activity. Results After abdominal breathing, compared to that before breathing, the tear meniscus volume increased significantly 15 min after breathing (P<.01). Furthermore, systolic blood pressure showed a significant decrease immediately after abdominal breathing (P<0.05). No significant difference was found in the test parameters in the normal breathing group. Conclusion Abdominal breathing for 3 minutes increases the tear meniscus volume in healthy women. Consequently, abdominal breathing may be considered in the treatment of dry eye disease.

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Screening of dry eye disease in visual display terminal workers during occupational health examinations

Kawashima Motoko, Yamatsuji Motoko, Yokoi Norihiko, Fukui Masaki, Ichihashi Yoshiyuki, Kato Hiroaki, Nishida Mitsuko, Uchino Miki, Kinoshita Shigeru, Tsubota Kazuo

Journal of Occupational Health 57 （ 3 ） 253 - 258 2015年

ISSN 1341-9145

Screening of dry eye disease in visual display terminal workers during occupational health examinations: The Moriguchi study: Motoko KAWASHIMA, et al. Department of Ophthalmology, Keio University School of Medicine-Purpose: The aim of this study was to estimate the prevalence of dry eye disease (DED) in Japanese visual display terminal (VDT) workers and identify simple methods for screening DED during occupational health examinations. Methods: This study involved 369 (331 men and 38 women; mean age, 44.4 [8.8] years) workers engaged in PC development with approximately 6 hours of VDT use daily. The participants completed questionnaires on dry eye and physical symptoms affecting QoL, and their ability to keep their eyes open for 10 seconds was tested for DED screening. They also underwent assessment of conjunctival and corneal vital staining with lissamine green and fluorescein, measurement of tear film breakup time, and Schirmer's test for DED diagnosis. Sensitivity, specificity, and positive predictive value of the screening methods were assessed. Results: The DED group included 218 (definite, 14; probable, 204) participants. They had markedly high frequencies of 11 dry eye symptoms, especially ocular fatigue (OR, 17.1; 95% CI, 9.9 to 29.7) and dry sensation (OR, 8.2; 95% CI, 3.6 to 18.4), and were more often unable to keep their eyes open for 10 s. With either ocular fatigue or dry sensation as the cutoff criterion, the sensitivity, specificity, and positive predictive value were 89.9, 66.9, and 79.7%, respectively. Conclusions: Approximately 60% of the VDT workers were diagnosed with DED on the basis of diverse eye symptoms affecting their ability to work. The dry eye symptom questionnaire and 10-s eye-opening workerstest are simple, noninvasive, and inexpensive methods for screening DED during occupational health examinations.

Glaucomatous visual field defect severity and the prevalence of motor vehicle collisions in Japanese

Ono Takeshi, Yuki Kenya, Asaoka Ryo, Kouyama Keisuke, Abe Takayuki, Tanabe Sachiko, Fukagawa Kazumi, Uchino Miki, Shimoyama Masaru, Ozawa Yoko, Ozeki Naoki, Shiba Daisuke, Tsubota Kazuo

Journal of Ophthalmology 2015 2015年

ISSN 2090-004X

Purpose. This study examined the association between the severity of visual field defects and the prevalence of motor vehicle collisions (MVCs) in subjects with primary open-angle glaucoma (POAG). Methods. This is a cross-sectional study. Japanese patients who have had driver's licence between 40 and 85 years of age were screened for eligibility. Participants answered a questionnaire about MVCs experienced during the previous 5 years. Subjects with POAG were classified as having mild, moderate, or severe visual field defect. We evaluated associations between the severity of POAG and the prevalence of MVCs by logistic regression models. Results. The prevalence of MVCs was significantly associated with the severity of POAG categorized by worse eye MD (control: 30/187 = 16.0%; mild POAG: 17/92 = 18.5%; moderate POAG: 14/60 = 23.3%; severe POAG: 14/47 = 29.8%; P = 0.025, Cochran-Armitage trend test). Compared to the control group, the adjusted OR for MVC prevalence in subjects with mild, moderate, or severe POAG in the worse eye was 1.07 (95% CI: 0.55 to 2.10), 1.44 (95% CI: 0.68 to 3.08), and 2.28 (95% CI: 1.07 to 4.88). Conclusions. There is a significant association between the severity of glaucoma in the worse eye MD and the prevalence of MVCs.

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New eye cleansing product improves makeup-related ocular problems

Okura Masako, Kawashima Motoko, Katagiri Mikiyuki, Shirasawa Takuji, Tsubota Kazuo

Journal of Ophthalmology 2015 2015年

ISSN 2090-004X

Purpose. This study evaluated the effects of using a newly developed eye cleansing formulation (Eye Shampoo) to cleanse the eyelids for 4 weeks in a parallel-group comparative study in women with chronic eye discomfort caused by heavy use of eye makeup and poor eye hygiene habits. Methods. Twenty women participants who met the inclusion criteria were randomly allocated to 2 groups comprising 10 participants each. The participants were asked to use either artificial tears alone or artificial tears in conjunction with Eye Shampoo for 4 weeks. The participants answered the questionnaire again and were reexamined, and changes in symptoms within each group and variations of symptoms between the two groups were statistically analyzed. Results. In the group using only artificial tears, improvements in subjective symptoms but not in ophthalmologic examination results were found. In the group using Eye Shampoo together with artificial tears, significant improvements were observed in the subjective symptoms, meibomian orifice obstruction, meibum secretion, tear breakup time, and superficial punctate keratopathy. Conclusion. In patients with chronic eye discomfort thought to be caused by heavy eye makeup, maintaining eyelid hygiene using Eye Shampoo caused a marked improvement in meibomian gland blockage and dry eye symptoms.

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The relationship between central visual field damage and motor vehicle collisions in primary open-angle glaucoma patients

Yuki Kenya, Asaoka Ryo, Tsubota Kazuo

PLoS ONE 9 （ 12 ） 2014年12月

Purpose: To investigate the relationship between visual field (VF) damage and history of motor vehicle collisions (MVCs) in subjects with primary open-angle glaucoma (POAG). Methods: MVC history and driving habits were recorded using patient questionnaires in 247 POAG patients. Patients' driving attitudes (carefulness) were estimated using Rasch analysis. The relationship between MVC outcomes and 52 total deviation (TD) values of integrated binocular VF (IVF), better and worse visual acuities (VAs), age and gender was analyzed using principal component analysis and logistic regression. Results: 51 patients had the history of MVCs. Significant difference was observed between patients with and without history of MVCs only for: better VA, a single TD value in the superior-right VF, and the typical distance driven in a week (unpaired t-test, p=0.002, 0.015 and 0.006, respectively). There was not a significant relationship between MVCs and mean deviation (MD) of IVF (p=0.41, logistic regression). None of the principal components were significantly correlated with MVC outcome (p>0.05, polynomial logistic regression analysis). There was a significant relationship between IVF MD and Rasch derived Person parameter (R²=0.023, p=0.0095). There was also a significant positive relationship between MVCs and the distance driven in a week (p=0.005, logistic regression). Conclusions: In this study of POAG patients, MVCs were not related to central binocular VF damage. These results suggest the relationship between visual function and driving is not straightforward, and careful consideration should be given when predicting patients' driving ability using their VF.

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Resveratrol prevents the development of choroidal neovascularization by modulating AMP-activated protein kinase in macrophages and other cell types

Nagai Norihiro, Kubota Shunsuke, Tsubota Kazuo, Ozawa Yoko

Journal of Nutritional Biochemistry 25 （ 11 ） 1218 - 1225 2014年11月

ISSN 0955-2863

The development of choroidal neovascularization (CNV) is a critical step in the pathogenesis of age-related macular degeneration (AMD), a vision-threatening disease. In this study, we used a mouse model of AMD to study the protective effects of resveratrol (RSV) supplementation against CNV as well as the underlying molecular mechanisms. Mice were orally pretreated with RSV daily for 5. days. On the fifth day, the mice underwent laser photocoagulation to induce CNV. One week after laser treatment, CNV volume was significantly lower in the RSV-treated mice compared with vehicle-treated animals. In addition, RSV treatment significantly inhibited macrophage infiltration into the retinal pigment epithelium (RPE)-choroid and suppressed the expression of inflammatory and angiogenic molecules, including vascular endothelial growth factor, monocyte chemotactic protein-1 and intercellular adhesion molecule-1. Importantly, RSV prevented the CNV-induced decrease in activated AMP-activated protein kinase and increase in activated nuclear factor-κB in the RPE-choroid complex. The regulatory effects of RSV on these molecules were confirmed in RPE, microvascular endothelial and macrophage cell lines. Inhibition of macrophage infiltration by RSV was confirmed by in vitro scratch and migration assays. RSV suppressed CNV development, reducing the levels of multiple cytokines secreted from several cell types and inhibiting macrophage migration. The direct effects of RSV on each cell type were confirmed in vitro. Although further studies are needed, RSV could potentially be applied in the clinic to prevent CNV development in AMD.

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Functional visual acuity assessment of severe atopic keratoconjunctivitis

Ibrahim Osama M A, Dogru Murat, Kaido Minako, Kojima Takashi, Fujishima Hiroshi, Tsubota Kazuo

Cornea 33 S13 - S18 2014年11月

ISSN 0277-3740

PURPOSE: To evaluate changes in functional visual acuity (FVA) measurements before and after treatment with 0.1% cyclosporine ophthalmic solution for 3 months in patients with severe atopic keratoconjunctivitis (AKC).METHODS: Pairs of eyes were analyzed from 3 boys (mean age 9 ± 3.6 years) who complained of having severe AKC and were recruited for the study. Conventional Landolt visual acuity, FVA, and visual maintenance ratio (VMR) measurements were conducted before and after 3 months of 0.1% cyclosporine eye drop treatment. Tear film lipid layer interferometry, tear film break-up time, fluorescein and rose bengal vital stainings, and the Schirmer test were also performed before and after treatment.RESULTS: Eye drop treatment was associated not only with improvement of tear function and ocular surface status but also with better quality of visual function. The mean logarithm of the minimum angle of resolution FVA and Landolt visual acuity values improved from 0.45 ± 0.26 and 0.13 ± 0.17 before treatment to 0.16 ± 0.03 and -0.06 ± 0.05 after treatment, respectively. Similarly, the mean VMR values were markedly improved from 0.88 ± 0.06 to 0.95 ± 0.03 after treatment.CONCLUSIONS: FVA and VMR are promising parameters in the assessment of dynamic visual acuity changes in AKC-affected patients and evaluation of treatment outcome.

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Ocular surface reconstruction by cultivated epithelial sheet transplantation

Satake Yoshiyuki, Yamaguchi Takefumi, Hirayama Masatoshi, Higa Kazunari, Shimazaki-Den Seika, Dogru Murat, Kawakita Tetsuya, Kawashima Motoko, Shimmura Shigeto, Tsubota Kazuo, Shimazaki Jun

Cornea 33 S42 - S46 2014年11月

ISSN 0277-3740

Recent advances in ocular surface reconstruction for patients with severe ocular surface diseases have significantly improved the prognosis of patients with vision-impairing corneal abnormalities. The history of cultivated epithelial sheet transplantation is short, and debate on the current approaches for these procedures is continuing. Limbal stem cell transplantation, including conjunctivolimbal autograft and keratolimbal allograft, has brought opportunities for vision improvement. In addition, the use of cultivated limbal epithelial transplantation from both allogeneic and autologous sources has provided further options for immediate postoperative epithelialization of the corneal surface. Finally, cultivated oral mucosal epithelial transplantation, which allows autologous transplantation for patients with bilateral limbal stem cell deficiency, has provided the best overall midterm and long-term results. Its biggest advantages are the absence of rejection reactions and the reduction of postoperative complications associated with steroid therapy. However, a solitary surgical approach is not sufficient for obtaining a good clinical outcome. To maximize the possibility of success using these procedures, it is important to preoperatively enhance aggressive treatment of the ocular surface, especially with factors that facilitate moisture retention. In this review article, we also discuss our clinical experience in relation to these surgical procedures.

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Clinical Backgrounds of Postoperative Keratoplasty Patients With Spontaneous Wound Dehiscence or Gaps After Suture Removal

Fujii Shota, Matsumoto Yukihiro, Fukui Masaki, Fujitake Junichi, Kawakita Tetsuya, Shimmura Shigeto, Tsubota Kazuo

Cornea 2014年10月

ISSN 0277-3740

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

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Intraoperative and fluorescein angiographic findings of a secondary macular hole associated with age-related macular degeneration treated by pars plana vitrectomy

Okamoto Tomohiro, Shinoda Hajime, Kurihara Toshihide, Nagai Norihiro, Tsubota Kazuo, Ozawa Yoko

BMC Ophthalmology 14 （ 1 ） 2014年09月

Background: Macular hole results from a tractional force at the vitreo-retinal interface which is developed by modification and subsequent degeneration of the posterior precortical vitreous and the internal limiting membrane (ILM). Meanwhile, the wet type of age-related macular degeneration (AMD) is caused by the submacular formation of choroidal neovascularization (CNV). Although exudative changes derived from CNV may cause epiretinal membrane (ERM) formation, which can also cause tractional force at the vitreo-retinal interface, there have been few reports of AMD-associated macular hole development in which the full thickness of the retinal tissue is completely torn by the tractional force. Moreover, intraoperative finding of macular hole associated with AMD with a possible involvement of subretinal lesion has not been described.Case presentation. A 78-year-old man diagnosed with wet AMD with subretinal fluid and mild cataract received 8 treatments with intravitreal pegaptanib. After AMD remission, he developed a secondary macular hole in the same eye. He underwent a pars plana vitrectomy that successfully closed the macular hole. Intraoperatively, it was found that the patient's vitreous was formed and that the ERM and ILM were adherent, suggesting the involvement of a tractional force at the vitreo-retinal interface due to an inflammatory reaction related to AMD and/or intravitreally injected chemical compounds, resulting in macular hole development. Changes in the condition of his AMD and the RPE were observed on a fluorescein angiogram (FA) and an indocyanine green angiogram (IA) that preceded macular hole development, suggesting that subretinal changes may also have been involved in the pathogenesis.Conclusion: These clinical data, including the intraoperative findings and the temporal changes in the angiograms, suggest that an inflammatory reaction at the vitreo-retinal interface and subretinal lesion related to AMD contribute to the macular hole development in AMD patients treated with intravitreal injection.

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Oral administration of royal jelly restores tear secretion capacity in rat blink-suppressed dry eye model by modulating lacrimal gland function

Imada Toshihiro, Nakamura Shigeru, Kitamura Naoki, Shibuya Izumi, Tsubota Kazuo

PLoS ONE 9 （ 9 ） 2014年09月

Tears are secreted from the lacrimal gland (LG), a dysfunction in which induces dry eye, resulting in ocular discomfort and visual impairment. Honey bee products are used as a nutritional source in daily life and medicine; however, little is known about their effects on dry eye. The aim of the present study was to investigate the effects of honey bee products on tear secretion capacity in dry eye. We selected raw honey, propolis, royal jelly (RJ), pollen, or larva from commercially available honey bee products. Tear secretion capacity was evaluated following the oral administration of each honey bee product in a rat blink-suppressed dry eye model. Changes in tear secretion, LG ATP content, and LG mitochondrial levels were measured. RJ restored the tear secretion capacity and decrease in LG ATP content and mitochondrial levels to the largest extent. Royal jelly can be used as a preventative intervention for dry eye by managing tear secretion capacity in the LG. Copyright:

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First multicenter survey on infectious keratitis following excimer laser surgery in Japan

Ide Takeshi, Kurosaka Daijiro, Senoo Tadashi, Kinoshita Shigeru, Ohashi Yuichi, Inoue Yoshitsugu, Tsubota Kazuo

Taiwan Journal of Ophthalmology 4 （ 3 ） 116 - 119 2014年09月

ISSN 2211-5056

Purpose: To report the first multicenter survey in Japan on infectious keratitis after excimer laser surgery. Methods: The laser in situ keratomileusis (LASIK) Safety Network (LSN) Committee sent questionnaires to 28 LSN member hospitals to assess the total number of laser corneal surgeries, the number of infection cases (including suspicious cases), and the postoperative follow-up rate during a 3-year period. Results: Responses were obtained from 27 (96.4%) of 28 institutions. One phototherapeutic keratectomy infection case was reported among 22,415 excimer laser surgery cases, which equates to an incidence rate of 0.004%. The follow-up rate was 94.14% (67.2-100%), 80.11% (41.0-96.1%), 57.95% (11.5-93.0%), and 46.64% (4.7-93.0%) at 1 month, 3 months, 6 months, and 12 months of follow-up, respectively. Conclusion: Infectious keratitis is a potentially devastating complication of excimer laser surgery. We did not see any infectious keratitis for refractive cases. This first multicenter survey in Japan on infectious keratitis provides important information on the safety of this therapy.

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Delphinidin 3,5-O-diglucoside, a constituent of the maqui berry (Aristotelia chilensis) anthocyanin, restores tear secretion in a rat dry eye model

Nakamura Shigeru, Tanaka Junji, Imada Toshihiro, Shimoda Hiroshi, Tsubota Kazuo

Journal of Functional Foods 10 346 - 354 2014年09月

ISSN 1756-4646

Dry eye disease is a disorder in tear film physiology, which leads to various abnormal states of ocular surface cells. In the present study, we evaluated the potential usefulness of orally applied maqui berry (. Aristotelia chilensis) extract and the constituent anthocyanin as a preventative intervention in dry eye. Tear secretion capacity was evaluated following the oral administration of maqui berry extract to a rat blink-suppressed dry eye model. This suppressive effect of maqui berry extract and its constituent anthocyanins on reactive oxygen species formation from lacrimal gland was elevated by 2', 7'-dichlorofluorescin diacetate. Maqui berry extract and delphinidin 3,5-O-diglucoside, an anthocyanin specifically contained in the maqui berry, suppressed reactive oxygen species formation from lacrimal gland tissue and preserved tear secretion. The result of the present study demonstrates that maqui berry extract can be used as a preventative intervention for dry eye by managing tear secretion capacity in the lacrimal gland.

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