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Soichiro Hanada,1,* Masato Muraki,1,* Yoshiyuki Kawabata,1 Kazuya Yoshikawa,1 Toshiyuki Yamagata,1 Tadao Nagasaki,1 Yushiro Ohara,2 Naoki Oiso,2 Hisako Matsumoto,3 Yuji Tohda4 1Department of Respiratory Medicine and Allergology, Kindai University Nara Hospital, Ikoma, Nara, Japan; 2Department of Dermatology, Kindai University Nara Hospital, Ikoma, Nara, Japan; 3Department of Respiratory Medicine and Allergology, Kindai University Hospital, Osakasayama, Osaka, Japan; 4Kindai University Hospital, Osakasayama, Osaka, Japan*These authors contributed equally to this workCorrespondence: Masato Muraki, Department of Respiratory Medicine and Allergology, Kindai University Nara Hospital, 1248-1 Otoda-cho, Ikoma, Nara, 630-0293, Japan, Tel +81 743 77 0880, Fax +81 743 77 0890, Email muraki-m@med.kindai.ac.jpPatients and Methods: A questionnaire survey was administered to 18, 14, and 3 patients introduced to home self-injection of dupilumab or mepolizumab using a pen-type device for atopic dermatitis, asthma alone, and asthma plus chronic rhinosinusitis with nasal polyps, respectively.Results: All but one participant wished to continue self-injection. Most participants affirmed the reduction in copayment (88.6%) and saving time and labor for hospital visits (88.6%). Six patients who received dupilumab complained of side effects, but all, except for one, continued the treatment. Of the 13 patients who had previously used a syringe-type device, 10 preferred the pen type because of its ease of use, while 3 (23%) preferred the syringe type because of the self-adjustable injection speed for pain control.Conclusion: Administration of biologics using pen-type devices is easier, and the introduction of home self-injection leads to a reduction in outpatient visits and copayment.Keywords: dupilumab, mepolizumab, self-injection, asthma, atopic dermatitis, chronic sinusitis with nasal polyps

Tomoko Tajiri,1 Motohiko Suzuki,2,3 Takeo Kutsuna,4 Hirono Nishiyama,1 Keima Ito,1 Norihisa Takeda,1 Kensuke Fukumitsu,1 Yoshihiro Kanemitsu,1 Satoshi Fukuda,1 Takehiro Umemura,1 Hirotsugu Ohkubo,1 Ken Maeno,1 Yutaka Ito,1 Tetsuya Oguri,1 Masaya Takemura,1 Kosho Yoshikawa,4 Akio Niimi1 1Department of Respiratory Medicine, Allergy and Clinical Immunology, Graduate School of Medical Sciences, Nagoya City University, Nagoya, Aichi, Japan; 2Department of Otorhinolaryngology, Graduate School of Medical Sciences, Nagoya City University, Nagoya, Aichi, Japan; 3Department of Otorhinolaryngology, Nagoya City East Medical Center, Nagoya, Aichi, Japan; 4Department of Respiratory Medicine, Daido Hospital, Nagoya, Aichi, JapanCorrespondence: Tomoko Tajiri, Department of Respiratory Medicine, Allergy and Clinical Immunology, Graduate School of Medical Sciences, Nagoya City University, 1 Kawasumi, Mizuho-cho, Mizuho-ku, Nagoya, Aichi, 467-8601, Japan, Tel +81-52-853-8216, Email tomokot@med.nagoya-cu.ac.jpObjective: Omalizumab has demonstrated clinical efficacy in patients with severe allergic asthma sensitized to perennial allergens and/or severe pollinosis through inhibition of IgE-dependent allergic response. When considering the “one airway, one disease” concept, sensitization to pollen could predict responsiveness to omalizumab. This study aimed to assess whether the pretreatment specific IgE response could be a predictor of responsiveness to omalizumab in severe allergic asthma sensitized to perennial allergens.Methods: In this retrospective study, 41 adult patients with severe allergic asthma sensitized to perennial allergens (27 females; mean age 59 years) who had completed 52-week omalizumab treatment were enrolled. The Global Evaluation of Treatment Effectiveness was performed, and demographic characteristics and the positive ratios of specific IgE responses classified into five subgroups (pollen, dust mite, house dust, mold, and animal dander) were compared between responders and non-responders. Multivariate logistic regression analyses were performed to identify predictors of responsiveness to omalizumab.Results: Thirty-one patients (76%) were identified as responders. The number of sensitized aeroallergen subgroups and sensitization to pollens were significantly higher in responders than in non-responders (both p< 0.05). Multivariate logistic regression analysis showed that sensitization to pollen (OR = 8.41, p = 0.02) was independently associated with the effectiveness of omalizumab.Conclusion: Pretreatment serum pollen-specific IgE could be a predictor of responsiveness to omalizumab.Keywords: omalizumab, antigen-specific IgE, pollen, allergic rhinitis, allergic asthma

Hirotaka Suzumura,1 Keiji Yoshikawa,2 Tairo Kimura,3 Mami Nanno,4 Toyoaki Tsumura5 1Suzumura Eye Clinic, Tokyo, Japan; 2Yoshikawa Eye Clinic, Tokyo, Japan; 3Ueno Eye Clinic, Tokyo, Japan; 4Minamino Eye Clinic, Tokyo, Japan; 5Department of Ophthalmology, Fussa Municipal Hospital, Tokyo, JapanCorrespondence: Hirotaka Suzumura, Tel +81 3 3382 1109, Fax +81 3 3384 7090, Email suzumura.ec@gmail.comPurpose: To develop a cluster system to analyze the retinal sensitivity loss of 68 test points in the central 10 degrees of standard automated perimetry (SAP) in eyes with normal tension glaucoma (NTG).Patients and Methods: Patients with NTG who met the following criteria were included: visual acuity ≥ 0.7, SAP-derived mean deviation ≥− 15 dB, and pattern deviation probability plots with at least one point with a probability of < 0.5% and/or two or more contiguous points with a probability of < 1% that did not cross the horizontal meridian in the central 12 points of the 24-2 test points. SAP with the Swedish Interactive Threshold Algorithm Standard (SITA-S) 10-2 program (10-2) was performed within 6 months of the SITA-S 24-2. The averaged total deviation (TD) for each of the 68 test points in the 10-2 was calculated. Hierarchical cluster analyses were performed based on the deviation of the TDs of the test points, and a dendrogram was created. The number of clusters was determined following the Sturges’ rule.Results: One hundred and twenty-six eyes of 126 patients (61.9± 11.4 years) were studied. Hierarchical cluster analysis of the TD values statistically obtained a dendrogram that divided the 68 test points into 7 clusters. Of these 7 clusters, 21 points belonging to the clusters in the papillomacular region included cluster 5. Cluster 5 was distributed above and below the horizontal meridian, which does not agree with the course of the retinal nerve fiber layer (RNFL).Conclusion: The hierarchical cluster analysis of the TD values stratified the 68 test points of the 10-2 into seven clusters. Considering the course of the RNFL, cluster 5 was divided into clusters of 5a and 5b, and consequently eight clusters were considered to be appropriate for detecting glaucomatous visual field defects in the central 10 degrees in NTG eyes.Keywords: normal tension glaucoma, 10-2 visual field, retinal sensitivity, retinal nerve fiber layer flow, cluster formation

Keiji Yoshikawa,1 Shiro Mizoue,2,3 Koji Nitta,4 Hiroshi Onishi,5 Masaharu Ikeda,5 Akemi Mizuno,5 Kaori Kawazoe,5 Yoshiyuki Tamada,5 Ryuji Takeda,6 Shun Matsumoto7 1Yoshikawa Eye Clinic, Tokyo, Japan; 2Ehime University Hospital, Toon, Ehime, Japan; 3Minami-Matsuyama Hospital, Matsuyama, Ehime, Japan; 4Fukui-ken Saiseikai Hospital, Fukui, Japan; 5Senju Pharmaceutical Co. Ltd., Hyogo, Japan; 6Kansai University of Welfare Sciences, Osaka, Japan; 7Ideta Eye Hospital, Kumamoto, JapanCorrespondence: Keiji YoshikawaYoshikawa Eye Clinic, 1-3-1 Nakamachi, Machida, Tokyo, 194-0021, JapanTel +81-42-739-0781Fax +81-42-739-0782Email mayokasyg51@galaxy.ocn.ne.jpPurpose: We previously investigated the efficacy and safety of adding 0.1% brimonidine (Brim) or 0.5% timolol (Tim) to prostaglandin analogue (PGA) monotherapy to treat patients with normal-tension glaucoma (NTG) with intraocular pressure (IOP) of ≤ 16 mmHg. Herein, we describe an additional post-hoc stratifying analysis of the possible differences in the effect of IOP-lowering and pulse rate (PR) after adjunctive Brim or Tim to PGA.Patients and Methods: This study included 128 subjects. Patients with NTG treated with PGA were stratified based on their baseline IOP. The changes in IOP from baseline and the effect of patient factors on IOP changes were investigated. Patients were stratified by age for investigation of their PR and blood pressure (BP). The change and the effect of patient factors on PR and BP were investigated.Results: After stratification analysis, in 52 eyes treated with Brim and 61 eyes with Tim with baseline IOP 12 ≤ IOP ≤ 16 mmHg, both eye drops lowered IOP significantly (P < 0.0001), and the IOP-lowering efficacy of Brim was non-inferior to that of Tim. However, in 9 Brim- and 6 Tim-treated eyes with baseline IOP of < 12 mmHg, no statistically significant decrease in IOP was evident with either eye drop. In the Tim group, PR decreased significantly (P < 0.05) after stratification by age.Conclusion: The IOP-lowering efficacy of Brim was non-inferior to that of Tim after stratification by baseline IOP (12 ≤ IOP ≤ 16 mmHg). The discrepancy in the IOP-lowering effects of Brim and Tim observed in the previous study was thought to be related to enrolled subjects with low baseline IOP. PR decreased significantly in the Tim group even after age stratification. PR should be considered when selecting β-blockers for glaucoma treatment.Keywords: adjunctive therapy, brimonidine, intraocular pressure reduction, post-hoc analysis, pulse rate, timolol

Reimi Nishijima,1,2 Shumpei Ogawa,1 Euido Nishijima,1 Yoshinori Itoh,1 Keiji Yoshikawa,1,3 Tadashi Nakano1 1Department of Ophthalmology, The Jikei University School of Medicine, Tokyo, Japan; 2Department of Ophthalmology, The Jikei University Katsushika Medical Center, Tokyo, Japan; 3Yoshikawa Eye Clinic, Machida-city, Tokyo, JapanCorrespondence: Shumpei OgawaDepartment of Ophthalmology, The Jikei University School of Medicine, 3-19-18 Nishi-Shinbashi, Minato-ku, Tokyo, 105-8471, JapanTel +813 3433 1111Fax +813 3433 1936Email shmp0722@gmail.comPurpose: We conducted cross-sectional examinations to determine the frequency of peripapillary retinoschisis (PRS) in eyes with glaucoma and suspected glaucoma and analyzed the pathogenesis of PRS by using spectral-domain optical coherence tomography (SD-OCT).Patients and Methods: In 1516 cases involving glaucoma and suspected glaucoma, we retrospectively reviewed the disc and macular volume scans obtained by SD-OCT and categorized PRS into two groups based on whether the retinoschisis was closer to the optic nerve over the Bruch’s membrane opening (BMO) (ahead group) or did not go past the BMO (behind group) and then compared the characteristics between both groups.Results: The total frequency of PRS was 1.49% (20/1342 eyes) in primary open-angle glaucoma (POAG) eyes and 0.59% (10/1687 eyes) in glaucoma suspects. In the behind group, PRS was mostly detected in the inner layers of the retina (retinal nerve fiber layer: 30.9%, ganglion cell layer: 21.8%, inner plexiform layer: 7.3%). However, in the ahead group, PRS was detected in the outer layers (inner nuclear layer: 10%, outer plexiform layer: 20%, outer nuclear layer: 50%). In addition, the eyes in the ahead group had significantly greater axial lengths and significantly smaller spherical equivalent values. These two differences suggest that the pulling force of the vitreous traction may play an important role in PRS only in the behind group and that the scleral stretching force may play a role in the development of PRS in the ahead group.Conclusion: The frequency of PRS in patients with POAG is higher than that in patients with suspected glaucoma. Both forms of PRS are affected by posterior vitreous detachment and axial length elongation. Careful follow-up is required to assess the development of PRS in glaucoma suspects. The pathogenesis of PRS has been elucidated to some degree by classifying the morphological condition of the PRS and BMO.Keywords: peripapillary retinoschisis, optical coherent tomography, glaucoma, myopia

Keiji Yoshikawa,1 Kazunori Santo,2 Hiroko Hizaki,2 Masayo Hashimoto2 1Yoshikawa Eye Clinic, Machida, Tokyo, Japan; 2Japan Medical Affairs, Santen Pharmaceutical Co., Ltd, Osaka, Japan Purpose: To quantitatively evaluate the association of intraocular pressure (IOP) reduction with visual field defect (VFD) progression in normal tension glaucoma (NTG) under medical therapy. Patients and methods: Clinical data for 622 eyes of 311 primary open-angle glaucoma and NTG patients were collected from April 2006 to March 2016. Of these patients, those with normal IOP, glaucomatous VFD by Anderson’s criteria, corrected visual acuity ≥0.7, >5 years of medical therapy, ≥5 visual field tests at least five times at 12-month intervals, visual field testing reliability coefficients of ≤33%, and mean deviation (MD) exceeding below -20 dB in the initial visual field test were included in this retrospective data analysis. MD and IOP data were collected at baseline and after 5 years. Following MD categorization into stages I to IV, stage transition matrices were generated using a Markov model to evaluate VFD changes. Eyes were divided based on IOP reduction (0%, 10%, 15%, 20%, 25%, 30%) from baseline. VFD aggravations were compared using the Markov model and MD slopes with IOP reduction rates as cutoff values. Results: Overall, 132 eyes of 132 NTG patients fulfilled the eligibility criteria. MD decreased significantly (P

Yuka Hasebe,1 Kenji Kashiwagi,1 Toyoaki Tsumura,2 Yasuyuki Suzuki,3 Keiji Yoshikawa,4 Hirotaka Suzumura,5 Toshine Maeda,6 Ryuji Takeda,7 Hitomi Saito,8 Makoto Araie8 1Department of Ophthalmology, University of Yamanashi, Yamanashi, Japan; 2Department of Ophthalmology, Fussa Hospital, Tokyo, Japan; 3Department of Ophthalmology, Tokai University, Kanagawa, Japan; 4Yoshikawa Eye Clinic, Tokyo, Japan; 5Suzumura Eye Clinic, Tokyo, Japan; 6Maeda Eye Clinic, Tokyo, Japan; 7Faculty of Agriculture, Kinki University, Nara, Japan; 8Department of Ophthalmology, Kanto Central Hospital of the Mutual Aid Association of Public School, Tokyo, Japan Purpose: We investigated patient adherence and factors related to a newly introduced prostaglandin analog and timolol fixed-combination eye drops (PGTFC).Patients and methods: The Glaucoma Research on Adherence to fixed-Combination Eye drops in Japan (GRACE) study group performed a nationwide prospective questionnaire survey. Participants in this study were patients with glaucoma who were scheduled to receive any type of PGTFC for the first time. The participants answered a questionnaire on the day of PGTFC introduction and again at a return visit 4–6 weeks after PGTFC introduction. The physicians in charge were asked to complete a separate questionnaire on the day of PGTFC introduction. One of two leaflets was randomly delivered to each participant before the description of the PGTFC. One leaflet explained how to correctly instill the eye drops, and the other explained the clinical meaning of intraocular pressure reduction in addition to explaining how to correctly instill the eye drops. Nonadherence was defined as forgetting to instill the eye drops one or more times during the week before the return visit.Results: In total, 3,597 patients (age, 68.4±12.2 years) met the study protocol requirements. PGTFC introduction significantly reduced the number of antiglaucoma eye drops from 1.93±0.78 to 1.34±0.54 (P

Keiji Yoshikawa,1 Kazunori Santo,2 Hiroko Hizaki,2 Masayo Hashimoto2 1Yoshikawa Eye Clinic, Tokyo, 2Medical Affairs, Santen Pharmaceutical Co. Ltd., Osaka, Japan Purpose: To analyze factors related to long-term progression of visual field defects (VFD) in patients with normal tension glaucoma (NTG) under medical therapy. Patients and methods: Clinical data from 622 eyes of 311 primary open-angle glaucoma and NTG patients were collected from April 2006 to March 2016. Of these patients, those with normal intraocular pressure (IOP); glaucomatous VFD judged by Anderson’s criteria; corrected visual acuity ≥0.7; receiving more than 6 years medical therapy; having undergone ≥10 visual field tests performed at 6-month intervals using a Humphrey field analyzer (Swedish Interactive Threshold Algorithms standard, C 24-2 program); and having reliability coefficients of visual field testing

Tadashi Nakano,1 Shiro Mizoue,2 Nobuo Fuse,3 Aiko Iwase,4 Shun Matsumoto,5 Keiji Yoshikawa6 On behalf of the I.CHANGE2 study group 1Department of Ophthalmology, The Jikei University School of Medicine, Nishi-Shimbashi, Minato-ku, Tokyo, 2Department of Ophthalmology, Ehime University Graduate School of Medicine, Shitsukawa, Toon-city, Ehime, 3Department of Integrative Genomics, Tohoku Medical Megabank Organization, Seiryo-machi, Sendai, Miyagi, 4Tajimi Iwase Eye Clinic, Hon-machi, Tajimi, Gifu, 5Department of Ophthalmology, Tokyo Teishin Hospital, Fujimi, Chiyoda-ku, 6Yoshikawa Eye Clinic, Naka-machi, Machida, Tokyo, Japan Background: We have shown a decrease in mean intraocular pressure (IOP) by switching to travoprost/timolol fixed combination (TTFC) in subjects receiving prostaglandin analogue (PGA) monotherapy and requiring additional medication in a previous report. For analyzing factors affecting IOP reduction, baseline IOP and preceding PGA were selected as statistically and clinically significant factors. In this report, we examine IOP-lowering effect and adverse drug reactions by preceding PGA.Methods: Patients with primary open angle glaucoma or ocular hypertension who received monotherapy with one of four PGAs (travoprost, latanoprost, tafluprost, or bimatoprost) for at least 3 months at 26 institutions and were determined to require additional medication by their primary physician were included. IOP reduction and adverse events were examined at 4, 8, and 12 weeks for each of four PGAs after switching to TTFC.Results: In total, 157 patients who could be followed up for at least 4 weeks after switching to TTFC were included in the efficacy analysis. Multiple regression analysis was performed, and baseline IOP and PGA were found to be significant factors to IOP reduction. IOP reduction at week 12, adjusted with the regression model, was -3.5, -1.8, and -1.4 mmHg in the tafluprost, latanoprost, and travoprost groups, whereas it was -0.5 mmHg in the bimatoprost group. Along with differences in baseline IOP between groups, an IOP-lowering effect of >1 mmHg was noted in the tafluprost, latanoprost, and travoprost groups after the switch. IOP was maintained at 13.8–14.8 mmHg throughout the follow-up period. No serious adverse events or noteworthy issues were observed in any group after the switch.Conclusion: Clinically significant IOP-reducing effects of TTFC were observed in the latanoprost, travoprost, and tafluprost groups when switching from each PGA monotherapy, while there were some differences in effects between groups, with minimal safety concerns. Keywords: adverse event intraocular pressure, prostaglandin analogue, switching therapy, travoprost/timolol fixed combination

Tomoko Naito,1 Keiji Yoshikawa,2 Shiro Mizoue,3 Mami Nanno,4 Tairo Kimura,5 Hirotaka Suzumura,6 Yuzo Umeda,7 Fumio Shiraga1 1Department of Ophthalmology, Okayama University Graduate School of Medicine, Okayama, Japan; 2Yoshikawa Eye Clinic, Tokyo, Japan; 3Department of Ophthalmology, Ehime University Graduate School of Medicine, Ehime, Japan; 4Kagurazaka Minamino Eye Clinic, 5Ueno Eye Clinic, 6Suzumura Eye Clinic, Tokyo, Japan; 7Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Okayama, Japan Purpose: To analyze the relationship between visual field (VF) progression and baseline refraction in Japanese patients with primary open-angle glaucoma (POAG) including normal-tension glaucoma.Patients and methods: In this retrospective study, the subjects were patients with POAG who had undergone VF tests at least ten times with a Humphrey Field Analyzer (Swedish interactive thresholding algorithm standard, Central 30-2 program). VF progression was defined as a significantly negative value of mean deviation (MD) slope at the final VF test. Multivariate logistic regression models were applied to detect an association between MD slope deterioration and baseline refraction.Results: A total of 156 eyes of 156 patients were included in this analysis. Significant deterioration of MD slope was observed in 70 eyes of 70 patients (44.9%), whereas no significant deterioration was evident in 86 eyes of 86 patients (55.1%). The eyes with VF progression had significantly higher baseline refraction compared to those without apparent VF progression (-1.9±3.8 diopter [D] vs -3.5±3.4 D, P=0.0048) (mean ± standard deviation). When subject eyes were classified into four groups by the level of baseline refraction applying spherical equivalent (SE): no myopia (SE > -1D), mild myopia (-1D ≥ SE > -3D), moderate myopia (-3D ≥ SE > -6D), and severe myopia (-6D ≥ SE), the Cochran–Armitage trend analysis showed a decreasing trend in the proportion of MD slope deterioration with increasing severity of myopia (P=0.0002). The multivariate analysis revealed that baseline refraction (P=0.0108, odds ratio [OR]: 1.13, 95% confidence interval [CI]: 1.03–1.25) and intraocular pressure reduction rate (P=0.0150, OR: 0.97, 95% CI: 0.94–0.99) had a significant association with MD slope deterioration.Conclusion: In the current analysis of Japanese patients with POAG, baseline refraction was a factor significantly associated with MD slope deterioration as well as intraocular pressure reduction rate. When baseline refraction was classified into four groups, MD slope in myopia groups was less deteriorated as compared to those in the emmetropic/hyperopic group.Keywords: primary open-angle glaucoma, normal-tension glaucoma, myopia, refraction, visual field progression, MD slope, intraocular pressure reduction rate

Tomoko Naito,1 Keiji Yoshikawa,2 Shiro Mizoue,3 Mami Nanno,4 Tairo Kimura,5 Hirotaka Suzumura,6 Ryuji Takeda,7 Fumio Shiraga1 1Department of Ophthalmology, Okayama University Graduate School of Medicine, Okayama, 2Yoshikawa Eye Clinic, Tokyo, 3Department of Ophthalmology, Ehime University Graduate School of Medicine, Ehime, 4Kagurazaka Minamino Eye Clinic, 5Ueno Eye Clinic, 6Suzumura Eye Clinic, Tokyo, 7Department of Agriculture, Kinki University, Nara, Japan Purpose: To analyze the relationship between consecutive deterioration of mean deviation (MD) value and glaucomatous visual field (VF) progression in open-angle glaucoma (OAG), including primary OAG and normal tension glaucoma.Patients and methods: The subjects of the study were patients undergoing treatment for OAG who had performed VF tests at least 10 times with a Humphrey field analyzer (SITA standard, C30-2 program). The VF progression was defined by a significantly negative MD slope (MD slope worsening) at the final VF test during the follow-up period. The relationship between the MD slope worsening and the consecutive deterioration of MD value were retrospectively analyzed.Results: A total of 165 eyes of 165 patients were included in the analysis. Significant progression of VF defects was observed in 72 eyes of 72 patients (43.6%), while no significant progression was evident in 93 eyes of 93 patients (56.4%). There was significant relationship between the frequency of consecutive deterioration of MD value and MD slope worsening (P

Tomoko Naito,1 Keiji Yoshikawa,2 Shiro Mizoue,3 Mami Nanno,4 Tairo Kimura,5 Hirotaka Suzumura,6 Fumio Shiraga1 1Department of Ophthalmology, Okayama University Graduate School of Medicine, Okayama, Japan; 2Yoshikawa Eye Clinic, Tokyo, Japan; 3Department of Ophthalmology, Ehime University Graduate School of Medicine, Ehime, Japan; 4Kagurazaka Minamino Eye Clinic, 5Ueno Eye Clinic, 6Suzumura Eye Clinic, Tokyo, Japan Purpose: To analyze the relationship between intraocular pressure (IOP) and the progression of visual field defects in Japanese primary open-angle glaucoma (POAG) and normal-tension glaucoma (NTG) patients.Patients and methods: The subjects of the study were patients undergoing treatment for POAG or NTG who had performed visual field tests at least ten times with a Humphrey field analyzer (Swedish interactive thresholding algorithm standard, C30-2 program). The progression of visual field defects was defined by a significantly negative value of the mean deviation slope at the final visual field test during the follow-up period. The relationships between the progression of visual field defects and IOP, as well as other clinical factors, were retrospectively analyzed.Results: A total of 156 eyes of 156 patients were included in the analysis. Significant progression of visual field defects was observed in 70 eyes of 70 patients (44.9%), while no significant progression was evident in 86 eyes of 86 patients (55.1%). The eyes with visual field defect progression had significantly lower baseline IOP (P

Toyoaki Tsumura,1 Keiji Yoshikawa,2 Tairo Kimura,3 Hirotaka Suzumura,4 Miwako Kawashima,5 Mami Nanno,6 Kiyotaka Ishijima,7 Ryuji Takeda8 1Fussa Hospital, Tokyo, Japan; 2Yoshikawa Eye Clinic, Tokyo, Japan; 3Ueno Eye Clinic, Tokyo, Japan; 4Suzumura Eye Clinic, Tokyo, Japan; 5Nakano General Hospital, Tokyo, Japan; 6Kagurazaka Minamino Eye Clinic, Tokyo, Japan; 7Irumagawa Hospital, Saitama, Japan; 8Department of Biological Chemistry, Faculty of Agriculture, Kinki University, Nara, Japan Background: To evaluate the efficacy and safety of newly formulated brimonidine (0.1% brimonidine tartrate preserved with sodium chlorite: brimonidine) as add-on therapy in on-treatment Japanese normal-tension glaucoma (NTG) patients.Methods: Brimonidine was added to on-treatment NTG patients with intraocular pressures (IOP) of between 13 mmHg and 16 mmHg after three consecutive IOP measurements. The time courses of IOP, conjunctival hyperemia, superficial punctate keratitis, and adverse events were examined at 4, 8, and 12 weeks after brimonidine instillation.Results: Though 75 of 83 patients (31 males and 52 females; mean age: 63.4±11.6 years) completed the study, six patients discontinued because of side effects and two patients withdrew. The mean IOP after brimonidine addition at week 4 (12.6±1.8 mmHg, P

Shiro Mizoue,1 Tadashi Nakano,2 Nobuo Fuse,3 Aiko Iwase,4 Shun Matsumoto,5 Keiji Yoshikawa6 On behalf of the IOP CHANGE Study Group7 1Department of Ophthalmology, Ehime University Graduate School of Medicine, Ehime, Japan; 2Department of Ophthalmology, Jikei University School of Medicine, Tokyo, Japan; 3Department of Integrative Genomics, Tohoku Medical Megabank Organization, Miyagi, Japan; 4Tajimi Iwase Eye Clinic, Gifu, Japan; 5Department of Ophthalmology, Tokyo Teishin Hospital, 6Yoshikawa Eye Clinic, Tokyo, Japan; 7IOP CHecked and Assessed in Normal tension Glaucoma by Exceptional Glaucomatologists Study Group, Japan Background: This study aimed to evaluate the effect of travoprost with sofZia® preservative system for lowering the intraocular pressure (IOP) of Japanese normal tension glaucoma (NTG) patients. Methods: In this prospective, multicenter, open-label study, Japanese NTG patients with baseline IOPs

Keiji Yoshikawa,1 Jun Kozaki,2 Hidetaka Maeda3 1Yoshikawa Eye Clinic, Tokyo, Japan; 2Kozaki Eye Clinic, Osaka, Japan; 3Maeda Eye Clinic, Osaka, Japan Purpose: To evaluate the efficacy and safety of brinzolamide 1%/timolol 0.5% fixed-combination (BRINZ/TIM-FC) therapy compared with timolol 0.5% (TIM) monotherapy in Japanese patients with open-angle glaucoma or ocular hypertension. Methods: This randomized, double-masked, multicenter study included Japanese patients aged ≥20 years. Patients were treated during a 4-week observation period with TIM monotherapy in advance of randomization to treatment with topical BRINZ/TIM-FC or TIM monotherapy twice daily for 8 weeks. The primary endpoint was mean reduction in intraocular pressure (IOP) from baseline to week 8 at 2 hours postinstillation. Adverse events (AEs) were recorded at each visit. Results: A total of 301 patients (BRINZ/TIM-FC, n=150; TIM, n=151; age [mean ± standard deviation], 61±13 years) were enrolled. Mean IOP reductions from baseline were greater with BRINZ/TIM-FC than with TIM at weeks 4 and 8 at 0 and 2 hours postinstillation (all P≤0.0001), with mean reductions of -3.2 mmHg with BRINZ/TIM-FC and -1.4 mmHg with TIM at week 8, 2 hours postinstillation. Although AEs were observed in 19% of all patients (BRINZ/TIM-FC, 20%; TIM, 19%), all AEs were mild or moderate. Conclusion: BRINZ/TIM-FC therapy was associated with significantly greater reductions in IOP compared with TIM, and it was well tolerated in Japanese patients with open-angle glaucoma or ocular hypertension. Keywords: Azarga, intraocular pressure, carbonic anhydrase inhibitor, beta blocker

Hirotaka Suzumura,1 Keiji Yoshikawa,2 Shiro Mizoue,3 Ryoko Hyodo,4 Tairo Kimura5 1Eye Department, Nakano General Hospital, Tokyo, 2Yoshikawa Eye Clinic, Tokyo, 3Department of Ophthalmology, Ehime University, Ehime, 4Eye Department, Minami Matsuyama Hospital, Ehime, 5Ueno Eye Clinic, Tokyo, JapanBackground: The purpose of this study was to compare retinal sensitivities in normal individuals obtained using the Swedish Interactive Threshold Algorithm Standard (SITA-S) on the Humphrey field analyzer with those obtained using the Dynamic strategy on the Octopus.Methods: Prior to visual field examinations, the background luminance, stimulus size, and exposure time with the Octopus 101 were conformed to the Humphrey field analyzer II settings. Volunteers over 20 years of age without apparent ophthalmic abnormalities were examined with the SITA-S central 30-2 program followed by the Dynamic 32 program. Eye with corrected visual acuity ≥0.8, refraction ≥ −6.0 diopters, and fields with satisfactory levels of reliability in SITA-S and Dynamic were selected.Results: Sixty-seven eyes from 67 normal individuals of mean age 51.3 ± 16.3 (range 22–76) years satisfied the selection criteria and were analyzed. Mean retinal sensitivity was significantly (P < 0.0001) higher with SITA-S (29.0 ± 2.4 dB) than with Dynamic (26.8 ± 2.1 dB). Changes in retinal sensitivity with increasing age were significantly (P = 0.0003) greater with Dynamic (−0.09 ± 0.04 dB/year; 95% confidence interval [CI] −0.10 to −0.08 dB/year) than with SITA-S (−0.07 ± 0.04 dB/year, 95% CI −0.08 to −0.06 dB/year). When classifying the visual field into three areas (central, mid-peripheral, and peripheral), retinal sensitivities with SITA-S were significantly higher in all areas than with Dynamic (P < 0.0001 for all three areas).Conclusion: Differences in Dynamic and SITA-S strategies may contribute to the differences in retinal sensitivities observed in normal individuals.Keywords: time-saving strategy, frequency-of-seeing curve, dynamic, Swedish Interactive Threshold Algorithm Standard, Octopus perimeter, Humphrey field analyzer

Toyoaki Tsumura,1 Keiji Yoshikawa,2 Hirotaka Suzumura,3 Tairo Kimura,4 Satoshi Sasaki,5 Itaru Kimura,6 Ryuji Takeda71Department of Ophthalmology, Fussa Hospital, Fussa, Tokyo, Japan; 2Yoshikawa Eye Clinic, Machida, Tokyo, Japan; 3Department of Ophthalmology, Nakano General Hospital, Nakano, Tokyo, Japan; 4Ueno Eye Clinic, Ueno, Tokyo, Japan; 5Sasaki Eye Clinic, Ueno, Tokyo, Japan; 6Department of Ophthalmology, Juntendo University Urayasu Hospital, Urayasu, Chiba, Japan; 7Department of Biological Chemistry, Faculty of Agriculture, Kinki University, Nara, Nara, JapanPurpose: The aim of this study was to evaluate the efficacy and safety of bimatoprost ophthalmic solution 0.03% (bimatoprost) in Japanese normal-tension glaucoma (NTG) patients with an intraocular pressure (IOP) of 18 mmHg or less.Methods: Bimatoprost was instilled into the unilateral conjunctival sac of Japanese NTG patients with a baseline IOP of 18 mmHg or less. The time courses of IOP, conjunctival hyperemia, superficial punctate keratitis, and adverse events were examined at 2, 4, 8, and 12 weeks post bimatoprost instillation.Results: Thirty-two of the 38 enrolled NTG patients (mean age, 64.1 ± 12.6 years; 19 males and 19 females) completed the study, with six patients unable to complete the study (two patients discontinued because of side effects and four patients withdrew). The levels of IOP in the treated eyes were significantly reduced (P < 0.0001) from the baseline IOP levels. No significant change in IOP was observed in the fellow eyes. There were significant increases in conjunctival hyperemia. No significant superficial punctate keratitis scores were noted between the baseline and each point examined. Eyelash disorder, eyelid pigmentation, and deepening of the upper eyelid sulcus were observed in 28, six, and three eyes, respectively.Conclusion: Bimatoprost effectively lowered the IOP. It was well tolerated in Japanese NTG patients, with few patients having to discontinue because of adverse events.Keywords: intraocular pressure reduction, superficial punctate keratitis, conjunctival hyperemia, antiglaucoma drugs

Micro pixel chambers (μ-PIC) are gaseous two-dimensional imaging detectors originally manufactured using printed circuit board (PCB) technology. They are used in MeV gamma-ray astronomy, medicalimaging, neutron imaging, the search for dark matter, and dose monitoring. The position resolution of the present μ-PIC is approximately 120 μm (RMS), however some applications require a fine position resolution of less than 100 μm. To this end, we have started to develop a μ-PIC based on micro electro mechanical system (MEMS) technology, which provides better manufacturing accuracy than PCB technology. Our simulation predicted the gains of MEMS μ-PICs to be twice those of PCB μ-PICs at the same anode voltage. We manufactured two MEMS μ-PICs and tested them to study their behavior. In these experiments, we successfully operated the fabricatedMEMS μ-PICs and we achieved a maximum gain of approximately 7×103 and collected their energy spectra under irradiation of X-rays from 55Fe. However, the measured gains of the MEMS μ-PICs were less than half of the values predicted in the simulations. We postulated that the gains of the MEMS μ-PICs are diminished by the effect of the silicon used as a semiconducting substrate.

The efficacy and safety of add-on 0.1% brimonidine tartrate preserved with sodium chlorite in on-treatment Japanese normal-tension glaucoma patients [Corrigendum] Tsumura T, Yoshikawa K, Kimura T, et al. Clin Ophthalmol. 2014;8:1681–1687. The authors wish to advise of the following errors: on page 1684, right column, line 18, “10.72” should be replaced with “–10.72”; on page 1685, right column, line 2, “

Tsumura T, Yoshikawa K, Suzumura H, Kimura T, Sasaki S, Kimura I, Takeda R. Clinical Opthalmology. 2012;6:1547–1552. On page 1549 the significant difference in MD values was stated as in Table 1: −5.22 ± 4.07 It should have been: −5.47 ± 4.78Read the original article

Tsumura T, Yoshikawa K, Suzumura H, Kimura T, Sasaki S, Kimura I, Takeda R. Clinical Ophthalmology. 2012;6:1547–1552.On page 1549 the significant difference in MD values was stated as:(−5.22 ± 4.07 dB and −2.72 ± 4.06 dB, P = 0.0385)It should have been:(−5.47± 4.78 dB and −5.26 ± 5.22 dB, P = 0.6757)Figure 2 legend was missing the words:Left axis relates to the bars and right axis relates to the line chart.Read the original article