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Rijo Hayashi,1 Shimmin Hayashi,1,2 Tomoharu Nishimura,1 Shigeki Machida1 1Department of Ophthalmology, Saitama Medical Center, Dokkyo Medical University, Koshigaya, Saitama, Japan; 2Lively Eye Clinic, Soka, Saitama, JapanCorrespondence: Rijo Hayashi, Department of Ophthalmology, Saitama Medical Center, Dokkyo Medical University, 2-1-50, Minamikoshigaya, Koshigaya, Saitama, 3438555, Japan, Tel/Fax +81-48-965-8659, Email lhayashi@dokkyomed.ac.jpPurpose: Acute acquired concomitant esotropia induced by excessive digital device usage, especially smartphones (SAACE), has been increasing over the past few years. Convergence spasm induced by excessive near work has been suggested as a mechanism. Anatomical differences could also potentially contribute to SAACE onset. The present study investigated the conformation of horizontal recti between SAACE patients and normal subjects.Patients and Methods: In 15 SAACE patients (SAACE group), the distances between the limbus and insertion of the horizontal recti (LI distance) and the widths of horizontal recti on the insertion (insertion width) were measured. The control group consisted of 30 patients who underwent retinal detachment surgery. Differences in LI distances and insertion widths were compared between SAACE and control groups.Results: While there were no differences between the two groups for LI distances and insertion widths of lateral recti, there were significantly shorter LI distances for the medial recti in the SAACE group (P< 0.05). Moreover, the SAACE group tended to exhibit larger insertion widths of the medial recti. Medial/lateral ratio of LI distances were significantly lower and insertion widths were significantly higher in the SAACE compared to the control group (P< 0.05).Conclusion: Based on the observations of more anterior insertion and larger muscle widths, this suggests there are stronger forces of medial recti in SAACE. In addition to excessive accommodation followed by increases in medial recti tonus, the results also suggest that an anatomical imbalance between lateral and medial recti contributes to esotropia onset following excessive near work.Keywords: acute acquired concomitant esotropia, digital devices, extraocular muscles, insertion distance, insertion width

Naoko Koike,1 Tsuyoshi Otsuji,1 Akiko Tsumura,1 Katsuaki Miki,1 Yukio Sakai,1 Tetsuya Nishimura,1 Kanji Takahashi21Department of Ophthalmology, Kansai Medical University Medical Center, Osaka, Japan; 2Department of Ophthalmology, Kansai Medical University, Osaka, JapanPurpose: Intravitreal injection of anti-VEGF drugs has become standard therapy for patients with exudative age-related macular degeneration (AMD). However, some patients do not exhibit sufficient response to the drugs for suppression of choroidal neovascularization activity. We investigated the efficacy of switchback from ranibizumab to aflibercept in patients with AMD who could not achieve further benefit beyond initial therapy of aflibercept injection.Methods: Eleven eyes of eleven patients were included in this study. Two patients were nonresponders, and nine exhibited tachyphylaxis to aflibercept. All patients received three monthly injections of ranibizumab as an initial phase of switching and received aflibercept as a switchback drug. We investigated changes in injection interval, visual acuity, and central retinal thickness.Results: In four patients (36.4%), injection interval was extended. The interval was 6.73 weeks before switch and 9.27 weeks after switchback (P=0.96). LogMAR visual acuity was 0.22 before switch and 0.24 after switchback (P=0.62). Central retinal thickness was 306.8 μm before switch and 256.1 after switchback (P=0.13). In all patients who were nonresponders to aflibercept, injection interval could not be extended.Conclusion: A switchback from ranibizumab to aflibercept may be beneficial in some patients with AMD who exhibit tachyphylaxis to aflibercept.Keywords: AMD, aflibercept, ranibizumab, switchback, anti-VEGF drugs

Tetsuya Muto,1 Tomoharu Nishimura,1 Masaaki Sakamoto,1 Takenori Inomata,2 Shigeki Machida11Department of Ophthalmology, Dokkyo Medical University Saitama Medical Center, Koshigaya, Japan; 2Department of Ophthalmology, Juntendo University Faculty of Medicine, Tokyo, JapanPurpose: To identify from the anterior segment the structural variables of the eyes that can be used to distinguish acute primary angle-closure (APAC) eyes or primary angle-closure suspect (PACS) eyes from normal eyes.Patients and methods: We used a Pentacam scanner to measure participants’ anterior eye segments. We assessed each anterior segment structure variable on the basis of receiver operating characteristic curves using the area under the curve (AUC).Results: AUCs for eyes in men with APAC were 1.000 for central anterior chamber depth (ACD), 0.982 for peripheral ACD, 0.916 for anterior chamber angle (ACA), and 0.992 for anterior chamber volume (ACV). AUCs for eyes in women with APAC were 0.997 for central ACD, 0.942 for peripheral ACD, 0.922 for ACA, and 0.946 for ACV. AUCs for eyes in men with PACS were 0.933 for central ACD, 0.930 for peripheral ACD, 0.887 for ACA, and 0.937 for ACV. AUCs for eyes in women with PACS were 0.960 for central ACD, 0.957 for peripheral ACD, 0.937 for ACA, and 0.937 for ACV. The negative predictive values (%) in men with APAC were 100 for all the four variables (central ACD, peripheral ACD, ACA, and ACV). The negative predictive values (%) in women with APAC were 100 for central ACD, 98.7 for peripheral ACD, 97.1 for ACA, and 97.9 for ACV. The negative predictive values (%) in men with PACS were 98.6 for central ACD, 100 for peripheral ACD, 98.5 for ACA, and 99.4 for ACV. The negative predictive values (%) in women with PACS were 100 for central ACD, 98.7 for peripheral ACD, 97.1 for ACA, and 97.9 for ACV.Conclusions: The central ACD, peripheral ACD, ACA, and ACV measurements seem to be excellent markers to identify eyes without APAC or PACS.Keywords: acute primary angle-closure, anterior segment, Pentacam, glaucoma

Tetsuya Muto,1 Tomoharu Nishimura,1 Takefumi Yamaguchi,2 Makoto Chikuda,1 Shigeki Machida1 1Department of Ophthalmology, Dokkyo Medical University Koshigaya Hospital, Koshigaya, Japan; 2Department of Ophthalmology, Tokyo Dental College Ichikawa General Hospital, Ichikawa, Japan Purpose: Cataract progression after lens-sparing vitrectomy might differ according to original posterior segment diseases. Our objective was to analyze the refractive values after lens-sparing vitrectomy for macular hole (MH) and epiretinal membrane (ERM). Materials and methods: We reviewed the medical records of 25 MH patients (25 eyes) and 23 ERM patients (23 eyes) who underwent lens-sparing vitrectomy. Refractive changes in both groups were compared. All patients underwent 20-gauge three-port pars plana vitrectomy. Fluid–air exchange was performed during vitrectomy only in the MH group. The results were analyzed using the unpaired t-test, chi-square test, or Fisher exact probability test, and multivariate analysis. Results: There were no significant differences in the patient’s age (P=0.45). The myopia progression rate (D/month) was higher in the MH group after surgery than that in the ERM group (P=0.035). MH group had more females (P=0.043), longer surgical time (P

Tsuyoshi Otsuji,1 Kenichiro Sho,2 Akiko Tsumura,1 Naoko Koike,1 Tetsuya Nishimura,1 Kanji Takahashi2 1Department of Ophthalmology, Kansai Medical University, Takii Hospital, 2Department of Ophthalmology, Kansai Medical University, Hirakata Hospital, Osaka, Japan Background: To evaluate the effect of photodynamic therapy (PDT) using a modified procedure on exudative age-related macular degeneration having been conventionally difficult to treat. Methods: The medical records of eight consecutive patients (eight eyes) with age-related macular degeneration treated with modified PDT were reviewed retrospectively. Modified PDT was used for the lesions that could not be covered by conventional use of PDT, either because the lesion was too large or too close to the optic disc. A moving PDT laser spot at constant speed, for 83 seconds, was used to cover the entire lesion, and was named “Ironing PDT.” This retrospective study was performed with informed patient consent. It was approved by the Institutional Review Board of Kansai Medical University.Results: No exudation could be found 36 months after treatment in five eyes (62.5%). There was no significant difference between the best-corrected visual acuity before PDT (0.95 logMAR) and after PDT (1.09 logMAR). The logMAR best-corrected visual acuity was improved in one eye, maintained in five eyes, and deteriorated in two eyes. Conclusion: Ironing PDT decreased subfoveal fluid and preserved visual acuity in some patients with age-related macular degeneration difficult to treat with conventional therapy. Keywords: AMD, PCV, PDT, Ironing PDT, modified PDT, large lesions

Mei Mii, Masato Matsuoka, Kayako Matsuyama, Yayoi Otsu, Tetsuya Nishimura Department of Ophthalmology, Kansai Medical University, Takii Hospital, Osaka, Japan Purpose: To report the surgical outcomes of 25-gauge vitrectomy in eyes with myopic foveoschisis (MF). Methods: The medical records of 40 eyes of 36 patients that had undergone 25-gauge vitrectomy with internal limiting membrane peeling for MF were studied. The main outcome measures were the best-corrected visual acuity (BCVA) and the optical coherence tomography (OCT) findings. The eyes were divided into two groups: 1) those with a foveal detachment (FD; FD group); and 2) those without a FD (no-FD group). Results: The postoperative OCT images showed a resolution of the MF with a significant reduction in the central foveal thickness from the preoperative values in both the FD group (479±150 µm to 196±56 µm; P=0.002, mean ± standard deviation) and in the no-FD group (369±116 µm to 245±50 µm; P=0.001). The final mean BCVA significantly improved from the preoperative values in the FD group (0.96±0.53 logarithm of the minimum angle of resolution [logMAR] units to 0.70±0.56 logMAR units; P=0.009) and in the no-FD group (0.46±0.38 logMAR units to 0.34±0.36 logMAR units; P=0.007). The final BCVA in the FD group improved in 63%, remained unchanged in 31%, and worsened in 6%. In the no-FD group, the final BCVA improved in 21%, remained unchanged in 71%, and worsened in 8% of the eyes. A better final BCVA was significantly correlated with a better preoperative BCVA in both groups (P

Yayoi Otsu, Masato Matsuoka, Kayako Matsuyama, Tetsuya Nishimura Department of Ophthalmology, Kansai Medical University, Takii Hospital, Osaka, Japan Background: The purpose of this study was to determine the clinical features of patients with type 2 diabetes, and less ophthalmic examinations, referred by general physicians to ophthalmologists. Methods: The medical charts of 327 patients with type 2 diabetes referred to our department from general physicians were reviewed. A detailed medical history was taken and a complete ophthalmic examination was performed for all patients. The patients were divided into two groups, ie, those with a history of missing ophthalmic examinations for more than a year (noncompliant group) and those with no previous ophthalmic examinations (never-examined group). Serum levels of glycosylated hemoglobin and creatinine, estimated glomerular filtration rate, and urine albumin/creatinine ratio were obtained from medical records. Results: Of the 327 patients, 102 had diabetic retinopathy (31.2%), with a mean best-corrected visual acuity of 0.037±0.36 logMAR (logarithm of the minimum angle of resolution) units. Of the 327 patients, 203 were in the never-examined group and 124 were in the noncompliant group. The incidence of diabetic retinopathy in the noncompliant group was significantly higher than that in the never-examined group (P

Koichi Nishimura,1 Takashi Nishimura,2 Katsuya Onishi,3 Toru Oga,4 Yoshinori Hasegawa,5 Paul W Jones61Department of Pulmonary Medicine, National Center for Geriatrics and Gerontology, Obu, Japan; 2Kyoto-Katsura Hospital, Kyoto, Japan; 3Onishi Heart Clinic, Tsu, Japan; 4Department of Respiratory Care and Sleep Control Medicine, Graduate School of Medicine, Kyoto University, Kyoto, Japan; 5Division of Respiratory Medicine, Department of Medicine, Nagoya University Graduate School of Medicine, Nagoya, Aichi, Japan; 6Division of Clinical Science, St George's Hospital Medical School, London, EnglandBackground: Elevated plasma B-type natriuretic peptide (BNP) levels and their association with heart failure have been reported in subjects with acute exacerbations of chronic obstructive pulmonary disease (AECOPD).Purpose: To examine and compare plasma BNP levels and diastolic and systolic dysfunction in subjects with AECOPD and stable chronic obstructive pulmonary disease (COPD).Methods: In all, 87 unselected consecutive hospitalizations due to AECOPD in 61 subjects and a total of 190 consecutive subjects with stable COPD were recruited. Plasma BNP levels were compared cross-sectionally and longitudinally. Transthoracic echocardiographic examinations were also performed in the hospitalized subjects.Results: In the hospitalized subjects, the median plasma BNP level (interquartile range) was 55.4 (26.9–129.3) pg/mL and was higher than that of patients with stable COPD: 18.3 (10.0–45.3) for Global Initiative for Chronic Obstructive Lung Disease grade I; 25.8 (11.0–53.7) for grade II; 22.1 (9.1–52.6) for grade III; and 17.2 (9.6–22.9) pg/mL for grade IV, all P240 ms. BNP levels were weakly correlated with the E/peak early diastolic velocity of the mitral annulus (Ea) ratio (Spearman's rank correlation coefficient =0.353, P=0.018), but they were not correlated with the LVEF (Spearman's rank correlation coefficient =-0.221, P=0.108).Conclusion: A modest elevation of plasma BNP is observed during AECOPD. It appears that AECOPD may have an impact on plasma BNP levels that is not attributable to heart failure.Keywords: chronic obstructive pulmonary disease, acute exacerbations of chronic obstructive pulmonary disease, B-type natriuretic peptide, heart failure

Toshiki Nishimura,1 Aya Nakae,2 Masahiko Shibata,3 Takashi Mashimo,4 Yuji Fujino21Osaka University Medical School, 2Department of Anesthesiology and Intensive Care Medicine, 3Department of Pain Medicine, Osaka University Graduate School of Medicine, Suita, Japan; 4Toyonaka Municipal Hospital, Toyonaka, JapanBackground: Even though pain is a subjective phenomenon, its objective evaluation in humans is important because subjects requiring pain evaluation may be unable to describe their pain intensity because of decreased awareness or impaired cognitive function. Previous reports indicate that the perfusion index (PI), which is calculated from pulse oximeter waveforms, has some utility in assessing pain. However, age-associated and sex-associated differences in change of PI have hitherto not been evaluated for assessment of pain. Therefore, we aimed to estimate the utility of age-related differences in PI change among healthy volunteers subjected to electrical stimulation.Methods: We measured PI and pulse rate in 70 healthy volunteers exposed to gradually increasing electrical stimulation. The subjects were classified into four groups, ie, young men, young women, aged men, and aged women. Stimulation was stopped when subjects reached their pain tolerance threshold. The average PI and pulse rate were calculated 10 seconds before and after electrical stimulation and compared across the four groups. Changes in PI and pulse rate were analyzed using the paired t-test.Results: The PI was significantly decreased in response to pain stimulation in young men (P

Koichiro Tanaka,1 Kazuhiko Nara,1 Tetsuya Nishimura,1 Keiko Serizawa,1 Taito Miyazaki,2 Yoshihisa Urita,2 Oto Miura11Division of Traditional Japanese Medicine, Department of General Medicine and Emergency Care, Faculty of Medicine, Toho University, 2Department of General Medicine and Emergency Care, Faculty of Medicine, Toho University, Tokyo, JapanAbstract: Oren-gedoku-to is a traditional medicine used for treating inflammatory conditions and is given by prescription in Japan, People's Republic of China, and Korea. Its anti-inflammatory effect is related to the arachidonate cascade and inhibition of cyclo-oxygenase, but research on other anti-inflammatory pathways is ongoing. We report a case of fever of unknown origin in a 33-year-old woman. The possibility of infection due to human immunodeficiency virus, autoimmune, neoplastic, or other disease was examined and excluded. Oren-gedoku-to was successfully used to treat her symptoms and may thus be a suitable treatment for patients with undiagnosed fever of unknown origin.Keywords: fever of unknown origin, oren-gedoku-to, huanglian-jie-du-tang, kampo

Tsuyoshi Otsuji,1 Yoshimi Nagai,2 Kenichiro Sho,1 Akiko Tsumura,1 Naoko Koike,1 Mei Tsuda,1 Tetsuya Nishimura,1 Kanji Takahashi2 1Department of Ophthalmology, Kansai Medical University, Takii Hospital, Osaka, Japan; 2Department of Ophthalmology, Kansai Medical University, Hirakata Hospital, Osaka, Japan Background: Patients with exudative age-related macular degeneration (AMD) who did not respond to ranibizumab at the induction phase were assessed and referred to as initial non-responders. Methods: We retrospectively reviewed the medical records of 215 patients (218 eyes) with exudative AMD. For the initial treatments, patients received three intravitreal injections of ranibizumab (IVR) every 4 weeks. Minimum follow-up period was 12 months. We defined patients with no improvement of best corrected logMAR visual acuity (BCVA), and with no decrease of central retinal thickness (CRT) at the end of the initial treatment, as initial non-responders. Patients who had previous treatment history prior to this investigation were included, but patients who had photodynamic therapy (PDT) with IVR were excluded. Results: Twenty-two eyes (10.1%) were identified as initial non-responders. The mean BCVA of initial non-responders before IVR and after induction phase were 0.39 and 0.36, respectively. There was no significant difference between these values, however the mean BCVA decreased significantly to 0.55 at 12 months after the beginning of the induction phase (P = 0.021). The mean greatest linear dimension (GLD) of the lesion before IVR of initial non-responders was 4,121 µm. We found 16 eyes with typical AMD, and six eyes with polypoidal choroidal vasculopathy. One eye had predominantly classic choroidal neovascularization (CNV), and others had occult CNV of typical AMD. As additional treatments, twelve eyes received PDT, and in three of the eyes exudation remained after PDT. Conclusion: Initial non-responders were more prevalent in patients with occult CNV than in patients with other CNV types. Some of the initial non-responders did not respond to PDT. This study suggested possible involvement of other factors, in addition to vascular endothelial growth factor, in the occurrence of CNV in initial non-responder patients. Keywords: AMD, anti-VEGF drug, ranibizumab, initial non-responders

Masato Matsuoka,1 Hideyuki Yoshida,1 Yuichi Kinoshita,2 Tetsuya Nishimura11Department of Ophthalmology, 2Department of Histopathology, Kansai Medical University, Takii Hospital, Osaka, JapanPurpose: Intraocular lymphomas are rare, and they have poor prognosis. Thus, early diagnosis and treatment are needed. A definitive diagnosis of a lymphoma is based on cytological analysis of the intraocular fluids or tissues. We report two cases of intraocular lymphoma diagnosed by the analyses of vitreous and infusion fluid.Patients: Case 1 was a 66-year-old woman who complained of eye floaters and was found to have diffuse vitreous opacification bilaterally. She received corticosteroid therapy, however the vitreous opacification was not resolved, and her visual acuity (VA) remained reduced. She underwent pars plana vitrectomy (PPV), and vitreous and infusion fluid were collected to determine the cause of the reduced VA. The undiluted vitreous obtained from core PPV was submitted for cytokine analysis, and infusion fluid was obtained from the machine cassette after full PPV and used for cytological analysis. Case 2 was a 62-year-old man referred with low vision and was found to have diffuse vitreous opacification in the right eye and dot hemorrhages in both eyes. Four years earlier, he had been diagnosed with diffuse large B-cell lymphoma of the paranasal sinuses and was in remission after chemotherapy. Because metastasis of the lymphoma was suspected, he underwent PPV, and intraocular samples were collected as in Case 1.Results: Atypical lymphoid cells were detected from the infusion fluid in both cases. The ratio of interleukin (IL)-10 to IL-6 was greater than 1.0 in both cases. These results allowed us to make a diagnosis of intraocular lymphoma: primary intraocular lymphoma in Case 1 and metastatic intraocular lymphoma in Case 2.Conclusion: Vitreous and infusion fluid collected during PPV can be used for diagnosing an intraocular lymphoma.Keywords: intraocular lymphoma, cytological analysis, vitreous, pars plana vitrectomy, infusion fluid

Tomoharu Nishimura, Shigeki Machida, Tomomi Harada, Daijiro KurosakaDepartment of Ophthalmology, Iwate Medical University School of Medicine, Morioka, Iwate, JapanBackground: The purpose of this study was to evaluate the safety of intravitreal ranibizumab injection in patients with age-related macular degeneration.Materials and methods: We examined retinal ganglion cell function using the photopic negative response of the electroretinogram (ERG) in patients with age-related macular degeneration (AMD) treated with intravitreal injections of ranibizumab. We studied 32 eyes of 32 patients with AMD and aged 50–84 years with a mean of 71 years. An intravitreal ranibizumab injection was given three times at monthly intervals. Additional injections were given according to an optical coherence tomography-guided variable dosing regimen. ERG recordings were made before treatment (baseline) and at 3, 6, 9, and 12 months postoperatively. Full-field cone ERGs were elicited by red stimuli on a blue background. The focal macular ERGs were elicited by a 15 degree white stimulus spot centered on the macular region. We measured the amplitudes of the a and b waves, oscillatory potentials, and the photopic negative response of the full-field cone and focal macular ERGs.Results: Visual acuity was significantly better than the baseline acuity, and macular thickness was significantly reduced after the intravitreal injections of ranibizumab. The amplitudes and implicit times of each wave of the full-field cone ERGs were not significantly changed after intravitreal ranibizumab injections. However, the amplitudes of each wave of the focal macular ERGs were increased after the injections. The implicit times of the a and b waves of the focal macular ERGs were significantly shortened after intravitreal injections of ranibizumab. The ratio of the full-field and focal photopic negative response/b-wave amplitude was not significantly changed after the injections.Conclusion: The amplitudes of the focal macular ERGs, including the photopic negative response improved after repeated intravitreal ranibizumab injections, accompanied by a recovery of visual acuity and macular structure. The results of the full-field cone ERGs indicate that retinal ganglion cell function was not altered by repeated intravitreal ranibizumab injection.Keywords: age-related macular degeneration, retinal ganglion cell, photopic negative response, electroretinogram, ranibizumab

Koichi Nishimura1, Maya Yasui2, Takashi Nishimura2, Toru Oga31Department of Internal Medicine, Kaikoukai Jousai Hospital, Aichi, Japan; 2Kyoto-Katsura Hospital, Kyoto, Japan; 3Department of Respiratory Care and Sleep Control Medicine, Graduate School of Medicine, Kyoto University, Kyoto, JapanBackground: Randomized controlled trials, evidence-based medicine, clinical guidelines, and total quality management are some of the approaches used to render science-based health care services. The clinical pathway for hospitalized patients suffering from acute exacerbations of chronic obstructive pulmonary disease (AECOPD) is poorly established, although a clinical pathway is an integral part of total quality management.Aim: To evaluate the outcomes of patients hospitalized with AECOPD in Japan, treated with a clinical pathway following published guidelines.Methods: Prospective data were collected for patients with AECOPD admitted to a general hospital over a 5-year period since 2003. The clinical pathway was designed to establish general rules for the entire treatment protocol. The clinical pathway indicates which treatments and interventions should be performed, and when. In this study, health care providers were required to check the clinical pathway sheets to determine the next step of treatment.Results: This study analyzed 276 hospitalizations in 165 patients. The clinical pathway was interrupted and defined as a dropout in 45 cases (16.3%). Nine patients died during hospitalization (3.3%). Oxygen was administered in 232 hospitalizations (84.1%). Noninvasive positive pressure ventilation (NPPV) treatment was administered in 110 hospitalizations (39.9%). The rate of intubation in those cases where NPPV treatment had been administered was 8.2% (9 cases out of 110). The average length of stay (LOS) was 20.3 days, and the median value was 15 days. The LOS was longer than 30 days in 34 admissions (12.3%), mainly due to complications.Conclusion: AECOPD can be managed using a clinical pathway. This clinical pathway could fill the gap between guidelines and clinical practice.Keywords: COPD, AECOPD, mortality, pulmonary rehabilitation

Objective: The objective of this study was to identify problems in the approval, pharmacovigilance, and post-approval regulatory decision-making procedures involving gefitinib and to propose countermeasures to prevent further drug-induced suffering in Japan in the future. Methods: We comprehensively reviewed reports regarding gefitinib published during the period from 2000 to 2006 by regulatory agencies, the manufacturer of the gefitinib-containing drug, cancer clinical study groups, and a scientific society.Results: We identified the following major problems in the approval, pharmacovigilance, and regulatory decision-making procedures: 1) the results of animal experiments and pre-marketing clinical trials, and reports of adverse drug reactions from other countries were not properly reflected in the label; 2) indications for the drug were expanded without strict evaluation of the external validity of pre-marketing clinical trials; and 3) despite many serious cases of interstitial lung disease (ILD) being spontaneously reported, well-designed post-marketing surveillance was not immediately performed. Conclusions: We propose a mandatory total registry of all drug users and surveillance (i.e. a prospective outcome study) as one of the rational solutions for preventing further drug-induced suffering in Japan.

Masato Matsuoka,1 Nahoko Ogata,2 Kanji Takahashi,3 Yuichi Kinoshita,4 Tetsuya Nishimura11Department of Ophthalmology, Kansai Medical University, Takii Hospital, Osaka, 2Department of Ophthalmology, Nara Medical University, Nara, 3Department of Ophthalmology, Kansai Medical University, Hirakata Hospital, Osaka, 4Department of Histopathology, Kansai Medical University, Takii Hospital, Osaka, JapanAbstract: The purpose of this paper is to report two cases of sarcoidosis with conflicting signs in which vitreous cytology was useful for supporting the diagnosis. Case 1 was a 56-year-old man who was referred with blurred vision, and was found to have iridocyclitis, vitreous opacities, and optic neuritis bilaterally. He also had a swelling of both mandibular glands. He received pulsed corticosteroid therapy, but the vitreous opacities and papilledema did not resolve. The second case was a 77-year-old man referred with blurred vision, and both eyes had snowball-like vitreous opacities and optic neuritis. The ocular findings in both cases strongly suggested sarcoidosis, but the systemic findings did not meet the diagnostic criteria for sarcoidosis. We performed pars plana vitrectomy to remove the vitreous opacities, and the collected vitreous samples were sent for cytological analyses. Epithelioid and multinucleated giant cells pathognomonic of sarcoidosis were found in the vitreous samples which enabled us to make a diagnosis of sarcoidosis. Vitreous cytology can help in supporting a diagnosis of sarcoidosis, especially in cases of ocular inflammation suggesting sarcoidosis but systemic findings that do not satisfy the diagnostic criteria for this disease.Keywords: sarcoidosis, cytology, vitreous, pars plana vitrectomy, papilledema

Distributed acoustic sensing (DAS) technology enables the detection of waves generated by seismic events, generally as uniaxial strain/strain rate time-series observed for dense, subsequent, portions of a Fibre Optic Cable (FOC). Despite the advantages in measurement density, data quality is often affected by uniaxial signal polarization, site effects and cable coupling, beyond the physical energy decay with distance. To better understand the relative importance of these factors for data inversion, we attempt a first modelling of noise patterns affecting DAS arrival times for a set of seismic events. The focus is on assessing the impact of noise statistics, together with the geometry of the problem, on epicentral location uncertainties. For this goal, we consider 15 'real-world' cases of DAS arrays with different geometry, each associated with a seismic event of known location. We compute synthetic P -wave arrival times and contaminate them with four statistical distributions of the noise. We also estimate P -wave arrival times on real waveforms using a standard seismological picker. Eventually, these five data sets are inverted using a Markov chain Monte Carlo method, which offers the evaluation of the relative event location differences in terms of posterior probability density (PPD). Results highlight how cable geometry influences the shape, extent and directionality of the PPDs. However, synthetic tests demonstrate how noise assumptions on arrival times often have important effects on location uncertainties. Moreover, for half of the analysed case studies, the observed and synthetic locations are more similar when considering noise sources that are independent of the geometrical characteristics of the arrays. Thus, the results indicate that axial polarization, site conditions and cable coupling, beyond other intrinsic features (e.g. optical noise), are likely responsible for the complex distribution of DAS arrival times. Overall, the noise sensitivity of DAS suggests caution when applying geometry-only-based approaches for the a priori evaluation of novel monitoring systems. [ABSTRACT FROM AUTHOR]