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To compare the ability of imo binocular random single-eye test (BRSET) to detect visual field (VF) defects due to chiasmal and postchiasmal lesions (C/PCLs) with a Humphrey Field Analyzer (HFA) monocular test.Prospective multicenter study METHODS: This study enrolled 40 patients with C/PCLs and measured their VFs using both imo BRSET and HFA monocular test. The VFs were classified into three groups using the cluster criterion: 1) bitemporal group, 2) homonymous group, and 3) others. The agreement and correlation of VF results between imo and HFA were analyzed using the Bland-Altman plot and Spearman correlation coefficient.The VFs of 34 patients were analyzed and classified. There were 13 patients in the bitemporal, 6 in the homonymous, and 15 in the others group. BRSET showed a significantly shorter test duration than HFA. The imo systematically yielded a lower sensitivity than HFA. The average sensitivity at each test location correlated well between the perimeters in all groups, with the correlation coefficients ranging from 0.89 to 0.98. Bland-Altman plots showed wider limits of agreement in the affected quadrants compared to the unaffected quadrants in the bitemporal and homonymous groups. The fixation loss rate did not differ between the perimeters, but there were significant differences in the false positive and false negative rates between perimeters.BRSET detected VF defects due to C/PCLs as accurately as the HFA monocular test with a shorter test duration.

Patients with asymmetric glaucomatous optic neuropathy (GON) present a relative afferent pupillary defect (RAPD) in the eye with more advanced damage. Although useful, pupillometric RAPD quantification is not widely used as it is not portable. Whether asymmetry of the peripapillary capillary perfusion density (CPD) detected using optical coherence tomography angiography correlates with the severity of RAPD remains unknown. This study assessed RAPD in 81 patients with GON using Hitomiru, a novel hand-held infrared binocular pupillometer. The correlation and ability to detect clinical RAPD based on the swinging flash light test of two independent RAPD parameters (the maximum pupil constriction ratio and the constriction maintenance capacity ratio) were assessed. The coefficient of determination (R2) was calculated between each of the two RAPD parameters and asymmetry of the circumpapillary retinal nerve fiber layer thickness (cpRNFLT), ganglion cell layer/inner plexiform layer thickness (GCL/IPLT), and CPD. The two RAPD parameters showed a correlation coefficient of 0.86 and areas under the receiver operating characteristic (ROC) curve of 0.85–0.88, with R2 being 0.63–0.67 for the visual field, 0.35–0.45 for cpRNFLT, 0.45–0.49 for GCL/IPLT, and 0.53–0.59 for CPD asymmetry. Hitomiru has high discriminatory performance in detecting RAPD in patients with asymmetric GON. CPD asymmetry may better correlate with RAPD than cpRNFLT and GCL/IPLT asymmetry.

Purpose We have previously demonstrated that prolonged use of glaucoma medications was associated with a poor surgical outcome of ab interno trabeculotomy (µTLO). Given that almost all types of glaucoma eye drop either enhance the drainage through the uveoscleral pathway or reduce aqueous humor production, we hypothesized that prolonged use of these medications might cause disuse atrophy of the conventional pathway. In contrast, ripasudil increases the conventional outflow and eventually shows a favorable outcome of µTLO. This study aimed to evaluate the effect of ripasudil use on µTLO outcomes. Method The medical charts of 218 patients who underwent µTLO were analyzed retrospectively. We compared the 1-year outcome between ripasudil users versus nonusers by using propensity score matching. We set the covariates as age, sex, glaucoma types, preoperative intraocular pressure (IOP), the mean deviation values of visual field tests, the presence or absence of concomitant cataract surgery, trabecular meshwork incision range, the presence or absence of any glaucoma medication except ripasudil and duration of glaucoma medical therapy. Success was defined as a postoperative IOP between 5 and 21 mmHg, a ≥ 20% IOP reduction from baseline, and no additional glaucoma surgery at postoperative 1 year. Result Fifty-seven patients each were allocated to the ripasudil users or nonusers. The 1-year success rates were 74% in ripasudil users and 51% in nonusers (p = 0.01). Kaplan‒Meier survival curves also showed that the ripasudil users had a higher survival distribution (p = 0.01). Conclusion The patients who took ripasudil showed a favorable 1-year outcome of µTLO.

We report a rare case of granulomatosis with polyangiitis (GPA) presenting with bilateral orbital apex syndrome (OAS). A 73-year-old woman with a history of endoscopic sinus surgery for ethmoidal sinusitis experienced a sudden decrease in visual acuity (VA) of both eyes. At the initial examination, her VA had decreased to 0.01 in the right eye and 0.03 in the left eye, and eye movement in both eyes was mildly limited in all directions. Visual field tests of both eyes showed a large central scotoma. Laboratory tests revealed an elevation of myeloperoxidase-anti-neutrophil cytoplasmic antibody. Facial computed tomography demonstrated a thickened mucosal membrane in the entire ethmoidal sinus, and the posterosuperior walls of Onodi cells filled with infiltrative lesions had thinned. Orbital magnetic resonance imaging showed severe inflammation in the orbital apex. From these clinical findings, the patient was diagnosed with GPA presenting with OAS associated with ethmoid sinusitis. Emergent endoscopic sinus surgery was performed for biopsy and debridement of the ethmoidal and sphenoid sinusitis to decompress the optic nerve. One day after endoscopic sinus surgery, the patient’s VA and visual field were improved, and steroid pulse therapy was commenced postoperatively. Four days later, VA had recovered to 1.0 in both eyes, and eye movement and visual field had were improved. Although OAS is a rare manifestation, early surgical treatment should be considered when the orbital lesion presents as risk of rapid deterioration of visual function in patients with GPA.

Purpose: The purpose of this retrospective study was to determine the extent to which the use of antithrombotic drugs during glaucoma surgery contributes to surgical failure and postsurgical hemorrhagic complications. Methods: Glaucoma surgeries were categorized into three groups: trabeculotomy (TLO), trabeculectomy (TLE), and long-Tube shunt surgery (Tube). At 1 year after surgery, the following criteria for surgical success were met: intraocular pressure (IOP) in the 5–21-mmHg range, IOP reduction of at least 20% from the preoperative level, and no additional glaucoma surgeries. We compared the percentages of the success rates and hemorrhagic complications between antithrombotic medication experiencers and non-experiencers. Furthermore, we adjusted the preoperative factors between the two groups using a propensity score analysis in TLO and TLE surgeries. Results: A total of 910 glaucoma surgeries were included, with TLO, TLE, and Tube accounting for 353, 444, and 113 surgeries, respectively. Preoperative antithrombotic medications were administered to 149 patients in all glaucoma surgeries: 37 patients used only anticoagulants, 102 used only antiplatelets, and 10 used both. There was no significant difference in the success rates of any of the procedures. The hemorrhagic complications (hyphema and vitreous hemorrhage rate) were significantly higher in the patients who underwent TLE and Tube. The surgical success rates of TLO and TLE were not significantly different after the two groups were matched by propensity score. Conclusion: The perioperative use of antithrombotic drugs did not affect success for any of the procedures. However, it increased early postoperative hemorrhagic complications for TLE and Tube.

This study examined the perioperative factors affecting surgical success in ab interno microhook trabeculotomy (μTLO).A total of 146 consecutive patients who underwent μTLO were included in this retrospective study. We performed Cox proportional hazard modelling by setting surgical success at 1 year as an objective variable. The explanatory variables included age, sex, glaucoma type, preoperative intraocular pressure (IOP), glaucoma drug score, mean deviation (MD) of the Humphrey visual field test, duration of glaucoma drug use, antithrombotic drug use, combined cataract surgery, incision range and diabetes mellitus. Additionally, we performed 1:1 matching using propensity score analysis and compared the perioperative parameters between durations of glaucoma drug use of4.5 years and ≥ 4.5 years (50 patients each). We defined surgical success as satisfaction of all three criteria: IOP 5-21 mmHg, IOP reduction of ≥20% from the preoperative IOP and no additional glaucoma surgery.The Cox proportional hazard model revealed that a longer duration of anti-glaucoma medication was significantly associated with surgical failure. Propensity score matching analysis showed that the4.5-year users of anti-glaucoma drugs had significantly higher success rates than the ≥4.5-year users (72% versus 52%; p = 0.04).The prolonged use of multiple glaucoma drugs adversely affected the outcome of μTLO at least at 1 year postoperatively.

Langerhans cell histiocytosis (LCH) is characterised by tissue destruction caused by the abnormal proliferation of pathogenic dendritic cells. We report a rare case of multi-system LCH with local invasion of the orbital apex.A 56-year-old woman suffered from a decrease of visual acuity in the left eye caused by central scotoma and the limitation of eye movement in all directions. Magnetic resonance imaging revealed an enhanced lesion in the left orbital apex, suggesting optic nerve compression. She had been diagnosed with eosinophilic granuloma 24 years previously. Two weeks after the current presentation, we admitted the patient for optic canal and orbital apex decompression and subtotal tumour resection. Histopathological analysis confirmed the diagnosis of LCH. Post-surgical treatment with low-dose cytarabine was initiated for the residual tumour. However, it was ceased because of myelosuppression-induced pyelonephritis. After surgery, the central scotoma disappeared on day 5 and eye movement palsy resolved by 6 months. After the cessation of cytarabine, she has received low-dose steroid therapy for 2 years with no recurrence. Early surgical intervention with low-dose steroid therapy can lead to recovery of visual acuity and resolve eye movement palsy in patients with lesions of the orbital apex caused by multi-system LCH.

Purpose: The present study aimed to assess the ability of en face slab images of maculae to detect residual nerve fiber bundles in eyes with advanced glaucoma. Methods: This study included 36 eyes with diffuse thinning of the ganglion cell and inner plexiform layers (GCL+IPL). Inclusion criterion was GCL+IPL thickness of

Takuji Kurimoto, Kaori Ueda, Sotaro Mori, Mari Sakamoto, Yuko Yamada-Nakanishi, Wataru Matsumiya, Makoto NakamuraDivision of Ophthalmology, Department of Surgery, Kobe University Graduate School of Medicine, Kobe, JapanBackground: Leber hereditary optic neuropathy (LHON) is a maternally inherited disease caused by three missense mutations of mitochondrial (mt) DNA, ie, m 3460 G>A, m 11778 G>A, or m 14484 T>C in the greater portion of LHON. m 11778 G>A mutation is especially observed in >90% of the cases in Japanese families. Although spontaneous remission of visual function infrequently occurs, effective treatment for LHON remains unestablished. Transcorneal electrical stimulation has been shown to be efficacious in individuals with optic neuropathy. However, due to potential risk of corneal damage, repeated treatments are not permissible. In this exploratory study, we will be conducting skin electrical stimulation (SES) as an intervention for patients with LHON having 11778 missense mutation and investigate effectiveness and safety of SES.Methods: This is a single-arm, prospective, open-label exploratory trial focused on patients with LHON having 11778 missense mutation. Eleven patients will be enrolled and receive six consecutive SES once every 2 weeks up to 10 weeks. The safety of the SES will be monitored with specular microscopy, slit-lamp biomicroscopy, fundus examinations, and the observation of facial skin. The primary outcome measure will be the averaged l ogarithm of minimum angle resolution (logMAR) converted visual acuity 1 week after the last SES. Secondary outcome measures include changes, in logMAR at 4 and 8 weeks after the last SES, such as visual field indices measured using Humphrey visual field and microperimetry-3, the thickness of peripapillary retinal fiber and macular ganglion cell complex, multifocal visual evoked potentials, critical flicker frequency, and color vision.Discussion: The results of this proposed proof-of-concept feasibility trial will help plan and execute a larger definitive trial to test SES as an effective strategy for LHON and related optic neuropathies and help establish a beneficial treatment for LHON.Keywords: skin electrical stimulation, Leber hereditary optic neuropathy, logarithm of minimum angle resolution, single-arm study

Purpose The purpose of this study was to evaluate the concordance of a temporal raphe architecture estimated using optical coherence tomography (OCT) and MP-3 microperimetry. Methods We enrolled 25 eyes with either an upper or lower glaucomatous hemifield defect, as detected on the Humphrey visual field 30-2 test. A structural temporal raphe was extrapolated from visible end points of retinal nerve fiber bundles present in a perimetrically normal hemiretina on an en face Spectralis OCT image. A functional temporal raphe was drawn as a line from the fovea to the border of at least a 10-dB difference in sensitivity, at vertically adjacent test points, with at least three consecutive pairs among 25 test points placed at 8° to 18° from the fovea (2° intervals) on the MP-3. An angle determined by the optic disc center, the fovea, and the temporal raphe line (the DFR angle) was calculated. Correlations and agreement of the OCT- and MP-3-derived DFR angles and factors affecting discordance of the two estimates were evaluated. Results Despite no significant demographic differences, the functional DFR angle (mean ± SD, 171.8° ± 3.5°) was significantly larger than that of the structural DFR angle (166.5° ± 3.2°) in 14 eyes with upper hemifield defects and vice versa in 11 eyes with lower hemifield defects (163.4° ± 3.0° vs. 170.5° ± 3.2°). The mean deviation was significantly associated with the functional and structural DFR angle difference in eyes with only upper hemifield defects. Conclusions The structural temporal raphe was more deviated to the perimetrically normal hemiretina side than to the functional temporal raphe, thereby suggesting that a structural change may precede a functional loss.

Background: Invasive aspergillosis is often fatal. Here, we report a patient with invasive aspergillosis primarily involving the optic nerve diagnosed on autopsy. Case Presentation: A 77-year-old female with underlying diabetes mellitus, hyperlipidemia, and hypertension presented with disc swelling of the left eye. Although mini-pulse steroid therapy improved visual acuity (VA) of the left eye, it abruptly decreased to no light perception within a month, followed by a decrease in VA of the right eye to 0.5. At referral, VA was 0.3 in the right eye, and there was no light perception in the left eye. Results: Fundus examination revealed optic disc swelling of both eyes. Goldmann perimetry showed irregular visual field defects, whereas magnetic resonance imaging (MRI), general, and cerebrospinal fluid (CSF) examinations revealed no distinct abnormalities. We suspected anterior ischemic optic neuropathy and invasive optic neuropathy. As with the left eye, steroid pulse therapy temporarily improved VA of the right eye and then decreased to 0.2. Additional anticoagulant therapy did not improve VA. Concurrent to therapy, the patient became febrile with depressed consciousness. Repeat MRI identified suspected midbrain infarction, and CSF examination indicated cerebral meningitis. In spite of administering transfusions and antibiotics, she died on hospital day 40. Autopsy revealed large amounts of Aspergillus hyphae mainly localized in the dura mater of the optic nerve and destruction of the cerebral artery wall, suggesting an etiology of subarachnoid hemorrhage. Conclusions: When examining refractory and persistent disc swelling, we should rule out fungal infections of the optic nerve.

Purpose The purpose of this study was to evaluate the 3-year surgical outcome of the sulcus fixation of Baerveldt glaucoma implant (BGI), focusing on corneal damage. Methods This prospective observational study included 37 patients who underwent a median of two previous glaucoma surgeries and sulcus fixation of BGI for the first time. Each patient's intraocular pressure (IOP), glaucoma drug score, corneal endothelial cell density (ECD), and logMAR-converted best-corrected visual acuity (VA) were measured preoperatively and postoperatively until 36 months after surgery. Complete success was defined as reduced IOP (5-21 mmHg and >20% rate), without corneal damage (postoperative development of decompensation, unmeasurable ECD, or reduction in ECD of >20%), without loss of light perception, and without additional surgery requirement. Qualified success was defined by excluding the corneal criteria from complete success. Results A total of 51% (19/37) patients experienced complete treatment success, whereas 86% (32/37) had qualified success. The median IOP (glaucoma drug score) decreased from 26 mmHg (5) to 15 mmHg (2) at three years postoperatively. The median postoperative ECD (reduction rate) decreased from 1838 cells/cm2 preoperatively to 1587 cells/mm2 (14%) at one year, 1358 cells/mm2 (26%) at two years, and 1228 cells/mm2 (33%) at three years postoperatively. One month after surgery, the VA was significantly reduced from preoperative values but did not decline after that. Conclusion Sulcus fixation of BGI was effective for IOP reduction. However, ECD decreased over time.

Purpose We report a case of neurosarcoidosis that presented simultaneously with oculomotor nerve palsy, contralateral abducens nerve palsy, and paresthesia of both lower limbs. Observations A 69-year-old Japanese woman who suffered from repeated diplopia and lower-limb paresthesia was referred to our hospital. Ophthalmic findings included oculomotor nerve and contralateral abducens nerve palsies. No remarkable abnormalities were detected via enhanced brain magnetic resonance imaging (MRI), chest X-ray, and cerebrospinal fluid analysis. Chest computed tomography (CT) was performed to exclude neoplastic lesions; this revealed right hilar lymphadenopathy, and positron emission tomography MRI showed strong 18-F fluorodeoxyglucose uptake in the hilar lymph node. Biopsy of the lymph node showed non-caseating epithelioid granulomatous tissue, leading to a diagnosis of probable neurosarcoidosis. After the initiation of oral prednisolone treatment, the patient experienced complete remission without any recurrence. Conclusions and importance When examining a patient presenting with multiple cranial neuropathies of unknown cause, neurosarcoidosis should be considered as a differential diagnosis and chest CT should be performed even when the chest X-ray and angiotensin-converting enzyme appears normal.

Purpose We compared the 1-year outcomes and early surgery-related complications between 1-quadrant and 2-quadrant microhook ab interno trabeculotomy (TLO). Methods Medical chart extraction was performed on 47 consecutive patients with 1-quadrant incision and 37 consecutive patients with 2-quadrant incision of trabecular meshwork. Logistic regression analysis was conducted to calculate the propensity score to create a 1:1 match for a comparative analysis of 1-year postoperative success. Success was defined as postoperative intraocular pressure (IOP) between 5-21 mmHg, >20% IOP reduction from baseline, and no additional glaucoma surgery. Outcome-related covariates were age, glaucoma type, mean deviation of visual field tests, preoperative IOP, the number of preoperative glaucoma eye drops and the presence of combined cataract surgery. Thirty eyes from each group were compared. Results The median preoperative IOP was not different between the 1-quadrant and 2-quadrant groups (28.5 mmHg, quartile range 23-33.5 versus 27 mmHg, 23.3-30.0, p = 0.47). There was no difference in median postoperative IOP at 1 year (15 mmHg versus 16 mmHg, p = 0.80). The success rate was 73% in the 1-quadrant group versus 70% in the 2-quadrant group (p = 1.00). The 2-quadrant group had a significantly higher proportion of patients with transiently elevated IOP (47%) than the 1-quadrant (17%; Fisher's exact test, p = 0.02). There was no difference of hyphema formation (Fisher's exact test, p = 0.18). Conclusion The 1-year success rate was not significantly different between 1- and 2-quadrant incisions of microhook TLO. However, the 2-quadrant TLO showed significantly higher proportion of post-surgical transient IOP elevation.

Purpose: To present a unique case of neuro-neutrophilic disease with inflammation and thrombosis of the superior ophthalmic vein (SOV). Observations: A 43-year-old Japanese man with past histories of oculomotor paralysis, auditory disorder, ischemic enteritis, and recurrent oral ulceration was referred to our hospital because of blurred vision in his right eye. Ophthalmic examination revealed decreased best corrected visual acuity and central scotoma in his right eye. Orbit magnetic resonance imaging (MRI) revealed an enlarged SOV in the right eye, with Gadolinium (Gd) enhancement in the wall of the vein but not inside the vein, indicating thrombosis. Multiple Gd-enhanced hyperintense lesions were also observed in the juxtacortical area of the brain. We diagnosed the patient with vasculitis in the right SOV that was adversely affecting the optic nerve. We ruled out systemic thrombophilia, infections, and malignancy by systemic examinations. The human leukocyte antigen (HLA) typing was Cw1-, B54-, B61-, A2-, A24-, and DR4-positive and B51-negative. We treated the patient with systemic steroid and anticoagulant therapy. After three courses of steroid pulse therapy, his symptoms and the MRI findings of the right SOV and brain improved; therefore, we decided to discontinue the anticoagulant therapy. One month after anticoagulant cessation, MRI revealed recurrence of the thrombus and enlargement of the right SOV despite the lack of vision worsening. We restarted the anticoagulant therapy while continuing the oral prednisolone treatment. At the final visit, 14 months after the onset of the disease, the patient was still receiving oral anticoagulation with warfarin potassium and prednisolone (5 mg/day). His symptoms and the right eye's visual function remained normal with a mildly enlarged SOV; there was less Gd enhancement and no brain lesions on MRI. Conclusions and importance: We treated a unique case of possible neuro-neutrophilic disease that presented visual disturbances due to right SOV inflammation and thrombosis. Anticoagulation and systemic steroid therapies were required to reduce the inflammation and to prevent the recurrence of thrombosis. Keywords: Neuro-neutrophilic disease, Neuro-Sweet disease, Neuro-Behçet disease, Thrombosis, Human leukocyte antigen

Background: Recent immune therapy with checkpoint inhibitors (CPIs) has demonstrated remarkable antitumor effects on specific tumors, such as malignant lymphoma and non-small cell lung carcinoma. By contrast, CPIs cause an imbalance in the immune system, triggering a wide range of immunological side effects termed immune-related adverse effects (irAEs). Here, we report a rare case of optic neuritis and hypopituitarism during anti-programmed death-ligand 1 (PD-L1) antibody treatment. Case Presentation: A patient with non-small cell lung carcinoma received anti-PD-L1 antibody treatment every 3 weeks; however, the patient started experiencing headaches, general fatigue, anorexia, and diarrhea approximately 1 year after the initiation of the treatment. Moreover, sudden visual loss of the right eye occurred 1 week after the interruption of the anti-PD-L1 antibody treatment. MRI findings showed gadolinium enhancement in the left optic nerve, but no enlargement of the pituitary gland and stalk. Laboratory data showed decreased serum adrenocorticotropic hormone (ACTH), cortisol, and free T4 levels, and a hormone tolerance test indicated hypopituitarism, hypothyroidism, and hypoadrenocorticism. The central scotoma caused by optic neuritis completely disappeared immediately after a course of steroid pulse therapy, and no recurrence occurred up to 2 years after initiation of the steroid pulse therapy while replacement therapy for hypothyroidism and hypoadrenocorticism was continued. Conclusions: The patient presented with optic neuritis and hypopituitarism, possibly due to irAEs of the anti-PD-L1 antibody treatment. Steroid pulse therapy was effective for optic neuritis, suggesting underlying immunological mechanisms. Neurological complications including optic neuritis should be considered when examining patients with cancer undergoing CPI treatment.

Background In previous retrospective studies, we identified the 50 most influential clinical predictors of cardiovascular outcomes in patients with heart failure (HF). The present study aimed to use the novel limitless-arity multiple-testing procedure to filter these 50 clinical factors and thus yield combinations of no more than four factors that could potentially predict the onset of cardiovascular events. A Kaplan–Meier analysis was used to investigate the importance of the combinations. Methods In a multi-centre observational trial, we prospectively enrolled 213 patients with HF who were hospitalized because of exacerbation, discharged according to HF treatment guidelines and observed to monitor cardiovascular events. After the observation period, we stratified patients according to whether they experienced cardiovascular events (rehospitalisation or cardiovascular death). Findings Among 77,562 combinations of fewer than five clinical parameters, we identified 151 combinations that could potentially explain the occurrence of cardiovascular events. Of these, 145 combinations included the use of inotropic agents, whereas the remaining 6 included the use of diuretics without bradycardia or tachycardia, suggesting that the high probability of cardiovascular events is exclusively determined by these two clinical factors. Importantly, Kaplan–Meier curves demonstrated that the use of inotropes or of diuretics without bradycardia or tachycardia were independent predictors of a markedly worse cardiovascular prognosis. Interpretation Patients treated with either inotropic agents or diuretics without bradycardia or tachycardia were at a higher risk of cardiovascular events. The uses of these drugs, regardless of heart rate, are the strongest clinical predictors of cardiovascular events in patients with HF.

The purpose of this study was to evaluate the surgical success of sulcus fixation of Baerveldt glaucoma implant (BGIs) in special reference to corneal damage.This observational prospective cohort study included 24 patients who underwent a median of 3.0 previous intraocular surgeries and sulcus fixation of BGIs for the first time. The intraocular pressure (IOP), the number of ocular hypotensives used, corneal endothelial cell density (ECD), and logMAR-converted best-corrected visual acuity (VA) of each patient were measured preoperatively and postoperatively until 12 months after surgery. Surgical success was evaluated after 12 months based on the reduction of IOP (5-21 mmHg and 20% reduction), corneal damage (postoperative development of decompensation, unmeasurable ECD, or ECD reduction of 20%), loss of light perception, and need for additional surgeries.Surgical success was noted in 16 (66.7%) patients when corneal damage was included as a failure criterion, whereas surgery was successful in 21 (87.5%) patients when solely judged using IOP control similarly as previous clinical trials. The median IOP decreased from 27.5 mmHg preoperatively to 14.5 mmHg postoperatively (P 0.0001). The number of ocular hypotensives was significantly reduced postoperatively (P 0.0001). The median postoperative ECD reduction was only 0.15%, although ECD could not be measured during follow-up or it was significantly reduced by 20% in six patients. VA was not significantly reduced after surgery. Adverse effects were observed in 15 patients (62.5 cumulative %).Sulcus fixation of BGIs may be effective and safe in patients with glaucomatous eyes who underwent multiple prior intraocular surgeries.

Purpose Cytomegalovirus (CMV)-related keratouveitis elevates intraocular pressure (IOP). Antiviral therapy does not always control IOP and some patients do not tolerate systemic antiviral therapy because of the side effects. The purpose of this study is to evaluate the clinical characteristics of patients with CMV-related keratouveitis and determine the impact of glaucoma surgeries on the postoperative antiviral therapy regimen. Methods We enrolled twenty-two patients with CMV-DNA-positive keratouveitis between June 2012 and July 2019 in Kobe University Hospital. The following clinical parameters were collected: gender, age, history of previous intraocular surgery, antiviral medications, visual acuity, IOP, glaucoma drug score, corneal endothelial cells density, and the mean deviation of a Humphrey visual field test at the first visit and before and 1 year after glaucoma surgery. Results All twenty-two patients started on oral and/or topical antiviral therapy. Eighteen patients needed glaucoma surgery despite their antiviral medications. Nine patients underwent trabeculotomy (TLO) and nine underwent trabeculectomy (TLE) as the first surgical intervention. Six of patients who initially underwent TLO and two of the patients who initially underwent TLE required additional TLE within 1 year. Each of the 15 patients who underwent at least 1 TLE showed a reduction in the magnitude and variation of IOP and glaucoma drug scores and 13 patients were able to discontinue antiviral therapy. For the remaining 4 patients, IOP and inflammation were controlled but with antiviral medications. Conclusions In patients with CMV-related keratouveitis, TLE decreases and stabilizes IOP and contributes to withdrawal from antiviral medications.

IntroductionLeber hereditary optic neuropathy (LHON) is an acute or subacute inherited optic neuropathy caused by mitochondrial mutations. More than 90% of patients with LHON have one of three point mutations (ie, G3460A, G11778A and T14484C). We previously reported that a 12-week session of skin electrical stimulation (SES) with a 2-week interval significantly improved visual acuity and field tests 1 week after the last stimulation and without adverse effects in 10 cases of LHON carrying the mt DNA G11778A mutation. In the present study, we will examine the magnitude and persistence of the efficacy and presence or absence of adverse events using SES with a more frequent stimulation protocol.Methods and analysisThis study will be a single-arm, open-labelled, non-randomised clinical study that analyses 15 cases of LHON with G11778A mutation. All participants will take a portable SES device home and perform SES by themselves every other day for 12 weeks. The logarithm for the minimum angle of resolution (logMAR) best-corrected visual acuity (BCVA) at 1 week after the last SES will be measured as the primary outcome. LogMAR BCVA will be measured at four and 8 weeks after the last SES treatment. The Humphrey visual field sensitivity test using size V stimulation and critical fusion frequency at 1, 4 and 8 weeks after the last SES session will be secondary outcome measurements. Slit-lamp examination, optical coherence tomography and specular microscopy will also be performed to verify the safety of SES.Ethics and disseminationThe protocol was approved by the Institutional Review Board at Kobe University, Japan (Approval No.C190030). This study is in progress and deserves Pre-result. All documents communicating with the ethics committee will be reposited by the researcher. Modifications to the protocol will be reviewed by the ethics committee and implemented after approval. Data monitoring will be performed by a researcher who is not involved in the study every 6 months after approval. The research summary results will be registered in the Japan Registry of Clinical Trials (jRCTs) and made available to participants in accordance with the terms described in the documents. In addition, the results of this study will be presented at domestic and international meetings and published in peer-reviewed journals within a year after data is fixed.Trial registration numberjRCTs052200033.

This retrospective study was conducted to investigate the clinical factors associated with low-contrast visual acuity after reduced-fluence photodynamic therapy (RFPDT) in patients with resolved central serous chorioretinopathy (CSC) and good baseline visual acuity. A total of 45 eyes of 45 patients with resolved CSC at post-RFPDT and best-corrected visual acuity of &gt, 1.0 (logarithm of the minimal angle of resolution [logMAR], 0) at baseline were examined. Visual acuities of both eyes were measured at four contrast levels (100%, 25%, 12%, and 6%) at post-RFPDT. The low-contrast visual acuity (6%, 12%, and 25%) was significantly lower than the 100% contrast visual acuity in the affected eyes. Visual acuities of affected eyes were significantly worse than those of fellow eyes at any contrast levels. The degree of changes in 6% and 100% contrast visual acuities was significantly greater in affected eyes than that in fellow eyes (p &lt, 0.05). The 6% contrast visual acuities in affected eyes at post-RFPDT were significantly associated with the symptom duration (p &lt, 0.05). Patients with a long duration of symptoms might have disturbed low-contrast visual acuities at post-RFPDT even if their baseline visual acuities were good.

Myosin and actin denaturation (0.1 M NaCl, 20 mM Tris–HCl, pH 7.5) of tilapia myofibrils (Mf) during frozen storage at −10, −20, and −40 °C was studied. Ca2+-ATPase inactivation was rapid at −10 °C but very slow at −20 and −40 °C. Myosin retained its solubility at 0.5 M NaCl even after Ca2+-ATPase inactivation. The amount of subfragment-1 generated from the Mf by chymotryptic digestion decreased with decreasing Ca2+-ATPase inactivation. The amount of rod produced in the frozen Mf remained at a high level, explaining the high salt solubility of myosin. Actin denaturation occurred in the Mf during freezer storage, as revealed by chymotrypic digestion patterns that showed a decreased actin content in the digest, and occurred much faster than Ca2+-ATPase inactivation. Analysis of tilapia meat during freezer storage revealed that Ca2+-ATPase inactivation was very slow in the frozen tissue and was ninefold slower at −10 °C than at −20, and −40 °C. Practically no actin denaturation occurred in the frozen meat. Based on these results, we conclude that native actin in frozen meat protects myosin from denaturation during the frozen storage period but that such protection by actin does not extend to Mf due to rapid actin denaturation. Consequently, the Ca2+-ATPase inactivation rate in Mf represents that of myosin itself—with no protection provided by actin. Therefore, the myosin denaturation rate obtained with Mf should not be used for frozen meat. Mf suspended in 0.1 M NaCl is not a suitable model by which to obtain the myosin denaturation rate in frozen fish meat.

Purpose. Although oral prednisolone is the first-line treatment for preventing recurrent optic neuritis (ON) after the completion of acute-phase treatment, especially anti-aquaporin 4 (AQP4) antibody-positive ON, and anti-myelin oligodendrocyte glycoprotein (MOG) antibody-positive ON, some patients experience relapses. Immunosuppressants could be effective in reducing the recurrence rate for neuromyelitis optica spectrum disorder and MOG antibody-related diseases, but there have been few studies addressing this issue focusing on the changes in ophthalmic parameters. The objective of the study was to analyze the impact of off-label uses of immunosuppressants to reduce recurrent ON. Design. Retrospective observational study, clinical case series. Methods. We reviewed the medical charts of 11 cases (22 eyes) who underwent immunosuppressive therapy in Kobe University Hospital and compared the annualized relapse rate (ARR) before and after immunosuppressive therapy. We also evaluated the dosage of prednisolone, complications of immunosuppressants, and other visual functional ophthalmologic parameters. Results. Eleven cases in total had AQP4 antibody (9 cases) and/or MOG antibody (3 cases). One case was double positive for these antibodies. Nine patients received azathioprine and two received mycophenolate mofetil as an initial immunosuppressive therapy. The median duration of immunosuppressant treatment was 2.8 years. The median ON ARR before immunosuppressive therapy was 0.33, and this decreased significantly to 0 after the therapy ( p = 0.02 ). The dose of prednisolone was reduced from 17.8 ± 7.1 mg/day before to 5.8 ± 2.2 mg/day after immunosuppressive therapy ( p < 0.01 ). Although two patients presented with mild elevation of liver enzymes and nausea, all patients were able to continue taking the immunosuppressants. Conclusions. Immunosuppressants can potentially decrease relapses and steroid dosage in patients with anti-AQP4 or MOG antibody-positive ON without severe adverse events and the exacerbation of visual acuities.

Leber hereditary optic neuropathy (LHON) is an intractable disease associated with mitochondrial DNA (mtDNA) mutations. In this preliminary, single-arm, prospective, open-label exploratory trial, we investigated the effectiveness and safety of skin electrical stimulation (SES) for cases of LHON harboring the mtDNA 11,778 mutation. Of the 11 enrolled patients, 10 completed six sessions of SES once every two weeks over a 10-week period. The primary outcome measure was the change in logarithm of the minimum angle of resolution (logMAR)-converted best-corrected visual acuity (BCVA) at one week after the last session of SES. The main secondary outcome measures were the logMAR BCVA at four and eight weeks and Humphrey visual field test sensitivities at one, four, and eight weeks. At all follow-up points, the logMAR BCVA had improved significantly from baseline (1.74 &plusmn, 0.13 at baseline, 1.66 &plusmn, 0.20 at one week, 1.65 &plusmn, 0.21 at four weeks, and 1.66 &plusmn, 0.20 at eight weeks, p &lt, 0.05). At eight weeks of follow-up, five patients showed &gt, 2-fold increase in the summed sensitivity at 52 measurement points from baseline. No adverse effects were observed. In conclusion, SES could be a viable treatment option for patients with LHON in the chronic phase harboring the mtDNA 11,778 mutation.

ObjectiveTo compare the 1-year outcomes of trabeculotomy ab externo (ab externo TLO) and trabeculotomy ab interno using a microhook (ab interno TLO) for glaucoma patients using propensity score analysis.Methods and analysisThe medical charts of 65 consecutive patients who underwent ab externo TLO and those of 69 patients who underwent ab interno TLO were reviewed. Logistic regression analysis was conducted to calculate the propensity score using 1:1 matched analysis, which indicates the likelihood of surgical success at 12 months. We set the outcome-related covariates as age, glaucoma type, mean deviation, preoperative intraocular pressure (IOP), the number of preoperative glaucoma eye drops and the presence or absence of combined cataract surgery. Fifty eyes per each surgery group were subsequently compared.ResultsThe mean preoperative IOP was 32.5±11.2 mm Hg in the ab externo TLO group and 28.4±7.8 mm Hg in the ab interno TLO group (p=0.08). The mean postoperative IOP at 12 months was 18.3±7.4 mm Hg in the former group and 17.8±6.3 mm Hg in the latter (p=0.91). When surgical success was defined as a postoperative IOP of between 5 and 21 mm Hg with a more than 20% IOP reduction from baseline and no additional glaucoma surgery, the rate at 12 months was 78% in the ab externo TLO group and 74% in the ab interno TLO group (p=1.00).ConclusionThe 1-year success rate was not significantly different between ab externo and ab interno TLO.

Purpose: To evaluate Icare® HOME for home monitoring of intraocular pressure (IOP) and to observe diurnal IOP patterns for a short term. Patients and methods: Twenty six eyes of 16 patients with open angle glaucoma were included. After instruction and practice in using Icare® HOME, patients were asked to measure their IOP by themselves at home or in a sick room. Patients measured their IOP four times a day with a four hour interval between each measurement for three days. Patients repeated measurements until three successful measurements were obtained at each time. Intra-rater reliability was assessed calculating intraclass correlation coefficient (ICC) of the three measurements. Diurnal IOP patterns were assessed for three days. Results: No adverse events occurred. ICC of three measurements was 0.76 (95% confidence coefficient; 0.71 to 0.81). The median of the difference between the highest and the lowest IOP during a day was 4.26 mmHg (95% CI; 4.06 to 4.67). Repeatable patterns were not found in diurnal IOP for three days. Three out of ten patients who answered the questionnaire after measurements found difficulties in handling the device. Conclusions: Although Icare® HOME is safe and could be used for home monitoring of IOP, some patients had difficulties in using the instrument. Diurnal IOP patterns did not show repeatability during a short term.

Purpose: To evaluate the effects of trabeculotomy (TLO) combined with Schlemm's canal endothelium removal (SER) and deep sclerectomy (DS). Method: This retrospective study involved 131 adults eyes, diagnosed with glaucoma that were enrolled with at least 1 year follow-up after TLO. Fifty three eyes received TLO+SER+DS and 78 eyes underwent TLO+DS without SER. SER was performed as peeling of Schlemm's canal endothelium opening under the scleral flap. Surgical success was defined by the need for additional glaucoma surgery, or intraocular pressure (IOP) ≤20 mmHg (criterion A) and ≤16 mmHg (criterion B). Results: The occurrence rate of transient ocular hypertension (≥30 mmHg) was significantly less (p0.001) in SER (3.8%) compared with Non-SER (21.8%). SER decreased IOP at 3 years without significant efficacy in terms of lowered IOP compared with Non-SER. At 3 years, Kaplan-Meier survival analysis revealed that the success rate of SER was higher than Non-SER for criterion A (p=0.008), but comparable for criterion B (p=0.06). Conclusions: SER was effective for reducing the rate of transient ocular hypertension in TLO and controlling IOP≤20 mmHg in adult eyes.

Since our retrospective study has formed a mathematical formula, α = f(x1, …, x252), where α is the probability of cardiovascular events in patients with heart failure (HF) and x1 is each clinical parameter, we prospectively tested the predictive capability and feasibility of the mathematical formula of cardiovascular events in HF patients. First of all, to create such a mathematical formula using limited number of the parameters to predict the cardiovascular events in HF patients, we retrospectively determined f(x) that formulates the relationship between the most influential 50 clinical parameters (x) among 252 parameters using 167 patients hospitalized due to acute HF; the nonlinear optimization could provide the formula of α = f(x1, …, x50) which fitted the probability of the actual cardiovascular events per day. Secondly, we prospectively examined the predictability of f(x) in other 213 patients using 50 clinical parameters in 3 hospitals, and we found that the Kaplan–Meier curves using actual and estimated occurrence probabilities of cardiovascular events were closely correlated. We conclude that we created a mathematical formula f(x) that precisely predicted the occurrence probability of future cardiovascular outcomes of HF patients per day. Mathematical modelling may predict the occurrence probability of cardiovascular events in HF patients.

Summary Background Diastolic dysfunction is a major cause of heart failure (HF) with a preserved ejection fraction (HFpEF); however, there is no clear strategy for treating diastolic dysfunction. Myocardial and vascular abnormalities may cause HFpEF, which indicates that correcting both abnormalities may specifically improve the severity of diastolic dysfunction. Candesartan primarily affects the myocardium, but azilsartan affects the myocardium and the aortic vasculature. This study was undertaken to test the hypothesis that azilsartan, but not candesartan, improves left ventricular (LV) diastolic dysfunction in patients with hypertension and HFpEF. Methods Among patients with HF in our database, the patients who received azilsartan or candesartan were retrospectively screened. Fifteen patients treated with azilsartan were identified, and sex-matched patients who received candesartan were blindly selected. Results At baseline, there were no significant differences between the two groups in clinical findings, echocardiographic parameters, and plasma brain natriuretic peptide levels. At 3–6 months, blood pressure decreased to similar levels in both groups. However, the early LV filling velocity/early diastolic velocity (E/e′) ratio decreased in the azilsartan group (13.0 ± 4.2 vs. 10.9 ± 3.2, p = 0.03), but remained unchanged in the candesartan group (12.0 ± 3.6 vs. 12.5 ± 5.0, p = 0.58; for interaction, p = 0.04). Other echocardiographic parameters were unaltered by azilsartan or candesartan. Conclusion Azilsartan improves diastolic function in HF patients with hypertension, and it may be the preferred option over other angiotensin II receptor blockers in patients with HFpEF.

Purpose: To assess the combined estimate of retinal ganglion cell (RGC) count developed by Medeiros et al. as a tool for diagnosis of glaucoma in Japanese patients. Study design: Cross-sectional study. Methods: Thirty-one eyes of 19 healthy controls and 106 eyes of 70 glaucoma patients underwent standard automated perimetry (SAP) and three types of spectral domain optical coherence tomography (SD-OCT) imaging using the Cirrus, RTVue, and 3D-OCT instruments. RGC counts derived from SAP and SD-OCT data were estimated using the Harwerth model (SAPrgc and OCTrgc, respectively), from which the combined RGC count estimates (CRGC) were calculated using the formula developed by Medeiros et al. Receiver operating characteristic curve (ROC) analyses were conducted for mean deviation (MD), retinal nerve fiber layer thickness (RNFLT), and CRGC. Results: The mean OCTrgc derived from the Cirrus, RTVue, and 3D-OCT instruments were 1150, 1245, and 1316 (x1000 cells), respectively, for the control group and 463, 519, and 516 (x1000 cells), respectively, for the patient group. SAPrgc of the controls’group was 1526 and the patients’group, 731 (x1000 cells), and were consistently greater than OCTrgc in both groups (a generalized estimating equation model, p < 0.001). Partial area under the curve (pAUC) of MD was 0.178, and that of RNFLT and CRGC for the three OCT instruments were 0.185, 0.18, 0.189 and 0.196, 0.196, 0.197, respectively. CRGC had larger pAUC than MD, whereas there was no or marginal difference in pAUC between CRGC and cpRNFLT, irrespective of OCT device used or glaucoma severity. Conclusion: CRGC proved well suited to discriminate glaucoma patients from controls. However, its clinical utility did not seem to overwhelm isolated structural measures in the tested Japanese patients.

Both chronic heart failure (CHF) and cancer are among the most frequent causes of death in developed countries. Given that CHF activates neurohumoral factors, such as cytokines, the pathophysiology of CHF could prime the onset or progression of cancer. We consecutively enrolled 5238 patients with CHF who had been hospitalized in the Department of Cardiovascular Medicine in our institute between 2001 and 2013. We followed these patients until April 2015. We examined the cohort of patients from our hospital and compared it with a control cohort derived from the 2008 cancer database 'Monitoring of Cancer Incidence in Japan' from the National Cancer Center, Japan. The incidence of cancer in CHF patients (198 cases out of the 5238 patients) was approximately four times higher than that in control patients (2.27% vs 0.59%, P