New method to differentiate between lupus anticoagulants, progressive coagulation inhibitors and coagulation factor deficiencies in the mixing tests.

INTRODUCTION: Mixing tests in activated partial thromboplastin time (APTT) are used for the differentiation between lupus anticoagulants (LA), coagulation inhibitors, and factor deficient samples with APTT prolongation. However, the indexes for the differentiation have not been established. The present study aimed to develop new mixing test indexes for the differentiation. METHODS: Twenty-six LA-positive, 8 progressive coagulation factor VIII inhibitor, and 35 coagulation deficient samples were employed. APTT were measured for normal plasma, patient plasma, and mixing plasma prepared at a ratio of 1:1 proportion in both without incubation and 2 h-incubation. New two parameters named as ALD50 and mixture plasma-patient plasma after Warming change rate Subtraction (WaS) calculated from the clotting times of normal, 1:1 mixing and patient samples with/without 2 h-incubation were established. In the samples with WaS result of <10.2%, ALD50 of ≥87.8%, and < 87.8% were defined as LA and coagulation factor deficiency, respectively, and WaS of ≥10.2% defined progressive coagulation factor inhibitors. RESULTS: Sensitivity and specificity to LA were 80.8% and 93.0% for ALD50, and sensitivity and specificity to progressive coagulation factor inhibitor were 100.0% and 100.0% for WaS, respectively. The agreement between sample classification and WaS-ALD50 was 88.4% (61/69). CONCLUSIONS: ALD50 and WaS showed acceptable sensitivity and specificity to LA and progressive coagulation factor inhibitor, respectively. These indexes would be useful for the differentiation between LA, factor deficiency, and progressive coagulation factor inhibitor in the mixing tests.

Simultaneous evaluation of brain metastasis and thoracic cancer using semiconductor 11C-methionine PET/CT imaging.

OBJECTIVE: To investigate the potential of whole-body digital 11C-methionine (MET) PET/CT imaging for simultaneous evaluation of thoracic cancer patients suspected of local recurrence (LR) after stereotactic radiosurgery (SRS) for brain metastasis. METHODS: A total of 45 lung or breast cancer patients suspected of LR after SRS were investigated using brain and whole-body MET-PET/CT scans. We compared the tumor-to-normal ratio (TNR) and maximum standardized uptake values (SUVmax) between patients with LR and radiation necrosis (RN) and performed receiver operating characteristic (ROC) analyses. We also investigated associations among extracranial recurrence, intracranial recurrence, primary site, and initial treatment type. RESULTS: A total of 44 LR and 14 RN lesions were analyzed. In the ROC analyses for differentiating LR from RN, TNR showed higher area under the curve (AUC) (0.82) than SUVmax (0.79), and the cutoff TNR value (2.12) was higher than current cutoff values of conventional PET systems. The whole-body scans detected extracranial recurrences in 31.1% of the patients. Recurrence rates were not significantly correlated with existence of intracranial recurrence or primary site, but patients who underwent non-surgical treatment (consisting of stage III/ IV patients according to the Union for International Cancer Control TNM classification or small-cell lung cancer patients) showed significantly higher recurrence than the surgically treated patients (68.8% vs. 10.3%, p = 0.0001). CONCLUSION: In digital MET-PET/CT imaging, TNR was a more useful parameter to differentiate LR from RN than SUVmax, and the cutoff value was higher than those with conventional PET systems. Additional whole-body scans could detect extracranial recurrence and would be especially useful for advanced thoracic cancer patients who underwent non-surgical treatment.

Potentially compromised systemic and local lactate metabolic balance in glaucoma, which could increase retinal glucose and glutamate concentrations.

To investigate the association between lactate metabolism and glaucoma, we conducted a multi-institutional cross-sectional clinical study and a retinal metabolomic analysis of mice with elevated intraocular pressure (IOP) induced by intracameral microbead injection. We compared lactate concentrations in serum and aqueous humor in age-matched 64 patients each with primary open-angle glaucoma (POAG) and cataract. Neither serum nor aqueous humor lactate concentrations differed between the two groups. Multiple regression analysis revealed that only body mass index showed a significant positive correlation with serum and aqueous humor lactate concentration in POAG patients (rs = 0.376, P = 0.002, and rs = 0.333, P = 0.007, respectively), but not in cataract patients. L-Lactic acid was one of the most abundantly detected metabolites in mouse retinas with gas chromatography and mass spectrometry, but there were no significant differences among control, 2-week, and 4-week IOP elevation groups. After 4 weeks of elevated IOP, D-glucose and L-glutamic acid ranked as the top two for a change in raised concentration, roughly sevenfold and threefold, respectively (ANOVA, P = 0.004; Tukey-Kramer, P < 0.05). Glaucoma may disrupt the systemic and intraocular lactate metabolic homeostasis, with a compensatory rise in glucose and glutamate in the retina.

FIVE-YEAR VISUAL OUTCOME OF TREATMENT FOR RETINOPATHY OF PREMATURITY IN INFANTS WEIGHING <500 G AT BIRTH: A Multicenter Cohort Study From J-CREST.

PURPOSE: To investigate the 5-year treatment outcomes of retinopathy of prematurity in infants <500 g birth weight and compare laser and anti-vascular endothelial growth factor therapies. METHODS: A multicenter retrospective study comprised 24 eyes of 13 patients treated for Type 1 retinopathy of prematurity, followed for 5 years. Initial treatment was laser and anti-vascular endothelial growth factor in 13 and 11 eyes, respectively. Data collected included sex, birth characteristics, retinopathy of prematurity characteristics at the time of treatment, best-corrected visual acuity (BCVA), spherical equivalent, and astigmatism at 5 years posttreatment. RESULTS: Median BCVA was 0.15 logarithm of the minimum angle of resolution (interquartile range, 0.0-0.5). Snellen BCVA was ≥20/40 in 73% and ≥20/20 in 27% of eyes. Median spherical equivalent was -2.37 (interquartile range, -6.1 to -0.1); 75% had myopia (≤-0.5 D), and 25% had high myopia (≤-6.0 D). Median astigmatism was 1.25 (interquartile range, 0.9-3.0); 46% had ≥1.5 D. Anti-vascular endothelial growth factor-treated eyes showed less myopia ( P < 0.009), with no BCVA or astigmatism difference ( P = 0.997, P = 0.271) compared with laser-treated eyes. CONCLUSION: One-quarter of the eyes exhibited good visual acuity (Snellen BCVA of ≥20/20) 5 years after retinopathy of prematurity treatment. Refractive errors were common. Anti-vascular endothelial growth factor therapy may be superior to laser therapy in myopic refractive error.

Correlation between Residual Sensitivity in the Central Inferior Nasal Visual Field and Visual Function in Chronic Leber Hereditary Optic Neuropathy Patients.

INTRODUCTION: Leber hereditary optic neuropathy (LHON) is a maternally inherited, acute or subacute, optic neuropathy. The typical symptoms include reduced visual acuity and central scotoma. Despite the presence of deep central scotoma, some patients with LHON are able to perform daily activities. This study aimed to investigate the correlation between the residual visual field and visual acuity, critical flicker frequency, and fixation ellipse in patients with chronic LHON. METHODS: Residual visual function (defined as sensitivity points where patients sensed the size V stimulus) of both eyes was evaluated in 10 patients with LHON carrying the m.11778 mitochondrial DNA mutation and with median age of onset and disease duration of 29 and 16.5 years, respectively. The central visual field was measured as static perimetry using the Humphrey visual field testing 30-2 program with the size III or V stimulus. Moreover, best-corrected visual acuity, critical flicker frequency, and the correlation between fixation ellipse and residual central visual fields were determined. The analysis was performed through a linear mixed-effects model. RESULTS: The residual visual sensitivity in the inferior nasal visual field was significantly correlated with the logMAR (p < 0.05). The fixation ellipse fell within the residual visual field region with higher sensitivity. CONCLUSIONS: Patients with chronic LHON tended to retain the sensitivity detectable with the size V stimulus at the central inferior nasal visual field regions, where the fixation ellipse fell. Visual acuity, which influences daily activity, was spatially correlated with residual visual sensitivity.

Impact of glaucoma medications on subsequent Schlemm's canal surgery outcome: Cox proportional hazard model and propensity score-matched analysis.

PURPOSE: The impact of various preoperative glaucoma medications on Schlemm's canal surgery outcomes remains unclear. This study aimed to investigate the impact of preoperative glaucoma medications on the postoperative 1-year outcomes of µTLO. METHODS: We analyzed the medical records of 218 patients who underwent their first µTLO to investigate the 1-year postoperative outcomes. Cox proportional hazard regression analysis was performed with surgical failure as the dependent variable and each type of preoperative medication as the independent variable. We also compared the 1-year outcomes of µTLO between users and non-users of specific medications using propensity score matching. Surgical success was defined as a postoperative intraocular pressure ranging from 5 to 21 mmHg, a ≥20% reduction in IOP from baseline, and no additional glaucoma surgery within 1 year postoperatively. RESULTS: The Cox proportional hazard analysis showed that all drugs that do not increase the conventional outflow exhibited hazard ratios greater than 1.0, and the preoperative use of ß-blockers and oral CAI was a significant surgical risk factor (hazard ratio: 2.65 and 2.45, p = 0.04 and <0.001). In the propensity score matching analysis, success rates at 1 year postoperatively were 55/85, 54/79, 60/73, and 40/76% for users/non-users of ß-blockers, topical CAIs, an alpha-2 adrenergic agonist, and an oral CAI, respectively. Kaplan-Meier survival curves in these comparisons also demonstrated that preoperative ß-blockers and oral CAI use were significant surgical risks (p = 0.01, <0.001). CONCLUSION: Our study suggests that preoperative medications that do not involve conventional pathway outflow have a detrimental effect on subsequent Schlemm's canal surgery outcomes.

Factors influencing postoperative bleeding after dental extraction in older adult patients receiving anticoagulation therapy.

OBJECTIVES: To investigate factors influencing postoperative bleeding occurrence after dental extraction in older patients receiving anticoagulation therapy. MATERIALS AND METHODS: This retrospective study included patients aged ≥ 65 years receiving one of the following anticoagulants: apixaban, edoxaban, rivaroxaban, and warfarin. Patients who underwent one to multiple tooth extractions in the geriatric dentistry clinic at Tokyo Medical and Dental University Hospital between August 1, 2016, and November 30, 2020, were included. The outcome variable was postoperative bleeding occurrence. Logistic regression analysis was performed with the following ten factors as explanatory variables: age, sex, maximum systolic blood pressure during the extraction, type of local anesthesia, vertical incision, osteotomy, usage of surgical splints, the mesiodistal width of the extracted tooth on a radiograph, use of antiplatelet agents, and history of diabetes requiring medication. RESULTS: Among 395 participants (mean age, 82.3 ± 6.5 years) included in this study, 75 patients experienced postoperative bleeding after tooth extraction. Logistic regression analysis revealed that the odds ratios for the vertical incision (18.400, p < 0.001), osteotomy (3.630, p = 0.00558), usage of surgical splints (1.860, p = 0.0395), and the mesiodistal width of the extracted tooth on a radiograph (1.060, p = 0.0261) were statistically significant. CONCLUSIONS: For dental extraction in older patients receiving anticoagulants, postoperative bleeding is more likely to occur in patients with vertical incision, osteotomy, and posterior or multiple tooth extractions. CLINICAL RELEVANCE: Dentists should consider suturing and adjunctive hemostatic procedures for patients undergoing vertical incision, osteotomy, and multiple tooth extractions while receiving anticoagulation therapy to minimize the risk of postoperative bleeding.

Test-retest repeatability of the imo binocular random single-eye test and Humphrey monocular test in patients with glaucoma.

PURPOSE: To evaluate the reproducibility of the imo binocular random single-eye test (BRSET) and Humphrey Field Analyzer (HFA) monocular test in patients with glaucoma. STUDY DESIGN: Retrospective observational study. METHODS: We measured the visual fields (VF) of patients with glaucoma using the BRSET and HFA. All tests were repeated two months later. Mean sensitivity (MS), mean deviation (MD), sensitivity at each test location, and reliability indices were compared between the test days. Wilcoxon signed-rank test, interclass correlation coefficient (ICC), correlation coefficients, and Bland-Altman plots were generated for analysis. RESULTS: We analyzed the VFs of 46 patients with glaucoma. There were no test-retest differences for MS and MD, and ICCs were > 0.9 for MS and MD in both perimeters. Inter-test correlations for MS and MD were high. The limits of agreement (LoAs) (lower, upper limit) between test days for MS were (- 3.4, 4.0) for BRSET and (-3.3, 3.0) for HFA. The LoA for MD was (- 3.3, 3.8) for BRSET and (- 3.2, 2.9) for HFA. Sensitivity at each testing location was more variable between testing days for BRSET than for HFA. For reliability indices, LoAs between testing days were wider for BRSET than for HFA. CONCLUSION: The imo BRSET showed similar reproducibility to HFA in MS and MD. However, sensitivity at each test location varied more for BRSET than for HFA. Further studies are needed to verify the reproducibility of the imo BRSET.

The Landscape of MYB/MYBL1- and Peri-MYB/MYBL1-Associated Rearrangements in Adenoid Cystic Carcinoma.

Approximately 60% of adenoid cystic carcinoma (AdCC) cases are positive for MYB::NFIB or MYBL1::NFIB, whereas MYB/MYBL1 oncoprotein, a key driver of AdCC, is overexpressed in most cases. Juxtaposition of superenhancer regions in NFIB and other genes into the MYB/MYBL1 locus is an attractive oncogenic hypothesis for AdCC cases, either negative or positive for MYB/MYBL1::NFIB. However, evidence supporting this hypothesis is insufficient. We examined 160 salivary AdCC cases for rearrangements in MYB/MYBL1 loci and peri-MYB/MYBL1 areas (centromeric and telomeric areas of 10 Mb each) using formalin-fixed, paraffin-embedded tumor sections. For the detection of the rearrangements, we employed conventional fluorescence in situ hybridization split and fusion assays and a 5 Mb fluorescence in situ hybridization split assay. The latter is a novel assay that enabled us to detect any possible splits within a 5 Mb distance of a chromosome. We found MYB/MYBL1- and peri-MYB/MYBL1-associated rearrangements in 149/160 patients (93%). AdCC cases positive for rearrangements in MYB, MYBL1, the peri-MYB area, and the peri-MYBL1 area numbered 105 (66%), 20 (13%), 19 (12%), and 5 (3%), respectively. In 24 peri-MYB/MYBL1 rearrangement-positive cases, 14 (58%) were found to have a juxtaposition of the NFIB or RAD51B locus into the MYB/MYBL1 loci. On comparing with a tumor group positive for MYB::NFIB, a hallmark of AdCC, other genetically classified tumor groups had similar features of overexpression of the MYB transcript and MYB oncoprotein as detected by semiquantitative RT-qPCR and immunohistochemistry, respectively. In addition, clinicopathological and prognostic features were similar among these groups. Our study suggests that peri-MYB/MYBL1 rearrangements may be a frequent event in AdCC and may result in biological and clinicopathological consequences comparable to MYB/MYBL1 rearrangements. The landscape of MYB/MYBL1 and peri-MYB/MYBL1 rearrangements shown here strongly suggests that juxtaposition of superenhancers into MYB/MYBL1 or peri-MYB/MYBL1 loci is an alteration that acts as a key driver for AdCC oncogenesis and may unify MYB/MYBL1 rearrangement-positive and negative cases.

Randomized Multicenter Clinical Trial Comparing 0.1% Brimonidine/0.5% Timolol Versus 1% Dorzolamide/0.5% Timolol as Adjuncts to Prostaglandin Analogues: Aibeta Crossover Study.

INTRODUCTION: This multicenter, randomized, comparative, and investigator-masked crossover clinical trial sought to compare the efficacy and tolerability of fixed combinations of 0.1% brimonidine/0.5% timolol (BTFC) versus 1% dorzolamide/0.5% timolol (DTFC) as adjunctive therapies to prostaglandin analogues. METHODS: A total of 110 patients with open-angle glaucoma or ocular hypertension previously treated with prostaglandin analogue monotherapy were randomized to receive either BTFC or DTFC as adjunctive therapy for 8 weeks. These patients were then crossed over to the alternative treatment arm for another 8 weeks. The reduction in intraocular pressure (IOP) (primary outcome), occurrence of adverse events, ocular discomfort after instillation, and patient preference (secondary outcomes) were recorded through patient interviews. RESULTS: BTFC instillation for 8 weeks reduced IOP by 3.55 mmHg, demonstrating non-inferiority to DTFC instillation (3.60 mmHg; P < 0.0001, mixed-effects model). Although adverse events were rare with both combinations, patients reported greater discomfort with DTFC than with BTFC (P < 0.0001). More patients preferred BTFC (P < 0.0001) over DTFC, as BTFC caused minimal or no eye irritation. CONCLUSION: As BTFC offered better tolerability than DTFC with comparable reduction in IOP, we recommend it as an alternative for patients who experience ocular discomfort with DTFC-prostaglandin analogue combination therapy. TRIAL REGISTRATION NUMBER: jRCTs051190125.

Patients with glaucoma who require further reduction in intraocular pressure while undergoing monotherapy with prostaglandin analogue ophthalmic solution have been prescribed two enhanced treatment options: 0.1% brimonidine/0.5% timolol fixed combination ophthalmic solution (BTFC) and 1% dorzolamide/0.5% timolol fixed combination ophthalmic solution (DTFC). The Aibeta Crossover Study Group in Japan compared the efficacy and tolerability of fixed combinations of BTFC versus DTFC when an additional fixed combination ophthalmic solution was prescribed in patients with open-angle glaucoma or ocular hypertension who had been treated with prostaglandin analogue monotherapy. We recruited 110 patients previously treated with prostaglandin analogue monotherapy at 20 clinical centers in Japan, then randomly assigned them to two alternative treatment groups: the BTFC to DTFC group or the DTFC to BTFC group, as an adjunctive therapy to prostaglandin analogues for total of 16 weeks. We compared the reduction in intraocular pressure, occurrence of side effects, eye discomfort after instillation, and patient preference between BTFC versus DTFC instillations. The intraocular pressure reduction of BTFC instillation was comparable to that of DTFC instillation, showing non-inferiority to DTFC (3.55 mmHg vs. 3.60 mmHg; P < 0.0001, mixed-effects model). Both eye drops caused few side effects; however, patients felt greater eye discomfort with DTFC than with BTFC (P < 0.0001). Because of less eye irritation, more patients preferred BTFC (P < 0.0001) over DTFC. We can recommend using BTFC for patients who feel eye discomfort with DTFC­prostaglandin analogue combination therapy.

Detection of Relative Afferent Pupillary Defect and Its Correlation with Structural and Functional Asymmetry in Patients with Glaucoma Using Hitomiru, a Novel Hand-Held Pupillometer.

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.

Comparison of long-term treatment outcomes of laser and anti-VEGF therapy in retinopathy of prematurity: a multicentre study from J-CREST group.

OBJECTIVES: To compare real-world, long-term outcomes of laser and anti-vascular endothelial growth factor (VEGF) therapies in patients with retinopathy of prematurity (ROP). METHODS: This was a multicentre retrospective study. We included 264 eyes of 139 patients treated for type 1 ROP or aggressive ROP (AROP) who were followed for at least 4 years. Laser treatment was initially performed in 187 eyes (the laser group), and anti-VEGF therapy was initially performed in 77 eyes (the anti-VEGF group). We collected data on sex, birth characteristics, zone, stage, and the presence of plus disease at the time of treatment and best-corrected visual acuity (BCVA), spherical equivalent (SE), and ocular complications (amblyopia and strabismus) in patients aged 4-6 years. We investigated the associations between treatment outcomes (BCVA, SE and the presence of amblyopia and strabismus) and influencing factors, including treatment procedure (anti-VEGF or laser therapy), sex, birth characteristics, zone, stage, and the presence of plus disease, using multivariable analysis and logistic regression analyses. RESULTS: The initial treatment procedure was not associated with any specific treatment outcome. Subgroup analysis of patients with zone I ROP revealed that the anti-VEGF-treated eyes had significantly better BCVA and higher SE than laser-treated eyes (p = 0.004, p = 0.009, respectively). Female patients presented significantly better BCVA, less amblyopia and less strabismus than male patients (p < 0.001, p = 0.029, p = 0.008, respectively). CONCLUSIONS: In zone I ROP, anti-VEGF therapy led to better visual acuity and less myopic refractive error than laser treatment.

Favorable effect of ripasudil use on surgical outcomes of microhook ab interno trabeculotomy.

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.

Fully Digital Workflow for the Fabrication of Three-Dimensionally Printed Surgical Splints for Preventing Postoperative Bleeding: A Case Report.

The management of postoperative bleeding is mandatory in patients receiving anticoagulants. In this case report, we introduce a fully digital workflow for surgical splint fabrication to prevent postoperative bleeding in patients receiving anticoagulants and/or at risk of inadvertent extraction of a mobile tooth during impression making. An 87-year-old woman using apixaban had a left mandibular canine that required extraction due to chronic apical periodontitis. A digital impression was obtained using an intraoral scanner. First, the tooth to be extracted was deleted using three-dimensional (3D) computer-aided design (CAD) software (Geomagic Freeform, 3D Systems) and a stereolithography (STL) file was exported. This modified STL file was imported into another CAD software (3Shape Dental System, 3Shape) and a surgical splint was designed. The splint was fabricated using a 3D printer (Form 3; Formlabs) and light-curable resin (Dental LT Clear, Formlabs) and was delivered after the tooth extraction. The patient was followed-up 2 days after the extraction; no postoperative bleeding was detected and the surgical splint was removed. The additively manufactured surgical splint fabricated using a fully digital workflow was efficacious for managing postoperative bleeding after a dental extraction.

Incidence of Leber hereditary optic neuropathy in 2019 in Japan: a second nationwide questionnaire survey.

BACKGROUND: Leber hereditary optic neuropathy (LHON) is an acute or subacute optic neuropathy that mainly affects young males. The first nationwide epidemiological survey of LHON was conducted in 2014 in Japan, and LHON was officially designated as a rare intractable disease by the Japanese government in 2015. We conducted a second survey of the annual incidence of LHON in 2019, and estimated the total number of patients with LHON in Japan. RESULTS: A questionnaire was sent to 997 facilities accredited by the Japanese Ophthalmological Society and/or affiliated with the councilors of the Japanese Neuro-Ophthalmology Society. Responses were received from 791 facilities, with a response rate of 79%. Fifty-five newly diagnosed cases (49 males and 6 females) of LHON were reported from 35 institutions in 2019, with a median age of 28.5 for males and 49.5 years for females. The total number of newly diagnosed cases was calculated as 69 (62 were males and 7 were females, 95% confidence interval 55-83), and the total number of patients was estimated to be 2491 (95% confidence interval: 1996-2986), suggesting a prevalence of LHON in Japan of 1:50,000. CONCLUSION: The incidence of LHON in 2019 was lower than the estimate in 2014, whereas its prevalence may be similar to that reported in other countries. The accurate estimation of the incidence and prevalence of patients with LHON requires prospective registration.

Risk of surgical failure and hemorrhagic complications associated with antithrombotic medication in glaucoma surgery.

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.

The implicated clinical factors for outcomes in 304 patients with salivary duct carcinoma: Multi-institutional retrospective analysis in Japan.

BACKGROUND: Salivary duct carcinoma (SDC) is a high-grade salivary malignancy that frequently occurs as the carcinomatous component of carcinoma ex pleomorphic adenoma. We herein examined the clinical factors affecting outcomes in a large cohort of SDC. METHODS: We selected 304 SDC cases and investigated clinical characteristics and the factors affecting outcomes. RESULTS: The median age of the cases examined was 68 years, the most common primary site was the parotid gland (238 cases), and there was a male predominance (M/F = 5:1). Outcomes were significantly worse when the primary tumor site was the minor salivary glands (SG) than when it was the major SG. Outcomes were also significantly worse in pN(+) cases (161 cases) than in pN0 cases, particularly those with a metastatic lymph node number ≥11. The cumulative incidence of relapse and distant metastases was significantly higher in stage IV cases than in stage 0-III cases. CONCLUSIONS: The absolute number of lymph node metastases, higher stages, and the minor SG as the primary tumor site were identified as factors affecting the outcome of SDC.

Association of the prolonged use of anti-glaucoma medications with the surgical failure of ab interno microhook trabeculotomy.

PURPOSE: This study examined the perioperative factors affecting surgical success in ab interno microhook trabeculotomy (µTLO). METHODS: 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 of <4.5 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. RESULTS: 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 the <4.5-year users of anti-glaucoma drugs had significantly higher success rates than the ≥4.5-year users (72% versus 52%; p = 0.04). CONCLUSIONS: The prolonged use of multiple glaucoma drugs adversely affected the outcome of µTLO at least at 1 year postoperatively.

Pleomorphic adenoma: detection of PLAG1 rearrangement-positive tumor components using whole-slide fluorescence in situ hybridization.

Pleomorphic adenoma (PA) consists of heterogeneous histological architecture mixed with epithelioid and mesenchymal forms. Various types of epithelial or myoepithelial malignancies arise from PA, but sarcomas are extremely rare. A human androgen receptor gene (HUMARA) clonality assay has suggested that PA is clonal in nature. However, clonality of various tumor components of PA would be difficult to determine with this assay. In addition, the results obtained should be carefully interpreted. PLAG1 rearrangements are considered a good molecular marker for neoplasticity in PA. We aimed to clarify the neoplasticity of the various tumor components present in PA using whole-slide fluorescence in situ hybridization (FISH). Five PA cases positive for PLAG1 rearrangements were examined. Using an immunohistochemistry panel, cell components in PA were classified into eight cell types. To precisely localize PLAG1 rearrangement-positive cell components at the cellular level, sequential retrieval of whole-slide imaging (WSI) data of HE histology and FISH for PLAG1 rearrangement was carried out. PLAG1 rearrangements were detected in ductal cells, myoepithelial spindle cells, myoepithelial oncocytic cells, myoepithelial plasmacytoid cells, and mesenchymal chondroid cells, but not in mesenchymal lipid cells, mesenchymal fibrous cells, or vascular endothelial cells. Immunohistochemical PLAG1 expression was restricted to cell components harboring PLAG1 rearrangements.The results of the present study indicate that ductal and myoepithelial, chondroid cells are neoplastic but lipid, fibrous, and endothelial cells are not. PLAG1 immunohistochemistry is useful in discriminating neoplastic from non-neoplastic cell components. These findings may be important for elucidating tumorigenesis and the process of malignant transformation in PA.

Comparison of Two Cases of Foveal Laceration Caused by a Mower.

We report and compare 2 cases of open globe injury with foveal damage incurred while mowing. Case 1 is a healthy 67-year-old man presenting with an intraocular metallic foreign body and eye pain in his right eye after using a mower. The foreign body perforated the cornea's inferior area and damaged the foveal centralis, leading to central scotoma and decreased visual acuity. 27G pars plana vitrectomy was performed, and the final corrected decimal visual acuity was 0.1, but the visual field was preserved, except for the central scotoma. Case 2 is a healthy 50-year-old man presenting open globe injury with an intraocular metallic foreign body while using a mower. The foreign body damaged the fovea and triggered extensive retinal detachment. One month after surgery, proliferative vitreoretinopathy occurred, requiring additional surgery. The final corrected decimal visual acuity dropped to 0.05, resulting in an extensive visual field defect. Both cases of eye trauma were caused by mower injury, but the visual function outcomes differed with the size of the foreign body and the injury severity at the time of onset. Mower eye trauma is preventable, and efforts to educate users on safety measures are needed.