Functional characterization of variants found in Japanese patients with hereditary hemorrhagic telangiectasia.

Hereditary hemorrhagic telangiectasia (HHT) is an autosomal dominant form of vascular dysplasia. Genetic diagnosis is made by identifying loss-of-function variants in genes, such as ENG and ACVRL1. However, the causal mechanisms of various variants of unknown significance remains unclear. In this study, we analyzed 12 Japanese patients from 11 families who were clinically diagnosed with HHT. Sequencing analysis identified 11 distinct variants in ACVRL1 and ENG. Three of the 11 were truncating variants, leading to a definitive diagnosis, whereas the remaining eight were splice-site and missense variants that required functional analyses. In silico splicing analyses demonstrated that three variants, c.526-3C > G and c.598C > G in ACVRL1, and c.690-1G > A in ENG, caused aberrant splicing, as confirmed by a minigene assay. The five remaining missense variants were p.Arg67Gln, p.Ile256Asn, p.Leu285Pro, and p.Pro424Leu in ACVRL and p.Pro165His in ENG. Nanoluciferase-based bioluminescence analyses demonstrated that these ACVRL1 variants impaired cell membrane trafficking, resulting in the loss of bone morphogenetic protein 9 (BMP9) signal transduction. In contrast, the ENG mutation impaired BMP9 signaling despite normal cell membrane expression. The updated functional analysis methods performed in this study will facilitate effective genetic testing and appropriate medical care for patients with HHT.

Comparison of functional and morphologic changes between brolucizumab and faricimab in neovascular age-related macular degeneration.

PURPOSE: This study aimed to compare functional and morphologic changes in the loading phase between patients with treatment-naïve macular neovascularization (MNV) due to neovascular age-related macular degeneration (nAMD) treated with either intravitreal brolucizumab (IVBr) or intravitreal faricimab (IVF) injections in a clinical setting. METHODS: We retrospectively studied 92 consecutive eyes of 90 patients with neovascular nAMD who were scheduled to receive IVBr (42 eyes of 41 patients) or IVF (50 eyes of 49 patients) injections between October 2021 and December 2022. All patients received three consecutive monthly injections of 6.0 mg/0.05 mL brolucizumab or 6.0 mg/0.05 mL faricimab. The best-corrected visual acuity (BCVA), central foveal thickness (CFT), and central choroidal thickness (CCT) at baseline and 1, 2, and 4 months after the initial treatment were measured and compared between the groups. RESULTS: Thirty-seven eyes in IVBr group and forty-seven eyes in IVF group who finished treatments in the loading phase were assessed at the follow-up examination. The BCVA, CFT, and CCT changed significantly after loading phase in both groups (P < 0.05 for both comparisons). The IVBr group had more rapid improvement of the BCVA (P = 0.037) at 1 month than the IVF group, but there was no difference at 4 months (P = 0.367). The CFT and CCT decreases tended to be greater in the IVBr group than in the IVF group throughout the follow-up period. Of the five eyes excluded from the IVBr group, one eye (2.4%) each had intraocular inflammation (IOI) and was a non-responder, and two eyes (4.8%) had retinal pigment epithelial tears after treatment. Of the three eyes excluded from the IVF group, two eyes (4.0%) did not respond to the treatment. CONCLUSIONS: Both IVBr and IVF injections were well-tolerated and improved the VA in treatment-naïve patients with MNV due to nAMD after a loading phase, although IVBr caused a trend toward faster visual improvements in the BCVA. The IVBr group also had greater reductions of the CFT and CCT than the IVF group. However, the potential for adverse events and no response to treatment with each drug are considerations.

Three-year outcome of photodynamic therapy combined with VEGF inhibitor for pachychoroid neovasculopathy.

BACKGROUND: Long-term results of photodynamic therapy (PDT) combined with vascular endothelial growth factor (VEGF) inhibitors for pachychoroid neovasculopathy (PNV) are not yet clear. METHODS: This study is a retrospective, observational case series. We retrospectively examined untreated PNV cases (22 cases, 22 eyes, mean age of 71.0 years) who underwent PDT therapy in combination with VEGF inhibitors followed by additional treatments with pro re nata protocol. Visual acuity, number of treatments, and time to recurrence were examined. In addition, foveal choroidal thickness and choroidal vascularity index (CVI) were evaluated in 13 of 22 patients who were followed up with SpectralisOCTR from baseline. RESULTS: Fifteen (68%) cases had polyps at baseline. LogMAR visual acuity averaged 0.24 ± 0.20 (range, - 0.079 to 0.82) at baseline and significantly improved after 1, 2, and 3 years (p = 0. 004, 0.0003, 0.002, respectively). Fourteen patients (64%) recurred, with an average time to recurrence of 1.8 ± 0.9 years. Foveal choroidal thickness decreased significantly after 1 year (average from 326 µm to 263 µm) and remained unchanged up to 3 years (255 µm). CVI also decreased after 1 year (average from 0.62 to 0.61) and remained unchanged until 3 years later (0.60). CONCLUSIONS: We examined the 3-year course of PDT in combination with the VEGF inhibitor for untreated PNV. Visual acuity was improved, foveal choroidal thickness and CVI were decreased after 3 years.

Biomechanical properties measured with dynamic Scheimpflug analyzer in central serous chorioretinopathy.

PURPOSE: Recent evidence suggests that venous congestion at the vortex vein significantly contributes to the development of central serous chorioretinopathy (CSCR), and sclera is observed to be thicker in affected eyes. This study aims to investigate whether eyes with CSCR exhibit stiff corneas, measured using Corneal Visualization Scheimflug Technology (Corvis ST), which may serve as an indicator of scleral stiffness. METHODS: This retrospective case-control study comprises 52 eyes from 33 patients diagnosed with CSCR and 52 eyes from 32 normal controls without CSCR. We compared biomechanical parameters measured with Corvis ST and anterior scleral thickness measured using anterior segment swept-source optical coherence tomography between the two groups. RESULTS: Age, sex, axial length, intraocular pressure, and central corneal thickness showed no significant differences between the two groups (p > 0.05, linear mixed model). Three biomechanical parameters-peak distance, maximum deflection amplitude, and integrated inverse radius-indicated less deformability in CSCR eyes compared to control eyes. The stress-strain index (SSI), a measure of stiffness, and anterior scleral thickness (AST) at temporal and nasal points were significantly higher in the CSCR eyes. SSI and AST were not correlated, yet both were significantly and independently associated with CSCR in a multivariate logistic regression model. CONCLUSIONS: Eyes affected by CSCR have stiffer corneas, irrespective of thicker scleral thickness. This suggests that stiffer sclera may play a role in the pathogenesis of CSCR.

Intravitreal anti-vascular endothelial growth factor and combined photodynamic therapy for pachychoroid neovasculopathy: long-term treatment outcomes.

PURPOSE: To examine the long-term visual outcomes after initial treatment with combined photodynamic therapy (PDT) or aflibercept treat-and-extend (TAE) monotherapy in patients with pachychoroid neovasculopathy (PNV). METHODS: Patients diagnosed with PNV, initially treated with PDT combined with anti-vascular endothelial growth factor (VEGF) or intravitreal aflibercept (IVA) monotherapy in the TAE protocol and followed up for at least 6 months, were included in the study. Medical records were retrospectively reviewed. Survival analysis was performed, in which deterioration in logMAR visual acuity by 0.1 or 0.3 is defined as "death." The annual number of treatments was also analyzed. Sub-analysis was performed on 33 patients diagnosed with PNV without polypoidal lesions. RESULTS: This study included 46 patients (23 in the initial combined PDT group and 23 in the IVA TAE group). Mean age, sex, mean baseline logMAR visual acuity, or duration of observation (3.6 ± 3.2 years vs. 3.1 ± 1.9 years) in both groups were comparable. As for visual outcome, no significant differences were found in survival analysis based on worsening of 0.1 or 0.3 logMAR (3-year survival; 26% vs. 26%, 91% vs. 90%, respectively). Meanwhile, the additional number of anti-VEGF injections per year was significantly lower in the initial combined PDT group than in the IVA TAE group (1.0 ± 1.3 vs. 4.1 ± 1.5, p < 0.0001). No significant differences were found in the number of additional PDTs per year (0.07 ± 0.20 vs. 0.02 ± 0.09, p = 0.27). Similar results were found in a sub-analysis of 33 patients without polyps. CONCLUSION: In the treatment of PNV, regardless of the presence of polyps, the long-term visual outcomes were similar between the initial combined PDT and IVA TAE monotherapy. However, the annual number of anti-VEGF injections was lower in the initial combined PDT group than in the aflibercept TAE group, whereas that of PDT was comparable.

Comparison of efficacy between clazosentan and fasudil hydrochloride-based management of vasospasm after subarachnoid hemorrhage focusing on older and WFNS grade V patients: a single-center experience in Japan.

Subarachnoid hemorrhage often leads to poor outcomes owing to vasospasm, even after successful aneurysm treatment. Clazosentan, an endothelin receptor inhibitor, has been proven to be an effective treatment for vasospasms in a Japanese randomized controlled trial. However, its efficacy in older patients (≥ 75 years old) and those with World Federation of Neurosurgical Societies (WFNS) grade V has not been demonstrated. We retrospectively evaluated the efficacy of clazosentan in older patients and those with WFNS grade V, using real-world data. Patients with subarachnoid hemorrhage treated before and after the introduction of clazosentan were retrospectively evaluated. The patients were categorized into two groups (clazosentan era versus pre-clazosentan era), in which vasospasm management and outcomes were compared. Vasospasms were managed with fasudil hydrochloride-based (pre-clazosentan era) or clazosentan-based treatment (clazosentan era). Seventy-eight patients were included in this study: the clazosentan era (n = 32) and pre-clazosentan era (n = 46). Overall, clazosentan significantly reduced clinical vasospasms (clazosentan era: 31.3% versus pre-clazosentan era: 60.9%, p = 0.01), delayed cerebral ischemia (DCI) (9.4% versus 39.1%, p = 0.004), and vasospasm-related morbidity and mortality (M/M) (3.1% versus 19.6%, p = 0.03). In subgroup analysis of older patients or those with WFNS grade V, no significant difference was observed in clinical outcomes, although both DCI and vasospasm-related M/M were lower in the clazosentan era. Clazosentan was more effective than fasudil-based management in preventing DCI and reducing vasospasm-related M/M. Clazosentan could be used safely in older patients and those with WFNS grade V, although clinical outcomes in these patients were comparable to those of conventional treatment.

Dosimetric evaluation in Helical TomoTherapy for lung SBRT using Monte Carlo-based independent dose verification software.

PURPOSE: To elucidate the dosimetric errors caused by a model-based algorithm in lung stereotactic body radiation therapy (SBRT) with Helical TomoTherapy (HT) using Monte Carlo (MC)-based dose verification software. METHODS: For 38 plans of lung SBRT, the dose calculation accuracy of a treatment planning system (TPS) of HT was compared with the results of DoseCHECK, the commercial MC-based independent verification software. The following indices were extracted to evaluate the correlation of dosimetric errors: (1) target volume, (2) average computed tomography (CT) value of the planning target volume (PTV) margin, and (3) average CT value of surrounding 2-mm area of the PTV (PTV ring). Receiver operating characteristic (ROC) analyses determined the threshold for 5% of differences in PTV D95%. Then, the 38 plans were classified into two groups using the cutoff values of ROC analysis for these three indices. Dosimetric differences between groups were statistically compared using the Mann-Whitney U test. RESULTS: TPS of HT overestimated by more than 5% in the PTV D95% in 16 of 38 plans. The PTV ring showed the strongest correlation with dosimetric differences. The cutoff value for the target volume, the PTV margin, and the PTV ring was 14.7 cc, -754 HU, and -708 HU, respectively. The area under the curve (AUC) for the target volume, the PTV margin, and the PTV ring were 0.835, 0.878, and 0.932, respectively. Dosimetric errors more than 5% were observed when the PTV volume was less than 15 cc or when the CT value around the target was less than -700 HU. CONCLUSION: The TPS of HT might overestimate the PTV dose by more than 5% if any the three indices in this study were below threshold. Therefore, independent verification with an MC-based algorithm should be strongly recommended for lung SBRT in HT.

Synthesis and Characterization of Hypervalent Pentacoordinate Carbon Compounds Bearing a 7-6-7-Ring Skeleton.

To stabilize SN 2 transition state-like penta-coordinate carbon species, triaryl-substituted cationic carbon compounds bearing a moderately flexible 7-6-7-ring skeleton with sulfur donors were synthesized and characterized. Electronic effects of para substituents (R=Cl, F, H, CH3 , SMe, OMe) of the two equatorial aryl groups bound to the cationic central carbon were investigated systematically along with a planar bidentate thioxanthene derivative. X-ray analysis on their solid-state structures showed that the parent (R=H), chloro-, fluoro- and methyl-derivatives were tetracoordinate carbon (sulfonium) structures, while the p-MeO and thioxanthenyl system were pentacoordinate carbocation structures. The Hammett substituent constants for the para substituents (σp + ) correlates well with the bonding in these compounds. The methylthio-derivative with intermediate Hammett substituent constants (p-MeS; σp + =-0.60) showed a tetracooridnate solid-state structure, though solution UV-Vis properties suggested the presence of a penta-coordinate structure. These findings amount to the first unambiguous solution evidence of the hypervalent apical 3c-4e interactions in pentacoordinate carbon compounds.

Postsurgical dural supply to the spinal cord arteriovenous malformation in spinal arteriovenous metameric syndrome.

Dural supply from the external carotid system in cerebral arteriovenous malformations (AVMs) is well known, but actual angiographic evidence of dural supply to spinal cord AVMs (SCAVMs) has not been reported. Here, we report a case of dural supply to the conus SCAVM in the spinal arteriovenous metameric syndrome segment 25-30. Thirteen years after spinal surgery (T12-L2 laminoplasty), spinal angiography showed multiple dural supplies from the dorsal somatic branches, prelaminar arteries, and radiculomeningeal arteries to the SCAVM at the level of the previous spinal surgery. To the best of our knowledge, this is the first reported case with dural supply to the spinal cord. This case demonstrates that the extradural and extraspinal branches can supply the spinal cord in rare instances of spinal dural adhesions following repeated hemorrhages and surgical intervention under a metameric link background.

IMPACT OF GAS/AIR TAMPONADE ON REFRACTIVE OUTCOMES AFTER FLANGED INTRASCLERAL INTRAOCULAR LENS FIXATION.

PURPOSE: This study aims to investigate the postoperative refractive outcomes in eyes that underwent the flanged intrascleral intraocular lens (IOL) fixation combined with vitrectomy with or without gas/air tamponade. METHODS: The eyes were divided into two groups (Group A; eyes that underwent flanged intrascleral IOL fixation with gas/air tamponade, and Group B; eyes that underwent flanged intrascleral IOL fixation without gas/air tamponade). The predicted spherical equivalent (SE) refraction values were calculated using the Sander-Retzlaff-Kraff Theoretical formula. Then, the prediction error was calculated by subtracting the predicted SE refraction from the postoperative objective SE refraction and the absolute prediction error was calculated as the absolute value of the prediction error for each eye. RESULTS: A total of 68 eyes were included in the current study. There was a significant correlation between the predicted and postoperative SE refraction in both groups (Group A, r = 0.968, P < 0.0001, Group B, r = 0.943, P < 0.0001, linear regression analysis). The prediction error demonstrated a mild myopic shift after the flanged intrascleral IOL fixation in both groups (Group A, -0.40 ± 0.96 diopter, Group B, -0.59 ± 0.95 diopter). There was no significant difference in prediction error and absolute prediction error between the two groups ( P = 0.44, P = 0.70, Wilcoxon rank sum test). CONCLUSION: The postoperative SE refraction after flanged intrascleral IOL fixation was not influenced by gas/air tamponade.

Hyperreflective material in patients with non-neovascular pachychoroid disease.

BACKGROUND: This study aimed to report eleven cases of non-neovascular pachychoroid disease with hyperreflective material (HRM) that occurred in Japanese patients. METHODS: A retrospective review of data from eleven patients who had non-neovascular retinal pigment epithelium (RPE) protrusion with HRM in the neurosensory retina between March 2017 and June 2022 was conducted. Clinical examination, color fundus photography, fluorescein angiography, spectral-domain optical coherence tomography (SD-OCT), and OCT angiography data were analyzed. Main outcome measures were patient characteristics, changes in SD-OCT findings, and symptom outcomes. RESULTS: All cases had RPE protrusion and HRM with dilated choroidal veins, which were characteristic of pachychoroid disease. However, none of the cases had macular neovascularization (MNV). In 9 eyes (81.8%), HRM improved spontaneously without intervention and resulted in alterations in RPE, referred to as pachychoroid pigment epitheliopathy (PPE) or focal choroidal excavation (FCE). In these cases, symptoms such as metamorphopsia and distortion improved without treatment. In the remaining two cases (18.2%), HRM still persisted during the follow-up period. CONCLUSION: There are some cases of non-neovascular pachychoroid disorder with HRM, which might be a new entity of pachychoroid spectrum disease or an early stage of PPE or FCE. These cases should not be misdiagnosed as MNV, and careful observation is necessary.

Effectiveness of robust optimization against geometric uncertainties in TomoHelical planning for prostate cancer.

BACKGROUND: Geometrical uncertainties in patients can severely affect the quality of radiotherapy. PURPOSE: We evaluated the dosimetric efficacy of robust optimization for helical intensity-modulated radiotherapy (IMRT) planning in the presence of patient setup uncertainty and anatomical changes. METHODS: Two helical IMRT plans for 10 patients with localized prostate cancer were created using either minimax robust optimization (robust plan) or a conventional planning target volume (PTV) margin approach (PTV plan). Plan robustness was evaluated by creating perturbed dose plans with setup uncertainty from isocenter shifts and anatomical changes due to organ variation. The magnitudes of the geometrical uncertainties were based on the patient setup uncertainty considered during robust optimization, which was identical to the PTV margin. The homogeneity index, and target coverage (TC, defined as the V100% of the clinical target volume), and organs at risk (OAR; rectum and bladder) doses were analyzed for all nominal and perturbed plans. A statistical t-test was performed to evaluate the differences between the robust and PTV plans. RESULTS: Comparison of the nominal plans showed that the robust plans had lower OAR doses and a worse homogeneity index and TC than the PTV plans. The evaluations of robustness that considered setup errors more than the PTV margin demonstrated that the worst-case perturbed scenarios for robust plans had significantly higher TC while maintaining lower OAR doses. However, when anatomical changes were considered, improvement in TC from robust optimization was not observed in the worst-case perturbed plans. CONCLUSIONS: For helical IMRT planning in localized prostate cancer, robust optimization provides benefits over PTV margin-based planning, including better OAR sparing, and increased robustness against systematic patient-setup errors.

FLOW-diverted Glue Embolization to Target lesions (FLOW-GET) technique for spinal vascular diseases: A technical note.

We present and exemplify the flow-diverted glue embolization to target lesions (FLOW-GET) technique for spinal vascular diseases. In this technique, the occlusion of the posterior intercostal artery or dorsal muscular branch by coils diverts the injected glue from the segmental artery to the target lesions. This technique was applied to a ruptured retrocorporeal artery aneurysm and spinal dural arteriovenous fistulas. The FLOW-GET accomplished the complete obliteration of all lesions. This simple and useful technique can be applied to spinal vascular lesions even if a microcatheter is not placed in proper feeders or advanced close to the shunt points or aneurysms.

Alpha-actinin-4 (ACTN4) gene amplification is a predictive biomarker for adjuvant chemotherapy with tegafur/uracil in stage I lung adenocarcinomas.

Although adjuvant tegafur/uracil (UFT) is recommended for patients with completely resected stage I non-small-cell lung cancer (NSCLC) in Japan, only one-third of cases has received adjuvant chemotherapy (ADJ) according to real-world data. Therefore, robust predictive biomarkers for selecting ADJ or observation (OBS) without ADJ are needed. Patients who underwent complete resection of stage I lung adenocarcinoma with or without adjuvant UFT were enrolled. The status of ACTN4 gene amplification was analyzed by FISH. Statistical analyses to determine whether the status of ACTN4 gene amplification affected recurrence-free survival (RFS) were carried out. Formalin-fixed, paraffin-embedded samples from 1136 lung adenocarcinomas were submitted for analysis of ACTN4 gene amplification. Ninety-nine (8.9%) of 1114 cases were positive for ACTN4 gene amplification. In the subgroup analysis of patients aged 65 years or older, the ADJ group had better RFS than the OBS group in the ACTN4-positive cohort (hazard ratio [HR], 0.084, 95% confidence interval [CI], 0.009-0.806; P = .032). The difference in RFS between the ADJ group and the OBS group was not significant in ACTN4-negative cases (all ages: HR, 1.214; 95% CI, 0.848-1.738; P = .289). Analyses of ACTN4 gene amplification contributed to the decision regarding postoperative ADJ for stage I lung adenocarcinomas, preventing recurrence, improving the quality of medical care, preventing the unnecessary side-effects of ADJ, and saving medical costs.

Predicting retinal sensitivity using optical coherence tomography parameters in central serous chorioretinopathy.

PURPOSE: To predict changes in retinal sensitivity using optical coherence tomography (OCT) in eyes with central serous chorioretinopathy (CSC). METHODS: Twenty-three eyes in 23 patients with CSC were enrolled. Retinal sensitivity was measured twice using microperimetry in all the examined eyes. Spectral domain OCT measurements were simultaneously conducted. The relationship between retinal sensitivity and the thicknesses of (i) the retinal nerve fiber layer plus the ganglion cell layer (RNFL + GCL), (ii) the inner nuclear layer (INL), (iii) the outer nuclear layer (ONL), and (iv) the serous retinal detachment height (SRDH) were investigated in a point-wise manner. The associations between the change in retinal sensitivity and the OCT parameters at baseline were also investigated. RESULTS: The mean age of the participants was 49.8 ± 10.7 years. The mean SRDH was significantly lower (p < 0.001), and the mean retinal sensitivity (p < 0.001) was significantly higher at the second examination, compared with the first; however, the logMAR visual acuity (VA) did not differ significantly between the two examinations (p = 0.063). The logMAR VA was associated with retinal sensitivity at both the first and second examinations (p < 0.001). The retinal sensitivity at the second examination was significantly correlated with the retinal sensitivity, RNFL + GCL, INL, ONL, and SRDH at the first examination and with the improvement in SRDH. CONCLUSIONS: Retinal sensitivity was associated with the retinal structure in eyes with CSC; these parameters could be useful for predicting the change in visual function prior to treatment.

Relationship between the vessel density around the optic nerve head and visual field deterioration in eyes with retinitis pigmentosa.

PURPOSE: To analyze the vessel density around the optic nerve head (ONH) by optical coherence tomography angiography (OCTA) in patients with retinitis pigmentosa (RP), and to evaluate its correlation with visual functions. METHODS: Thirty-eight eyes with RP with visual field constriction within the central 10° were enrolled. The mean (± SD) age of the patients was 43.7 ± 15.1 years. In addition to visual acuity (VA) measurements and visual field tests (Humphrey Field Analyzer 10-2 test), we also measured the vessel density at the macula by OCTA (superficial and deep vessel density: sVD(m) and dVD(m)) and in multiple layers around the ONH (vessel density in the radial peripapillary capillary [RPC] layer and in the nerve head [NH] layer: VDrpc and VDnh). The vessel density was calculated by binarizing the OCTA images. The associations between the logMAR VA and mean deviation (MD) values and the variables of central retinal thickness (CRT), sVD(m), dVD(m), VDrpc, VDnh, and also the size of the foveal avascular zone were investigated. RESULTS: The mean logMAR VA was 0.16 ± 0.34 and the MD value was - 17.2 ± 10.3 dB; the MD value was significantly related to the logMAR VA (p = 0.0028). Multivariate analysis with AICc model selection suggested only dVD(m) was associated with logMAR VA. On the other hand, the optimal model for the MD value included the CRT, dVD(m), and VDnh. CONCLUSION: The vessel density in the deep layer around the ONH was significantly associated with the visual field deterioration in patients with RP.

LOCATIONAL AGREEMENT OF NEAR-INFRARED AUTOFLUORESCENCE WITH CHOROIDAL VASCULAR HYPERPERMEABILITY IN CENTRAL SEROUS CHORIORETINOPATHY.

PURPOSE: To characterize the findings of eyes with choroidal vascular hyperpermeability (CVH), a hallmark of central serous chorioretinopathy, using multimodal imaging and investigate the locational agreement between these findings and CVH. METHODS: Among patients with central serous chorioretinopathy in either eye, eyes with CVH identified using indocyanine green angiography without exudative changes were included. All eyes were examined using funduscopy, fluorescein angiography, spectral-domain optical coherence tomography, and short-wavelength or near-infrared autofluorescence (SWAF or NIRAF). The locational agreement between CVH and imaging findings was evaluated for each modality. The relative index on how they overlapped was calculated as the overlapping index. Binarized images, particularly for NIRAF, were also evaluated. RESULTS: This study included 69 CVH sites in 33 eyes of 28 patients. Pachydrusen was detected in 36% of CVH sites. Fluorescein angiography revealed hyperfluorescent areas in 39% of CVH sites. Optical coherence tomography findings identified 65% of CVH sites, but the overlapping index was 5%. Short-wavelength or near-infrared autofluorescence imaging identified 89% of CVH sites, but they exhibited variable autofluorescence. NIRAF imaging revealed hypoautofluorescence findings in all CVH sites. When binarized, near-infrared autofluorescent dark dots were observed in all CVH sites. Overlapping indices before and after binarization were 78% and 98%, respectively. The near-infrared autofluorescent dark dots area corresponded well with that of CVH (intraclass correlation coefficient, 0.987 [95% confidence interval, 0.952-0.995]). CONCLUSION: Hypoautofluorescent findings revealed on NIRAF imaging, especially after binarization processing, corresponded well with CVH sites. These multimodal imaging results may help investigate the anatomical or locational characteristics of CVH in patients with central serous chorioretinopathy.

EVALUATION OF THE RETINAL HAZARD WITH 3D DIGITALLY ASSISTED VISUALIZATION SYSTEM AND CONVENTIONAL MICROSCOPE IN MACULAR SURGERIES.

PURPOSE: To investigate the retinal light hazard during macular surgery using a digital three-dimensional visualization system (3D) and a conventional microscope (CM). DESIGN: Experimental study and retrospective evaluation of a case-control study. SUBJECTS: A total of 20 and 10 patients who underwent pars plana vitrectomy for epiretinal membrane using 3D and CM, respectively. METHODS: Spectral irradiances of endoilluminators were measured for representative settings used during core vitrectomy and macular manipulations with 3D and CM. From the medical record of the patients, time needed for core vitrectomy and macular manipulations was extracted. The total retinal light hazard index and the macular hazard index were calculated based on the spectral irradiances weighted by the standard functions. Total retinal light hazard index, macular hazard index, and the number of cases that exceeded the maximum permissible radiant power exposure were compared between the two groups. RESULTS: The spectral irradiance were 1.6 and 3.9 mW/cm 2 for core vitrectomy and 3.4 and 8.1 mW/cm 2 for macular manipulations using typical settings for 3D and CM groups, respectively. The total retinal light hazard index ranged from 4.31 kJ/m 2 to 17.37 kJ/m 2 for 3D and 11.09 kJ/m 2 to 27.70 kJ/m 2 for CM groups, respectively, whereas the macular hazard index ranged from 2.93 kJ/m 2 to 14.58 kJ/m 2 for 3D and from 6.84 kJ/m 2 to 23.55 kJ/m 2 for CM, respectively ( P < 0.001). One (5%) and 6 (60%) pars plana vitrectomy cases exceeded the threshold limits with 3D and CM groups, respectively ( P < 0.05, chi-square test). CONCLUSION: The 3D digitally assisted visualization system offers significantly safer macular surgery compared with the CM, considering the potential retinal hazard.

Relationship between resting 12-lead electrocardiogram and all-cause death in patients without structural heart disease: Shinken Database analysis.

BACKGROUND: Resting 12-lead electrocardiography is widely used for the detection of cardiac diseases. Electrocardiogram readings have been reported to be affected by aging and, therefore, can predict patient mortality. METHODS: A total of 12,837 patients without structural heart disease who underwent electrocardiography at baseline were identified in the Shinken Database among those registered between 2010 and 2017 (n = 19,170). Using 438 electrocardiography parameters, predictive models for all-cause death and cardiovascular (CV) death were developed by a support vector machine (SVM) algorithm. RESULTS: During the observation period of 320.4 days, 55 all-cause deaths and 23 CV deaths were observed. In the SVM prediction model, the mean c-statistics of 10 cross-validation models with training and testing datasets were 0.881 ± 0.027 and 0.927 ± 0.101, respectively, for all-cause death and 0.862 ± 0.029 and 0.897 ± 0.069, respectively for CV death. For both all-cause and CV death, high values of permutation importance in the ECG parameters were concentrated in the QRS complex and ST-T segment. CONCLUSIONS: Parameters acquired from 12-lead resting electrocardiography could be applied to predict the all-cause and CV deaths of patients without structural heart disease. The ECG parameters that greatly contributed to the prediction were concentrated in the QRS complex and ST-T segment.

Left atrial dimension and ischemic stroke in patients with and without atrial fibrillation.

The incidence of ischemic stroke (IS) increases in patients with enlarged left atrium (LA) irrespective of whether or not the existence of atrial fibrillation (AF). In such situation, it is unclear whether the impact of LA on incidence of IS still significant in young, non-AF patients with enlarged LA who are primarily unconcerned on anticoagulation therapy. The study population consisted of 18,511 consecutive patients not receiving oral anticoagulants and undergoing echocardiography with measurement of LAD at baseline. The incidence rate of ischemic stroke was calculated in 3 groups according to left atrial dimension (LAD; < 30, 30-45 and ≥ 45 mm) in AF and non-AF patients. Further subgroup analysis was performed in stratification by elderly and young (aged ≥ 65 and < 65 years, respectively). The incidences of IS (per 100 patient-years) were 0.11 and 0.71 in non-AF and AF patients with LAD < 30 mm, respectively, which increased to 0.58 and 1.35 in LAD ≥ 45 mm (adjusted hazard ratios [HRs]; 1.95 [95% confidence intervals, CIs: 0.76-5.01] and 1.22 [95% CIs: 0.27-5.58], interaction P was 0.246). In non-AF patients, the incidences of IS were 0.30 and 0.04 in elderly and young patients with LAD < 30 mm, which increased to 0.67 and 0.48 in LAD ≥ 45 mm (adjusted HRs; 1.34 [95% CIs: 0.43-4.15] and 4.21 [95% CIs: 0.77-23.12], interaction P was 0.158). The incidence of IS significantly increased with increase of LAD in non-AF, especially in non-AF and young patients, although the difference was not independent of other clinical factors. The impact of LAD on IS was numerically larger in non-AF than in AF, and larger in young and non-AF than in elderly counterpart, although a significant interaction was not observed in this small population. Further studies with large population are necessary to judge whether these population with enlarged LA need antithrombotic therapy.