Binding of Gtf2i-ß/δ transcription factors to the ARMS2 gene leads to increased circulating HTRA1 in AMD patients and in vitro.

The disease-initiating molecular events for age-related macular degeneration (AMD), a multifactorial retinal disease affecting many millions of elderly individuals worldwide, are still unknown. Of the over 30 risk and protective loci so far associated with AMD through whole genome-wide association studies (GWAS), the Age-Related Maculopathy Susceptibility 2 (ARMS2) gene locus represents one of the most highly associated risk regions for AMD. A unique insertion/deletion (in/del) sequence located immediately upstream of the High Temperature Requirement A1 (HTRA1) gene in this region confers high risk for AMD. Using electrophoretic mobility shift assay (EMSA), we identified that two Gtf2i-ß/δ transcription factor isoforms bind to the cis-element 5'- ATTAATAACC-3' contained in this in/del sequence. The binding of these transcription factors leads to enhanced upregulation of transcription of the secretory serine protease HTRA1 in transfected cells and AMD patient-derived induced pluripotent stem cells (iPSCs). Overexpression of Htra1 in mice using a CAG-promoter demonstrated increased blood concentration of Htra1 protein, caused upregulation of vascular endothelial growth factor (VEGF), and produced a choroidal neovascularization (CNV)-like phenotype. Finally, a comparison of 478 AMD patients to 481 healthy, age-matched controls from Japan, India, Australia, and the USA showed a statistically increased level of secreted HTRA1 blood concentration in AMD patients compared with age-matched controls. Taken together, these results suggest a common mechanism across ethnicities whereby increased systemic blood circulation of secreted serine protease HTRA1 leads to subsequent degradation of Bruch's membrane and eventual CNV in AMD.

RETINAL SURFACE WRINKLING AS AN INDICATOR FOR INTERNAL LIMITING MEMBRANE PEELING DURING VITRECTOMY FOR RETINAL DETACHMENT.

PURPOSE: To assess the validity of retinal surface wrinkling (RSW) as an indicator to select patients relevant for internal limiting membrane peeling during vitrectomy for rhegmatogenous retinal detachment, to prevent postoperative visual decline due to epiretinal membrane growth. METHODS: This was a prospective, interventional case series of 78 consecutive eyes that underwent initial vitrectomy to repair rhegmatogenous retinal detachments and were followed for 6 months. The presence/absence of RSW was evaluated presurgically on en face optical coherence tomographic images. The internal limiting membrane was peeled if RSW was identified. The main outcome measure was the prevalence of postsurgical epiretinal membrane growth that caused a visual decline of 0.2 or more in logarithm of the minimum angle of resolution unit. RESULTS: The internal limiting membrane was peeled for RSW appearance in 22 eyes (28.2%). Mild epiretinal membranes developed in 8 of the 56 internal limiting membrane-unpeeled eyes (10.3% of total, 6 eyes at stage 1 in the classification of Govetto); however, visual decline occurred in none of them with the mean visual acuity of these 8 eyes maintained at -0.08 ± 0.11 in logarithm of the minimum angle of resolution (≈20/16). CONCLUSION: Visual decline due to epiretinal membrane growth after rhegmatogenous retinal detachment repair was entirely prevented by peeling the internal limiting membrane in about 30% of cases selected for the presence of RSW.

Prospective assessment of plate-haptic rotationally asymmetric multifocal toric intraocular lens with near addition of + 1.5 diopters.

BACKGROUND: To prospectively evaluate surgical results following implantation of rotationally asymmetric, plate-haptic, refractive segmented multifocal toric intraocular lenses (IOLs) with near addition of + 1.5 diopters (D) (Lentis Comfort LS-313 MF15T, Oculentis GmbH). METHODS: In 59 eyes of 41 patients, ocular examinations were conducted before and 1 day, 1 week, 1, 3, and 6 months after surgery. Uncorrected (UDVA) and corrected (CDVA) distance visual acuity, uncorrected (UIVA) and distance-corrected (DCIVA) intermediate visual acuity at 70 cm, and uncorrected (UNVA) and distance-corrected (DCNVA) near visual acuity at 30 cm were tested. A defocus curve was drawn, and the degree of disturbing photic phenomena were questioned. RESULTS: The IOL showed excellent rotational stability; the average absolute rotation was 1.66 ± 1.17 degrees from 1 day 1 to 6 months postoperatively, and 98.1 and 100% of eyes yielded rotation of less than 5 and 10 degrees, respectively. Postoperative distance and intermediate visual acuity were highly satisfactory; UDVA, CDVA, UIVA, and DCIVA were about 20/20, 20/16, 20/25, 20/25, respectively. Near visual acuity was suboptimal; UNVA and DCNVA were at approximately 20/60. The defocus curve analysis showed that 20/25 and 20/40 uncorrected visual acuity was attained at as close as 60 and 40 cm, respectively. Contrast sensitivity was within a normal range, and subjective photic phenomena were minimum. CONCLUSIONS: The refractive segmented, rotationally asymmetric multifocal toric IOLs with + 1.5 D near addition showed superb rotational stability and highly satisfactory distance and intermediate vision. Contrast sensitivity was high and incidence of photic symptoms was very low. TRIAL REGISTRATION: This study was registered at JAPIC Clinical Trials Information, ID: JapicCTI-183,877, https://www.clinicaltrials.jp/cti-user/trial/Search.jsp (February 5, 2018).

Impact of Bedside Tracheostomy on Procalcitonin Kinetics in Critically Ill Patients.

BACKGROUND: Critically ill patients are particularly vulnerable to invasive procedures and complications; however, tracheostomy is frequently performed in the intensive care unit (ICU). We analyzed the effects of tracheostomy on procalcitonin (PCT) kinetics and investigated whether PCT could reliably predict septic complications after tracheostomy. METHODS: We retrospectively identified 134 patients who underwent bedside tracheostomy during their ICU stay at a Japanese university hospital from October 2010 to December 2015. We extracted PCT data from the day of the procedure (day 0) to postoperative day 2 and defined alert PCT as a PCT level ≥0.5 ng/mL, which had not decreased from the previous day. We divided patients into the following groups: nonevent, aseptic complication, and septic complication. RESULTS: Twelve (9.2%) patients developed acute aseptic complications, and 12 (9.2%) patients developed septic complications. In the nonevent group, the PCT value decreased continuously in the initial PCT ≥ 0.5 ng/mL subgroup (P < .001, P <.001 for trend). In contrast, significant changes were not observed in the initial PCT < 0.5 ng/mL subgroup. Significant differences and an upward trend in alert PCT incidence rate existed between the groups (P < .001, P < .001 for trend): nonevent group, 5.5%; aseptic complication group, 41.7%; and septic complication group, 66.7%. In a multivariate linear regression model, septic complications were independently associated with PCT change at postoperative days 1 and 2 (adjusted ß = 3.58, P < .001; adjusted ß = 9.84, P < .001, respectively). Procalcitonin predicted septic complications more accurately than C-reactive protein, with the area under the receiver operating characteristic curves of 0.8 versus 0.63 (P = .058) and 0.91 versus 0.69 (P = .036) at postoperative days 1 and 2, respectively. CONCLUSION: Our results demonstrated that PCT was not elevated after uncomplicated surgical tracheostomy in critically ill patients.

HTRA1 (high temperature requirement A serine peptidase 1) gene is transcriptionally regulated by insertion/deletion nucleotides located at the 3' end of the ARMS2 (age-related maculopathy susceptibility 2) gene in patients with age-related macular degeneration.

Dry age-related macular degeneration (AMD) accounts for over 85% of AMD cases in the United States, whereas Japanese AMD patients predominantly progress to wet AMD or polypoidal choroidal vasculopathy. Recent genome-wide association studies have revealed a strong association between AMD and an insertion/deletion sequence between the ARMS2 (age-related maculopathy susceptibility 2) and HTRA1 (high temperature requirement A serine peptidase 1) genes. Transcription regulator activity was localized in mouse retinas using heterozygous HtrA1 knock-out mice in which HtrA1 exon 1 was replaced with ß-galactosidase cDNA, thereby resulting in dominant expression of the photoreceptors. The insertion/deletion sequence significantly induced HTRA1 transcription regulator activity in photoreceptor cell lines but not in retinal pigmented epithelium or other cell types. A deletion construct of the HTRA1 regulatory region indicated that potential transcriptional suppressors and activators surround the insertion/deletion sequence. Ten double-stranded DNA probes for this region were designed, three of which interacted with nuclear extracts from 661W cells in EMSA. Liquid chromatography-mass spectrometry (LC-MS/MS) of these EMSA bands subsequently identified a protein that bound the insertion/deletion sequence, LYRIC (lysine-rich CEACAM1 co-isolated) protein. In addition, induced pluripotent stem cells from wet AMD patients carrying the insertion/deletion sequence showed significant up-regulation of the HTRA1 transcript compared with controls. These data suggest that the insertion/deletion sequence alters the suppressor and activator cis-elements of HTRA1 and triggers sustained up-regulation of HTRA1. These results are consistent with a transgenic mouse model that ubiquitously overexpresses HtrA1 and exhibits characteristics similar to those of wet AMD patients.

Prediction of Postoperative Intraocular Lens Position with Angle-to-Angle Depth Using Anterior Segment Optical Coherence Tomography.

PURPOSE: To evaluate the accuracy of a new formula for predicting postoperative anterior chamber depth (ACD) with preoperative angle-to-angle (ATA) depth using anterior segment (AS) optical coherence tomography (OCT) and to compare it with established methods. DESIGN: Retrospective consecutive case series. PARTICIPANTS: Three hundred four eyes (276 patients) implanted with acrylic intraocular lenses (IOLs) were divided randomly into a training set (152 eyes) and a validation set (152 eyes). METHODS: Based on the training set data, the postoperative ACD measured 1 month after surgery was analyzed via multiple linear regression analysis with 5 preoperatively measured variables: ATA depth, ATA width, preoperative ACD measured with AS OCT, axial length (AL), and corneal power. A new regression formula for predicting postoperative ACD was developed using the results of the stepwise analysis. In the validation set data, the coefficients of determination (R2) between the measured postoperative ACD and the predicted postoperative ACD obtained using the new formula were compared with those obtained using the Sanders-Retzlaff-Kraff theoretic (SRK/T) and Haigis formulas. The absolute prediction errors were compared with each formula. MAIN OUTCOME MEASURES: Postoperative ACD, median absolute prediction error of postoperative ACD, and ocular biometric parameters. RESULTS: In the training set, ATA depth yielded the highest standard partial regression coefficient value, indicating that ATA depth is the most effective parameter for predicting postoperative ACD. The new regression formula was developed with 3 variables; ATA depth, preoperative ACD, and AL. In the validation set, the postoperative ACDs of the new formula, the SRK/T formula, and Haigis formula were predicted with R2 of 0.71, 0.36, and 0.55, respectively, and the medians of the absolute prediction errors were 0.10 mm, 0.65 mm, and 0.30 mm, respectively. The absolute prediction error with the new formula was significantly smaller than those obtained with the SRK/T and Haigis formulas (P < 0.0001). CONCLUSIONS: The new formula with 3 preoperative parameters-ATA depth, preoperative ACD, and AL-predicted postoperative ACD more accurately than the SRK/T and Haigis formulas. It may be possible to improve the accuracy of IOL power calculation using an improved postoperative ACD prediction with the ATA depth measured by AS OCT.

Efficacy of continuous plasma diafiltration therapy in critical patients with acute liver failure.

BACKGROUND AND AIMS: Acute liver failure (ALF) is a critical illness with high mortality. Plasma diafiltration (PDF) is a blood purification therapy that is useful for ALF patients, but it is difficult to use when those patients have multiple organ failure or unstable hemodynamics. In these patients, symptoms are also likely to exacerbate immediately after PDF therapy. We developed continuous PDF (CPDF) as a new concept in PDF therapy, and assessed its efficacy and safety in ALF patients. METHODS: Ten ALF patients (gender: M/F 6/4, Age: 47 ± 14) were employed CPDF therapy. The primary outcomes were altered liver function, measured by the model for end-stage liver disease (MELD) score, and total bilirubin and prothrombin time international normalized ratios (PT-INR), 5 days after CPDF therapy. Secondary outcomes included sequential organ failure assessment (SOFA) scores, 5 days after CPDF therapy, and the survival rate 14 days after this therapy. RESULTS: The MELD score (34.5-28.0; P = 0.005), total bilirubin (10.9-7.25 mg/dL; P = 0.048), PT-INR (1.89-1.31; P = 0.084), and SOFA score (10.0-7.5; P < 0.039) were improved 5 days after CPDF therapy. Nine patients were alive, and one patient died because of acute pancreatitis, complicated by ALF. There were no major adverse events related to this therapy under hemodynamic stability. CONCLUSION: In the present study, CPDF therapy safely supported liver function and generally improved the condition of critically ill patients with ALF.

Attitudes toward automated external defibrillator use in Japan in 2011.

PURPOSE: Early use of an automated external defibrillator (AED) improves the chances of successful resuscitation and survival. We have surveyed Japanese individuals on their attitude towards using an AED if they witnessed a cardiac arrest and compared the results with those of our previous study in 2006. METHODS: Participants were asked to complete questionnaires regarding their familiarity with the AED concept and their willingness to use AEDs. RESULTS: A total of 2,527 high school students, teachers, medical nurses, and medical students completed the questionnaire; the characteristics of these individuals were not statistically different from those of the participants of our previous study. In total, 47 % of the high school students, 89 % of the teachers, 93 % of the nurses, and all of the medical students responded that they were familiar with the concept and use of AEDs. The percentages of high school students, teachers, and nurses indicating a familiarity with AEDs were significantly higher in the current study than in the 2006 study. In total, 73 % of the high school students, 87 % of the teachers, 98 % of the nurses, and all of the medical students surveyed in the current study claimed they would definitely use AEDs if required; these values were also significantly higher than those obtained in 2006. CONCLUSIONS: The number of Japanese individuals who are familiar with the concept of AEDs and who are also willing to use these devices was considerably higher in the current study than in the 2006 study. However, more Japanese individuals should be made aware of AEDs and become familiar with their use.

Corneal refractive error and astigmatism in patients aged 6 to 18 years with a history of retinopathy of prematurity and birth weight of <1500 g.

PURPOSE: To investigate corneal refractive power (CR) and astigmatism (AS) in 6- to 18-year-old children with a history of retinopathy of prematurity (ROP) and birth weight of <1500 g who either did or did not undergo retinal photocoagulation (PC). STUDY DESIGN: Retrospective study. METHODS: We examined 143 eyes of 77 children in 2021. The children were divided into three groups for evaluation of CR and AS: those with a birth weight of ≥2500 g (normal birth weight [NBW] group, 13 eyes) as controls, those with spontaneously resolved ROP (sr-ROP group, 27 eyes), and those who underwent PC for treatment of ROP (PC-ROP group, 103 eyes). Swept-source anterior segment optical coherence tomography was used to analyze the cornea. RESULTS: The median CR in the NBW, sr-ROP, and PC-ROP groups was 42.2 (41.3, 42.8) diopters (D), 44.5 (43.2, 45.5) D, and 45.2 (43.8, 46.6) D, respectively. The median AS in the NBW, sr-ROP, and PC-ROP groups was 1.2 (1.0, 1.5) D, 1.1 (0.8, 1.6) D, and 2.1 (1.4, 2.7) D. In the PC-ROP group, the with-the-rule astigmatic axis was 97%. In all three groups, a strong positive correlation was found between the mean anterior and posterior CR (NBW: r=0.795, sr-ROP: r=0.842, PC-ROP: r=0.890) and AS (NBW: r=0.883, sr-ROP: r=0.841, PC-ROP: r=0.860). CONCLUSION: CR was significantly higher in the sr-ROP (p=0.013) and PC-ROP (p<0.001) groups than in the NBW group. The PC-ROP group had significantly more AS than the sr-ROP group. There was a strong correlation between the anterior and posterior CR and AS.

Impact of segmented optical axial length on the performance of intraocular lens power calculation formulas.

PURPOSE: To investigate the difference between the segmented axial length (AL) and the composite AL on a swept-source optical coherence tomography biometer and to evaluate the subsequent effects on artificial intelligence intraocular lens (IOL) power calculations: the Kane and Hill-RBF 3.0 formulas compared with established vergence formulas. SETTING: National Hospital Organization, Tokyo Medical Center, Japan. DESIGN: Retrospective case series. METHODS: Consecutive patients undergoing cataract surgery with a single-piece IOL were reviewed. The prediction accuracy of the Barrett Universal II, Haigis, Hill-RBF 3.0, Hoffer Q, Holladay 1, Kane, and SRK/T formulas based on 2 ALs were compared for each formula. The heteroscedastic test was used with the SD of prediction errors as the endpoint for formula performance. RESULTS: The study included 145 eyes of 145 patients. The segmented AL (24.83 ± 1.89) was significantly shorter than the composite AL (24.88 ± 1.96, P < .001). Bland-Altman analysis revealed a negative proportional bias for the differences between the segmented AL and the composite AL. The SD values obtained by Hoffer Q, Holladay 1, and SRK/T formulas based on the segmented AL (0.52 diopters [D], 0.54 D, and 0.50 D, respectively) were significantly lower than those based on the composite AL (0.57 D, 0.60 D, and 0.52 D, respectively, P < .01). CONCLUSIONS: The segmented ALs were longer in short eyes and shorter in long eyes than the composite ALs. The refractive accuracy can be improved in the Hoffer Q, Holladay 1, and SRK/T formulas by changing the composite ALs to the segmented ALs.

Molecular characteristics of four Japanese cases with KCNV2 retinopathy: report of novel disease-causing variants.

PURPOSE: To describe the molecular characteristics of four Japanese patients with cone dystrophy with supernormal rod responses (CDSRR). METHODS: Four individuals with a clinical and electrophysiological diagnosis of CDSRR were ascertained. The pathognomonic findings of the full-field electroretinograms (ERGs) included a decrease in the rod responses, a square-shaped a-wave, an excessive increase in the b-wave in the bright flash responses, and decreased cone-derived responses. Mutational screening of the coding regions and flanking intronic sequences of the potassium channel, subfamily V, member 2 (KCNV2) gene was performed with bidirectional sequencing. The segregation of each allele was confirmed by screening other family members. Subsequent in silico analyses of the mutational consequences for protein function were performed. RESULTS: There were two siblings from one family and one case in each of the two families. One family had a consanguineous marriage. Mutational screening revealed compound heterozygosity for the two alleles, p.C177R and p.G461R, in three patients, and homozygosity for complex alleles, p.R27H and p.R206P, in one patient from the consanguineous family. There were three putative novel variants, p.R27H, p.C177R, and p.R206P. The four variants in the families with KCNV2 were highly conserved in other species. In silico analyses predicted that all of the missense variants would alter protein function. CONCLUSIONS: Biallelic disease-causing variants were identified in four Japanese patients with CDSRR suggesting that the pathognomonic electrophysiological features are helpful in making a molecular diagnosis of KCNV2. Three novel variants were identified, and we conclude that there may be a distinct spectrum of KCNV2 alleles in the Japanese population.

Nutcracker phenomenon: An unusual presentation of acute aortic dissection.

We report a case of acute aortic dissection leading to compression of the left renal vein (LRV), thereby resulting in the nutcracker phenomenon. A 49-year-old previously healthy woman presented with intermittent gross hematuria and mild left flank pain of five days' duration. Laboratory examinations were within normal limits, except for the elevated C-reactive protein. Cystoscopy revealed bleeding from the left ureteral orifice. Contrast-enhanced computed tomography demonstrated acute Type B aortic dissection and compression of LRV between the enlarged aorta and superior mesenteric artery with an associated dilatation of the left gonadal vein as a collateral circulation.

Effect of Segmented Optical Axial Length on the Performance of New-Generation Intraocular Lens Power Calculation Formulas in Extremely Long Eyes.

PURPOSE: To evaluate the performance of traditional vergence formulas with segmented axial length (AL) compared to traditional composite AL in extremely long eyes, and to determine whether the segmented AL can be extended to the new-generation formulas, including the Barrett Universal II, Emmetropia Verifying Optical 2.0 (EVO2), Hill-RBF 3.0 (Hill3), Kane, and Ladas Super formula (LSF) formulas in extremely long eyes. SETTING: National Hospital. Organization, Tokyo Medical Center, Japan. DESIGN: Retrospective case series. METHODS: Consecutive patients who underwent uncomplicated cataract surgery implanted with a three-piece intraocular lens between December 2015 and March 2021 were retrospectively reviewed. The composite AL was measured with a swept-source optical coherence tomography (SS-OCT) biometer using a mean refractive index. The segmented AL was calculated by summing the geometric lengths of the ocular segments (cornea, aqueous, lens, and vitreous) using multiple specific refractive indices based on the data obtained by the SS-OCT-based biometer. When refraction was measured at three months postoperatively, the median absolute errors (MedAEs) were calculated with two ALs for each formula. RESULTS: The study included 31 eyes of 22 patients. The segmented AL (30.45 ± 1.23 mm) was significantly shorter than the composite AL (30.71 ± 1.28 mm, p < 0.001). The MedAEs were significantly reduced when using segmented AL for SRK/T, Haigis, Hill3, and LSF, compared to those obtained using composite AL (0.38 vs. 0.62, 0.48 vs. 0.79, 0.50 vs. 0.90, 0.34 vs. 0.61, p < 0.001 for all formulas, respectively). On the contrary, the MedAE obtained by Kane with segmented AL was significantly worse compared to the one with composite AL (0.35 vs. 0.27, p = 0.03). CONCLUSION: In extremely high myopic eyes, the segmented AL improves the performance of SRK/T, Haigis, Hill3, and LSF formulas compared to the composite AL, while the segmented AL worsens the prediction accuracy of the Kane formula.

Overexpression of optineurin E50K disrupts Rab8 interaction and leads to a progressive retinal degeneration in mice.

Glaucoma is one of the leading causes of bilateral blindness affecting nearly 8 million people worldwide. Glaucoma is characterized by a progressive loss of retinal ganglion cells (RGCs) and is often associated with elevated intraocular pressure (IOP). However, patients with normal tension glaucoma (NTG), a subtype of primary open-angle glaucoma (POAG), develop the disease without IOP elevation. The molecular pathways leading to the pathology of NTG and POAG are still unclear. Here, we describe the phenotypic characteristics of transgenic mice overexpressing wild-type (Wt) or mutated optineurin (Optn). Mutations E50K, H486R and Optn with a deletion of the first (amino acids 153-174) or second (amino acids 426-461) leucine zipper were used for overexpression. After 16 months, histological abnormalities were exclusively observed in the retina of E50K mutant mice with loss of RGCs and connecting synapses in the peripheral retina leading to a thinning of the nerve fiber layer at the optic nerve head at normal IOP. E50K mice also showed massive apoptosis and degeneration of entire retina, leading to approximately a 28% reduction of the retina thickness. At the molecular level, introduction of the E50K mutation disrupts the interaction between Optn and Rab8 GTPase, a protein involved in the regulation of vesicle transport from Golgi to plasma membrane. Wt Optn and an active GTP-bound form of Rab8 complex were localized at the Golgi complex. These data suggest that alternation of the Optn sequence can initiate significant retinal degeneration in mice.

Highly reflective foveal region in optical coherence tomography in eyes with vitreomacular traction or epiretinal membrane.

OBJECTIVE: To report the optical coherence tomography (OCT) findings in eyes with vitreomacular traction (VMT) or with an epiretinal membrane (ERM). DESIGN: Retrospective case series. PARTICIPANTS: Fifty-four eyes of 45 consecutive patients with subjective visual disturbances resulting from VMT or idiopathic ERM were studied. METHODS: The morphologic features of the photoreceptor layer at the foveal center were determined and the central foveal thickness (CFT) was measured by spectral-domain (SD) OCT. MAIN OUTCOME MEASURES: The morphologic characteristics of the foveal region observed by SD OCT. RESULTS: A roundish or diffuse highly reflective region was observed between the photoreceptor inner segment/outer segment junction line and the cone outer segment tip line at the center of the fovea. This highly reflective region was present in 7 of 7 cases of VMT and 30 of 47 cases of ERM. In the ERM cases, the mean CFT of the cases with the highly reflective region was significantly thicker than that in cases without it. The highly reflective region disappeared when the inward traction on the fovea was released surgically or spontaneously. CONCLUSIONS: The highly reflective region is a characteristic sign observed in the OCT images of eyes with VMT and ERM, and it has been termed the cotton ball sign after its appearance. The presence of the cotton ball sign indicates an inward traction on the fovea and may be a predictor of visual impairment.

Comparison of two one-piece acrylic foldable intraocular lenses: Short-term change in axial movement after cataract surgery and its effect on refraction.

PURPOSE: To compare the change in intraocular lens (IOL) axial movement, corneal power, and postoperative refraction of eyes implanted with two different single-piece, open loop, acrylic foldable IOLs with planar-haptic design: one IOL with hinges vs. one IOL without hinges. The role of IOL axial movement on short-term refractive shift after cataract surgery was also evaluated. METHODS: This retrospective comparative study enrolled consecutive patients who had phacoemulsification with aspheric IOL implantation. The IOL depth (the distance from corneal endothelium to IOL surface) and corneal power were measured via anterior-segment optical coherence tomography at 4 days and 1 month postoperatively. The changes in axial movement of the IOL, corneal power, and manifest refractive spherical equivalent (MRSE) were compared among groups, and the correlations between each lens were evaluated. RESULTS: IOL with hinges was implanted in 42 eyes of 42 patients and IOL without hinges was implanted in 42 eyes of 42 patients. The change in axial movement between 4 days and 1 month was significantly smaller in the IOL with hinges group than in the IOL without hinges group (p < 0.001). The axial movement of IOL with hinges did not correlate with the MRSE change; however, the forward shift of IOL without hinges correlated with the myopic refractive change (Pearson r = 0.62, p < 0.001). CONCLUSION: The postoperative axial movement of IOL was more stable in the IOL with hinges group than the IOL without hinges group between 4 days and 1 month after cataract surgery. Even though the two study IOLs with planar-haptic design are made of similar acrylic materials, other characteristics such as hinge structure may affect IOL stability in the bag.

Whole-cell observation of ZIO-stained Golgi apparatus in rat hepatocytes with serial block-face scanning electron microscope, SBF-SEM.

The Golgi apparatus, which plays a role in various biosynthetic pathways, is usually identified in electron microscopy by the morphological criteria of lamellae. A 3-dimensional analyses with serial block-face scanning electron microscope (SBF-SEM), a volume-SEM proficient in obtaining large volumes of data at the whole-cell level, could be a promising technique for understanding the precise distribution and complex ultrastructure of Golgi apparatus, although optimal methods for such analyses remain unclear since the observation can be hampered with sample charging and low image contrast, and manual segmentation often requires significant manpower. The present study attempted the whole-cell observation and semi-automatic classification and segmentation of the Golgi apparatus in rat hepatocytes for the first time by SBF-SEM via ZIO staining, a classical osmium impregnation. The staining electron-densely visualized individual Golgi lamellae, and their ultrastructure could stably be observed without any noticeable charging. The simple thresholding of the serial images enabled the efficient reconstruction of the labeled Golgi apparatus, which revealed plural Golgi apparatus in one hepatocyte. The combination of the heavy metal-based histochemistry of zinc, iodine and osmium (ZIO) staining and SBF-SEM was useful in the 3-dimensional observation of the Golgi apparatus at the whole-cell level because of two technical advantages: (i) visualization of the Golgi apparatus without any heavy metal staining and efficient acquisition of the block-face images without additional conductive staining or any devices for eliminating charging; (ii) easy identification of the staining and hassle-free, semi-automatic classification and segmentation by simple thresholding of the images. This novel approach could elucidate the topographic characteristics of the Golgi apparatus in hepatocytes.

Preliminary demonstration of a novel intraocular lens power calculation: the O formula.

PURPOSE: To evaluate the performance of a new formula of intraocular lens (IOL) power calculation (the O formula) based on ray tracing without commonly used parameters, including ultrasound-compatible axial length, keratometry readings, and A-constant. SETTING: Tokyo Medical Center, Tokyo, Japan. DESIGN: Retrospective consecutive case series. METHODS: 423 eyes (423 patients) implanted with a single-piece, L-loop, acrylic IOL were enrolled. All biometric data for the O formula were obtained by anterior segment swept-source optical coherence tomography (SS-OCT) and SS-OCT-based biometer. The performance of the O formula was compared with those of the Barrett Universal II (BUII) and Kane formulas at 1 month postoperatively. Statistical analysis was applied according to a heteroscedastic test with SD of prediction errors as the main parameter for formula performance. RESULTS: The SD of the O formula (0.426) was statistically significantly lower than that of the BUII formula (0.464, P = .034) but not statistically significantly different from that of the Kane formula (0.433, P = .601). The percentages of patients with refractive prediction errors within ±0.50 diopter (D) and ±1.00 D of the O, BUII, and Kane formulas were 75.4% and 98.6%, 77.1% and 97.9%, and 76.6% and 98.1%, respectively. CONCLUSIONS: The O formula, based on ray tracing using SS-OCT-based devices, is one of the promising approaches for IOL power calculation, although additional larger scale studies are needed. It may be used as an alternative in IOL power calculation because of its independence from commonly used parameters.

Suicidal attempt with caffeine overdose treated with dexmedetomidine: a case report.

BACKGROUND: Caffeine is a widely used dietary stimulant, and cases of caffeine overdoses, sometimes leading to death, are increasing. We encountered a case of caffeine intoxication resolved with administration of the sedative agent dexmedetomidine. CASE PRESENTATION: We administered dexmedetomidine for sedation and to suppress sympathetic nerve stimulation in the case of an 18-year-old Japanese male who ingested a massive dose of caffeine with the intention of committing suicide. The patient was in an excited state and had hypertension, sinus tachycardia, and hypokalemia with prominent QT prolongation. After dexmedetomidine administration, the patient's mental state, hemodynamics, and electrolyte levels were improved immediately. He was discharged without any sequelae 3 days later. CONCLUSION: Cases of acute caffeine intoxication with agitation, sympathetic overactivity and adverse cardiac events would benefit with dexmedetomidine treatment.