Immune checkpoint inhibitors for metastatic uveal melanoma: a meta-analysis.

Several studies have evaluated immune checkpoint inhibitors (ICIs) for metastatic uveal melanoma; however, the efficacy of ICIs in the previous studies varied greatly. In this systematic review, we searched for prospective or retrospective studies on single or dual-ICIs for metastatic uveal melanoma treatment. A random-effect model meta-analysis with generic inverse-variance was conducted, and 36 articles representing 41 cohorts of 1414 patients with metastatic uveal melanoma were included. The pooled outcomes were as follows: objective response rate (ORR) was 5.6% (95% confidence interval [95%CI] 3.7-7.5%; I2, 36%), disease control rate (DCR) was 32.5% (95% CI 27.2-37.7%; I2, 73%), median progression-free survival was 2.8 months (95% CI 2.7-2.9 months; I2, 26%), and median overall survival (OS) was 11.2 months (95% CI 9.6-13.2 months; I2, 74%). Compared to single-agent ICI, dual ICI led to better ORR (single-agent: 3.4% [95% CI 1.8-5.1]; dual-agent: 12.4% [95% CI 8.0-16.9]; P < 0.001), DCR (single-agent: 29.3%, [95% CI 23.4-35.2]; dual-agent: 44.3% [95% CI 31.7-56.8]; P = 0.03), and OS (single-agent: 9.8 months [95% CI 8.0-12.2]; dual-agent: 16.3 months [95% CI 13.5-19.7]; P < 0.001). Our analysis provided treatment outcomes as described above. Dual-ICIs appear better than single-agent ICIs for the treatment of metastatic uveal melanoma.

Mood and physiological effects of visual stimulation with images of the natural environment in individuals with depressive and anxiety disorders.

BACKGROUND: Nature therapies are gaining attention as non-pharmacological treatments for depressive and anxiety disorders, but research on their effectiveness in patients is limited. This study investigates the mood-improving effects of visual stimulation with natural environmental images in patients with depressive and anxiety disorders. METHODS: We conducted a randomized crossover comparison trial involving 60 right-handed adult participants with depressive or anxiety disorders and receiving outpatient treatment. Visual stimuli of natural environments consisted of green-themed nature images, while the control stimuli featured urban scenes dominated by buildings. The stimulation lasted for 3 min, during which orbital prefrontal brain activity was measured using a 2-channel Near-infrared Spectroscopy (NIRS) system, and heart rate variability was assessed using fingertip accelerated plethysmography. RESULTS: Mood enhancement effects were observed in both the depressive and anxiety disorder groups following visual stimulation with nature images. In the depression group, orbital prefrontal oxygenated hemoglobin concentration significantly increased after visual stimulation with nature images, while there were no significant changes in the anxiety group. However, in the anxiety group, a correlation was found between reduced orbital prefrontal oxygenated hemoglobin in response to nature images and increased mood-enhancement. Furthermore, the severity of depressive symptoms did not significantly affect the intervention effects, whereas heightened anxiety symptoms was associated with a smaller mood enhancement effect. DISCUSSION: Our study demonstrates the benefits of nature image stimulation for patients with depressive and anxiety disorders. Differential orbital prefrontal brain activity impacts notwithstanding, both conditions exhibited mood enhancement, affirming the value of nature image stimulation.

HLA-DRB1*04:05 is involved in the development of Vogt-Koyanagi-Harada disease-like immune-related adverse events in patients receiving immune checkpoint inhibitors.

Immune checkpoint inhibitors (ICIs) activate anti-tumor activity by inhibiting immune checkpoint molecules that suppress inflammatory T-cell activity. However, ICIs can initiate excessive immune responses, thereby causing immune-related adverse events (irAEs). ICI-associated uveitis (ICIU) is an irAE that affects the eyes. Although Vogt-Koyanagi-Harada disease (VKH)-like uveitis is a common form of ICIU, it is unclear which factors determine the ICIU form. We retrospectively reviewed the medical records of nine ICIU cases treated with ICIs for malignancies. We also performed HLA typing in seven cases to investigate the association between HLA and disease type. Fisher's exact test was used for the statistical analysis. Five of the ICIU cases were VKH-like ICIUs, and four were non-VKH-like ICIUs. No association was found between mean age, sex, primary disease, ICI, time to onset, and disease type. Four patients with VKH-like uveitis underwent HLA genotyping and were all positive for HLA-DRB1*04:05. All 3 patients with non-VKH-like uveitis were negative for HLA-DRB1*04:05. Statistical analysis showed that HLA-DRB1*04:05 was significantly associated with developing VKH-like ICIU (P = 0.029). In ICIU, HLA-DRB1*04:05 was associated with the pathogenesis of VKH-like uveitis, suggesting that ICI-associated VKH-like uveitis has a similar pathogenesis to VKH.

Interferon signaling and hypercytokinemia-related gene expression in the blood of antidepressant non-responders.

Only 50% of patients with depression respond to the first antidepressant drug administered. Thus, biomarkers for prediction of antidepressant responses are needed, as predicting which patients will not respond to antidepressants can optimize selection of alternative therapies. We aimed to identify biomarkers that could predict antidepressant responsiveness using a novel data-driven approach based on statistical pattern recognition. We retrospectively divided patients with major depressive disorder into antidepressant responder and non-responder groups. Comprehensive gene expression analysis was performed using peripheral blood without narrowing the genes. We designed a classifier according to our own discrete Bayes decision rule that can handle categorical data. Nineteen genes showed differential expression in the antidepressant non-responder group (n = 15) compared to the antidepressant responder group (n = 15). In the training sample of 30 individuals, eight candidate genes had significantly altered expression according to quantitative real-time polymerase chain reaction. The expression of these genes was examined in an independent test sample of antidepressant responders (n = 22) and non-responders (n = 12). Using the discrete Bayes classifier with the HERC5, IFI6, and IFI44 genes identified in the training set yielded 85% discrimination accuracy for antidepressant responsiveness in the 34 test samples. Pathway analysis of the RNA sequencing data for antidepressant responsiveness identified that hypercytokinemia- and interferon-related genes were increased in non-responders. Disease and biofunction analysis identified changes in genes related to inflammatory and infectious diseases, including coronavirus disease. These results strongly suggest an association between antidepressant responsiveness and inflammation, which may be useful for future treatment strategies for depression.

Genetic polymorphisms in CYP19A1 and ESR1 are associated with serum CK activity after prolonged running in men.

This study aimed to clarify 1) the influence of genetic polymorphisms in the cytochrome P450 aromatase gene (CYP19A1) on circulating estradiol levels in men and 2) whether estrogen-related genetic polymorphisms, such as the CYP19A1 rs936306 and estrogen receptor-α (ESR1) rs2234693 polymorphisms, predict exercise-induced serum creatine kinase (CK) activity, which is an index of skeletal muscle membrane disruption. Serum estradiol levels were examined in young men (n = 167). In a different cohort, serum CK activity was analyzed in a 2-day ultramarathon race: baseline, after the first day, and after the second day (114 males and 25 females). Genetic polymorphisms in CYP19A1 rs936306 C/T and ESR1 rs2234693 T/C were analyzed using the TaqMan SNP Genotyping Assay. Male subjects with the TT genotype of the CYP19A1 polymorphism exhibited significantly higher serum estradiol levels than the C allele carriers. Male runners had significantly higher postrace serum CK activity than female runners. The change in the CK activity during the ultramarathon race was significantly lower in male subjects with the CYP19A1 TT genotype than in those with the CC + CT genotypes and was correlated with the number of C alleles in ESR1 rs2234693 in male subjects. Furthermore, the genotype scores of these two polymorphisms were significantly correlated with changes in serum CK activity during race (r = -0.279, P = 0.003). The results of this study suggest that genetic polymorphisms in CYP19A1 rs936306 influence serum estradiol levels in men, and genetic polymorphisms in CYP19A1 and ESR1 are associated with serum CK activity in men.NEW & NOTEWORTHY Men with the TT genotype of the CYP19A1 polymorphism exhibited higher circulating estradiol levels than the TC + CC genotype. The TT genotype in the CYP19A1 polymorphism and the C allele of the ESR1 polymorphism, an allele increasing ESR1 expression, were associated with low serum CK activity after the ultramarathon. A combination of these polymorphisms was correlated with changes in the serum CK activity. Therefore, estrogen-related genetic polymorphisms partially predict exercise-induced muscle damage, that is, skeletal muscle membrane disruption.

One-year limb outcome and mortality in patients undergoing revascularization therapy for acute limb ischemia: short-term results of the Edo registry.

The present study aimed to clarify the current status, therapeutic strategy, and 1-year outcome in acute limb ischemia (ALI) patients in Japan. The EnDOvascular treatment (Edo) registry database includes 324 patients from 10 institutes who were registered between November 2011 and October 2013. A total of 70 ALI patients (mean age 74.0 years) from the Edo registry database were enrolled in this study. Of the 70 included patients, 72.9% were male and 35.7% had embolism. Of patients, 38.6%, 42.9%, and 18.6% underwent EVT, surgery, and hybrid thrombectomy, respectively, in primary revascularization strategy. Limb ischemia was categorized into four classes at initial evaluation: SVS/ISCVS class I (n = 13, 18.6%), SVS/ISCVS class IIa (n = 36, 51.4%), SVS/ISCVS class IIb (n = 21, 30%), and SVS/ISCVS class III (n = 0, 0%). Three patients with SVS/ISCVS class IIb limb ischemia developed myonephropathic metabolic syndrome. No catheter-directed thrombolysis was employed as a primary revascularization strategy. The 1-year rates of all-cause death, major amputation, and a composite of perioperative death or major adverse limb event were 28.6%, 5.7%, and 40.0%, respectively. Lower age, male sex, dyslipidemia, high estimated glomerular filtration rate, high albumin level, and low C-reactive protein level were independent positive predictors of all-cause death. In this registry, SVS/ISCVS class IIa ALI was predominant. Approximately 40% of primary revascularization strategy was surgery and EVT, followed by hybrid therapy. All-cause death and major amputation rates at 1 year were less than 30% and 6%, respectively.

Predictors of increase in pacing threshold after transcatheter pacing system implantation due to micro-dislodgement.

BACKGROUND: Achieving a favorable pacing threshold with a Micra transcatheter pacing system (Micra-TPS) is needed to reduce battery depletion. In some cases, the threshold increases shortly after the device is implanted, and a higher pacing threshold may be required. This study aims to identify the causes and predictors of the increase in pacing threshold observed shortly after Micra-TPS implantation. METHODS: The study included 64 consecutive patients who underwent Micra-TPS implantation between 2017 and 2020. The patients were divided into two groups depending on their pacing threshold: the increased pacing threshold (IPT) group (threshold increased by ≥0.5 V/0.24 ms within 1 month of implantation) and the stable pacing threshold (SPT) group. RESULTS: Excluding four patients who could not be followed up, of the 60 remaining patients, nine (15%) were in the IPT group and 51 (85%) were in the SPT group. The IPT group had significantly lower implant impedance values and higher implant thresholds than the SPT group (582 ± 59 vs 755 ± 167 Ω [P < .001] and 1.29 ± 0.87 vs 0.71 ± 0.40 V/0.24 ms [P = .014]). Implant impedance and threshold may serve as predictors of a threshold increase after implantation (area under the curve: 0.737-0.943 and 0.586-0.926, respectively). CONCLUSIONS: An IPT was noted shortly after Micra-TPS implantation owing to micro-dislodgement because of insufficient anchoring of the device to the myocardium. Impedance >660 Ω and threshold <1.0 V/0.24 ms may predict an increase in pacing threshold.

Genome-Wide Association Study in Asians Identifies Novel Loci for High Myopia and Highlights a Nervous System Role in Its Pathogenesis.

PURPOSE: To identify novel susceptibility loci for high myopia. DESIGN: Genome-wide association study (GWAS) followed by replication and meta-analysis. PARTICIPANTS: A total of 14 096 samples from East and Southeast Asian populations (2549 patients with high myopia and 11 547 healthy controls). METHODS: We performed a GWAS in 3269 Japanese individuals (1668 with high myopia and 1601 control participants), followed by replication analysis in a total of 10 827 additional samples (881 with high myopia and 9946 control participants) from Japan, Singapore, and Taiwan. To confirm the biological role of the identified loci in the pathogenesis of high myopia, we performed functional annotation and Gene Ontology (GO) analyses. MAIN OUTCOME MEASURES: We evaluated the association of single nucleotide polymorphisms with high myopia and GO terms enriched among genes identified in the current study. RESULTS: We identified 9 loci with genome-wide significance (P < 5.0 × 10-8). Three loci were previously reported myopia-related loci (ZC3H11B on 1q41, GJD2 on 15q14, and RASGRF1 on 15q25.1), and the other 6 were novel (HIVEP3 on 1p34.2, NFASC/CNTN2 on 1q32.1, CNTN4/CNTN6 on 3p26.3, FRMD4B on 3p14.1, LINC02418 on 12q24.33, and AKAP13 on 15q25.3). The GO analysis revealed a significant role of the nervous system related to synaptic signaling, neuronal development, and Ras/Rho signaling in the pathogenesis of high myopia. CONCLUSIONS: The current study identified 6 novel loci associated with high myopia and demonstrated an important role of the nervous system in the disease pathogenesis. Our findings give new insight into the genetic factors underlying myopia, including high myopia, by connecting previous findings and allowing for a clarified interpretation of the cause and pathophysiologic features of myopia at the molecular level.

Bacterial Detection Rate and Surgical Outcome in Povidone-Iodine Irrigation After Nasolacrimal Duct Intubation.

PURPOSE: In various ophthalmic surgical procedures, 0.25% povidone-iodine (PI) solution is used to prevent infections. This study examined the bacterial colonisation before and after endoscopic nasolacrimal duct intubation irrigated with PI solution and investigated the relationship between bacterial detection and surgical failure. METHODS: A retrospective study at Saitama Medical University Hospital. We enrolled 113 patients (33 men, 80 women) who underwent lacrimal intubation surgery between April 2016 and December 2018. Preoperatively, the lacrimal pathways were washed with normal saline solution, which was subsequently cultured. The sites of obstruction in the lacrimal pathway were endoscopically determined, perforated, and intubated. The tubes were afterward either irrigated with 0.25% PI or normal saline every 2 weeks. After 8 weeks, a piece of the removed lacrimal tube was cultured. We characterized the pre- and postoperative bacterial cultures. RESULTS: We enrolled 54 and 52 patients in PI and saline groups (mean age: 69.1±9.2 and 73.2±7.2 years), respectively. In the PI group, Staphylococcus epidermidis was less frequently detected postoperatively than preoperatively. S. oralis and Candida parapsilosis were identified more often postoperatively (P=0.02, P=0.01, respectively). The PI group had significantly lower bacterial detection rate than the saline group (P=0.01). However, the surgical failure rates did not differ between groups. In surgical failure patients, the postoperative rate of Pseudomonas aeruginosa was very high (75%). CONCLUSION: PI reduces the bacterial detection rate but does not improve the surgical success rate. P. aeruginosa is associated with an increased risk of surgical failure.

Iris Posterior Synechiae After Descemet Membrane Endothelial Keratoplasty in Asian Eyes: Prevention and Management of Posterior Synechiae.

OBJECTIVES: To evaluate the efficacy of a mydriatic agent for posterior synechiae after phacoemulsification and intraocular lens (IOL) implantation followed by Descemet membrane endothelial keratoplasty (staged DMEK). METHODS: In this prospective study, the outcomes of DMEK with or without mydriasis (0.5% tropicamide and 0.5% phenylephrine hydrochloride [Mydrin-P; Santen, Osaka, Japan]) after the DMEK procedure were analyzed. Patients underwent IOL implantation approximately 4 weeks before DMEK. Six months after DMEK, the iris posterior synechiae severity score was evaluated based on the extent of posterior synechiae affecting the eight areas (45° each) of the pupillary rim (posterior synechiae score; grades 0-8). Best spectacle-corrected visual acuity, central corneal thickness, endothelial cell density, axial length, and the amount of air at the end of the surgery were also evaluated. RESULTS: Fifteen eyes of 15 patients (mydriatic: n=8, control: n=7) were eligible for inclusion. Iris posterior synechiae were detected in all seven eyes (100.0%) in the control group, whereas they were noted in two eyes in the mydriatic group (25%). The mean iris posterior synechiae score was 0.69±1.20 in the mydriatic group and was significantly lower than that in the control group (4.57±0.90; P<0.001). There was no significant difference in other clinical factors. Although the incidence and scores of posterior synechiae in the control group were higher, the incidence was significantly reduced with the use of a mydriatic agent (in the mydriatic group). CONCLUSIONS: Use of a mydriatic agent is an effective measure to prevent postoperative synechiae after DMEK.

Association between axial length and in vivo human crystalline lens biometry during accommodation: a swept-source optical coherence tomography study.

PURPOSE: To evaluate the association between axial length and crystalline lens biometry with and without accommodation using the CASIA2 swept-source (SS) optical coherence tomography (OCT) system on the anterior segment. STUDY DESIGN: Intervention study. METHODS: Individuals aged 20 to 39 years were enrolled for SS-OCT imaging at 2 separate visits within 1 week. Each eye was imaged under accommodation stimuli with different amplitudes (0 D, -1 D, -3 D, -5 D, and -7 D). The anterior and posterior lens curvature radii and lens thicknesses were measured. The participants were divided into 4 groups according to axial length. RESULTS: Forty-eight participants (96 eyes) were initially enrolled. All 96 eyes were included in the analyses, as they met the eligibility criteria and each had proper OCT images. The mean participant age was 25.9 ± 4.3 years, and the mean spherical error was -3.5 ± 2.5 D. The mean axial length was 25.1 ± 1.2 mm. Multivariate analysis revealed that the anterior curvature radius became flatter and the lens thickness became thicker as the axial length increased (all P < .01). Furthermore, axial length independently contributed to the shape of the lens after adjusting for the effects of age and accommodation stimuli. CONCLUSION: Axial length was associated with lens shape after adjusting for age and accommodation stimuli. These measurements can provide a glimpse of dynamic lens biometry changes, which may help us better understand the role of lenses in various physiologic changes, including accommodation and myopia.

Efficacy of Strip Meniscometry for Detecting Lacrimal Obstructive Diseases Among Patients With Epiphora.

PURPOSE: Strip meniscometry (SM) is a new technique for evaluating tear film volume. The aim of the present study was to evaluate the efficacy of SM in detecting lacrimal obstructive diseases (LODs) in patients with epiphora retrospectively. METHODS: One-hundred sixty-six patients (53 men, 113 women; mean age: 72.4 ± 8.0 years) who were referred to Saitama Medical University Hospital with epiphora as their chief complaint were enrolled; finally, 72 patients with and 89 patients without LOD were examined. We assessed tear volume using SM, tear meniscus height (TMH), tear meniscus area (TMA), and Schirmer-1 test values. Patients with LOD underwent lacrimal intubation surgery to treat their epiphora; their SM scores were assessed before and 8 weeks after surgery. RESULTS: SM, TMH, TMA, and Schirmer-1 values were significantly higher in the LOD group (10.80 ± 3.63 mm, 0.49 ± 0.24 mm, 0.06 ± 0.06 mm2, 18.46 ± 8.00 mm, respectively) than in the non-LOD group (5.44 ± 3.20 mm, 0.30 ± 0.18 mm, 0.03 ± 0.04 mm2, 11.84 ± 7.16 mm). The area under the receiver operating characteristic curve (AUC) for SM was 0.88, the sensitivity and specificity were 82% and 84%. The AUC was significantly larger for SM than for the Schirmer-1 test and TMA. The SM scores significantly improved after surgery (5.30 ± 2.20 mm) compared with those before (10.69 ± 3.20 mm). CONCLUSIONS: SM was significantly better than the Schirmer-1 test, TMH, and TMA for detecting LOD and evaluating the effect of lacrimal surgery. TRANSLATIONAL RELEVANCE: SM, widely used for dry eye, is also useful for using epiphora.

Outcomes of Descemet Membrane Endothelial Keratoplasty for Vitrectomized Eyes with Sutured Posterior Chamber Intraocular Lens.

PURPOSE: To evaluate the clinical outcomes of Descemet membrane endothelial keratoplasty (DMEK) for vitrectomized eyes that underwent pars plana vitrectomy (PPV) and transscleral-sutured intraocular lens (IOL) implantation. METHODS: In this retrospective study, DMEK cases were reviewed from medical records and divided into two groups: the eyes after PPV and transscleral-sutured IOL implantation (vitrectomized group) and the eyes with in-the-bag IOL implantation (control group) prior to DMEK. The main outcome measures included time of graft unfolding during surgery and best spectacle-corrected visual acuity (BSCVA), central corneal thickness (CCT), and endothelial cell density (ECD) at 1, 3, and 6 months after the DMEK. RESULTS: Twenty-three eyes (vitrectomized group, n = 8; control group, n = 15) in 23 patients were included in this study. The unfolding time was significantly longer in the vitrectomized group than in the control group (P < 0.001). Postoperative BSCVA was worse in the vitrectomized group (0.16 ± 0.15) than in the control group (-0.06 ± 0.06; P = 0.017). The improvement in BSCVA was negatively correlated with the patients' age and frequency of previous surgeries. CONCLUSIONS: Despite the longer graft unfolding time and limited visual recovery, DMEK should be applicable to vitrectomized eyes with transscleral-sutured IOL implantation.

Creating a Full-thickness Choroidal Incision: An Ex Vivo Analysis of Human and Porcine Tissue Contraction Dynamics.

PURPOSE: We hypothesized that the elastic nature of the choroid leads to tissue contraction following a full-thickness, sharp incision. Furthermore, we sought to quantify, measure, and compare tissue contraction in ex vivo porcine globes and human globes of various ages using predetermined variables. METHOD: A full-thickness, ex vivo choroidal incision was performed in either pig (n = 97) or human (n = 30) specimens. Variables included trephine diameter (1.5, 2.0, or 2.5 mm) versus a straight surgical blade, and temperature (1.7 °-4.4° vs. 36.6°F). Central centripetal and surround centrifugal tissue contractions were measured. Mean percentage tissue contraction was assessed as a ratio of trephine diameter to final tissue contraction measured immediately following each incision using a standardized device. RESULTS: For trephination in pig specimens, centripetal contraction ranged from 38% to 50% with a mean of 44%. Centrifugal contraction was approximately 15%. Human choroidal contraction was 39% and 15%, respectively, with a statistically significant inverse relationship to age (R2 = 0.35, P ≤ 0.01). Asymmetric contraction was noted when incisions were closer to choroidal attachment sites to the sclera, such as near vortex ampullae. Linear incisions resulted in contraction that correlated with incision length (R2 = 0.35, P ≤ 0.001). CONCLUSIONS: A full-thickness choroidal incision results in significant tissue contraction. For circular incisions, the centripetal contraction approaches 50% of the original incision size. For linear incisions, the contraction corresponds directly with incision length. In human specimens, there is less contraction with advancing age. TRANSLATIONAL RELEVANCE: Our findings have clinical relevance for choroidal biopsy, traumatic injury, and choroidal translocation surgery.

In vivo crystalline lens measurements with novel swept-source optical coherent tomography: an investigation on variability of measurement.

OBJECTIVE: To evaluate the reproducibility of in vivo crystalline lens measurements obtained by novel commercially available swept-source (SS) optical coherence tomography (OCT) specifically designed for anterior segment imaging. METHODS AND ANALYSIS: One eye from each of 30 healthy subjects was randomly selected using the CASIA2 (Tomey, Nagoya, Japan) in two separate visits within a week. Each eye was imaged twice. After image scanning, the anterior and posterior lens curvatures and lens thickness were calculated automatically by the CASIA2 built-in program at 0 dioptre (D) (static), -1 D, -3 D and -5 D accommodative stress. The intraobserver and intervisit reproducibility coefficient (RC) and intraclass correlation coefficient (ICC) were calculated. RESULTS: The intraobserver and intervisit RCs ranged from 0.824 to 1.254 mm and 0.789 to 0.911 mm for anterior lens curvature, from 0.276 to 0.299 mm and 0.221 to 0.270 mm for posterior lens curvature and from 0.065 to 0.094 mm and 0.054 to 0.132 mm for lens thickness, respectively. The intraobserver and intervisit ICCs ranged from 0.831 to 0.865 and 0.828 to 0.914 for anterior lens curvature, from 0.832 to 0.898 and 0.840 to 0.933 for posterior lens curvature and from 0.980 to 0.992 and 0.942 to 0.995 for lens thickness. High ICC values were observed for each measurement regardless of accommodative stress. RCs in younger subjects tended to be larger than those in older subjects. CONCLUSIONS: This novel anterior segment SS-OCT instrument produced reliable in vivo crystalline lens measurement with good repeatability and reproducibility regardless of accommodation stress.

Use of four asymmetric marks to orient the donor graft during Descemet's membrane endothelial keratoplasty.

INTRODUCTION: Maintaining the correct orientation of the donor graft is important during Descemet's membrane endothelial keratoplasty (DMEK). We describe a new method of marking the donor graft prior to DMEK. METHODS: Twelve eyes of 10 patients with bullous keratopathy who underwent DMEK were retrospectively analysed. Donor discs were created by stripping the endothelium-Descemet's membrane layer from corneoscleral buttons. Four semicircular marks, two 1.0 mm and two 1.5 mm in diameter, were created at the edge of the donor disc. The small and large marks were paired. Each donor graft was inserted into the anterior chamber, unfolded and attached to the posterior corneal stroma with an air bubble. RESULTS: The inserted grafts were all appropriately orientated when attached to the back surfaces of the corneas. The two pairs of asymmetric marks afforded valuable guidance. Even when the graft was partially folded or decentred, and one pair of marks was obscured, the other pair was always visible to indicate graft orientation. Best spectacle-corrected visual acuity improved significantly in all patients (p<0.001). Compared with the preoperative endothelial cell density of the donor graft, that of the corneal endothelium had decreased 44.0%±10.0% by 6 months after surgery. CONCLUSIONS: Two pairs of asymmetrical semicircular marks placed on the edge of the donor graft allowed appropriate graft orientation during DMEK.

Quantitative measurement of hydrophilicity/hydrophobicity of the plasma-polymerized naphthalene film (Super Support Film) and other support films and grids in electron microscopy.

Hydrophilicity/hydrophobicity of the surfaces of plasma-polymerized naphthalene film (Super Support Film, Nisshin EM Co. Ltd., Tokyo), carbon and formvar support films, and copper and nickel grids were quantitatively estimated by contact angles measured from diameters and heights of water droplets placed on various specimens. With treatment of glow discharge, the surfaces of plasma-polymerized naphthalene and carbon support films became fully hydrophilic in 20 s. They remained hydrophilic for 6 h. The surfaces of copper and nickel grids became fully hydrophilic with 60 s of glow discharge treatment. They remained hydrophilic for only 1 h. This information is useful for negative staining, ultrathin sectioning and rapid freezing of biological specimens using the sandwich method.

Routes for Drug Delivery to the Retina: Topical, Transscleral, Suprachoroidal and Intravitreal Gas Phase Delivery.

Local drug delivery to the posterior segment, particularly the macula, represents a significant challenge. In this chapter, we review current challenges, barriers and limitations. Due to the local drug delivery to the retina and macula, systemic side effects are limited. In this chapter, we also discuss the historical approaches, key aspects of ideal drug delivery systems, the use of animal models to study pharmacokinetics, and the principles of transscleral, suprachoroidal and gas phase drug delivery.

Effect of Hemodialysis on 7-Year Clinical Outcomes After Sirolimus-Eluting Stent Implantation.

BACKGROUND: Hemodialysis (HD) patients are reported to show poor clinical outcomes after percutaneous coronary intervention (PCI) with sirolimus-eluting stent (SES) compared with non-HD patients and their long-term prognosis remains unclear. METHODS AND RESULTS: We prospectively enrolled 489 consecutive patients undergoing PCI with SES and performed a retrospective analysis focusing on HD patients. Median follow-up was 7.0 years (interquartile range, 4.2-7.9) and the follow-up rate was 100%. At the 7-year follow-up, the cumulative incidences of all-cause death, target lesion revascularization (TLR) and major adverse cardiac events (MACE) were significantly higher in HD patients than in non-HD patients (HD vs. non-HD=34.7% vs. 9.6%, 42.6% vs. 10.2% and 75.3% vs. 24.4%, respectively; log-rank P<0.001). Cox-proportional hazard analysis revealed that independent predictors of all-cause death were HD (hazard ratio [HR] 2.88, 95% confidence interval [CI]: 1.39-6.00), insulin-treated diabetes mellitus (HR 2.19, 95% CI: 1.17-4.11), heart failure (HR 2.58, 95% CI: 1.25-5.32) and older age (HR 1.06/1-age, 95% CI: 1.02-1.10). Moreover, HD was an independent predictor of TLR (HR 3.63, 95% CI: 1.85-7.11) and MACE (HR 3.54, 95% CI: 2.19-5.73). CONCLUSIONS: In the present study, Japanese HD patients undergoing PCI with SES showed poorer long-term clinical outcomes than non-HD patients. HD was a strong predictor of long-term adverse events after SES implantation.

Contact Lens-Related Infectious Keratitis with White Plaque Formation Caused by Corynebacterium propinquum.

We report the first case of Corynebacterium propinquum keratitis in the compromised cornea of a diabetic patient wearing therapeutic contact lenses. The strain was identified to the species level based on sequencing of the 16S rRNA gene and RNA polymerase ß-subunit-encoding gene (rpoB). Ophthalmologists should be aware of nondiphtherial corynebacterial infection of compromised corneas.