Pulse-Wave Analysis of Optic Nerve Head Circulation Is Significantly Correlated with Kidney Function in Patients with and without Chronic Kidney Disease

Aim. To determine whether there is a significant correlation between the optic nerve head (ONH) circulation determined by laser speckle flowgraphy (LSFG) and kidney function. Materials. Seventy-one subjects were investigated. The estimated glomerular filtration rate (GFR) and serum creatinine, cystatin C, and urinary albumin excretion were measured. The ONH circulation was determined by an analysis of the pulse wave of LSFG, and this parameter was named blowout time (BOT). Chronic kidney disease (CKD) was defined to be present when the estimated GFR was <60 mL/min per 1.73 m2. Pearson’s correlation coefficients were used to determine the relationship between the BOT and the kidney function. We also examined whether there were significant differences in all parameters in patients with and without CKD. Results. BOT was significantly correlated with the level of creatinine (r=-0.24, P=0.04), the estimated GFR (r=0.42, P=0.0003), cystatin C (r=-0.29, P=0.01), and urinary albumin excretion (r=-0.29, P=0.01). The BOT level in subjects with CKD was significantly lower than that in subjects without CKD (P=0.002). Conclusion. BOT in ONH by LSFG can detect the organ damage such as kidney dysfunction, CKD

Efficacy and Safety of Intravitreal Aflibercept Treat-and-Extend Regimens in Exudative Age-Related Macular Degeneration: 52- and 96-Week Findings from ALTAIR : A Randomized Controlled Trial.

PURPOSE:To evaluate efficacy and safety of intravitreal injections of aflibercept (IVT-AFL) treat-and-extend (T&E) dosing regimens in treatment-naïve patients with exudative age-related macular degeneration (AMD).METHODS:Adults aged at least 50 years old with exudative AMD and best-corrected visual acuity (BCVA) of 73-25 Early Treatment Diabetic Retinopathy Study (ETDRS) letters were included. Patients received three monthly doses of IVT-AFL 2 mg. At week 16, patients were randomized 1:1 to IVT-AFL T&E with either 2- or 4-week adjustments. The primary endpoint was mean change in BCVA from baseline to week 52. Outcomes were assessed at weeks 52 and 96.RESULTS:Baseline characteristics were comparable between the groups (n = 123 each). Over 52 weeks, mean number of injections was 7.2 and 6.9 and mean last injection interval was 10.7 and 11.8 weeks, for the 2- and 4-week groups, respectively. From baseline, mean change in BCVA was + 9.0 and + 8.4 letters (week 52) and + 7.6 and + 6.1 letters (week 96); mean change in central retinal thickness was - 134.4 µm and - 126.1 µm (week 52) and - 130.5 µm and - 125.3 µm (week 96). Last injection interval before week 52 was at least 12 weeks in 42.3% and 49.6% of patients and 56.9% and 60.2% before week 96. Over 96 weeks, mean number of injections was 10.4 (both groups). The safety profile of IVT-AFL was consistent with previous reports.CONCLUSIONS:IVT-AFL administered using two different T&E regimens for treatment-naïve exudative AMD improved functional and anatomic outcomes at week 52 and outcomes were maintained to week 96. Outcomes were similar between the 2- and 4-week groups.TRIAL REGISTRATION:ClinicalTrials.gov identifier, NCT02305238

The whole blood transcriptional regulation landscape in 465 COVID-19 infected samples from Japan COVID-19 Task Force

「コロナ制圧タスクフォース」COVID-19患者由来の血液細胞における遺伝子発現の網羅的解析 --重症度に応じた遺伝子発現の変化には、ヒトゲノム配列の個人差が影響する--. 京都大学プレスリリース. 2022-08-23.Coronavirus disease 2019 (COVID-19) is a recently-emerged infectious disease that has caused millions of deaths, where comprehensive understanding of disease mechanisms is still unestablished. In particular, studies of gene expression dynamics and regulation landscape in COVID-19 infected individuals are limited. Here, we report on a thorough analysis of whole blood RNA-seq data from 465 genotyped samples from the Japan COVID-19 Task Force, including 359 severe and 106 non-severe COVID-19 cases. We discover 1169 putative causal expression quantitative trait loci (eQTLs) including 34 possible colocalizations with biobank fine-mapping results of hematopoietic traits in a Japanese population, 1549 putative causal splice QTLs (sQTLs; e.g. two independent sQTLs at TOR1AIP1), as well as biologically interpretable trans-eQTL examples (e.g., REST and STING1), all fine-mapped at single variant resolution. We perform differential gene expression analysis to elucidate 198 genes with increased expression in severe COVID-19 cases and enriched for innate immune-related functions. Finally, we evaluate the limited but non-zero effect of COVID-19 phenotype on eQTL discovery, and highlight the presence of COVID-19 severity-interaction eQTLs (ieQTLs; e.g., CLEC4C and MYBL2). Our study provides a comprehensive catalog of whole blood regulatory variants in Japanese, as well as a reference for transcriptional landscapes in response to COVID-19 infection

DOCK2 is involved in the host genetics and biology of severe COVID-19

「コロナ制圧タスクフォース」COVID-19疾患感受性遺伝子DOCK2の重症化機序を解明 --アジア最大のバイオレポジトリーでCOVID-19の治療標的を発見--. 京都大学プレスリリース. 2022-08-10.Identifying the host genetic factors underlying severe COVID-19 is an emerging challenge. Here we conducted a genome-wide association study (GWAS) involving 2, 393 cases of COVID-19 in a cohort of Japanese individuals collected during the initial waves of the pandemic, with 3, 289 unaffected controls. We identified a variant on chromosome 5 at 5q35 (rs60200309-A), close to the dedicator of cytokinesis 2 gene (DOCK2), which was associated with severe COVID-19 in patients less than 65 years of age. This risk allele was prevalent in East Asian individuals but rare in Europeans, highlighting the value of genome-wide association studies in non-European populations. RNA-sequencing analysis of 473 bulk peripheral blood samples identified decreased expression of DOCK2 associated with the risk allele in these younger patients. DOCK2 expression was suppressed in patients with severe cases of COVID-19. Single-cell RNA-sequencing analysis (n = 61 individuals) identified cell-type-specific downregulation of DOCK2 and a COVID-19-specific decreasing effect of the risk allele on DOCK2 expression in non-classical monocytes. Immunohistochemistry of lung specimens from patients with severe COVID-19 pneumonia showed suppressed DOCK2 expression. Moreover, inhibition of DOCK2 function with CPYPP increased the severity of pneumonia in a Syrian hamster model of SARS-CoV-2 infection, characterized by weight loss, lung oedema, enhanced viral loads, impaired macrophage recruitment and dysregulated type I interferon responses. We conclude that DOCK2 has an important role in the host immune response to SARS-CoV-2 infection and the development of severe COVID-19, and could be further explored as a potential biomarker and/or therapeutic target

Choroidal blood flow impairment demonstrated using laser speckle flowgraphy in a case of commotio retinae

Purpose: To report the time course of choroidal blood flow (CBF) in a commotio retinae case using laser speckle flowgraphy (LSFG). Observations: A 58-year-old Japanese man with complaints of worsening left visual acuity after blunt eye trauma was diagnosed with commotio retinae. A funduscopic examination showed macular opacity, and LSFG results demonstrated CBF impairment in the affected eye. Optical coherence tomography also showed disruption of the photoreceptor outer segment. Seven months after the initial visit, CBF was significantly increased, along with improvement in the photoreceptor outer segment. Conclusion: and importance: We revealed CBF impairment in a case of commotio retinae for the first time. CBF impairment may be involved in the pathogenesis of commotio retinae, and LSFG may be useful for examining CBF in commotio retinae

Comparison of Optic Nerve Head Blood Flow Autoregulation among Quadrants Induced by Decreased Ocular Perfusion Pressure during Vitrectomy

Purpose. The present study aimed to examine changes in optic nerve head (ONH) blood flow autoregulation in 4 quadrants (superior, nasal, inferior, and temporal) with decreased ocular perfusion pressure (OPP) during vitrectomy in order to determine whether there is a significant difference of autoregulatory capacity in response to OPP decrease at each ONH quadrant. Methods. This study included 24 eyes with an epiretinal membrane or macular hole that underwent vitrectomy at Toho University Sakura Medical Center. Following vitrectomy, the tissue mean blur rate (MBR), which reflects ONH blood flow, was measured. Mean tissue MBRs in the four quadrants were generated automatically in the software analysis report. Measurements were conducted before and 5 and 10 min after intraocular pressure (IOP) elevation of approximately 15 mmHg in the subjects without systemic disorders. Results. The baseline tissue MBR of the temporal quadrant was significantly lower than that of the other 3 quadrants (all P<0.05). However, the time courses of tissue MBR in response to OPP decrease were not significantly different among the four quadrants during vitrectomy (P=0.23). Conclusions. There is no significant difference in the autoregulatory capacity of the four ONH quadrants in patients without systemic disorders during vitrectomy

Effect of the Duration of Intraretinal or Subretinal Fluid on the Response to Treatment in Undertreated Age-Related Macular Degeneration

We investigated the association between the duration of intraretinal fluid (IRF) or subretinal fluid (SRF) and the response to antivascular endothelial growth factor injection in patients with undertreated age-related macular degeneration (ARMD). The Ethics Committee of Toho University Sakura Medical Center approved this study (no. S18030). Eighty eyes of ARMD patients with VA ≤20/100 were retrospectively assessed. Each injection’s efficacy was classified, and the fluid accumulation prior to each injection was evaluated. The effect changes following to accumulated IRF, SRF, the longest persistent IRF period (≥10 months), and their determining factors were evaluated. Throughout observation, acquired refractoriness was rarely associated with increased accumulation of IRF or SRF. The injection span had a tendency to be short, and the polypoidal choroidal vasculopathy and occult choroidal neovasculopathy (CNV) proportions had a tendency to be higher among patients with diminished effects than among those with maintained effects. VA differed significantly with continuous IRF duration, but not with accumulated fluid. The diminishing effect of injections during long-standing IRF was rarely associated with undertreatment. The mechanism underlying acquired refractoriness remains unknown; the effect change demonstrated various patterns, including diminished and improved responses. The longest continuous IRF duration was associated with VA decline. Shortening the duration of continuous IRF may be necessary

Two Cases of Acute Abdomen after an Intravitreal Injection of Bevacizumab

We report on a patient with ischemic colitis and another with paralytic ileus, both of whom experienced an acute abdomen after intravitreal injection of bevacizumab (IVB). Case 1 was a 78-year-old woman. Her medical history included surgery for colon carcinoma 10 years earlier. The patient developed acute severe abdominal pain and nausea the day after IVB for retinal vein occlusion with macular edema, and massive lower gastrointestinal bleeding occurred. Ischemic colitis was diagnosed. Case 2 was a 64-year-old man who presented with neovascular glaucoma with proliferative diabetic retinopathy. We performed vitreous surgery on the 9th day after IVB, and we reperformed IVB at the end of the vitreous surgery. On the first postoperative day, severe abdominal distension, vomiting and abdominal pain were observed, and paralytic ileus was diagnosed. It is possible that gastrointestinal disorders are induced after IVB, depending on the patient's background, including for example severe diabetes or a history of surgery for gastrointestinal cancer. Thus, ophthalmologists should apply alternative therapies instead of IVB to patients with severe diabetes mellitus or a history of gastrointestinal cancer

Migration of Intraocular Silicone Oil from the Vitreous Cavity into the Upper Eyelid Causing Ptosis

Introduction: To report a case in which intraocular silicone oil migrated into the upper eyelid and caused ptosis. Methods: A 65-year-old woman presented with proliferative vitreoretinopathy in the right eye. Vitrectomies, injection of silicone oil and encircling were performed. Two months after the last operation, swelling of her right eyelid occurred. Result: Magnetic resonance imaging revealed moisture in the palpebral fat tissue. We incised the bulbar conjunctiva and confirmed silicone oil leakage from the vitreous cavity through the scleral button hole of the encircling suture. Postoperatively, the right upper eyelid swelling decreased. Histopathologically, dense macrophage infiltration was seen in the palpebral tissues. Conclusions: We report a rare case with a postoperative complication caused by silicone oil. In cases with swelling of the eyelid and decreased silicon oil in the vitreous cavity postoperatively, clinicians should consider the possibility of silicone oil leakage

Postoperative Refractive Prediction Error Measured by Optical and Acoustic Biometry after Phacovitrectomy for Rhegmatogenous Retinal Detachment without Macular Involvement

Introduction. The aim of this study was to investigate the postoperative prediction error measured by optical biometry and acoustic biometry in eyes after phacovitrectomy for rhegmatogenous retinal detachment (RRD) with no macular involvement. Methods. Forty-nine eyes of 49 patients (32 male, 17 female; mean age 62.6 ± 7.5 years) with RRD without macular involvement who underwent phacovitrectomy (RRD group) and 49 eyes of 33 patients (21 male, 12 female; mean age 74.1 ± 7.1 years) without macular disease who underwent cataract surgery (control group) were included in this retrospective comparative study. The difference between the preoperative predictive value and the postoperative refractive value was measured both by optical and acoustic biometry and compared in each group. Results. The postoperative refractive error calculated by acoustic biometry was −0.81 ± 0.75D and that calculated by optic biometry was −0.44 ± 0.77D in the RRD group. The postoperative refractive error calculated by acoustic biometry was −0.21 ± 0.64D and that calculated by optic biometry was 0.27 ± 0.71D in the control group. Significant myopic shifts were observed in the RRD group using both acoustic biometry and optic biometry but not in the control group. Conclusion. Phacovitrectomy for RRD with no macular involvement resulted in a significant myopic shift when compared with cataract surgery alone in patients without macular disease when calculated by both acoustic biometry and optic biometry