Indications and Techniques of Endoscope Assisted Vitrectomy

The popularization of ophthalmic endoscopy has been promoted by recent technological advancements that increase the number of indications for endoscopy. These advancements have improved the endoscope’s capabilities in its two fundamental surgical advantages: (1) bypassing anterior segment opacities, and (2) visualizing anteriorly positioned structures such as the ciliary bodies and sub-iris space. In this article, the current state of the ophthalmic endoscope is reviewed alongside its growing number of applications in glaucoma, vitreoretinal, and ocular trauma surgery. We describe the role of endoscopy in endocyclophotocoagulation for glaucoma, cyclitic membrane peeling in hypotony, retinal detachment surgery, intraocular foreign body removal, severe endophthalmitis, and pediatric traumatic vitreoretinal surgery. This review examines both the pearls and limitations of the ophthalmic application of endoscopy. In doing so, we hope to provide guidelines for using the endoscope and also to highlight applications of endoscopy that merit further study

Prediction of Anti-VEGF Response in Diabetic Macular Edema After 1 Injection

Purpose With multiple anti-vascular endothelial growth factor and steroid therapies available for diabetic macular edema (DME), there is a need for early determination of the best treatment for a particular patient to prevent irreversible vision loss from chronic DME. In this study, we classify patients as responders or non-responders to anti-vascular endothelial growth factor (VEGF) monotherapy in the treatment of DME after a single anti-VEGF injection. Methods The study was designed as a single center, retrospective, interventional case series. We included patients who received 3 consecutive monthly injections with the same anti-VEGF agent. We excluded patients who were treated for DME in the preceding 3 months with any form of anti-VEGF therapy. Visual acuity and central retinal thickness (CRT) data were followed for one year. Receiver operating characteristic (ROC) curve analysis was performed in order to identify cutoff values for identifying responders. Results 107 eyes were reviewed, with 40 eyes of 34 patients meeting all inclusion criteria. Based on ROC curve analysis, a reduction in CRT by > 15% at 1-month, identified eyes that responded to treatment and had a >25% reduction in CRT at 3-months (sensitivity 0.75, specificity 0.92). Conclusion DME eyes that have early response to anti-VEGF treatment by reduction in CRT will have significant response to treatment by 3 months

Release and extraction of retained subfoveal perfluorocarbon liquid facilitated by subretinal BSS, vibration, and gravity: a case report.

BACKGROUND: Perfluorocarbon liquid (PFCL) is an effective surgical adjuvant in performing vitrectomy for severe vitreoretinal pathologies such as proliferative vitreoretinopathy and giant retinal tears. However, subretinal retention of PFCL can occur postoperatively and retained PFCL causes severe visual disorders, particularly when PFCL was retained under the fovea. Although several procedures have been proposed for subfoveal PFCL removal, such as direct aspiration or submacular injection of balanced salt solution (BSS) to dislodge the subfoveal PFCL, the retinal damage associated with these procedures has been a major problem. Here, we report a case of subfoveal retention of PFCL for which we performed a novel surgical technique that attempts to minimize retinal damage. CASE PRESENTATION: A 69-year-old man presented with subfoveal retained PFCL after surgery for retinal detachment. To remove the retained PFCL, the internal limiting membrane overlying the subretinal injection site is first peeled to allow low-pressure (8 psi) transretinal BSS infusion, using a 41-gauge cannula, to slowly detach the macula. A small drainage retinotomy is created with the diathermy tip at the inferior position of the macular bleb, sized to be slightly wider than that of the PFCL droplet. The head of the bed is then raised, and the surgeon gently vibrates the patient\u27s head to release the PFCL droplet to allow it to migrate inferiorly towards the drainage retinotomy. The bed is returned to the horizontal position, and the PFCL, now on the retinal surface, can be aspirated. The subfoveal PFCL is removed while minimizing iatrogenic foveal and macular damage. One month after PFCL removal, the foveal structure showed partial recovery on optical coherence tomography, and BCVA improved to 20/40. CONCLUSION: Creating a macular bleb with low infusion pressure and using vibrational forces and gravity to migrate the PFCL towards a retinotomy can be considered as a relatively atraumatic technique to remove subfoveal retained PFCL

Google Search Trends to Assess Public Interest in and Concern About Vuity for Treating Presbyopia

PURPOSE: To assess public awareness, interest, and concerns regarding Vuity (1.25% pilocarpine hydrochloride ophthalmic solution), an eye drop for the treatment of presbyopia, based on Google Trends. METHODS: We used Google Trends that provides a relative search volume for queried terms, to evaluate searches for Vuity from June 30, 2021, to June 30, 2022, in the United States. The data for this study were downloaded on June 30, 2022. Main outcome measures were changes in relative search volumes for the terms Vuity, Eye drops for reading, Eye drops for near vision, Presbyopia, Pilocarpine, and related popular search terms, such as Vuity side effects, and Vuity retinal detachment . RESULTS: Since the approval of Vuity on October 29, 2021, notable increases in the relative search volumes occurred for Vuity in October 2021, December 2021, and from March to April 2022, which coincided with its approval, availability, and subsequent direct-to-consumer advertising based on positive results of clinical trials. The direct-to-consumer advertising had the greatest impact on the search volume for Vuity. Specific interests included Vuity cost, where to buy it, and its side effects. Retinal detachment was the most highly searched Vuity side effect. Geographic variation was evident, with the relative search volumes highest for Vuity in Wyoming, followed by North Dakota. CONCLUSION: Google Trends is a useful tool for monitoring increases in public interest in Vuity for presbyopia. Public concerns regarding side effects warrant further real-world investigations of the causal relationship between Vuity and retinal detachment

Scleral Buckling for Primary Retinal Detachment: Outcomes of Scleral Tunnels versus Scleral Sutures

Purpose: There are primarily two techniques for affixing the scleral buckle (SB) to the sclera in the repair of rhegmatogenous retinal detachment (RRD): scleral tunnels or scleral sutures. Methods: This retrospective study examined all patients with primary RRD who were treated with primary SB or SB combined with vitrectomy from January 1, 2015 through December 31, 2015 across six sites. Two cohorts were examined: SB affixed using scleral sutures versus scleral tunnels. Pre- and postoperative variables were evaluated including visual acuity, anatomic success, and postoperative strabismus. Results: The mean preoperative logMAR VA for the belt loop cohort was 1.05 ± 1.06 (Snellen 20/224) and for the scleral suture cohort was 1.03 ± 1.04 (Snellen 20/214, p = 0.846). The respective mean postoperative logMAR VAs were 0.45 ± 0.55 (Snellen 20/56) and 0.46 ± 0.59 (Snellen 20/58, p = 0.574). The single surgery success rate for the tunnel cohort was 87.3% versus 88.6% for the suture cohort (p = 0.601). Three patients (1.0%) in the scleral tunnel cohort developed postoperative strabismus, but only one patient (0.1%) in the suture cohort (p = 0.04, multivariate p = 0.76). All cases of strabismus occurred in eyes that underwent SB combined with PPV (p = 0.02). There were no differences in vision, anatomic success, or strabismus between scleral tunnels versus scleral sutures in eyes that underwent primary SB. Conclusion: Scleral tunnels and scleral sutures had similar postoperative outcomes. Combined PPV/SB in eyes with scleral tunnels might be a risk for strabismus post retinal detachment surgery

Novel adsorptive type apheresis device Immunopure for ulcerative colitis from clinical perspectives based on clinical trials : Japan and Europe.

Several adsorptive type devices for ulcerative colitis are used for the induction of remission in patients with active severe disease worldwide. In 2020, the novel apheresis device Immunopure for ulcerative colitis was launched in Japan. Immunopure, like the polyethylene terephthalate column, uses polyarylate, a type of polyester resin, as the adsorbent. Similar to the cellulose acetate column, Immunopure is filled with adsorbent beads and expected to provide ease of use, with minimal risk of column clogging. Immunopure adsorbs leukocytes and platelets, especially activated platelets and platelet-leukocyte aggregates. In this article, the capability of Immunopure is evaluated from clinical perspective based on a clinical trial in Japan/Europe. As a result, Immunopure is comparable to other products in clinical effectiveness and indicated for the treatment of patients with refractory moderate ulcerative colitis, making it highly useful in clinical practice

A Comparative Study of Responses to Retina Questions from Either Experts, Expert-Edited Large Language Models, or Expert-Edited Large Language Models Alone

OBJECTIVE: To assess the quality, empathy, and safety of expert edited large language model (LLM), human expert created, and LLM responses to common retina patient questions. DESIGN: Randomized, masked multicenter study. PARTICIPANTS: Twenty-one common retina patient questions were randomly assigned among 13 retina specialists. METHODS: Each expert created a response (Expert) and then edited a LLM (ChatGPT-4)-generated response to that question (Expert + artificial intelligence [AI]), timing themselves for both tasks. Five LLMs (ChatGPT-3.5, ChatGPT-4, Claude 2, Bing, and Bard) also generated responses to each question. The original question along with anonymized and randomized Expert + AI, Expert, and LLM responses were evaluated by the other experts who did not write an expert response to the question. Evaluators judged quality and empathy (very poor, poor, acceptable, good, or very good) along with safety metrics (incorrect information, likelihood to cause harm, extent of harm, and missing content). MAIN OUTCOME: Mean quality and empathy score, proportion of responses with incorrect information, likelihood to cause harm, extent of harm, and missing content for each response type. RESULTS: There were 4008 total grades collected (2608 for quality and empathy; 1400 for safety metrics), with significant differences in both quality and empathy ( CONCLUSIONS: In this randomized, masked, multicenter study, LLM responses were comparable with experts in terms of quality, empathy, and safety metrics, warranting further exploration of their potential benefits in clinical settings. FINANCIAL DISCLOSURES: Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of the article

Oral tongue cancer gene expression profiling: Identification of novel potential prognosticators by oligonucleotide microarray analysis

<p>Abstract</p> <p>Background</p> <p>The present study is aimed at identifying potential candidate genes as prognostic markers in human oral tongue squamous cell carcinoma (SCC) by large scale gene expression profiling.</p> <p>Methods</p> <p>The gene expression profile of patients (n=37) with oral tongue SCC were analyzed using Affymetrix HG_U95Av2 high-density oligonucleotide arrays. Patients (n=20) from which there were available tumor and matched normal mucosa were grouped into stage (early vs. late) and nodal disease (node positive vs. node negative) subgroups and genes differentially expressed in tumor vs. normal and between the subgroups were identified. Three genes, <it>GLUT3</it>, <it>HSAL2</it>, and <it>PACE4</it>, were selected for their potential biological significance in a larger cohort of 49 patients via quantitative real-time RT-PCR.</p> <p>Results</p> <p>Hierarchical clustering analyses failed to show significant segregation of patients. In patients (n=20) with available tumor and matched normal mucosa, 77 genes were found to be differentially expressed (P< 0.05) in the tongue tumor samples compared to their matched normal controls. Among the 45 over-expressed genes, <it>MMP-1</it> encoding interstitial collagenase showed the highest level of increase (average: 34.18 folds). Using the criterion of two-fold or greater as overexpression, 30.6%, 24.5% and 26.5% of patients showed high levels of <it>GLUT3</it>, <it>HSAL2</it> and <it>PACE4</it>, respectively. Univariate analyses demonstrated that <it>GLUT3</it> over-expression correlated with depth of invasion (P<0.0001), tumor size (P=0.024), pathological stage (P=0.009) and recurrence (P=0.038). <it>HSAL2</it> was positively associated with depth of invasion (P=0.015) and advanced T stage (P=0.047). In survival studies, only <it>GLUT3</it> showed a prognostic value with disease-free (P=0.049), relapse-free (P=0.002) and overall survival (P=0.003). <it>PACE4</it> mRNA expression failed to show correlation with any of the relevant parameters. </p> <p>Conclusion</p> <p>The characterization of genes identified to be significant predictors of prognosis by oligonucleotide microarray and further validation by real-time RT-PCR offers a powerful strategy for identification of novel targets for prognostication and treatment of oral tongue carcinoma.</p

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