Management of corneal neovascularization: Current and emerging therapeutic approaches.

Corneal neovascularization (CoNV) is a sight-threatening condition affecting an estimated 1.4 million people per year, and the incidence is expected to rise. It is a complication of corneal pathological diseases such as infective keratitis, chemical burn, corneal limbal stem cell deficiency, mechanical trauma, and immunological rejection after keratoplasties. CoNV occurs due to a disequilibrium in proangiogenic and antiangiogenic mediators, involving a complex system of molecular interactions. Treatment of CoNV is challenging, and no therapy thus far has been curative. Anti-inflammatory agents such as corticosteroids are the mainstay of treatment due to their accessibility and well-studied safety profile. However, they have limited effectiveness and are unable to regress more mature neovascularization. With the advent of advanced imaging modalities and an expanding understanding of its pathogenesis, contemporary treatments targeting a wide array of molecular mechanisms and surgical options are gaining traction. This review aims to summarize evidence regarding conventional and emerging therapeutic options for CoNV.

ArCH: improving the performance of clonal hematopoiesis variant calling and interpretation.

MOTIVATION: The acquisition of somatic mutations in hematopoietic stem and progenitor stem cells with resultant clonal expansion, termed clonal hematopoiesis (CH), is associated with increased risk of hematologic malignancies and other adverse outcomes. CH is generally present at low allelic fractions, but clonal expansion and acquisition of additional mutations leads to hematologic cancers in a small proportion of individuals. With high depth and high sensitivity sequencing, CH can be detected in most adults and its clonal trajectory mapped over time. However, accurate CH variant calling is challenging due to the difficulty in distinguishing low frequency CH mutations from sequencing artifacts. The lack of well-validated bioinformatic pipelines for CH calling may contribute to lack of reproducibility in studies of CH. RESULTS: Here, we developed ArCH, an Artifact filtering Clonal Hematopoiesis variant calling pipeline for detecting single nucleotide variants and short insertions/deletions by combining the output of four variant calling tools and filtering based on variant characteristics and sequencing error rate estimation. ArCH is an end-to-end cloud-based pipeline optimized to accept a variety of inputs with customizable parameters adaptable to multiple sequencing technologies, research questions, and datasets. Using deep targeted sequencing data generated from six acute myeloid leukemia patient tumor: normal dilutions, 31 blood samples with orthogonal validation, and 26 blood samples with technical replicates, we show that ArCH improves the sensitivity and positive predictive value of CH variant detection at low allele frequencies compared to standard application of commonly used variant calling approaches. AVAILABILITY AND IMPLEMENTATION: The code for this workflow is available at: https://github.com/kbolton-lab/ArCH.

Measuring Caspase Activity Using a Fluorometric Assay or Flow Cytometry.

The activation of cysteine proteases, known as caspases, remains an important process in multiple forms of cell death. Caspases are critical initiators and executioners of apoptosis, the most studied form of programmed cell death. Apoptosis occurs during developmental processes and is a necessary event in tissue homeostasis. Pyroptosis is another form of cell death that utilizes caspases and is a critical process in activating the immune system through the activation of the inflammasome, which results in the release of members of the interleukin-1 (IL-1) family. To assess caspase activity, target substrates can be assessed. However, sensitivity can be an issue when examining single cells or low-level activity. We demonstrate how a fluorogenic substrate can be used with a population-based assay or single-cell assay by flow cytometry. With proper controls, different amino acid sequences can be used to identify which caspases are active. Using these assays, the simultaneous loss of the inhibitors of apoptosis proteins upon tumor necrosis factor (TNF) stimulation has been identified, which primarily induces apoptosis in macrophages rather than other forms of cell death.

GWAS Explorer: an open-source tool to explore, visualize, and access GWAS summary statistics in the PLCO Atlas.

The Prostate, Lung, Colorectal and Ovarian (PLCO) Cancer Screening Trial is a prospective cohort study of nearly 155,000 U.S. volunteers aged 55-74 at enrollment in 1993-2001. We developed the PLCO Atlas Project, a large resource for multi-trait genome-wide association studies (GWAS), by genotyping participants with available DNA and genomic consent. Genotyping on high-density arrays and imputation was performed, and GWAS were conducted using a custom semi-automated pipeline. Association summary statistics were generated from a total of 110,562 participants of European, African and Asian ancestry. Application programming interfaces (APIs) and open-source software development kits (SKDs) enable exploring, visualizing and open data access through the PLCO Atlas GWAS Explorer website, promoting Findable, Accessible, Interoperable, and Re-usable (FAIR) principles. Currently the GWAS Explorer hosts association data for 90 traits and >78,000,000 genomic markers, focusing on cancer and cancer-related phenotypes. New traits will be posted as association data becomes available. The PLCO Atlas is a FAIR resource of high-quality genetic and phenotypic data with many potential reuse opportunities for cancer research and genetic epidemiology.

Magnetic resonance imaging of disorders with white matter changes in children and adolescents: a pictorial essay.

White matter changes are seen in a spectrum of disorders in children and adolescents. Understanding their distribution and appearance helps to reach diagnoses in daily radiologic practice. This pictorial essay will outline the magnetic resonance imaging (MRI) appearances of diseases with white matter changes including demyelinating diseases, dysmyelinating disorders/leukodystrophies, infections, autoimmune diseases, vascular causes, mitochondrial disorders and neurocutaneous syndromes, along with a brief overview of clinical aspects of the diseases such as typical age of presentation, etiology, symptoms and signs and treatment options. This article highlights important features in common white matter diseases in children and adolescents.

Membrane Protein Modification Modulates Big and Small Extracellular Vesicle Biodistribution and Tumorigenic Potential in Breast Cancers In Vivo.

Extracellular vesicles (EVs) are released by cells to mediate intercellular communication under pathological and physiological conditions. While small EVs (sEVs; <100-200 nm, exosomes) are intensely investigated, the properties and functions of medium and large EVs (big EVs (bEVs); >200 nm, microvesicles) are less well explored. Here, bEVs and sEVs are identified as distinct EV populations, and it is determined that bEVs are released in a greater bEV:sEV ratio in the aggressive human triple-negative breast cancer (TNBC) subtype. PalmGRET, bioluminescence-resonance-energy-transfer (BRET)-based EV reporter, reveals dose-dependent EV biodistribution at nonlethal and physiological EV dosages, as compared to lipophilic fluorescent dyes. Remarkably, the bEVs and sEVs exhibit unique biodistribution profiles, yet individually promote in vivo tumor growth in a syngeneic immunocompetent TNBC breast tumor murine model. The bEVs and sEVs share mass-spectrometry-identified tumor-progression-associated EV surface membrane proteins (tpEVSurfMEMs), which include solute carrier family 29 member 1, Cd9, and Cd44. tpEVSurfMEM depletion attenuates EV lung organotropism, alters biodistribution, and reduces protumorigenic potential. This study identifies distinct in vivo property and function of bEVs and sEVs in breast cancer, which suggest the significant role of bEVs in diseases, diagnostic and therapeutic applications.

Treat and extend regimen for diabetic macular oedema-a systematic review and meta-analysis.

PURPOSE: Various treatment regimens are currently practiced in the treatment of CI-DMO (centre-involving diabetic macular oedema). In recent years, there has been a growing body of evidence supporting a treat and extend (T&E) regimen for DMO which offers the promise of comparable visual and anatomical outcomes while reducing injection burden. This meta-analysis was hence performed to evaluate the aforementioned outcomes in the treatment of DMO. Ten studies met the inclusion criteria. METHODS: A search of PubMed, MEDLINE, Current Contents, and Cochrane Central Register of Controlled Trials (CENTRAL) databases was performed. We employed the terms 'treat AND extend AND (diabetic AND macular AND edema OR oedema)' to ensure a comprehensive search. The search workflow adhered to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses. RESULTS: The pooled analysis of the mean number of injections in 1 year for T&E-aflibercept (AFL), T&E-ranibizumab (RBZ) and collectively was 9.1 (95% CI: 7.63-10.63), 10.0 (95% CI: 9.55-10.47) and 9.6 (95% CI: 8.62-10.49), respectively. Improvements in vision at 1 year for T&E-AFL, T&E-RBZ and collectively were 6.26 (95% CI: 3.24-9.29), 7.14 (95% CI: 4.76-9.52) and 7.08 (95% CI: 5.32-8.84) letters, respectively. The improvements in central subfield thickness at 1 year for T&E-AFL, T&E-RBZ and collectively were 131.94 (95% CI: 100.29-163.60), 108.64 (95% CI: 82.82-134.46) and 121.32 (95% CI: 102.89-139.75) microns, respectively. CONCLUSION: The meta-analysis of T&E for DMO did not show a clear advantage in reducing the number of injections compared to landmark clinical trials with pro-re-nata (PRN) treatment regimens in the first year of treatment with limited gains in visual and anatomical outcomes. However, the T&E approach offers the potential for fewer patient visits, thereby reducing treatment burden. Longer term studies on T&E with a standardised protocol would be required to assess the longevity of the vision gain in the first year despite a likely reduced treatment burden compared to the PRN trials.

Epstein Barr virus-mediated transformation of B cells from XIAP-deficient patients leads to increased expression of the tumor suppressor CADM1.

X-linked lymphoproliferative disease (XLP) is either caused by loss of the SLAM-associated protein (SAP; XLP-1) or the X-linked inhibitor of apoptosis (XIAP; XLP-2). In both instances, infection with the oncogenic human Epstein Barr virus (EBV) leads to pathology, but EBV-associated lymphomas only emerge in XLP-1 patients. Therefore, we investigated the role of XIAP during B cell transformation by EBV. Using humanized mice, IAP inhibition in EBV-infected mice led to a loss of B cells and a tendency to lower viral titers and lymphomagenesis. Loss of memory B cells was also observed in four newly described patients with XIAP deficiency. EBV was able to transform their B cells into lymphoblastoid cell lines (LCLs) with similar growth characteristics to patient mothers' LCLs in vitro and in vivo. Gene expression analysis revealed modest elevated lytic EBV gene transcription as well as the expression of the tumor suppressor cell adhesion molecule 1 (CADM1). CADM1 expression on EBV-infected B cells might therefore inhibit EBV-associated lymphomagenesis in patients and result in the absence of EBV-associated malignancies in XLP-2 patients.

PLCOjs, a FAIR GWAS web SDK for the NCI Prostate, Lung, Colorectal and Ovarian Cancer Genetic Atlas project.

MOTIVATION: The Division of Cancer Epidemiology and Genetics (DCEG) and the Division of Cancer Prevention (DCP) at the National Cancer Institute (NCI) have recently generated genome-wide association study (GWAS) data for multiple traits in the Prostate, Lung, Colorectal, and Ovarian (PLCO) Genomic Atlas project. The GWAS included 110 000 participants. The dissemination of the genetic association data through a data portal called GWAS Explorer, in a manner that addresses the modern expectations of FAIR reusability by data scientists and engineers, is the main motivation for the development of the open-source JavaScript software development kit (SDK) reported here. RESULTS: The PLCO GWAS Explorer resource relies on a public stateless HTTP application programming interface (API) deployed as the sole backend service for both the landing page's web application and third-party analytical workflows. The core PLCOjs SDK is mapped to each of the API methods, and also to each of the reference graphic visualizations in the GWAS Explorer. A few additional visualization methods extend it. As is the norm with web SDKs, no download or installation is needed and modularization supports targeted code injection for web applications, reactive notebooks (Observable) and node-based web services. AVAILABILITY AND IMPLEMENTATION: code at https://github.com/episphere/plco; project page at https://episphere.github.io/plco.

Navigating communication between conventional medicine and traditional Chinese medicine: a case study of cancer patients in Hong Kong.

BACKGROUND: Traditional Chinese medicine (TCM) is a growing phenomenon worldwide. Despite its historical role in Chinese society, however, few studies have explored the nature of communication among patients with cancer who receive TCM care in addition to conventional medicine. If TCM practitioners acquire adequate knowledge to understand the needs and communication issues for their patients with cancer, particularly those who are simultaneously receiving conventional medicine, this will lead to better quality of care and clinical outcomes, such as high patient satisfaction and treatment compliance. OBJECTIVES: To fill this knowledge gap, this study explored the nature of communication among patients with cancer in Hong Kong who receive TCM treatment in addition to conventional medicine. PARTICIPANTS: We conducted in-depth interviews with 20 patients, 5 oncologists and 5 TCM practitioners to elicit their views on TCM treatments. METHOD: We adopted a qualitative approach using an interpretative phenomenological analysis. RESULTS: Based on the themes that emerged from our interview transcripts, we outlined communication priorities when advising patients with cancer who are receiving both TCM and conventional medical care. We developed a framework to train TCM practitioners to better integrate their patients' conventional medical history when delivering patient care. CONCLUSIONS: Our study findings inform communication priorities when caring for patients who opt for TCM care in addition to conventional treatments. In addition, they provide useful information for developing future clinical research studies to explore integrated approaches between TCM and conventional medicine in treating patients with cancer.

Antiangiogenic Nanomicelles for the Topical Delivery of Aflibercept to Treat Retinal Neovascular Disease.

The traditional intravitreal injection delivery of antivascular endothelial growth factor (anti-VEGF) to the posterior segment of the eye for treatment of retinal diseases is invasive and associated with sight-threatening complications. To avoid such complications, there has been significant interest in developing polymers for topical drug delivery to the retina. This study reports a nanomicelle drug delivery system made of a copolymer EPC (nEPCs), which is capable of delivering aflibercept to the posterior segment topically through corneal-scleral routes. EPC is composed of poly(ethylene glycol) (PEG), poly(propylene glycol) (PPG), and polycaprolactone (PCL) segments. In this study, aflibercept-loaded nEPCs (nEPCs + A) are capable of penetrating the cornea in ex vivo porcine eye models and deliver a clinically significant amount of aflibercept to the retina in laser-induced choroidal neovascularization (CNV) murine models, causing CNV regression. nEPCs + A also demonstrate biocompatibility in vitro and in vivo. Interestingly, this study also suggests that nEPCs have intrinsic antiangiogenic properties. The ability to deliver anti-VEGF drugs and the intrinsic antiangiogenic properties of nEPCs may result in synergistic effects, which can be harnessed for effective therapeutics. nEPCs may be a promising topical anti-VEGF delivery platform for the treatment of retinal diseases.

cGMP-grade human iPSC-derived retinal photoreceptor precursor cells rescue cone photoreceptor damage in non-human primates.

BACKGROUND: Retinal regenerative therapies hold great promise for the treatment of inherited retinal degenerations (IRDs). Studies in preclinical lower mammal models of IRDs have suggested visual improvement following retinal photoreceptor precursors transplantation, but there is limited evidence on the ability of these transplants to rescue retinal damage in higher mammals. The purpose of this study was to evaluate the therapeutic potential of photoreceptor precursors derived from clinically compliant induced pluripotent stem cells (iPSCs). METHODS: Photoreceptor precursors were sub-retinally transplanted into non-human primates (Macaca fascicularis). The cells were transplanted both in naïve and cobalt chloride-induced retinal degeneration models who had been receiving systemic immunosuppression for one week prior to the procedure. Optical coherence tomography, fundus autofluorescence imaging, electroretinography, ex vivo histology and immunofluorescence staining were used to evaluate retinal structure, function and survival of transplanted cells. RESULTS: There were no adverse effects of iPSC-derived photoreceptor precursors on retinal structure or function in naïve NHP models, indicating good biocompatibility. In addition, photoreceptor precursors injected into cobalt chloride-induced retinal degeneration NHP models demonstrated an ability both to survive and to mature into cone photoreceptors at 3 months post-transplant. Optical coherence tomography showed restoration of retinal ellipsoid zone post-transplantation. CONCLUSIONS: These findings demonstrate the safety and therapeutic potential of clinically compliant iPSC-derived photoreceptor precursors as a cell replacement source for future clinical trials.

Prioritizing Chinese medicine clinical research questions in cancer palliative care from patient and caregiver perspectives.

BACKGROUND: Chinese medicine (CM) modalities, including acupuncture and Chinese herbal medicine (CHM), are popular palliative interventions among patients with cancer, but further clinical research is required to assess their effectiveness and safety. OBJECTIVE: To prioritize top ten important CM clinical research questions from patients with cancer, cancer survivors and caregivers' perspectives via a face-to-face prioritization workshop in Hong Kong. METHODS: A list of 25 CM clinical research questions for cancer palliative care, which were identified from existing systematic reviews (SRs) and overview of SRs, was presented to 17 participants (patients with cancer [n = 5], cancer survivors [n = 6] and caregivers [n = 6]). The participants were then invited to establish consensus on prioritizing top ten research questions. RESULTS: Among the top ten priorities, five (50%) focused on acupuncture and related therapies, while five (50%) were on CHM. The three most important research priorities were (i) manual acupuncture plus opioids for relieving pain; (ii) CHM for improving quality of life among patients receiving chemotherapy; and (iii) concurrent use of CHM plus loperamide for reducing stomatitis. CONCLUSION: The top ten participant-endorsed CM clinical research priorities for cancer palliative care can guide local researchers on future direction. They can also inform local research funders on patient-centred allocation of limited funding. Under limited research funding, the most important co-prioritized research question from professional and patient perspectives may be addressed first. PATIENT OR PUBLIC CONTRIBUTION: Patients with cancer, cancer survivors and caregivers participated in conduct of the study to prioritize CM clinical research questions.

Use of the Xpert Breast Cancer STRAT4 for Biomarker Evaluation in Tissue Processed in a Developing Country.

OBJECTIVES: Breast cancer immunohistochemistry (IHC) biomarker testing is limited in low-resource settings, and an alternative solution is needed. A point-of-care mRNA STRAT4 breast cancer assay for ESR1, PGR, ERBB2, and MKi67, for use on the GeneXpert platform, has been recently validated on tissues from internationally accredited laboratories, showing excellent concordance with IHC. METHODS: We evaluated STRAT4/IHC ESR1/estrogen receptor (ER), ERBB2/human epidermal growth factor receptor 2 (HER2) concordance rates of 150 breast cancer tissues processed in Rwanda, with undocumented cold ischemic and fixation time. RESULTS: Assay fail/indeterminate rate was 2.6% for ESR1 and ERBB2. STRAT4 agreement with ER IHC was 92.5% to 93.3% and 97.8% for HER2, for standard (1x) and concentrated (4x) reagent-conserving protocols, respectively. Eleven of 12 discordant ER/ESR1 cases were ESR1- negative/IHC-positive. These had low expression of ER by IHC in mostly very small tumor areas tested (7/12; <25 mm2). In two of three discordant HER2 cases, the STRAT4-ERBB2 result correlated with the subsequent fluorescence in situ hybridization (FISH) result. STRAT4-ERBB2 results in 9 of 10 HER2-IHC equivocal cases were concordant with FISH. CONCLUSIONS: The STRAT4 assay is an alternative for providing quality-controlled breast cancer biomarker data in laboratories unable to provide quality and/or cost-efficient IHC services.

Intimate Partner Sexual Violence and Mental Health Indicators Among Chinese Emerging Adults.

Intimate partner sexual violence (IPSV) among emerging adults, including heterosexuals and sexual minorities in the Chinese population, is poorly understood. Focusing on college students, the objectives of the present study were to estimate the prevalence of IPSV among Chinese emerging adults, examine the association between sexual orientation and IPSV, and evaluate the mental health and quality of life of survivors of IPSV. Data were collected from four university campuses in Hong Kong. A total of 1,015 participants were included in the data analysis. The prevalence of IPSV as identified by Conflict Tactics Scale (CTS)-2 was 12.1%. There was no gender difference in the prevalence of IPSV. Multiple logistic regression found that being older; having experienced childhood sexual abuse and having a smoking habit; and belonging to a sexual minority were factors associated with IPSV. Multiple linear regression found that IPSV survivors were more likely to have higher levels of anxiety and depression, more severe psychosomatic symptoms, and poorer quality of life in three domains: psychological, social relationships, and environment when compared with those without IPSV experience. The documented factors underscored the importance of awareness that men and sexual minorities might incur IPSV, which should receive more attention in IPSV prevention programs. Also, interventions for IPSV survivors should be targeted at improving their mental health and quality of life and sex education should place more emphasis on sexual consent and sexual health in dating relationships.

Gut microbial composition difference between pediatric ALL survivors and siblings.

Acute lymphoblastic leukemia (ALL) is the most common childhood cancer with high cure rates leading to rising numbers of long-term survivors. Adult survivors of childhood ALL are at increased risk of obesity, cardiovascular disease, and other chronic illnesses. We hypothesize that ALL therapy is associated with long-term gut microbiome alterations that contribute to predisposition to chronic medical conditions. We conducted a pilot study to test whether differences can be detected between stool microbiota of pediatric ALL survivors and their siblings. Stool samples were collected from 38 individuals under age 19 who were at least 1 year after completion of therapy for ALL. Stool samples collected from 16 healthy siblings served as controls. 16S ribosomal RNA gene sequencing was performed on the stool samples. Comparing microbiota of survivors to sibling controls, no statistically significant differences were found in alpha or beta diversity. However, among the top 10 operational taxonomic units (OTUs) from component 1 in sparse partial least squares discriminant analysis (sPLS-DA) with different relative abundance in survivors versus siblings, OTUs mapping to the genus Faecalibacterium were depleted in survivors. Differences in gut microbial composition were found between pediatric survivors of childhood ALL and their siblings. Specifically, the protective Faecalibacterium is depleted in survivors, which is reminiscent of gut microbiota alteration found in adult survivors of childhood ALL and reported in obesity, suggesting that microbiota alterations in pediatric ALL survivors start in childhood and may play a role in predisposition to chronic illness in later years of survivorship.

Studying the urine microbiome in superficial bladder cancer: samples obtained by midstream voiding versus cystoscopy.

BACKGROUND: Preliminary data suggest that the urinary microbiome may play a role in bladder cancer. Information regarding the most suitable method of collecting urine specimens is needed for the large population studies needed to address this. To compare microbiome metrics resulting from 16S ribosomal RNA gene sequencing between midstream, voided specimens and those obtained at cystoscopy. METHODS: Adults, with a history of superficial urothelial cell carcinoma (non-muscle invasive bladder cancer) being followed with periodic surveillance cystoscopy had a urine sample collected by a mid-stream, voided technique and then from the bladder at cystoscopy. Urine samples underwent 16S ribosomal RNA gene sequencing on the Illumina MiSeq platform. RESULTS: 22 subjects (8 female, 14 male) were included. There was no significant difference in beta diversity (diversity between samples) in all samples between collection methods. However, analysis by sex revealed a difference between voided and cystoscopy samples from the same individual in males (p = 0.006, Adonis test) but not in females (p = 0.317, Adonis test). No differences were seen by collection method in any alpha diversity (diversity within a sample) measurement or differential abundance of taxa. CONCLUSIONS: Beta diversity of the urine microbiome did differ by collection method for males only. This suggests that the urinary microbiomes of the two collection methods are not equivalent to each other, at least in males, which is the sex that bladder cancer occurs most frequently in. Therefore, the same collection method within a given study should be used.

Quantitative assessments and clinical outcomes in HER2 equivocal 2018 ASCO/CAP ISH group 4 breast cancer.

We quantified human epidermal growth factor receptor 2 (HER2) RNA and protein expression in 2018 American Society of Clinical Oncology/College of American Pathologists (ASCO/CAP) in situ hybridization (ISH) group 4 (HER2/centromeric probe 17 (CEP17) ratio <2.0, average HER2 copy number ≥4.0 and <6.0, and 2013 ASCO/CAP ISH equivocal) breast cancers. Breast cancers in 2018 ASCO/CAP ISH group 4 between 2014 and 2017 were identified from the Yale archives. Sixty-three patients (34 with HER2 immunohistochemistry (IHC) 0/1+ and 29 with HER2 IHC 2+) were included. We compared patient characteristics, systemic treatments, and outcomes. We assessed HER2 by real-time quantitative reverse transcription polymerase chain reaction (RT-qPCR) and quantitative immunofluorescence (QIF). Among ISH group 4 cancers, higher HER2 mRNA (P < 0.0001) but similar HER2 protein levels were observed in IHC 2+ compared to IHC 0/1+ cancers. The distribution of RT-qPCR and QIF scores were independent of fluorescence in situ hybridization (FISH) ratio/copy number. Concordance between HER2 RT-qPCR and QIF was 69.8% (r = 0.52). Among 29 patients with IHC2+ results, 16 were HER2 positive by RT-qPCR and 12 were HER2 positive by QIF. Systemic treatment, recurrence, and survival outcomes were comparable among ISH group 4 cancers regardless of IHC 0/1+ or 2+ results. ISH group 4 cancers appear to form a distinct group with intermediate levels of RNA/protein expression, close to positive/negative cut points. Therefore, adjudication into positive or negative categories may not be meaningful. Our results support the 2018 ASCO/CAP recommendation to refrain from routine additional testing of these samples. Additional outcome information after trastuzumab treatment for patients in this special group might help to guide treatment decisions in these patients.

Clinical spectrum, treatment and outcomes of uveal melanoma in a tertiary centre.

INTRODUCTION: We aimed to describe the clinical characteristics, diagnostic challenges, treatment patterns and outcomes of uveal melanoma (UM) in a tertiary care centre. METHODS: This is a retrospective case series of 11 consecutive patients with UM who were managed in a tertiary referral centre between 2002 and 2017. Epidemiological, clinical, pathological and radiological characteristics were reviewed. Classification of choroidal melanoma as small, medium or large was based on the criteria established by the Collaborative Ocular Melanoma Study. RESULTS: Mean age at presentation was 42.9 (range 27‒67) years. In 7 (64%) patients, a definitive diagnosis of UM was made after a mean follow-up period of 6.4 (range 1‒17) months. There were one, six and four patients with small-, medium- and large-sized choroidal melanomas, respectively. Treatment was enucleation in 5 (45.5%) patients, plaque brachytherapy in 4 (36.4%) patients, transpupillary thermotherapy in 1 (9.1%) patient, and observation in 1 (9.1%) patient. Median follow-up was 29 months. Metastatic disease developed in 5 (45.5%) patients at the mean age of 46.6 (range 38‒56) years, with median overall survival of 20 months. Genetic mutations in three patients were monosomy 3 (n = 2), and gain of 3q and 8q (n = 1). CONCLUSION: Our study supports the finding that UM in Chinese and Asian Indian patients presents at a younger age than in Caucasians. Although it is rare, ophthalmologists should remain mindful of this life-threatening disease. We propose establishing a national and regional registry for ocular tumours with genetic information to characterise the disease spectrum in Southeast Asia.

Endoscopic Brow Lift Fixation With Mitek Suture Anchors: A 9-Year Experience of a New "Ideal" Technique.

PURPOSE: In recent years, the endoscopic technique has emerged as a minimally invasive approach to forehead rejuvenation, although the specific need for and mode of brow fixation for endoscopic brow lifts remain under considerable debate. An ideal fixation device should provide non-palpable long-lasting fixation and allow retention of the device post-operatively without the need for removal. It should also allow precise intraoperative adjustment for symmetry and correction of brow ptosis. METHODS: The authors describe an endoscopic brow lift technique using an absorbable bone anchor, Mitek Microfix. A retrospective chart review was conducted in patients who underwent endoscopic brow lift procedures utilizing this fixation method at an academic practice. Outcomes evaluated included operative times, reoperation rates, palpability, fixation device permanence, incremental costs comparisons to conventional methods, efficacy, and technical learning curve. Complication rates were evaluated and the economic, incremental cost analysis of current fixation methods was reviewed. RESULTS: Eighty-two patients underwent single-procedure endoscopic brow fixation using the Mitek anchor over a 9-year period (2005-2014). The mean operative time was 100 minutes. There were no cases of implant palpability, alopecia, or other postoperative complications. Two patients underwent revision secondary lifts after an average of 5.5 months for temporal ptosis. CONCLUSION: The Mitek Microfix QuickAnchor provides durable, long-lasting fixation without device palpability. Its technical ease of use is demonstrated by the reasonable mean operative time achieved with the active involvement of resident surgeons. This device is operator-friendly, easy to use, fully indwelling, and provides lasting fixation without the development of palpability or alopecia.

OBJECTIFS: Ces dernières années, la technique endoscopique est devenue une approche peu invasive du rajeunissement du front, mais la nécessité et le moyen de fixer les sourcils font l'objet de vifs débats. Le dispositif de fixation idéal doit être non palpable, durable et demeurer en place sans devoir être retiré. Il doit également assurer le rajustement intraopératoire précis de la symétrie et de la correction de la ptose des sourcils. MÉTHODOLOGIE: Les auteurs décrivent une technique de redrapage endoscopique des sourcils à l'aide de l'ancre osseuse absorbable Mitek Microfix. Ils ont procédé à une analyse rétrospective des dossiers des patients qui avaient subi un redrapage endoscopique des sourcils à l'aide de cette méthode de fixation dans un cabinet universitaire. Ils ont évalué la durée de l'opération, le taux de réopérations, la palpabilité, la permanence du dispositif de fixation, les comparaisons des coûts différentiels par rapport aux méthodes traditionnelles, l'efficacité et la courbe d'apprentissage technique. Ils ont également évalué le taux de complications et examiné l'analyse des coûts différentiels des méthodes de fixation. RÉSULTATS: Sur une période de neuf ans (de 2005 à 2014), 82 patients ont subi une seule intervention de fixation endoscopique des sourcils à l'aide de l'ancre Mitek. L'opération durait 100 minutes en moyenne. Il n'y a eu aucun cas de palpabilité de l'implant, d'alopécie ou d'autres complications postopératoires. Deux patients ont subi un redrapage secondaire après une ptose temporale au bout d'une période moyenne de 5,5 mois. CONCLUSION: L'ancre Mitek Microfix QuickAnchor procure une fixation durable sans palpabilité du dispositif. La simplicité de la technique est démontrée par le temps moyen raisonnable de l'opération obtenu avec la participation active de résidents en chirurgie. Ce dispositif à demeure est facile à utiliser pour l'opérateur et procure une fixation durable sans apparition de palpabilité ou d'alopécie.