Using Electronic Health Record Data to Determine the Safety of Aqueous Humor Liquid Biopsies for Molecular Analyses.

Purpose: Knowing the surgical safety of anterior chamber liquid biopsies will support the increased use of proteomics and other molecular analyses to better understand disease mechanisms and therapeutic responses in patients and clinical trials. Manual review of operative notes from different surgeons and procedures in electronic health records (EHRs) is cumbersome, but free-text software tools could facilitate efficient searches. Design: Retrospective case series. Participants: A total of 1418 aqueous humor liquid biopsies from patients undergoing intraocular surgery. Methods: Free-text EHR searches were performed using the Stanford Research Repository cohort discovery tool to identify complications associated with anterior chamber paracentesis and subsequent endophthalmitis. Complications of the surgery unrelated to the biopsy were not reviewed. Main Outcome Measures: Biopsy-associated intraoperative complications and endophthalmitis. Results: A total of 1418 aqueous humor liquid biopsies were performed by 17 experienced surgeons. EHR free-text searches were 100% error-free for surgical complications, >99% for endophthalmitis (<1% false positive), and >93.6% for anesthesia type, requiring manual review for only a limited number of cases. More than 85% of cases were performed under local anesthesia without ocular muscle akinesia. Although the most common indication was cataract (50.1%), other diagnoses included glaucoma, diabetic retinopathy, uveitis, age-related macular degeneration, endophthalmitis, retinitis pigmentosa, and uveal melanoma. A 50- to 100-µL sample was collected in all cases using either a 30-gauge needle or a blunt cannula via a paracentesis. The median follow-up was >7 months. There was only one minor complication (0.07%) identified: a case of a small tear in Descemet membrane without long-term sequelae. No other complications occurred, including other corneal injuries, lens or iris trauma, hyphema, or suprachoroidal hemorrhage. There was no case of postoperative endophthalmitis. Conclusions: Anterior chamber liquid biopsy during intraocular surgery is a safe procedure and may be considered for large-scale collection of aqueous humor samples for molecular analyses. Free-text EHR searches are an efficient approach to reviewing intraoperative procedures. Financial Disclosures: Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

Emerging Oral Pharmaceuticals for Dry Age-Related Macular Degeneration: Mechanism of Action, Current Clinical Status, and Future Directions.

Dry age-related macular degeneration (AMD) has been historically managed with lifestyle modifications, monitoring for conversion to wet AMD, and vitamins. Recently there has been a flurry of research focused on discovering new targets to prevent worsening of dry AMD. In 2023, the US Food and Drug Administration approved the first two intravitreal complement inhibitors to slow the rate of geographic atrophy progression. However, serial intravitreal injections for a chronic progressive disease are burdensome for patients and have procedural risks. Therefore, there is significant research to discover novel oral medications to manage dry AMD. Several oral medications are currently in phase 2 and 3 clinical trials for dry AMD, whereas others have had recent readouts on their clinical trials and efficacy. The purpose of this review is to describe the therapeutic pathways currently being investigated and to provide an update on the clinical status of novel oral medications for the management of dry AMD. [Ophthalmic Surg Lasers Imaging Retina 2024;55:XX-XX.].

Macular dystrophy in Kabuki syndrome due to de novo KMT2D variants: refining the phenotype with multimodal imaging and follow-up over 10 years: insight into pathophysiology.

BACKGROUND: Kabuki Syndrome is a rare and genetically heterogenous condition with both ophthalmic and systemic complications and typical facial features. We detail the macular phenotype in two unrelated patients with Kabuki syndrome due to de novo nonsense variants in KMT2D, one novel. A follow-up of 10 years is reported. Pathogenicity of both de novo nonsense variants is analyzed. METHODS: Four eyes of two young patients were studied by full clinical examination, kinetic perimetry, short wavelength autofluorescence, full field (ff) ERGs, and spectral-domain optical coherence tomography (SD-OCT). One patient had adaptive optic (AO) imaging. Whole exome sequencing was performed in both patients. RESULTS: Both patients had de novo nonsense variants in KMTD2. One patient had c.14843C>G; p. (Ser4948ter) novel variant and the second c.11119C>T; p. (Arg3707ter). Both had a stable Snellen visual acuity of 0.2-0.3. The retinal multimodal imaging demonstrated abnormalities at the fovea in both eyes: hyperreflectivity to blue light and a well-delimited gap-disruption of ellipsoid and interdigitation layer on OCT. The dark area on AO imaging is presumed to be absent for, or with structural change to photoreceptors. The ff ERGs and kinetic visual fields were normal. The foveal findings remained stable over several years. CONCLUSION: Kabuki syndrome-related maculopathy is a distinct loss of photoreceptors at the fovea as shown by multimodal imaging including, for the first time, AO imaging. This report adds to the literature of only one case with maculopathy with two additional macular dystrophies in patients with Kabuki syndrome. Although underestimated, these cases further raise awareness of the potential impact of retinal manifestations of Kabuki syndrome not only among ophthalmologists but also other healthcare professionals involved in the care of patients with this multisystem disorder.

Liquid Biopsy Proteomics in Ophthalmology.

Minimally invasive liquid biopsies from the eye capture locally enriched fluids that contain thousands of proteins from highly specialized ocular cell types, presenting a promising alternative to solid tissue biopsies. The advantages of liquid biopsies include sampling the eye without causing irreversible functional damage, potentially better reflecting tissue heterogeneity, collecting samples in an outpatient setting, monitoring therapeutic response with sequential sampling, and even allowing examination of disease mechanisms at the cell level in living humans, an approach that we refer to as TEMPO (Tracing Expression of Multiple Protein Origins). Liquid biopsy proteomics has the potential to transform molecular diagnostics and prognostics and to assess disease mechanisms and personalized therapeutic strategies in individual patients. This review addresses opportunities, challenges, and future directions of high-resolution liquid biopsy proteomics in ophthalmology, with particular emphasis on the large-scale collection of high-quality samples, cutting edge proteomics technology, and artificial intelligence-supported data analysis.

Treatment for lymphedema following head and neck cancer therapy: A systematic review.

OBJECTIVE: To perform the first systematic review evaluating all established treatment modalities of head and neck lymphedema resulting from head and neck cancer therapy. Since craniofacial lymphedema treatment represents unique challenges not addressed by extremity lymphedema therapies, a systematic review and evaluation of treatment modalities specific to this area is needed to guide clinical management and further research. DATA SOURCES: Four electronic databases were searches from inception to September 2018. These included Scopus (Embase), PubMed (Medline), Clinicaltrials.gov, and Cochrane Databases. REVIEW METHODS: A search string was developed, and all databases queried for keywords on three subjects: head and neck cancer, lymphedema, and therapy. Results were uploaded to an EndNote database where relevant items were identified by hand-searching all titles and abstracts. Subsequently results were combined, duplicates removed, and full papers screened according to eligibility criteria. RESULTS: Of a total 492 search results, twenty-six items met eligibility criteria for this review. These included fourteen cohort studies, seven case reports, two randomized controlled trials, two systematic reviews, and one narrative review totaling 1018 study subjects. The manual lymph drainage group had the largest number of studies and participants, with fewer studies investigating selenium, liposuction, and lymphaticovenular anastomosis. CONCLUSION: Evidence for the efficacy of all types of lymphedema therapy is limited by paucity of large randomized controlled trials. While manual lymph drainage is best studied, liposuction and surgical treatments have also been effective in a small number of patients.

Butterfly cartilage tympanoplasty outcomes: A single-institution experience and literature review.

PURPOSE: In 1998, Dr. Eavey described the trans-canal inlay butterfly cartilage tympanoplasty technique, also known as cartilage button tympanoplasty. Many retrospective studies have since demonstrated its efficacy and decreased operative time when compared to underlay and overlay tympanoplasty techniques. The butterfly cartilage tympanoplasty approach uses only a cartilage graft to repair tympanic membrane perforations. The aim of this study was to review the literature for studies that examined butterfly cartilage tympanoplasty success rates and outcomes and compare them to outcomes from our cohort. MATERIALS AND METHODS: Butterfly cartilage tympanoplasties were performed in 23 pediatric patients and 7 adult patients. We evaluated the tympanic membrane perforation closure rate and hearing results measured by closure of the air-bone gap. RESULTS: The reviewed studies evaluating butterfly cartilage tympanoplasties demonstrated perforation closure rates between 71%-100%. The hearing outcomes in the reviewed literature varied, although the majority reported improved hearing. In our cohort, 21 of the 32 repaired tympanic membrane perforations demonstrated complete perforation closure. The mean follow-up length was 13.4 months. The mean air-bone gap decreased from 13.4 dB to 6.9 dB. CONCLUSIONS: The butterfly cartilage/cartilage button technique is effective in closing tympanic membrane perforations and decreasing the air-bone gap in both adults and children.

Survival after refusal of surgical treatment for locally advanced laryngeal cancer.

OBJECTIVE: Survival of advanced laryngeal cancer is declining while the popularity of organ preservation protocols grows. This study assesses the survival impact of refusing surgical treatment for locally advanced, resectable laryngeal cancer. METHODS: Adult patients with T3 and T4a non-metastatic laryngeal squamous cell carcinoma were identified from the Surveillance, Epidemiology and End Results 18 database from 2004 to 2013. Patients were stratified based on a recommendation for extirpative surgery and the refusal of surgery. Multivariate logistic regression modeling identified variables associated with refusal. A multivariate cox proportional hazard model produced adjusted Kaplan-Meier survival curves. Survival was compared using adjusted hazard ratios (aHR) with 95% confidence intervals (CI). RESULTS: Of 5786 patients in the study, 2877 were recommended for surgical treatment and 138 (4.8%) refused. Refusal of surgery was associated with unmarried status (Single, odds ratio (OR) 1.79, CI 1.10-2.92), black race (OR 1.50, CI 1.00-2.22), T3 tumors (OR 1.80, CI 1.26-2.61) and N3 nodal disease (OR 3.50, CI 1.24-8.48). Compared to patients undergoing surgery, those who refused had lower 5-year cancer specific survival and increased hazard of cancer-specific mortality (aHR 1.60, CI 1.24-2.07) which resulted in decreased 5-year survival (50.0vs 60.1%), after controlling for other factors. CONCLUSION: Refusal of surgery for locally advanced laryngeal cancer is more common in patients without marital support and with T3 tumors. This decision results in a 10% survival decrease at 5-year. Future study is needed to understand patients' reasoning behind this decision and to investigate additional factors not available in this dataset.

Reconstruction of midface defect from idiopathic destructive process using Medpor implant.

IMPORTANCE: Reconstruction of the midface remains a challenging task for even the most experienced surgeon, with a host of reconstructive options including free tissue transfer, allografts, or prosthetic implants. Presented here is a case of idiopathic bony destruction of the right midface in a 19year old female, creating a unique defect requiring repair. OBJECTIVE: Demonstrate a unique case of severe maxillary degeneration and discuss the associated reconstructive challenges and final repair with a prosthetic implant. DESIGN: Case report. RESULTS: The patient presented with a 7month history of an idiopathic progressive deformity of the right cheek. Computed tomography of the paranasal sinuses revealed extensive bone loss of the right midface and orbit. The patient underwent facial reconstruction using a customized Medpor (Stryker Corp, Kalamazoo, MI) implant. At 6month follow-up the patient and physician were both pleased with the patient's overall appearance. The patient did have some residual lower lid retraction present as well as some lateral pull at the lateral canthus outward from the orbit itself. CONCLUSIONS: Preoperative planning for midface reconstruction requires a deep understanding of the aesthetic, functional, and supportive roles this structure holds. Computer assistance allows the creation of custom made implants, providing the reconstructive surgeon with innovative options for reconstruction with minimal morbidity to the patient. As the technology around the design and creation of the custom implants continues to improve, the role of computer assistance in reconstruction will become more prominent.

Diagnostic Delays and Errors in Head and Neck Cancer Patients: Opportunities for Improvement.

A retrospective review of 100 sequential patients (2009-2012) with head and neck cancer was performed to determine the frequency of 5 types of diagnostic delays and errors outlined by the Institute of Medicine. There were a total of 105 diagnostic delays/errors. The most common was delay in being seen in the otolaryngology clinic after referral placement (28.6%), followed by diagnostic error by the referring physician (22%), delay in referral of a symptomatic patient to the otolaryngology clinic (16.2%), delay in employing an appropriate diagnostic test or procedure (15.2%), delay in action following reporting of pathology or imaging results for an incidental lesion (11.4%), diagnostic error by the otolaryngology clinic (2.8%), delay in action following reporting of pathology or imaging results for the symptomatic lesion (2.8%), and use of outmoded tests or therapy (1%). Increased awareness of these types of delays/errors will direct actions and processes to reduce or eliminate them.

Sistemas de Informação

A unidade aborda, inicialmente, o conceito de informação em seus aspectos históricos e a importância da mesma na área da saúde. Assim, a unidade segue aprofundando o conceito no que diz respeito ao planejamento de ações e controle do sistema de saúde (DATASUS), seja nas características dos diversos territórios e seus respectivos processos de saúde-doença e necessidades de suas populações bem como na produção de serviços por parte das equipes responsáveis pela assistência à saúde, em todos os níveis de atenção do SUS. A unidade apresenta também os principais sistemas de informações utilizados atualmente no SUS, dando ênfase ao SIAB (atenção básica) com as respectivas fichas cadastrais e metodologias de preenchimento.