Engaging Australian Aboriginal narratives to challenge attitudes and create empathy in health care: A methodological perspective

Background: Unconscious bias and negative attitudes towards minority groups have detrimental effects on the way health care is, or is not, provided to these groups. Recognition of racist attitudes and behaviours as well as understanding clients’ experiences of health and health care are pivotal to developing better health care strategies to positively impact on the quality and safety of care provided to Indigenous people. Indigenous research demands inclusive research processes and the use of culturally appropriate methodologies. This paper presents a methodological account of collecting narratives which accurately and respectfully reflect Aboriginal Australians’ experiences with health care in Western Australia. The purpose of these narratives is to provide health students and professionals with an opportunity to ‘walk-in the shoes’ of Aboriginal people where face-to-face interaction is not feasible. Methods: With the incorporation of Indigenous peoples’ voices being an important link in cultural safety, the project was led by an Indigenous Reference group, who encouraged active participation of Aboriginal people in all areas of the project. Using a phenomenological approach and guided by the Indigenous Reference group, yarning data collection was implemented to collect stories focusing on Aboriginal people’s experiences with health care services. An open-access, on-line website was established to host education resources developed from these “yarns”. Results: Yarning provided a rich source of information on personal experiences and encouraged the story provider to recognise their facilitative role in the research process. While the methodology used in this project was lengthy and labour-intensive it afforded a respectful manner for story collection and highlighted several innate flaws when Western methods are applied to an Indigenous context. Conclusion: Engagement of an Indigenous Reference Group was pivotal to designing an appropriate methodology that incorporated the voices of Aboriginal people in a multimedia resource of Aboriginal narratives. However further research is warranted to understand how the resources are being used and integrated into curricula, and their impact on students and health care outcomes

Quantitative analysis of vitreous inflammation using optical coherence tomography in patients receiving sub-Tenon's triamcinolone acetonide for uveitic cystoid macular oedema

Background/aims: To evaluate the vitreous signals obtained on spectral domain optical coherence tomography (SD-OCT) in patients with uveitic cystoid macular oedema (CMO) and compare these signals before and after sub-Tenon's triamcinolone acetonide injection. Methods: Retrospective study with standardised longitudinal imaging preintervention and postintervention. The study cohort comprises 22 patients (22 eyes) with uveitic CMO receiving a sub-Tenon's triamcinolone acetonide (STTA) injection. Post hoc analysis of SD-OCT images using custom software provided an ‘absolute’ measurement of vitreous signal intensity, which was expressed as a ratio to the retinal pigment epithelium intensity (‘VIT/RPE-relative intensity’) in arbitrary units. Main outcome measure: Difference in VIT/RPE-relative intensity before and after treatment. Results: Treatment with STTA resulted in a significant reduction in VIT/RPE-relative intensity, which was associated with both a reduction in central retinal thickness (CRT) and improvement in visual acuity. Mean (SD) VIT/RPE-relative intensity pretreatment was 0.139 (0.074) versus 0.053 (0.028) post-treatment (p=3×10−5). Mean (SD) CRT was 581 μm (119 μm) pretreatment versus 333 μm (95 μm) post-treatment (p=2×10−8); the mean reduction in CRT was 248 (95% CI 189 to 306). The correlation coefficient between VIT/RPE-relative intensity and CRT was 0.534 (p=0.011) and between VIT/RPE-relative intensity and visual acuity was 0.702 (p=0.0001). Conclusions: This study provides evidence that the OCT-derived VIT/RPE-relative intensity may be useful as a quantitative and objective marker of disease activity and treatment response in uveitis complicated by CMO. This first longitudinal study of this novel OCT parameter is an encouraging step in the development of sensitive objective OCT-based endpoints for trials of efficacy in uveitis

Strategies for improving early detection and diagnosis of neovascular age-related macular degeneration

Treatment of the neovascular form of age-related macular degeneration (AMD) has been revolutionized by the introduction of such agents as ranibizumab, bevacizumab, and aflibercept. As a result, the incidence of legal blindness occurring secondary to AMD has fallen dramatically in recent years in many countries. While these agents have undoubtedly been successful in reducing visual impairment and blindness, patients with neovascular AMD typically lose some vision over time, and often lose the ability to read, drive, or perform other important activities of daily living. Efforts are therefore under way to develop strategies that allow for earlier detection and treatment of this disease. In this review, we begin by providing an overview of the rationale for, and the benefits of, early detection and treatment of neovascular AMD. To achieve this, we begin by providing an overview of the pathophysiology and natural history of choroidal neovascularization, before reviewing the evidence from both clinical trials and "real-world" outcome studies. We continue by highlighting an area that is often overlooked: the importance of patient education and awareness for early AMD detection. We conclude the review by reviewing an array of both established and emerging technologies for early detection of choroidal neovascularization, ranging from Amsler chart testing, to hyperacuity testing, to advanced imaging techniques, such as optical coherence tomography

Automated Analysis of Vitreous Inflammation Using Spectral-Domain Optical Coherence Tomography

Purpose: To develop an automated method for quantifying vitreous signal intensity on optical coherence tomography (OCT), with particular application for use in the assessment of vitreous inflammation. Methods: This retrospective, observational case-control series comprised 30 patients (30 eyes), with vitreous haze secondary to intermediate, posterior, or panuveitis; 12 patients (12 eyes) with uveitis without evidence of vitreous haze; and 18 patients (18 eyes) without intraocular inflammation or vitreoretinal disease. The presence and severity of vitreous haze was classified according to the National Eye Institute system; other inflammatory indices and clinical parameters were also documented. Spectral-domain OCT images were analyzed using custom VITreous ANalysis software (termed 'VITAN'), which is fully automated and avoids the need for manual segmentation. Results: VITAN performed accurate segmentation in all scans. Automated measurements of the vitreous:retinal pigment epithelium (RPE) signal ratio showed a moderate correlation with clinical vitreous haze scores (r ¼ 0.585, P , 0.001), comparable to that reported using manual segmentation in our previous study (r ¼ 0.566, P ¼ 0.0001). The novel parameter of vitreous:RPE textural ratio showed a marginally stronger correlation (r ¼ 0.604, P , 0.001) with clinical vitreous haze scores than the Vitreous:RPE signal ratio. Conclusions: The custom OCT image analysis software (VITAN) allows rapid and automated measurement of vitreous parameters, that is comparable to our previously reported vitreous:RPE index, and correlates with clinically measured disease activity. Such OCT-based indices may provide the much needed objective markers of vitreous activity, which may be used in both clinical assessment, and as outcome measures in clinical trials for intermediate, posterior, and panuveitis. Translational Relevance: We describe a rapid automated method for quantifying vitreous signal intensity on optical coherence tomography (OCT) and show that this correlates with clinical assessment of vitreous inflammation. Such OCT-based indices may provide the much needed objective markers of vitreous activity, which may be used both in routine clinical assessment, and as outcome measures in clinical trials for intermediate, posterior, and panuveitis

Evaluation of objective vitritis grading method using optical coherence tomography: influence of phakic status and previous vitrectomy

PURPOSE: To evaluate a proposed method for objective measurement of vitreous inflammation using a spectral. domain optical coherence tomography (SD OCT) device in a large cohort of uveitis eyes, including pseudophakic eyes and vitrectomized eyes. DESIGN: Retrospective, observational cohort study. METHODS: One hundred five uveitis eyes (105 patients) with different vitreous haze score grades according to standardized protocols and corresponding SD OCT images (Cirrus HD-OCT; Carl Zeiss Meditec, Dublin, California, USA) were included. Clinical data recorded included phakic status, previous vitreoretinal surgery, and anterior chamber (AC) cells and flare. SD OCT images were analyzed using custom software that provided absolute measurements of vitreous (VIT) and retinal pigment epithelium (RPE) signal intensities, which were compared to generate a relative optical density ratio with arbitrary units (VIT/RPE-relative intensity) and compared to VHS. RESULTS: VIT/RPE-relative intensity showed a significant positive correlation with vitreous haze score (r = 0.535, P <.001) that remained significant after adjusting for factors governing media clarity, such as AC cells, AC flare, and phakic status (R-2-adjusted = 0.424, P <.001). Significant differences were also observed between the different vitreous haze score groups (P <.001). Preliminary observation did not observe differences in VIT/RPE-relative intensity values between phakic and pseudophakic eyes (0.3522 vs 0.3577, P =.48) and between nonvitrectomized and vitrectomized eyes (0.3540 vs 0.3580, P = .52), overall and respectively for each vitreous haze score subgroup. CONCLUSIONS: VIT/RPE-relative intensity values provide objective measurements of vitreous inflammation employing an SD OCT device. Phakic status and previous vitrectomy su

Determinants of non-attendance at face-to-face and telemedicine ophthalmic consultations

BACKGROUND/AIMS: Evaluation of telemedicine care models has highlighted its potential for exacerbating healthcare inequalities. This study seeks to identify and characterise factors associated with non-attendance across face-to-face and telemedicine outpatient appointments. METHODS: A retrospective cohort study at a tertiary-level ophthalmic institution in the UK, between 1 January 2019 and 31 October 2021. Logistic regression modelled non-attendance against sociodemographic, clinical and operational exposure variables for all new patient registrations across five delivery modes: asynchronous, synchronous telephone, synchronous audiovisual and face to face prior to the pandemic and face to face during the pandemic. RESULTS: A total of 85 924 patients (median age 55 years, 54.4% female) were newly registered. Non-attendance differed significantly by delivery mode: (9.0% face to face prepandemic, 10.5% face to face during the pandemic, 11.7% asynchronous and 7.8%, synchronous during pandemic). Male sex, greater levels of deprivation, a previously cancelled appointment and not self-reporting ethnicity were strongly associated with non-attendance across all delivery modes. Individuals identifying as black ethnicity had worse attendance in synchronous audiovisual clinics (adjusted OR 4.24, 95% CI 1.59 to 11.28) but not asynchronous. Those not self-reporting their ethnicity were from more deprived backgrounds, had worse broadband access and had significantly higher non-attendance across all modes (all p<0.001). CONCLUSION: Persistent non-attendance among underserved populations attending telemedicine appointments highlights the challenge digital transformation faces for reducing healthcare inequalities. Implementation of new programmes should be accompanied by investigation into the differential health outcomes of vulnerable populations

Intravenous indocyanine green dye is insufficient for robust immune cell labelling in the human retina

It is not currently possible to reliably visualise and track immune cells in the human central nervous system or eye. Previous work demonstrated that indocyanine green (ICG) dye could label immune cells and be imaged after a delay during disease in the mouse retina. We report a pilot study investigating if ICG can similarly label immune cells within the human retina. Twelve adult participants receiving ICG angiography as part of routine standard of care were recruited. Baseline retinal images were obtained prior to ICG administration then repeated over a period ranging from 2 hours to 9 days. Matched peripheral blood samples were obtained to examine systemic immune cell labelling and activation from ICG by flow cytometry with human macrophage cultures as positive controls. Differences between the delayed near infrared ICG imaging and 488 nm autofluorescence was observed across pathologies, likely arising from the retinal pigment epithelium (RPE). Only one subject demonstrated ICG signal on peripheral blood myeloid cells and only three distinct cell-sized signals appeared over time within the retina of three participants. No significant increase in immune cell activation markers were detected after ICG administration. ICG accumulated in the endosomes of macrophage cultures and was detectable above a minimum concentration, suggesting cell labelling is possible. ICG can label RPE and may be used as an additional biomarker for RPE health across a range of retinal disorders. Standard clinical doses of intravenous ICG do not lead to robust immune cell labelling in human blood or retina and further optimisation in dose and route are required

Clinical Validation of an Ultra High-Throughput Spiral Microfluidics for the Detection and Enrichment of Viable Circulating Tumor Cells

Background: Circulating tumor cells (CTCs) are cancer cells that can be isolated via liquid biopsy from blood and can be phenotypically and genetically characterized to provide critical information for guiding cancer treatment. Current analysis of CTCs is hindered by the throughput, selectivity and specificity of devices or assays used in CTC detection and isolation. Methodology/Principal Findings: Here, we enriched and characterized putative CTCs from blood samples of patients with both advanced stage metastatic breast and lung cancers using a novel multiplexed spiral microfluidic chip. This system detected putative CTCs under high sensitivity (100%, n = 56) (Breast cancer samples: 12–1275 CTCs/ml; Lung cancer samples: 10–1535 CTCs/ml) rapidly from clinically relevant blood volumes (7.5 ml under 5 min). Blood samples were completely separated into plasma, CTCs and PBMCs components and each fraction were characterized with immunophenotyping (Pan-cytokeratin/CD45, CD44/CD24, EpCAM), fluorescence in-situ hybridization (FISH) (EML4-ALK) or targeted somatic mutation analysis. We used an ultra-sensitive mass spectrometry based system to highlight the presence of an EGFR-activating mutation in both isolated CTCs and plasma cell-free DNA (cf-DNA), and demonstrate concordance with the original tumor-biopsy samples. Conclusions/Significance: We have clinically validated our multiplexed microfluidic chip for the ultra high-throughput, low-cost and label-free enrichment of CTCs. Retrieved cells were unlabeled and viable, enabling potential propagation and real-time downstream analysis using next generation sequencing (NGS) or proteomic analysis.Singapore-MIT Alliance for Research and Technolog

Long-term remission of myopic choroidal neovascular membrane after treatment with ranibizumab: a case report

<p>Abstract</p> <p>Introduction</p> <p>Myopia has become a big public health problem in certain parts of the world. Sight-threatening complications like choroidal neovascularisation membranes occur in up to 10% of pathological myopia, and natural history studies show a trend towards progressive visual loss. There are long-term financial and quality-of-life implications in this group of patients, and treatment strategies should aim for long-term preservation of vision.</p> <p>Case presentation</p> <p>A 56-year-old Caucasian woman presented with a best-corrected visual acuity of 6/6-1 in her right eye and 6/24 in her left. Fundal examination revealed pathological myopia in both eyes and an elevated lesion associated with pre-retinal haemorrhage in the left macula. Ocular coherence tomography and fundus fluorescein angiogram confirmed a subfoveal classic choroidal neovascularisation membrane. The patient decided to proceed with intravitreal ranibizumab (0.5 mg) therapy. One month after treatment, best-corrected visual acuity improved to 6/12 in her left eye, with complete resolution subretinal fluid on ocular coherence tomography. After three months, best-corrected visual acuity further improved to 6/9, which was maintained up to 16 months post-treatment.</p> <p>Conclusion</p> <p>We suggest intravitreal ranibizumab as an alternative treatment for long-term remission of myopic choroidal neovascular membrane. It also suggests that myopic choroidal neovascularisation membranes may require fewer treatments to achieve sustained remission. Furthermore, this could serve as a feasible long-term management option if used in conjunction with ocular coherence tomography.</p