Ophthalmology (Eye & Ear Hospital) - Research Publications
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ItemNo Preview AvailableVision-Related quality of life and ocular parameters in end-stage renal disease patients undergoing hemodialysis(WOLTERS KLUWER MEDKNOW PUBLICATIONS, 2023)PURPOSE: To evaluate the vision-related quality of life (VRQoL) of patients receiving hemodialysis through the assessment of the impact of vision impairment (IVI) questionnaire and ocular parameters, including best-corrected visual acuity (BCVA), intraocular pressure (IOP), and refraction as calculated by spherical equivalent (SE) of each eye. METHODS: Fifty-one patients with end-stage renal disease undergoing hemodialysis at a single center were recruited, and a total of 77 eyes were evaluated. BCVA, IOP, and SE were evaluated before and after hemodialysis (within 30 min). RESULTS: Of the 51 patients recruited, 13 (25%) were female, 37 (73%) were male, and one (2%) chose not to specify gender. The mean age was 61.85 ± 32 years. The mobility IVI score was correlated significantly with the presence of hypertension (P = 0.01), eye drop usage (P = 0.04), and gender (P = 0.04). Emotional IVI scores were correlated significantly with diabetes (P = 0.03) and hypertension (P < 0.01). IOP significantly correlated with the IVI overall score (P = 0.02), including the reading IVI subscale and the emotional IVI subscale. Several factors were associated with posthemodialysis ocular parameters, including predialysis ocular parameters, age, and hypertension (P < 0.05 for all). CONCLUSIONS: IOP significantly correlated with VRQoL in hemodialysis patients. Demographic variables such as diabetes status, hypertension, eye drop usage, and gender also significantly correlated with subsections of the IVI questionnaire. This study investigated the relationship between ocular parameters and VRQoL in hemodialysis patients, and future longitudinal research is needed to further elucidate the mechanisms.
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ItemNo Preview AvailableKeratoconus International Consortium (KIC)- advancing keratoconus research(BMC, 2023-07-27)CLINICAL RELEVANCE: The Keratoconus International Consortium (KIC) will allow better understanding of keratoconus. BACKGROUND: Keratoconus is a disorder characterised by corneal elevation and thinning, leading to reduced vision. The current gaps in understanding of this disease will be discussed and the need for a multi-pronged and multi-centre engagement to enhance our understanding of keratoconus will be highlighted. DESIGN: KIC has been established to address the gaps in our understanding of keratoconus with the aim of collecting baseline as well as longitudinal data on several fields. PARTICIPANTS: Keratoconus and control (no corneal condition) subjects from different sites globally will be recruited in the study. METHODS: KIC collects data using an online, secure database, which enables standardised data collection at member sites. Data fields collected include medical history, clinical features, quality of life and economic burden questionnaires and possible genetic sample collection from patients of different ethnicities across different geographical locations. RESULTS: There are currently 40 Australian and international clinics or hospital departments who have joined the KIC. Baseline data has so far been collected on 1130 keratoconus patients and indicates a median age of 29.70 years with 61% being male. A total of 15.3% report a positive family history of keratoconus and 57.7% self-report a history of frequent eye rubbing. CONCLUSION: The strength of this consortium is its international, collaborative design and use of a common data collection tool. Inclusion and analyses of cross-sectional and longitudinal data will help answer many questions that remain in keratoconus, including factors affecting progression and treatment outcomes.
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ItemNo Preview AvailableExamining Corneal Tissue Exportation Fee and Its Impact on Equitable Allocation(LIPPINCOTT WILLIAMS & WILKINS, 2022-03)METHODS: We conducted grounded theory semistructured interviews, purposively inviting participants until themed saturation was met. Sentiment analysis was used to determine opinion. RESULTS: We interviewed n = 92 global eye tissue and eye bank professionals. We determined that corneal tissue, which is exported, costs between US $100 and US $6000 or is provided as gratis. Collectively, interviewees indicated that, globally, there were no fixed fee structures in place, and the fee was influenced by multiple factors on both export and import sides. They indicated that ultimately corneas were allocated based on the importers' ability to pay the price determined by the exporting eye bank. DISCUSSION: Allocation of corneal tissue, which is exported, is influenced by the fees charged by the exporters to meet their bottom line and the funds available to importers. Therefore, export allocation is not equitable, with those who can pay a higher fee, prioritized. Steps to guide and support exporters with the development of fee structures that promote equitable allocation are essential. This will assist both export and import eye bank development, corneal tissue access development, and those awaiting a corneal transplant.
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ItemNo Preview AvailableNon-genetic risk factors for keratoconus(TAYLOR & FRANCIS LTD, 2023-05-19)Keratoconus is a complex and multifactorial disease and its exact aetiology remains unknown. This current study examined the important environmental risk factors and their association with keratoconus. This study was registered in the PROSPERO International Prospective Register of systematic reviews under registration number CRD42021256792 in 2021. Scopus, Web of Science, PubMed, and Cochrane CENTRAL databases were searched for all relevant articles published from 1 January 1900 to 31 July 2021. National Institutes of Health Quality Assessment Tool was used to assess the methodological quality of the studies. The assessment for statistical heterogeneity was assessed using the Z-statistics on RevMan v5.4. P-value of <0.05 was considered as statistically significant and I2 < 25% as homogenous. Thirty studies were included in this meta-analysis. Pooled odds ratio was calculated with 95% CI. The pooled odds ratio (OR) of eye rubbing, atopy, asthma, and eczema was 3.64 (95% CI, 2.02, 6.57), 1.90 (95% CI, 1.22, 2.94), 1.36 (95% CI, 1.15, 1.61) and 1.90 (95% CI, 1.22, 2.94), respectively. The OR for diabetes was 0.86 (95% CI 0.73, 1.02), and use of sunglasses, contact lens, allergic conjunctivitis, side sleep position and prone sleep position was 0.40 (95% CI, 0.16, 0.99), 1.68 (0.70, 4.00), 2.24 (95% CI, 0.68, 7.36), 3.81 (95% CI, 0.31, 46.23), 12.76 (95% CI, 0.27, 598.58), respectively. Twenty studies were considered to be of high quality, nine to be moderate and one to be low. Environmental risk factors have been identified to play a role in the susceptibility of keratoconus. However, further large-scale longitudinal studies are needed to understand the mechanisms between environmental risk factors and keratoconus.
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ItemNo Preview AvailableExploring the contribution of ARMS2 and HTRA1 genetic risk factors in age-related macular degeneration(PERGAMON-ELSEVIER SCIENCE LTD, 2023-11)Age-related macular degeneration (AMD) is the leading cause of severe irreversible central vision loss in individuals over 65 years old. Genome-wide association studies (GWASs) have shown that the region at chromosome 10q26, where the age-related maculopathy susceptibility (ARMS2/LOC387715) and HtrA serine peptidase 1 (HTRA1) genes are located, represents one of the strongest associated loci for AMD. However, the underlying biological mechanism of this genetic association has remained elusive. In this article, we extensively review the literature by us and others regarding the ARMS2/HTRA1 risk alleles and their functional significance. We also review the literature regarding the presumed function of the ARMS2 protein and the molecular processes of the HTRA1 protein in AMD pathogenesis in vitro and in vivo, including those of transgenic mice overexpressing HtrA1/HTRA1 which developed Bruch's membrane (BM) damage, choroidal neovascularization (CNV), and polypoidal choroidal vasculopathy (PCV), similar to human AMD patients. The elucidation of the molecular mechanisms of the ARMS2 and HTRA1 susceptibility loci has begun to untangle the complex biological pathways underlying AMD pathophysiology, pointing to new testable paradigms for treatment.
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ItemNo Preview AvailableStratification of keratoconus progression using unsupervised machine learning analysis of tomographical parameters(Elsevier BV, 2023-01-01)Purpose: This study aimed to stratify eyes with keratoconus (KC) based on longitudinal changes in all Pentacam parameters into clusters using unsupervised machine learning, with the broader objective of more clearly defining the characteristics of KC progression. Methods: A data-driven cluster analysis (hierarchical clustering) was undertaken on a retrospective cohort of 1017 kC eyes and 128 control eyes. Clusters were derived using 6-month tomographical change in individual eyes from analysis of the reduced dimensionality parameter space using all available Pentacam parameters (406 principal components). The optimal number of clusters was determined by the clustering's capacity to discriminate progression between KC and control eyes based on change across parameters. One-way ANOVA was used to compare parameters between inferred clusters. Complete Pentacam data changes at 6, 12 and 18-month time points provided validation datasets to determine the generalizability of the clustering model. Results: We identified three clusters in KC progression patterns. Eyes designated within cluster 3 had the most rapidly changing tomographical parameters compared to eyes in either cluster 1 or 2. Eyes designated within cluster 1 reflected minimal changes in tomographical parameters, closest to the tomographical changes of control (non-KC) eyes. Thirty-nine corneal curvature parameters were identified and associated with these stratified clusters, with each of these parameters changing significantly different between three clusters. Similar clusters were identified at the 6, 12 and 18-month follow-up. Conclusions: The clustering model developed was able to automatically detect and categorize KC tomographical features into fast, slow, or limited change at different time points. This new KC stratification tool may provide an opportunity to provide a precision medicine approach to KC.
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ItemComparison of CT derived body composition at the thoracic T4 and T12 with lumbar L3 vertebral levels and their utility in patients with rectal cancer(BMC, 2023-01-16)BACKGROUND: Computed tomography (CT) derived body composition measurements of sarcopenia are an emerging form of prognostication in many disease processes. Although the L3 vertebral level is commonly used to measure skeletal muscle mass, other studies have suggested the utilisation of other segments. This study was performed to assess the variation and reproducibility of skeletal muscle mass at vertebral levels T4, T12 and L3 in pre-operative rectal cancer patients. If thoracic measurements were equivalent to those at L3, it will allow for body composition comparisons in a larger range of cancers where lumbar CT images are not routinely measured. RESEARCH METHODS: Patients with stage I - III rectal cancer, undergoing curative resection from 2010 - 2014, were assessed. CT based quantification of skeletal muscle was used to determine skeletal muscle cross sectional area (CSA) and skeletal muscle index (SMI). Systematic differences between the measurements at L3 with T4 and T12 vertebral levels were evaluated by percentile rank differences to assess distribution of differences and ordinary least product regression (OLP) to detect and distinguish fixed and proportional bias. RESULTS: Eighty eligible adult patients were included. Distribution of differences between T12 SMI and L3 SMI were more marked than differences between T4 SMI and L3 SMI. There was no fix or proportional bias with T4 SMI, but proportional bias was detected with T12 SMI measurements. T4 CSA duplicate measurements had higher test-retest reliability: coefficient of repeatability was 34.10 cm2 for T4 CSA vs 76.00 cm2 for T12 CSA. Annotation time (minutes) with L3 as reference, the median difference was 0.85 for T4 measurements and -0.03 for T12 measurements. Thirty-seven patients (46%) had evidence of sarcopenia at the L3 vertebral level, with males exhibiting higher rates of sarcopenia. However, there was no association between sarcopenia and post-operative complications, recurrence or hospital LOS (length of stay) in patients undergoing curative resection. CONCLUSIONS: Quantifying skeletal muscle mass at the T4 vertebral level is comparable to measures achieved at L3 in patients with rectal cancer, notwithstanding annotation time for T4 measurements are longer.
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ItemA genome-wide association study of corneal astigmatism: The CREAM Consortium(MOLECULAR VISION, 2018-02-05)PURPOSE: To identify genes and genetic markers associated with corneal astigmatism. METHODS: A meta-analysis of genome-wide association studies (GWASs) of corneal astigmatism undertaken for 14 European ancestry (n=22,250) and 8 Asian ancestry (n=9,120) cohorts was performed by the Consortium for Refractive Error and Myopia. Cases were defined as having >0.75 diopters of corneal astigmatism. Subsequent gene-based and gene-set analyses of the meta-analyzed results of European ancestry cohorts were performed using VEGAS2 and MAGMA software. Additionally, estimates of single nucleotide polymorphism (SNP)-based heritability for corneal and refractive astigmatism and the spherical equivalent were calculated for Europeans using LD score regression. RESULTS: The meta-analysis of all cohorts identified a genome-wide significant locus near the platelet-derived growth factor receptor alpha (PDGFRA) gene: top SNP: rs7673984, odds ratio=1.12 (95% CI:1.08-1.16), p=5.55×10-9. No other genome-wide significant loci were identified in the combined analysis or European/Asian ancestry-specific analyses. Gene-based analysis identified three novel candidate genes for corneal astigmatism in Europeans-claudin-7 (CLDN7), acid phosphatase 2, lysosomal (ACP2), and TNF alpha-induced protein 8 like 3 (TNFAIP8L3). CONCLUSIONS: In addition to replicating a previously identified genome-wide significant locus for corneal astigmatism near the PDGFRA gene, gene-based analysis identified three novel candidate genes, CLDN7, ACP2, and TNFAIP8L3, that warrant further investigation to understand their role in the pathogenesis of corneal astigmatism. The much lower number of genetic variants and genes demonstrating an association with corneal astigmatism compared to published spherical equivalent GWAS analyses suggest a greater influence of rare genetic variants, non-additive genetic effects, or environmental factors in the development of astigmatism.
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ItemNo Preview AvailableThe extracellular microenvironment in immune dysregulation and inflammation in retinal disorders(FRONTIERS MEDIA SA, 2023-03-01)Inherited retinal dystrophies (IRDs) as well as genetically complex retinal phenotypes represent a heterogenous group of ocular diseases, both on account of their phenotypic and genotypic characteristics. Therefore, overlaps in clinical features often complicate or even impede their correct clinical diagnosis. Deciphering the molecular basis of retinal diseases has not only aided in their disease classification but also helped in our understanding of how different molecular pathologies may share common pathomechanisms. In particular, these relate to dysregulation of two key processes that contribute to cellular integrity, namely extracellular matrix (ECM) homeostasis and inflammation. Pathological changes in the ECM of Bruch's membrane have been described in both monogenic IRDs, such as Sorsby fundus dystrophy (SFD) and Doyne honeycomb retinal dystrophy (DHRD), as well as in the genetically complex age-related macular degeneration (AMD) or diabetic retinopathy (DR). Additionally, complement system dysfunction and distorted immune regulation may also represent a common connection between some IRDs and complex retinal degenerations. Through highlighting such overlaps in molecular pathology, this review aims to illuminate how inflammatory processes and ECM homeostasis are linked in the healthy retina and how their interplay may be disturbed in aging as well as in disease.
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ItemAccuracy of Machine Learning Assisted Detection of Keratoconus: A Systematic Review and Meta-Analysis(MDPI, 2022-02)(1) Background: The objective of this review was to synthesize available data on the use of machine learning to evaluate its accuracy (as determined by pooled sensitivity and specificity) in detecting keratoconus (KC), and measure reporting completeness of machine learning models in KC based on TRIPOD (the transparent reporting of multivariable prediction models for individual prognosis or diagnosis) statement. (2) Methods: Two independent reviewers searched the electronic databases for all potential articles on machine learning and KC published prior to 2021. The TRIPOD 29-item checklist was used to evaluate the adherence to reporting guidelines of the studies, and the adherence rate to each item was computed. We conducted a meta-analysis to determine the pooled sensitivity and specificity of machine learning models for detecting KC. (3) Results: Thirty-five studies were included in this review. Thirty studies evaluated machine learning models for detecting KC eyes from controls and 14 studies evaluated machine learning models for detecting early KC eyes from controls. The pooled sensitivity for detecting KC was 0.970 (95% CI 0.949-0.982), with a pooled specificity of 0.985 (95% CI 0.971-0.993), whereas the pooled sensitivity of detecting early KC was 0.882 (95% CI 0.822-0.923), with a pooled specificity of 0.947 (95% CI 0.914-0.967). Between 3% and 48% of TRIPOD items were adhered to in studies, and the average (median) adherence rate for a single TRIPOD item was 23% across all studies. (4) Conclusions: Application of machine learning model has the potential to make the diagnosis and monitoring of KC more efficient, resulting in reduced vision loss to the patients. This review provides current information on the machine learning models that have been developed for detecting KC and early KC. Presently, the machine learning models performed poorly in identifying early KC from control eyes and many of these research studies did not follow established reporting standards, thus resulting in the failure of these clinical translation of these machine learning models. We present possible approaches for future studies for improvement in studies related to both KC and early KC models to more efficiently and widely utilize machine learning models for diagnostic process.