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Contains fulltext : 292919.pdf (Publisher’s version ) (Open Access) BACKGROUND: High myopia (HM), defined as a spherical equivalent refractive error (SER) ≤ -6.00 diopters (D), is a leading cause of sight impairment, through myopic macular degeneration (MMD). We aimed to derive an improved polygenic score (PGS) for predicting children at risk of HM and to test if a PGS is predictive of MMD after accounting for SER. METHODS: The PGS was derived from genome-wide association studies in participants of UK Biobank, CREAM Consortium, and Genetic Epidemiology Research on Adult Health and Aging. MMD severity was quantified by a deep learning algorithm. Prediction of HM was quantified as the area under the receiver operating curve (AUROC). Prediction of severe MMD was assessed by logistic regression. FINDINGS: In independent samples of European, African, South Asian and East Asian ancestry, the PGS explained 19% (95% confidence interval 17-21%), 2% (1-3%), 8% (7-10%) and 6% (3-9%) of the variation in SER, respectively. The AUROC for HM in these samples was 0.78 (0.75-0.81), 0.58 (0.53-0.64), 0.71 (0.69-0.74) and 0.67 (0.62-0.72), respectively. The PGS was not associated with the risk of MMD after accounting for SER: OR = 1.07 (0.92-1.24). INTERPRETATION: Performance of the PGS approached the level required for clinical utility in Europeans but not in other ancestries. A PGS for refractive error was not predictive of MMD risk once SER was accounted for. FUNDING: Supported by the Welsh Government and Fight for Sight (24WG201).

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Purpose: Identification of single-nucleotide polymorphisms (SNP) associated with development of advanced colorectal adenomas.Experimental Design: Discovery phase: 1,406 Caucasian patients (139 advanced adenoma cases and 1,267 controls) from the Adenoma Prevention with Celecoxib (APC) trial were included in a genome-wide association study (GWAS) to identify variants associated with postpolypectomy disease recurrence. Genome-wide significance was defined as false discovery rate less than 0.05, unadjusted P = 7.4 × 10−7. Validation phase: results were further evaluated using 4,175 familial colorectal adenoma cases and 5,036 controls from patients of European ancestry [COloRectal Gene Identification consortium (CORGI), Scotland, Australia, and VQ58].Results: Our study identified eight SNPs associated with advanced-adenoma risk in the APC trial (rs2837156, rs7278863, rs2837237, rs2837241, rs2837254, rs741864 at 21q22.2, and rs1381392 and rs17651822 at 3p24.1, at P < 10−7 level with OR > 2). Five variants in strong pairwise linkage disequilibrium (rs7278863, rs2837237, rs741864, rs741864, and rs2837241; r2 = 0.8–1) are in or near the coding region for the tight junction adhesion protein, IGSF5. An additional variant associated with advanced adenomas, rs1535989 [minor allele frequency, 0.11; OR, 2.09; 95% confidence interval (CI), 1.50–2.91], also predicted colorectal cancer development in a validation analysis (P = 0.019) using a series of adenoma cases or colorectal cancer (CORGI study) and 3 sets of colorectal cancer cases and controls (Scotland, VQ58, and Australia; N = 9,211).Conclusions: Our results suggest that common polymorphisms contribute to the risk of developing advanced adenomas and might also contribute to the risk of developing colorectal cancer. The variant at rs1535989 may identify patients whose risk for neoplasia warrants increased colonoscopic surveillance. Clin Cancer Res; 19(23); 6430–7. ©2013 AACR.

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The global "myopia boom" has raised significant international concerns. Despite a higher myopia prevalence in Asia, previous large-scale genome-wide association studies (GWASs) were mostly based on European descendants. Here, we report a GWAS of spherical equivalent (SE) in 1852 Chinese Han individuals with extreme SE from Guangzhou (631 -6.00D and 574 0.00D) and Wenzhou (593 -6.00D and 54 -1.75D), followed by a replication study in two independent cohorts with totaling 3538 East Asian individuals. The discovery GWAS and meta-analysis identify three novel loci, which show genome-wide significant associations with SE, including 1q25.2 FAM163A, 10p11.22 NRP1/PRAD3, and 10p11.21 ANKRD30A/MTRNR2L7, together explaining 3.34% of SE variance. 10p11.21 is successfully replicated. The allele frequencies of all three loci show significant differences between major continental groups (P 0.001). The SE reducing (more myopic) allele of rs10913877 (1q25.2 FAM163A) demonstrates the highest frequency in East Asians and much lower frequencies in Europeans and Africans (EAS = 0.60, EUR = 0.20, and AFR = 0.18). The gene-based analysis additionally identifies three novel genes associated with SE, including EI24, LHX5, and ARPP19. These results provide new insights into myopia pathogenesis and indicate the role of genetic heterogeneity in myopia epidemiology among different ethnicities.

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.

Although an estimated 23% of all global corneal transplants occur because corneal tissue is moved from one nation to another (export and import), the fee structures, fees charged, and use of reimbursement or profit models, to support this practice, have not been evaluated. This article describes the fee structures and determines whether they support or hinder the equitable allocation of corneal tissue. 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.

Recovery and access to end-of-life corneal tissue for corneal transplantation, training and research is globally maldistributed. The reasons for the maldistribution are complex and multifaceted, and not well defined or understood. Currently there are few solutions available to effectively address these issues. This review provides an overview of the system, key issues impacting recovery and allocation and emphasises how end-user ophthalmologists and researchers, with support from administrators and the wider sector, can assist in increasing access long-term through sustaining eye banks nationally and globally. We posit that prevention measures and improved surgical techniques, together with the development of novel therapies will play a significant role in reducing demand and enhance the equitable allocation of corneas.

Background:Computed tomography (CT) derived body composition measurements of sarcopenia are an emerging form of prognostication in many disease processes. Outcomes in advanced rectal cancer treatment are typically dependent on success of using a combination of chemotherapy and surgery. There is growing evidence that body composition determines chemotherapy tolerance and surgical outcomes. Although the L3 vertebral level is commonly used to measure skeletal muscle mass, other studies have suggested the utilisation of other segments may also be appropriate. This study was performed to determine the variation and reproducibility in assessment of skeletal muscle mass at vertebral levels T4, T12 and L3 in pre-operative rectal cancer patients. Research Methods:118 adult 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). Agreement between the measurements at L3 with T4 and T12 vertebral levels were evaluated using goodness-of-fit, Pearson’s correlation coefficient, and Bland-Altman plots.Results:80 of 118 patients were included in our study. There were 21 (26%) female and 59 (74%) male patients (30-86years, Mean±SD; 63.0 ± 13.0). The correlation between SMI at L3 and SMI at T12 was stronger (r = 0.84, P r = 0.80, P 0.96 at all levels with agreement being highest at T12 and L3. Conclusions:This study demonstrated that quantifying skeletal muscle mass at the T12 vertebral level is straightforward, reproducible, reliable and comparable to measures achieved at L3 in patients with rectal cancer.

Keratoconus is a potentially blinding condition that slowly deforms the cornea in young people. Despite the increasing prevalence of keratoconus, the exact aetiology of the condition is unknown. This first systematic review examines the evidence of eye rubbing and its association with keratoconus and presents the findings of the meta-analysis. Two independent reviewers searched the electronic databases for all potential articles published from 1st of January 1900 to 31st of July 2020 on eye rubbing and keratoconus. The researchers assessed the methodological quality of the studies using the Newcastle-Ottawa scale for observational studies. The assessment for statistical heterogeneity was estimated using chi-square and I-square (I2) tests. A p value of

Our results show that asthmatic patients tend to have more severe KC and thus close monitoring for disease progression would be advised, and appropriate treatment strategies may be actioned stabilise the condition that may reduce the need for future corneal transplantation. To explore a wide range of risk factors associated with the severity of keratoconus (KC). A cross-sectional study of KC patients was undertaken in Melbourne, Australia. A questionnaire addressing age, gender, educational background, ocular and medical history, smoking and alcohol consumption, and physical examination comprising anthropometric measurements was collected; eye examination was undertaken. The associations between a range of risk factors and the severity of KC were determined using univariate and multivariable linear regression analyses. A total of 260 KC subjects were included in this study. Mean age of subject was 35.5 (SD = 14.8) years and the majority of the subjects were European 171 (68.2%). Initial univariate regression analysis identified the following risk factors at the p

Purpose There is a global demand for corneal tissue (CT) for transplantation, with some nations potentially able to export donations to those nations without. Unfortunately, there remains a global paucity of information that explains the process of exportation and importation (transnational activity), supports or defines practice, or informs those seeking to engage. Without knowledge, inclusive of the pros and cons, participating nations and decision makers are unable to make effective and informed decisions. Methods Through the example of our own nation, Australia, which may be entering a surplus-to-domestic demand phase and able to export, we conducted qualitative grounded-theory semistructured interviews with sector experts. Our approach ascertained whether Australia should export and under what arrangements. Through saturation and sentiment methods, we capture for the first time, global opinion on CT transnational activity (although primarily exportation), key themes, and finally determine whether Australia should engage. Results Eighty-four (91%) of 92 participants directly commented on our question "should Australia export corneal tissue?" Of 84, n = 67 (80%) stated yes, n = 17 (20%) indicated mixed opinions. No participant categorically stated that there should be no export. Conclusions Eye tissue and eye care experts whom we interviewed, supported the concept of Australia exporting CT; however, they advise several safeguards to protect both import and export nations. Principally, they recommended practice be transparent with donors, nationally coordinated, part of a wider humanitarian program, nonprofit, short term for the importing nations as they move toward self-sufficiency and that Australia must define and confirm domestic need and ensure that demand is met before routine exportation.

IMPORTANCE: This is the first study to estimate the lifetime costs associated with keratoconus based on a questionnaire completed by patients and highlights the significant economic burden of the disease. As keratoconus affects individuals from a young age, the study highlights keratoconus as a public health concern. BACKGROUND: Keratoconus is a disorder characterised by corneal steepening and thinning, leading to reduced visual acuity. To date, there have been no studies evaluating the economic costs of keratoconus from a patient's perspective. DESIGN: A randomised cross-sectional study undertaken in Australia where keratoconus subjects were recruited from public and private ophthalmology and optometry clinics. PARTICIPANTS: A total of 100 participants completed the questionnaire: median age was 31 years and 57% were males. METHODS: A keratoconus health expenditure questionnaire was designed to assess direct and indirect expenditures for each individual. MAIN OUTCOME MEASURES: Total direct and indirect costs associated with the condition were calculated along with the estimated lifetime per capita costs. RESULTS: The total cost related to direct and indirect care was estimated to be AUD 3365. By applying our cost data to keratoconus prevalence data for the Australian population, the total cost is estimated to be approximately AUD 44.7 million per year in Australia. CONCLUSIONS AND RELEVANCE: Our results show that the costs associated with the diagnosis and management of keratoconus represent a significant cost to patients. An understanding of this is important not only to individuals and their families, but also health care providers, health insurers and the wider health system. This article is protected by copyright. All rights reserved.

Purpose Globally, an estimated 12.7 million people await a corneal transplant. Of these, 53% are without routine access to a domestic supply and are reliant on transnational activity (TNA) (importation) of corneal tissue (CT) for transplantation. Although CT TNA commenced in 1961, there has been no evaluation of its impact on import and export nations. Methods We wished to examine the impact of clinical and nonclinical CT TNA on export and import nations, with nonclinical aspects our primary focus, to help guide future practice. We conducted a review of the academic literature through various search engines. We prefix and place our review in the relevant historical practice and global context. Results Despite commencement in 1961, we only located 14 studies (11 clinical and 3 nonclinical) pertaining to CT TNA. These were published between 1991 and 2018. Clinical papers reported death-to-preservation time, preservation-to-transplantation time, logistics, donor and recipient selection, and quality as relevant. Nonclinical studies identified emerging themes pertaining to financial, ethical, and sustainability aspects of TNA. Conclusions All aspects of CT TNA are grossly under-reported, resulting in our inability to effectively analyze the overall impact to export and import nations. The few clinical studies in our review concluded that despite endothelial cell loss and other risk factors, imported CT appears comparable with domestic CT and remains an option in the absence of domestic supply. Nonclinical aspects (eg, ethical, equitable, and economic) have also not been adequately addressed.

(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.

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 2 < 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.

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.

Twin registries have developed as a valuable resource for the study of many aspects of disease and society over the years in many different countries. A number of these registries include large numbers of twins with data collected at varying information levels for twin cohorts over the past several decades. More recent expansion of twin datasets has allowed for the collection of genetic data, together with many other levels of ‘omic’ information along with multiple demographic, physiological, health outcomes and other measures typically used in epidemiologic research. Other twin data sources outside these registries reflect research interests in particular aspects of disease or specific phenotypic assessment. Twin registries have the potential to play a key role in many aspects of the artificial intelligence/machine learning-driven projects of the future and will continue to keep adapting to the changing research landscape.

The Asian Eye Genetics Consortium (AGEC) established in 2014 brought collective thinking and ideas of the Asian and non-Asian researchers who have an interest in genetic eye research. As the consortium grew, requests to join the consortium from outside of Asia were increasing. During the AGEC meeting at ARVO 2018 in Honolulu, USA, the members unanimously voted to expand the consortium activities beyond Asia and explore unique phenotype and genotype populations in the rest of the world, particularly in Africa and South America. The consortium was renamed the Global Eye Genetics Consortium (GEGC, https://gegc.org) by the general membership. The consortium aims were adjusted and the new GEGC phenotype-genotype database GenEye (https://geneye.kankakuki.jp) was constructed to collect and catalog genetic eye diseases at global scale. GEGC membership has grown to over 200 from five continents, performing GEGC meetings and sessions during ARVO, AIOS, APAO, WOC, and ISER meetings. A number of scientific collaboration and young investigator visiting programs have been successfully launched over the past 6 years.

PURPOSE: International export and import of corneas is dependent on the stakeholders involved in the process and how those organizations engage to move corneas from one point to another. Our article presents the pathway of corneal donation from the export nation until its use in the import nation. It presents opinion on how aspects, such as competition and promotional behaviors, the use of online systems, and third-party engagement may influence allocation. METHODS: We interviewed n = 92 international eye tissue and eye bank (EB) professionals to garner their opinion. We used saturation and sentiment methods to extract and consolidate group opinion. RESULTS: Interviewees indicated that competition and promotional behaviors existed in some EB nations-although it was not universal. They indicated that the behavioral approach used by the individual EB, rather than the act of information sharing, influenced allocation. They also indicated that organizational models and allocation systems (eg, online ordering) and engagement with nonstate actors were important in allocation practice and decision making. CONCLUSION: We mapped the pathways for corneas involved in export and import from the point of recovery to their point of transplantation. Although generalist in nature and limited by the paucity of the existing literature, our article outlines that different business models, partnerships, and applied methods influence corneal export and import.

Keratoconus is a potentially blinding condition that slowly deforms the cornea in young people. Despite the increasing prevalence of keratoconus, the exact aetiology of the condition is unknown. This first systematic review examines the evidence of eye rubbing and its association with keratoconus and presents the findings of the meta-analysis.Two independent reviewers searched the electronic databases for all potential articles published from 1st of January 1900 to 31st of July 2020 on eye rubbing and keratoconus. The researchers assessed the methodological quality of the studies using the Newcastle-Ottawa scale for observational studies. The assessment for statistical heterogeneity was estimated using chi-square and I-square (IEight case-control studies were included in this systematic review. Two studies assessed eye rubbing without odds ratios and thus were excluded. The pooled odds ratios for the six remaining studies included in the meta-analysis was 6.46 (95% CI 4.12-10.1). The study results were heterogenous (IEye rubbing showed consistent association with keratoconus. However, the current evidence is limited to only a small number of case-control studies which present as heterogeneous and of sub-optimal methodological quality. Additionally, the cause-effect temporal relationship cannot be determined. Further studies are needed to address this intricate relationship of eye rubbing and its induction, ongoing progression, and severity of keratoconus.

Purpose Corneal tissue importation is only possible if another country is able to export corneas without impacting its own domestic demand. Currently, there is little evidence to indicate whether export nations have such surplus capacity and in a position to export. To explore this concept, we examined our nation, Australia, which is reported to routinely decline donations because of its ability to meet domestic corneal transplant demand. Our research offers insights and opportunities for Australia and other nations to evaluate their domestic and international supply and allocation of corneal tissue in this space. Method We collated 12 months of data on collected and noncollected donations, through participating Australian Eye Banks. The explanation of why some known donors were declined or not pursued indicated if demand was met and potential surplus-for-export levels. Results There were 7.5% (n = 11,889) of deaths in Australia that were notified to Australian Eye Banks during our reporting period. Of those, 9.3% (n = 1106/11,889) were recovered and allocated, 15.7% (n = 1863/11,889) were known but declined, and 75% (n = 8920/11,889) were not pursued. Of those that were declined, 64.3% (n = 1197/1863) were declined because of limitations with service/manpower at the eye bank, whereas 35.7% (n = 666/1863) were declined because demand was met. Conclusions Australia did not meet demand all the time, during our data period. There were adequate quantities of potential donors to support increasing recovery for domestic allocation and provide for exportation without hindrance to Australian demand. Further examination of domestic supply and demand cycles and the export process is required before routine exportation.

Purpose: The purpose of this study was to summarize and evaluate artificial intelligence (AI) algorithms used in geographic atrophy (GA) diagnostic processes (e.g. isolating lesions or disease progression). Methods: The search strategy and selection of publications were both conducted in accordance with the Preferred of the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. PubMed and Web of Science were used to extract literary data. The algorithms were summarized by objective, performance, and scope of coverage of GA diagnosis (e.g. lesion automation and GA progression). Results: Twenty-seven studies were identified for this review. A total of 18 publications focused on lesion segmentation only, 2 were designed to detect and classify GA, 2 were designed to predict future overall GA progression, 3 focused on prediction of future spatial GA progression, and 2 focused on prediction of visual function in GA. GA-related algorithms reported sensitivities from 0.47 to 0.98, specificities from 0.73 to 0.99, accuracies from 0.42 to 0.995, and Dice coefficients from 0.66 to 0.89. Conclusions: Current GA-AI publications have a predominant focus on lesion segmentation and a minor focus on classification and progression analysis. AI could be applied to other facets of GA diagnoses, such as understanding the role of hyperfluorescent areas in GA. Using AI for GA has several advantages, including improved diagnostic accuracy and faster processing speeds. Translational Relevance: AI can be used to quantify GA lesions and therefore allows one to impute visual function and quality-of-life. However, there is a need for the development of reliable and objective models and software to predict the rate of GA progression and to quantify improvements due to interventions.

PURPOSE: Corneal tissue international activity is only possible because of the willingness of export populations to donate their corneas on their death. Current predonation public education campaigns and at-the-point-of-donation consent practice generally includes consent for transplantation, research, and/or training. It is unclear whether a consent-for-export step is universally included in the consent process or, indeed, whether it should. We interviewed eye tissue and eye care professionals from around the world, who exported, imported, or did neither to understand current consent-for-export awareness and determine opinion on future practice. METHOD: During wider qualitative grounded-theory semistructured interviews with sector experts, to determine whether Australia should export, we captured sector opinion on consent-for-export. We used saturation and sentiment methods to determine opinion and χ correlation coefficients to examine association, using an α of P = 0.05. RESULTS: We interviewed 92 individuals, 83 of whom discussed consent-for-export. Of those, 51% (42/83) demonstrated some awareness of the practice; however, there were contradictions between interviewees from the same location. Regardless of current awareness, 57% (41/72) believed donors should be informed or consented for export. Their approval did not extend to donor-directed decisions, which would allow donors to decide which nation their donation should be sent, with 62.5% (45/72) opposing that notion. CONCLUSIONS: Our research indicates that the consent-for-export practice is not universally applied by exporting nations and that eye tissue and eye care professionals have limited awareness of the practice. Universally implementing a consent-for-export step within general consent practice would improve awareness, reduce confusion, and support donor wishes.

Background: A cross-sectional study was undertaken in Australia to explore a wide range of risk factors associated with keratoconus. A questionnaire addressing age, gender, educational background, ocular and medical history, smoking and alcohol consumption, and physical examination comprising anthropometric measurements was collected; eye examination was undertaken. The associations between a range of risk factors and keratoconus was determined using univariate and multivariable linear regression analyses.Main Text: A total of 260 keratoconus subjects were included in this study. Mean age of subject was 35.5 (SD= 14.8) years and the majority of the subjects were European 171 (68.2%). Initial univariate regression analysis identified the following risk factors at the p

Importance Advanced age-related macular degeneration (AMD) is a leading cause of blindness in Western countries. Causal, modifiable risk factors need to be identified to develop preventive measures for advanced AMD. Objective To assess whether smoking, alcohol consumption, blood pressure, body mass index, and glycemic traits are associated with increased risk of advanced AMD. Design, Setting, Participants This study used 2-sample mendelian randomization. Genetic instruments composed of variants associated with risk factors at genome-wide significance (P

PURPOSE: To investigate the performance of a machine learning model based on a reduced dimensionality parameter space derived from complete Pentacam parameters to identify subclinical keratoconus (KC). METHODS: All 1692 available parameters were obtained from the Pentacam imaging machine on 145 subclinical KC and 122 control eyes. We applied a principal component analysis (PCA) to the complete Pentacam dataset to reduce its parameter dimensionality. Subsequently, we investigated machine learning performance of the random forest algorithm with increasing numbers of components to identify their optimal number for detecting subclinical KC from control eyes. RESULTS: The dimensionality of the complete set of 1692 Pentacam parameters was reduced to 267 principal components using PCA. Subsequent selection of 15 of these principal components explained over 85% of the variance of the original Pentacam-derived parameters and input to train a random forest machine learning model to achieve the best accuracy of 98% in detecting subclinical KC eyes. The model established also reached a high sensitivity of 97% in identification of subclinical KC and a specificity of 98% in recognizing control eyes. CONCLUSIONS: A random forest-based model trained using a modest number of components derived from a reduced dimensionality representation of complete Pentacam system parameters allowed for high accuracy of subclinical KC identification.

Purpose: This study describes the development of a deep learning algorithm based on the U-Net architecture for automated segmentation of geographic atrophy (GA) lesions in fundus autofluorescence (FAF) images. Methods: Image preprocessing and normalization by modified adaptive histogram equalization were used for image standardization to improve effectiveness of deep learning. A U-Net-based deep learning algorithm was developed and trained and tested by fivefold cross-validation using FAF images from clinical datasets. The following metrics were used for evaluating the performance for lesion segmentation in GA: dice similarity coefficient (DSC), DSC loss, sensitivity, specificity, mean absolute error (MAE), accuracy, recall, and precision. Results: In total, 702 FAF images from 51 patients were analyzed. After fivefold cross-validation for lesion segmentation, the average training and validation scores were found for the most important metric, DSC (0.9874 and 0.9779), for accuracy (0.9912 and 0.9815), for sensitivity (0.9955 and 0.9928), and for specificity (0.8686 and 0.7261). Scores for testing were all similar to the validation scores. The algorithm segmented GA lesions six times more quickly than human performance. Conclusions: The deep learning algorithm can be implemented using clinical data with a very high level of performance for lesion segmentation. Automation of diagnostics for GA assessment has the potential to provide savings with respect to patient visit duration, operational cost and measurement reliability in routine GA assessments. Translational Relevance: A deep learning algorithm based on the U-Net architecture and image preprocessing appears to be suitable for automated segmentation of GA lesions on clinical data, producing fast and accurate results.

Age-related macular degeneration (AMD) is a leading cause of irreversible, severe vision loss in Western countries. Recently, we identified a novel pathway involving P2X7 receptor scavenger function expressed on ocular immune cells as a risk factor for advanced AMD. In this study, we investigate the effect of loss of P2X7 receptor function on retinal structure and function during aging. P2X7-null and wild-type C57bl6J mice were investigated at 4, 12, and 18 months of age for macrophage phagocytosis activity, ocular histological changes, and retinal function. Phagocytosis activity of blood-borne macrophages decreased with age at 18 months in the wild-type mouse. Lack of P2X7 receptor function reduced phagocytosis at all ages compared to wild-type mice. At 12 months of age, P2X7-null mice had thickening of Bruchs membrane and retinal pigment epithelium dysfunction. By 18 months of age, P2X7-null mice displayed phenotypic characteristics consistent with early AMD, including Bruchs membrane thickening, retinal pigment epithelium cell loss, retinal functional deficits, and signs of subretinal inflammation. Our present study shows that loss of function of the P2X7 receptor in mice induces retinal changes representing characteristics of early AMD, providing a valuable model for investigating the role of scavenger receptor function and the immune system in the development of this age-related disease.

Contains fulltext : 177791.pdf (Publisher’s version ) (Open Access) Purpose: Presently, 52 independent nuclear single nucleotide polymorphisms (nSNPs) have been associated with age-related macular degeneration (AMD) but their effects do not explain all its variance. Genetic interactions between the nuclear and mitochondrial (mt) genome may unearth additional genetic loci previously unassociated with AMD risk. Methods: Joint effects of nSNPs and selected mtSNPs were analyzed by two degree of freedom (2df) joint tests of association in the International AMD Genomics Consortium (IAMDGC) dataset (17,832 controls and 16,144 advanced AMD cases of European ancestry). Subjects were genotyped on the Illumina HumanCoreExome array. After imputation using MINIMAC and the 1000 Genomes Project Phase I reference panel, pairwise linkage disequilibrium pruning, and quality control, 3.9 million nSNPs were analyzed for interaction with mtSNPs chosen based on association in this dataset or publications: A4917G, T5004C, G12771A, and C16069T. Results: Novel locus TRPM1 was identified with genome-wide significant joint effects (P < 5.0 x 10-8) of two intronic TRPM1 nSNPs and AMD-associated nonsynonymous MT-ND2 mtSNP A4917G. Stratified analysis by mt allele identified an association only in 4917A (major allele) carriers (P = 4.4 x 10-9, odds ratio [OR] = 0.90, 95% confidence interval [CI] = 0.87-0.93). Intronic and intergenic ABHD2/RLBP1 nSNPs demonstrated genome-wide significant joint effects (2df joint test P values from 1.8 x 10-8 to 4.9 x 10-8) and nominally statistically significant interaction effects with MT-ND5 synonymous mtSNP G12771A. Although a positive association was detected in both strata, the association was stronger in 12771A subjects (P = 0.0020, OR = 2.17, 95% CI = 1.34-3.60). Conclusions: These results show that joint tests of main effects and gene-gene interaction reveal associations at some novel loci that were missed when considering main effects alone.

A 2016 Price Waterhouse Cooper Report, commissioned by the Australian Commonwealth Government's Organ and Tissue Authority, indicated that Australia had been meeting its human ocular tissue for transplant needs. It further suggested that Australia should consider exportation as a management strategy for excess tissue. Although we do not seek to discuss how the Price Waterhouse Cooper Report determined that need was being met, nor the potential value of exportation in this article, we propose that Ocular Tissue for Research (OTR), and particularly identification of donors for research, and timely access to fresh domestic tissue, be considered as an alternate or simultaneous surplus management strategy. A robust OTR system could provide long-term domestic support and investment into research and development of therapies in Australia. Such a system would also provide a meaningful donation option for those otherwise unable to donate for transplant. This article attempts to document, for the first time to our knowledge, the current recovery and distribution processes of deceased OTR in Australia. It maps the process steps, identifies the stakeholders and needs, discusses the limitations and barriers, and proposes key policy and practice reform strategies that may assist in improving access to OTR. Translational relevance To improve and increase access to human ocular tissue for research, and in turn, advance vision science and clinical application.

Background Keratoconus (KC) is a common corneal condition with an unknown gender predominance. Although numerous studies have investigated the genetic component of KC, no specific genes have yet been attributed to the condition. We recently reported posterior segment changes occurring in the eyes of KC patients. However, it is not clear whether these changes are part of KC pathogenesis or reflect changes in anatomical features of the eye manifested by changes at the cornea. Given retinal changes represent the main characteristics observed in age-related macular degeneration (AMD) and that pleiotropy has been demonstrated between different eye diseases, we wished to assess if known AMD associated genes were also associated with KC. Methods A total of 248 KC subjects and 366 non-KC (control) subjects were recruited from public and private clinics in Melbourne for this analysis. Nineteen single nucleotide polymorphisms (SNPs) previously associated with AMD, including rs10490924 (ARMS2/HTRA1), rs10737680 (CFH), rs13278062 (TNFRSF10A), rs1864163 (CETP), rs2230199 (C3), rs3130783 (IER3/DDR1), rs334353 (TGFBR1), rs3812111 (COL10A1), rs429608 (C2/CFB), rs4420638 (APOE), rs4698775 (CFI), rs5749482 (TIMP3), rs6795735 (ADAMTS9), rs8017304 (RAD51B), rs8135665 (SLC16A8), rs920915 (LIPC), rs943080 (VEGFA), rs9542236 (B3GALTL) and rs13081855 (COL8A1/FILIP1L), were genotyped in this cohort. Logistic regression was applied to evaluate the association between these SNPs and KC on both genders together, as well as each gender separately. Linear regression was also applied to assess the association between SNPs and corneal curvature. Bonferroni correction was applied to adjust for multiple testing. Results Genotyping data were available for 18 SNPs. The SNP, rs6795735 (ADAMTS9) was significantly associated with KC (p = 3.5 × 10− 4) when both genders were assessed, whereas rs5749482 (TIMP3) was only associated in males (p = 7.7 × 10− 4) following Bonferroni multiple correction. However, when the covariates of age and gender were included, the associations became non-significant. In addition, none of the SNPs appeared significant for corneal curvature. Conclusions Our study suggested a potential association of rs6795735 in the ADAMTS9 gene and rs5749482 in the TIMP3 gene in KC and that different associations may be gender specific. Overall, SNPs initially identified as associated with AMD following multiple correction may be further impacted by other factors such as age or gender and further studies are needed to resolve this issue.