Paul Mitchell

Westmead Institute for Medical Research · Centre for Vision Research

Background: We quantified the individual and joint contribution of contemporaneous causal behavioural exposures on the future burden of oesophageal and stomach cancers and their subtypes and assessed whether these burdens differ between population groups in Australia, as such estimates are currently lacking. Methods: We combined hazard ratios fr...

Introduction: Visual impairment resulting from diseases such as neovascular age-related macular degeneration (nAMD) may cause behavioural, environmental, psychological, and logistical challenges that could act as barriers to effective uptake and sustainability of treatment with anti-vascular endothelial growth factor agents (anti-VEGFs). Understan...

Common single-nucleotide polymorphisms (SNPs) are predicted to collectively explain 40–50% of phenotypic variation in human height, but identifying the specific variants and associated regions requires huge sample sizes¹. Here, using data from a genome-wide association study of 5.4 million individuals of diverse ancestries, we show that 12,111 inde...

Importance Myopia in school-aged children is a public health issue worldwide; consequently, effective interventions to prevent onset and progression are required. Objective To investigate whether SMS text messages to parents increase light exposure and time outdoors in school-aged children and provide effective myopia control. Design, Setting, an...

The present study aimed to assess the longitudinal associations of coffee and tea consumption with metabolic syndrome and its component conditions in a group of Australian older adults who participated in the Blue Mountains Eye Study ( n 2554, mean age: 64 years, 43 % female). Participants’ coffee and tea intake were measured using a validated food...

A major challenge of genome-wide association studies (GWASs) is to translate phenotypic associations into biological insights. Here, we integrate a large GWAS on blood lipids involving 1.6 million individuals from five ancestries with a wide array of functional genomic datasets to discover regulatory mechanisms underlying lipid associations. We fir...

Introduction: The aim of this post hoc analysis of the ARIES study is to explore the requirement for intravitreal aflibercept (IVT-AFL) treatment intervals of < 8 weeks (w) in patients with neovascular age-related macular degeneration (nAMD), and to assess vision and anatomic outcomes in such patients who require more intensive treatment. Methods...

Study objectives There has been long-standing interest in potential links between obstructive sleep apnea (OSA) and eye disease. This study used retinal photography to identify undiagnosed retinal abnormalities in a cohort of sleep clinic patients referred for polysomnography (PSG) and then determined associations with PSG-quantified sleep-disorder...

Purpose: The main clinical intervention for older adults with hearing loss is the provision of hearing aids. However, uptake and usage in this population have historically been reported as low. The aim of this study was to understand the hearing loss characteristics, from measured audiometric hearing loss and self-perceived hearing handicap, that...

Purpose Impaired digital reactive hyperaemia and flicker-stimulated retinal vascular response are commonly reported risk markers of cardiovascular disease. This is the first study to determine the correlation of these risk markers with diabetes mellitus by comparing our novel flicker-modulated ECG-gated fundoscope with the EndoPAT2000 system. Meth...

Purpose Dietary flavonoids are bioactive compounds that have been widely investigated for their associations with vascular health outcomes. As the development of tinnitus has been linked to vascular pathways, dietary flavonoids may have role in the prevention of tinnitus symptoms. This study reports the associations between the intakes of major cla...

Purpose To investigate the association between the apolipoprotein E (APOE) E4 dementia-risk allele and prospective longitudinal retinal thinning in a cohort study of suspect and early manifest glaucoma. Design Retrospective analysis of prospective cohort data. Participants This study included all available eyes from participants recruited to the...

Introduction: Recently, there has been growing interest in exploring the relationship between visual acuity and fluid localization in different retinal compartments. This post hoc analysis of the ARIES study explores the relationship between the presence of intraretinal fluid (IRF) and subretinal fluid (SRF), both at baseline and throughout treatm...

Age-related cataracts are the leading cause of visual impairment among older adults. Many significant cases remain undiagnosed or neglected in communities, due to limited availability or accessibility to cataract screening. In the present study, we report the development and validation of a retinal photograph-based, deep-learning algorithm for auto...

Aims: Endothelial dysfunction is an early risk marker of cardiovascular disease in diabetes mellitus. Timely screening is important in reducing cardiovascular disease-associated morbidity and mortality. This cross-sectional study investigates the acceptability and preferability of non-invasive cardiovascular risk procedures (EndoPAT2000 system and...

Background To reduce treatment burden and optimise patient outcomes in diabetic macular oedema, we present 1-year results from two phase 3 trials of faricimab, a novel angiopoietin-2 and vascular endothelial growth factor-A bispecific antibody. Methods YOSEMITE and RHINE were randomised, double-masked, non-inferiority trials across 353 sites world...

Background Faricimab is a bispecific antibody that acts through dual inhibition of both angiopoietin-2 and vascular endothelial growth factor A. We report primary results of two phase 3 trials evaluating intravitreal faricimab with extension up to every 16 weeks for neovascular age-related macular degeneration (nAMD). Methods TENAYA and LUCERNE we...

Hearing loss and cognitive impairments are both highly prevalent neurological complications for older adults. While there is growing evidence to suggest that these two conditions are interrelated, little research has been conducted that directly examines the progression and developmental trajectories of these complications contemporaneously. The ai...

Genetic variants within nearly 1,000 loci are known to contribute to modulation of blood lipid levels. However, the biological pathways underlying these associations are frequently unknown, limiting understanding of these findings and hindering downstream translational efforts such as drug target discovery. To expand our understanding of the underl...

Thyroid cancer incidence and the prevalence of overweight and obesity are increasing, but the future thyroid cancer burden attributable to contemporary levels of overweight and obesity has not been evaluated before. We quantified this burden in Australia, and assessed whether the overweight/obesity‐attributable burden differed by sex or other popul...

Increased blood lipid levels are heritable risk factors of cardiovascular disease with varied prevalence worldwide owing to different dietary patterns and medication use¹. Despite advances in prevention and treatment, in particular through reducing low-density lipoprotein cholesterol levels², heart disease remains the leading cause of death worldwi...

A major challenge of genome-wide association studies (GWAS) is to translate phenotypic associations into biological insights. Here, we integrate a large GWAS on blood lipids involving 1.6 million individuals from five ancestries with a wide array of functional genomic datasets to discover regulatory mechanisms underlying lipid associations. We firs...

Retinal vessel calibre metrics were evaluated at baseline and 2 years in a FIELD substudy (n = 208). Central retinal venule calibre was significantly reduced by fenofibrate and unchanged by placebo. Arteriole metrics did not change. Larger studies relating retinal vessel calibre to future diabetes complications and response to therapy are merited.

PurposeTo assess whether dietary intake of flavonoids are associated with longitudinal treatment outcomes of patients with neovascular age-related macular degeneration (nAMD). Methods547 participants with nAMD were recruited at baseline, 494 were followed-up after receiving 12 months of anti-vascular endothelial growth factor (anti-VEGF) therapy. B...

Purpose: Review and provide consensus recommendations on use of treat-and-extend (T&E) regimens for neovascular age-related macular degeneration (nAMD) and polypoidal choroidal vasculopathy (PCV) management with relevance for clinicians in the Asia-Pacific region. Methods: A systematic search of MEDLINE, EMBASE, and Cochrane databases, and abstr...

Tinnitus is the phantom perception of sound in the ears or head that increases in prevalence as age increases. With strong evidence supporting the benefits of dietary fibre for vascular health and hearing loss, intake of dietary fibre may also have a role in the prevention of tinnitus symptoms. This longitudinal study aims to determine the associat...

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 in...

Objectives : We examined the association between birthweight and objectively measured hearing loss in older men and women. Study design : 893 community-dwelling participants aged 50+ years with pure-tone audiometry data and self-reported birthweight were included for cross-sectional analysis. Participants were asked how much they weighed at birth...

Aims To report the 6-year incidence of optical coherence tomography (OCT)-derived age-related changes in drusen volume and related systemic and ocular associations. Methods Chinese adults aged 40 years and older were assessed at baseline and 6 years with colour fundus photography (CFP) and spectral domain (SD) OCT. CFPs were graded for age-related...

Purpose : To investigate the impact of physical activity (PA) on the incidence or progression of age-related macular degeneration (AMD) in the general population. Design : Meta-analysis of longitudinal cohort studies. Methods : We included a total of 14,630 adults with no or early AMD at baseline from seven population-based studies and examined a...

Purpose To investigate prevalence and age of onset of choroidal melanocytic lesions (other than nevi) in pediatric patients. Methods The pooled data of participants 6 months to 18 years of age in the Sydney Paediatric Eye Disease Study, the Sydney Myopia Study, and the Sydney Adolescent Vascular Eye Disease Study were reviewed retrospectively to i...

Background Estimates of the future burden of invasive cancer attributable to current modifiable causal exposures can guide cancer prevention. Methods We linked pooled data from seven Australian cohort studies (N = 367,058) to national cancer and death registries, and estimated exposure-cancer and exposure-death associations using adjusted proporti...

Objectives We aimed to analyse the degree of carer burden and depressive symptoms in family carers of persons with age-related macular degeneration (AMD) and explore the factors independently associated with carer burden and depressive symptoms. Methods Cross-sectional study using self-administered and interviewer-administered surveys, involving 9...

Aim To evaluate the effectiveness of dexamethasone intravitreal implant 0.7 mg (DEX; Ozurdex) monotherapy in the patient subgroup of the AUSSIEDEX study with treatment-naïve diabetic macular oedema (DME). Methods The open-label, prospective, phase 4, real-world study included pseudophakic eyes and phakic eyes scheduled for cataract surgery that we...

Background: The prevalence of myopia is increasing globally including in Europe and parts of Asia but Australian data are lacking. This study aim described the change in myopia prevalence in middle-aged Australian adults over approximately a 20-year period. Methods: Two contemporary Western Australian studies (conducted in mid-late 2010s): the c...

There is paucity of population-based data on occupational noise exposure and risk of age-related hearing loss. Therefore, we assessed cross-sectional and longitudinal associations of past workplace noise exposure with hearing loss in older adults. At baseline, 1923 participants aged 50+ years with audiological and occupational noise exposure data i...

Purpose To determine the age of onset and prevalence of choroidal nevi in children. Methods In this cross-sectional study, the fundus photographs of a pooled sample of children 6 months to 18 years of age with 6-year longitudinal follow-up who participated in the Sydney Paediatric Eye Disease Study, Sydney Myopia Study, and the Sydney Adolescent V...

Importance Poor adherence or persistence to treatment can be a barrier to optimizing clinical practice (real-world) outcomes to intravitreal injection therapy in patients with neovascular age-related macular degeneration (nAMD). Currently, there is a lack of consensus on the definition and classification of adherence specific to this context. Obje...

Retinal blood vessels provide information on the risk of cardiovascular disease (CVD). Here, we report the development and validation of deep-learning models for the automated measurement of retinal-vessel calibre in retinal photographs, using diverse multiethnic multicountry datasets that comprise more than 70,000 images. Retinal-vessel calibre me...

Purpose: To identify functionally related genes associated with diabetic retinopathy (DR) risk using gene set enrichment analyses (GSEA) applied to genome-wide association study (GWAS) meta-analyses. Methods: We analyzed DR GWAS meta-analyses performed on 3,246 Europeans and 2,611 African Americans with type 2 diabetes. Gene sets relevant to five k...

Background: Estimates of future burden of cancer attributable to current modifiable causal exposures can guide cancer prevention. We quantified future head and neck cancer burden in Australia attributable to individual and joint causal exposures, and assessed whether these burdens differ between population subgroups. Methods: We estimated the st...

Importance: Treatments for geographic atrophy (GA), a late stage of age-related macular degeneration (AMD), are currently under development. Understanding the natural course is needed for optimal trial design. Although enlargement rates of GA and visual acuity (VA) in the short term are known from clinical studies, knowledge of enlargement in the...

Purpose/Aim of this study:Retinal vessel caliber is an independent risk marker of cardiovascular disease risk. However, variable mechanical delays in capturing retinal photographs and cardiac cycle-induced retinal vascular changes have shown to reduce the accuracy of retinal vessel caliber measurements, but this has only ever been investigated in h...

Background: The objective of this study was to examine the association of an integrated model (composed of retinal arteriolar caliber, height, and sex) with blood pressure (BP) among a group of Chinese children, and assess the predictive value of the integrated model for childhood hypertension. Methods: This study included 1460 candidates aged 1...

Purpose To develop and validate optical coherence tomography (OCT) and color fundus photography (CFP) criteria in differentiating polypoidal choroidal vasculopathy (PCV) from typical neovascular age-related macular degeneration (nAMD) in eyes with suboptimal response to anti-vascular endothelial growth factor (VEGF) monotherapy, and to determine wh...

Purpose To describe the prevalence, risk factors and associations of vitreoretinal interface abnormalities (VRIs) in a population-based study of older adults. Design Cross sectional analysis of cohort study participants. Participants There were 1149 participants (mean age 76.1 ±6.9 years) at the 15-year Blue Mountains Eye Study follow-up examinat...

Purpose: Treating neovascular age-related macular degeneration (nAMD) with intravitreal aflibercept (IVT-AFL) treat-and-extend (T&E) can reduce treatment burden. ARIES assessed whether IVT-AFL early-start T&E was noninferior (NI) to late-start T&E. Methods: A randomized, open-label, Phase 3b/4 study that included treatment-naïve patients aged ≥5...

Background: The evidence regarding the association between added sugar (AS) intake and obesity remains inconsistent. The aim of this study was to investigate the association between changes in the percentage of energy intake from AS (EAS%) and changes in body weight in a cohort study of older Australians during 15 years of follow-up. In addition, a...

Keratoconus is characterised by reduced rigidity of the cornea with distortion and focal thinning that causes blurred vision, however, the pathogenetic mechanisms are unknown. It can lead to severe visual morbidity in children and young adults and is a common indication for corneal transplantation worldwide. Here we report the first large scale gen...

Objective MYOC (myocilin) mutations account for 3-5% of primary open angle glaucoma (POAG). We aimed to understand the true population-wide penetrance and characteristics of glaucoma among individuals with the most common MYOC variant (p.Gln368Ter) and the impact of a POAG polygenic risk score (PRS) in this population. Design Cross-sectional popul...

Primary open-angle glaucoma (POAG), is a heritable common cause of blindness world-wide. To identify risk loci, we conduct a large multi-ethnic meta-analysis of genome-wide association studies on a total of 34,179 cases and 349,321 controls, identifying 44 previously unreported risk loci and confirming 83 loci that were previously known. The majori...

Primary open-angle glaucoma (POAG), is a heritable common cause of blindness world-wide. To identify risk loci, we conduct a large multi-ethnic meta-analysis of genome-wide association studies on a total of 34,179 cases and 349,321 controls, identifying 44 previously unreported risk loci and confirming 83 loci that were previously known. The majori...

Background and purpose: Fractal analysis is a method of quantifying the branching complexity and density of the retinal vessels. We hypothesized that reduced fractal dimension, signifying a sparser vascular network, is associated with long-term stroke mortality. Methods: We examined the relationship of fractal dimension and stroke mortality in a...

Purpose: To evaluate the efficacy and safety of intravitreal aflibercept (IVT-AFL) versus IVT-AFL plus rescue photodynamic therapy (IVT-AFL + rPDT) in the subgroup of Japanese patients with polypoidal choroidal vasculopathy (PCV) enrolled in the PLANET study. Study design: A 96-week, double-masked, sham-controlled phase-3b/4 randomized clinical...

Purpose People with age‐related macular degeneration (AMD) experience high rates of depression, but rarely engage in or have access to tailored mental wellbeing programmes. This qualitative study investigated the perspectives of those primarily with late AMD on mental health and mental wellbeing programmes. Methods Twenty‐eight people with late AM...

Objective We aimed to prospectively examine the relationship between vision and hearing loss and successful aging in a cohort of older adults. Study design We analyzed 5-year data (1997-9 to 2002-4) from 1,085 adults aged 55+ years, who were free of cancer, coronary artery disease and stroke at baseline and who had complete data on sensory loss....

Background In current approaches to vision screening in the community, a simple and efficient process is needed to identify individuals who should be referred to tertiary eye care centres for vision loss related to eye diseases. The emergence of deep learning technology offers new opportunities to revolutionise this clinical referral pathway. We ai...

Despite the growing importance of real‐world evidence (RWE) for guiding clinical decisions in retinal disease, there is currently no widely used guidance available for assessing the quality and relevance of RWE studies in ophthalmology. This paper summarizes the development of a user‐friendly tool that facilitates assessment of the quality of avail...

Purpose: This article aims to review current evidence on the development, diagnosis, and management of retinal pigment epithelium (RPE) tear during anti-vascular endothelial growth factor (VEGF) therapy. Methods: Literature searches were performed using MEDLINE/PubMed databases (cut-off date: August 2019). Results: Three key recommendations we...

Nuclear cataract is the most common type of age-related cataract and a leading cause of blindness worldwide. Age-related nuclear cataract is heritable (h² = 0.48), but little is known about specific genetic factors underlying this condition. Here we report findings from the largest to date multi-ethnic meta-analysis of genome-wide association studi...

Purpose: Topical carbonic anhydrase inhibitors (CAIs) can influence retinal fluid distribution, but their role in treating central serous chorioretinopathy (CSCR) has not been studied. We examined the efficacy of a topical CAI (dorzolamide) in treating chronic CSCR. Methods: Prospective, nonrandomized, controlled intervention study of patients w...

The aim of this work was to evaluate the contribution of real-world evidence (RWE) in changing anti-vascular endothelial growth factor (VEGF) therapy treatment practices and improving real-world treatment strategies for neovascular age-related macular degeneration (nAMD). A PubMed literature search was performed to review the large number of Engli...

Dietary flavonoids are vasoactive phytochemicals with promising anti-inflammatory properties. We aimed to assess the associations between baseline intakes of six commonly consumed flavonoid subclasses and 10-year incidence of age-related hearing loss. At baseline, 1691 participants aged 50+ years had information on dietary intakes and hearing statu...

There is an evidence–practice gap between the dietary recommendations for age-related macular degeneration (AMD) presented in the literature and those practiced by patients. This study reports on the 3-month post-intervention results of a randomised controlled trial (RCT) evaluating telephone-delivered counselling to improve dietary behaviours amon...

Objectives: To determine whether a collaborative model of care that uses task-sharing for the management of low-risk diabetic retinopathy, Community Eye Care (C-EYE-C), can improve access to care and better use resources, compared with hospital-based care. Design: Retrospective audit of medical and financial records to compare two models of care...

Purpose In this study, we assessed whether there are independent associations between dietary total flavonoid intake and major flavonoid classes with retinal arteriolar and venular calibre. Methods Blue Mountains Eye Study participants aged 49+ years who had complete data on diet and retinal vessel measures were analysed (n = 2821). Dietary intake...

Purpose: To examine the prevalence and risk factors for depressive symptoms in patients with neovascular age-related macular degeneration (nAMD) presenting for anti-vascular endothelial growth factor (anti-VEGF) therapy. Methods: In a clinic-based cohort of 547 patients with nAMD who presented for treatment, the Centre of Epidemiological Studies...

Background: There is an evidence-practice gap between the dietary recommendations for age-related macular degeneration (AMD) presented in the literature and those practiced by patients. This study reports on the 3-months post-intervention results of a randomised controlled trial (RCT) evaluating telephone-delivered dietary counselling aiming to imp...

Purpose Existing research suggests that changes to retinal vascular caliber reflect nitric oxide (NO)-dependent endothelial dysfunction. Dietary nitrate is an important source of NO; however, studies on the link between dietary nitrate intake and retinal microvasculature are lacking. We aimed to assess the cross-sectional association between intake...

Topic Systematic review of risk factors for non-adherence and non-persistence to intravitreal anti-vascular endothelial growth factor (anti-VEGF) injection therapy for neovascular age-related macular degeneration (nAMD). Clinical Relevance Lack of adherence (non-adherence) or under-treatment (non-persistence) with respect to evidence from clinical...

Purpose To develop consensus terminology in the setting of polypoidal choroidal vasculopathy (PCV), and to develop and validate a set of diagnostic criteria not requiring indocyanine green angiograph (ICGA) for differentiating PCV from typical neovascular age-related macular degeneration (nAMD) based on a combination of OCT and color fundus photogr...

Previously, variation in retinal vascular caliber has been reported in association with chronic kidney disease (CKD) but findings remain inconsistent. To help clarify this we conducted individual participant data meta-analysis and aggregate data meta-analysis on summary estimates to evaluate cross-sectional associations between retinal vascular cal...

Purpose Abnormalities in lipid metabolism are implicated in age-related macular degeneration (AMD), but the pathways involved remain unclear. We assessed whether acylcarnitine concentrations, a marker of lipid and mitochondrial metabolism, differed between patients with AMD and controls. Methods In this cross-sectional case-control study, cases (n...

Background: Systematically review the evidence describing the impact of anti-vascular endothelial growth factor (anti-VEGF) therapy on neovascular age-related macular degeneration (nAMD) patient outcomes and healthcare resource utilization. Methods: A systematic literature review was completed using Medline and EMBASE for publications prior to J...