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Importance The effect of sub‐threshold nano‐second laser (SNL) treatment on retinal function remains unknown. Background: SNL treatment has been studied as a potential intervention in intermediate age‐related macular degeneration (iAMD). This study investigated the longitudinal effect of SNL treatment on retinal function. Design This was a sub‐study of the LEAD trial; a 36‐month, multi‐centre, randomized and sham‐controlled trial. Participants: Subjects with iAMD. Methods: Eligible participants were assigned randomly to receive SNL or sham treatment to the study eye at 6‐monthly visits. Multi‐focal electro‐retinography (mfERG) was performed at each study visit from a study site. The mfERG responses were grouped into three regions (central, middle and outer rings) and compared between the SNL and sham group. Main Outcome Measures: mfERG P1 response amplitude and implicit time. Results: Data were collected from 50 subjects (26 in the SNL group, 24 in the sham group). At baseline, the P1 amplitudes of both the study eyes and the fellow eyes were similar between the groups at all rings. In the sham group, the P1 amplitude gradually decreased over time (P <.05). In the SNL group, there was an improvement in P1 amplitude which became statistically significant at the 36‐month visit, detected in both the treated and fellow eyes at the central (P =.005) and middle ring (P =.007) but not at the outer ring (P =.070). No difference in P1 implicit time detected between the groups (P >.05). Conclusions and Relevance: SNL treatment improved electro‐physiological function. mfERG could be useful for monitoring AMD progression and evaluating the efficacy of SNL treatment. [ABSTRACT FROM AUTHOR]

Importance: Detection of early onset neovascular age‐related macular degeneration (AMD) is critical to protecting vision. Background: To describe the development and validation of a deep‐learning algorithm (DLA) for the detection of neovascular age‐related macular degeneration. Design: Development and validation of a DLA using retrospective datasets. Participants: We developed and trained the DLA using 56 113 retinal images and an additional 86 162 images from an independent dataset to externally validate the DLA. All images were non‐stereoscopic and retrospectively collected. Methods: The internal validation dataset was derived from real‐world clinical settings in China. Gold standard grading was assigned when consensus was reached by three individual ophthalmologists. The DLA classified 31 247 images as gradable and 24 866 as ungradable (poor quality or poor field definition). These ungradable images were used to create a classification model for image quality. Efficiency and diagnostic accuracy were tested using 86 162 images derived from the Melbourne Collaborative Cohort Study. Neovascular AMD and/or ungradable outcome in one or both eyes was considered referable. Main Outcome Measures: Area under the receiver operating characteristic curve (AUC), sensitivity and specificity. Results: In the internal validation dataset, the AUC, sensitivity and specificity of the DLA for neovascular AMD was 0.995, 96.7%, 96.4%, respectively. Testing against the independent external dataset achieved an AUC, sensitivity and specificity of 0.967, 100% and 93.4%, respectively. More than 60% of false positive cases displayed other macular pathologies. Amongst the false negative cases (internal validation dataset only), over half (57.2%) proved to be undetected detachment of the neurosensory retina or RPE layer. Conclusions and Relevance: This DLA shows robust performance for the detection of neovascular AMD amongst retinal images from a multi‐ethnic sample and under different imaging protocols. Further research is warranted to investigate where this technology could be best utilized within screening and research settings. [ABSTRACT FROM AUTHOR]

Osteoarthritis is the leading cause of total hip replacement, accounting for more than 80% of all total hip replacements. Emerging evidence suggests that osteoarthritis has a chronic inflammatory component to its pathogenesis similar to age-related macular degeneration. We evaluated the association between age-related macular degeneration and total hip replacement as proxy for severe osteoarthritis or fractured neck of femur in the Melbourne Collaborative Cohort Study. 20,744 participants had complete data on both age-related macular degeneration assessed from colour fundus photographs taken during 2003–2007 and total hip replacement. Total hip replacements due to hip osteoarthritis and fractured neck of femur during 2001–2011 were identified by linking the cohort records to the Australian Orthopedic Association National Joint Replacement Registry. Logistic regression was used to examine the association between age-related macular degeneration and risk of total hip replacement due to osteoarthritis and fracture separately, adjusted for confounders. There were 791 cases of total hip replacement for osteoarthritis and 102 cases of total hip replacement due to fractured neck of femur. After adjustment for age, sex, body mass index, smoking, and grouped country of birth, intermediate age-related macular degeneration was directly associated with total hip replacement for osteoarthritis (odds ratio 1.22, 95% CI 1.00–1.49). Late age-related macular degeneration was directly associated with total hip replacement due to fractured neck of femur (odds ratio 5.21, 95% CI2.25–12.02). The association between intermediate age-related macular degeneration and an increased 10-year incidence of total hip replacement due to osteoarthritis suggests the possibility of similar inflammatory processes underlying both chronic diseases. The association of late age-related macular degeneration with an increased 10-year incidence of total hip replacement due to fractured neck of femur may be due to an increased prevalence of fractures in those with poor central vision associated with the late complications of age-related macular degeneration. [ABSTRACT FROM AUTHOR]

Purpose: To determine and compare the prevalence of age-related macular degeneration (AMD) in older Australians of Anglo-Celtic and Southern European origin. Methods: A total of 21,132 participants of the Melbourne Collaborative Cohort Study, aged 47-86 years, were assessed for AMD in 2003-2007 with non-mydriatic fundus photography. Of these, 14% were born in Southern Europe (Greece, Italy or Malta), with the remaining 86% of Anglo-Celtic origin, born in Australia, the United Kingdom or New Zealand. Results: Overall, 2694 participants (12.7%) had early stages of AMD, defined as either one or more drusen ≥125 μm (with or without pigmentary abnormalities) or one or more drusen 63-124 μm with pigmentary abnormalities in a 6000-μm diameter grading grid, in the absence of late AMD in either eye. A total of 122 participants (0.6%) had late AMD, defined as either geographic atrophy or neovascular AMD. In logistic regression analysis, adjusted for age, sex, smoking, education and physical activity, Southern Europeans compared to Anglo-Celts had a higher prevalence of the early stages of AMD (odds ratio, OR, 1.15, 95% confidence interval, CI, 1.00-1.34), and lower prevalence of late AMD (OR 0.36, 95% CI 0.17-0.78). Conclusions: Australians of Southern European origin have a higher prevalence of the early stages of AMD and lower prevalence of late AMD compared to those of Anglo-Celtic origin. Although AMD prevalence in the older age group(s) of Southern Europeans could be underestimated due to disparity in participation rates, it is likely that both lifestyle and genetic factors play their parts in differential AMD prevalence in these ethnic groups. [ABSTRACT FROM AUTHOR]

Background A novel, ultra-low energy nanosecond laser (retinal rejuvenation therapy) has been developed with the aim to slow progression of early age-related macular degeneration ( AMD). The safety, changes in fundus characteristics and macular function in a cohort of participants with bilateral intermediate AMD are reported. Design Prospective non-randomised, pilot intervention study. Participants or Samples Subjects with bilateral intermediate AMD ( n = 50, aged 50-75 years). Methods Ultra-low energy laser pulses applied in 12 spots around the macula of one eye (0.15-0.45 mJ), using 400 μm diameter spot, 3 nanosecond pulse length, 532 nm wavelength and energy titrated to each patient. Main Outcome Measures Best corrected visual acuity, drusen area and macular sensitivity (flicker perimetry) at baseline and at 3, 6 and 12 months post-laser. Results Treatment was painless with no clinically visible lesions. No participant developed choroidal neovascularization, while two with thin central retinal thickness at baseline developed atrophy at 12-month follow up. Drusen area was reduced in 44% of treated eyes and 22% of untreated fellow eyes, with changes in drusen and function not being coincident. Improvement in flicker threshold within the central 3° was observed in both the treated and untreated fellow eyes at 3 months post-laser. Of the 11 eyes at greatest risk of progression (flicker defect >15 d B), seven improved sufficiently to be taken out of this high-risk category. Conclusions A single unilateral application of nanosecond laser to the macula produced bilateral improvements in macula appearance and function. The nanosecond retinal rejuvenation therapy laser warrants ongoing evaluation as an early intervention for AMD. [ABSTRACT FROM AUTHOR]

Background: HMG Co-A reductase inhibitors are ubiquitous in our community yet their potential role in age-related macular degeneration (AMD) remains to be determined. Methodology/Principal Findings: Objectives: To evaluate the effect of simvastatin on AMD progression and the effect modification by polymorphism in apolipoprotein E (ApoE) and complement factor H (CFH) genes. Design: A proof of concept double-masked randomized controlled study. Participants: 114 participants aged 53 to 91 years, with either bilateral intermediate AMD or unilateral non-advanced AMD (with advanced AMD in fellow eye), BCVA≥20/60 in at least one eye, and a normal lipid profile. Intervention: Simvastatin 40 mg/day or placebo, allocated 1∶1. Main outcome measures: Progression of AMD either to advanced AMD or in severity of non-advanced AMD. Results. The cumulative AMD progression rates were 70% in the placebo and 54% in the simvastatin group. Intent to treat multivariable logistic regression analysis, adjusted for age, sex, smoking and baseline AMD severity, showed a significant 2-fold decrease in the risk of progression in the simvastatin group: OR 0.43 (0.18–0.99), p = 0.047. Post-hoc analysis stratified by baseline AMD severity showed no benefit from treatment in those who had advanced AMD in the fellow eye before enrolment: OR 0.97 (0.27–3.52), p = 0.96, after adjusting for age, sex and smoking. However, there was a significant reduction in the risk of progression in the bilateral intermediate AMD group compared to placebo [adjusted OR 0.23 (0.07–0.75), p = 0.015]. The most prominent effect was observed amongst those who had the CC (Y402H) at risk genotype of the CFH gene [OR 0.08 (0.02–0.45), p = 0.004]. No evidence of harm from simvastatin intervention was detected. Conclusion/Significance: Simvastatin may slow progression of non-advanced AMD, especially for those with the at risk CFH genotype CC (Y402H). Further exploration of the potential use of statins for AMD, with emphasis on genetic subgroups, is warranted. Trial Registration: Australian New Zealand Clinical Trial Registry (ANZCTR) ACTRN1260500032065 [ABSTRACT FROM AUTHOR]

Little evidence exists regarding associations between age-related macular degeneration (AMD) and moderate alcohol consumption, patterns of consumption, or different types of alcoholic beverage. The authors examined associations between AMD prevalence and alcohol intake using 20,963 participants from the Melbourne Collaborative Cohort Study aged 40–69 years at baseline (1990–1994). Participants' alcohol consumption was determined from a structured interview at baseline. At follow-up from 2003 to 2007, digital macula photographs of both eyes were taken and evaluated for early and late AMD signs. Drinking more than 20 g of alcohol per day was associated with an approximate 20% increase in the odds of early AMD (odds ratio = 1.21, 95% confidence interval: 1.06, 1.38; P = 0.004) when compared with those who reported no alcohol intake at baseline, having adjusted for sex, age, smoking, country of birth, education, physical activity, and energy from food. This positive association was apparent for wine, beer, and spirits. The estimates were similar for both sexes. The odds ratio for those drinking more than 20 g of alcohol per day for late AMD was 1.44 (95% confidence interval: 0.85, 2.45; P = 0.17). These results show a modest association between alcohol consumption and increased AMD risk. [ABSTRACT FROM PUBLISHER]

Evidence for an association between age-related macular degeneration (AMD) and obesity is inconsistent. The authors examined associations between adiposity and AMD prevalence using 21,287 participants from the Melbourne Collaborative Cohort Study aged 40–69 years at baseline (1990–1994). For men, each increase of 0.1 in waist/hip ratio (∼1 standard deviation) was associated with a 13% increase in the odds of early AMD (odds ratio = 1.13, 95% confidence interval: 1.01, 1.26; P = 0.03) and a 75% increase in the odds of late AMD (odds ratio = 1.75, 95% confidence interval: 1.11, 2.76; P = 0.02). No other adiposity measure was associated with early AMD for men. Smoking status modified the relation between waist/hip ratio and early AMD (P = 0.05), with no association for former smokers. For women, there were inverse associations with early AMD for all adiposity measures (odds ratios = 0.89–0.93; P = 0.002–0.02), but no associations were observed for late AMD. This study confirms abdominal obesity as an AMD risk factor for men despite a survivorship effect from competing risks in morbidity and mortality. The inverse associations for women may reflect weaker true positive associations with AMD that are insufficient to overcome the survivorship effect. New data are provided on complex interactions between environmental exposures and AMD risk. [ABSTRACT FROM PUBLISHER]

Objective: To evaluate the association between dietary patterns and age-related macular degeneration (AMD). Design: Food frequency data were collected from Melbourne Collaborative Cohort Study (MCCS) participants at the baseline study in 1990-1994. During follow-up in 2003-2007, retinal photographs were taken and evaluated for AMD. Participants: At baseline, 41 514 participants aged 40 to 70 years and born in Australia or New Zealand (69%), or who had migrated from the United Kingdom, Italy, Greece, or Malta (31%) were recruited. Of these, 21 132 were assessed for AMD prevalence at follow-up. Methods: Principal component analysis was used to identify dietary patterns (Factors F1 -6) among the food items. Logistic regression was used to assess associations of dietary patterns with AMD. Main Outcome Measures: Odds ratios (ORs) for early stages and advanced AMD in association with dietary patterns. Results: A total of 2508 participants (12.8%) had early stages of AMD, and 108 participants (0.6%) had advanced AMD. Six factors characterized by predominant intakes of fruits (F1); vegetables (F2); grains, fish, steamed or boiled chicken, vegetables, and nuts (F3); red meat (F4); processed foods comprising cakes, sweet biscuits, and desserts (F5); and salad (F6) were identified. Higher F3 scores were associated with a lower prevalence of advanced AMD (fourth vs. first quartile) (OR, 0.49; 95% confidence interval [CI], 0.28-0.87), whereas F4 scores greater than the median were associated with a higher prevalence of advanced AMD (OR, 1.46; 95% CI, 1.0-2.17). Conclusions: Rather than specific individual food items, these factors represent a broader picture of food consumption. A dietary pattern high in fruits, vegetables, chicken, and nuts and a pattern low in red meat seems to be associated with a lower prevalence of advanced AMD. No particular food pattern seemed to be associated with the prevalence of the earliest stages of AMD. [ABSTRACT FROM AUTHOR]