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This paper introduces a bottleneck game with finite sets of commuters and departing time slots as an extension of congestion games of Konishi et al. (J Econ Theory 72:225–237, 1997a). After characterizing Nash equilibrium of the game, we provide sufficient conditions for which the equivalence between Nash and strong equilibria holds. Somewhat surprisingly, unlike in congestion games, a Nash equilibrium in pure strategies may often fail to exist, even when players are homogeneous. In contrast, when there is a continuum of atomless players, the existence of a Nash equilibrium and the equivalence between the set of Nash and strong equilibria hold as in congestion games (Konishi et al. 1997a). [ABSTRACT FROM AUTHOR]

The progression of age-related macular degeneration (AMD) is determined by environmental and genetic factors, and phenotypic or molecular risk factors have been investigated extensively. Interestingly, risk factor profiles for advanced AMD differ among individuals, and one of the causes of variation may be explained by their ethnic background. Recent advances in retinal imaging technology have led to the identification of previously unrecognized risk factors for advanced AMD on optical coherence tomography (OCT) and OCT angiography, which expands the concept of traditional imaging risk factors such as drusen and pigmentary abnormalities visible on color fundus photographs. This OCT imaging modality has identified novel pathognomonic changes for early AMD, including the associated photoreceptor, retinal pigment epithelium, and underlying choroidal changes. Regarding features of multimodal imaging associated with the presence or progression of geographic atrophy, there is an international expert consensus classification system; however, features associated with the progression of macular neovascularization (MNV) are still obscure. To make a consensus towards understanding features associated with the risk of MNV, this review focuses on the early stages of AMD by summarizing imaging characteristics and early signs and classifications in view of advanced multimodal imaging technology. Recent evidence suggests that neovascular AMD is not a single disease entity but a heterogeneous disease characterized by MNV. Besides drusen, OCT features associated with pigment abnormalities, such as shallow irregular RPE elevation (SIRE, also known as double-layer sign), pachychoroid pigment epitheliopathy, and choriocapillaris ischemia, seem to confer a high risk of MNV developing, especially for Asian populations. [ABSTRACT FROM AUTHOR]

We show that the core of a generalized assignment problem satisfies two types of stability properties. First, the core is the unique stable set defined using the weak domination relation when outcomes are restricted to individually rational and pairwise feasible ones. Second, the core is the unique stable set with respect to a sequential domination relation that is defined by a sequence of weak domination relations that satisfy outsider independence. An equivalent way of stating this result is that the core satisfies the property commonly stated as the existence of a path to stability. These results add to the importance of the core in an assignment problem where agents' preferences may not be quasilinear. [ABSTRACT FROM AUTHOR]

Purpose Methods Results Conclusions To report the incidence of post‐injection endophthalmitis (PIE) and the cumulative risk associated with repeated injections of intravitreal anti‐vascular endothelial growth factor (anti‐VEGF).We employed nationwide registries in Denmark to include all individuals aged ≥40 years who received at least one intravitreal anti‐VEGF injection in 2007–2022. Our primary endpoint PIE was identified using specific diagnostic codes for endophthalmitis and procedure codes for vitreous biopsy within 10 days prior to and 120 days post‐injection. Patients were stratified according to the underlying diagnoses for which they received the treatment. The relative risk (RR) for PIE was calculated between groups based on the number of injections received by the patients.We identified 60 825 patients who received intravitreal anti‐VEGF treatment during study time, with a median age of 77.2 years and females constituting 58.1%. We identified 232 cases of PIE after 1 051 549 injections during follow‐up, resulting in an incidence of 0.022% [95% CI 0.019%–0.025%]. Despite a linear growth in annual anti‐VEGF use, the incidence remained stable at 0.020% [95% CI 0.017%–0.023%] from 2013 to 2022. Compared to patients receiving 1–3 injections, RR for patients receiving 4–20, 21–40, and >40 injections were 0.46 [95% CI 0.34–0.63], 0.32 [95% CI 0.21–0.50], and 0.54 [95% CI 0.36–0.81], respectively. Findings were similar across the different diagnoses.Based on 16 years of nationwide registry data, this study identified a low and stable incidence of PIE. Notably, the highest risk of endophthalmitis was within the first three anti‐VEGF injections. [ABSTRACT FROM AUTHOR]

Purpose: To describe treatment patterns in patients diagnosed with neovascular age-related macular degeneration (nAMD), retinal vein occlusion (RVO), or diabetic macular edema (DME), newly-treated with anti-vascular endothelial growth factor (anti-VEGF) agents as recorded in the Japanese Medical Data Center (JMDC) database. Study design: This non-interventional, descriptive, retrospective, observational cohort study included insured Japanese patients aged ≥ 21 and ≤ 75 years at index date (anti-VEGF treatment initiation). Methods: Patients with minimum one claim in JMDC database with a diagnosis code for nAMD, RVO, or DME between October 2007–May 2015 and with minimum of one claim for anti-VEGF agents on or after the date of diagnosis were included. Frequency and proportion of claims submitted for anti-VEGF injections were assessed during 12 months post-index date. Results: The median (interquartile range) number of claims for anti-VEGF injections during 12 months post-index date were 3 (1, 4) for nAMD (n = 255), 2 (1, 3) for RVO (n = 223) and 2 (1, 4) for DME (n = 125) patients. Frequencies of nAMD, RVO and DME patients with one or more claims for a retinal disease treatment other than an anti-VEGF agent were 4 (1.57%), 59 (26.46%) and 68 (54.40%) during the 12 months pre-index date and 21 (8.24%), 85 (38.12%) and 62 (49.60%) in the 12 months post-index date, respectively. Conclusions: The median number of anti-VEGF injections per patient was lower than those reported in clinical trials. Although various pre- and concomitant treatments were used in RVO and DME, anti-VEGF monotherapy was the first-line treatment in > 90% of nAMD patients. [ABSTRACT FROM AUTHOR]

Aims: We investigated the efficacy of AI‐based screenings in preventing blindness, specifically assessing cost‐effectiveness when two further detection opportunities are incorporated: "DR screening during national health checkups" and "DR screening during diabetes clinic visits at a physician's office", or a combination of the two. We also examined potential additional costs associated with AI screening under various conditions. Methods: We employed a Markov Model in this simulation study. We constructed the modelling of diabetes detection, treatment, and retinopathy treatment based on transition probabilities derived from epidemiological and clinical studies. These covered incidence and progression rates of diabetes and diabetic retinopathy, treatment options and their efficacy, and visual prognosis. The age range for the model was set at 40–90 years with a 1‐year cycle, assuming a population of 500 000 individuals with a discount rate of 2%. Simulations were conducted using TreeAge. Costs were calculated using the direct costs of general health examinations and insurance treatments. We assumed diabetic retinopathy would result in a consistent visual acuity following detection, progression, and treatment, providing utility values based on the severity of DR. Results: DR screening via AI in health check‐up programs proved not to be cost‐effective, as it led to a 0.9% increase in cumulative blindness and the ICERs were dominated. The addition of an annual AI screening at physicians' clinics, with referrals to ophthalmology based on the results, resulted in an ICER of 8192751JPY/QALY, which was not cost‐effective. However, assuming that 75% of patients received AI screening during medical examinations and that 75% of these underwent ophthalmological examinations per the results, AI screening proved to be dominant and cost‐effective, reducing the cumulative number of blindness by 2.8%. Conclusions: Even though automated AI diagnosis of DR is becoming a reality, our findings suggest that merely introducing AI screening in health checkups and physicians' clinics in Japan will not be cost‐effective. However, cost‐effectiveness can be improved by increasing the rate of screening and the follow‐up rate of ophthalmological examinations. If this is achieved, there might also be a possibility of incurring additional costs due to AI screening. Our study underlines the importance of a seamless link from diabetes detection to ophthalmologic care for successful DR screening with AI systems. [ABSTRACT FROM AUTHOR]

Although there have been many population-based studies of age-related macular degeneration (AMD), only limited information is available in Asia on the epidemiology of geographic atrophy (GA). We aimed to determine the prevalence and patterns of GA through an analysis of multiple studies conducted within the Asian Eye Epidemiology Consortium (AEEC). Cross-sectional meta-analyses. A total of 97 213 individuals aged 40 years and older. Data from 22 population-based studies from countries belonging to the AEEC were included. In all studies, AMD was defined on the basis of standardized grading systems. Geographic atrophy was defined as an area of pallor in the fundus with visibility of the underlying choroidal blood vessels and sharply defined borders. Random-effects meta-analysis was performed to estimate overall and age-, gender-, and region-specific pooled prevalence of GA. Prevalence of GA per 1000 persons. The mean age was 60.8 ± 10.0 years, and 42 673 (43.9%) were male. Overall, a total of 223 individuals (0.2%) had GA. The pooled overall prevalence of GA was 1.57 per 1000 persons (95% confidence interval [CI], 1.04–2.10), which was 3 times less than that of neovascular AMD of 5.20 per 1000 persons (95% CI, 3.97–6.43). Compared with those aged 50 to 59 years, the prevalence of GA increased from 0.34 per 1000 persons (95% CI, 0.07–0.62) to 2.90 per 1000 persons (95% CI, 1.55–4.25) in those aged ≥70 years. The GA prevalence per 1000 persons was similar between urban (2.22; 95% CI, 1.22–3.23) and rural residents (1.33; 95% CI, 0.70–1.96). Geographic atrophy was more prevalent in South Asia (based on studies from India and Nepal, 3.82 per 1000 persons; 95% CI, 1.72–5.93) compared with East Asia (based on studies from China, Korea, Hong Kong, Taiwan, and Japan, and the Singapore Chinese Eye Study, 0.76 per 1000 persons; 95% CI, 0.31–1.22, P = 0.005). Geographic atrophy is uncommon in Asian populations compared with those of European ancestry. Even within Asia, geographic differences in GA prevalence were seen. The findings of this meta-analysis suggest that better dissection of risk factors in the Asian population for GA may provide insights into the biological pathways that drive these late-stage manifestations, thus suggesting better targets for prevention. [ABSTRACT FROM AUTHOR]

Background: To determine the preoperative factors associated with selecting scleral buckling (SB) or pars plana vitrectomy (PPV) to treat rhegmatogenous retinal detachments (RRDs) in the era of microincision vitrectomy surgery. Methods: A nationwide, multicenter, observational study in the Japan Retinal Detachment Registry was done. From February 2016 to March 2017, 3446 cases were registered, and 3219 among them were analyzed. The factors related to the patient or surgeon were selected; the surgeon's factor included years of experience, number of cases registered, and current activity. The odds ratio (OR) for factors associated with SB or PPV was estimated by a mixed logistic regression model. Results: SB was selected in 24.2% (779/3219), PPV was in 71.5% (2238/3219), and PPV+SB was in 6.3% (202/3219). Multivariate analysis showed that age [< 70 years old, OR 4.27, 95% confidence interval (CI) 2.34–7.79, P < 0.001], visual acuity [1.0+ (OR 7.41, 95% CI 3.47–15.82, P < 0.001)], pseudo-phakia (OR 4.83, 95%CI 2.11-10.56, P < 0.001), retinal tear (OR 6.92, 95% CI 4.83–9.92, P < 0.001), breaks at/near the vitreous base (OR 8.07, 95% CI 3.50–18.62, P < 0.001), 90+° retinal tear (OR 108.24, 95% CI 7.44–1574.34, P < 0.001), and number of breaks 4+ (OR 3.15, 95% CI 1.95–5.09, P < 0.001), were significantly associated with selecting PPV over SB. The surgeons' activity defined as the number of cases experienced during the registry period was related to the selection of PPV (OR 3.83, 95% CI 2.11–6.93, P < 0.001). Conclusions: The choice of PPV for the RRD was associated not only with patients' preoperative factors but also the surgeon's activity. Active surgeons selected PPV more than SB. [ABSTRACT FROM AUTHOR]

Aims: Fenofibrate and statins reduced the need for diabetic retinopathy (DR)‐related treatment in clinical trials. We aimed to determine whether use of lipid‐lowering medication reduces the risk of DR and the need for treatment in patients with type 2 diabetes using a real‐world health claims database. Methods: This was an observational analysis using a nation‐wide health claims database of the Japan Medical Data Center (JMDC). Type 2 diabetes was defined according to ICD‐10 codes for use of glucose‐lowering medication. Use of lipid‐lowering medication for at least 1 year was confirmed by the Anatomical Therapeutic Chemical Classification System. DR and diabetic macular edema (DME) were determined by ICD‐10 codes. DR‐related treatments were determined by health insurance claims. A propensity score for use of lipid‐lowering medication was estimated, and a doubly robust estimator, using the inverse probability weighting model with regression adjustment, was obtained to determine odds ratios (OR) with 95% confidence interval (95% CI) for cumulative incidence of DR and its treatments over 3 years. Results: There were 69 070 individuals with type 2 diabetes at baseline, among whom DR developed in 5687 over a period of 3 years. Use of lipid‐lowering medication was associated with decreased risk of incidence of DR (OR, 0.772; 95% CI, 0.720‐0.827; P < .001). Use of lipid‐lowering medication was also associated with decreased incidence of DME, any treatments for DR, laser photocoagulation and vitrectomy in patients with DR at baseline. Conclusions: In a population of patients with type 2 diabetes with a variety of risk profiles, use of lipid‐lowering medication reduced the risk of DR and thus the risks involved in treatment with laser photocoagulation and vitrectomy. [ABSTRACT FROM AUTHOR]

Aim: Diabetic retinopathy (DR) screening is one of the keys in successful diabetes care, but the participation in DR screening is sub-optimal. This study aims to assess the factors associated with participation in a DR screening program in a rural district of Bangladesh.Method: 213 persons with diabetes identified in a population-based assessment of over 3000 persons ≥ 40 years were offered free of cost screening for DR. Awareness, attitudes and practice about diabetes and common eye diseases along with socio-demographic factors were assessed.Results: 68 (32%) patients participated in the screening program. After multivariate adjustment, awareness related to diabetes causes eye disease (odds ratio (OR) 8.47, 95% confidence interval (CI) 3.95-18.18), awareness of DR (OR 5.15, 95% CI 1.89-14.01) and awareness of the possibility to prevent DR-related vision loss (OR 3.15, 95% CI 1.53-6.51) were associated with higher proportion of participation. Lack of confidence upon skills of ophthalmic assistants and fear of complications were barriers but socio-economic condition was not a barrier in attending the screening program.Conclusions: The major factor associated with participation in DR screening is diabetes-related health literacy in rural Bangladesh. Public health promotion program should be designed to provide health education to increase participation in the screening program. [ABSTRACT FROM AUTHOR]

Purpose: We aimed to investigate changes in retinal vascular geometry over time after panretinal photocoagulation (PRP) in patients with proliferative diabetic retinopathy (PDR). Methods: Thirty‐seven eyes with PDR were included. Wide‐field fluorescein angiography (Optomap, Optos PLC., Dunfermline, Scotland, UK) was used to diagnose PDR at baseline and to assess activity at follow‐up month three and six. At each time‐point, a trained grader measured retinal vessel geometry on optic disc (OD) centred images using semiautomated software (SIVA, Singapore I Vessel Assessment, National University of Singapore, Singapore) according to a standardized protocol. Results: At baseline, the mean age and duration of diabetes were 52.8 and 22.3 years, and 65% were male. Mean HbA1c was 69.9 mmol/mol, and blood pressure was 155/84 mmHg. Of the 37 eyes with PDR, eight (22%) eyes had progression at month three and 13 (35%) progressed over six months. Baseline characteristics, including age, sex, duration of diabetes, HbA1c, blood pressure, vessel geometric variables and total amount of laser energy delivered did not differ by progression status. However, compared to patients with progression of PDR, patients with favourable treatment outcome had alterations in the retinal arteriolar structures from baseline to month six (calibre, 154.3 μm versus 159.5 μm, p = 0.04, tortuosity 1.12 versus 1.10, p = 0.04) and in venular structures from baseline to month three (fractal dimension 1.490 versus 1.499, p = 0.04, branching coefficient (BC) 1.32 versus 1.37, p = 0.01). Conclusion: In patients with PDR, successful PRP leads to alterations in the retinal vascular structure. However, baseline retinal vascular geometry characteristics did not predict treatment outcome. [ABSTRACT FROM AUTHOR]

Purpose: To determine the status of visual impairment certification in Japan in the fiscal year 2019 and the impact of revising the criteria for visual impairment certification implemented in 2018. Study Design: Observational cross-sectional study. Methods: We requested welfare offices throughout Japan to submit data of age, sex, causative diseases, and visual impairment grades for newly certified visually impaired individuals aged ≥ 18 years during the fiscal year 2019. The certification was based on criteria of the Act on Welfare of Physically Disabled Persons. Results: Altogether, data were collected for 16,504 newly certified visually impaired individuals. The most common age group was 80–89 years (29.6%), followed by 70–79 (28.2%) and 60–69 (15.3%) years. The most common causative disease was glaucoma (40.7%), followed by retinitis pigmentosa (13.0%), diabetic retinopathy (10.2%), and macular degeneration (9.1%). The most common impairment grade was grade 2 (40.8%), followed by 5 (21.2%) and 1 (17.0%). Compared to the fiscal year 2015, there was a considerable increase in the number of individuals certified with glaucoma in the fiscal year 2019. Moreover, there was a significant increase in the number of individuals with certified grades 1 and 2 visual impairment, with a decrease in the number of individuals with certified grade 6 visual impairment. Conclusion: The changes revealed in this study were primarily due to the revised certification criteria implemented in July 2018, indicating that it is important to review the certification criteria and to repeat surveys similar to the present study. [ABSTRACT FROM AUTHOR]

This article analyzes the tariff negotiation game between two countries when the countries are sufficiently farsighted. It extends the research of Nakanishi (2000) and Oladi (2005) for the tariff retaliation game in which countries take into account subsequent retaliations that may occur after their own retaliation. We show that when countries are sufficiently farsighted, all farsighted stable sets of the tariff game of Nakanishi (2000) are singletons, which are Pareto efficient and strictly individually rational tariff combinations. These results hold regardless of whether coalitional deviations are allowed or not. [ABSTRACT FROM AUTHOR]

In this note, we investigate the relationship between the classical concepts of maximin and minimax, which were originally defined in the context of zero-sum games in von Neumann and Morgenstern (1953) , and the von Neumann–Morgenstern (vNM) farsighted stable set using the indirect domination defined in Chwe (1994). We show two main results for two-player games: an existence result and an almost-uniqueness result. Under a mild assumption, we show that any strategy profile that is Pareto efficient and strictly individually rational–that is, strictly above each player’s maximin value–is generically a singleton vNM farsighted stable set. Moreover, there does not exist a vNM farsighted stable set that includes a strategy profile that is strictly individually rational and yields a payoff greater than the minimax value for a player, but not Pareto efficient. [ABSTRACT FROM AUTHOR]

Purpose: To evaluate the cost-effectiveness for a screening interval longer than 1 year detecting diabetic retinopathy (DR) through the estimation of incremental costs per quality-adjusted life year (QALY) based on the best available clinical data in Japan. Methods: A Markov model with a probabilistic cohort analysis was framed to calculate incremental costs per QALY gained by implementing a screening program detecting DR in Japan. A 1-year cycle length and population size of 50,000 with a 50-year time horizon (age 40-90 years) was used. Best available clinical data from publications and national surveillance data was used, and a model was designed including current diagnosis and management of DR with corresponding visual outcomes. One-way and probabilistic sensitivity analyses were performed considering uncertainties in the parameters. Results: In the base-case analysis, the strategy with a screening program resulted in an incremental cost of 5,147 Japanese yen (¥; US$64.6) and incremental effectiveness of 0.0054 QALYs per person screened. The incremental cost-effectiveness ratio was ¥944,981 (US$11,857) per QALY. The simulation suggested that screening would result in a significant reduction in blindness in people aged 40 years or over (−16%). Sensitivity analyses suggested that in order to achieve both reductions in blindness and cost-effectiveness in Japan, the screening program should screen those aged 53-84 years, at intervals of 3 years or less. Conclusions: An eye screening program in Japan would be cost-effective in detecting DR and preventing blindness from DR, even allowing for the uncertainties in estimates of costs, utility, and current management of DR. [ABSTRACT FROM AUTHOR]

. Purpose: To determine the reliability and reproducibility of the Vesselmap Oximetry Module for arteriolar and venular oxygen saturation (SO2) of the same retinal area, specified by a peripapillary annulus, in healthy subjects. Methods: Fundus oximetry images were obtained, using a standardized protocol by a single observer, from the right eye of 20 healthy individuals. Age range was 19-45 years old, and images were analysed using the oximetry module of the Vesselmap System (Imedos, UG, Germany). Intra-observer reliability (assessment of two measurements of SO2 values performed 5 days apart); interobserver reliability (assessment of SO2 performed by two different trained observers); and intrasubject reproducibility (comparison of SO2 measurements of two different images of the same subject and retinal area, taken 10 min apart) were assessed. The standard deviations between the repeated measurements (SDr), together with the intraclass correlation coefficient (ICC), of these three parameters were calculated. Results: The SDr for intra-observer reliability was 0.56% and 0.55% for arteriolar and venular SO2, respectively. The results were similar for intrasubject reproducibility (0.69% and 0.79% for arteriolar and venular SO2, respectively); interobserver reliability, however, was higher (SDr 1.22% and 1.01% for arteriolar and venular SO2, respectively). The ICC values for intra-observer reliability were 0.99 for both arteriolar and venular SO2. The results were similar for both interobserver reliability (0.94 for arteriolar SO2 and 0.96 for venular SO2) and intrasubject reproducibility (0.98 for both arteriolar and venular SO2). Conclusion: Retinal oxygen saturation values taken using the oximetry module of the Vesselmap System are highly reliable and reproducible, provided the image quality is standardized, the same measurement area is analysed in each image, and the number of observers analysing the images is kept to a minimum. [ABSTRACT FROM AUTHOR]

Purpose/aim: To identify retinal vascular features that precede the development of branch retinal vein occlusion (BRVO) by comparing case eyes and fellow eyes. Materials and methods: We identified 25 persons who attended an annual health screening program at Osaka Health Science Center, Osaka, Japan, and then developed BRVO in one eye between 1995 and 2009. We retrospectively reviewed retinal images of these subjects taken 1-5 years prior to the development of BRVO and compared the prevalence of retinal vascular features between case eyes and contralateral fellow eyes. Potential local retinal vascular features considered were (1) severe arterio-venous (AV) nicking, (2) a smaller angle at the crossing of the arteriole and venule, (3) double crossing, (4) crossing near venular bifurcation and (5) isolated retinopathy. The central retinal artery equivalent (CRAE), vein equivalent (CRVE) and AV ratio (CRAE divided by CRVE) were quantitatively estimated using a standardized imaging software (University of Wisconsin). Results: Compared to the fellow eye, severe AV nicking (39.1% versus 2.6%, <0.001), isolated retinopathy (47.8% versus 7.69%, p < 0.001) and a smaller angle at the crossing site (82.6% versus 46.2%, p = 0.005) were more prevalent in eyes with BRVO compared with fellow eyes. Case eyes had a significantly smaller AV ratio at 1-5 years prior to the development of BRVO compared with fellow eyes (0.68 versus 0.73, p = 0.03). Conclusions: In addition to severe AV nicking, a well-known sign linked to BRVO, this study identified two new potential retinal vascular features - isolated retinopathy and a smaller angle at the crossing site - associated with BRVO development. We also found that a discrepancy in the AV ratio between eyes (i.e. a smaller AV ratio than the fellow eye) can be a quantitative indicator of a higher BRVO risk. These findings warrant further validation in longitudinal studies. [ABSTRACT FROM AUTHOR]

Abstract: Recent research suggests that retinal vessel caliber (or cross-sectional width) measured from retinal photographs is an important feature for predicting cardiovascular diseases (CVDs). One of the most utilized measures is to quantify retinal arteriolar and venular caliber as the Central Retinal Artery Equivalent (CRAE) and Central Retinal Vein Equivalent (CRVE). However, current computer tools utilize manual or semi-automatic grading methods to estimate CRAE and CRVE. These methods involve a significant amount of grader's time and can add a significant level of inaccuracy due to repetitive nature of grading and intragrader distances. An automatic and time efficient grading of the vessel caliber with highly repeatable measurement is essential, but is technically challenging due to a substantial variation of the retinal blood vessels’ properties. In this paper, we propose a new technique to measure the retinal vessel caliber, which is an “edge-based” vessel tracking method. We measured CRAE and CRVE from each of the vessel types. We achieve very high accuracy (average 96.23%) for each of the cross-sectional width measurement compared to manually graded width. For overall vessel caliber measurement accuracy of CRAE and CRVE, we compared the results with an existing semi-automatic method which showed high correlation of 0.85 and 0.92, respectively. The intra-grader reproducibility of our method was high, with the correlation coefficient of 0.881 for CRAE and 0.875 for CRVE. [Copyright &y& Elsevier]

. Purpose: To assess the relation between retinal vascular caliber and renal function. Patients and methods: Eighty apparently healthy subjects screened for cardiovascular risk factors (mean age 47 years, 51% female, 36% hypertensive, without diabetes or renal dysfunction) were recruited. Retinal vascular calibers were measured from fundus photographs and expressed as central retinal artery and venular equivalent. Renal function was assessed by measurement of glomerular filtration rate (urinary clearance of 99mTc-DTPA) and urinary albumin/creatinine ratio. Results: Mean glomerular filtration rate was 117 ml/min/1.73m2. Overall, central retinal artery and venular equivalent were positively correlated with glomerular filtration rate ( r = +0.31, p = 0.005 and r = +0.30, p = 0.006, respectively). In addition, central retinal artery equivalent was negatively correlated with urinary albumin/creatinine ratio ( r = −0.34, p = 0.002). No significant relationship was found between central retinal venular equivalent and urinary albumin/creatinine ratio ( r = +0.12, p = 0.32). The observed relations between retinal vascular calibers and renal function parameters remained significant after adjusting for potential confounding factors. Conclusion: In apparently healthy subjects with normal renal function, retinal arteriolar and venular calibers were negatively correlated with kidney function, suggesting common determinants of these preclinical target organ damages. [ABSTRACT FROM AUTHOR]

We consider a problem in which a policy is chosen from a one-dimensional set over which voters have single-peaked preferences. While Moulin (Public Choice 35:437-455, ) and others subsequent works have focused on strategy-proof rules, Renault and Trannoy (Mimeo ) and Renault and Trannoy (J Pub Econ Theory 7:169-199, ) have shown that the average rule implements a generalized median rule in Nash equilibria and provide an interpretation of the parameters in Moulin's rule. In this article, we first extend their result by showing that a wide range of voting rules which includes the average rule can implement Moulin's rule in Nash equilibria. Moreover, we show additionally that within this class, generalized average rules are Cournot stable. That is, from any strategy profile, any best response path must converge to a Nash equilibrium. [ABSTRACT FROM AUTHOR]

Objective: Diabetic retinopathy (DR) is linked to cardiovascular risk in diabetic patients. This study examined whether mild-stage DR is associated with risk of coronary heart disease (CHD) and stroke in type 2 diabetic patients of the Japan Diabetes Complications Study (JDCS). Design: Prospective cohort study. Participants: In the JDCS, there were 2033 Japanese persons with type 2 diabetes free of cardiovascular diseases at baseline. Methods: Diabetic retinopathy was ascertained from clinical and photographic grading (70%) following the international clinical diabetic retinopathy and diabetic macular edema disease severity scales. Incident CHD and stroke were followed up prospectively annually up to 8 years. Main Outcome Measures: Eight-year incidence of CHD and stroke compared between persons with or without DR. Results: After adjusting for traditional cardiovascular risk factors, persons with mild to moderate nonproliferative DR had a higher risk of CHD (hazard ratio [HR], 1.69; 95% confidence interval [CI], 1.17–2.97) and stroke (HR, 2.69; 95% CI, 1.03–4.86). Presence of retinal hemorrhages or microaneurysms was associated with risk of CHD (HR, 1.63; 95% CI, 1.04–2.56) but was not associated with stroke (P = 0.06). Presence of cotton-wool spots was associated with risk of incident stroke (HR, 2.39; 95% CI, 1.35–4.24) but was not associated with CHD (P = 0.66). When information about DR was added in the prediction models for CHD and stroke based on traditional cardiovascular risk factors, the area under the receiver operating curve improved from 0.682 to 0.692 and 0.640 to 0.677, and 9% and 13% of persons were reclassified correctly for CHD and stroke, respectively. Conclusions: Type 2 diabetic patients with even a mild stage of DR, such as dot hemorrhages, are already at higher risk of CHD and stroke independent of traditional risk factors. Financial Disclosure(s): The author(s) have no proprietary or commercial interest in any materials discussed in this article. [Copyright &y& Elsevier]

Purpose: To examine associations between quantitatively measured retinal vessel caliber and the 10-year incidence of primary open-angle glaucoma (OAG). Design: Population-based cohort study. Participants: The Blue Mountains Eye Study examined 3654 persons at baseline and 2461 persons at either 5 years, 10 years, or both times. After excluding 44 subjects with OAG at baseline, 2417 participants at risk of OAG at the 5- or 10-year examinations were included. Methods: Retinal vessel calibers of baseline retinal photographs were measured using a computer-based program and summarized as central retinal artery and vein equivalents (CRAE, CRVE). Incident OAG was defined as the development of typical glaucomatous visual field loss combined with matching optic disc rim thinning and an enlarged cup-to-disc (C:D) ratio of >0.7 or C:D asymmetry between the 2 eyes (≥0.3) at either the 5- or 10-year examination. Generalized estimating equation models were used to account for correlation between eyes while adjusting for glaucoma risk characteristics including intraocular pressure (IOP) or ocular perfusion pressure (OPP). Main Outcome Measures: We assessed the 10-year incidence of OAG. Results: There were 82 persons (104 eyes) who developed incident OAG over the 10-year follow-up. After adjusting for age, sex, family history of glaucoma, smoking, diabetes, hypertension, hypercholesterolemia, body mass index, spherical equivalent refraction, and C:D ratio, narrower CRAE was associated with higher risk of incident OAG (adjusted odds ratio [OR], 1.77; 95% confidence interval [CI], 1.12–2.79, per standard deviation decrease in CRAE). This association persisted after further adjustment for IOP (adjusted OR, 1.87; 95% CI, 1.14–3.05) or OPP (adjusted OR, 1.76; 95% CI, 1.11–2.78), and remained significant when analyses were confined to eyes with IOP <20 mmHg and C:D ratio <0.6 at baseline. There were no independent associations between CRVE and incident OAG. Conclusions: Retinal arteriolar narrowing, quantitatively measured from retinal photographs, was associated with long-term risk of OAG. These data support the concept that early vascular changes are involved in the pathogenesis of OAG and suggest that computer-based measurements of retinal vessel caliber may be useful to identify people with an increased risk of developing the clinical stage of glaucoma. Financial Disclosure(s): The authors have no proprietary or commercial interest in any of the materials discussed in this article. [Copyright &y& Elsevier]

Background: Whether the increase in vascular disease prevalence and mortality in OA populations is a result of co-occurrence of cardiovascular disease and OA, which are both common in the older population, is due to OA treatments or to the common association with reduced physical activity and/or obesity is unclear. One way to explore this non-invasively is to examine the cross-sectional relationship between changes in retinal microvasculature, which have been shown to be markers of generalized vascular pathology, and knee structural changes in an asymptomatic community-based population. Methods: A community sample of 289 (61% women) aged 50-79 years with no knee symptoms underwent magnetic resonance imaging (MRI) of their dominant knee in 2003. Cartilage volume and bone marrow lesions (BMLs) were determined. All subjects also had retinal photographs taken from which retinal arteriolar and venular diameters were determined and summarized as the central retinal arteriolar equivalent (CRAE) and the central retinal venular equivalent (CRVE). Results: Retinal venular diameter was significantly wider in subjects with a BML compared with subjects without a BML (mean (SD) 214.2 (2.8) μm versus 207.5 (1.1) μm respectively independent of age, gender and BMI. A trend for decreased medial tibial cartilage with increasing CRAE was also observed (regression coefficient -2.70 μl,95%CI-5.74, 0.5, p=0.08). Conclusion: These findings suggest that vascular pathology, indicative of inflammatory processes, is associated with early structural knee changes. The role of micro-vascular changes in the pathogenesis of OA warrants further investigation [ABSTRACT FROM AUTHOR]

Abstract: We apply the farsighted stable set to two versions of Hotelling’s location games: one with a linear market and another with a circular market. It is shown that there always exists a farsighted stable set in both games, which consists of location profiles that yield equal payoff to all players. This stable set contains location profiles that reflect minimum differentiation as well as those profiles that reflect local monopoly. These results are in contrast to those obtained in the literature that use some variant of Nash equilibrium. While this stable set is unique when the number of players is two, uniqueness no longer holds for both models when the number of players is at least three. [Copyright &y& Elsevier]

Purpose: To compare the frequency and pattern of bilateral involvement of early and late age-related macular degeneration (AMD) between Asian Malays and Caucasians. Methods: We used cross-sectional data from the baseline examination for subjects aged 50-79 years in the Singapore Malay Eye Study (SiMES) ( N == 2,453) and the Blue Mountains Eye Study (BMES) ( N == 3,265). We assessed AMD signs using a common protocol modified from the Wisconsin Age-related Maculopathy Grading System at the University of Sydney. We compared frequencies or proportions of AMD cases with bilateral involvement between the two populations. Results: There were 173 cases and 169 cases with any AMD (either early or late AMD in at least one eye), and 78 cases (45.1%) and 52 cases (30.8%) with bilateral AMD in the BMES and the SiMES, respectively. Age-standardized frequency of bilateral involvement was comparable between the BMES (29.5%, 95% confidence interval(CI) 18.5-40.5%) and the SiMES (25.6%, 95%CI 17.0-34.0%). Older age was associated with higher risk of bilateral AMD (gender-adjusted odds ratio per 1 year for the BMES and the SiMES: 1.08 [95% CI 1.05-1.11] and 1.06 [95% CI 1.02-1.10], respectively). Conclusions: The frequency of bilateral AMD was comparable between Asian Malays in the SiMES and the Caucasian population of the BMES. Other than older age, we did not find any characteristics associated with the bilateral involvement of AMD. [ABSTRACT FROM AUTHOR]

Purpose: To examine the association between glucose metabolism and central corneal thickness (CCT) in Japanese adults. Methods: A sub-sample of 322 Japanese adults participating in the Funagata Study was included in this analysis. CCT was measured using a specular microscope. Glucose metabolism was examined using 75-g oral glucose tolerance test. Mean differences in CCT (μm) and 95% confidence intervals were estimated with univariate, age-sex-adjusted and multivariate models using multiple linear regression. Results: The mean (± standard deviation) age of the study sample was 63.7 ± 11.4 years and 44% were men. The mean fasting plasma glucose (FPG), 2-hour post-load plasma glucose (2hPG) and haemoglobin A1c (HbA1c) concentrations were 96.8 ± 12.6mg/dl, 123.6 ± 41.2mg/dl and 5.3 ± 0.4%, respectively. CCT was normally distributed in the study sample, and the mean CCT was 544.7 ± 34.6μm. After multivariate adjustment, characteristics associated with increased CCT were 2hPG and HbA1c concentrations, impaired glucose tolerance, diabetes, body weight or body mass index and current smoking. Conclusion: Impaired glucose tolerance, diabetes, obesity and current smoking are associated with increased CCT. Additional studies are required to examine whether interventions to affect these characteristics may reduce CCT. [ABSTRACT FROM AUTHOR]

Objective: Persons with diabetic retinopathy (DR) have an increased risk of clinical cardiovascular events. This study aimed to determine whether DR is associated with a range of measures of subclinical cardiovascular disease (CVD) in persons without clinical CVD. Design: Population-based, cross-sectional epidemiologic study. Participants: Nine hundred twenty-seven persons with diabetes without clinical CVD in the Multi-Ethnic Study of Atherosclerosis. Methods: Diabetic retinopathy was ascertained from retinal photographs according to modification of the Airlie House Classification system. Vision-threatening DR (VTDR) was defined as severe nonproliferative DR, proliferative DR, or clinically significant macular edema. Subclinical CVD measures were assessed and defined as follows: high coronary artery calcium (CAC) score, defined as CAC score of 400 or more; low ankle-brachial index (ABI), defined as ABI of less than 0.9; high ABI, defined as ABI of 1.4 or more; high carotid intima-media thickness (IMT), defined as highest 25% of IMT; and carotid stenosis, defined as more than 25% stenosis or presence of carotid plaque. Main Outcome Measures: Associations between DR and subclinical CVD measures. Results: The prevalence of DR and VTDR in this sample was 30.0% and 7.2%, respectively, and VTDR was associated with a high CAC score (odds ratio [OR], 2.33; 95% confidence interval [CI], 1.15–4.73), low ABI (OR, 2.54; 95% CI, 1.08–5.99), and high ABI (OR, 12.6; 95% CI, 1.14–140.6) after adjusting for risk factors including hemoglobin A1c level and duration of diabetes. The association between VTDR and high CAC score remained significant after further adjustment for hypoglycemic, antihypertensive, and cholesterol-lowering medications. Diabetic retinopathy was not significantly associated with measures of carotid artery disease. Conclusions: In persons with diabetes without a history of clinical CVD, the presence of advanced-stage DR is associated with subclinical coronary artery disease. These findings emphasize the need to be careful about the use of anti–vascular endothelial growth factor for the treatment of DR. Financial Disclosure(s): The author(s) have no proprietary or commercial interest in any materials discussed in this article. [Copyright &y& Elsevier]

Glaucoma, one of the major causes of blindness in the world, is a progressive optic neuropathy. Elevated intraocular pressure is a well-known major risk factor for glaucoma. In addition, there is growing evidence that vascular factors may play a role in glaucoma pathogenesis. Systemic (e.g. hypertension, diabetes) and ocular vascular factors (e.g. ocular blood flow, ocular perfusion pressure) have been assessed for associations with glaucoma. However, direct and convincing evidence for primary mechanisms of glaucoma is still lacking. The aim of this review is to summarize the evidence implicating vascular factors in the pathogenesis of glaucoma, with particular emphasis on the role of ocular blood flow and ocular circulation as risk factors for primary open angle glaucoma. [ABSTRACT FROM AUTHOR]

Objective: To determine the prevalence of age-related macular degeneration (AMD) in Asian populations and to compare this with prevalence in white populations. Design: A clear understanding of AMD prevalence in Asians is essential to meet future demands for eye health care. Methods: We searched published literature reporting AMD prevalence in Asian populations. We limited studies examined to those using standardized grading systems (either the Wisconsin Age-Related Maculopathy Grading System or the international classification proposed by the International ARM Epidemiological Study Group). We used metaanalytical methods to calculate age-specific pooled prevalence of AMD using inverse-variance weighting in a random effect model. We also calculated pooled estimates of age-standardized prevalence. A metaregression model was used to examine gender differences and differences between Asian and white populations. Results: We identified 9 studies reporting AMD prevalence from 4 Asian populations. Pooled prevalence estimates of early and late AMD in Asian populations aged 40 to 79 years were 6.8% (95% confidence interval [CI], 4.6%–8.9%) and 0.56% (95% CI, 0.30%–0.81%), respectively; corresponding prevalence estimates in white populations were 8.8% (95% CI, 3.8%–13.8%) and 0.59% (95% CI, 0.35%–0.84%), respectively. Reliable prevalence estimates of AMD in Asian persons aged ≥80 years were not available owing to small subject numbers in this age category. Conclusions: Among persons aged 40 to 79 years, the age-specific prevalence of late AMD in Asians was comparable with that reported from white populations, but early AMD signs were less common among Asians. Further studies in Asian populations are warranted to investigate whether certain specific AMD phenotypes or subtypes, such as polypoidal choroidal vasculopathy, are more common. Financial Disclosure(s): Proprietary or commercial disclosure may be found after the references. [Copyright &y& Elsevier]

Microcirculation (2010) 17, 1–9. doi: 10.1111/j.1549-8719.2009.00006.x Objective: To determine whether retinal arteriolar narrowing, possibly reflecting peripheral arteriolar vasoconstriction, predicts risk of hypertension in Japanese persons. Methods: The Funagata study is a population-based cohort study of Japanese aged 35+ years. Baseline examinations were conducted in 2000–2002 among 1058 persons without hypertension. Of these, 581 persons (55%) returned for a 5-year follow-up examination, with data on 563 available for analyses. Retinal photographs taken at the baseline visits were assessed for retinal arteriolar or venular diameter and retinal vessel wall signs using standardized protocols. Hypertension was defined if systolic blood pressure ≥140 mmHg, diastolic blood pressure ≥90 mmHg or from self-reported clinical diagnosis, including the use of antihypertensive medications. Incident hypertension was defined as an absence of hypertension at baseline but presence of hypertension at the follow-up visit. Results: One hundred ninety-three subjects (34.3%) had developed hypertension at 5-year follow-up. After adjusting for age, gender, baseline blood pressure and other risk factors, narrower retinal arterioles at baseline was significantly associated with an increased risk of incident hypertension (odds ratio per standard deviation decrease in arteriolar diameter: 1.53, 95% confidence interval: 1.08–2.18). Conclusions: Our findings support the concept that arteriolar narrowing, evident in the retina, signals an increased risk of developing hypertension in Japanese persons. [ABSTRACT FROM AUTHOR]

Abstract: The set of competitive allocations in an exchange economy with indivisible goods of is an important solution concept in the literature. In this paper, we consider a farsighted version of the von Neumann and Morgenstern stable set by using the farsighted approach of and by modifying the domination relation defined by to incorporate farsightedness. We show that there exists a unique farsighted stable set, which coincides with the set of competitive allocations. [Copyright &y& Elsevier]

OBJECTIVE -- Flicker light-induced retinal vasodilation may reflect endothelial function in the retinal circulation. We investigated flicker light-induced vasodilation in individuals with diabetes and diabetic retinopathy. RESEARCH DESIGN AND METHODS -- Participants consisted of 224 individuals with diabetes and 103 nondiabetic control subjects. Flicker light-induced retinal vasodilation (percentage increase over baseline diameter) was measured using the Dynamic Vessel Analyzer. Diabetic retinopathy was graded from retinal photographs. RESULTS -- Mean ± SD age was 56.5 ± 11.8 years for those with diabetes and 48.0 ± 16.3 years for control subjects. Mean arteriolar and venular dilation after flicker light stimulation were reduced in participants with diabetes compared with those in control subjects (1.43 ± 2.10 vs. 3.46 ± 2.36%, P < 0.001 for arteriolar and 2.83 ± 2.10 vs. 3.98 ± 1.84%, P < 0.001 for venular dilation). After adjustment for age, sex, diabetes duration, fasting glucose, cholesterol and triglyceride levels, current smoking status, systolic blood pressure, and use of antihypertensive and lipid-lowering medications, participants with reduced flicker light-induced vasodilation were more likely to have diabetes (odds ratio 19.7 [95% CI 6.5-59.1], P < 0.001 and 8.14 [3.1-21.4], P < 0.001, comparing lowest vs. highest tertile of arteriolar and venular dilation, respectively). Diabetic participants with reduced flicker light-induced vasodilation were more likely to have diabetic retinopathy (2.2 [1.2-4.0], P = 0.01 for arteriolar dilation and 2.5 [1.3-4.5], P = 0.004 for venular dilation). CONCLUSIONS -- Reduced retinal vasodilation after flicker light stimulation is independently associated with diabetes status and, in individuals with diabetes, with diabetic retinopathy. Our findings may therefore support endothelial dysfunction as a pathophysiological mechanism underlying diabetes and its microvascular manifestations. [ABSTRACT FROM AUTHOR]

Abstract: We examine farsighted stable sets in a public good provision game where the public good is perfectly “lumpy” as defined by Taylor [Taylor, M., 1987. The possibility of cooperation. Cambridge University Press, Cambridge]. In this case, Taylor argues that the game is not a prisoners’ dilemma game. While Suzuki and Muto [Suzuki, A., Muto, S., 2005. Farsighted stability in an -Person Prisoner’s dilemma. International Journal of Game Theory 33, 431–445] have shown that almost all outcomes included in a farsighted stable set of a prisoners’ dilemma game are Pareto efficient, we show in our game that almost all strictly individually rational outcomes are included in a farsighted stable set, including those that are not Pareto efficient. [Copyright &y& Elsevier]

Purpose: To investigate the relationship between retinal vascular caliber and age-related macular degeneration (AMD). Design: Population-based cross-sectional study. Methods: Three thousand two hundred and eighty (78.7% response rate) Malay Singaporeans aged 40 to 80 years residing in 15 districts of Singapore underwent retinal photography. Retinal vessel caliber was measured from retinal photographs using a validated computer-based technique. AMD was assessed following a modified Wisconsin Age-Related Maculopathy Grading System. Results: Retinal data were available from 3,265 subjects (99.5% of 3,280) for this study. Early and late AMD prevalence were 4.9% (n = 160) and 0.7% (n = 23) of the population, respectively, or in 205 (3.1%) and 30 (0.5%) eyes examined, respectively. After controlling for age and arteriolar caliber, wider venular caliber was associated with higher prevalence of early AMD (odds ratio [OR] per one standard deviation [SD] increment in venular caliber, 1.53; 95% confidence interval [CI], 1.13 to 2.09). This association remained significant after further adjustment for gender, smoking, hypertension, diabetes, and body mass index (OR per one SD, 1.52; 95% CI, 1.11 to 2.09). There was no significant association between retinal arteriolar caliber and early AMD, or between arteriolar or venular caliber and late AMD. Conclusions: Wider venular caliber was associated independently with early AMD. This finding may suggest that pathogenic processes linking to wider venular caliber be shared by early AMD and common cardiovascular risk factors such as inflammation, dyslipidemia, and endothelial dysfunction. [Copyright &y& Elsevier]

Objective: To describe the prevalence of age-related macular degeneration (AMD) in an Asian Malay population. Design: Population-based cross-sectional study. Participants: An age-stratified random sample of Malay persons aged 40 to 80 years living in Singapore. Methods: Participants were invited to a central clinic for a comprehensive examination. Main Outcome Measures: Early and late AMD signs were graded from retinal photographs following the Wisconsin grading system. Results: Of 3280 participants who participated (78.7% response rate), 3265 had photographs of sufficient quality for grading of AMD signs. Early and late AMD were present in 160 (4.9%) and 23 (0.70%) participants, respectively. After age standardization, the prevalence of early AMD in Malay persons aged 40 to 80 years was estimated to be 3.5% (95% confidence interval [CI], 2.9%–4.1%) and that of late AMD was 0.34% (95% CI, 0.20%–0.49%). Early AMD was more prevalent in men than in women (6.1% vs. 3.8%); this was significant despite adjusting for age and smoking (odds ratio [OR], 1.56; 95% CI, 1.11–2.20). Late AMD also was more prevalent in men than in women (1.0% vs. 0.4%), although this was not statistically significant after adjusting for age and smoking (OR, 1.39; 95% CI, 0.52–3.68). The prevalence of early and late AMD was similar to that reported in the Blue Mountains Eye Study among white persons. Conclusions: The prevalence of AMD in Asian Malay people is similar to that in white persons from the Blue Mountains Eye Study. Early AMD signs were more frequent in men compared with women, an association that was not fully explained by the higher smoking rates in men. Financial Disclosure(s): The authors have no proprietary or commercial interest in any materials discussed in this article. [Copyright &y& Elsevier]

Objective: To describe the prevalence and risk factors for age-related macular degeneration (AMD) in a Japanese population and to compare these with data from a white population. Design: Population-based cross-sectional epidemiologic study. Participants: A population-based sample of Japanese persons 35 years or older from Funagata, Japan. Methods: The Funagata study is a population-based study of 1758 (43% of eligible) Japanese persons 35 years or older from Funagata, Japan. In 2000 to 2002, 1625 (92.4%) participants had a nonmydriatic fundus photograph of one eye with sufficient quality for grading of AMD lesions, using the Wisconsin protocol. Age-standardized prevalence rates compared with the Blue Mountains Eye Study (BMES) population, odds ratios (ORs), and 95% confidence intervals (CIs) were calculated. Risk factors were assessed by logistic regression. Main Outcome Measures: Early and late AMD. Results: Of 1625 participants, early AMD and late AMD were present in 3.5% and 0.5%, respectively. Age-standardized early AMD prevalence in right eyes was 4.1%, similar to the corresponding prevalence of 4.4% in the BMES. For men, age-standardized prevalences of late AMD in right eyes were 1.1% and 1.2% in the BMES; for women, the corresponding prevalences were 0.3% and 2.1%, respectively. Increasing age (per 10 years; gender-adjusted OR, 2.27; 95% CI, 1.10–4.67) and current cigarette smoking (age- and gender-adjusted OR, 5.03; 95% CI, 1.00–25.47) were associated with late AMD. Conclusions: In this Japanese population, prevalence of early AMD was similar to that for whites in the BMES. Although the late AMD prevalence was lower in Japanese women, in Japanese men it was similar to that in whites. This could have resulted from the substantially high proportion of Japanese men who are smokers. Cigarette smoking and increasing age were the 2 principal factors found associated with late AMD. [Copyright &y& Elsevier]

Abstract: Square lattice gas models for heteroepitaxial growth are studied by means of kinetic Monte Carlo simulations, in order to find a possible origin of anisotropic island shape observed in growth experiments of long organic molecules. When deposited molecules form clusters irreversibly at their encounter during surface diffusion, islands grow in a ramified dendritic shape, similar to DLA. Introduction of molecular detachment from edges makes islands compact with smooth edges. Tilting of adsorbed long molecules or steps in a vicinal substrate may induce orientation dependence in the detachment rate of edge molecules from an island. In simulations with orientation-dependent detachment rates, a clear anisotropy in an island shape is observed. Shape anisotropy on a vicinal substrate is enhanced as steps get dense, in agreement to the experimental observation. [Copyright &y& Elsevier]

Objective: To describe the prevalence of retinal vascular signs and their association with cardiovascular risk factors in a Japanese population. Design: Population-based cross-sectional study. Participants: Adult persons aged 35 years or older from Funagata, Yamagata Prefecture, Japan (n = 1481). Methods: The Funagata Study is a Japanese population-based study of persons aged 35 years or older, and included 1961 nondiabetic participants (53.3% of 3676 eligible subjects). A nonmydriatic retinal photograph was taken of 1 eye to assess retinal microvascular signs. Retinal arteriolar wall signs (focal arteriolar narrowing, arteriovenous nicking, enhanced arteriolar wall reflex) and retinopathy were assessed in 1481 participants without diabetes (40.3% of eligible persons) using a standardized protocol. Using a computer-assisted method, retinal vessel diameters were measured in 921 participants with gradable retinal image (25.1% of eligible persons). Main Outcome Measures: Prevalence of retinal microvascular signs and their association with cardiovascular risk factors. Results: Moderate or severe focal arteriolar narrowing, arteriovenous nicking, enhanced arteriolar wall reflex, and retinopathy were found in 8.3%, 15.2%, 18.7%, and 9.0%, respectively, of the study population. Mean (±standard error) values for retinal arteriolar diameter were 178.6±21.0 μm, and mean values (±standard error) for venular diameter were 214.9±20.6 μm. Older persons were more likely to have retinal arteriolar wall signs, retinopathy, and narrower retinal vessel diameters. After adjusting for multiple factors, each 10-mmHg increase in mean arterial blood pressure was associated with a 20% to 40% increased likelihood of retinal arteriolar signs and a 2.8-μm reduction in arteriolar diameter. Retinopathy was associated with higher body mass index and both impaired glucose tolerance and impaired fasting glucose. Conclusions: In nondiabetic Japanese adults, retinal arteriolar wall signs were associated with older age and increased blood pressure, whereas retinopathy was associated with older age, higher body mass index, impaired glucose tolerance, and impaired fasting glucose. These findings are comparable with data from white populations. [Copyright &y& Elsevier]

Type 2 diabetes is a heterogeneous disease that can be subdivided on the basis of β-cell function and insulin sensitivity. We investigated the presence, incidence, and progression of diabetic retinopathy (DR) according to subtypes of type 2 diabetes. In a national cohort, we identified three subtypes of type 2 diabetes: classical, hyperinsulinemic, and insulinopenic type 2 diabetes, based on HOMA2 measurements. From the Danish Registry of Diabetic Retinopathy we extracted information on level of DR. We used several national health registries to link information on comorbidity, medications, and laboratory tests. We found individuals with hyperinsulinemic type 2 diabetes were less likely to have DR at entry date compared with those with classical type 2 diabetes, whereas individuals with insulinopenic type 2 diabetes were more likely to have DR. In multivariable Cox regression analysis, individuals with hyperinsulinemic type 2 diabetes had a decreased risk of both incidence and progression of DR compared to those with classical type 2 diabetes. We did not find any clear difference in risk of incident or progression of DR in individuals with insulinopenic compared to classical type 2 diabetes. These findings indicate that subcategorization of type 2 diabetes is important in evaluating the risk of DR. Article Highlights: Type 2 diabetes can be subcategorized on the basis of β-cell function and insulin sensitivity, but little is known about the association of subtypes of type 2 diabetes with risk of diabetic retinopathy (DR). Do individuals with hyperinsulinemic or insulinopenic type 2 diabetes have an increased risk of DR compared with individuals with classical type 2 diabetes? Individuals with hyperinsulinemic type 2 diabetes had almost half the risk of prevalent or incident DR or progression of DR compared with individuals with classical type 2 diabetes. These results suggest that more individualized screening intervals for DR may be possible within subgroups of type 2 diabetes. [ABSTRACT FROM AUTHOR]

Purpose Methods Results Conclusion To evaluate the five‐year incidence of diabetic retinopathy (DR) and associated risk markers in patients with type 1 diabetes in the national Danish DR‐screening programme.Based on national data, we included all 16 999 patients with type 1 diabetes in the Danish Registry of Diabetic Retinopathy, who attended the national screening programme in the period 2013–2018. According to the worse eye at first screening, DR was classified (levels 0–4) and linked with various national health registries to retrieve information on diabetes duration, systemic comorbidity, and medication.At first screening, median age and duration of diabetes were 45.0 and 16.7 years, and 57.5% were males. The prevalence and five‐year incidences for DR and progression to proliferative DR (PDR) were 44.2%, 8.9% and 2.0%, respectively. In multivariable Cox models, the incidence endpoints were associated with duration of diabetes (hazard ratio [HR] 1.76, 95% confidence interval [CI] 1.63–1.89, and HR 2.04, 95% CI 1.73–2.40 per 10 years), moderately low Charlson Comorbidity Index score (HR 1.27, 95% CI 1.10–1.47, and HR 2.80, 95% CI 2.23–3.51), and use of blood pressure lowering medication (HR 1.20, 95% CI 1.05–1.36, and HR 1.98, 95% CI 1.53–2.57).In a study of all patients with type 1 diabetes from the Danish DR‐screening programme, we identified duration of diabetes, systemic disease and use of anti‐hypertensive treatment as consistent risk markers for incident and progressive DR. [ABSTRACT FROM AUTHOR]

PurposeMethodsResultsConclusionsTo evaluate the association between quantitative parameters derived from volume analysis of optical coherence tomography (OCT) data and disease worsening in Vogt-Koyanagi-Harada disease (VKHD) and sympathetic ophthalmia (SO).This retrospective study, conducted at Osaka University Hospital, employed swept-source OCT scans from patients diagnosed with VKHD or SO between October 2012 and January 2021. The choroidal vessel structure was segmented and visualized in three dimensions, generating quantitative vessel volume maps. Region-specific choroidal vessel volume (CVV), choroidal volume (CV), and vessel index (VI) were scrutinized for their potential correlation with disease severity.Thirty-five eyes of 18 VKHD and 2 SO patient (8 females, 10 males) were evaluated. OCT-derived CVV maps revealed regional CV alterations in VKHD and SO patients. Two parameters, i.e. CV at 3- and 6-month follow-ups (p = 0.044, p = 0.040, respectively, with area under the ROC curve of 0.70) and CVV at 6 months (p = 0.046, area under the ROC curve of 0.71), were significantly higher in recurrent VKHD and SO compared to effectively treated cases.The volume analysis of OCT images facilitates a three-dimensional visualization of choroidal alterations, which may serve as a reflection of disease severity in VKHD and SO patients. Furthermore, noninvasive initial CVV or CV measurements may serve as potential biomarkers for predicting disease recurrence in VKHD and SO. [ABSTRACT FROM AUTHOR]

: PurposeTo report the optical coherence tomography (OCT)-determined progressive changes in a macular hole (MH) following vitreous surgery with a gas tamponade.: DesignObservational case report.: MethodsA 60-year-old woman with an idiopathic full-thickness MH (Gass, Stage 2) in the left eye underwent vitreous surgery with a gas tamponade. The progressive closure of the MH was followed by OCT because an unplanned decrease of the gas tamponade made the macula accessible to OCT examination.: ResultsOn day 1, the tissue surrounding the MH extended into the center, and on day 2, the subretinal fluid and foveal cysts decreased and the retinal separation was reduced. On the third postoperative day, the MH was closed and the foveal contour was similar to that of normal retinas.: ConclusionThese results demonstrated that a small MH appears to be closed by 3 days after vitrectomy with gas tamponade. Although we cannot generalize to all sizes of MH, our findings suggest that small MHs are closed much earlier than reported and that the duration of maintaining a prone position can be shortened. [Copyright &y& Elsevier]

Purpose: The purpose of this study was to evaluate the association between retinal laser burden and vascular oxygen saturation in patients with proliferative diabetic retinopathy (PDR) treated with different extent of retinal laser. Methods: The study was a prospective, interventional study of patients with treatment‐naïve PDR. Patients were treated with navigated retinal laser (Navilas®, OD‐OS GmbH, Teltow, Germany) in different doses. Retinal oximetry was obtained at baseline (BL) prior to laser and after 6 months (M6). Patients were divided into three groups according to total laser spots applied: <1500 spots (Group 1), 1500–2000 spots (Group 2), and >2000 spots (Group 3). Results: We included 33 eyes of 28 patients with treatment‐naïve PDR. The groups did not differ according in BL characteristics. Between BL and M6, retinal arteriolar oxygen saturation did not change but retinal venular oxygen saturation (median with interquartile range) decreased in Groups 1 and 2 (1: 65.5 ± 8.8% versus 60.5 ± 9.5%, p = 0.04; 2: 65.3 ± 7.3% versus 63.0 ± 13.5%, p = 0.04). Focal retinal venular oxygen saturation, located to quadrants with retinal neovascularization, decreased in Group 2 from BL to M6 (67.5 ± 13.3% versus 61.5 ± 8.8%, p = 0.04). Retinal venular diameter decreased from BL to M6 in Group 1 (174.5 ± 15.3 μm versus 165.1 ± 28.7 μm, p = 0.01). Conclusions: In this study of patients with treatment‐naïve PDR, we showed that a less extensive laser treatment caused a reduction in retinal venular oxygen saturation and diameter 6 months after treatment. Our results suggest that less extensive laser treatment may be sufficient to improve the retinal metabolic environment conducive to PDR regression. [ABSTRACT FROM AUTHOR]

Purpose: To determine the prognostic factors for success 3 years after Baerveldt glaucoma implant (BGI) surgery. Study design: Single-center retrospective clinical study. Methods: We analyzed 27 eyes (24 patients) treated with BGI surgery between 2012 and 2016 at Osaka University Hospital. Patients were followed for a minimum of 3 years postoperatively. We analyzed the success rates and risk factors. Failure was defined as the need for additional surgery for IOP reduction, loss of light perception, and intraocular pressure (IOP) ≧22 mmHg (definition 1) or ≧17 mmHg (definition 2) at two consecutive follow-up visits. Results: The mean number of previous eye surgeries was 4.1 ± 3.3. The success rates were 81.5% and 77.8%, respectively, 1 year and 3 years after surgery based on definition 1 and 51.9% and 48.2%, respectively, based on definition 2. The early and late surgical complication rates, respectively, were 29.6% and 22.2%. An IOP 2 months after BGI surgery of ≧17 mmHg and the number of previous eye surgeries were significant risk factors for failure based on definition 2. Conclusion: The long-term results and complication rates after BGI surgery for refractory glaucoma in our hospital were similar to previous reports, and the IOP 2 months after BGI surgery and the number of previous eye surgeries were associated with the prognosis. [ABSTRACT FROM AUTHOR]

Purpose Methods Results Conclusion To investigate diabetic retinopathy (DR) as a potential marker of cardiovascular disease (CVD) in adults with type 1 diabetes attending the Danish DR‐screening programme and non‐diabetes adults.In this registry‐based matched case–cohort study, we identified 16 547 adults with type 1 diabetes, who were registered in the Danish Registry of Diabetic Retinopathy (DiaBase). Each case was age‐ and sex‐matched by five non‐diabetes individuals (n = 82 399), and odds ratios (ORs) and hazard ratios (HRs) were estimated for incident and upcoming CVD in multivariable models.Adults with type 1 diabetes (median age 44.5 years, 57.6% male) were more likely to have prevalent CVD (OR 1.29; 95% CI, 1.20–1.38) and to develop CVD within 5 years (HR 1.19; 95% CI, 1.08–1.30) as compared to non‐diabetes control. However, adults without DR were less likely to develop CVD (HR 0.84; 95% CI, 0.72–0.97) compared to the reference population. For adults with type 1 diabetes, there was an increasing risk for incident CVD for increasing levels of DR (HR 1.33, 1.95, 1.71 and 2.39 for DR‐levels 1–4, respectively). Patients with CVD at the time of the first screening had a higher risk to develop DR during follow‐up (HR 1.23; 95% CI, 1.02–1.49).In a nationwide matched case–cohort study adjusted for potential confounders, DR was identified as an independent marker of prevalent and incident CVD in type 1 diabetes with increasing risk demonstrated for higher levels of DR. Likewise, CVD also independently predicted the risk of incident DR. [ABSTRACT FROM AUTHOR]

Background: Epiretinal membrane (ERM) causes visual impairment such as reduction in visual acuity and metamorphopsia due to retinal traction. With the improvement of optical coherence tomography (OCT) and microincision vitrectomy surgery (MIVS), the surgery of ERM has significantly advanced. However, there have been no large-scale studies on the following: (1) how to evaluate visual impairment in ERM, (2) the relationship between OCT findings and visual function, (3) when is the optimal timing of surgery, and (4) the relationship between the surgical instruments as well as techniques and prognosis. The purpose of this study was to obtain evidence regarding these ERM surgeries. Methods and design: This is a prospective, multicenter cohort study of ERM surgery in Japan from March 1, 2023, to March 31, 2027 (UMIN000048472, R-3468-2). Patients who underwent ERM surgery during the study period and agreed to participate in this study will be included. The goal is to have a total of 5,000 eyes surgically treated for ERM. The following data will be collected: age, gender, medical history, subjective symptoms, visual function before and 6 and 12 months after surgery, clinical findings, OCT data, surgical technique, instruments used in surgery, and complications. Discussion: The results of this study will support the surgical decisions and procedures in ERM practices. [ABSTRACT FROM AUTHOR]

To investigate the prevalence, associated factors, and inter-eye differences of myopia and astigmatism in an adult Japanese population-based cohort. A total of 4282 participants from the Tohoku Medical Megabank Organization Eye Study (ToMMo Eye Study) underwent comprehensive ocular examinations as well as extensive physiological tests and a lifestyle questionnaire. The spherical equivalent (SE) and cylinder power were obtained as refractive parameters. The age- and gender-stratified prevalences of high myopia (SE < −5D), myopia (SE < −0.5D), hyperopia (SE > 0.5D), astigmatism (cylinder power < −0.5D), and anisometropia (SE difference >1D) were calculated. Multivariable analyses were performed to identify associated factors for refractive error (RE). Distribution and associated factors of the inter-eye difference in RE were also investigated. The age-adjusted prevalence of high myopia, myopia, hyperopia, astigmatism, and anisometropia was 15.9%, 63.5%, 14.7%, 51.1%, and 14.7%, respectively. Both myopia and high myopia were more prevalent in the younger age group, while astigmatism was more prevalent in the older age group. Age, education, blood pressure, intraocular pressure, and corneal thickness are significantly associated with myopic refraction. Age, gender, intraocular pressure, and corneal thickness are correlated with astigmatism. Older age was associated with against-the-rule astigmatism. Older age, myopia, and longer education showed a significant correlation with large inter-eye differences in SERE. This study demonstrated the high prevalence of myopia in young Japanese, which may be caused by a generational shift. This study also confirmed the influence of age and education on both the prevalence and inter-eye differences of RE. [ABSTRACT FROM AUTHOR]

Purpose: To report a new severity grading system for Fuchs endothelial corneal dystrophy (FECD) using anterior segment optical coherence tomography (AS‐OCT). Methods: This observational case series included 75 eyes of 43 patients with FECD and 33 eyes of 33 healthy subjects. Pachymetry and posterior elevation maps were used to determine the AS‐OCT‐based grading scores. FECD severity was graded from 0–3 as follows: 0, normal; 1, guttae only; 2, stromal oedema; and 3, epithelial and stromal oedema. We further investigated the central corneal thickness (CCT), thinnest corneal thickness (TCT), anterior and posterior best‐fit spheres (BFS), and the distance between the central cornea and the thinnest point. Results: Thirty‐three eyes were graded as 0, four as 1, thirteen as 2, fourteen as 3, twenty‐nine as 4, eleven as 5 and four as 6 by the modified Krachmer grade. Thirty‐three, 41, 30 and 4 eyes were graded as 0, 1, 2 and 3, respectively, by the AS‐OCT‐based grading system. The inter‐observer agreement was 100% for the AS‐OCT‐based grading system. The CCT, TCT, posterior BFS, and distance between the central cornea and thinnest point were significantly different between AS‐OCT‐based grades (p = 0.0001, 0.0001, 0.0036 and 0.0001, respectively). Anterior BFS was not significantly different with the AS‐OCT‐based grades (p = 0.1184). Conclusion: We devised a new severity grading using only objective evaluation and quantitatively demonstrated corneal thickening, predominant flattening of the posterior corneal surface compared with the anterior surface, and displacement of the thinnest point away from the central cornea with FECD progression. [ABSTRACT FROM AUTHOR]

The Glaucoma Stereo Analysis Study (GSAS) is a multicenter collaborative study of the characteristics of glaucomatous optic disc morphology using a stereo fundus camera. This study evaluated the retinal vessel calibers and correlations using GSAS fundus photographs between retinal vessels and 38 optic nerve head (ONH) morphologic parameters comprehensively. In all 240 eyes, the mean central retinal arteriolar equivalent (CRAE) and central retinal venular equivalent (CRVE) were 138.4 and 216.5 μm, respectively; the CRAE correlated with age, visual field scores and 19 ONH parameters and CRVE correlated with age, intraocular pressure, visual field scores and 11 ONH parameters. Among the different optic disc appearances including focal ischemia (FI) (n = 53, 22%), generalized enlargement (GE) (n = 53, 22%), myopic glaucoma (MY) (n = 112, 47%), and senile sclerosis (SS) (n = 22, 9%), the CRAE did not differ significantly; CRVE was significantly narrower in SS than in FI and MY. In FI, GE, MY, and SS disc types, CRAE correlated with 3, 14, 9, and 2 ONH parameters, respectively, and CRVE corelated with 9, 0, 12, and 6 ONH parameters, respectively. We confirmed previous observations on the effect of retinal vessel narrowing on glaucomatous changes in the ONH and visual field. The associations between retinal vessel caliber and ONH morphologic parameters vary among different optic disc appearances, suggesting different effects of vascular changes in each disc type. [ABSTRACT FROM AUTHOR]

Purpose: To conduct a systematic review of clinical research on the use of regenerative medicine for the cornea in human patients. Methods: A systematic literature search of MEDLINE and the Cochrane Library was performed in May 2020. Results: Forty-two articles were identified. Thirty-eight of those articles focused on the treatment for limbal stem cell deficiency (LSCD), of which 17 articles involved autologous cultured limbal epithelial cell sheet transplantation (CLET), 13 involved allogeneic CLET, and 14 involved autologous cultured oral mucosal epithelial cell sheet transplantation (COMET). For autologous CLET, the median ocular surface reconstruction rate, visual recovery rate, incidence of immunologic rejection, infectious keratitis, and ocular hypertension/glaucoma were 74.1%, 54.5%, 0%, 4.6%, and 6.3%, respectively. For allogeneic CLET, they were 71.4%, 71.4%, 7.1%, 12.0%, and 7.1%, respectively. For autologous COMET, they were 66.7%, 66.7%, 0%, 5.3%, and 8.1%, respectively. Systemic immunosuppressants and steroid medications were predominantly used following allogeneic CLET, whereas they were not routinely used after autologous CLET. Three studies focused on the treatment of keratoconus using autologous adipose-derived adult stem cells and reported no marked adverse events. One study reported on the treatment of bullous keratopathy using allogeneic cultured corneal endothelial cells. All patients achieved an endothelial cell density of >500 cells, and the corrected distance visual acuity improved in 82% of the treated eyes. Conclusions: The results show that regenerative medicine for the cornea demonstrated a satisfactory efficacy and safety. Through translational research, we are expecting to establish a new treatment for waiting patients. [ABSTRACT FROM AUTHOR]