Sickle Eye Project: a cross-sectional, non-interventional study of the prevalence of visual impairment due to sickle cell retinopathy and maculopathy in the UK.

INTRODUCTION: Sickle cell disease (SCD) is one of the most common genetic disorders in the UK, with over 15 000 people affected. Proliferative sickle cell retinopathy (SCR) is a well-described complication of SCD and can result in significant sight loss, although the prevalence in the UK is not currently known. There are currently no national screening guidelines for SCR, with wide variations in the management of the condition across the UK. METHODS AND ANALYSIS: The Sickle Eye Project is an epidemiological, cross-sectional, non-interventional study to determine the prevalence of visual impairment due to SCR and/or maculopathy in the UK. Haematologists in at least 16 geographically dispersed hospitals in the UK linked to participating eye clinics will offer study participation to consecutive patients meeting the inclusion criteria attending the sickle cell clinic. The following study procedures will be performed: (a) best corrected visual acuity with habitual correction and pinhole, (b) dilated slit lamp biomicroscopy and funduscopy, (c) optical coherence tomography (OCT), (d) OCT angiography where available, (e) ultrawide fundus photography, (f) National Eye Institute Visual Function Questionnaire-25 and (g) acceptability of retinal screening questionnaire. The primary outcome is the proportion of people with SCD with visual impairment defined as logarithm of the minimum angle of resolution ≥0.3 in at least one eye. Secondary outcomes include the prevalence of each stage of SCR and presence of maculopathy by age and genotype; correlation of stage of SCR and maculopathy to severity of SCD; the impact of SCR and presence of maculopathy on vision-related quality of life; and the acceptability to patients of routine retinal imaging for SCR and maculopathy. ETHICS AND DISSEMINATION: Ethical approval was obtained from the South Central-Oxford A Research Ethics Committee (REC 23/SC/0363). Findings will be reported through academic journals in ophthalmology and haematology.

Nighttime Outdoor Artificial Light and Risk of Age-Related Macular Degeneration.

Importance: Light pollution's impact on human health is increasingly recognized, but its link to exudative age-related macular degeneration (EAMD) remains unclear. Objective: To investigate the association between exposure to outdoor artificial light at night (OALAN) and the risk of incident EAMD. Design, Setting, and Participants: In this nationwide population-based case-control study, all individuals 50 years or older with newly diagnosed EAMD between January 1, 2010, and December 31, 2011, were identified with reference to the Korean National Health Insurance Service registration program database for rare and intractable diseases. Birth year- and sex-matched controls (with no EAMD diagnosis until 2020) were selected at a 1:30 ratio. Data were acquired from May 1 to December 31, 2021, and analyzed from June 1 to November 30, 2022. Exposures: Mean levels of OALAN at participants' residential addresses during 2008 and 2009 were estimated using time-varying satellite data for a composite view of persistent nighttime illumination at an approximate scale of 1 km2. Main Outcomes and Measures: The hazard ratios (HRs) and 95% CIs of the association between residential OALAN and risk of incident EAMD were determined based on maximum likelihood estimation after adjusting for sociodemographic characteristics, comorbidities, and area-level risk factors (ie, nighttime traffic noise and particulate matter of aerodynamic diameter ≤10 µm in each participant's administrative district of residence). Results: A total of 126 418 participants were included in the analysis (mean [SD] age, 66.0 [7.9] years; 78 244 men [61.9%]). Of these, 4078 were patients with newly diagnosed EAMD and 122 340 were EAMD-free matched controls. In fully adjusted models, an IQR (55.8 nW/cm2/sr) increase in OALAN level was associated with an HR of 1.67 (95% CI, 1.56-1.78) for incident EAMD. The exposure-response curve demonstrated a nonlinear, concave upward slope becoming more pronounced at higher levels of light exposure (ie, at approximately 110 nW/cm2/sr). In a subgroup analysis, an IQR increase in OALAN was associated with increased risk of incident EAMD in urban areas (HR, 1.46 [95% CI, 1.33-1.61]) but not in rural areas (HR, 1.01 [95% CI, 0.84-1.22]). Conclusions and Relevance: In this nationwide population-based case-control study, higher levels of residential OALAN were associated with an increased risk of incident EAMD. Future studies with more detailed information on exposure, individual adaptive behaviors, and potential mediators are warranted.

Age-Related Macular Degeneration: A Review.

Importance: Age-related macular degeneration (AMD) affects approximately 20 million people in the US and 196 million people worldwide. AMD is a leading cause of severe vision impairment in older people and is expected to affect approximately 288 million people worldwide by 2040. Observations: Older age, genetic factors, and environmental factors, such as cigarette smoking, are associated with development of AMD. AMD occurs when extracellular deposits accumulate in the outer retina, ultimately leading to photoreceptor degeneration and loss of central vision. The late stages of AMD are characterized by outer retinal atrophy, termed geographic atrophy, or neovascularization associated with subretinal and/or intraretinal exudation, termed exudative neovascular AMD. The annual incidence of AMD ranges from 0.3 per 1000 in people who are aged 55 to 59 years to 36.7 per 1000 in people aged 90 years or older. The estimated heritability of late-stage AMD is approximately 71% (95% CI, 18%-88%). Long-term prospective cohort studies show a significantly higher AMD incidence in people who smoke more than 20 cigarettes per day compared with people who never smoked. AMD is diagnosed primarily with clinical examination that includes a special lens that focuses light of the slit lamp through the pupil. Exudative neovascular AMD is best identified using angiography and by optical coherence tomography. Individuals with AMD who take nutritional supplements consisting of high-dose vitamin C, vitamin E, carotenoids, and zinc have a 20% probability to progress to late-stage AMD at 5 years vs a 28% probability for those taking a placebo. In exudative neovascular AMD, 94.6% of patients receiving monthly intravitreal anti-vascular endothelial growth factor (anti-VEGF) injections experience less than a 15-letter visual acuity loss after 12 months compared with 62.2% receiving sham treatment. Conclusions and Relevance: The prevalence of AMD is anticipated to increase worldwide to 288 million individuals by 2040. Intravitreally administered anti-VEGF treatment is first-line therapy for exudative neovascular AMD.

[Blue light and intraocular lenses (IOLs): Beliefs and realities]. / Lumière bleue et implants intraoculaires : croyances et réalités.

The first intraocular lenses (IOLs) used for cataract surgery transmitted both ultraviolet (UV) radiation and visible light to the retina. Colorless UV-blocking IOLs were introduced and rapidly adopted in the 1980s. Yellow-tinted blue-blocking (also known as blue-filtering) IOLs were marketed in the early 1990s. Blue-blocking IOLs were intended to simulate age-related crystalline lens yellowing to reduce the cyanopsia that some patients experienced after cataract surgery. When blue-filtering IOLs were introduced in North America, however, blue-blocking chromophores were advocated as a way to protect patients from age-related macular degeneration (AMD) despite the lack of evidence that normal environmental light exposure causes AMD. The "blue light hazard" is a term that describes the experimental finding that acute, abnormally intense light exposures are potentially more phototoxic to the retina when short rather than long wavelengths are used. Thus, in brief exposures to intense light sources such as welding arcs, ultraviolet radiation is more hazardous than blue light, which is more hazardous than longer wavelength green or red light. International commissions have cautioned that the blue light hazard does not apply to normal indoor or outdoor light exposures. Nonetheless, the hazard is used for commercial purposes to suggest misleadingly that ambient environmental light can cause acute retinal phototoxicity and increase the risk of AMD. Very large epidemiological studies show that blue-blocking IOLs do not reduce the risk or progression of AMD. Additionally, blue-filtering IOLs or spectacles cannot decrease glare disability, because they decrease image and glare illuminance in the same proportion. Blue light is essential for older adults' scotopic photoreception needed to reduce the risk of nighttime falling and related injuries. It is also critical for circadian photoreception that is essential for good health, sleep and cognitive performance. Unfortunately, age-related pupillary miosis, retinal rod and ganglion cell photoreceptor degeneration and decreased outdoor activity all reduce the amount of healthful blue light available to older adults. Blue-restricting IOLs further reduce the available blue light at a time when older adults need it most. Patients and ophthalmologists are exposed to hypothesis-based advertisements for blue-filtering optical devices that suppress short wavelength light critical for vision in dim lighting and for good physical and mental health. Spectacle and intraocular lens selections should be based on scientific fact, not conjecture. Ideal IOLs should improve photoreception rather than limit it permanently. Practice efficiency, surgical convenience and physician-manufacturer relationships may eliminate a patient's opportunity to choose between colorless blue-transmitting IOLs and yellow-tinted, blue-restricting IOLs. Cataract surgeons ultimately determine whether their patients have the opportunity to make an informed choice about their future photoreception.

PREVALENCE AND RISK FACTORS OF AGE-RELATED MACULAR DEGENERATION FEATURES AMONG PILOTS.

PURPOSE: To investigate the prevalence and risk factors of age-related macular degeneration features among pilots of Republic of Korea Air Force. METHODS: This retrospective, cross-sectional study was performed with a total of 2781 Republic of Korea Air Force pilots who underwent regular medical examinations between 2020 and 2021. Age-related macular degeneration features were determined and graded by fundus photographs. Risk factors were identified with logistic regression analysis in odds ratio (OR) and 95% confidence interval (CI). RESULTS: The prevalence was 12.9% in the Republic of Korea Air Force pilots and 35.2% in those older than 50 years. Pilots with age-related macular degeneration features were positively associated with age (OR: 1.082, CI: 1.067-1.096, P < 0.001), male sex (OR: 0.229, CI: 0.056-0.939, P = 0.041), smoking (OR: 1.027, CI: 1.008-1.047, P = 0.006), flight time (OR: 1.004, CI: 1.003-1.005, P < 0.001), total cholesterol (OR: 1.004, CI: 1.000-1.007, P = 0.033), and low-density lipoprotein (OR: 1.005, CI: 1.001-1.008, P = 0.011). Aircraft type was also identified as a risk factor (OR: 0.617, CI: 0.460-0.827 for carrier, OR: 0.572, CI: 0.348-0.940 for helicopter, P = 0.002), with fighter pilots having a higher risk than carrier and helicopter pilots. The results were similar for pilots older than 50 years. CONCLUSION: The prevalence of age-related macular degeneration features in Republic of Korea Air Force pilots was higher than in other general populations studied. Identified risk factors such as flight time and aircraft type suggest potential occupational risk of age-related macular degeneration in aviators.

LIFETIME AMBIENT ULTRAVIOLET RADIATION EXPOSURE AND INCIDENCE OF AGE-RELATED MACULAR DEGENERATION.

PURPOSE: To investigate the link between lifelong exposure to ultraviolet radiation (UVR) and the development of age-related macular degeneration (AMD). METHODS: The Alienor study is a prospective population-based cohort involving 963 residents of Bordeaux, France, older than 73 years. A subset of 614 participants for advanced AMD and 422 participants for early AMD were included in the analysis. The participants' residential history combined with UVR estimates from the EuroSun satellite were used to estimate the amount of ambient UVR they have been exposed to over their lifetime. Age-related macular degeneration was classified from retinal fundus photographs and spectral domain optical coherence tomography at 2 to 3 years intervals over the 2006 to 2017 period. Associations between cumulative exposure to ultraviolet A, ultraviolet B, and total (total UV) and the incidence of early and advanced AMD were estimated using multivariate Cox models. RESULTS: Intermediate quartiles of total UV, ultraviolet A, and ultraviolet B exposures were associated with a higher risk for incident early AMD (Hazard Ratio [HR] =2.01 [95% confidence interval [CI] = 1.27-3.13], HR = 2.20 [95% CI = 1.38-3.50], HR = 1.79 [95% CI = 1.13-2.80], respectively) as compared with the lower quartile. However, this risk did not further increase in the highest quartiles of exposure. None of the three types of UVR exposure was significantly associated with incident advanced AMD. CONCLUSION: Despite an increased risk with intermediate compared with low UVR exposure, our study cannot confirm a dose-response relationship of UVR exposure with early AMD onset.

Rubus suavissimus S. Lee Extract Alleviates Oxidative Stress and Inflammation in H2O2-Treated Retinal Pigment Epithelial Cells and in High-Fat Diet-Fed Mouse Retinas.

BACKGROUND: Age-related macular degeneration (AMD) is the most common cause of visual disorders in the aged population and is characterized by the formation of retinal pigment epithelium (RPE) deposits and dysfunction/death of the RPE and photoreceptors. It is supposed that both oxidative stress and inflammation play a critical role in the pathogenesis of AMD. The development of therapeutic strategies against oxidative stress and inflammation in AMD is urgently needed. Rubus suavissimus S. Lee (RS), a medicinal plant growing in the southwest region of China, has been used as an herbal tea and medicine for various diseases. METHODS: In this project, we evaluate the therapeutic potential of RS extract for AMD. We prepared RS extracts from dried leaves, which contained the main functional compounds. RESULTS: RS extract significantly increased cell viability, upregulated the expression of antioxidant genes, lowered the generation of malondialdehyde and reactive oxygen species, and suppressed inflammation in H2O2-treated human RPE cells. In the in vivo study, treatment with RS extract attenuated body weight gain, lowered cholesterol and triglyceride levels in the liver and serum, increased antioxidant capacity, and alleviated inflammation in the retina and RPE/choroid of mice fed a high-fat diet. CONCLUSIONS: Our findings suggest that RS extract offers therapeutic potential for treating AMD patients.

Associations Between Autoimmune Disease and the Development of Age-Related Macular Degeneration.

Purpose: The pathogenesis of age-related macular degeneration (AMD) likely implicates the dysregulation of immune response pathways. Several studies demonstrate that the pathogenic elements of AMD resemble those of autoimmune diseases, yet the association between AMD development and most autoimmune diseases remain unexplored. Methods: We conducted a case-control analysis of patients ages 55 and older with new-onset International Classification of Diseases (ICD) coding of dry, wet, or unspecified AMD between 2005 and 2019 in the Merative MarketScan Commercial and Medicare Databases. The diagnosis of an autoimmune disease was defined by an outpatient or inpatient claim with a relevant ICD code in the 12 months before the index visit. Conditional multivariable logistic regression, adjusted for AMD risk factors, was used to calculate odd ratios and 95% confidence intervals. Results: We identified 415,027 cases with new-onset ICD coding for AMD matched with propensity scores to 414,853 controls. In total, 16.1% of cases and 15.9% of controls were diagnosed with any autoimmune disease. The diagnosis of any autoimmune disease did not affect the odds of new-onset ICD coding for AMD in multivariable regression (OR = 1.01; 95% CI, 0.999-1.02). Discoid lupus erythematosus (OR = 1.29; 95% CI, 1.12-1.48), systemic lupus erythematosus (SLE) (OR = 1.21; 95% CI, 1.15-1.27), giant cell arteritis (OR = 1.19; 95% CI, 1.09-1.30), Sjogren's syndrome (OR = 1.17; 95% CI, 1.09-1.26), and Crohn's disease (OR = 1.13; 95% CI, 1.06-1.22) increased the odds of a new-onset ICD coding for AMD. Conclusions: Most autoimmune diseases do not affect the odds of developing AMD but several common autoimmune disorders such as SLE and Crohn's disease were associated with modestly increased odds of AMD. Further studies are needed to validate and investigate the underlying mechanisms of these associations.

PREVALENCE OF AGE-MACULAR DEGENERATION IN PERSONS OF WORKING AGE WHO APPLIED TO PARTICIPATE IN WORK IN ACTION CONDITIONS IONIZING RADIATION: PRELIMINARY RESULTS. / ПОПЕРЕДНІ РЕЗУЛЬТАТИ ДОСЛІДЖЕННЯ ПОШИРЕНОСТІ ВІКОВОЇ МАКУЛЯРНОЇ ДЕГЕНЕРАЦІЇ У ОСІБ ПРАЦЕЗДАТНОГО ВІКУ, ЯКІ ПРЕТЕНДУВАЛИ НА УЧАСТЬ В РОБОТАХ В УМОВАХ ДІЇ ІОНІЗУЮЧОГО ВИПРОМІНЮВАННЯ.

In recent decades, several large-scale epidemiological surveys of the eyes have been conducted to determine the global prevalence of retinal degenerative diseases (for example, the Blue Mountains Eye Study). The results of such studies were evaluated several decades, and the studies themselves required significant material resources. Such large-scale projects have not been carried out in Ukraine.Objective of the work is to study the prevalence of age-related macular degeneration in a pilot group of non-irradiated persons of working age to determine the suitability of using the results for further epidemiological studies in Ukraine. MATERIALS AND METHODS: A retrospective-prospective analysis of the prevalence of degenerative diseases of the retina in a pilot group of persons who underwent an in-depth examination, as they claimed to participate in works in harmful conditions (with ionizing radiation) was carried out. The results of primary ophthalmological examinations of 1,064 people, conducted between January 18, 2007 and October 29, 2009, were randomly selected. The age of the examinees at the time of examination ranged from 18.94 to 67.49 years, the number of persons aged 18 to 30, 30 to 40, and 40 to 50 years was approximately the same. The results of a standardized ophthalmological examination were used. RESULTS: In the pilot group of people in working age, the prevalence of age-related macular degeneration was 196.4 per 1,000 people. Hazard analysis showed that the relative risk of age-related macular degeneration increased with age and was 1.14 (95% CI 1.07-1.21) for individuals aged 30-39 years; in comparison with persons under the age of 30; 1.3 (95% CI 1.21-1.41) - for persons aged 40-49; 1.3 (95% CI 1.18-1.52) - for persons aged 50-59; 1.86 (95% CI 1.0-3.47) - for persons over 60 years of age. The odds ratio (OR) of having age-related macular degeneration for those aged 30-39 years compared with those younger than 30 years was 3.04 (95% CI 1.79-5.15); for persons aged 40-49 years - 5.49 (95% CI 3.31-9.09); for persons aged 50-59 years - 6.04 (95% CI 3.36-10.88); for persons aged 50-59 years - 6.04 (95% CI 3.36-10.88) and for persons older than 60 years - 13.71 (95% CI 3.68-51.15), p in all cases < 0.0001. CONCLUSIONS: It was established that the prevalence of age-related macular degeneration in non-irradiated individuals determined in the pilot group was high and statistically significantly increased with age. It is shown that the results of primary ophthalmological examinations of a pilot group of persons who applied for participation in works in harmful conditions (with ionizing radiation) are suitable for epidemiological studies of the frequency and course of degenerative retinal diseases in persons of working age in Ukraine. The obtained results are important for practical medicine, as they will allow us to assess the prospects needs for medical care in the secondary and tertiary care.

Protective role of IL-17-producing γδ T cells in a laser-induced choroidal neovascularization mouse model.

BACKGROUND: Vision loss in patients with wet/exudative age-related macular degeneration (AMD) is associated with choroidal neovascularization (CNV), and AMD is the leading cause of irreversible vision impairment in older adults. Interleukin-17A (IL-17A) is a component of the microenvironment associated with some autoimmune diseases. Previous studies have indicated that wet AMD patients have elevated serum IL-17A levels. However, the effect of IL-17A on AMD progression needs to be better understood. We aimed to investigate the role of IL-17A in a laser-induced CNV mouse model. METHODS: We established a laser-induced CNV mouse model in wild-type (WT) and IL-17A-deficient mice and then evaluated the disease severity of these mice by using fluorescence angiography. We performed enzyme-linked immunosorbent assay (ELISA) and fluorescence-activated cell sorting (FACS) to analyze the levels of IL-17A and to investigate the immune cell populations in the eyes of WT and IL-17A-deficient mice. We used ARPE-19 cells to clarify the effect of IL-17A under oxidative stress. RESULTS: In the laser-induced CNV model, the CNV lesions were larger in IL-17A-deficient mice than in WT mice. The numbers of γδ T cells, CD3+CD4+RORγt+ T cells, Treg cells, and neutrophils were decreased and the number of macrophages was increased in the eyes of IL-17A-deficient mice compared with WT mice. In WT mice, IL-17A-producing γδ T-cell numbers increased in a time-dependent manner from day 7 to 28 after laser injury. IL-6 levels increased and IL-10, IL-24, IL-17F, and GM-CSF levels decreased in the eyes of IL-17A-deficient mice after laser injury. In vitro, IL-17A inhibited apoptosis and induced the expression of the antioxidant protein HO-1 in ARPE-19 cells under oxidative stress conditions. IL-17A facilitated the repair of oxidative stress-induced barrier dysfunction in ARPE-19 cells. CONCLUSIONS: Our findings provide new insight into the protective effect of IL-17A in a laser-induced CNV model and reveal a novel regulatory role of IL-17A-producing γδ T cells in the ocular microenvironment in wet AMD.

Chinese medicine, Qijudihuang pill, mediates cholesterol metabolism and regulates gut microbiota in high-fat diet-fed mice, implications for age-related macular degeneration.

Background: Traditional Chinese Medicines have been used for thousands of years but without any sound empirical basis. One such preparation is the Qijudihuang pill (QP), a mixture of eight herbs, that has been used in China for the treatment of various conditions including age-related macular degeneration (AMD), the most common cause of blindness in the aged population. In order to explain the mechanism behind the effect of QP, we used an AMD model of high-fat diet (HFD) fed mice to investigate cholesterol homeostasis, oxidative stress, inflammation and gut microbiota. Methods: Mice were randomly divided into three groups, one group was fed with control diet (CD), the other two groups were fed with high-fat-diet (HFD). One HFD group was treated with QP, both CD and the other HFD groups were treated with vehicles. Tissue samples were collected after the treatment. Cholesterol levels in retina, retinal pigment epithelium (RPE), liver and serum were determined using a commercial kit. The expression of enzymes involved in cholesterol metabolism, inflammation and oxidative stress was measured with qRT-PCR. Gut microbiota was analyzed using 16S rRNA sequencing. Results: In the majority of the lipid determinations, analytes were elevated by HFD but this was reversed by QP. Cholesterol metabolism including the enzymes of bile acid (BA) formation was suppressed by HFD but again this was reversed by QP. BAs play a major role in signaling between host and microbiome and this is disrupted by HFD resulting in major changes in the composition of colonic bacterial communities. Associated with these changes are predictions of the metabolic pathway complexity and abundance of individual pathways. These concerned substrate breakdowns, energy production and the biosynthesis of pro-inflammatory factors but were changed back to control characteristics by QP. Conclusion: We propose that the ability of QP to reverse these HFD-induced effects is related to mechanisms acting to lower cholesterol level, oxidative stress and inflammation, and to modulate gut microbiota.

Small-Molecule Drug Repurposing for Counteracting Phototoxic A2E Aggregation.

Despite the well-established role of oxidative stress in the pathogenesis of age-related macular degeneration (AMD), the mechanism underlying phototoxicity remains unclear. Herein, we used a drug repurposing approach to isolate an FDA-approved drug that blocks the aggregation of the photoinducible major fluorophore of lipofuscin, the bis-retinoid N-retinylidene-N-retinylethanolamine (A2E). Our fluorescence-based screening combined with dynamic light scattering (DLS) analysis led to the identification of entacapone as a potent inhibitor of A2E fluorescence and aggregation. The entacapone-mediated inhibition of A2E aggregation blocks its photodegradation and offers photoprotection in A2E-loaded retinal pigment epithelial (RPE) cells exposed to blue light. In-depth mechanistic analysis suggests that entacapone prevents the conversion of toxic aggregates by redirecting A2E into off-pathway oligomers. These findings provide evidence that aggregation contributes to the phototoxicity of A2E.

[Nutrition and age-related macular degeneration]. / Nutrition et dégénérescence maculaire liée à l'âge.

Age-related macular degeneration (AMD) is the leading cause of vision loss in France and in other industrialized countries. AMD affects around 20 % of the population over the age of 80 years. This complex and multifactorial disease involves both genetic susceptibility and environmental factors. Smoking and nutrition are well-known modifiable risk factors for AMD. Numerous studies provide convincing arguments in favor of micronutrients to encourage dietary advice and the prescription of nutritional supplements containing antioxidant vitamins, lutein and omega-3 fatty acids. Attention to modifiable risk factors is of utmost importance to reduce progression to advanced AMD and associated medical and societal burdens.

Diabetes-Related Risk Factors for Exudative Age-Related Macular Degeneration: A Nationwide Cohort Study of a Diabetic Population.

Purpose: The purpose of this study was to identify diabetes-related risk factors for exudative age-related macular degeneration (AMD). Methods: This was a nationwide population-based cohort study using authorized clinical data provided by the Korean National Health Insurance Service. A total of 1,768,018 participants with diabetes over 50 years of age participated in the Korean National Health Screening Program between 2009 and 2012. Data on covariates, including age, sex, income level, systemic comorbidities, behavioral factors, and diabetes-related parameters, including duration of diabetes, use of insulin for diabetes control, number of oral hypoglycemic agents used, and accompanying vision-threatening diabetic retinopathy, were collected from health screening results and claims data. Patients were followed up until December 2018. Incident cases of exudative AMD were identified using registered diagnostic codes from the claims data. The prospective association of diabetes-related parameters with incident exudative AMD was investigated using the multivariable-adjusted Cox proportional hazard model. Results: During an average follow-up period of 5.93 years, 7331 patients were newly diagnosed with exudative AMD. Compared to those who had diabetes for less than 5 years, individuals with diabetes for 5 years or more had a greater risk of future exudative AMD development, with a hazard ratio (95% confidence interval) of 1.13 (1.07-1.18) in the fully adjusted model. Use of insulin for diabetes control and the presence of vision-threatening diabetic retinopathy were also associated with an increased risk of exudative AMD with a hazard ratio (95% confidence interval) of 1.16 (1.07-1.25) and 1.40 (1.23-1.61), respectively. Conclusions: A longer duration of diabetes, administration of insulin for diabetes control, and comorbid vision-threatening diabetic retinopathy were associated with an increased risk of developing exudative AMD.

Dysregulation of Resolvin E1 Metabolism and Signaling in a Light-Damage Model of Age-Related Macular Degeneration.

Resolvin E1 (RvE1) is an eicosapentaenoic acid-derived lipid mediator involved in the resolution of inflammation. Here, we investigated whether RvE1 alterations may occur in an animal model of age-related macular degeneration (AMD). To this end, Sprague Dawley albino rats underwent light damage (LD), and retinas and serum were analyzed immediately or seven days after treatment. Western blot of retinas showed that the RvE1 receptor ChemR23 and the RvE1 metabolic enzymes 5-LOX and COX-2 were unchanged immediately after LD, but they were significantly up-regulated seven days later. Instead, the RvE1 receptor BLT1 was not modulated by LD, and neither was the RvE1 degradative enzyme 15-PGDH. Moreover, ChemR23, 5-LOX, COX-2 and BLT1 were found to be more expressed in the inner retina under all experimental conditions, as observed through ImageJ plot profile analysis. Of note, amacrine cells highly expressed BLT1, while ChemR23 was highly expressed in the activated microglia of the outer retina. ELISA assays also showed that LD rats displayed significantly higher circulating levels and reduced retinal levels of RvE1 compared to controls. Altogether, our data indicate that RvE1 metabolism and signaling are modulated in the LD model, suggesting a potentially relevant role of this pathway in AMD.