The Association Between Metformin Use and New-Onset ICD Coding of Geographic Atrophy.

Purpose: Metformin has been suggested to protect against the development of age-related macular degeneration (AMD) in multiple observational studies. However, the association between metformin and geographic atrophy (GA), a debilitating subtype of AMD, has not been analyzed. Methods: We conducted a case-control study of patients ages 60 years and older with new-onset International Classification of Diseases (ICD) coding of GA in the Merative MarketScan Commercial and Medicare Databases between 2017 and 2021. Cases were matched with propensity scores estimated by age, region, hypertension, and Charlson Comorbidity Index to a control without GA of the same year. Exposure to metformin was assessed for cases and controls in the year prior to their index visit. Conditional multivariable logistic regression, adjusting for AMD risk factors, was used to calculate odd ratios and 95% confidence intervals (CIs). This study design and analysis were repeated in a sample of patients without diabetes. Results: In the full sample, we identified 10,505 cases with GA and 10,502 matched controls without GA. In total, 1149 (10.9%) cases and 1277 (12.2%) controls were exposed to metformin, and in multivariable regression, metformin decreased the odds of new-onset ICD coding of GA by 12% (95% CI, 0.79-0.99). In the sample of patients without diabetes, we identified 7611 cases with GA and 7608 matched controls without GA. Twenty-nine (0.4%) cases and 63 (0.8%) controls were exposed to metformin, and in multivariable regression, metformin decreased the odds of new-onset ICD coding of GA by 47% (95% CI, 0.33-0.83). Conclusions: Metformin may hold promise as a noninvasive, alternative agent to prevent the development of GA. This finding is notable due to shortcomings in recently approved therapeutics for GA and metformin's overall ease of use and few adverse effects. Additional studies are required to explore our findings further and motivate a clinical trial.

[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.

INTERACTIONS OF METFORMIN AND OTHER MEDICATIONS IN REDUCING THE ODDS OF AGE-RELATED MACULAR DEGENERATION IN A COHORT OF PATIENTS WITH DIABETES.

PURPOSE: A previous study from our group demonstrated protective effects of the use of metformin in the odds of developing age-related macular degeneration (AMD). This is a subgroup analysis in a cohort of patients with diabetes to assess the interaction of metformin and other medications in protecting diabetic patients against developing AMD. METHODS: This is a case-control analysis using data from the Merative MarketScan Commercial and Medicare databases. Patients were 55 years and older with newly diagnosed AMD and matched to controls. We performed multivariable conditional logistic regressions, which adjusted for known risk factors of AMD and tested multiple interaction effects between metformin and 1) insulin, 2) sulfonylureas, 3) glitazones, 4) meglitinides, and 5) statins. RESULTS: The authors identified 81,262 diabetic cases and 79,497 diabetic controls. Metformin, insulin, and sulfonylureas demonstrated independent protective effects against AMD development. Sulfonylureas in combination with metformin demonstrated further decreased odds of AMD development compared with metformin alone. The other medication group (exenatide, sitagliptin, and pramlintide) slightly increased the odds of developing AMD when taken alone, but the combination with metformin alleviated this effect. CONCLUSION: The authors believe that their results bring them one step closer to finding an optimal effective hypoglycemic regimen that also protects against AMD development in diabetic patients.

A novel lipophenol quercetin derivative to prevent macular degeneration: Intravenous and oral formulations for preclinical pharmacological evaluation.

Drugs with properties against oxidative and carbonyl stresses are potential candidates to prevent dry age-related macular degeneration (Dry-AMD) and inherited Stargardt disease (STGD1). Previous studies have demonstrated the capacity of a new lipophenol drug: 3-O-DHA-7-O-isopropyl-quercetin (Q-IP-DHA) to protect ARPE19 and primary rat RPE cells respectively from A2E toxicity and under oxidative and carbonyl stress conditions. In this study, first, a new methodology has been developed to access gram scale of Q-IP-DHA. After classification of the lipophenol as BCS Class IV according to physico-chemical and biopharmaceutical properties, an intravenous formulation with micelles (M) and an oral formulation using lipid nanocapsules (LNC) were developed. M were formed with Kolliphor® HS 15 and saline solution 0.9 % (mean size of 16 nm, drug loading of 95 %). The oral formulation was optimized and successfully allowed the formation of LNC (25 nm, 96 %). The evaluation of the therapeutic potency of Q-IP-DHA was performed after IV administration of micelles loaded with Q-IP-DHA (M-Q-IP-DHA) at 30 mg/kg and after oral administration of LNC loaded with Q-IP-DHA (LNC-Q-IP-DHA) at 100 mg/kg in mice. Results demonstrated photoreceptor protection after induction of retinal degeneration by acute light stress making Q-IP-DHA a promising preventive candidate against dry-AMD and STGD1.

Clinical effectiveness of screening for age-related macular degeneration: A systematic review.

INTRODUCTION: Age-related macular degeneration (AMD) is an eye disease that occurs in patients over 50 years old. Early diagnosis enables timely treatment to stabilize disease progression. However, the fact that the disease is asymptomatic in its early stages can delay treatment until it progresses. As such, screening in specific contexts can be an early detection tool to reduce the clinical and social impact of the disease. OBJECTIVE: Assess the effectiveness of screening methods for early detection of AMD in adults aged 50 years or older. METHODS: A systematic review of comparative observational studies on AMD screening methods in those aged 50 years or older, compared with no screening or any other strategy. A literature search was conducted in the MEDLINE (via PubMed), Embase, Cochrane Library and Lilacs database. RESULTS: A total of 5,290 studies were identified, three of which met the inclusion criteria and were selected for the systematic review. A total of 8,733 individuals (16,780 eyes) were included in the analysis. The screening methods assessed were based on optical coherence tomography (OCT) compared with color fundus photography, and OCT and telemedicine testing compared to a standard eye exam. CONCLUSION: The systematized data are limited and only suggest satisfactory performance in early screening of the population at risk of developing AMD. OCT and the telemedicine technique showed promising results in AMD screening. However, methodological problems were identified in the studies selected and the level of evidence was considered low.

Antioxidant vitamin and mineral supplements for slowing the progression of age-related macular degeneration.

BACKGROUND: Age-related macular degeneration (AMD) is a degenerative condition of the back of the eye that occurs in people over the age of 50 years. Antioxidants may prevent cellular damage in the retina by reacting with free radicals that are produced in the process of light absorption. Higher dietary levels of antioxidant vitamins and minerals may reduce the risk of progression of AMD. This is the third update of the review. OBJECTIVES: To assess the effects of antioxidant vitamin and mineral supplements on the progression of AMD in people with AMD. SEARCH METHODS: We searched CENTRAL, MEDLINE, Embase, one other database, and three trials registers, most recently on 29 November 2022. SELECTION CRITERIA: We included randomised controlled trials (RCTs) that compared antioxidant vitamin or mineral supplementation to placebo or no intervention, in people with AMD. DATA COLLECTION AND ANALYSIS: We used standard methods expected by Cochrane. MAIN RESULTS: We included 26 studies conducted in the USA, Europe, China, and Australia. These studies enroled 11,952 people aged 65 to 75 years and included slightly more women (on average 56% women). We judged the studies that contributed data to the review to be at low or unclear risk of bias. Thirteen studies compared multivitamins with control in people with early and intermediate AMD. Most evidence came from the Age-Related Eye Disease Study (AREDS) in the USA. People taking antioxidant vitamins were less likely to progress to late AMD (odds ratio (OR) 0.72, 95% confidence interval (CI) 0.58 to 0.90; 3 studies, 2445 participants; moderate-certainty evidence). In people with early AMD, who are at low risk of progression, this means there would be approximately four fewer cases of progression to late AMD for every 1000 people taking vitamins (one fewer to six fewer cases). In people with intermediate AMD at higher risk of progression, this corresponds to approximately 78 fewer cases of progression for every 1000 people taking vitamins (26 fewer to 126 fewer). AREDS also provided evidence of a lower risk of progression for both neovascular AMD (OR 0.62, 95% CI 0.47 to 0.82; moderate-certainty evidence) and geographic atrophy (OR 0.75, 95% CI 0.51 to 1.10; moderate-certainty evidence), and a lower risk of losing 3 or more lines of visual acuity (OR 0.77, 95% CI 0.62 to 0.96; moderate-certainty evidence). Low-certainty evidence from one study of 110 people suggested higher quality of life scores (measured with the Visual Function Questionnaire) in treated compared with non-treated people after 24 months (mean difference (MD) 12.30, 95% CI 4.24 to 20.36). In exploratory subgroup analyses in the follow-on study to AREDS (AREDS2), replacing beta-carotene with lutein/zeaxanthin gave hazard ratios (HR) of 0.82 (95% CI 0.69 to 0.96), 0.78 (95% CI 0.64 to 0.94), 0.94 (95% CI 0.70 to 1.26), and 0.88 (95% CI 0.75 to 1.03) for progression to late AMD, neovascular AMD, geographic atrophy, and vision loss, respectively. Six studies compared lutein (with or without zeaxanthin) with placebo and one study compared a multivitamin including lutein/zeaxanthin with multivitamin alone. The duration of supplementation and follow-up ranged from six months to five years. Most evidence came from the AREDS2 study in the USA; almost all participants in AREDS2 also took the original AREDS supplementation formula. People taking lutein/zeaxanthin may have similar or slightly reduced risk of progression to late AMD (RR 0.94, 95% CI 0.87 to 1.01), neovascular AMD (RR 0.92, 95% CI 0.84 to 1.02), and geographic atrophy (RR 0.92, 95% CI 0.80 to 1.05) compared with control (1 study, 4176 participants, 6891 eyes; low-certainty evidence). A similar risk of progression to visual loss of 15 or more letters was seen in the lutein/zeaxanthin and control groups (RR 0.98, 95% CI 0.91 to 1.05; 6656 eyes; low-certainty evidence). Quality of life (Visual Function Questionnaire) was similar between groups (MD 1.21, 95% CI -2.59 to 5.01; 2 studies, 308 participants; moderate-certainty evidence). One study in Australia randomised 1204 people to vitamin E or placebo with four years of follow-up; 19% of participants had AMD. The number of late AMD events was low (N = 7) and the estimate of effect was uncertain (RR 1.36, 95% CI 0.31 to 6.05; very low-certainty evidence). There was no evidence of any effect of treatment on visual loss (RR 1.04, 95% CI 0.74 to 1.47; low-certainty evidence). There were no data on neovascular AMD, geographic atrophy, or quality of life. Five studies compared zinc with placebo. Evidence largely drawn from the largest study (AREDS) found a lower progression to late AMD over six years (OR 0.83, 95% CI 0.70 to 0.98; 3 studies, 3790 participants; moderate-certainty evidence), neovascular AMD (OR 0.76, 95% CI 0.62 to 0.93; moderate-certainty evidence), geographic atrophy (OR 0.84, 95% CI 0.64 to 1.10; moderate-certainty evidence), or visual loss (OR 0.87, 95% CI 0.75 to 1.00; 2 studies, 3791 participants; moderate-certainty evidence). There were no data on quality of life. Gastrointestinal symptoms were the main reported adverse effect. In AREDS, zinc was associated with a higher risk of genitourinary problems in men, but no difference was seen between high- and low-dose zinc groups in AREDS2. Most studies were too small to detect rare adverse effects. Data from larger studies (AREDS/AREDS2) suggested there may be little or no effect on mortality with multivitamin (HR 0.87, 95% CI 0.60 to 1.25; low-certainty evidence) or lutein/zeaxanthin supplementation (HR 1.06, 95% CI 0.87 to 1.31; very low-certainty evidence), but confirmed the increased risk of lung cancer with beta-carotene, mostly in former smokers. AUTHORS' CONCLUSIONS: Moderate-certainty evidence suggests that antioxidant vitamin and mineral supplementation (AREDS: vitamin C, E, beta-carotene, and zinc) probably slows down progression to late AMD. People with intermediate AMD have a higher chance of benefiting from antioxidant supplements because their risk of progression is higher than people with early AMD. Although low-certainty evidence suggested little effect with lutein/zeaxanthin alone compared with placebo, exploratory subgroup analyses from one large American study support the view that lutein/zeaxanthin may be a suitable replacement for the beta-carotene used in the original AREDS formula.

[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.

Association of Metformin and Other Diabetes Medication Use and the Development of New-Onset Dry Age-Related Macular Degeneration: A Case-Control Study.

Purpose: To investigate if metformin use is associated with decreased odds of developing new non-neovascular ("dry") age-related macular degeneration (AMD). Methods: Case-control study examining 194,135 cases with diagnoses of new-onset AMD between 2008 and 2017 and 193,990 matched controls in the Merative MarketScan Research Databases. The diabetic subgroup included 49,988 cases and 49,460 controls. Multivariable conditional logistic regressions identified the risks of exposures on the development of dry AMD. Main outcome measures were odds ratios (ORs) of developing dry AMD with metformin use. Results: In multivariable conditional logistic regression, any metformin use was associated with decreased odds of developing dry AMD (OR = 0.97; 95% confidence interval [CI], 0.95-0.99). This protective effect was noted for cumulative 2-year doses of metformin of 1 to 270 g (OR = 0.93; 95% CI, 0.90-0.97) and 271 to 600 g (OR = 0.92; 95% CI, 0.89-0.96). In a diabetic subgroup, metformin use below 601 g per 2 years decreased the odds of developing dry AMD (1-270 g: OR = 0.95; 95% CI, 0.91-0.99; 271-600 g: OR = 0.92; 95% CI, 0.89-0.96). Unlike in diabetic patients with diabetic retinopathy, diabetic patients without diabetic retinopathy had decreased odds of developing dry AMD with any metformin use (OR = 0.97; 95% CI, 0.94-0.998) and cumulative two-year doses of 1 to 270 g (OR 0.96; 95% CI, 0.91-0.998) and 271 to 600 g (OR = 0.92; 95% CI, 0.88-0.96). Conclusions: Metformin use was associated with decreased odds of developing dry AMD. The protective effect was observed for cumulative 2-year doses below 601 g. In diabetics, this association persisted, specifically in those without diabetic retinopathy. Therefore, metformin may be a strategy to prevent development of dry AMD.

Lutein and zeaxanthin - radio- and chemoprotective properties. Mechanism and possible use.

Lutein and zeaxanthin are naturally occurring xanthophylls, mainly present in green, leafy vegetables and egg's yolk. Their presence is connected with blue spectrum light absorbance, including UV. This property, and fact, that these xanthophylls are accumulated by human eye's macula, leads to eye's protective functions of them including protection from age-related macular degeneration (AMD). Also, antioxidative features of lutein and zeaxanthin are boosting overall health of human body. Numerous studies proves anti-inflammatory and protective attributes of these compounds, based on many, different mechanisms. One of them is regulating redox potential in cells, and impact on expression of linked genes. In preventing of eye diseases, an important gene that is regulated by lutein and zeaxanthin is the Nrf2 gene, whose increased activity leads to optimizing the cellular response to reactive oxygen species (ROS) and preventing related diseases. Other research confirms antiproliferative properties of mentioned compounds in case of certain human cancer cell lines. There are e.g.: HepG2 (hepatitis cancer), MCF-7 (breast cancer), which treated in vitro with lutein solution showed reduction of cell growth. Lutein alone, during in vivo studies conducted on mice, exhibited also radioprotective properties, positively affecting the vitality of animals. Lutein provides also increasing of tolerance to UV radiation, reducing inflammatory processes in the skin and preventing oncogenesis. Low intake of lutein and zeaxanthin, associated with "western diet", rich in simple carbohydrates and processed food, common in developed countries, including Poland, is linked with diabetes and obesity incidence. Assuming, lutein and zeaxanthin significantly affect the well-being of the human body, and their appropriate amount in diet can help reduce risk of many diseases. For supplementation, the optimized dosage of these xanthophylls includes doses of 10 mg for lutein and 2 mg for zeaxanthin, and it is recommended to consume along with fats or meals rich in fats.

Association of Plasma Vitamins and Carotenoids, DNA Methylation of LCAT, and Risk of Age-Related Macular Degeneration.

Dysregulation of lipid metabolism has been implicated in age-related macular degeneration (AMD), the leading cause of blindness among the elderly. Lecithin cholesterol acyltransferase (LCAT) is an important enzyme responsible for lipid metabolism, which could be regulated by DNA methylation during the development of various age-related diseases. This study aimed to assess the association between LCAT DNA methylation and the risk of AMD, and to examine whether plasma vitamin and carotenoid concentrations modified this association. A total of 126 cases of AMD and 174 controls were included in the present analysis. LCAT DNA methylation was detected by quantitative real-time methylation-1specific PCR (qMSP). Circulating vitamins and carotenoids were measured using reversed-phase high-performance liquid chromatography (RP-HPLC). DNA methylation of LCAT was significantly higher in patients with AMD than those in the control subjects. After multivariable adjustment, participants in the highest tertile of LCAT DNA methylation had a 5.37-fold higher risk (95% CI: 2.56, 11.28) of AMD compared with those in the lowest tertile. Each standard deviation (SD) increment of LCAT DNA methylation was associated with a 2.23-fold (95% CI: 1.58, 3.13) increased risk of AMD. There was a J-shaped association between LCAT DNA methylation and AMD risk (Pnon-linearity = 0.03). Higher concentrations of plasma retinol and ß-cryptoxanthin were significantly associated with decreased levels of LCAT DNA methylation, with the multivariate-adjusted ß coefficient being -0.05 (95% CI: -0.08, -0.01) and -0.25 (95% CI: -0.42, -0.08), respectively. In joint analyses of LCAT DNA methylation and plasma vitamin and carotenoid concentrations, the inverse association between increased LCAT DNA methylation and AMD risk was more pronounced among participants who had a lower concentration of plasma retinol and ß-cryptoxanthin. These findings highlight the importance of comprehensively assessing LCAT DNA methylation and increasing vitamin and carotenoid status for the prevention of AMD.

Repurposing medications for treatment of age-related macular degeneration: Insights from novel approaches to data mining.

The economic and visual burdens associated with age-related macular degeneration (AMD) are expected to significantly increase in the coming years. As of now, interventions to delay or prevent AMD are limited. Hence, there is an urgent and unmet need to expand our therapeutic tools for AMD in a manner, that is, both efficient and cost-effective. In this review, we consider the idea of drug repurposing, in which existing medications with other indications can be re-imagined for treating AMD. We detail the results of several population-level studies that have shown associations between several candidates and decreased risk of AMD development or progression. Such candidates include the more extensively studied metformin and statins, in addition to recently identified candidates fluoxetine and l-DOPA (levodopa) that show promise. We then briefly explore results from an advanced bioinformatics study, which provides further evidence that existing medications are associated with AMD risk genes. Many of these candidates warrant further study in prospective, clinical trials, where their potential causal relationships with AMD can be thoroughly assessed.

Chemiexcitation and melanin in photoreceptor disc turnover and prevention of macular degeneration.

Age-related macular degeneration, Stargardt disease, and their Abca4-/- mouse model are characterized by accelerated accumulation of the pigment lipofuscin, derived from photoreceptor disc turnover in the retinal pigment epithelium (RPE); lipofuscin accumulation and retinal degeneration both occur earlier in albino mice. Intravitreal injection of superoxide (O2•-) generators reverses lipofuscin accumulation and rescues retinal pathology, but neither the target nor mechanism is known. Here we show that RPE contains thin multi-lamellar membranes (TLMs) resembling photoreceptor discs, which associate with melanolipofuscin granules in pigmented mice but in albinos are 10-fold more abundant and reside in vacuoles. Genetically over-expressing tyrosinase in albinos generates melanosomes and decreases TLM-related lipofuscin. Intravitreal injection of generators of O2•- or nitric oxide (•NO) decreases TLM-related lipofuscin in melanolipofuscin granules of pigmented mice by ~50% in 2 d, but not in albinos. Prompted by evidence that O2•- plus •NO creates a dioxetane on melanin that excites its electrons to a high-energy state (termed "chemiexcitation"), we show that exciting electrons directly using a synthetic dioxetane reverses TLM-related lipofuscin even in albinos; quenching the excited-electron energy blocks this reversal. Melanin chemiexcitation assists in safe photoreceptor disc turnover.

ß-secretase 1 overexpression by AAV-mediated gene delivery prevents retina degeneration in a mouse model of age-related macular degeneration.

We reported previously that ß-site amyloid precursor protein cleaving enzyme (BACE1) is strongly expressed in the normal retina and that BACE1-/- mice develop pathological phenotypes associated with age-related macular degeneration (AMD). BACE1 expression is increased within the neural retina and retinal pigment epithelium (RPE) in AMD donor eyes suggesting that increased BACE1 is compensatory. We observed that AAV-mediated BACE1 overexpression in the RPE was maintained up to 6 months after AAV1-BACE1 administration. No significant changes in normal mouse visual function or retinal morphology were observed with low-dose vector while the high-dose vector demonstrated some early pathology which regressed with time. No increase in ß-amyloid was observed. BACE1 overexpression in the RPE of the superoxide dismutase 2 knockdown (SOD2 KD) mouse, which exhibits an AMD-like phenotype, prevented loss of retinal function and retinal pathology, and this was sustained out to 6 months. Furthermore, BACE1 overexpression was able to inhibit oxidative stress, microglial changes, and loss of RPE tight junction integrity (all features of AMD) in SOD2 KD mice. In conclusion, BACE1 plays a key role in retina/RPE homeostasis, and BACE1 overexpression offers a novel therapeutic target in the treatment of AMD.

Dietary nutrient intake and cognitive function in the Age-Related Eye Disease Studies 1 and 2.

INTRODUCTION: The objective was to analyze associations between dietary intake of multiple nutrients and altered cognitive function and/or decline. METHODS: Observational analyses of participants (n = 6334) in two randomized trials of nutritional supplements for age-related macular degeneration: Age-Related Eye Disease Study (AREDS) and AREDS2. RESULTS: In AREDS, for 4 of 38 nutrients examined, higher intake quintiles were significantly associated with decreased risk of cognitive impairment on the Modified Mini-Mental State test (<80): ß-carotene, copper, docosahexaenoic acid, and insoluble fiber. In AREDS2, for 13 of 44 nutrients, higher intake quintiles were associated with decreased risk on the Telephone Interview Cognitive Status-Modified (<30). Rate of cognitive decline over up to 10 years was not significantly different with higher intake of any nutrient. DISCUSSION: Higher dietary intake of multiple nutrients, including specific vitamins, minerals, carotenoids, fatty acids, and fiber, was associated with lower risk of cognitive impairment but not slower decline in cognitive function.

Chitooligosaccharides Derivatives Protect ARPE-19 Cells against Acrolein-Induced Oxidative Injury.

Age-related macular degeneration (AMD) is the leading cause of vision loss among the elderly. The progression of AMD is closely related to oxidative stress in the retinal pigment epithelium (RPE). Here, a series of chitosan oligosaccharides (COSs) and N-acetylated derivatives (NACOSs) were prepared, and their protective effects on an acrolein-induced oxidative stress model of ARPE-19 were explored using the MTT assay. The results showed that COSs and NACOs alleviated APRE-19 cell damage induced by acrolein in a concentration-dependent manner. Among these, chitopentaose (COS-5) and its N-acetylated derivative (N-5) showed the best protective activity. Pretreatment with COS-5 or N-5 could reduce intracellular and mitochondrial reactive oxygen species (ROS) production induced by acrolein, increase mitochondrial membrane potential, GSH level, and the enzymatic activity of SOD and GSH-Px. Further study indicated that N-5 increased the level of nuclear Nrf2 and the expression of downstream antioxidant enzymes. This study revealed that COSs and NACOSs reduced the degeneration and apoptosis of retinal pigment epithelial cells by enhancing antioxidant capacity, suggesting that they have the potential to be developed into novel protective agents for AMD treatment and prevention.

The relationship between dietary patterns and ophthalmic disease.

PURPOSE OF REVIEW: There is a rising interest in the impact of diet on the pathogenesis of common ophthalmic conditions. The purpose of this review is to summarize the potential preventive and therapeutic power of dietary interventions described in recent basic science and epidemiological literature. RECENT FINDINGS: Basic science investigations have elucidated a variety of mechanisms by which diet may impact ophthalmic disease, particularly through its action on chronic oxidative stress, inflammation and macular pigmentation. Epidemiologic investigations have shown the real-world influence of diet on the incidence and progression of a number of ophthalmic diseases, particularly cataract, age-related macular degeneration (AMD) and diabetic retinopathy. A large observational cohort study found a 20% reduction in the incidence of cataract among vegetarians compared with nonvegetarians. Two recent systematic reviews found that higher adherence to Mediterranean dietary patterns was associated with a decreased risk of progression of AMD to later stages. Finally, large meta-analyses found that patients following plant-based and Mediterranean diets had significant reductions of mean haemoglobin A1c scores and incidence of diabetic retinopathy as compared with controls. SUMMARY: There is a significant and growing body of evidence that Mediterranean diet and plant-based diets - those that maximize fruits, vegetables, legumes, whole grains and nuts; and that minimize animal products and processed foods - help prevent vision loss from cataract, AMD and diabetic retinopathy. These diets may hold benefits for other ophthalmic conditions, as well. Nevertheless, there is a need for further randomized, controlled and longitudinal studies in this area.