Lower Risk Of Age-related Macular Degeneration Research Articles

The relationship between metformin administration and age-related macular degeneration; a systematic review and meta-analysis of observational studies

Introduction: Vision loss due to age-related macular degeneration (AMD) is a major and growing health issue. Given that no definitive treatment is available for AMD, this study aims to evaluate the association between metformin use and AMD risk using a systematic review and meta-analysis approach. Materials and Methods: In this study, databases including ProQuest, PubMed, Web of Science, Cochrane, and Google Scholar search engines were searched without time restriction until April 20, 2024, based on PRISMA statement guidelines. Data were analyzed using STATA 14 software at a significance level of P < 0.05. Results: Overall, metformin administration reduced the risk of AMD (OR: 0.86, 95% CI: 0.80, 0.94). Concerning the dosage, a metformin dose of 1-270 g per 2 years (OR: 0.93, 95% CI: 0.90, 0.96) and 271-600 g per 2 years (OR: 0.91, 95% CI: 0.89, 0.94) mitigated the risk of AMD. Metformin use in women increased the risk of AMD (OR: 1.14, 95% CI: 1.09, 1.18). However, no significant relationship was noticed between metformin use and AMD risk in men (OR: 0.86, 95% CI: 0.73, 1.01). In addition, metformin was associated with a lower risk of AMD in case-control (OR: 0.93, 95% CI: 0.89, 0.97) and cohort (OR: 0.69, 95% CI: 0.51, 0.95) studies. Likewise, metformin use was associated with a lower risk of AMD in the age groups of 50-59 years (OR: 0.54, 95% CI: 0.50, 0.58) and 70-79 years (OR: 0.90, 95% CI: 0.84, 0.97). Conclusion: Metformin administration lowered the risk of AMD by 14%. Moreover, female gender was identified as a risk factor for AMD development. However, further studies are required on this subject to reach a definite conclusion. Registration: This study has been compiled based on the PRISMA checklist, and its protocol was registered on the PROSPERO (ID: CRD42024539904) and Research Registry (UIN: reviewregistry1824) website.

Blue Light Exposure: Ocular Hazards and Prevention-A Narrative Review.

Exposure to blue light has seriously increased in our environment since the arrival of light emitting diodes (LEDs) and, in recent years, the proliferation of digital devices rich in blue light. This raises some questions about its potential deleterious effects on eye health. The aim of this narrative review is to provide an update on the ocular effects of blue light and to discuss the efficiency of methods of protection and prevention against potential blue light-induced ocular injury. The search of relevant English articles was conducted in PubMed, Medline, and Google Scholar databases until December 2022. Blue light exposure provokes photochemical reactions in most eye tissues, in particular the cornea, the lens, and the retina. In vitro and in vivo studies have shown that certain exposures to blue light (depending on the wavelength or intensity) can cause temporary or permanent damage to some structures of the eye, especially the retina. However, currently, there is no evidence that screen use and LEDs in normal use are deleterious to the human retina. Regarding protection, there is currently no evidence of a beneficial effect of blue blocking lenses for the prevention of eye diseases, in particular age-related macular degeneration (AMD). In humans, macular pigments (composed of lutein and zeaxanthin) represent a natural protection by filtering blue light, and can be increased through increased intake from foods or food supplements. These nutrients are associated with lower risk for AMD and cataract. Antioxidants such as vitamins C, E, or zinc might also contribute to the prevention of photochemical ocular damage by preventing oxidative stress. Currently, there is no evidence that LEDs in normal use at domestic intensity levels or in screen devices are retinotoxic to the human eye. However, the potential toxicity of long-term cumulative exposure and the dose-response effect are currently unknown.

Association of Diabetes Medication With Open-Angle Glaucoma, Age-Related Macular Degeneration, and Cataract in the Rotterdam Study

Recent studies suggest that the diabetes drug metformin has a protective effect on open-angle glaucoma (OAG) and age-related macular degeneration (AMD). However, studies have not addressed the critical issue of confounding by indication, and associations have not been evaluated in a large prospective cohort. To determine the association between diabetes medication and the common eye diseases OAG, AMD, and cataract and to evaluate their cumulative lifetime risks in a large cohort study. This cohort study included participants from 3 independent cohorts from the prospective, population-based Rotterdam Study between April 23, 1990, and June 25, 2014. Participants were monitored for incident eye diseases (OAG, AMD, cataract) and had baseline measurements of serum glucose. Data on diabetes medication use and data from ophthalmologic examinations were gathered. Type 2 diabetes (T2D) and the diabetes medications metformin, insulin, and sulfonylurea derivatives. Diagnosis and cumulative lifetime risk of OAG, AMD, and cataract. This study included 11 260 participants (mean [SD] age, 65.1 [9.8]; 6610 women [58.7%]). T2D was diagnosed in 2406 participants (28.4%), OAG was diagnosed in 324 of 7394 participants (4.4%), AMD was diagnosed in 1935 of 10 993 participants (17.6%), and cataract was diagnosed in 4203 of 11 260 participants (37.3%). Untreated T2D was associated with a higher risk of OAG (odds ratio [OR], 1.50; 95% CI, 1.06-2.13; P = .02), AMD (OR, 1.35; 95% CI, 1.11-1.64; P = .003), and cataract (OR, 1.63; 95% CI, 1.39-1.92; P < .001). T2D treated with metformin was associated with a lower risk of OAG (OR, 0.18; 95% CI, 0.08-0.41; P < .001). Other diabetes medication (ie, insulin, sulfonylurea derivates) was associated with a lower risk of AMD (combined OR, 0.32; 95% CI, 0.18 to 0.55; P < .001). The cumulative lifetime risk of OAG was lower for individuals taking metformin (1.5%; 95% CI, 0.01%-3.1%) than for individuals without T2D (7.2%; 95% CI, 5.7%-8.7%); the lifetime risk of AMD was lower for individuals taking other diabetes medication (17.0%; 95% CI, 5.8%-26.8% vs 33.1%; 95% CI, 30.6%-35.6%). Results of this cohort study suggest that, although diabetes was clearly associated with cataract, diabetes medication was not. Treatment with metformin was associated with a lower risk of OAG, and other diabetes medication was associated with a lower risk of AMD. Proof of benefit would require interventional clinical trials.

Risk of age-related macular degeneration in patients with prostate cancer: a nationwide, population-based cohort study.

Prostate cancer (PC) can be related to increased systemic oxidative stress and dihydrotestosterone level, which are also reported to be involved in the pathogenesis of age-related macular degeneration (AMD). We conducted a cohort study to determine whether patients with PC have an increased risk of AMD. Data were collected from the Taiwan Longitudinal Health Insurance Database for the 1999-2010 period. The study PC cohort comprised 22 084 patients aged ≥18 years with a first diagnosis of PC. The comparison cohort consisted of age-, occupation-, and urbanization level-matched patients at a ratio of 1 : 1. The primary outcome was the incidence of AMD, which was evaluated using Kaplan-Meier survival analysis and proportional hazards modeling. The mean follow-up periods (standard deviation) for the patients with AMD in the age-, occupation-, and urbanization level-matched PC cohort and non-PC cohorts were 4.69 (2.90) and 5.51 (2.82) years. The mean age of the PC cohort was 73.9 years and that of the non-PC cohort was 73.2 years, with approximately 85.9% of the patients aged >65 years. The PC cohort had a higher risk of AMD than did the propensity score-matched non-PC cohort with an adjusted hazard ratio of 1.25 (95% confidence interval, 1.12-1.39). Compared with PC cohort receiving no injection hormone therapy, the PC cohort receiving injection hormone therapy had a lower risk of AMD (adjusted hazard ratio, 0.56; 95% confidence interval, 0.41-0.76). PC is associated with an increased risk of AMD. Patients with PC receiving injected form of androgen deprivation therapy had a lower risk of AMD than patients with PC not receiving injected form of androgen-deprivation therapy.

The Association between LIPC rs493258 Polymorphism and the Susceptibility to Age-Related Macular Degeneration

The purpose of this study was to evaluate the association of the hepatic lipase (LIPC) rs493258 polymorphism and susceptibility to age-related macular degeneration (AMD). A systematic search in PubMed, EMBASE, and ISI web of science databases was performed to identify eligible published studies without language restrictions up to April 2016. Pooled odds ratios (ORs) with 95% confidence intervals (CIs) in different stages of AMD were estimated under different genetic models using meta-analytic methods. Seven studies comprising 20,559 cases and 17,200 controls met the inclusion criteria and were included in the meta-analysis. The LIPC rs493258 polymorphism showed a significant association with a lower risk of AMD under the allelic model (OR = 0.87, 95% CI = 0.84–0.90). Significant relationships between the variant and AMD were also observed in other genetic models (OR ranging from 0.71 to 0.86, all p < 0.05). Stratified analysis based on ethnicity found that LIPC rs493258 polymorphism had a significant association with the decreased risk of the disease in the Caucasian population, but not in the Asian population. For late AMD, significant associations of the rs493258 polymorphism with a lower risk of this disease were also observed in the allelic genetic model (OR = 0.87, 95% CI = 0.83–0.90). This meta-analysis demonstrates that the T allele in the LIPC rs493258 polymorphism was significantly associated with the risk of any and late AMD. The associations of the locus with early and late AMD risk in various populations need further exploration.

Age-Related Macular Degeneration and Its Risk Factors in North Africans Living in Algeria and Italy

Purpose: To determine the risk factors for age-related macular degeneration (AMD) in Algerians, and compare these data with those on North Africans living in Italy. Methods: All patients over 55 years of age consulting one of the 23 involved Algerian ophthalmologists were invited to participate, and 1,183 patients were included. Data collection was standardized based on the Simplified Théa Risk Assessment Scale (STARS) questionnaire. A similar study was conducted in North Africans living in Italy (n = 1,011). Patients with only soft drusen and/or pigmentary abnormalities were classified as early AMD, and patients with geographic atrophy and/or neovascular AMD were classified as late AMD. Results: In the final multivariate model, risk for early and/or late AMD was significantly increased with older age, family history of AMD, Black ethnicity, atherosclerosis, beer consumption, high fruit consumption, cataract surgery, myopia, and hyperopia. High consumption of green vegetables was associated with lower risk for both early and late AMD. In comparison with North Africans from Italy, Algerians generally had a healthier profile (younger, less obesity, smoking, and cardiovascular diseases, and higher consumption of fruits and vegetables) and a lower risk for AMD. Conclusion: This study documents risk factors for AMD in North-African populations for the first time.

ASSOCIATION OF PARAOXONASE 1 L55M AND Q192R SINGLE-NUCLEOTIDE POLYMORPHISMS WITH AGE-RELATED MACULAR DEGENERATION

To determine if paraoxonase 1 (PON1) gene polymorphisms have an effect on the risk of having age-related macular degeneration (AMD). The study population consisted of 142 patients who were diagnosed with either exudative or atrophic AMD and 138 sex- and age-matched controls without AMD. Genotyping of the PON1 L55M and Q192R single-nucleotide polymorphisms was performed using real-time polymerase chain reaction and commercially produced kits. A full ophthalmic evaluation was performed in each subject, and all subjects were screened for hypertension, diabetes, hypercholesterolemia, and smoking history. The PON1 MM and QQ genotypes were less frequent in patients with AMD than in control subjects (MM: 4 vs. 13%, P = 0.015; QQ: 15 vs. 27%, P = 0.020). A multivariate logistic regression analysis was also conducted. After adjusting for age, gender, and the prevalence of smoking, hypertension, diabetes, and hypercholesterolemia, the MM and QQ genotypes (MM/QQ vs. LL + LM/QR + RR) were found to be associated with a decreased risk of AMD (MM: odds ratio = 0.24, P = 0.007, 95% confidence interval: 0.09-0.68; QQ: odds ratio = 0.46, P = 0.013, 95% confidence interval: 0.25-0.85). The authors found that subjects with the PON1 MM and QQ genotypes had a lower risk of AMD.

Dietary and lifestyle risk factors associated with age-related macular degeneration: a hospital based study.

Aim:To establish the frequency, associations and risk factors for age-related macular degeneration (AMD) in hospital population of South India.Materials and Methods:In this cross-sectional hospital based study, 3549 subjects (2090 men and 1459 women) above 45 years of age were screened randomly for AMD. Participants underwent ocular evaluation and were interviewed for lifestyle variables and dietary intake of carotenoids by structured food frequency questionnaire. AMD was defined according to the international classifications and grading system.Results:Either form of AMD was detected in 77 (2.2%) participants. Of which, early and late AMD was present in 63 (1.8%) and 14 (0.4%) subjects, respectively. Binary logistic analysis showed that the incidence of AMD was significantly higher with increasing age (Odds ratio [OR] 1.17; 95% CI 1.13-1.22) and diabetes (OR 3.97; 95% CI 2.11-7.46). However, AMD was significant among heavy cigarette smokers (OR 5.58; 95% CI 0.88-7.51) and alcoholics (OR 4.85; 95% CI 2.45-12.22). Dietary lutein/zeaxanthin (L/Z) and β-carotene intake were associated (P < 0.001) with the reduction in risk for AMD, with an OR of 0.38 and 0.65, respectively.Conclusions:Higher dietary intake of carotenoids, especially L/Z, was associated with lower risk for AMD. Risk of AMD is higher with increasing age and was prevalent among subjects with diabetes. Cessation of smoking and alcohol may reduce the risk of AMD in this population.

Prevalence of and Risk Factors for Age-Related Macular Degeneration in a Multiethnic Asian Cohort

To describe the prevalence of and risk factors for age-related macular degeneration (AMD) in a multiethnic Asian cohort of Chinese, Malay, and Indian persons. In this population-based study, 3172 persons of Chinese, Malay, and Indian ethnicities 40 years and older were included. Participants underwent comprehensive systemic and ocular examination, retinal photography, and laboratory investigations. Early and late AMD signs were graded from retinal photographs. Age-standardized prevalence estimates were calculated using the 2010 Singapore adult population as the standard population. Association with a range of systemic risk factors was analyzed. Of 3172 participants, AMD was present in 211 subjects. Age-standardized prevalence of AMD was 7.0% in persons 40 years and older. The age-standardized prevalence was similar in all 3 Asian ethnic groups: Chinese, 7.3%; Malay, 7.7%; and Indian, 5.7% (P value = .44). The prevalence increased with age and was higher in men. Of the range of risk factors evaluated, only myopic refractive error (<-0.5 D) was significantly associated with a lower risk for AMD (odds ratio, 0.44; P < .001, compared with emmetropia) in Chinese men. The prevalence of AMD was similar in the 3 major ethnic groups in Asia and comparable with white populations. Myopic refractive error was associated with reduced risk of AMD in Chinese men.

Towards Therapy in Genetic Kidney Diseases

The finding of drusen-like lesions beneath the retina in patients with membranoproliferative (or mesangiocapillary) glomerulonephritis (MPGN) type II, with or without partial lipodystrophy, was first reported in 1989. This was confirmed subsequently and has not been reported in other types of glomerulonephritis. These drusen develop at an early age, often in the second decade of life. Some authors have suggested a correlation between the development of eye changes and the duration of renal disease. Many patients do not develop visual impairment, but some may lose vision as a result of development of choroidal neovascularization (CNV) or central serous retinopathy. D’souza et al. studied four patients who had MPGN type II and these eye changes and were followed up during 14 to 37 yr. Three of them received a kidney transplant. There was no progression of retinopathy during 10 yr in any patient. None developed CNV or central serous retinopathy. Type II MPGN (also called dense-deposit disease [DDD]) is associated in 70% of the cases with an IgG autoantibody named C3 nephritic factor (C3NeF) and low C3 serum level, as a result of uncontrolled alternative pathway C3 activation. This C3NeF is also found in 30% of patients with MPGN type I. The principle function of complement function H is to downregulate alternative pathway complement activation. Regulation of fluid-phase C3 activation requires the N-terminal five short consensus repeat domains of the protein. In contrast, targeting of the protein to cell surfaces (surface recognition function) is mediated by C-terminal domains. Various factor H defects were detected in the whole spectrum of MPGN, with or without C3NeF, called “C3 glomerulopathy” by Pickering and Cook in their excellent review (1). This group included DDD, atypical DDD, and other forms MPGN-like diseases. This brings me back to ophthalmology. Age-related macular degeneration (AMD) is one of the most common causes of visual disability in the elderly in developed countries. The hallmark of early-stage disease is the development of drusen lipoproteinaceous deposits localized between the retinal pigment epithelium and Bruch’s membrane. Subsequently, an extensive atrophy of pigment epithelium and overlaying photoreceptor cells or aberrant choroidal angiogenesis is observed. This CNV under the macular area is a leading cause of blindness. Two major AMD susceptibility loci have been identified. One of these is the complement factor H (CFH) locus. The most studied single nucleotide polymorphism at this locus causes Tyr402His amino acid substitution in CFH. There are also common CFH haplotypes or complement fraction B polymorphisms that are associated with lower risk for AMD. These data are summarized in the comprehensive review by de Cordoba and de Jorge (2). AMD and MPGN type II share pathologic similarities with accumulation of complement-containing debris within the eye and the kidney. The hallmark of AMD is drusen, complementcontaining material that accumulates beneath the retinal pigment epithelial. These similarities are striking. Do not forget to check retinal fundi in patients with C3 glomerulopathy. We should keep our eyes open on the future progress in AMD (and MPGN) pathophysiology.

Dietary ω-3 Fatty Acid and Fish Intake in the Primary Prevention of Age-Related Macular Degeneration

To systematically review the evidence on dietary omega-3 fatty acid and fish intake in the primary prevention of age-related macular degeneration (AMD). Seven databases were systematically searched with no limits on publication year or language using standardized criteria. Randomized controlled trials and prospective cohort, case-control, and cross-sectional studies were included. Of 2754 abstracts identified, 3 prospective cohort, 3 case-control, and 3 cross-sectional studies met the criteria. Measures of associations were pooled quantitatively using meta-analytic methods. Nine studies provided data on a total sample of 88 974 people, including 3203 AMD cases. A high dietary intake of omega-3 fatty acids was associated with a 38% reduction in the risk of late AMD (pooled odds ratio [OR], 0.62; 95% confidence interval [CI], 0.48-0.82). Fish intake at least twice a week was associated with a reduced risk of both early AMD (pooled OR, 0.76; 95% CI, 0.64-0.90) and late AMD (pooled OR, 0.67; 95% CI, 0.53-0.85). Although this meta-analysis suggests that consumption of fish and foods rich in omega-3 fatty acids may be associated with a lower risk of AMD, there is insufficient evidence from the current literature, with few prospective studies and no randomized clinical trials, to support their routine consumption for AMD prevention.