Risk Of AMD Research Articles

Detection and biological activities of carboxyethylpyrrole ethanolamine phospholipids (CEP-EPs).

Oxidation of docosahexaenoate phospholipids produces 4-hydroxy-7-oxo-hept-5-eonyl phospholipids (HOHA-PLs) that react with protein lysyl ε-amino residues to generate 2-ω-carboxyethylpyrrole (CEP) derivatives, endogenous factors that induce angiogenesis in the retina and tumors. It seemed likely, but remained unproven, that HOHA-PLs react with ethanolamine phospholipids (EPs) in vivo to generate CEP-EPs. We now show that CEP-EPs are present in human blood at 4.6-fold higher levels in age-related macular degeneration plasma than in normal plasma. We also show that CEP-EPs are pro-angiogenic, inducing tube formation by human umbilical vein endothelial cells by activating Toll-like receptor 2. CEP-EP levels may be a useful biomarker for clinical assessment of AMD risk and CEP-associated tumor progression and a tool for monitoring the efficacy of therapeutic interventions.

Genetic determinants of age-related macular degeneration in diverse populations from the PAGE study.

Substantial progress has been made in identifying susceptibility variants for AMD in European populations; however, few studies have been conducted to understand the role these variants play in AMD risk in diverse populations. The present study aims to examine AMD risk across diverse populations in known and suspected AMD complement factor and lipid-related loci. Targeted genotyping was performed across study sites for AMD and lipid trait-associated single nucleotide polymorphism (SNPs). Genetic association tests were performed at individual sites and then meta-analyzed using logistic regression assuming an additive genetic model stratified by self-described race/ethnicity. Participants included cases with early or late AMD and controls with no signs of AMD as determined by fundus photography. Populations included in this study were European Americans, African Americans, Mexican Americans, and Singaporeans from the Population Architecture using Genomics and Epidemiology (PAGE) study. Index variants of AMD, rs1061170 (CFH) and rs10490924 (ARMS2), were associated with AMD at P=3.05×10(-8) and P=6.36×10(-6), respectively, in European Americans. In general, none of the major AMD index variants generalized to our non-European populations with the exception of rs10490924 in Mexican Americans at an uncorrected P value<0.05. Four lipid-associated SNPS (LPL rs328, TRIB1 rs6987702, CETP rs1800775, and KCTD10/MVK rs2338104) were associated with AMD in African Americans and Mexican Americans (P<0.05), but these associations did not survive strict corrections for multiple testing. While most associations did not generalize in the non-European populations, variants within lipid-related genes were found to be associated with AMD. This study highlights the need for larger well-powered studies in non-European populations.

Sunlight exposure, pigmentation, and incident age-related macular degeneration.

Examine potential effects of sunlight exposure, hair color, eye color, and selected gene single-nucleotide polymorphisms (SNPs) on incidence of AMD. Subjects participated in up to five examinations over a 20-year period. Eye color, self-reported hair color as a teenager, and sunlight exposure were ascertained at the baseline examination. Presence and severity of AMD and its lesions were determined via fundus photographs. Genetic data were available on a subset of participants. The SNPs CFH Y402H rs1061170 and ARMS2 A69S rs10490924 were used to analyze genetic risk of AMD; OCA2 rs4778241 and HERC2 rs12913832 represented genetic determinants of eye color. Incidence of early AMD was higher in blond/red-haired persons compared with brown/black-haired persons (hazard ratio [HR] 1.25, P = 0.02) and in persons with high sun exposure in their thirties (HR 1.41, P = 0.02). However, neither was significant after adjustment for multiple comparisons. Eye (HR 1.36, P = 0.006) and hair color (HR 1.42, P = 0.003) were associated with incidence of any retinal pigmentary abnormalities (RPAs). Both remained significant after adjustment for multiple comparisons. Neither presence of alleles for light-colored eyes nor those associated with high risk of late AMD altered the association of eye or hair color with early AMD. None of the characteristics studied were significantly associated with late AMD. Modest associations of eye color, hair color, and HERC2 genotype with any RPAs were found. Genes for AMD did not affect these associations. Eye color phenotype was more strongly associated with outcomes than HERC2 or OCA2 genotype.

Measuring dark adaptation in the elderly: a predictor of who may develop macular degeneration?

and patient fatigue). The authors show that, after adjustment for age, 22% of subjects had impaired, baseline dark-adaptation kinetics despite absence of AMD, and that these abnormalities correlated with elevated C-reactive protein, a serological marker of inflammation, and with high blood pressure, and exhibited a J-shaped correlation with alcohol intake. This study is of special interest to AMD research in that it provides potential evidence for a functional biomarker that could precede the onset of detectable AMD. It will now be interesting to see if the abnormal dark-adaptation kinetics found at baseline will translate in greater risk of developing AMD and if they will correlate with any nutritional factor and/or genetic marker of AMD. If so, studies of dark adaptometry in the elderly may prove invaluable in predicting who is at greatest risk of AMD, leading to earlier and better treatment, and providing an important outcome measure for trials of AMD.

Rare complement factor H variant associated with age-related macular degeneration in the Amish.

Age-related macular degeneration is the leading cause of blindness among the adult population in the developed world. To further the understanding of this disease, we have studied the genetically isolated Amish population of Ohio and Indiana. Cumulative genetic risk scores were calculated using the 19 known allelic associations. Exome sequencing was performed in three members of a small Amish family with AMD who lacked the common risk alleles in complement factor H (CFH) and ARMS2/HTRA1. Follow-up genotyping and association analysis was performed in a cohort of 973 Amish individuals, including 95 with self-reported AMD. The cumulative genetic risk score analysis generated a mean genetic risk score of 1.12 (95% confidence interval [CI]: 1.10, 1.13) in the Amish controls and 1.18 (95% CI: 1.13, 1.22) in the Amish cases. This mean difference in genetic risk scores is statistically significant (P = 0.0042). Exome sequencing identified a rare variant (P503A) in CFH. Association analysis in the remainder of the Amish sample revealed that the P503A variant is significantly associated with AMD (P = 9.27 × 10(-13)). Variant P503A was absent when evaluated in a cohort of 791 elderly non-Amish controls, and 1456 non-Amish cases. Data from the cumulative genetic risk score analysis suggests that the variants reported by the AMDGene consortium account for a smaller genetic burden of disease in the Amish compared with the non-Amish Caucasian population. Using exome sequencing data, we identified a novel missense mutation that is shared among a densely affected nuclear Amish family and located in a gene that has been previously implicated in AMD risk.

Measures of Body Shape and Adiposity as Related to Incidence of Age-Related Eye Diseases: Observations From the Beaver Dam Eye Study

To examine the effect of obesity on the incidence of age-related eye disease. Participants of the Beaver Dam Eye Study were examined every 5 years over a 20-year period (1988-1990 through 2008-2010). Lens and fundus photographs were used to evaluate presence and severity of cataract and macular degeneration. Height and weight were measured at all examinations. Waist and hip circumference were measured at all examinations beginning at the first follow-up (1993-1995). Models of ocular outcomes over 15 years were stratified by sex and smoking status. Overall, 2641 participants contributed 5567 person-visits to 15-year incidence analysis. Female nonsmokers had increased risk of late AMD associated with higher body mass index (BMI; hazard ratio [HR] per 2.5 kg/m(2) 1.31, 95% confidence interval [CI] 1.15-1.50, P < 0.001), waist to hip ratio (HR per 0.1 cm/cm 1.95, 95% CI 1.33-2.86, P < 0.001), waist circumference (HR per 5 cm 1.21, 95% CI 1.10-1.34, P < 0.001), and waist to height ratio (HR per 0.1 cm/cm 1.74, 95% CI 1.31-2.31, P < 0.001). Increased BMI was also associated with early AMD in female nonsmokers (HR 1.10, 95% CI 1.02-1.19, P = 0.02). Female nonsmokers had risk of late AMD associated with increasing measures of greater obesity and increased risk of early AMD associated with greater BMI.

The Spatial Profile of Macular Pigment in Subjects From a Singapore Chinese Population

To examine the spatial profile of macular pigment (MP) and its relationship with serum concentrations of lutein (L) and zeaxanthin (Z) in subjects from a Singapore Chinese population. In this cross-sectional study, the following details were recorded in 95 healthy subjects: sociodemographic, lifestyle information, body mass index (BMI), visual acuity, MP spatial profile using a macular densitometer, and serum L and Z. The mean (SD) age of the population was 42.40 (± 13) years, ranging from 21 to 68 years. Females demonstrated significantly lower MP optical density (MPOD) than males (MPOD: females = 0.52 ± 0.17; males = 0.61 ± 0.21, P = 0.03). MP spatial profile was typical and atypical with central dip in 68 (85%) and 12 (15%) subjects, respectively. Age and BMI were found to be significant predictors for atypical MP spatial profile (age: odds ratio, OR = 1.06, 95% confidence interval, CI = 1.01-1.13, P = 0.04; BMI: OR = 1.17, 95% CI = 1.01-1.34, P = 0.03). A positive relationship was observed between MPOD and serum concentrations of L and Z, but only the latter relationship reached statistical significance (serum L: r = 0.12, P = 0.30; serum Z: r = 0.26, P = 0.02). A central dip in MP spatial profile was observed with older age and higher BMI, the two known risk factors for AMD, suggesting that atypical MP spatial profile may be associated with an increased risk of AMD. Further studies with larger sample sizes are required to confirm these observations.

Complement Factor I Polymorphism Is Not Associated with Neovascular Age-Related Macular Degeneration and Polypoidal Choroidal Vasculopathy in a Chinese Population

Purpose: To identify the associations of the two complement factor I (CFI) polymorphisms rs10033900 and rs2285714 with risk of neovascular age-related macular degeneration (nAMD) and polypoidal choroidal vasculopathy (PCV) in a Chinese case-control study. Methods: A total of 900 subjects - 300 controls, 300 cases with nAMD and 300 cases with PCV - were included in the present study. Genomic DNA was extracted from venous blood leukocytes. The allelic variants of rs10033900 and rs2285714 were determined by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry. The differences in allele distribution between the cases and controls were tested by a χ² test with age and gender adjusted for by logistic regression analysis. We also performed a meta-analysis of the case-control studies of rs10033900 and rs2285714 based on the currently available evidence from the literature. The meta-analysis was conducted via an inverse-variance, fixed-effects model, as previously described. Results: No statistically significant association was observed between the two polymorphisms of CFI and AMD risk, including nAMD, PCV and combined AMD (p > 0.05 for all comparisons). By meta-analysis, we detected significant associations between both of the SNPs and late AMD, which is consistent with previous results (odds ratio, OR, rs10033900 = 0.814, p rs10033900 < 0.001; OR rs2285714 = 1.221, p rs2285714 < 0.001). For rs2285714, the results of the meta-analysis were less reliable due to its heterogeneity. Conclusions: In our case-control study, neither of the two SNPs most studied (rs10033900 or rs2285714) in the CFI gene was a risk factor for developing nAMD or PCV in a Chinese population. Additional large, comprehensive and well-designed association studies are needed to better understand the role of ethnicity and other gene interactions in the association between the CFI gene and AMD.

ADAMTS9 locus associates with increased risk of wet AMD

<i><scp>ADAMTS</scp>9</i> locus associates with increased risk of wet <scp>AMD</scp>

Nutritional risk factors for age-related macular degeneration.

Purpose. To evaluate the role of nutritional factors, serum lipids, and lipoproteins in late age-related macular degeneration (late AMD). Methods. Intake of red meat, fruit, fish, vegetables, and alcohol, smoking status, and body mass index (BMI) were ascertained questionnaire-based in 1147 late AMD cases and 1773 controls from the European Genetic Database. Serum levels of lipids and lipoproteins were determined. The relationship between nutritional factors and late AMD was assessed using logistic regression. Based on multivariate analysis, area-under-the-curve (AUC) was calculated by receiver-operating-characteristics (ROC). Results. In a multivariate analysis, besides age and smoking, obesity (odds ratio (OR): 1.44, P = 0.014) and red meat intake (daily: OR: 2.34, P = 8.22 × 10−6; 2–6x/week: OR: 1.67, P = 7.98 × 10−5) were identified as risk factors for developing late AMD. Fruit intake showed a protective effect (daily: OR: 0.52, P = 0.005; 2–6x/week: OR: 0.58, P = 0.035). Serum lipid and lipoprotein levels showed no significant association with late AMD. ROC for nutritional factors, smoking, age, and BMI revealed an AUC of 0.781. Conclusion. Red meat intake and obesity were independently associated with increased risk for late AMD, whereas fruit intake was protective. A better understanding of nutritional risk factors is necessary for the prevention of AMD.

TNFRSF10A-LOC389641 rs13278062 But Not REST-C4orf14-POLR2B-IGFBP7 rs1713985 Was Found Associated With Age-Related Macular Degeneration in a Chinese Population

To reassess the association between TNFRSF10-LOC389641 rs13278062 and REST-C4orf14-POLR2B-IGFBP7 rs1713985 with the risk of AMD in a Chinese case-control collection. The primary study consisted of 1826 subjects, including 1226 controls, 300 cases with nAMD, and 300 cases with PCV. Genomic DNA was extracted from venous blood leukocytes. The allelic variants of rs13278062 and rs1713985 were determined by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry. The difference in allele distribution between cases and controls was tested using a χ² test. We also performed a meta-analysis of case-control studies for rs13278062 and rs1713985 in Hong Kong and Singaporean late AMD collections of Chinese descent (1273 cases and 1652 controls) via an inverse-variance, fixed effects model as previously described. Subgroup analysis of CNV and PCV subtypes were also performed. We found no evidence to support a significant association of markers rs13278062 or rs1713985 with either nAMD or PCV, or total AMD in our Beijing study (P > 0.05 for all comparisons). Upon meta-analysis of all sample collections, we note nominally significant association between rs13278062 and increased risk of late AMD, consistent with previous findings in Japanese individuals (ORmeta = 1.17, Pmeta = 0.004). No association was detected between rs1713985 and AMD when all data were meta-analyzed. SNP rs13278062, but not rs1713985 showed nominal evidence of association with AMD in a total of 1273 cases and 1652 controls of Chinese descent. The difference between different effect sizes in our study and other studies suggested that future studies with much larger sample sizes is necessary.

Dry Age-Related Macular Degeneration: Mechanisms, Therapeutic Targets, and Imaging

Age-related macular degeneration is the leading cause of irreversible visual dysfunction in individuals over 65 in Western Society. Patients with AMD are classified as having early stage disease (early AMD), in which visual function is affected, or late AMD (generally characterized as either "wet" neovascular AMD, "dry" atrophic AMD or both), in which central vision is severely compromised or lost. Until recently, there have been no therapies available to treat the disorder(s). Now, the most common wet form of late-stage AMD, choroidal neovascularization, generally responds to treatment with anti-vascular endothelial growth factor therapies. Nevertheless, there are no current therapies to restore lost vision in eyes with advanced atrophic AMD. Oral supplementation with the Age-Related Eye Disease Study (AREDS) or AREDS2 formulation (antioxidant vitamins C and E, lutein, zeaxanthin, and zinc) has been shown to reduce the risk of progression to advanced AMD, although the impact was in neovascular rather than atrophic AMD. Recent findings, however, have demonstrated several features of early AMD that are likely to be druggable targets for treatment. Studies have established that much of the genetic risk for AMD is associated with complement genes. Consequently, several complement-based therapeutic treatment approaches are being pursued. Potential treatment strategies against AMD deposit formation and protein and/or lipid deposition will be discussed, including anti-amyloid therapies. In addition, the role of autophagy in AMD and prevention of oxidative stress through modulation of the antioxidant system will be explored. Finally, the success of these new therapies in clinical trials and beyond relies on early detection, disease typing, and predicting disease progression, areas that are currently being rapidly transformed by improving imaging modalities and functional assays.

Dietary fat consumption and AMD: Epidemiological facts

AbstractIn 2000, a 50 % lower risk for AMD in regular fish consumers was reported for the first time, in a cross‐sectional analysis of the Blue Mountains Eye Study. Since then, 8 cross‐sectional and case‐control studies have produced similar results, although not always reaching statistical significance. However, cross‐sectional and case‐control studies are subject to reverse causality: subjects with AMD may have decreased their fish consumption because of the disease itself, for instance because of difficulties in shopping and cooking. Six prospective studies, in which dietary habits are assessed before the onset of AMD, have also all shown a reduced risk for AMD in high consumers of fish or omega 3 LC‐PUFA, although not always reaching statistical significance. Finally, use of biomarkers may help overcome many methodological difficulties of dietary assessment (recall bias, imprecisions in assessment of food intake and nutritional content of foods…). In the French Alienor Study, we have recently shown that subjects with high plasma omega3 LC‐PUFA had a lower risk of AMD within the next 10 years. Overall, epidemiological data are strikingly consistent, showing a major reduction of risk for AMD in subjects with high omega3 LC‐PUFA status. Commercial interest

Variability of oxidative stress‐related genes in keratoconus and Fuchs endothelial corneal dystrophy

AbstractPurpose In the present work we investigated polymorphism in nuclear genes encoding proteins important for the cellular reaction to oxidative stress and mutations in mitochondrial DNA in two eye diseases with established role of oxidative stress in their pathology: keratoconus (KC) and Fuchs endothelial corneal dystrophy (FECD).Methods Over 200 FECD and KC patients as well as more than 300 sex‐ and age‐matched controls were enrolled in this study. Genetic variation in nuclear DNA was determined in peripheral blood lymphocytes by allele‐specific and restriction length fragment polymorphism PCR. Quantitative real‐time PCR with TaqMan probes was employed to study mutagenesis in mitochondrial DNA (mtDNA).Results Genotypes of polymorphisms of genes encoding catalase and superoxide dismutase, glutathione transferase, enzymes neutralizing reactive oxygen species, were associated with the increased risk of AMD, FECD and KC. Polymorphism of numerous DNA repair genes, including hOGG1, MUTYH, UNG and SMUG1 was associated with AMD and KC. Finally, we found some associations between the occurrence of FECD and mtDNA mutagenesis, expressed by the number of mtDNA copies and specific deletions and point mutations, including 4977 bp deletion in mtDNA encoding 5 tRNAs and 7 proteins of respiratory chain as well as the 414T&gt;G transversion.Conclusion Polymorphism in nuclear genes encoding oxidative stress‐related proteins and mutations in mitochondrial DNA may contribute to the risk of occurrence and development of KC and FECD by modulating the cellular reaction to the stress.

Macular Pigment Optical Density in Young Adults of South Asian Origin

To assess the range of macular pigment optical density (MPOD) in a healthy group of young adults of South Asian origin; to investigate whether any dietary factors or personal characteristics were related to intersubject variations in MPOD; and to compare the mean MPOD of the South Asian group with the mean MPOD of a white group. Heterochromatic flicker photometry was used to measure the macular pigment (MP) levels of 169 healthy volunteers, of which 117 were Asian and 52 were white. In addition, the Asian participants completed a questionnaire pertaining to the various physical, ocular, lifestyle, dietary, and environmental factors that may be associated with MPOD or AMD. The mean MPOD of the Asian subjects was 0.43 ± 0.14. The male participants had a higher mean MPOD than the females (0.47 ± 0.13 vs. 0.41 ± 0.14, P < 0.01). Possible associations also emerged between MPOD and form of refractive correction, and iris color. No MPOD associations were found for the other variables examined in the questionnaire. The mean MPOD of the white subject group was 0.33 ± 0.13, which was significantly lower than the Asian group (P < 0.0005). This study adds to the currently limited information on MPOD in South Asians, and while a comparison between Asians and Whites was not the main focus here, highly significant differences between these two ethnicities were revealed. This provokes the possibility that South Asian individuals could have a lower risk for AMD, and it warrants further study.

A prospective study of dietary omega‐3 fatty acids and the risk of age‐related macular degeneration

MethodFrom 1984 to 2008, we prospectively followed 67,206 women aged ≥ 50 y in the Nurses’ Health Study who had omega‐3 fatty acids intake assessed by a validated food frequency questionnaire and were free of AMD, cancer and cardiovascular disease at baseline.ResultsOver 24 years of follow‐up, we accrued 1,307 AMD cases with 700 early and 607 late AMD. Comparing the highest quintile to the lowest of docosahexaenoic acid intake, the multivariate‐adjusted hazard ratios (HR) for total, early and late AMD were 0.81 (95% confidence interval, 0.66, 0.99), 0.64 (0.48, 0.84; p for trend, 0.003), and 1.08 (0.80, 1.46), respectively. The results were similar for eicosapentaenoic acid. For alpha‐linolenic acid, the corresponding HRs were 1.26 (1.02, 1.57), 1.36 (1.02, 1.83; p for trend, 0.02) and 1.16 (0.84, 1.59). Compared with women who consumed seafood &lt;1 serving/m, women who consumed ≥5 servings/wk had a HR of 0.50 (0.29, 0.87; p for trend, 0.004) for early AMD. The inverse associations between docosahexaenoic acid and total and early AMD were more evident in women &lt;70 years old and those who took ≥1 tablet of aspirin/wk.ConclusionBoth docosahexaenoic acid and eicosapentaenoic acid were associated with decreased risk of early AMD but not late AMD. Alpha‐linolenic acid was associated with increased risk of early AMD and warrants further investigation. Higher intake of seafood may benefit primary prevention of AMD.

Long-Term Blood Pressure and Age-Related Macular Degeneration: The ALIENOR Study

To explore the association of AMD with long-term average blood pressure (BP) parameters, including pulse pressure (PP). The ALIENOR study is a population-based study on age-related eye diseases in 963 residents of Bordeaux, France, aged 73 years or older. AMD was graded from nonmydriatic color retinal photographs, in three exclusive stages: no AMD (1015 eyes), large soft distinct drusen and/or large soft indistinct drusen and/or reticular drusen and/or pigmentary abnormalities (early AMD, 276 eyes), and late AMD (66 eyes). BP parameters were measured at four occasions over a 7-year period. PP was defined as systolic BP minus diastolic BP. Associations of AMD with BP parameters were estimated using generalized estimating equation logistic regressions. Statistical analyses included 702 subjects (1357 eyes) with complete data. After adjustment for age, sex, educational level, smoking, body mass index, plasma HDL and LDL cholesterol, CFH Y402H, ApoE2, ApoE4, and ARMS2 A69S polymorphisms, elevated PP was significantly associated with an increased risk of late AMD (odds ratio [OR] = 1.37 for a 10-mm Hg increase, 95% confidence interval [CI]: 1.03-1.82). Associations were similar for late atrophic and late neovascular AMD (OR = 1.39, 95% CI: 1.01-1.92, P = 0.04, and OR = 1.43, 95% CI: 0.90-2.23, P = 0.13, respectively). Association with early AMD was in the same direction but did not reach statistical significance (OR = 1.12, 95% CI: 0.98-1.28). Early and late AMD were not significantly associated with systolic or diastolic BP, hypertension, or use of antihypertensive medications. This study suggests that high PP may be associated with increased risk for AMD.

AMD risk alleles fail to predict treatment response

AMD risk alleles fail to predict treatment response

Education Is Positively Associated with Macular Pigment: The Irish Longitudinal Study on Ageing (TILDA)

The three carotenoids lutein, zeaxanthin, and meso-zeaxanthin, are found at the macula and referred to as macular pigment (MP). This study was undertaken to investigate determinants of MP in a large randomly selected sample from the Republic of Ireland (as part of The Irish Longitudinal Study on Ageing [TILDA]).MP optical density (MPOD) was measured using customized heterochromatic flicker photometry in 4373 participants. Sociodemographic and self reported health data was obtained using computer assisted personal interview (CAPI).Mean (SD) MPOD for the study group was 0.203 (0.156) with a range of 0 to 1.01. MPOD was higher for participants with secondary education (mean [SD] = 0.205 [0.148]) than for those with only primary education or no education (mean [SD] = 0.183 [0.113]; P < 0.001). MPOD was also higher for those with tertiary education (mean [SD] = 0.232 [0.231]) compared with primary/no education or secondary education (P < 0.001 for both comparisons).We report that MP is lower amongst those participants of a population-representative study who did not have secondary or third level education when compared with participants who had such education. Given the emerging evidence that MP is important for visual performance and comfort, and given the putative protection that this pigment confers against AMD (especially important in the context of increased risk of AMD in this social group), public health measures aimed at improving diet for this at-risk population need to be considered.

Vascular endothelial growth factor A genetic polymorphisms and AMD in Tunisians

AbstractPurpose To determine whether vascular endothelial growth factor (VEGF) gene polymorphism plays a role in either susceptibility risk for exudative AMD, serum VEGF levels variations and treatment with intravitreal bevacizumab in TunisiansMethods In this case–control study, we included 96 patients with exudative AMD and 207 age‐matched controls treated with intravitreal bevacizumab. Single nucleotide polymorphism (SNP) genotyping was performed using restriction fragment length polymorphism (RFLP) analysis of polymerase chain reaction (PCR) products. The serum VEGF was assayed by ELISA (R&amp;D).Results The frequency of the VEGF ‐2578 A allele was significantly higher in AMD patients than in controls (p=0.005; OR: 2.12[1.23‐3.66]) and was statistically associated to higher serum levels of VEGF (93.30 pg/ml versus 39.75 pg/ml for C allele) (p: 0.021). When examining the effect of this polymorphism on post‐treatment visual acuities (VA), we observed that A variant allele was also statistically more prevalent among patients with better outcome for distance and reading visual acuity after three bevacizumab injections compared to those with loss of 3 or more lines in visual acuity (OR = 2.5, 95% CI [1.13‐5.73], p = 0.02). Furthermore, the mean of VEGF plasma level is significantly higher (170.97 pg/ml) in patients with enhanced VA compared to those with worse outcome for distance and reading visual acuity (45.52pg/ml) (p=0.003).Conclusion In addition to the higher risk for exudative AMD in Tunisian patients with the ‐2578 A VEGF, our results show that this allelic variant also correlates with better visual acuity outcome after treatment with bevacizumab probably through a functional or quantitative variation of plasma levels of this molecule.