Exudative Age-related Macular Degeneration Patients Research Articles

Pigment Epithelium-Derived Factor Gene Polymorphisms in Exudative Age-Related Degeneration in a Chinese Cohort

Purpose: To investigate polymorphisms in the pigment epithelium-derived factor (PEDF) gene in a Chinese cohort with exudative age-related macular degeneration (AMD).Methods: Two common single nucleotide polymorphisms (SNPs), Met72Thr (rs1136287) and -5736T>C (rs12150053), were genotyped, and four tagSNPs (tSNPs) were detected statistically in the PEDF gene of 168 exudative AMD patients and 230 age- and sex-matched control participants. Genetic analyses for additive, dominant, and recessive models were performed on all the available genotype data. All the possible haplotypes of these six SNPs were detected.Results: No association was found between the patients and the control participants in the allele frequencies for any individual SNP. There was evidence to suggest that heterozygotes for rs1136287 (C/T) exerted a protective effect against exudative AMD (additive model, OR 0.59, CI 0.36–0.95, p = 0.03), but none of the p-values in the other genotype groups were statistically significant. Likewise, haplotype analyses did not provide any evidence for an association between SNPs in the PEDF gene and the risk of exudative AMD in this Chinese cohort (p > 0.05).Conclusions: Detection of SNPs in the PEDF gene was not found to be significantly associated with exudative AMD in the Chinese cohort. Further studies of comprehensive PEDF gene variations are required to characterize the susceptibility of PEDF gene in the pathogenesis of AMD.

Correlation of complement factor H gene polymorphisms with exudative age-related macular degeneration in a Chinese cohort

To evaluate the association between complement factor H ( CFH) gene polymorphism and the risk of exudative age-related macular degeneration (AMD) in a case–control study in a Chinese cohort. One hundred and thirty-six exudative AMD patients and 140 age- and sex-matched control subjects were recruited. We genotyped 3 common single nucleotide polymorphisms (SNPs), namely, −257C > T (rs3753394), Y402H (rs1061170) and IVS15 (rs1329428), genetic analyses were performed on all available genotype data. All the possible haplotypes of these 3 SNPs were detected. Polymerase chain reaction (PCR) and allele-specific restriction endonuclease digestion were performed, some PCR products of these 3 SNPs were sequenced. The risk alleles (T, C or G) of the 3 SNPs conferred 1.72-fold, 3.14-fold, and 1.79-fold of increased likelihood of the disease, respectively ( P < 0.05). The heterozygous genotype in rs1061170 (TC) revealed significant association, meanwhile rs3753394 and rs1329428 had a slight association with the disease, respectively. Significant differences were shown in the risk alleles in the 3 SNPs among different Chinese cohort. Low linkage disequilibrium was found among the 3 SNPs. The haplotypes TCG and CTG revealed as risk factors, whereas the protective haplotype CTA was over-represented in controls. We found significant association between risk alleles (T, C or G) of the 3 SNPs and the disease. The genetic divergence across multiple populations within Chinese existed. Risk haplotypes and protective haplotype were found in this study.

Serum vitamin B12 and folic acid in exudative age-related macular degeneration patients

Objective To investigate the serum levels of vitamin B12 and folic acid (FA) of exudative age-related macular degeneration (AMD). Methods A total of 84 patients with exudative AMD(AMD group)and 78 patients with non-exudative AMD (control group) diagnosed at Xijing Hospital between June 2008 and September 2009 were assessed in this study. Serum vitamin B12 and FA levels were measured by chemiluminescence immunoassay. The statistical information of epidemiology and risk factors exposure histories were collected and compared. Results AMD group had significantly lower serum vitamin B12 levels[(247.51±93. 92) ng/ml]compared with the control group [(312. 52±143.08) ng/ml], the difference was statistical significance (t=5. 013, P<0.001). Serum FA levels in AMD group [(5. 64±3.72) ng/ml]were slightly lower than the control group [( 10.14±4. 48) ng/ml], the difference was not statistical significance (t=0. 780, P= 0. 437). Conclusion People with lower serum vitamin B12 have higher risk of exudative AMD. Low levels of serum vitamin B12 may relate with the occurrence of exudative AMD. Key words: Macular degeneration/etiology; Vitamin B12/lack; Folic acid/lack

Dynamic retinal vessel response to flicker in age-related macular degeneration patients before and after vascular endothelial growth factor inhibitor injection

Retinal vessel responses to flickering light are different in various systemic and ocular diseases and can be improved after successful therapy. We investigated retinal vessel response to flickering light in age-related macular degeneration (AMD) patients before and after treatment with a single intravitreal bevacizumab (Avastin(®) ) injection. In 10 patients with exudative AMD [age: median (1.quartile; 3.quartile) 76.0 (73.5; 80.0) years], retinal vessel reactions were examined by Dynamic Vessel Analyser (DVA) before and 3 months after a single intravitreal application of bevacizumab (1.25 mg). A baseline measurement was followed by three consecutive monochromatic flicker stimulations (530-600 nm, 12.5 Hz, 20 seconds). Temporal retinal vessel reaction was analysed and compared with the reaction in healthy controls. Mean arterial dilation at the end of flicker was not different in all groups. For veins this parameter amounted to: pre-treatment, 2.6 (1.7; 3.9)%; post-treatment, 2.9 (2.4; 4.0)%; control, 4.3 (3.2; 5.7)%; significant: pre-treatment - control (Dunnett's procedure, p < 0.05). Maximal dilation occurred in arteries at: pre-treatment, 17.5 (14.8; 32.5) seconds; post-treatment, 18.0 (16.6; 30.6) seconds; control, 14.5 (10.8; 17.3) seconds. Both AMD groups were slower (p < 0.05): in veins at 17.0 (14.5; 20.0) seconds, 12.8 (8.6; 14.8) seconds and 18.5 (17.1; 19.9) seconds, respectively; significant post-treatment - control (p < 0.05). In the post-treatment AMD group arterial constriction after stimulation occurred more slowly compared with the control group (p < 0.05). Dynamic retinal arterial and venous reactions to flickering light are altered in AMD compared with controls. Three months after a single injection of a vascular endothelial growth factor inhibitor, the investigated retinal dynamic vascular parameters were not altered in our study.

The Results of Nation-Wide Registry of Age-related Macular Degeneration in Korea

Purpose: To evaluate the incidence and clinical features of age-related macular degeneration (AMD) in Korea Methods: Web-based (www.armd-nova.or.kr) registration was conducted for AMD patients aged 50 or more who were newly diagnosed by retinal specialists in Korea from August 20, 2005 to August 20, 2006. Patient data including ophthalmologic examination, fundus photography, fluorescein angiogram and/or indocyanin green angiogram (ICG), past medical history, behavioral habit, combined systemic diseases were up-loaded. Results: Among finally enrolled 1,141 newly diagnosed AMD patients, 690 patients (60.5%) were male and 451 patients (39.5%) were female. The average age of AMD patients was 69.78.0. Early AMD was observed in 190 patients and 951 patients had late AMD. Classic choroidal neovascular membrane (CNVM) was observed in 18.6% of exudative AMD patients and 63.4 % had occult CNVM. Subfoveal CNVM was observed in 80.4% of the patients with CNVM. Among the 580 exudative AMD eyes that performed indocyanin green angiography (ICG), 184 eyes (31.7%) had polypoidal choroidal vasculopathy (PCV) and 36 eyes (6.2%) showed retinal angiomatous proliferation (RAP). Age, male gender, smoking, diabetes and hypertension significantly increased the risk of the AMD among Koreans. Conclusions: Because of the low rate of participation by retinal specialists, definite incidence of AMD was not obtainable. However, the estimated 1-year AMD incidence in the Pusan area of Korea is at least 0.4%. In contrast to Western people, 31.7% of exudative AMD cases were revealed to be PCV and 6.2% were revealed to be RAP. This discrepancy between ethnic groups should be considered in the diagnosis and treatment modality selection of Korean AMD patients.

Age-Related Macular Degeneration in a Screened South Korean Population: Prevalence, Risk Factors, and Subtypes

To identify the prevalence, risk factors, and subtypes of age-related macular degeneration (AMD) in a screened South Korean population. A total of 10,890 participants (aged 50-92) who underwent a health check-up at Kangbuk Samsung Hospital from January to December 2006 were included. Fundus photographs and systemic risk factors were assessed. Subtype frequencies of neovascular AMD were recorded according to angiograms. AMD was defined in accord with the international classification and grading system. Logistic regression analyses were performed to identify risk factors for AMD. The mean age of the 10,890 participants was 57.2 +/- 6.3 years (50-92 years), and 56.2% were men. The age-gender-adjusted prevalence of early AMD was 5.07%. Multiple logistic regression analysis showed that age (OR per 10-year increment, 2.22) and high blood pressure (adjusted OR: 1.35) were independent risk factors for early AMD. The age-gender-adjusted prevalence of late AMD was 0.34%. Only age was significantly associated with late AMD. Of 9 exudative AMD patients who received fluorescein angiography or indocyanine green angiography, 6 eyes (66.7%) showed choroidal neovascularization, 2 eyes (22.2%) had polypoidal choroidal vasculopathy (PCV), and 1 eye (11.1%) had retinal angiomatous proliferation. In this study, the prevalence of early AMD was similar to other studies though the prevalence of late AMD was low. High blood pressure as well as age was a risk factor of early AMD. South Koreans may have a higher prevalence of PCV than white populations. These findings provide preliminary information for further investigation of AMD in South Koreans.

ANALYSES OF SINGLE NUCLEOTIDE POLYMORPHISMS AND HAPLOTYPE LINKAGE OF LOC387715 AND THE HTRA1 GENE IN EXUDATIVE AGE-RELATED MACULAR DEGENERATION IN A CHINESE COHORT

To investigate the effect of single nucleotide polymorphisms (SNPs) and haplotypes in the genes encoding age-related maculopathy susceptibility 2 (LOC387715/ARMS2) and high-temperature requirement A-1 (HTRA1) in a case-control study in a Chinese cohort of individuals with exudative age-related macular degeneration (AMD). We genotyped 2 SNPs, namely, LOC387715 rs10490924 and HTRA1 rs11200638, in 159 exudative AMD patients and 140 age- and sex-matched control subjects. All the four possible haplotypes of these two SNPs were detected. Comparisons of the risk genotypes and risk or protective haplotypes across multiple populations were performed. Allelic or genotype association tests yielded significant results at P < 0.001. We observed that homozygous risk genotypes (TT in rs10490924 and AA in rs11200638) were more strongly associated with AMD than the heterozygous genotypes (GT in rs10490924 and geographic atrophy in rs11200638) for both SNPs. Comparisons of the odds ratios for genotypes revealed that there is ethnic disparity in AMD prevalence, even within the Chinese population. The haplotype TA, comprising both the SNPs, was identified as an at-risk factor and was significantly associated with AMD, whereas the protective haplotype GG was significantly overrepresented in the controls (P < 0.001). The frequency of the TA haplotype was relatively higher in the Chinese population than in the white population in both groups, whereas the frequency of the GG haplotype was relatively lower in the Chinese controls than in the white and Japanese controls. Both SNPs are significantly associated with exudative AMD in the Chinese cohort and seem to contribute equally to the disease status. A higher frequency of homozygous risk genotypes and risk haplotype and a lower frequency of protective haplotype in the Chinese may be the cause of higher prevalence of exudative AMD in the Chinese than in the whites.

Age-Related Macular Degeneration in a Screened South Korean Population: Prevalence, Risk Factors, and Subtypes

Purpose: To identify the prevalence, risk factors, and subtypes of age-related macular degeneration (AMD) in a screened South Korean population. Methods: A total of 10,890 participants (aged 50–92) who underwent a health check-up at Kangbuk Samsung Hospital from January to December 2006 were included. Fundus photographs and systemic risk factors were assessed. Subtype frequencies of neovascular AMD were recorded according to angiograms. AMD was defined in accord with the international classification and grading system. Logistic regression analyses were performed to identify risk factors for AMD. Results: The mean age of the 10,890 participants was 57.2 ± 6.3 years (50–92 years), and 56.2% were men. The age-gender-adjusted prevalence of early AMD was 5.07%. Multiple logistic regression analysis showed that age (OR per 10-year increment, 2.22) and high blood pressure (adjusted OR: 1.35) were independent risk factors for early AMD. The age-gender-adjusted prevalence of late AMD was 0.34%. Only age was significantly associated with late AMD. Of 9 exudative AMD patients who received fluorescein angiography or indocyanine green angiography, 6 eyes (66.7%) showed choroidal neovascularization, 2 eyes (22.2%) had polypoidal choroidal vasculopathy (PCV), and 1 eye (11.1%) had retinal angiomatous proliferation. Conclusion: In this study, the prevalence of early AMD was similar to other studies though the prevalence of late AMD was low. High blood pressure as well as age was a risk factor of early AMD. South Koreans may have a higher prevalence of PCV than white populations. These findings provide preliminary information for further investigation of AMD in South Koreans.

Genetic variants in three genes and smoking show strong associations with susceptibility to exudative age-related macular degeneration in a Chinese population

The present study was undertaken to replicate the associations of representative polymorphisms in three genes (complement factor H (CFH), complement factor B (BF) and HtrA serine peptidase 1 (HTRA1)) with exudative age-related macular degeneration (AMD) in a Han Chinese population, and to test if the modifiable environmental factors affect AMD susceptibility associated with different type of genotype in these genes. An age, gender and ethnicity matched case-control study was conducted to genotype the representative single neucleotide polymorphisms (SNPs) loci including rs1061170 and rs1410996 in CFH, rs641153 and rs4151667 in BF and rs11200638 in HTRA1 gene in 144 exudative AMD patients and 126 normal controls using PCR-RFLP and direct resequencing. The demographic characteristics and behavioral risk factors were also recorded. Allelic and genotypic associations for individual SNP and joint associations with two loci were performed. The gene-gene and gene-environment interactions were analyzed using multivariate non-conditional Logistic regression analysis. The C risk allele frequencies for CFH Y402H (rs1061170) in cases and controls were 12.5% and 5.4% respectively, which were much lower than those in Caucasians (P < 0.001). Compared with TT homozygous genotype, the CT heterozygous genotype was positively associated with AMD with odds ratio (OR) of 3.23 (1.36 - 5.07). However, the population attributable risk (PAR) of C allele was only 3.3% (1.4% - 4.3%). rs1410996 was also associated with AMD independent of Y402H. The ORs of exudative AMD for individuals carrying one copy risk allele and two copy risk alleles were 2.57 (1.21 - 5.45) and 4.76 (2.15 - 10.55) respectively, with correspondent PARs of 28.3% (2.0% - 40.5%) and 38.2% (21.8% - 45.4%). rs11200638 in HTRA1 was another susceptible locus for AMD and the risk homozygotes were significantly susceptible for exudutive AMD (OR = 3.98, 1.88 - 8.43) with PAR of 38.9% (24.3% - 45.8%). Education status and cigarette smoking were also related to exudative AMD. After controlling for environmental risk factors, CFH and HTRA1 SNPs were independently associated with exudative AMD, with OR of 3.50 (1.45 - 8.45) for CT genotype in Y402H, 3.34 (1.33 - 8.36) for GG genotype in rs1410996 and 3.85 (1.58 - 9.42) for AA genotype in rs11200638 respectively. The interaction analysis between gene and environmental factors showed that smoking synergistically increased susceptibility of AMD for heterozygotes of rs1410996, with OR(interaction) of 7.33 (P(interaction) = 0.029). In a Han Chinese population, CFH and HTRA1 polymorphisms appear to be independently and possibly additively hereditary contributors to exudative AMD. Y402H polymorphism conferred a significant but relatively lower contribution in Chinese than in Caucasians with a low frequency of risk allele. The gene-environment interaction may be a best way to encourage those with a high genetic risk to prevent AMD by avoiding modifiable factors until there is effective treatment for AMD.

Correlation between CFH Y402H and HTRA1 rs11200638 genotype to typical exudative age‐related macular degeneration and polypoidal choroidal vasculopathy phenotype in the Japanese population

Typical exudative age-related macular degeneration (AMD) and polypoidal choroidal vasculopathy (PCV) are two of the major macular diseases found in Asians. Although genomic studies have shown a contribution by CFH and LOC387715/HTRA1 polymorphisms to the development of these two diseases, the correlation of the clinical phenotypes to these genotypes has not been determined in Asian patients. The prevalence of the CFH Y402H and HTRA1 rs11200638 genotypes was determined in 116 patients with typical exudative AMD and in 204 patients with PCV. Potential correlations of these polymorphisms were tested retrospectively and cross-sectionally for bilaterality of the disease, final visual acuity and the greatest linear dimension of the choroidal neovascular (CNV) lesion. There was no significant difference in the incidence of CFH Y402H (P = 0.598) and HTRA1 rs11200638 (P = 0.290) between eyes with typical exudative AMD and with PCV. There was a significant association between the lesion size and HTRA1 rs11200638. For eyes with typical AMD, the size of the lesion (6363 +/- 2837 microm) was significantly larger in the high-risk homozygous group (AA), than in the low-risk homozygous group (GG) (3866 +/- 1947 microm; P = 0.0003). The same tendency was observed for the size of the lesion in PCV cases (homozygous group: 6347 +/- 2673 microm, non-risk homozygous group: 4405 +/- 2066 microm, P = 1.3 x 10(-5). A common genetic background may exist between typical exudative AMD and PCV patients. Among the patients with these two clinical entities, those with a homozygous HTRA1 rs11200638 risk allele had larger CNV lesions.

Incidence and clinical patterns of polypoidal choroidal vasculopathy in Korean patients

To determine the incidence, demographic features, and clinical characteristics of polypoidal choroidal vasculopathy (PCV) in Korean patients. A retrospective review was undertaken of 392 eyes of 321 symptomatic patients suspected of having exudative age-related macular degeneration (AMD) after their first visit to a tertiary hospital between February 2002 and May 2006. All patients underwent a complete ophthalmic examination, including fluorescein and indocyanine green angiography (ICGA). Of the 321 patients (392 eyes), 79 (98 eyes, 24.6%) were diagnosed with PCV. The mean PCV patient age was 64.6 +/- 7.6 years. PCV was more common in men (78.5%), and was usually unilateral (75.9%). In terms of PCV clinical manifestation, 52% of patients showed an exudative pattern, 34.7%, a hemorrhagic pattern, and 13.3%, an extensive hemorrhagic pattern. The mean visual acuity at presentation was 0.231 +/- 0.256. Classification was based on ICGA findings; 52% of patients showed relatively large aneurismal dilations, 25.5% showed atypical vessel deformations, and 22.5% showed dense clusters of numerous small hyperfluorescent dots. The incidence of PCV in Korean exudative AMD patients was relatively high compared with that in other ethnic groups. As in other Asian patient populations, PCV occurred more commonly in men and was predominantly unilateral.

A new approach for visualisation of dye leakage in fluorescein angiography

INTRODUCTION: Fluorescein angiography (FA) is the more common investigation performed for macular diseases.1 Frozen FA pictures are obtained but direct visualisation of the kinetics of FA is possible only once,...

Leucine 7−proline 7 polymorphism in the signal peptide of neuropeptide Y is not a risk factor for exudative age-related macular degeneration

Because of the regulatory role of neuropeptide Y (NPY) in angiogenesis, we set out to determine the presence of the leucine 7-proline 7 (Leu7Pro) polymorphism in exudative age-related macular degeneration (AMD) patients and to analyse its implications. Genotype analysis of the Leu7Pro polymorphism in the signal peptide region of the human prepro-NPY was performed in blood samples from exudative AMD patients (n = 240) and control subjects (n = 79). In all, 11% of exudative AMD patients and 14% of control subjects exhibited the NPY signal peptide Leu7Pro polymorphism. There were no statistically significant differences in Leu7Pro polymorphism frequency between the exudative AMD and control cases, as analysed by Fisher's exact two-sided test. Leu7Pro polymorphism in the signal peptide region of the human prepro-NPY is not a risk factor for exudative AMD.

No association between complement factor H gene polymorphism and exudative age-related macular degeneration in Japanese

Age-related macular degeneration (ARMD) is the leading cause of blindness in the elderly population not only Western but also Asian industrial countries. In Caucasian, a polymorphism of the complement factor H gene (CFH), the C allele of rs1061170 (Y402H), was established as the first strong genetic factor for excursively exudative type of ARMD. In this study, we performed an extensive sequencing of the 22 exons in the CFH gene by recruiting 146 exudative ARMD patients and 105 normal controls of Japanese origin and identified 61 polymorphisms. We found that the frequency of the C allele of rs1061170 (Y402H) is much lower (0.04) in Japanese controls than in Caucasians (0.45). No case disease susceptibility to exudative ARMD was noted for rs1061170 (Y402H) (chi (2) = 3.19, P (corr) = 0.423), or other 12 single nucleotide polymorphisms (SNPs) whose frequency is greater than 0.05. When haplotypes were inferred for 13 SNPs (these 12 SNPs with a frequency greater than 0.05 and rs1061170), three haplotypes whose pattern was similar to those in Caucasians were identified but with substantial difference in frequency. Again we failed to identify genetic association between Japanese exudative ARMD and any of the haplotypes including the J1 haplotype which was shown to be susceptible to ARMD in Caucasians (chi (2 )=( )3.92, P (corr) = 0.157). CFH does not appear to be a primary hereditary contributor to ARMD in Japanese. The absence of CFH contribution to ARMD in Japanese may correlate with the findings in ethnic differences of ARMD phenotypes.

Ocular perfusion and age-related macular degeneration.

To review the role of ocular perfusion in the pathophysiology of age-related macular degeneration (AMD), the leading cause of irreversible blindness in the industrialized world. Medline search of the literature published in English or with English abstracts from 1966 to 2000 was performed using various combinations of relevant key words. Vascular defects have been identified in both nonexudative and exudative AMD patients using fluorescein angiographic methods, laser Doppler flowmetry, indocyanine green angiography, and color Doppler imaging. Although these studies lend some support to the vascular pathogenesis of AMD, it is not possible to determine if the choroidal perfusion abnormalities play a causative role in nonexudative AMD, if they are simply an association with another primary alteration, such as a primary RPE defect or a genetic defect at the photoreceptor level, or if they are more strongly associated with one particular form of this heterogeneous disease. Further study is warranted.

Does Coenzyme Q10 Play a Role in Opposing Oxidative Stress in Patients with Age-Related Macular Degeneration?

To seek some specific biochemical markers of age-related macular degeneration (AMD), coenzyme Q₁₀ (CoQ₁₀) levels were determined in plasma and platelets from 19 exudative AMD patients and 19 age-matched controls. Lipid peroxidation was followed in plasma in vitro after the addition of a free radical initiator. Most patients had lower plasma CoQ₁₀ content than most controls. Plasma from controls showed greater capacity to oppose the oxidative damage. These results support the concept that free radicals play a pathogenic role in AMD and that CoQ₁₀ may have a protective effect.

The Apolipoprotein E ε4 Allele Is Unlikely to Be a Major Risk Factor of Age-Related Macular Degeneration in Chinese

Apolipoprotein E (ApoE) is a major transporter of lipids and cholesterol in the nervous system. Age-related macular degeneration (ARMD), characterized by drusen containing lipids, was reported to show a lower frequency of the ApoE ε4 allele than control subjects. We sought to examine the association of this polymorphism with ARMD in Hong Kong Chinese. Among 98 ARMD subjects, the frequency of ε4 carriers showed a trend toward a decrease compared to controls, but it was not significant (11.2 vs. 15.0%, p < 0.52). The association of ε4 with an apparent reduced risk of ARMD was reported previously in the exudative form of the disease, however among 39 exudative ARMD patients there was also no significant difference in ε4 frequency (12.8%, p < 0.93). The lack of a statistically significant effect of ε4 may be due to the lower frequency of ε4 in Chinese than Europeans. Thus we cannot exclude a possible effect of this allele on ARMD risk, but we can conclude that this allele is likely not a major factor influencing ARMD risk in the Chinese.