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Purpose: To investigate factors affecting patient response to intravitreal ranibizumab treatment for age-related macular degeneration (AMD)., Design: Retrospective chart review., Methods: We reviewed medical records of 105 consecutive eyes with AMD treated with intravitreal ranibizumab injections and followed for more than 1 year after treatment. Response to ranibizumab treatment was compared between typical neovascular AMD and polypoidal choroidal vasculopathy (PCV). Furthermore, we investigated associations of age, lesion size, and single nucleotide polymorphisms (SNPs) in CFH and ARMS2 genes with treatment response., Results: Forty-nine eyes were diagnosed with typical neovascular AMD and 56 eyes with PCV. Serous retinal detachment and retinal edema resolved similarly in both typical neovascular AMD and PCV after treatment. However, visual acuity (VA) significantly improved in eyes with PCV, whereas VA was maintained in typical neovascular AMD. At the third and twelfth months after injection, VA was better in PCV than in typical neovascular AMD (P = .027 and P = .044, respectively), although there were no differences in baseline VA between the 2 groups. Age and size of greatest linear dimension were significantly associated with visual prognosis in typical neovascular AMD but not in PCV. There was no clear association between 3 SNPs and responsiveness to ranibizumab treatment., Conclusions: Although exudative changes were equivalent following ranibizumab treatment in both typical neovascular AMD and PCV, there was a significant increase in VA in PCV compared to typical neovascular AMD. Age and greatest linear dimension correlated with visual prognosis only in typical neovascular AMD and not in PCV., (Copyright © 2012 Elsevier Inc. All rights reserved.)

Purpose: To investigate the progression of vascular lesions of polypoidal choroidal vasculopathy (PCV) as viewed with indocyanine green angiography and the visual prognosis of these eyes., Design: Retrospective case study., Methods: We reviewed retrospectively the medical records of 88 consecutive patients (88 eyes) with PCV who had been examined with indocyanine green angiography for more than 2 years., Results: Depending on the initial area of the vascular lesion, eyes were divided into smaller PCV (baseline area of lesion being < 1 disc area [DA], n = 22) and larger PCV (baseline area of lesion being ≥ 1 DA, n = 66). In larger PCV, the mean area of the lesion progressed significantly from 6.49 ± 8.96 mm(2) to 16.27 ± 14.19 mm(2) (P < .0001) with marked deterioration of visual acuity (P < .0001) during follow-up. In contrast, smaller PCV often showed minimal progression of the lesion, only limited exudative change, and the eyes maintained their initially good vision to the final visit. Smaller PCV lesions rarely progressed to extensive PCV lesions. Severe vision-threatening complications (ie, suprachoroidal hemorrhage, vitreous hemorrhage, and tears of the retinal pigment epithelium) were seen only in eyes with larger PCV, and in studying single nucleotide polymorphisms A69S of ARMS2 genes, there was a significant difference in T allele frequency between individuals with smaller PCV and those with larger PCV (20.2% vs 79.8%; P = .0235)., Conclusions: PCV with small vascular lesions shows minimal progression and no vision-threatening complications, and these eyes often maintain good visual acuity for a long time., (Copyright © 2011 Elsevier Inc. All rights reserved.)

Purpose: To determine whether polymorphisms in the ARMS2 (LOC387715) gene and the lysyl oxidase-like 1 (LOXL1) gene are associated with age-related macular degeneration (AMD) in Japanese patients., Design: Clinically relevant laboratory investigation., Methods: Forty-one unrelated Japanese subjects with dry AMD, 50 subjects with exudative (wet) AMD, and 60 subjects with polypoidal choroidal vasculopathy (PCV) were studied. The single nucleotide polymorphisms (SNPs), p.Ala69Ser of the ARMS2 gene and p.Arg141Leu of the LOXL1 gene, were amplified by polymerase chain reaction, directly sequenced, and genotyped., Results: For the ARMS2 gene, the genotype frequency of the p.Ala69Ser single nucleotide polymorphism in eyes with dry AMD was not significantly different from that in the controls (P = .04), but the frequency was significantly higher in the exudative AMD group (P = 3.1 × 10(-8)) and PCV group (P = 6.9 × 10(-3)). For the LOXL1 gene, the genotype frequency of the p.Arg141Leu single nucleotide polymorphism was not statistically higher in the dry AMD and PCV groups than in the control group (dry AMD, P = .05; PCV, P = .16), but was statistically higher in the exudative AMD group (P = 6.8 × 10(-3)). Regression analyses showed significant associations between the ARMS2 gene and LOXL1 gene in patients with exudative AMD., Conclusions: The p.Ala69Ser polymorphism of the ARMS2 gene is strongly associated with exudative AMD and PCV and is associated marginally with dry AMD. The polymorphisms in the LOXL1 gene did not predispose the individual to dry AMD and PCV. These findings suggest that there is a significant association between the ARMS2 gene and LOXL1 gene in exudative AMD., (Copyright © 2011 Elsevier Inc. All rights reserved.)

Purpose: To determine the characteristics of the polymorphisms in the ARMS2 gene in Japanese patients with age-related macular degeneration (AMD) and those with polypoidal choroidal vasculopathy (PCV) and in healthy controls, and also to show possible associations of the polymorphisms with the disease., Design: Case-control association study., Methods: Fifty-six unrelated Japanese individuals with AMD, 55 with PCV, and 77 controls were studied. The most common polymorphism in the ARMS2 gene on chromosome 10 was resequenced. Association tests were performed for inferred haplotypes., Results: A total of 22 polymorphisms were identified, and 13 were shared with those in White persons with AMD. The sequence of the deletion-and-insertion polymorphism, de1443ins54, a functional polymorphism causing an instability of the messenger ribonucleic acid of ARMS2 in the Japanese, did not differ from that in White persons. Among the polymorphisms seen in the White population, rs10490923 (R3H) as well as 7 other polymorphisms were not observed in the Japanese. One haplotype, which contained the T allele of the rs10490924 (A69S) and the variant of de1443ins54 polymorphism, had an odds ratio of 3.14 (P = 7.8 x 10(-6)) for AMD and 2.00 (P = .0058) for PCV. Among the 9 polymorphisms that were unique to the Japanese population, 2 had a minor allelic frequency of more than 0.05, and these 2 polymorphism were included as nonrisk haplotypes., Conclusions: The de1443ins54 polymorphism is a common variant between White and Japanese populations. It is strongly associated not only with AMD but also with PCV.

Objectives: Recent evidences suggest that the activation of peroxisome proliferator-activated receptor (PPAR)-gamma2, which plays an important role in vascular homeostasis, also regulates the expression of the Receptor for Advanced Glycation End products (RAGE). In turn, low levels of soluble RAGE (sRAGE) have recently emerged as a valuable biomarker of vascular inflammation. The potential alterations in sRAGE concentrations in peripheral arterial disease (PAD), however, have not been yet investigated. The aim of the present study was to clarify whether the Pro12Ala polymorphism of the PPAR-gamma2 gene is related to plasma sRAGE levels and the presence of PAD in nondiabetic Italian individuals., Design and Methods: A total of 201 patients with PAD and 201 PAD-free control subjects were investigated. Genotyping of the Pro12Ala polymorphism of the PPAR-gamma2 gene was performed by means of PCR-RFLPs. Plasma sRAGE levels were determined by ELISA., Results: Subjects carrying at least one Ala12 allele of the PPAR-gamma2 gene had lower sRAGE levels (all p values<0.001). The prevalence rate of the Ala12 allele was significantly higher in PAD patients (14.0%) than in controls (8.0%, p=0.009). In multivariate logistic regression analysis after adjustment for potential confounders, the Ala12 allele was significantly and independently associated with the risk of PAD (OR=1.57, 95% CI=1.11-2.65, p=0.021)., Conclusions: Our data indicate that the Ala12 allele of the PPAR-gamma2 gene is associated with lower levels of the soluble decoy receptor sRAGE and the presence of PAD.

Objectives: Microsomal triglyceride transfer protein (MTP) transfers lipids into apoprotein B-containing lipoproteins for secretion from liver, intestine, and heart. We hypothesized the -493T single nucleotide polymorphism in the MTP promoter region to be associated with altered lipoprotein levels and with presence of peripheral arterial disease (PAD)., Design and Methods: 433 patients with symptomatic PAD and 433 controls matched for sex and age from the Linz Peripheral Arterial Disease (LIPAD) study were genotyped cross-sectionally for the -493T single nucleotide polymorphism in the promoter region of the MTP gene., Results: The frequency of the -493T allele in patients with PAD was 0.320, whereas it was 0.255 in controls (p<0.001). The MTP -493TT genotype was independently associated with PAD, even after adjustment for LDL cholesterol. The odds ratio of the -493TT MTP genotype for PAD was 3.18 (95% CI, 1.76-5.71) when adjusted for current smoking, arterial hypertension, LDL cholesterol, triglycerides, glycohemoglobin, C-reactive protein, and homocysteine. Furthermore, we found an association between the MTP promoter polymorphism and the apolipoprotein B-containing lipoproteins total-cholesterol (p=0.011), LDL cholesterol (p=0.002) and apolipoprotein B (p=0.034)., Conclusions: Our results provide preliminary evidence for a potential role of the MTP -493TT genotype in the pathogenesis of PAD.

Purpose: To investigate whether the LOC387715 polymorphism is associated with polypoidal choroidal vasculopathy (PCV) and with vitreous hemorrhage (VH), one of the most severe clinical phenotypes, in the Japanese population., Design: Cross-sectional case-control association study., Methods: One hundred and nine Japanese patients with PCV, composed of nine patients associated with VH (VH group) and 100 patients without VH (non-VH group), and 85 control subjects were analyzed for the LOC387715 polymorphism (rs = 10490924), using denaturing high-performance chromatography., Results: There was a significant difference in the T allele frequency between PCV patients and control subjects (P < .0001). In comparison with wild-type homozygosity (GG), homozygosity for the at-risk allele genotype (TT) increased the likelihood for PCV 8.4-fold (3.6 to 19.5, 95% confidence interval [CI]) and heterozygosity for the at-risk allele genotype (TG) increased the likelihood for PCV 4.0-fold (1.9 to 8.4, 95% CI). There was a significant difference in the genotypic frequency at the LOC387715 site between the VH and non-VH groups (P = .0099, Chi-square test) with the TT genotype occurring in 88.9% in the VH group and 37.0% in the non-VH group. The frequency of the T allele in the VH group was significantly greater than that in the non-VH group (0.944 vs 0.610; P = .0039, Fisher exact test)., Conclusions: The LOC387715 polymorphism is associated with PCV and clinical severity in the subgroups of PCV in the Japanese population.

Purpose: To investigate whether variants in the LOC387715 locus and the HtrA serine peptidase 1 (HTRA1) gene within the 10q26 locus are associated with polypoidal choroidal vasculopathy (PCV) and wet age-related macular degeneration (AMD) in a Japanese population, and whether genetic diversity exists between PCV and wet AMD in this locus., Design: Cross-sectional study., Methods: We genotyped 243 Japanese individuals, including 76 PCV cases, 73 wet AMD cases, and 94 controls using two single nucleotide polymorphisms (SNPs) that are located in the LOC387715 locus (rs10490924) or the HTRA1 gene (rs11200638). Genotyping was performed using TaqMan assays (Applied Biosystems, Foster City, California, USA)., Results: Two SNPs generated highly significant allelic associations with PCV (rs10490924, P = 5.7 x 10(-6); rs11200638, P = 5.2 x 10(-6)) and AMD (rs10490924, P = 1.4 x 10(-6); rs11200638, P = 3.4 x 10(-7)). The odds ratios and population attributable risks were higher for the AMD cases than for the PCV cases. Homozygotes for the risk allele at rs11200638 had a 6.33-fold increased risk of PCV and a 13.77-fold increased risk of wet AMD when compared with homozygotes for the wild-type allele. There were no significant differences in either allelic or genotypic frequencies between PCV and AMD cases., Conclusions: The LOC387715/HTRA1 variants are associated with PCV and wet AMD in the Japanese population. The associations are stronger in AMD than in PCV. PCV and AMD share common genetic factors, which suggests that PCV and wet AMD are similar in some pathophysiologic aspects.