Macular Degeneration: Gotoh N

Gotoh N, Nakanishi H, Hayashi H, Yamada R, Otani A, Tsujikawa A, Yamashiro K, Tamura H, Saito M, Saito K, Iida T, Matsuda F, Yoshimura N. · Department of Ophthalmology, Kyoto University Graduate School of Medicine, Kyoto, Japan. · Am J Ophthalmol. · Pubmed #19268887 No free full text.

Abstract: 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.

Gotoh N, Yamada R, Nakanishi H, Saito M, Iida T, Matsuda F, Yoshimura N. · Department of Ophthalmology, Fukushima Medical University School of Medicine, Fukushima, Japan. · Clin Experiment Ophthalmol. · Pubmed #18939352 No free full text.

Abstract: BACKGROUND: 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. METHODS: 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. RESULTS: 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). CONCLUSIONS: 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.

Iwama D, Otani A, Sasahara M, Yodoi Y, Gotoh N, Tamura H, Tsujikawa A, Yoshimura N. · Department of Ophthalmology and Visual Sciences, Kyoto University Graduate School of Medicine, Kyoto, Japan. · Br J Ophthalmol. · Pubmed #18662914 No free full text.

Abstract: AIM: To examine the effects of photodynamic therapy (PDT) with verteporfin combined with low-dose intravitreal triamcinolone acetonide (IVTA) for exudative age-related macular degeneration (AMD) that is resistant to PDT alone. DESIGN: Retrospective case series. METHODS: A retrospective review was performed, using the medical records of 22 eyes of 21 patients who consecutively received combined PDT and 2 mg of IVTA for exudative AMD with a suspected chorioretinal anastomosis or for AMD that was resistant to prior PDT alone. Only those patients who could be followed up for more than 12 months after this combined therapy were enrolled in the study. Best corrected visual acuity and intraocular pressure measurements were taken during each examination. Colour photography, fluorescein/indocyanine green angiography and optical coherence tomography were carried out at baseline and every 3 months thereafter. Need for retreatment was based on dye leakage and the presence of serous retinal detachement (SRD) seen by optical coherence tomography. RESULTS: Visual acuity improved or was maintained in the majority of patients, with the mean change between baseline and the last visit being an improvement of 0.94 lines (p = 0.45). Seventeen (77%) of the 22 eyes showed improved or maintained visual acuity after 12 months of follow-up. Eight (36%) of the 22 eyes continued to show an SRD at the 12-month follow-up; this corresponded to unchanged or even decreased leakage of dye. The mean number of retreatments was 1.36, but the incidence of side effects accompanying treatment was not as high as that reported previously for combined therapy that utilised higher-dose IVTA. CONCLUSIONS: PDT combined with low-dose IVTA for exudative AMD seems to be as effective and safe as combined therapy with the higher-dose IVTA that was reported previously.

Sasahara M, Tsujikawa A, Musashi K, Gotoh N, Otani A, Mandai M, Yoshimura N. · Department of Ophthalmology and Visual Sciences, Kyoto University Graduate School of Medicine, Kyoto, Japan. · Am J Ophthalmol. · Pubmed #17011852 No free full text.

Abstract: PURPOSE: To describe the incidence and clinical characteristics of polypoidal choroidal vasculopathy (PCV) associated with choroidal vascular hyperpermeability. DESIGN: Retrospective observational case series. METHODS: We reviewed the medical records of 122 consecutive eyes with PCV and 106 consecutive eyes with exudative age-related macular degeneration (AMD). Fluorescein angiography and indocyanine green (ICG) angiography were performed using a confocal scanning laser system. In the midphase of ICG angiography, we evaluated choroidal vascular hyperpermeability, which is recognized as one of the characteristic findings in central serous chorioretinopathy (CSC). Choroidal vascular hyperpermeability appeared as multifocal patchy areas of hyperfluorescence with blurred margins within the choroid that increased in intensity with time after injection of the dye. RESULTS: Of 122 eyes with PCV, 12 (9.8%) eyes of 10 patients exhibited multifocal choroidal hyperfluorescence in the midphase of ICG angiography, whereas two (1.9%) of 106 eyes with exudative AMD showed a similar appearance (P = .013). Of the 12 eyes in 10 patients with PCV that demonstrated multifocal choroidal hyperfluorescence, we also noted that the early phase of ICG angiography showed choroidal filling delay in seven eyes (58%) and venous dilation in 12 eyes (100%). Four of these 12 eyes (33%) had a medical history of CSC, and nine (90%) of the 10 patients revealed multifocal choroidal hyperfluorescence bilaterally. CONCLUSIONS: Multifocal choroidal hyperfluorescence seen by ICG angiography occurs more frequently in eyes with PCV than in those with AMD. Choroidal vascular hyperpermeability, reportedly a characteristic finding in CSC, might be one of the risk factors of PCV.

Gotoh N, Yamada R, Hiratani H, Renault V, Kuroiwa S, Monet M, Toyoda S, Chida S, Mandai M, Otani A, Yoshimura N, Matsuda F. · Department of Ophthalmology, Kyoto University Graduate School of Medicine, Kyoto, Japan. · Hum Genet. · Pubmed #16710702 No free full text.

Abstract: 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.

Gotoh N, Kuroiwa S, Kikuchi T, Arai J, Arai S, Yoshida N, Yoshimura N. · Department of Ophthalmology, Shinshu University School of Medicine, Matsumoto, Japan. · Am J Ophthalmol. · Pubmed #15488782 No free full text.

Abstract: PURPOSE: To study the genotypes, allelic frequencies, and polymorphisms of apolipoprotein E (Apo E) in unrelated Japanese patients with polypoidal choroidal vasculopathy (PCV) or exudative age-related macular degeneration (AMD) and control subjects without macular degeneration. DESIGN: Cross-sectional study. METHODS: Blood samples from 225 subjects older than 50 years were used. The 225 subjects included 58 patients with PCV, 85 with AMD, and 82 without macular degeneration. Coding exons of the Apo E gene were amplified by polymerase chain reaction, and the DNA sequences were determined by direct sequencing with an automated sequencer. RESULTS: Apo E epsilon3/epsilon3 was the most frequent genotype with a prevalence of 79.3% in PCV patients, 76.5% in AMD patients, and 67.1% in the control subjects. However, the differences in the percentages were not statistically significant among the three groups. The most frequently found allele in the three groups was epsilon3. Patients with PCV and AMD were less likely to have epsilon2 and epsilon4 than the control subjects, but the differences were not statistically significant. Five minor Apo E single nucleotide polymorphisms, including epsilon5 and epsilon7, were found. CONCLUSION: Japanese patients with PCV and AMD were less likely to have epsilon2 and epsilon4 polymorphisms, but the differences from the normals were not statistically significant for the Apo E genotypes and allelic frequencies.

Gotoh N, Yamada R, Matsuda F, Yoshimura N, Iida T. · No affiliation provided · Am J Ophthalmol. · Pubmed #18573360 No free full text.

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