Macular Degeneration: Tamura H

Tsujikawa A, Nakanishi H, Ojima Y, Iwama D, Tamura H, Otani A, Yoshimura N. · Department of Ophthalmology and Visual Sciences, Kyoto University Graduate School of Medicine, Kyoto, Japan. · Clin Experiment Ophthalmol. · Pubmed #19278475 No free full text.

Abstract: PURPOSE: To report cases of the macular type of polypoidal choroidal vasculopathy with a remote lesion. METHODS: We report six patients (seven eyes) with polypoidal choroidal vasculopathy who had macular and remote lesions. These eyes were examined with angiography and tomography. RESULTS: All seven eyes showed an exudative macular lesion beneath the fovea. In addition, all eyes showed remote polypoidal lesions that were not connected to the macular lesions; the remote lesion was detected outside of the vascular arcade in five eyes, superotemporally beside the optic disc in one eye and on the nasal side of the optic disc in one eye. Indocyanine green angiography, fluorescein angiography and optical coherence tomography failed to reveal any sign of a branching vascular network or choroidal neovascularization that connected the macular lesion with the more remote lesion. At the initial visit, visual acuity in the seven eyes ranged from 6/150 to 6/9 (median, 6/15). Four eyes underwent photodynamic therapy to the exudative macular lesion. During 27.6 +/- 14.3 months of follow up, no worsening was detected in any of the remote lesions. Median visual acuity was 6/60 at the final visit. CONCLUSIONS: Some patients with macular polypoidal choroidal vasculopathy also have a remote lesion, although the remote lesion seems to have only a minor effect on visual outcome.

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.

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.

Kurashige Y, Otani A, Sasahara M, Yodoi Y, Tamura H, Tsujikawa A, Yoshimura N. · Department of Ophthalmology and Visual Sciences, Kyoto University Graduate School of Medicine, Sakyo-ku, Kyoto, Japan. · Am J Ophthalmol. · Pubmed #18614133 No free full text.

Abstract: PURPOSE: To report on the two-year visual outcomes of indocyanine green angiography-guided photodynamic therapy (PDT) for polypoidal choroidal vasculopathy (PCV) patients. DESIGN: Retrospective case study. METHODS: A retrospective analysis that examined the clinical and angiographic data related to 41 eyes of 38 PCV patients (25 males, 13 females; average age +/- standard deviation [SD], 72.9 +/- 7.4 years) with follow-up periods of 24 months or more. RESULTS: The average number of PDT treatments was 1.65. After the 12-month follow-up, 12 eyes required retreatment. Although the mean visual acuity (VA) +/- SD before PDT (0.55 +/- 0.38 logarithm of the minimum angle of resolution units) improved to 0.46 +/- 0.41 at 12 months after the initial PDT, at 24 months, it declined significantly to 0.59 +/- 0.44 (P = .0018). Although only seven of 41 eyes exhibited VA deterioration at the 12-month follow-up examination, a decreased VA was noted in 18 eyes during the period starting from the 12-month follow-up until the final examination. The cases were bilateral in 11 (61.1%) of the 18 eyes. At the final examination, the mean VA of the bilateral cases but not the unilateral cases was significantly lower than that observed for the initial VA. CONCLUSIONS: PDT is an effective treatment against PCV over the short-term for both unilateral and bilateral cases. However, the VA prognosis may not the same after 12 months, especially for those PCV patients who have exudative age-related macular degeneration in contralateral eye.

Tanimoto S, Tamura H, Ue T, Yamane K, Maruyama H, Kawakami H, Kiuchi Y. · Department of Ophthalmology and Visual Science, Graduate School of Biomedical Sciences, Hiroshima University, Japan. · Neurosci Lett. · Pubmed #17194541 No free full text.

Abstract: Age-related macular degeneration (AMD) is one of the leading causes of blindness among older adults in developed countries and also in Japan. Previous research suggests that AMD is etiologically a complex disease, caused by multiple genes and environmental factors. Association studies have identified that a complement factor H gene (CFH) variant is a major risk factor for AMD in Caucasians. However, we and two other groups have reported no association between CFH and AMD in the Japanese population. Recent studies have suggested that LOC387715 on chromosome 10q26 may be the second major risk loci for AMD in Caucasians. In this study, we examined the association between LOC387715 and AMD in Japanese, and our results show that polymorphism of the LOC387715 gene is associated with AMD in Japanese as well as in Caucasians. Our data show a disease odds ratio of 6.20 (95% CI: 2.87-13.40) conferred by homozygosity for risk alleles at LOC387715 compared with the non-risk genotype. A polymorphism of LOC387715 gene is associated with AMD in the Japanese population.

Uka J, Tamura H, Kobayashi T, Yamane K, Kawakami H, Minamoto A, Mishima HK. · Department of Ophthalmology and Visual Science, Graduate School of Biomedical Sciences, Hiroshima University, Hiroshima, Japan. · Retina. · Pubmed #17151483 No free full text.

Abstract: PURPOSE: The aim of this study was to determine whether genetic polymorphism of complement factor H (CFH) is associated with age-related macular degeneration (AMD) in the Japanese population. METHODS: Genomic DNA was examined in a cohort of 67 Japanese patients with AMD and 107 controls. TT/TC/CC genotypes on exon 9 were screened for sequence alternation by polymerase chain reaction analysis and through sequencing. RESULTS: The mean ages +/- SD of AMD patients and control subjects were 73 +/- 8.5 years and 72 +/- 8.7 years, respectively. There was no significant difference between CFH genotypes in the AMD group (TT, 76%; TC, 19%; CC, 5%) and the control group (TT, 80%; TC, 17%; CC, 3%). The frequencies of T and C alleles were 86% and 14%, respectively, in the AMD group and 89% and 11%, respectively, in the control group. CONCLUSION: CFH gene polymorphism is not associated with AMD in the Japanese population. Moreover, the frequency of the C allele is low among the Japanese population.

Noma H, Funatsu H, Yamasaki M, Tsukamoto H, Mimura T, Sone T, Hirayama T, Tamura H, Yamashita H, Minamoto A, Mishima HK. · Department of Ophthalmology and Visual Science, Graduate School of Biomedical Sciences, Hiroshima University, Minami-ku, Hiroshima, Japan. · Eye. · Pubmed #16826241 No free full text.

Abstract: AIM: To investigate whether the aqueous levels of vascular endothelial growth factor (VEGF) and interleukin-6 (IL-6) are correlated to the vitreous levels of these substances and to the severity of macular oedema in branch retinal vein occlusion (BRVO). METHODS: Aqueous and vitreous samples were obtained during cataract and vitreous surgery from 24 patients (24 eyes) with macular oedema in BRVO. The VEGF and IL-6 levels in aqueous humour, vitreous fluid, and plasma were determined by enzyme-linked immunosorbent assay. The degree of retinal ischaemia was evaluated in terms of the area of capillary nonperfusion using the Scion Image. The severity of macular oedema was evaluated using the OCT. RESULTS: The aqueous level of VEGF was significantly correlated with the vitreous level of VEGF (P<0.0001). Vitreous levels of VEGF and IL-6 were significantly correlated with the nonperfusion area of BRVO (P<0.0001, P=0.0061, respectively), as were the aqueous levels of VEGF and IL-6 (P<0.0001, P=0.0267, respectively). Furthermore, the vitreous levels of VEGF and IL-6 and the aqueous level of VEGF were significantly correlated with the severity of macular oedema of BRVO (P=0.0001, P=0.0331, P=0.0272, respectively). CONCLUSION: Our results suggest that the aqueous level of VEGF may reflect its vitreous level. Measurement of the aqueous level of VEGF may be clinically useful to indicate the severity of macular oedema with BRVO.

Musashi K, Kiryu J, Miyamoto K, Miyahara S, Katsuta H, Tamura H, Hirose F, Yoshimura N. · Department of Ophthalmology and Visual Sciences, Kyoto University Graduate School of Medicine, Kyoto, Japan. · Invest Ophthalmol Vis Sci. · Pubmed #15980248 links to  free full text

Abstract: PURPOSE: Macular edema is one of the most serious adverse effects after retinal scatter laser photocoagulation. It has been suggested that the inflammatory reaction after photocoagulation may be involved in the pathogenesis of macular edema. This study was designed to evaluate quantitatively the inhibitory effects of argatroban, a direct thrombin inhibitor, on leukocyte-endothelial cell interactions and vascular permeability after scatter laser photocoagulation. METHODS: Argon laser photocoagulation was performed in one half of the retina in pigmented male rats (n = 114). Argatroban was administered just before scatter laser photocoagulation. In the other half of the retina, AO leukocyte fluorography was used to evaluate in vivo leukocyte rolling along the retinal vein and accumulation in the retinal capillary bed. The expressions of P-selectin and intercellular adhesion molecule (ICAM)-1 were evaluated by reverse transcription-polymerase chain reaction. Retinal vessel permeability was quantified by using fluorescein isothiocyanate (FITC)-conjugated dextran. RESULTS: Scatter laser photocoagulation caused significant inflammatory leukocyte-endothelial cell interactions in the nonphotocoagulated half of the retina. Treatment with argatroban suppressed leukocyte-endothelial cell interactions. The maximum number of rolling and accumulating leukocytes was reduced by 46.6% (P < 0.01) and 51.4% (P < 0.01), respectively. The expression of P-selectin and ICAM-1 mRNA was suppressed significantly in the argatroban-treated retinas (P < 0.05). Retinal vascular permeability was also suppressed significantly (P < 0.05). CONCLUSIONS: Argatroban suppressed leukocyte-endothelial cell interactions and blood-retinal barrier breakdown after scatter laser photocoagulation, suggesting that argatroban prevents postlaser macular edema.

Tamura H, Miyamoto K, Kiryu J, Miyahara S, Katsuta H, Hirose F, Musashi K, Yoshimura N. · Department of Ophthalmology and Visual Sciences, Kyoto University Graduate School of Medicine, Kyoto, Japan. · Invest Ophthalmol Vis Sci. · Pubmed #15790913 links to  free full text

Abstract: PURPOSE: Recently, intravitreal injection of corticosteroids has been in wide use as a treatment for diabetic macular edema, and the outcomes have been favorable. However, the exact mechanism remains unclear. The hypothesis for the current study was that intravitreal corticosteroids may improve diabetic retinal edema by amelioration of blood-retinal barrier (BRB) breakdown, by inhibiting leukocyte stasis (leukostasis). METHODS: Diabetes was induced in 6-week-old male Long-Evans rats by intraperitoneal injection of streptozotocin (75 mg/kg). Three weeks after induction of diabetes, intravitreal injection of dexamethasone (40 microg/10 microL) was performed. At 2 days after intravitreal injection, accumulated leukocytes were counted in vivo by acridine orange leukocyte fluorography, and BRB breakdown was evaluated by measurement of retinal vascular permeability. The mRNA expression and protein levels of intercellular adhesion molecule (ICAM)-1 in the retina were also studied. RESULTS: The number of leukocytes accumulated in the retina, once increased in the diabetic group, was decreased by 31.6% (P = 0.0001) after dexamethasone injection. The level of BRB breakdown, also elevated in the diabetic group, was suppressed by 61.1% (P = 0.0046) after dexamethasone injection. The level of ICAM-1 mRNA expression and its protein, upregulated in the diabetic group, were downregulated by dexamethasone treatment by 70.0% (P < 0.0001) and 56.4% (P = 0.0003). CONCLUSIONS: Intravitreal injection of corticosteroids improves diabetic retinal edema through inhibiting leukocyte recruitment in the diabetic retina.

Kiryu J, Kita M, Tanabe T, Yamashiro K, Ieki Y, Miura S, Miyahara S, Tamura H, Honda Y. · Department of Ophthalmology and Visual Sciences, Kyoto University Graduate School of Medicine, Kyoto, Japan. · Jpn J Ophthalmol. · Pubmed #12967864 No free full text.

Abstract: PURPOSE: To examine retrospectively the visual outcomes in patients undergoing vitrectomy for epiretinal membranes secondary to sarcoid uveitis. METHODS: Eleven consecutive patients (11 eyes) with epiretinal membrane and uveitis associated with sarcoidosis underwent pars plana vitrectomy. RESULTS: Nine eyes (82%) gained two or more lines of Snellen visual acuity at 1-12 months after surgery. However, 4 of these 9 eyes lost two or more lines of Snellen visual acuity by the final visit. Overall, 5 eyes (45%) had attained at least two Snellen lines of visual acuity improvement, 5 eyes (45%) were unchanged, and 1 eye (10%) had worsened by two lines at the final visit. Nine eyes (81%) achieved visual acuity of 20/40 or better by the final visit. Slit-lamp biomicroscopy and fluorescein angiography showed that cystoid macular edema had resolved in 4 of 7 eyes postoperatively; vitritis improved in all cases. Postoperative complications included cataract formation, glaucoma, and membrane recurrence. Subsequent surgeries consisted of cataract extraction in 2 eyes and membrane peeling in 1 eye. CONCLUSIONS: Pars plana vitrectomy appears to have a beneficial effect on restoring vision in eyes with epiretinal membrane and uveitis associated with sarcoidosis, but final visual acuity was limited by the development of cataract and membrane recurrence.