Macular Degeneration: Yoshimura N

Yoshimura N. · No affiliation provided · Nippon Ganka Gakkai Zasshi. · Pubmed #17402559 No free full text.

This publication has no abstract.

Yoshimura N. · Department of Ophthalmology, Shinshu University School of Medicine, 3-1-1 Asahi, Matsumoto 390-8621, Japan. · Nippon Ganka Gakkai Zasshi. · Pubmed #11802459 No free full text.

Abstract: In retinitis pigmentosa, retinal detachment, age-related macular degeneration, and glaucoma, retinal neuronal cells are damaged by a common mechanism, apoptosis. Because apoptosis is an active process that requires de novo expression of a "death message", this process can be controlled by inhibiting the expression of the "death message". We first studied whether a retinal ischemia-reperfusion model can be used as a model for retinal neuronal apoptosis. In the retinal ischemia-reperfusion injuries, typical features of apoptosis, including TUNEL-positive cells, DNA ladder formation, and ultrastructural features of apoptosis were found. Using the model, systematic research to identify the "death message" was done by DNA microarray analysis. About 200 messages were found to be up- or down-regulated during the process of retinal ischemia-reperfusion. These genes were divided into four groups: (1) transcription factor genes, (2) cell cycle-related genes, (3) reactive oxygen scavenger genes and (4) molecular chaperon genes. The possible roles of such genes in neuronal apoptosis following retinal ischemia-reperfusion injury were studied. In the model, reactive oxygen species produced by reperfusion was found to generate lipid peroxides and induced up-regulation of a transcription factor, c-Jun, that further induced aberrant expression of cell cycle-related genes such as cyclin D1 in amacrine cells. However, because no controlled expression of cell cycle-related genes takes place in retinal neurons, amacrine cells died by a G1 arrest mechanism. On the other hand, horizontal cells never expressed cyclin D1 and the cells were found to die by necrosis. The study revealed a possible mechanism of retinal neuronal apoptosis and it also became apparent that different types of neurons use different "death messages". Furthermore, the possibility that inhibition of a "death message" sometimes induces necrosis rather than apoptosis was shown. This means that we need to try inhibition of the death mechanism upstream rather than downstream. Administration of thioredoxin, an endogenous reactive oxygen species that blocks generation of lipid peroxides and thus inhibits the death process upstream, was found to be neuroprotective against retinal ischemia-reperfusion injury. Aberrant expression of c-Jun and cyclin D1 was down-regulated by the treatment. Possible roles of caspases were also studied by using the ischemia-reperfusion injury, RCS rat, and excessive light exposure damage in wild type and caspase-1 deficient mice. Also, application of adeno-associated virus that carries Bcl-xL was tested to find possible neuroprotective effects on RCS rats. Our studies showed that caspase-1 played a more important role in the retinal photoreceptors and caspase-3 was important in neurons in the inner nuclear layer. Caspase-2 was found to be a major caspase in the retinal ganglion cell layer. In agreement with the findings, caspase-1 deficient mice showed less prominent light damage than wild type mice. Gene therapy by Bcl-xL was effective to protect retinal photoreceptor damage in RCS rats.

Otani A, Sasahara M, Yodoi Y, Kameda T, Tsujikawa A, Yoshimura N. · Department of Ophthalmology and Visual Sciences, Kyoto University Graduate School of Medicine, Japan. · Nippon Ganka Gakkai Zasshi. · Pubmed #19606806 No free full text.

Abstract: PURPOSE: The current study was designed to investigate the role of circulating bone marrow (BM)-derived stem cells in the pathogenesis of polypoidal choroidal vasculopathy (PCV), a distinct type of neovascular age-related macular degeneration (AMD). METHODS: Thirty one clinically documented PCV patients were enrolled. Circulating BM-derived stem cells were collected from the patients' peripheral blood and cultured. Colony forming capacity (Hill assay) and migration activity (Boyden chamber system) were examined and analyzed. RESULTS: Colony forming units (CFU-Hill) were significantly fewer in bilateral PCV patients than in unilateral PCV patients. CFU-Hill was impaired in patients with larger (> 5000 microm) PCV lesions compared with patients with smaller PCV lesions. Migration activity of BM-derived stem cells was also reduced significantly in the bilateral PCV patients than in the unilateral PCV patients. CONCLUSIONS: Similar to CNV associated with AMD, impaired functional activity of circulating BM-derived stem cells was observed in PCV patients with bilateral or larger lesions. Circulating BM-derived stem cells may have a role in the pathogenesis of PCV.

Suzuma K, Murakami T, Watanabe D, Miyamoto K, Kita M, Takagi H, Yoshimura N. · Department of Ophthalmology & Visual Sciences, Graduate School of Biomedical Sciences, Nagasaki University, Japan · Nippon Ganka Gakkai Zasshi. · Pubmed #19455970 No free full text.

Abstract: PURPOSE: To evaluate the effects of intravitreal injection of tissue plasminogen activator (tPA) on central retinal vein occlusion(CRVO) associated with diabetic retinopathy (DR). METHODS: A retrospective study of 42 eyes of 42 patients(mean age: 68 years, female/male = 20/22, 5 eyes associated with DR) with macular edema caused by CRVO treated with tPA. Best corrected visual acuity (BVCA or logarithm of the minimal angle of resolution: logMAR), macular thickness was mea sured by optical coherence tomography (OCT), and several variables were evaluated. RESULTS: The mean logMAR and macular thickness improved significantly in the DR (-) group, but, no significant changes were observed in the DR (+) group. Post-operative posterior vitreous detachment (PVD) developed in 62% of the DR (-) group and none of the DR (+) group. CONCLUSION: There may be no beneficial effects of intravitreal tPA on CRVO associated with diabetic retinopathy.

Hayashi H, Yamashiro K, Tsujikawa A, Ota M, Otani A, Yoshimura N. · Department of Ophthalmology and Visual Sciences, Kyoto University Graduate School of Medicine, Sakyo, Kyoto, Japan. · Am J Ophthalmol. · Pubmed #19327745 No free full text.

Abstract: PURPOSE: To evaluate the correlation between visual outcome and foveal photoreceptor integrity after successful treatment of eyes with neovascular age-related macular degeneration (AMD). DESIGN: Retrospective chart review. METHODS: We retrospectively studied the medical records of 51 eyes of 51 patients with neovascular AMD who were treated successfully with photodynamic therapy (PDT). All eyes were followed-up for more than 24 months after the initial treatment. Using spectral-domain optical coherence tomography, the status of the inner segment and outer segment (IS/OS) photoreceptor junction was assessed as a hallmark of the integrity of the foveal photoreceptor layer. RESULTS: At the final visit, no eyes showed an exudative change. A complete or discontinuous IS/OS line was detected beneath the fovea in 8 (15.7%) and 25 (29.4%) eyes, respectively, whereas 28 (54.9%) had no IS/OS line. Eyes with a continuous or discontinuous IS/OS line beneath the fovea had better final visual acuity (VA) than did eyes without an IS/OS line (P < .001, respectively). Of the 51 eyes, 36 showed polypoidal choroidal vasculopathy (PCV), whereas 15 were diagnosed as having typical AMD without PCV. Visual outcome was significantly better in eyes with PCV (P = .026). Most eyes (13/15; 86.7%) with typical AMD had no IS/OS line at the final visit, whereas only 13 (36.1%) of the 36 eyes with PCV had no IS/OS line beneath the fovea. CONCLUSIONS: Integrity of the photoreceptor layer beneath the fovea is associated with the final VA in neovascular AMD after successful PDT.

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.

Unoki N, Nishijima K, Kita M, Suzuma K, Watanabe D, Oh H, Kimura T, Sakamoto A, Yoshimura N. · Department of Ophthalmology, Kyoto University Graduate School of Medicine, Kyoto, Japan. · Br J Ophthalmol. · Pubmed #19218250 No free full text.

Abstract: AIMS: To evaluate the efficacy of a single posterior sub-Tenon capsule injection of triamcinolone acetonide (PSTA) before panretinal photocoagulation (PRP). METHODS: This 6-month study involved the randomisation of 82 eyes of 41 patients, with bilateral severe non-proliferative diabetic retinopathy or proliferative diabetic retinopathy to a single PSTA 20 mg or to no injection before PRP. The primary end-point was change in best-corrected visual acuity (BCVA) at 6 months compared with that at baseline using the logarithm of the minimum angle of resolution (logMAR). Secondary end-points were changes in retinal thickness and intraocular pressure. RESULTS: The mean changes in logMAR BCVA at 6 months compared with that at baseline were a worsening of 0.010 (SD 0.029) in the control group (no injection) and an improvement of 0.072 (0.028) in the PSTA group (p = 0.04). The mean changes in foveal thickness at 6 months compared with baseline measurements were an increase of 32.8 (82.8) mum in the control group and a lessening of 9.7 (85.6) mum in the PSTA group (p = 0.03). CONCLUSIONS: PSTA before PRP appears to be beneficial in preventing PRP-induced visual loss in eyes with diabetic retinopathy by reducing the chance of macular thickening.

Nakanishi H, Hangai M, Unoki N, Sakamoto A, Tsujikawa A, Kita M, Yoshimura N. · Department of Ophthalmology and Visual Sciences, Kyoto University Graduate School of Medicine, Shougoin, Sakyo-ku, Kyoto, Japan. · Retina. · Pubmed #18997641 No free full text.

Abstract: PURPOSE: To assess detached macula in rhegmatogenous retinal detachment by using spectral-domain optical coherence tomography. METHODS: This retrospective study included 15 eyes of 15 patients with macula-off rhegmatogenous retinal detachment and 16 eyes of 16 patients with acute central serous chorioretinopathy. These patients were examined with a prototype spectral-domain optical coherence tomography system. RESULTS: Spectral-domain optical coherence tomography of eyes with rhegmatogenous retinal detachment revealed macular structural abnormalities, such as small cystoid cavities in the inner nuclear layer (2/15 eyes, 13%), cystoid and/or diffuse edema in the outer nuclear layer (10/15 eyes, 67%), undulations of the photoreceptor layer (7/15 eyes, 47%), and dropout of the photoreceptor inner and outer segment layers in the fovea (6/15 eyes, 40%); such changes were not seen in eyes with acute central serous chorioretinopathy. The dropout of foveal photoreceptor inner and outer segment layers was correlated with preoperative and postoperative visual acuities (rs = 0.78, P < 0.005 and rs = 0.63, P < 0.05, respectively), thickness of the outer nuclear layer at the fovea (rs = -0.69, P < 0.01), and height of the retinal detachment at the fovea (rs = 0.60, P < 0.05). CONCLUSION: Dropout of the foveal photoreceptor inner and outer segment layers seen on spectral-domain optical coherence tomography imaging may be involved in incomplete recovery of visual acuity after successful retinal reattachment surgery.

Ota M, Tsujikawa A, Kita M, Miyamoto K, Sakamoto A, Yamaike N, Kotera Y, Yoshimura N. · Department of Ophthalmology and Visual Sciences, Kyoto University Graduate School of Medicine, Kyoto, Japan. · Retina. · Pubmed #18997611 No free full text.

Abstract: PURPOSE: To study the correlation between final visual acuity and integrity of the foveal photoreceptor layer after resolution of macular edema (ME) associated with central retinal vein occlusion (CRVO). METHODS: We studied retrospectively 27 eyes of 27 patients with resolved ME associated with central retinal vein occlusion. On optical coherence tomography, integrity of the foveal photoreceptor layer was studied using the junctions between inner and outer segments of the photoreceptor (IS/OS) line as a hallmark. RESULTS: At the final visit, foveal thickness was decreased to a physiologic level in all eyes. On optical coherence tomography, 14 eyes showed the IS/OS line in the fovea, whereas 13 eyes showed no IS/OS line. In concordance with resolution of the ME, visual acuity had improved significantly by the final visit. However, final visual acuity in eyes without an IS/OS line was significantly poorer than that in eyes with an IS/OS line (P < 0.0001). In addition, integrity of the foveal photoreceptor layer after resolution of the ME had a significant correlation with the initial retinal perfusion status (P = 0.0156) and with initial visual acuity (P = 0.0050). CONCLUSIONS: After resolution of the ME associated with central retinal vein occlusion, visual acuity is closely associated with integrity of the foveal photoreceptor layer.

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.

Sasahara M, Otani A, Yodoi Y, Yoshimura N. · Department of Ophthalmology and Visual Sciences, Kyoto University Graduate School of Medicine, Sakyo-ku, Kyoto, Japan. · Invest Ophthalmol Vis Sci. · Pubmed #18806291 No free full text.

Abstract: PURPOSE: In a prior study, the correlation was investigated between circulating hematopoietic stem cells (HSCs) and the activity or severity of choroidal neovascularization (CNV) in patients with age-related macular degeneration (AMD). The present study was designed to explore the role of circulating HSCs in the pathogenesis of CNV in patients with idiopathic (i)CNV. METHODS: Thirteen patients with clinically documented iCNV and 10 age-sex matched patients without iCNV or systemic disease were enrolled in a case-control study. Circulating HSCs were collected from the patients' peripheral blood and cultured. Colony-forming capacity, migration activity, and invasion activity of HSCs were experimentally analyzed. RESULTS: Colony-forming units by Hill's assay (CFU-Hill) were markedly lower (P<0.001) in patients with iCNV (12.8+/-3.2) than in healthy patients (67.6+/-12.6). Invasion activities of HSCs were reduced significantly in patients with iCNV. CFU-Hill was impaired in the patients (4.0+/-1.2) with CNV more than 1500 microm compared with the patients (20.3+/-4.0) with CNV less than 1500 microm (P=0.006). CONCLUSIONS: Similar to the previous finding of CNV associated with AMD, impaired functional activities of circulating HSCs were observed in patients with iCNV, which correlated with the size of iCNV. These results in young patients provide evidence to support the role of circulating HSCs in the pathogenesis of CNV.

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.

Yodoi Y, Sasahara M, Kameda T, Yoshimura N, Otani A. · Department of Ophthalmology and Visual Sciences, Kyoto University Graduate School of Medicine, Sakyo-ku, Kyoto, Japan. · Invest Ophthalmol Vis Sci. · Pubmed #18055794 links to  free full text

Abstract: PURPOSE: Circulating hematopoietic stem cells (HSCs) appear to have roles in the formation of choroidal neovascularization (CNV) in age-related macular degeneration (AMD). This study was conducted to investigate whether the number or function of HSCs plays a role in neovascular AMD. METHODS: Eighty-one patients with neovascular AMD who underwent comprehensive fundus examinations every 3 months were included. The number of CD34(+) HSCs isolated from peripheral blood was counted by flow cytometry. Serum cytokine levels were assessed by enzyme-linked immunosorbent assay. To examine the function of circulating HSCs, mononuclear cells were cultured and then colony forming unit (CFU-EC) and migration were measured. RESULTS: The number of circulating CD34(+) HSCs was significantly increased in the patients with active CNV without major systemic diseases (stable: 3.8 +/- 0.3 cells/microL, active: 5.5 +/- 0.7 cells/microL, stable versus active: P < 0.05). The number of HSCs correlated positively with the erythropoietin serum level (r = 0.47, P = 0.002). Although there was no significant difference in the CFU-EC between the patients with CNV and the control subjects, a significant decrease of CFU-EC was observed in the patients with bilateral or larger CNV. CONCLUSIONS: The findings suggest that CD34(+) HSCs may be recruited from bone marrow through a signal from active CNV. Furthermore, HSCs may play a role in the severity of CNV.

Ota M, Tsujikawa A, Murakami T, Yamaike N, Sakamoto A, Kotera Y, Miyamoto K, Kita M, Yoshimura N. · Department of Ophthalmology and Visual Sciences, Kyoto University Graduate School of Medicine, Sakyo-ku, Kyoto, Japan. · Am J Ophthalmol. · Pubmed #18045566 No free full text.

Abstract: PURPOSE: To study the correlation of visual acuity and the foveal photoreceptor layer in eyes with persistent cystoid macular edema associated with branch retinal vein occlusion (BRVO). DESIGN: Retrospective chart review. METHODS: We studied retrospectively the medical records of 42 eyes of 42 patients with persistent cystoid macular edema secondary to BRVO, eyes in which the foveal thickness was greater than 250 microm at final examination. On the vertical image obtained by optical coherence tomography at the final examination, we measured thickness of the foveal photoreceptor layer that was beneath the foveal cystoid spaces. We also assessed status of the junction between inner and outer segments of the photoreceptors (IS/OS) in the fovea. RESULTS: The photoreceptor layer beneath the foveal cystoid spaces was detected as a distinct layer with thickness varying between 33 microm and 124 microm (mean, 71.1 +/- 26.8 microm). Final visual acuity showed no correlation with total foveal thickness (r = 0.336, P = .092). However, it did show a close correlation with thickness of the foveal photoreceptor layer (r = -0.571, P < .0001). Of the 42 eyes, 15 showed a continuous IS/OS line in the fovea. Visual acuity in these eyes with a continuous IS/OS line in the fovea was significantly better than that in eyes with a discontinuous or interrupted IS/OS line (P < .0001). CONCLUSIONS: Both the thickness and the integrity of the foveal photoreceptor layer are associated with visual function in eyes with persistent cystoid macular edema associated with BRVO.

Murakami T, Takagi H, Ohashi H, Kita M, Nishiwaki H, Miyamoto K, Watanabe D, Sakamoto A, Yamaike N, Yoshimura N. · Department of Ophthalmology and Visual Sciences, Graduate School of Medicine, Kyoto University, Japan. · Retina. · Pubmed #18040240 No free full text.

Abstract: PURPOSE: To evaluate the effects of posterior vitreous detachment (PVD) in macular edema associated with central retinal vein occlusion (CRVO) treated with intravitreal tissue plasminogen activator (tPA). METHODS: The authors conducted a retrospective study of 36 eyes of 36 patients with macular edema by CRVO treated with intravitreal tPA. In 16 of 21 eyes without pretreatment PVD, PVD developed after the treatment. Multiple linear regression analysis was used to evaluate the correlation between logarithm of the minimum angle of resolution (logMAR) visual acuity (VA) changes and several variables. RESULTS: The VA and macular thickness significantly improved after treatment. The pretreatment logMAR VA (R = 0.646; P < 0.0001), PVD development after tPA (R = -0.303; P = 0.025), and age (R = 0.255; P = 0.050) correlated with the logMAR VA at final visit. The greater improvement in logMAR VA was correlated only with PVD development (R = 0.467; P = 0.0041). Macular thickness in the eyes with PVD development was significantly less than without PVD development at the 6-month visit and the end of follow-up. CONCLUSION: The findings suggest that PVD development after intravitreal tPA may partly contribute to the resolution of macular edema and a better VA outcome.

Yamaike N, Tsujikawa A, Ota M, Sakamoto A, Kotera Y, Kita M, Miyamoto K, Yoshimura N, Hangai M. · Department of Ophthalmology and Visual Sciences, Kyoto University Graduate School of Medicine, Kyoto, Japan. · Ophthalmology. · Pubmed #17675242 No free full text.

Abstract: OBJECTIVE: To study the pathomorphologic features of cystoid macular edema (CME) associated with retinal vein occlusion by three-dimensional (3D) optical coherence tomography (OCT) and to study the relationship of the ocular findings to visual function. DESIGN: Observational case series. PARTICIPANTS: Twenty eyes of 20 patients with retinal vein occlusion. METHODS: A prototype 3D OCT system based on Fourier-domain OCT technology was fabricated for patient examination in this study. This system uses a superluminescent diode, which has a center wavelength of 830 nm and a bandwidth of 50 nm, as the light source, resulting in 4.3-microm axial resolution in tissue. Data acquisition rates of approximately 18 700 axial scans per second and a sensitivity of 98 dB were achieved. Three-dimensional imaging was performed by volume rendering based on the 3D data set acquired with a raster scan of 256x256 axial scans. MAIN OUTCOME MEASURES: Images of CME pathologic features obtained by 3D OCT and by Stratus OCT (Carl Zeiss, Dublin, CA). RESULTS: The 3D OCT imaging system generates a realistic 3D image of CME with high resolution. In 16 eyes, 3D OCT showed large foveal cystoid spaces, most of which were accompanied by small cystoid spaces in the parafoveal region. Cystoid spaces were seen often in the inner nuclear layer and outer plexiform layer, but were detected to some extent in all retinal layers. The 3D OCT showed clearly a thin back-reflecting line corresponding to the external limiting membrane (ELM) in 18 eyes; of these, cystoid spaces were located on the inside of the ELM in 7 eyes and appeared to be in contact with the ELM in 9 eyes. In 2 eyes, the ELM line could not be seen clearly beneath the large foveal cystoid spaces. Integrity of the ELM in the foveal region had a direct correlation with visual acuity. CONCLUSIONS: Observation of CME using 3D OCT enabled visualization of its spatial extent in each retinal layer and discernment of its relationship to the ELM. The use of 3D OCT thus may improve the monitoring of CME progression and its response to treatment.

Ota M, Tsujikawa A, Murakami T, Kita M, Miyamoto K, Sakamoto A, Yamaike N, Yoshimura N. · Department of Ophthalmology, Kyoto University Graduate School of Medicine, Sakyo-ku, Kyoto 606-8507, Japan. · Br J Ophthalmol. · Pubmed #17504858 No free full text.

Abstract: AIM: To study the correlation between integrity of the photoreceptor layer after resolution of macular oedema (MO) associated with branch retinal vein occlusion (BRVO) and final visual acuity (VA), and to determine prognostic factors for visual outcome. METHODS: We retrospectively studied 46 eyes from 46 patients with resolved MO secondary to BRVO, the foveal thickness of which was less than 250 microm at final observation. We assessed the status of the third high reflectance band (HRB) in the fovea using optical coherence tomography (OCT) at final observation, and studied OCT images taken at the initial visit in the hope of identifying a factor that would be prognostic of visual outcome. RESULTS: No differences were found in initial VA or in foveal thickness between eyes with or without complete third HRB at final observation. However, final VA in eyes without a complete HRB was significantly poorer (p<0.002). Additionally, initial status of the third HRB in the parafoveal area of unaffected retina was associated with final VA; lack of visualisation of the third HRB at 500 microm (p = 0.0104) or 1000 microm (p = 0.0167) from the fovea on initial OCT images was associated with poor visual recovery after resolution of the MO. CONCLUSION: Integrity of the photoreceptor layer in the fovea is associated with VA in resolved MO, and status of the third HRB before treatment might be predictive of visual outcome.

Kawagoe N, Takahashi M, Mandai M, Akimoto M, Suzuki T, Murakami T, Hirami Y, Ikeda H, Yoshimura N. · Department of Ophthalmology and Visual Sciences, Graduate School of Medicine, Kyoto University, Japan. · Nippon Ganka Gakkai Zasshi. · Pubmed #17461040 No free full text.

Abstract: PURPOSE: To diagnose an atypical retinal degenerative disease with choroidal neovascularization by means of gene diagnosis. CASE: A 47-year-old woman had good visual acuity at the first examination. She had scattered chorioretinal degeneration and pigmentation in the peripheral retina. There was a symmetrical visual field defect in the upper and temporal periphery in both eyes. Seven years later, choroidal neovascular membrane (CNV) developed in the fovea of her left eye and visual acuity deteriorated to 0.4 in this eye. Optical coherence tomography revealed type 2 CNV with minimal subretinal fluid. Fluorescein angiography showed very little leakage from the CNV. We used denaturing high performance liquid chromatography(DHPLC) to perform gene diagnosis and found a peripherin/RDS gene mutation of Gly167-Ser. CONCLUSION: Our case had moderate peripheral retinal degeneration with CNV. It is possible that cases like this tend to be misdiagnosed as AMD (age-related macular degeneration) or CNV with high myopia. Evaluation of the gene mutation was useful for diagnosis in this case.

Yamaike N, Kita M, Tsujikawa A, Miyamoto K, Yoshimura N. · Department of Ophthalmology and Visual Sciences, Kyoto University Graduate School of Medicine, Kyoto, Japan. · Am J Ophthalmol. · Pubmed #17258527 No free full text.

Abstract: PURPOSE: To evaluate the relationship between retinal sensitivity and thickness of the macular edema associated with branch retinal vein occlusion (BRVO). DESIGN: Prospective case series. METHODS: We prospectively examined 15 eyes of 15 patients with macular edema associated with BRVO. In each patient, retinal sensitivity in the macular area was examined with the Micro Perimeter 1 (MP-1); retinal thickness was measured by optical coherence tomography (OCT). Eyes with marked retinal hemorrhage or macular nonperfusion were excluded from the current study. RESULTS: Retinal sensitivity measured with the MP-1 was significantly correlated with retinal thickness in the fovea (R(2) = 0.460) and in all extrafoveal regions (R(2) = 0.383 to 0.794). In four eyes treated with triamcinolone acetonide, retinal sensitivity showed marked improvement in parallel with the reduction of the macular edema. CONCLUSIONS: Retinal sensitivity in the macular area correlates linearly and negatively with increased retinal thickness in eyes with BRVO.

Murakami T, Tsujikawa A, Ohta M, Miyamoto K, Kita M, Watanabe D, Takagi H, Yoshimura N. · Department of Ophthalmology and Visual Sciences, Kyoto University Graduate School of Medicine, Sakyo-ku, Kyoto 606-8507, Japan. · Am J Ophthalmol. · Pubmed #17188062 No free full text.

Abstract: PURPOSE: To evaluate the integrity of photoreceptors in macular edema (ME) associated with branch retinal vein occlusion after intravitreal tissue plasminogen activator. DESIGN: Retrospective, interventional case series. METHODS: Nineteen eyes with ME by branch retinal vein occlusion were treated with intravitreal tissue plasminogen activator injection. We assessed visual acuity (VA) and the presence or absence in the fovea of a third high reflectance band (HRB) by optical coherence tomography at the final visit. RESULTS: No differences were found in age, preoperative VA, and foveal thickness between the groups with or without the third HRB. After treatment, the mean VA improved significantly (P < .05) in both groups. At the final visit, the mean VA in the group without HRB was significantly poorer than the group with HRB (P = .0042); foveal thickness did not differ between the groups. CONCLUSIONS: The integrity of the third HRB in the fovea is associated with VA after the resolution of ME.

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.

Murakami T, Takagi H, Kita M, Nishiwaki H, Miyamoto K, Ohashi H, Watanabe D, Yoshimura N. · Department of Ophthalmology and Visual Sciences, Graduate School of Medicine, Kyoto University, Kyoto, Japan. · Am J Ophthalmol. · Pubmed #16876516 No free full text.

Abstract: PURPOSE: To evaluate the efficacy of intravitreal tissue plasminogen activator (tPA) injection for branch retinal vein occlusion (BRVO). DESIGN: Retrospective, interventional case series. METHODS: Seventeen eyes presenting with macular edema caused by BRVO were treated with an intravitreal tPA (Monteplase, 40 k IU) injection. We assessed the visual acuity (VA) and foveal thickness measured with optical coherence tomography. RESULTS: The mean duration of symptoms before surgery was 3.6 +/- 3.8 weeks. The mean logMAR VA significantly improved from 0.603 +/- 0.327 at baseline to 0.388 +/- 0.248 (P < .01) at one month and 0.359 +/- 0.319 (P < .05) at six months. The mean foveal thickness significantly decreased from 738 +/- 156 microm at baseline to 454 +/- 213 microm (P < .001) at one month and 253 +/- 164 microm (P < .001) six months. CONCLUSION: Intravitreal tPA injection may be an effective treatment for resolving macular edema and improving the VA in BRVO.

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.