Macular Degeneration: Oshima Y

Takeuchi A, Takeuchi M, Oikawa K, Sonoda KH, Usui Y, Okunuki Y, Takeda A, Oshima Y, Yoshida K, Usui M, Goto H, Kuroda M. · Department of Ophthalmology, Tokyo Medical University, Tokyo, Japan. · Invest Ophthalmol Vis Sci. · Pubmed #19182260 No free full text.

Abstract: PURPOSE: Cigarette smoking is the most consistent risk factor for age-related macular degeneration (AMD), especially the choroidal neovascularization (CNV)-mediated exudative type. Dioxins and dioxin-like compounds have various effects on living organisms and are also contained in cigarette smoke. However, the effects of dioxins on the eye remain elusive. In this study, the authors examined the association between dioxins and neovascularization in the eye. METHODS: C57BL/6 mice were injected intraperitoneally with 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) every other day for 14 days. Messenger RNA expression of cytochrome P450 (CYP)1A1, CYP1B1, vascular endothelial growth factor (VEGF)-A and VEGF-B, and VEGF production were examined in the eyes of TCDD-treated mice and in human retinal pigment epithelial cell lines (ARPE-19) exposed to TCDD. In addition, CNV was induced by photocoagulation in mice injected with TCDD, and the volume of CNV was compared by fluorescence-labeled choroidal flat mount. RESULTS: TCDD injected intraperitoneally increased CYP1A1 mRNA expression in the iris/ciliary body and retina, indicating that TCDD acts directly on ocular tissues through the aryl hydrocarbon receptor (AhR) to promote the transcription of target genes. TCDD also promoted VEGF-A mRNA expression in the retina and the retinal pigment epithelium. TCDD-induced VEGF production at the molecular level was also observed in vivo by immunohistochemistry and in vitro using ARPE-19. Moreover, the injection of TCDD significantly exacerbated photocoagulation-induced CNV in mice. CONCLUSIONS: The authors demonstrate that dioxins are among the factors inducing abnormal vascularization in the eye through VEGF production mediated by AhR signaling.

Hijioka K, Sonoda KH, Tsutsumi-Miyahara C, Fujimoto T, Oshima Y, Taniguchi M, Ishibashi T. · Department of Ophthalmology, Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582, Japan. · Biochem Biophys Res Commun. · Pubmed #18606153 No free full text.

Abstract: Choroidal neovascularization (CNV) is directly related to visual loss in age-related macular degeneration and other macular disorders. We have investigated the role of CD1d-restricted invariant natural killer T (NKT) cells in laser-induced experimental CNV. Quantitative real-time PCR detected increased expression of NKT cell-related genes (Valpha14 and CXCL16) in whole eyes undergoing CNV, indicating local accumulation of NKT cells. We found a significant reduction of CNV and lower concentrations of vascular endothelial growth factor (VEGF) in ocular fluid in two different NKT cell-deficient mice, CD1d knockout (KO) and Jalpha18 KO mice. We also established in vitro co-cultures of retinal pigment epithelial cells and splenic NKT cells, and confirmed NKT cells could produce VEGF in the dish. Moreover, inoculating alpha-galactosylceramide, the ligand for NKT cells, into the vitreous cavity of C57BL/6 mice promoted CNV. We concluded that NKT cells play an important role in CNV as an inducer of VEGF.

Fang X, Sakaguchi H, Gomi F, Oshima Y, Sawa M, Tsujikawa M, Ikuno Y, Kamei M, Kusaka S, Tano Y. · Department of Ophthalmology, Osaka University Medical School, Osaka, Japan. · Acta Ophthalmol. · Pubmed #18547274 No free full text.

Abstract: PURPOSE: To assess the efficacy, duration of effect and safety of one intravitreal injection of bevacizumab in diabetic macular oedema (DMO). METHODS: Bevacizumab (1 mg/0.04 ml) was injected intravitreally into eyes with DMO (29 with and nine without previous treatments). Best corrected visual acuity (BCVA), intraocular pressure and central retinal thickness (CRT) were measured; slit-lamp examination, macular biomicroscopy, optical coherence tomography and fluorescein angiography were performed before and at 2-4, 8 and 12 weeks post-injection. Best corrected VA and CRT were analysed in both groups. RESULTS: In the non-pretreated group, mean BCVA improved from 0.76 +/- 0.33 (baseline) to 0.57 +/- 0.30 and 0.54 +/- 0.27 at 2-4 weeks and 8 weeks post-injection, respectively (p = 0.02, p = 0.014, paired t-test). Mean CRT decreased from 632.4 +/- 196.0 microm (baseline) to 392.3 +/- 113.6 microm and 370.4 +/- 141.7 microm at the same time-points, respectively (p = 0.01, p = 0.01). There was no difference in BCVA or CRT at 12 weeks. In the pretreated group, mean BCVA improved from 0.62 +/- 0.30 (baseline) to 0.53 +/- 0.33 at 2-4 weeks post-injection (p = 0.01), and mean CRT decreased from 583.9 +/- 180.7 microm (baseline) to 404.1 +/- 197.9 microm at 2-4 weeks post-injection (p < 0.001). Mean BCVA was unchanged at 8 weeks and 12 weeks post-injection, although mean CRT remained lower at 8 weeks (p = 0.004). No ocular or systemic side-effects developed during follow-up. CONCLUSIONS: One intravitreal injection of bevacizumab for DMO seems to be effective and safe in both eyes that have been treated previously and eyes that have not. The therapeutic effect is temporary and repeat treatment may be needed.

Shima C, Sakaguchi H, Gomi F, Kamei M, Ikuno Y, Oshima Y, Sawa M, Tsujikawa M, Kusaka S, Tano Y. · Department of Ophthalmology, Osaka University Medical School, Suita, Japan. · Acta Ophthalmol. · Pubmed #18028234 No free full text.

Abstract: PURPOSE: To report complications in patients after intravitreal injection of bevacizumab to treat ocular diseases associated with vascular endothelial growth factor. METHODS: We retrospectively reviewed the systemic and ocular complications that developed within 2 months of each intravitreal injection of bevacizumab in 707 patients (1300 injections) with intraocular neovascularization or macular oedema. RESULTS: Nine ocular (1.27%) and eight systemic (1.13%) complications occurred in 707 patients. The ocular complications included corneal abrasion (n = 2), chemosis (n = 2), lens injury (n = 1), ocular inflammation (n = 2), retinal pigment epithelial tear (n = 1) and acute vision loss (n = 1). The systemic complications included cerebral infarction (n = 1), elevation of systolic blood pressure (n = 2), facial skin redness (n = 1), itchy diffuse rash (n = 1) and menstrual irregularities (n = 3). CONCLUSION: Intravitreal injection of bevacizumab may cause systemic or ocular complications. Caution is advised when considering intravitreal injection of this drug.

Gomi F, Ohji M, Sayanagi K, Sawa M, Sakaguchi H, Oshima Y, Ikuno Y, Tano Y. · Department of Ophthalmology, Osaka University Medical School, Suita, Osaka, Japan. · Ophthalmology. · Pubmed #17582498 No free full text.

Abstract: PURPOSE: To determine the prevalence of polypoidal choroidal vasculopathy (PCV) in Japanese patients presumed to have age-related macular degeneration (AMD) and compare 1-year outcomes after photodynamic therapy between PCV and choroidal neovascularization secondary to AMD. DESIGN: Prospective interventional study. PARTICIPANTS: Ninety-three consecutive patients (93 eyes) met the inclusion criteria: at least 50 years old, best-corrected visual acuity (VA) of 34 to 73 on the Early Treatment Diabetic Retinopathy Study (ETDRS) letter chart, a subfoveal lesion 5400 mum or smaller in greatest linear dimension (GLD) on fluorescein angiography (FA), and eligibility for photodynamic therapy. METHODS: Indocyanine green angiography was performed in all participants, and PCV and AMD were differentiated, treated with photodynamic therapy, and the patients observed for 1 year. The GLD was determined by FA for AMD and by indocyanine green angiography for PCV, and the diameter of the laser spot size was chosen, with an extra 1000 microm added to the GLD. Photodynamic therapy was repeated if leakage occurred on FA at 3-month follow-up visits. MAIN OUTCOME MEASURES: Prevalence of PCV at baseline and visual and angiographic changes 1 year after photodynamic therapy in PCV and AMD. RESULTS: Using indocyanine green angiography, 36 eyes (39%) were diagnosed with PCV and 54 eyes (58%) with choroidal neovascularization secondary to AMD. The median change in VA using the ETDRS letter score from baseline to 1 year was -7.0 in AMD eyes and +8.0 in PCV eyes (Mann-Whitney rank sum test; P<0.001). The VA improved (> or =15 letters) in AMD and PCV by 6% and 25%, respectively, and decreased (> or =15 letters) by 31% and 8%, respectively. Fluorescein leakage stopped at 1 year in 86% of PCV and 61% of AMD eyes (P = 0.031). Polypoidal choroidal vasculopathy recurred in 2 PCV eyes (5.6%), and a new PCV lesion developed in 1 PCV eye (2.8%) and 2 AMD eyes (3.7%) on indocyanine green angiography at 1 year. CONCLUSION: The prevalence of PCV meeting the treatment criteria for photodynamic therapy for presumed AMD is high in Japanese patients. Photodynamic therapy is more efficacious for PCV than for AMD, which may explain the good results in Japanese patients. Further study should assess the long-term clinical results.

Oshima Y, Ohji M, Tano Y. · Department of Ophthalmology, Osaka University Medical School, 2-2 Yamadaoka (Rm. E7), Suita, Osaka 565-0871, Japan. · Br J Ophthalmol. · Pubmed #16916872 No free full text.

Abstract: AIMS: To report outcome of a modified procedure for draining massive subretinal haemorrhages (SRHs). METHODS: The charts of eight consecutive eyes from eight patients with massive SRHs extending to the periphery and involving two or more quadrants with haemorrhagic and bullous retinal detachment were reviewed. Tissue plasminogen activator (tPA) was injected intravitreally 12-24 h preoperatively; vitrectomy was carried out with peripheral retinotomy, drainage of the SRH from the retinotomy using perfluorocarbon liquid and gas tamponade with prone positioning postoperatively. RESULTS: The preoperative visual acuities ranged from light perception to 20/200. Most of the subretinal haematomas moved postoperatively to the vitreous cavity through the peripheral retinotomy using perfluorocarbon liquid. Residual SRHs were drained from the anterior chamber at the bedside after prone positioning overnight. SRH recurred in one eye 14 months postoperatively and was successfully retreated. No other serious complications developed. The final visual acuity improved in seven eyes (range 20/1000-20/60). Polypoidal lesions in choroidal vasculatures were present in three of seven patients. CONCLUSIONS: The technique seems safe and effective for treating massive SRH. However, visual recovery is limited by the underlying macular pathology. Polypoidal choroidal vasculopathy, other than age-related macular degeneration, may be another cause of massive SRHs.

Kim A, Gomi F, Sakaguchi H, Oshima Y, Ikuno Y, Kamei M, Oji M, Tano Y. · Department of Ophthalmology, Osaka University Hospital, Suita, Japan. · Nippon Ganka Gakkai Zasshi. · Pubmed #16491869 No free full text.

Abstract: PURPOSE: To evaluate the efficacy of sub-Tenon's injection of triamcinolone acetonide for age-related macular degeneration (AMD) and polypoidal choroidal vasculopathy (PCV). METHOD: Sub-Tenon's injection of triamcinolone acetonide was performed in patients (27 eyes) with the subfoveal choroidal neovascularization of AMD and in patients (10 eyes) with PCV, and its efficacy was evaluated. The visual acuity and the exudation from lesions evaluated by fluorescein angiography or optical coherence tomography (OCT) at three months or six months after injection were compared to the baseline values. RESULTS: Visual acuity was maintained in 23 of the 27 eyes (85.0%) with AMD and in 8 of the 10 eyes (80.0%) with PCV at three months after injection. Six months after infusion, the rate declined to 76.0% and 66.7%, respectively. Exudation from lesions had decreased in 10 eyes of 25 eyes(40.0%) with AMD and in 2 eyes of 9 eyes (22.2%) with PCV by six months after injection. Complete suppression of the lesions was observed in seven eyes (18.9%) with relatively small lesions. CONCLUSION: Sub-Tenon's injection of triamcinolone acetonide is useful as a treatment modality for AMD and PCV.

Esumi N, Oshima Y, Li Y, Campochiaro PA, Zack DJ. · The Guerrieri Center for Genetic Engineering and Molecular Ophthalmology, Wilmer Eye Institute, and Department of Ophthalmology, The Johns Hopkins University School of Medicine, Baltimore, Maryland 21287-9289, USA. · J Biol Chem. · Pubmed #14982938 links to  free full text

Abstract: The retinal pigment epithelium (RPE) is crucial for the normal development and function of retinal photo-receptors, and mutations in several genes that are preferentially expressed in the RPE have been shown to cause retinal degeneration. We analyzed the 5'-up-stream region of human VMD2, a gene that is preferentially expressed in the RPE and, when mutated, causes Best macular dystrophy. Transgenic mouse studies with VMD2 promoter/lacZ constructs demonstrated that a-253 to +38 bp fragment is sufficient to direct RPE-specific expression in the eye. Transient transfection assays using the D407 human RPE cell line with VMD2 promoter/luciferase reporter constructs identified two positive regulatory regions, -585 to -541 bp for high level expression and -56 to -42 bp for low level expression. Mutation of a canonical E-box located in the -56 to -42 bp region greatly diminished luciferase expression in D407 cells and abolished the bands shifted with bovine RPE nuclear extract in electrophoretic mobility shift assays. Independently a candidate approach was used to select microphthalmia-associated transcription factor (MITF) for testing because it is expressed in the RPE and associated with RPE abnormalities when mutated. MITF-M significantly increased luciferase expression in D407 cells in an E-box-dependent manner. These studies define the VMD2 promoter region sufficient to drive RPE-specific expression in the eye, identify positive regulatory regions in vitro, and suggest that MITF as well as other E-box binding factors may act as positive regulators of VMD2 expression.

Miyazaki M, Nakamura H, Kubo M, Kiyohara Y, Oshima Y, Ishibashi T, Nose Y. · Department of Medical Information Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan. · Br J Ophthalmol. · Pubmed #12642312 links to  free full text

Abstract: AIMS: To examine the risk factors for age related maculopathy (ARM) in a sample Japanese population. METHODS: In 1998, a cross sectional community survey was conducted among residents of Hisayama. A total of 596 men and 886 women living in Hisayama, Japan, aged 50 years or older consented to participate in the study. Each participant underwent a comprehensive examination that included an ophthalmic examination. The presence of ARM was determined by grading from fundus examination by indirect ophthalmoscopy, slit lamp examination, and colour fundus photographs. Using these cross sectional data, logistic regression analyses were performed to determine the risk factors for ARM. The following 10 possible risk factors were used: age, cataract, hypertension (history), hypertension (history or examination), diabetes, hyperlipidaemia, current smoker, alcohol intake, BMI, and WBC. RESULTS: ARM was detected in 19.5% of men and 14.9% of women. Men were found to have a significantly higher prevalence of ARM than women. Multiple logistic regression analysis showed that age and hypertension (history or examination) were significantly associated with ARM in men, whereas only age was a significant risk factor for ARM in women. CONCLUSIONS: This study suggests that higher age and male sex are relevant risk factors for ARM in Japan. In addition, hypertension is a relevant risk factor in men.

Oshima Y, Ishibashi T, Murata T, Tahara Y, Kiyohara Y, Kubota T. · Department of Ophthalmology, Faculty of Medicine, Kyushu University, Fukuoka, Japan. · Br J Ophthalmol. · Pubmed #11567955 links to  free full text

Abstract: AIM: To determine the prevalence of age related maculopathy (ARM) in a representative older Japanese population. METHODS: 1486 residents of Hisayama town, Fukuoka, Japan, aged 50 years or older were examined and the presence of ARM was determined by grading from fundus examination by indirect ophthalmoscope, slit lamp, and colour fundus photographs. RESULTS: The prevalence rate of drusen, which occurred with comparable frequency in men and women, was 9.6%. The frequency of drusen increased with age (p <0.01). Hyperpigmentation and/or hypopigmentation of the retina was present in 3.2%, geographic atrophy in 0.2%, and neovascular age related macular degeneration in 0.67%. The frequency of neovascular age related macular degeneration was significantly higher in the men (1.2% v. 0.34%, p <0.01). CONCLUSIONS: Early and late stage ARM is less common among Japanese people than among white people in Western countries, while late stage ARM is more common among Japanese than among black people.

Watanabe M, Oshima Y, Emi K. · Department of Ophthalmology, Osaka Rosai Hospital, Sakai-City, Japan. · Am J Ophthalmol. · Pubmed #10682989 No free full text.

Abstract: PURPOSE: To describe the resolution of cystoid macular edema associated with vitreomacular separation in a diabetic patient. METHODS: Case report. A 58-year-old man who had cataract surgery 3 years earlier developed diabetic macular edema after panretinal laser photocoagulation. For a detailed fundus examination, we performed neodymium: YAG (Nd:YAG) laser capsulotomy in the left eye as the initial management. RESULTS: Two days after the laser capsulotomy, fundus biomicroscopy and B-mode ultrasonography disclosed a vitreomacular separation in the left eye that was not detectable preoperatively. Optical coherence tomography through the macula disclosed a dramatic decrease in the size of intraretinal cystoid spaces with an improvement of visual acuity. Scanning retinal thickness analysis also confirmed the decrease of retinal thickness at the macula with the resolution of cystoid macular edema. CONCLUSION: Resolution of diabetic macular edema with subsequent visual recovery is potentially associated with the vitreomacular separation in a patient after Nd:YAG laser capsulotomy.