Macular Degeneration: Sakaguchi H

Shima C, Gomi F, Sawa M, Sakaguchi H, Tsujikawa M, Tano Y. · Department of Ophthalmology, Osaka University Medical School, Suita, Osaka, Japan. · Graefes Arch Clin Exp Ophthalmol. · Pubmed #19308441 No free full text.

Abstract: BACKGROUND: To evaluate the efficacy of combined photodynamic therapy (PDT) and intravitreal bevacizumab injection in eyes with a serous pigment epithelial detachment (PED) associated with age-related macular degeneration (AMD). METHODS: Twenty-two eyes with a serous PED exceeding two disc areas associated with AMD with choroidal vascular abnormalities [choroidal neovascularization (n = 10), polypoidal choroidal vasculopathy (n = 9), and retinal angiomatous proliferation (n = 3)] received combined PDT and intravitreal bevacizumab, and were followed about every 6 weeks for more than 1 year. Additional treatments were given for residual or recurrent lesions. The main outcome measures were changes in the PED height measured by optical coherence tomography, and the best-corrected visual acuity. RESULTS: After one treatment, the PED resolved in 12 eyes (55%) and the PED decreased in ten eyes (45%). There was no recurrence in eight (36%) eyes; however, PED recurred in 14 eyes. At 1 year, the average PED height decreased to 413 microns from the baseline 751 microns (p < 0.001). Twenty eyes (91%) had improved or stabilized vision; two eyes had decreased vision due to a retinal pigment epithelial tear and subretinal hemorrhage. CONCLUSIONS: Combined PDT and intravitreal bevacizumab may decrease the PED height and stabilize visual acuity at 1 year.

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.

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.

Crabb JW, Miyagi M, Gu X, Shadrach K, West KA, Sakaguchi H, Kamei M, Hasan A, Yan L, Rayborn ME, Salomon RG, Hollyfield JG. · Cole Eye Institute and Lerner Research Institute, Cleveland Clinic Foundation, and Department of Chemistry, Case Western Reserve University, OH 44195, USA. · Proc Natl Acad Sci U S A. · Pubmed #12391305 links to  free full text

Abstract: Drusen are extracellular deposits that accumulate below the retinal pigment epithelium on Bruch's membrane and are risk factors for developing age-related macular degeneration (AMD). The progression of AMD might be slowed or halted if the formation of drusen could be modulated. To work toward a molecular understanding of drusen formation, we have developed a method for isolating microgram quantities of drusen and Bruch's membrane for proteome analysis. Liquid chromatography tandem MS analyses of drusen preparations from 18 normal donors and five AMD donors identified 129 proteins. Immunocytochemical studies have thus far localized approximately 16% of these proteins in drusen. Tissue metalloproteinase inhibitor 3, clusterin, vitronectin, and serum albumin were the most common proteins observed in normal donor drusen whereas crystallin was detected more frequently in AMD donor drusen. Up to 65% of the proteins identified were found in drusen from both AMD and normal donors. However, oxidative protein modifications were also observed, including apparent crosslinked species of tissue metalloproteinase inhibitor 3 and vitronectin, and carboxyethyl pyrrole protein adducts. Carboxyethyl pyrrole adducts are uniquely generated from the oxidation of docosahexaenoate-containing lipids. By Western analysis they were found to be more abundant in AMD than in normal Bruch's membrane and were found associated with drusen proteins. Carboxymethyl lysine, another oxidative modification, was also detected in drusen. These data strongly support the hypothesis that oxidative injury contributes to the pathogenesis of AMD and suggest that oxidative protein modifications may have a critical role in drusen formation.

Marmorstein AD, Marmorstein LY, Sakaguchi H, Hollyfield JG. · Department of Ophthalmic Research, Cole Eye Institute, The Cleveland Clinic Foundation, Cleveland, Ohio 44195, USA. · Invest Ophthalmol Vis Sci. · Pubmed #12091448 links to  free full text

Abstract: PURPOSE: To compare the autofluorescence spectra of retinal pigment epithelium (RPE)-associated lipofuscin, Bruch's membrane, and sub-RPE deposits (drusen and basal laminar-linear deposits) in eyes of donors with age-related macular degeneration (AMD) against eyes of age-matched control donors. METHODS: Cryosections were cut from the maculae of unfixed human donor eyes with AMD or from age-matched control eyes. Tissues were excited at wavelengths of 364, 488, 568, and 633 nm. Emission spectra were collected with a confocal microscope equipped with a spectrophotometric detector at 10-nm wavelength intervals between 400 and 800 nm. RESULTS: RPE lipofuscin had strong autofluorescent emissions that were excited at all wavelengths. Bruch's membrane exhibited strong autofluorescence with an emission peak of 485 +/- 5 nm when excited with 364-nm light. At 488-, 568-, and 633-nm excitations, Bruch's membrane and sub-RPE deposits in normal eyes exhibited minimal autofluorescence. In AMD eyes, however, both the 364- and 488-nm excitation wavelengths stimulated substantial blue-green emissions from sub-RPE deposits and Bruch's membrane, with average pixel intensities substantially exceeding that elicited in the yellow-orange range by RPE lipofuscin. CONCLUSIONS: These data suggest that an increase in blue-green autofluorescence of Bruch's membrane relative to the yellow-orange autofluorescence of RPE-associated lipofuscin is associated with AMD. Knowledge of these spectra will be useful in evaluating animal models of macular degenerative disease and in diagnosis of AMD, and will provide a novel signature for further analysis of the molecular entities emitting these fluorescent signatures.

Sakaguchi H, Miyagi M, Shadrach KG, Rayborn ME, Crabb JW, Hollyfield JG. · No affiliation provided · Exp Eye Res. · Pubmed #12076098 No free full text.

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