Macular Degeneration: Yamashita H

Yamashita H. · No affiliation provided · Nippon Ganka Gakkai Zasshi. · Pubmed #18702348 No free full text.

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Haga M, Kawasaki R, Yamashita H. · Department of Ophthalmology and Visual Science, Yamagata University School of Medicine. · Nippon Rinsho. · Pubmed #15999702 No free full text.

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Funatsu H, Yamashita H. · Department of Ophthalmology, Diabetes Center, Tokyo Women's Medical University, 8-1 Kawada-cho, Shinjuku-ku, Tokyo, Japan. · Ophthalmic Physiol Opt. · Pubmed #14622351 No free full text.

Abstract: Despite the beneficial effects of good glycaemic control, loss of vision because of diabetic retinopathy (DR) still occurs. Recent studies have suggested that hypertension is a risk factor for the development and progression of DR and that blood pressure reduction can delay the progression of retinopathy. The renin-angiotensin system is activated by chronic hyperglycaemia, and the vitreous fluid level of angiotensin II (AII) is elevated in patients with proliferative diabetic retinopathy and diabetic macular oedema. AII increases vascular permeability and promotes neovascularization. It has been suggested that an autocrine-paracrine relationship may exist between AII and vascular endothelial growth factor in the ocular tissues. Accordingly, angiotensin-converting enzyme inhibitors or AII Type 1 (AT1) receptor blockers may be useful therapeutic agents for preventing the progression of DR.

Funatsu H, Yamashita H, Shimizu E, Mimura T, Nakamura S, Hori S. · Department of Ophthalmology, Diabetes Center, Tokyo Women's Medical University, 8-1 Kawada-cho, Shinjuku-ku, Tokyo 162-8666, Japan. · Diabetes Res Clin Pract. · Pubmed #15536018 No free full text.

Abstract: The effect of lisinopril (an angiotensin-converting enzyme inhibitor) on diabetic macular edema (DME) was investigated by quantitative measurement of macular thickness. In a nonrandomized clinical trial, 19 normotensive type 2 diabetic patients with DME prospectively received oral lisinopril therapy for 2 months. Another 10 normotensive type 2 diabetic patients with similar DME were prospectively followed for two months without treatment. Central macular thickness was measured with a retinal thickness analyzer (RTA). In the lisinopril group, visual acuity improved by two lines or more in two out of 19 eyes (11%), was unchanged in 15 eyes (78%), and deteriorated by two lines or more in two eyes (11%). The mean central macular thickness was significantly reduced after 2 months of treatment (381.3 +/- 121.1 microm) compared with that before administration (475.2 +/- 171.0 microm, P = 0.0093). In the control group, central macular thickness was not significantly decreased after 2 months (458.5 +/- 113.7 microm, P = 0.2178) compared with the baseline value (464.7 +/- 152.2). Fluorescein angiography showed that macular leakage was decreased in 10 patients from the lisinopril group (53%) and was unchanged in nine patients (47%). There was a significant difference of central macular thickness between the patients with and without improvement of macular leakage (P = 0.0040). Lisinopril therapy may reduce macular thickness in patients with DME, as shown by this quantitative study. In addition, quantitative measurement of retinal thickness is useful when evaluating therapeutic agents for DME.

Tsuchiya D, Yamamoto T, Kawasaki R, Yamashita H. · Department of Ophthalmology and Visual Science, Yamagata University Faculty of Medicine, Yamagata, Japan. · Retina. · Pubmed #19491727 No free full text.

Abstract: PURPOSE: To describe the visual outcomes 2 years after photodynamic therapy in Japanese patients with age-related macular degeneration (AMD) with or without polypoidal choroidal vasculopathy (PCV) lesions. METHODS: Sixty-three eyes of 63 consecutive patients with AMD or AMD + PCV who underwent photodynamic therapy were included in this study. Fluorescein and indocyanine green angiography were performed to diagnose AMD and AMD + PCV. Change in mean visual acuity and recurrence of active lesion during the follow-up period up to 2 years were assessed. RESULTS: Patients with typical AMD maintained visual acuity for 2 years after photodynamic therapy. For patients with AMD + PCV, the visual acuity was maintained during the first year but started decreasing by 0.09 logarithm of the minimum angle of resolution units per 3 months (95% confidence intervals [CI], 0.06-0.14) after 1 year. Moreover, patients with AMD + PCV had 82% higher risk of a recurrence of active lesions for each increase in 3 months of follow-up time after 1 year; this suggested that the risk of recurrence had increased later in follow-up after 1 year. Recurrence of active PCV lesions and massive subretinal hemorrhages were the main reasons for the late worsening of visual acuity. CONCLUSION: The visual acuity after photodynamic therapy in AMD patients was maintained for 2 years after the initial treatment. Patients with AMD + PCV had stable visual outcome within 1 year but not after 1 year; there are risks of late recurrences and massive hemorrhages after 1 year in patients with AMD + PCV.

Yamasaki M, Noma H, Funatsu H, Minamoto A, Mimura T, Shimada K, Yamashita H, Kiuchi Y. · Department of Ophthalmology and Visual Science, Graduate School of Biomedical Sciences, Hiroshima University, 1-2-3 Kasumi, Minami-ku, Hiroshima 734-8551, Japan. · Int Ophthalmol. · Pubmed #18797821 No free full text.

Abstract: Purpose To examine the outcome of vitrectomy for macular edema associated with branch retinal vein occlusion (BRVO) and determine the relationship between the severity of macular edema and the concentration of vascular endothelial growth factor (VEGF) and interleukin-6 (IL-6) in the vitreous fluid. Design Prospective observational case series. Patients and Methods Thirty-four consecutive patients (34 eyes) with macular edema associated with BRVO underwent vitrectomy. Retinal thickness was examined using optical coherence tomography. VEGF and IL-6 levels in the vitreous fluid were determined by enzyme-linked immunosorbent assay. The patients were followed for 6 months and longer after surgery. Results Visual acuity and the retinal thickness at 6 months after operation were significantly improved (P = 0.0042 and P < 0.0001, respectively). There was a significant positive correlation between the vitreous levels of VEGF and improved level of the severity of macular edema. The vitreous levels of VEGF were significantly higher in patients who showed greater improvement in the severity of macular edema (r = 0.4277, P = 0.0116). The vitreous levels of IL-6 were not significantly correlated with improvement in the severity of macular edema (r = 0.1996, P = 0.2578). Conclusion Vitrectomy appears effective for treatment of macular edema with BRVO. A higher VEGF level in the vitreous fluid may be associated with greater improvement of macular edema with BRVO.

Kawasaki R, Wang JJ, Ji GJ, Taylor B, Oizumi T, Daimon M, Kato T, Kawata S, Kayama T, Tano Y, Mitchell P, Yamashita H, Wong TY. · Yamagata University Faculty of Medicine, Yamagata, Japan. · Ophthalmology. · Pubmed #18222000 No free full text.

Abstract: OBJECTIVE: To describe the prevalence and risk factors for age-related macular degeneration (AMD) in a Japanese population and to compare these with data from a white population. DESIGN: Population-based cross-sectional epidemiologic study. PARTICIPANTS: A population-based sample of Japanese persons 35 years or older from Funagata, Japan. METHODS: The Funagata study is a population-based study of 1758 (43% of eligible) Japanese persons 35 years or older from Funagata, Japan. In 2000 to 2002, 1625 (92.4%) participants had a nonmydriatic fundus photograph of one eye with sufficient quality for grading of AMD lesions, using the Wisconsin protocol. Age-standardized prevalence rates compared with the Blue Mountains Eye Study (BMES) population, odds ratios (ORs), and 95% confidence intervals (CIs) were calculated. Risk factors were assessed by logistic regression. MAIN OUTCOME MEASURES: Early and late AMD. RESULTS: Of 1625 participants, early AMD and late AMD were present in 3.5% and 0.5%, respectively. Age-standardized early AMD prevalence in right eyes was 4.1%, similar to the corresponding prevalence of 4.4% in the BMES. For men, age-standardized prevalences of late AMD in right eyes were 1.1% and 1.2% in the BMES; for women, the corresponding prevalences were 0.3% and 2.1%, respectively. Increasing age (per 10 years; gender-adjusted OR, 2.27; 95% CI, 1.10-4.67) and current cigarette smoking (age- and gender-adjusted OR, 5.03; 95% CI, 1.00-25.47) were associated with late AMD. CONCLUSIONS: In this Japanese population, prevalence of early AMD was similar to that for whites in the BMES. Although the late AMD prevalence was lower in Japanese women, in Japanese men it was similar to that in whites. This could have resulted from the substantially high proportion of Japanese men who are smokers. Cigarette smoking and increasing age were the 2 principal factors found associated with late AMD.

Yamamoto T, Takeuchi S, Sato Y, Yamashita H. · Department of Ocular Cellular Engineering, Yamagata University Hospital, Yamagata, Japan. · Jpn J Ophthalmol. · Pubmed #17660989 No free full text.

Abstract: PURPOSE: To analyze the long-term effects of pars plana vitrectomy for diabetic macular edema. METHODS: Sixty-nine patients (73 eyes) with diabetic macular edema were examined retrospectively after pars plana vitrectomy. The mean follow-up time was 24.6 +/- 7.3 months. RESULTS: The postoperative best-corrected visual acuity (BCVA) at 12 months was significantly better than the preoperative BCVA, and the improvement was maintained for at least 24 months. The mean central retinal thickness (RT) at 3 months after surgery was significantly thinner than the preoperative central RT, and was maintained for at least 24 months in the cases followed for this period. The postoperative BCVA was significantly worse than the preoperative BCVA at 2 years after surgery in eyes with a preoperative BCVA of < or =0.05. In addition, there was lower probability that the postoperative BCVA would be > or =0.5 in eyes with a preoperative BCVA of <0.3. CONCLUSIONS: The results indicate that the improvement in the BCVA is attained by 12 months postvitrectomy, and is maintained for at least 24 months. The reduction in RT can be maintained for up to 24 months. The results also indicate that vitrectomy should be performed when the preoperative BCVA is >0.05 at worst.

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.

Funatsu H, Yamashita H, Nakamura S, Mimura T, Eguchi S, Noma H, Hori S. · Department of Ophthalmology, Diabetes Center, Tokyo Women's Medical University, Tokyo, Japan. · Ophthalmology. · Pubmed #16406543 No free full text.

Abstract: PURPOSE: To investigate whether vitreous levels of vascular endothelial growth factor (VEGF) and pigment epithelium-derived factor (PEDF) are related to diabetic macular edema (DME). DESIGN: Retrospective case-control study. PARTICIPANTS: Thirty-six patients with DME, 6 diabetic patients without retinopathy, and 13 patients with nondiabetic ocular disease. METHODS: After vitreous fluid samples were obtained at vitreoretinal surgery, VEGF and PEDF levels in the vitreous fluid were measured by enzyme-linked immunosorbent assay. MAIN OUTCOME MEASURES: Correlations between vascular permeability and the vitreous fluid levels of VEGF and PEDF. RESULTS: The vitreous level of VEGF was significantly higher in patients with DME than in nondiabetic patients and diabetic patients without retinopathy (P<0.0001 and P<0.0001, respectively). Conversely, the vitreous level of PEDF was significantly lower in patients with DME than in nondiabetic patients and diabetic patients without retinopathy (P<0.0001 and P<0.0001, respectively). The vitreous level of PEDF did not correlate significantly with that of VEGF (P = 0.1806). The vitreous level of VEGF was significantly higher in patients with hyperfluorescent DME than in those with minimally fluorescent DME (P = 0.0022). Conversely, the vitreous PEDF level was significantly lower in patients with hyperfluorescent DME than in those with minimally fluorescent DME (P = 0.0172). Vitreous levels of VEGF and PEDF were related to the retinal thickness at the central fovea (P<0.0001 and P = 0.0469, respectively). CONCLUSIONS: Our retrospective study suggests that VEGF and PEDF have an independent association with vascular permeability in the eye and on the DME, and we recommend that prospective validation of our findings be undertaken to confirm these observations.

Noma H, Minamoto A, Funatsu H, Tsukamoto H, Nakano K, Yamashita H, Mishima HK. · Department of Ophthalmology and Visual Science, Graduate School of Biomedical Sciences, Hiroshima University, 1-2-3, Kasumi-cho, Minami-ku, Hiroshima, 734-8551, Japan. · Graefes Arch Clin Exp Ophthalmol. · Pubmed #16133018 No free full text.

Abstract: BACKGROUND: To investigate whether vascular endothelial growth factor (VEGF) or interleukin-6 (IL-6) contributes to the pathogenesis of macular edema in eyes with branch retinal vein occlusion (BRVO), the correlations between these factors were investigated. METHODS: We studied 25 patients suffering from macular edema with BRVO and 14 patients with nonischemic ocular disease (control group). The degree of retinal ischemia was evaluated in terms of the area of capillary nonperfusion using Scion Images, and the severity of macular edema was examined using optical coherence tomography. Vitreous fluid samples were obtained at the time of vitreoretinal surgery, and VEGF and IL-6 levels in the vitreous fluid and plasma were determined by means of enzyme-linked immunosorbent assays. RESULTS: Vitreous fluid levels of VEGF and IL-6 were significantly elevated in patients with BRVO compared with control patients (P = 0.0011 and P < 0.0001, respectively). Also, the vitreous level of VEGF was significantly correlated with that of IL-6 (P = 0.0012), and vitreous levels of VEGF and IL-6 were correlated with the size of the BRVO nonperfusion area (P < 0.0001 and P = 0.0033, respectively). Furthermore, vitreous levels of VEGF and IL-6 were correlated with the severity of macular edema (P = 0.0008 and P = 0.0191, respectively) and the severity of macular edema of BRVO was significantly correlated with the size of the BRVO nonperfusion area (P=0.0044). CONCLUSIONS: The levels of VEGF and IL-6 are increased in patients with macular edema with BRVO and are significantly correlated with the size of the nonperfusion area and the severity of macular edema. Therefore, they may play a role in macular edema with BRVO.

Yamamoto T, Hitani K, Sato Y, Yamashita H, Takeuchi S. · Department of Ocular Cellular Engineering, Yamagata University Hospital, Yamagata, Japan. · Ophthalmologica. · Pubmed #16088239 No free full text.

Abstract: PURPOSE: To compare the efficacy of surgically removing or not removing the internal limiting membrane (ILM) during pars plana vitrectomy on the visual acuity and retinal thickness in eyes with diabetic macular edema. METHODS: A prospective, case-control study was carried out on 30 eyes of 29 patients undergoing pars plana vitrectomy for diabetic macular edema. Fifteen eyes underwent pars plana vitrectomy with ILM removal and 15 eyes without ILM removal. RESULTS: In 7 of 15 eyes (47%) in the ILM-removed group, the visual acuity improved by 0.2 or more log of the minimum angle of resolution (log MAR) units and remained unchanged in 8 eyes (53%). In the ILM-preserved group, the final visual acuity improved in 9 of 15 eyes (60%) and remained unchanged in 6 eyes (40%). The difference in visual acuity between the two groups after 11 months the surgery was not significant (Fisher's exact test, p=0.4938). In the ILM-removed group, the final retinal thickness decreased by more than 20% of the preoperative retinal thickness in 12 of 15 eyes (80%), remained unchanged in 2 of 15 eyes (13%), and increased in 1 of 15 eyes (7%). In the ILM-preserved group, the final retinal thickness decreased in 13 of 15 eyes (87%) and remained unchanged in 2 of 15 eyes (23%). The differences in the changes in the retinal thickness between the two groups were not statistically significant (Fisher's exact test, p=0.5945). CONCLUSION: Vitrectomy in eyes with diabetic macular edema without ILM removal was as effective in reducing the retinal thickness and improving the visual acuity as eyes with ILM removal. We conclude that ILM need not be removed to treat eyes with diabetic macular edema.

Noma H, Funatsu H, Yamasaki M, Tsukamoto H, Mimura T, Sone T, Jian K, Sakamoto I, Nakano K, Yamashita H, Minamoto A, Mishima HK. · Department of Ophthalmology and Visual Science, Graduate School of Biomedical Sciences, Hiroshima University, Hiroshima, Japan. · Am J Ophthalmol. · Pubmed #16086947 No free full text.

Abstract: PURPOSE: To determine whether correlations between vascular endothelial growth factor (VEGF) or interleukin-6 (IL-6) contribute to the pathogenesis of macular edema in eyes of patients with branch retinal vein occlusion (BRVO). DESIGN: Retrospective case-control study. METHODS: Nineteen patients with macular edema with BRVO and seven patients with non-ischemic ocular disease (control group) were studied. The degree of retinal ischemia was evaluated in terms of the area of capillary non-perfusion, and the severity of macular edema was examined by optical coherence tomography. Aqueous humor samples were obtained at the time of combined vitrectomy and cataract surgery, and VEGF and IL-6 levels in aqueous humor and plasma were determined by enzyme-linked immunosorbent assay. RESULTS: Aqueous levels of VEGF (351 +/- 273 pg/ml) and IL-6 (7.10 +/- 6.51 pg/ml) were significantly elevated in patients with BRVO compared with the control patients (119 +/- 38.7 pg/ml and 2.27 +/- 1.11 pg/ml, respectively) (P = .0017 and P = .0052, respectively). Aqueous level of VEGF was significantly correlated with that of IL-6 (P = .0396), and aqueous levels of VEGF and IL-6 were correlated with the size of the BRVO non-perfused area (P < .0001 and P = .0331, respectively). Aqueous level of VEGF was correlated with the severity of macular edema (P = .0306). CONCLUSIONS: VEGF and IL-6 may be involved in the pathogenesis of macular edema with BRVO. The increase in these cytokines might be used as a unique index of BRVO, through which we can determine the severity of the ischemic condition as being in a quiescent state or an exacerbation of macular edema.

Funatsu H, Yamashita H, Sakata K, Noma H, Mimura T, Suzuki M, Eguchi S, Hori S. · Department of Ophthalmology, Diabetes Center, Tokyo Women's Medical University, Tokyo, Japan. · Ophthalmology. · Pubmed #15878060 No free full text.

Abstract: PURPOSE: To investigate whether vascular endothelial growth factor (VEGF) or soluble intercellular adhesion molecule 1 (sICAM-1) is related to diabetic macular edema (DME). DESIGN: Retrospective case-control study. PARTICIPANTS: Thirty-three patients who had DME and 13 patients with nondiabetic ocular disease (control group). METHODS: Vitreous fluid samples were obtained at the time of vitreoretinal surgery, and the VEGF and sICAM-1 levels in vitreous fluid and plasma were measured by enzyme-linked immunosorbent assay. MAIN OUTCOME MEASURES: Relationship between vitreous levels of VEGF or sICAM-1 and DME. RESULTS: Vitreous levels of VEGF and sICAM-1 were significantly higher in DME patients than in control patients (P < 0.0001 and P = 0.0004, respectively). The vitreous level of VEGF was significantly correlated with that of sICAM-1 (P < 0.0001). Vitreous levels of both VEGF and sICAM-1 were significantly higher in patients with hyperfluorescent DME than in those with minimally fluorescent DME (P = 0.0027 and P = 0.0005, respectively). The vitreous levels of both VEGF and sICAM-1 were significantly correlated with retinal thickness at the central fovea (P < 0.0001 and P = 0.0005, respectively) CONCLUSIONS: We found that both VEGF and sICAM-1 were elevated in the vitreous fluid of patients with hyperfluorescent DME. These results suggest that VEGF and ICAM-1 are related to the increase of vascular permeability in DME patients.

Funatsu H, Yamashita H, Noma H, Mimura T, Nakamura S, Sakata K, Hori S. · Department of Ophthalmology, Diabetes Center, Tokyo Women's Medical University, 8-1 Kawada-cho, Shinjuku-ku, Tokyo 162-8666, Japan. · Graefes Arch Clin Exp Ophthalmol. · Pubmed #15258777 No free full text.

Abstract: BACKGROUND: Cytokine levels are elevated in the ocular fluid of diabetic patients. It is unclear whether aqueous humor levels of vascular endothelial growth factor (VEGF) and interleukin-6 (IL-6) are related to the vitreous fluid levels of these substances and to the progression of diabetic retinopathy. METHODS: Aqueous humor and vitreous fluid samples were obtained during cataract and vitreous surgery from ten eyes of ten patients with diabetic macular edema and 26 eyes of 26 patients with proliferative diabetic retinopathy (PDR). The VEGF and IL-6 levels in aqueous humor, vitreous fluid, and plasma were measured by enzyme-linked immunosorbent assay. RESULTS: VEGF and IL-6 levels in aqueous humor were significantly correlated with those in vitreous fluid (rho=0.793 and rho=0.737, respectively). VEGF levels in aqueous humor and vitreous fluid were significantly correlated with the corresponding IL-6 levels (rho=0.631 and rho=0.687, respectively). The aqueous and vitreous levels of VEGF were significantly correlated with the severity of diabetic retinopathy (rho=0.659 and rho=0.771, respectively). Aqueous and vitreous levels of IL-6 were also significantly correlated with the severity of diabetic retinopathy (rho=0.742 and rho=0.746, respectively). Aqueous and vitreous levels of both VEGF and IL-6 were significantly higher in the patients with active PDR than those in quiescent PDR. CONCLUSIONS: Our results suggest that there is a significant relationship between VEGF and IL-6 levels in aqueous humor and in vitreous fluid. Measurement of the aqueous levels of VEGF and IL-6 may be useful to analyze the pathogenesis of diabetic retinopathy and to predict disease activity.

Funatsu H, Yamashita H, Ikeda T, Mimura T, Eguchi S, Hori S. · Department of Ophthalmology, Diabetes Center, Tokyo Women's Medical University, Tokyo, Japan. · Ophthalmology. · Pubmed #13129863 No free full text.

Abstract: PURPOSE: To investigate whether interleukin-6 (IL-6) or vascular endothelial growth factor (VEGF) is related to diabetic macular edema (DME) in subjects without posterior vitreous detachment (PVD). DESIGN: Retrospective case-control study. PARTICIPANTS: Twenty-six subjects who had DME without PVD and 12 subjects who had nondiabetic ocular disease (the control group). METHODS: Vitreous fluid samples were obtained at vitreoretinal surgery, and the IL-6 and VEGF levels in vitreous fluid and plasma were measured by enzyme-linked immunosorbent assay. MAIN OUTCOME MEASURES: Vitreous levels of IL-6 and VEGF in DME subjects without PVD. RESULTS: The vitreous levels of both IL-6 and VEGF were significantly higher in the subjects with DME than in control subjects (P<0.0001 and P<0.0001, respectively). The vitreous level of IL-6 was significantly correlated with that of VEGF (P<0.0001). Vitreous levels of both IL-6 and VEGF were significantly higher in subjects with hyperfluorescent DME than in those with minimally fluorescent DME (P = 0.0008 and P = 0.0038, respectively). CONCLUSIONS: We found that the levels of both IL-6 and VEGF were elevated in the vitreous fluid of subjects with hyperfluorescent DME. Our results suggest that IL-6 and VEGF may promote an increase of vascular permeability in DME subjects without PVD. Interleukin-6 may possibly induce an increase of vascular permeability through a paracrine effect on VEGF in these subjects.

Funatsu H, Yamashita H, Ikeda T, Mimura T, Shimizu E, Hori S. · Department of Ophthalmology, Diabetes Center, Tokyo Women's Medical University, Tokyo, Japan. · Am J Ophthalmol. · Pubmed #12614749 No free full text.

Abstract: PURPOSE: To investigate whether angiotensin II (AII) or vascular endothelial growth factor (VEGF) is related to diabetic macular edema (DME) in patients with and without posterior vitreous detachment (PVD). DESIGN: A case-control study. METHODS: Vitreous fluid samples were obtained at vitreoretinal surgery from 28 eyes of 28 DME patients without PVD, 8 eyes of 8 DME patients with PVD, 14 eyes of 14 nondiabetic patients, and 8 eyes of diabetic patients without retinopathy. The VEGF levels in vitreous fluid and plasma were determined by enzyme-linked immunosorbent assay, while AII levels were measured by radioimmunoassay.RESULTS: The vitreous levels of AII and VEGF were significantly higher in DME patients with or without PVD than in nondiabetic patients or diabetic patients without retinopathy (without PVD: P < .0061, P < .0001, P = .0261, and P < .0001; with PVD: P < .0012, P < .0001, P = .0473, and P < .0001, respectively). There was no significant difference in the vitreous levels of AII or VEGF between patients with or without PVD (P = .4948 and P = .6642, respectively). The vitreous level of AII significantly correlated with that of VEGF in DME patients without PVD (P = .576) or with PVD (P = .488). AII and VEGF levels in vitreous fluid were significantly higher than the respective plasma levels. CONCLUSIONS: We found that the vitreous levels of AII and VEGF were elevated in DME patients irrespective of the status of PVD. Angiotensin II and VEGF may be induced in the eyes and be related to the pathogenesis of DME.

Yamamoto T, Hitani K, Tsukahara I, Yamamoto S, Kawasaki R, Yamashita H, Takeuchi S. · Department of Ophthalmology, Toho University Sakura Hospital, Chiba, Japan. · Am J Ophthalmol. · Pubmed #12504691 No free full text.

Abstract: PURPOSE: To determine the early postoperative changes in retinal thickness and complications after pars plana vitrectomy for diabetic macular edema. DESIGN: Consecutive interventional case series. METHODS: Studied retrospectively, pars plana vitrectomy was performed on 65 consecutive eyes of 63 patients with diabetic macular edema. The follow-up interval ranged from 6 to 36 months (12.6 +/- 7.4 months [mean +/- standard deviation (SD)]). The indications of pars plana vitrectomy in this study were (1) diffuse diabetic macular edema, (2) preoperative visual acuity less than 20/40, and (3) noneffective macular photocoagulation therapy. Preoperative and postoperative examinations by stereoscopic biomicroscopy, color fundus photography of the macula and optical coherence tomography (OCT) were performed on all eyes. Preoperatively, direct photocoagulation to microaneurysms in the macula had been performed in 48 eyes, and focal/grid photocoagulation had been performed in five eyes. Preoperative examination showed that epiretinal membranes were observed in 20 eyes, cystoid macular edema in 40 eyes, and 23 eyes had a complete posterior vitreous detachment (PVD). Epimacular membranes, removed during surgery, were examined histopathologically. RESULTS: The postoperative mean best-corrected visual acuity (logarithm of the minimum angle of resolution [logMAR] = 0.696 +/- 0.491 [mean +/- SD]) was significantly better than the preoperative mean best-corrected visual acuity (0.827 +/- 0.361; P <.0001; Wilcoxon signed-rank test). The final visual acuity improved by 2 or more lines in 32 of 65 eyes (45%), remained unchanged in 32 of 65 eyes (49%), and exacerbated after the surgery in 4 of 65 eyes (6%) due to neovascular glaucoma (2 eyes) and residual cystoid macular edema (2 eyes). The postoperative foveal retinal thickness (224.9 +/- 116.9 microm) at the last visit was significantly thinner than the preoperative foveal retinal thickness (463.7 +/- 177.3 microm; P <.0001; Wilcoxon signed-rank test). The foveal retinal thickness did not decrease linearly but fluctuated: The mean postoperative retinal thickness had decreased significantly 7 days after surgery, then remained unchanged for approximately 1 month, and thereafter gradually decreased until 4 months. The intraoperative and postoperative complications included peripheral retinal tear in 3 of 65 (4.6%) eyes, postoperative rhegmatogenous retinal detachment in 1 of 65 (1.5%) eyes, neovascular glaucoma in 3 of 65 (5%) eyes, recurrent vitreous hemorrhage in 1 of 65 (1.5%) eyes, hard exudates in the center of the macula in 3 of 56 (4.6%) eyes, postoperative epiretinal membrane formation in 9 of 65 (13.8%) eyes, and a lamellar macular hole in 1 of 65 (1.5%) eyes. CONCLUSIONS: Vitrectomy for diabetic macular edema is an effective procedure for reducing the edema and improving visual acuity. Because the postoperative reduction in retinal thickness is not complete until 4 months, the assessment of vitrectomy on foveal thickness should not be made until this time. In addition, there are severe complications from vitrectomy for diabetic macular edema, and careful preoperative and postoperative examinations and surgical methods are required.

Funatsu H, Yamashita H, Ikeda T, Nakanishi Y, Kitano S, Hori S. · Department of Ophthalmology, Diabetes Center, Tokyo Women's Medical University, Tokyo, Japan. · Am J Ophthalmol. · Pubmed #11931788 No free full text.

Abstract: PURPOSE: To investigate the correlation between angiotensin II (AII) or vascular endothelial growth factor (VEGF) levels in the vitreous fluid and the severity of diabetic macular edema (DME). DESIGN: A case-control study. METHODS: Vitreous fluid samples were obtained at the time of vitreoretinal surgery from 20 eyes of 20 patients with DME, 6 eyes of 6 diabetic patients without retinopathy, and 14 eyes of 14 nondiabetic patients. The VEGF levels in vitreous fluid and plasma were determined by enzyme-linked immunosorbent assay, while AII levels were measured by radioimmunoassay. RESULTS: The vitreous concentration of VEGF was significantly higher in patients with DME than in nondiabetic patients or diabetic patients without retinopathy (P <.0001 and P <.0001, respectively). Vitreous levels of AII were also higher in patients with DME than in nondiabetic patients (P =.0082). The vitreous concentration of AII was significantly correlated with that of VEGF (P =.0022). Vitreous concentrations of both AII and VEGF were significantly higher in patients with hyperfluorescent DME than in those with hypofluorescent (P =.0228 and P =.0068, respectively). CONCLUSIONS: We found that the levels of both AII and VEGF were elevated in the vitreous fluid of patients with hyperfluorescein DME. Our results suggest that both AII and VEGF are related to the increase of vascular permeability in DME.

Shimizu E, Funatsu H, Yamashita H, Yamashita T, Hori S. · Department of Ophthalmology, Diabetes Center, Tokyo Women's Medical University, Tokyo, Japan. · Jpn J Ophthalmol. · Pubmed #11853719 No free full text.

Abstract: PURPOSE: To find a predictor in the pathogenesis of macular edema, we investigated ocular and systemic risk factors. METHODS: One hundred and fifty-nine patients with mild diabetic retinopathy who showed one or more soft exudates were recruited. We selected the possible predictors on the basis of relevant factors, including concentration of vascular endothelial growth factor, interleukin-6 (IL-6), transforming growth factor (TGF)-beta(1), tumor necrosis factor (TNF)-alpha, and lipoprotein(a) in plasma, and serum level of von Willebrand factor and thrombomodulin. RESULTS: Macular edema was not detected in 94 eyes; focal macular edema was detected in 46 eyes; diffuse macular edema was detected in 18 eyes; and cystoid macular edema was present in 1 eye. The plasma level of IL-6 concentration and the state of the posterior vitreous detachment (PVD) correlated significantly with the severity of macular edema (odds ratios = 3.68, 1.70, respectively). Other risk factors were not significantly associated with macular edema. We estimated the probability of macular edema according to the IL-6 level in plasma and the state of the PVD, and were able to predict the probability of macular edema. CONCLUSION: The results of the present study indicate that IL-6 concentration in plasma and the state of the PVD can be predictors of macular edema.

Funatsu H, Yamashita H, Noma H, Mimura T, Yamashita T, Hori S. · Department of Ophthalmology, Diabetes Center, Tokyo Women's Medical University, Tokyo, Japan. · Am J Ophthalmol. · Pubmed #11755841 No free full text.

Abstract: PURPOSE: To investigate the relationship between diabetic macular edema and the levels of vascular endothelial growth factor (VEGF) and interleukin-6 (IL-6) in aqueous humor and plasma.DESIGN: Comparative cross-sectional study. METHODS: Fifty-four eyes from 54 diabetic patients were used. The concentrations of VEGF and IL-6 in undiluted aqueous specimens (obtained from the eyes during cataract surgery) and in plasma were measured by an enzyme-linked immunosorbent assay. To assess blood-aqueous barrier function, the aqueous flare intensity was measured by a laser flare-cell meter as an estimate of the aqueous protein level. RESULTS: The aqueous levels of VEGF and IL-6 were significantly correlated with the severity of macular edema (rho = 0.628, P <.001 and rho = 0.517, P <.01, respectively), as well as with the aqueous protein concentration (rho = 0.618, P <.001 and rho = 0.588, P <.001, respectively). Aqueous levels of VEGF and IL-6 were significantly higher than their respective plasma levels (both P <.001). In addition, the aqueous level of VEGF was significantly correlated with that of IL-6 (rho = 0.537, P <.01). Furthermore, the status of the posterior vitreous significantly correlated with the severity of macular edema (rho = 0.618, P <.0001). CONCLUSIONS: These results suggest that both VEGF and IL-6 are produced together in the intraocular tissues, and are involved in the pathogenesis of macular edema.

Yamashita H. · No affiliation provided · Nippon Ganka Gakkai Zasshi. · Pubmed #12647337 No free full text.

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