Macular Degeneration: Nakazawa T

Shimura M, Nakazawa T, Yasuda K, Kunikata H, Shiono T, Nishida K. · Department of Ophthalmology, NTT East Japan Tohoku Hospital, Sendai, Japan. · Acta Ophthalmol. · Pubmed #18039346 No free full text.

Abstract: PURPOSE: To investigate the relationship between vitreous levels of cytokines, including interleukin-6 (IL-6) and vascular endothelial growth factor (VEGF), and visual prognosis after pars plana vitrectomy (PPV) with arteriovenous sheathotomy in patients with branch retinal vein occlusion (BRVO) associated with macular oedema. METHODS: We studied 60 patients with logMAR visual acuity (VA) scores of < 0.3 and visual impairment secondary to BRVO-associated macular oedema. All patients underwent PPV with arteriovenous sheathotomy. At the time of PPV, vitreous samples were collected from the operated eye and vitreous levels of VEGF and IL-6 were measured. Best corrected VA (BCVA) (using a logMAR chart) and foveal thickness (FT) (using optical coherence tomography) were monitored for up to 6 months after PPV. RESULTS: Both BCVA and FT significantly improved after PPV. According to multiple regression analysis, both the improvement in BCVA and decrease in FT were closely related to the vitreous level of IL-6 but not to that of VEGF. The vitreous level of VEGF was strongly correlated with duration of BRVO. CONCLUSIONS: Both improvement in BCVA and decrease in FT were observed after PPV in BRVO patients with macular oedema. Interestingly, these visual prognoses strongly correlate with the vitreous level of IL-6, whereas the duration of BRVO strongly correlates with the vitreous level of VEGF.

Shimura M, Nakazawa T, Yasuda K, Nishida K. · Department of Ophthalmology, NTT East Japan Tohoku Hospital, Sendai, Japan. · J Ocul Pharmacol Ther. · Pubmed #17593013 No free full text.

Abstract: PURPOSE: This study compares the effect of topical diclofenac with that of betamethasone against postoperative cystoid macular edema (CME) following cataract surgery in patients with non- and mild nonproliferative diabetic retinopathy. METHODS: Forty-six (46) consecutive patients with mild nonproliferative- or nondiabetic retinopathy who had bilateral and symmetrical cataracts underwent uncomplicated cataract surgery in both eyes (92 eyes in total). Postoperatively, topical diclofenac was applied 4 times daily for 1 eye, and topical betamethasone 4 times daily for the other eye in each patient. Best corrected logMAR visual acuity (BCVA), averaged foveal thickness (FT) as measured by optical coherence tomography (OCT), and intraocular pressure (IOP) were monitored preoperatively, and also postoperatively at 1 day and 1, 4, and 8 weeks. RESULTS: VA in both the diclofenac- and betamethasone-treated eyes significantly improved following the cataract surgery; however, no statistical difference of VA was noted between the diclofenac- and betamethasone-treated eyes throughout the observational period (before and after the surgery until 8 weeks postoperatively). FT in both eyes increased after the cataract surgery. FT in the diclofenac-treated eyes did not increase 1 week after surgery, but gradually increased at week 4 and week 8. In contrast, the FT in the betamethasone-treated eyes increased during 1-8 weeks postoperatively. IOP in the diclofenac-treated eyes decreased with time, but IOP in the betamethasone-treated eyes showed no change throughout the observational period. CONCLUSIONS: Postoperative macular thickening following cataract surgery in patients with non- or mild nonproliferative-diabetic retinopathy cannot be fully suppressed by either topical diclofenac or betamethasone. Nonetheless, diclofenac protected against an early event of postoperative CME and also a decrease of IOP.

Noda K, She H, Nakazawa T, Hisatomi T, Nakao S, Almulki L, Zandi S, Miyahara S, Ito Y, Thomas KL, Garland RC, Miller JW, Gragoudas ES, Mashima Y, Hafezi-Moghadam A. · Angiogenesis Laboratory, Massachusetts Eye and Ear Infirmary, Boston, MA 02114, USA. · FASEB J. · Pubmed #18436961 links to  free full text

Abstract: Vascular adhesion protein-1 (VAP-1) is an endothelial cell adhesion molecule involved in leukocyte recruitment. Leukocytes and, in particular, macrophages play an important role in the development of choroidal neovascularization (CNV), an integral component of age-related macular degeneration (AMD). Previously, we showed a role for VAP-1 in ocular inflammation. Here, we investigate the expression of VAP-1 in the choroid and its role in CNV development. VAP-1 was expressed in the choroid, exclusively in the vessels, and colocalized in the vessels of the CNV lesions. VAP-1 blockade with a novel and specific inhibitor significantly decreased CNV size, fluorescent angiographic leakage, and the accumulation of macrophages in the CNV lesions. Furthermore, VAP-1 blockade significantly reduced the expression of inflammation-associated molecules such as tumor necrosis factor (TNF) -alpha, monocyte chemoattractant protein (MCP) -1, and intercellular adhesion molecule (ICAM) -1. This work provides evidence for an important role of VAP-1 in the recruitment of macrophages to CNV lesions, establishing a novel link between VAP-1 and angiogenesis. Inhibition of VAP-1 may become a new therapeutic strategy in the treatment of AMD.

Shimura M, Nakazawa T, Yasuda K, Shiono T, Iida T, Sakamoto T, Nishida K. · Department of Ophthalmology, NTT East Japan Tohoku Hospital, Sendai, Miyagi, Japan. · Am J Ophthalmol. · Pubmed #18328456 No free full text.

Abstract: PURPOSE: To compare the effect of an intravitreal injection of bevacizumab, an anti-vascular endothelial growth factor (VEGF) antibody, with that of triamcinolone acetonide, a corticosteroid for reduction of diabetic macular edema (DME). DESIGN: Prospective, comparative interventional case series. METHODS: Twenty-eight eyes of 14 patients with bilateral DME participated in this study. In each patient, one eye received an intravitreal injection of 4 mg triamcinolone acetonide and the other eye received 1.25 mg bevacizumab. The clinical course of best-corrected visual acuity (VA) with a logarithm of the minimum angle of resolution chart and averaged foveal thickness using optical coherence tomography was monitored for up to 24 weeks after the injection. RESULTS: Before the injection, foveal thickness and VA were 522.3 +/- 91.3 microm and 0.64 +/- 0.28 microm in the triamcinolone-injected eye, and 527.6 +/- 78.8 microm and 0.61 +/- 0.18 microm in the bevacizumab-injected eye, respectively; there was no significant difference between the eyes. One week after the injection, both eyes showed significant regression of macular edema. The triamcinolone-injected eye (342.6 +/- 85.5 microm and 0.33 +/- 0.21 microm) showed significantly better results than the bevacizumab-injected eye (397.6 +/- 103.0 microm and 0.37 +/- 0.17 microm). However, both eyes showed the recurrence of macular edema with time, even at 24 weeks. Triamcinolone (410.4 +/- 82.4 microm and 0.47 +/- 0.25 microm) kept better results than bevacizumab (501.6 +/- 92.5 microm and 0.61 +/- 0.17 microm). CONCLUSIONS: With the generally used concentration, intravitreal injection of triamcinolone acetonide showed better results in reducing DME and in the improvement of VA than that of bevacizumab, suggesting that the pathogenesis of DME is not only attributable to VEGF-dependency, but is also attributable to other mechanisms suppressed by corticosteroid.

Noda K, Miyahara S, Nakazawa T, Almulki L, Nakao S, Hisatomi T, She H, Thomas KL, Garland RC, Miller JW, Gragoudas ES, Kawai Y, Mashima Y, Hafezi-Moghadam A. · Department of Ophthalmology, Massachusetts Eye and Ear Infirmary and Harvard Medical School, Boston, Massachusetts, USA. · FASEB J. · Pubmed #18032635 links to  free full text

Abstract: Inflammatory leukocyte accumulation is a common feature of major ocular diseases, such as uveitis, diabetic retinopathy, and age-related macular degeneration. Vascular adhesion protein-1 (VAP-1), a cell surface and soluble molecule that possesses semicarbazide-sensitive amine oxidase (SSAO) activity, is involved in leukocyte recruitment. However, the expression of VAP-1 in the eye and its contribution to ocular inflammation are unknown. Here, we investigated the role of VAP-1 in an established model of ocular inflammation, the endotoxin-induced uveitis (EIU), using a novel and specific inhibitor. Our inhibitor has a half-maximal inhibitory concentration (IC(50)) of 0.007 microM against human and 0.008 microM against rat SSAO, while its IC(50) against the functionally related monoamine oxidase (MAO) -A and MAO-B is >10 microM. In the retina, VAP-1 was exclusively expressed in the vasculature, and its expression level was elevated during EIU. VAP-1 inhibition in EIU animals significantly suppressed leukocyte recruitment to the anterior chamber, vitreous, and retina, as well as retinal endothelial P-selectin expression. Our data suggest an important role for VAP-1 in the recruitment of leukocytes to the immune-privileged ocular tissues during acute inflammation. VAP-1 inhibition may become a novel strategy in the treatment of ocular inflammatory diseases.

Matsubara A, Nakazawa T, Noda K, She H, Connolly E, Young TA, Ogura Y, Gragoudas ES, Miller JW. · Angiogenesis and Laser Laboratories, Retina Service, Massachusetts Eye and Ear Infirmary, Harvard Medical School, Boston, Massachusetts, USA. · Invest Ophthalmol Vis Sci. · Pubmed #17898299 links to  free full text

Abstract: PURPOSE: To investigate the mechanism of cell death in laser-induced choroidal neovascularization (CNV) after photodynamic therapy (PDT). METHODS: PDT was performed in Brown-Norway rats using laser light at a wavelength of 689 nm, irradiance of 600 mW/cm(2), and fluence of 25 J/cm(2) after intravenous injection of verteporfin at the doses of 3, 6, and 12 mg/m(2). Apoptotic cells in CNV were detected by TUNEL assay at 1, 3, 6, 15, 24, and 48 hours after PDT. Caspase activation at 1, 3, 6, 15, and 24 hours after PDT was determined by immunohistochemistry (IHC) with a cleaved caspase-3 or -9 antibody. Akt activity was determined by Western blot and IHC with a phosphorylated-Akt (pAkt) antibody. To investigate the roles of Akt in PDT-induced apoptosis, insulin-like growth factor (IGF)-1, an Akt activator, with or without wortmannin, an inhibitor of PI3K-Akt pathway, was injected into the vitreous before PDT. RESULTS: The number of TUNEL-positive cells in CNV increased at 3 hours after PDT and peaked at 6 hours, showing a dose dependence of verteporfin. Caspase activation was detected in TUNEL-positive cells. Dephosphorylation of Akt in CNV occurred within 1 hour. IGF-1 significantly activated Akt and suppressed the number of TUNEL-positive cells in CNV, and the effects of IGF-1 were diminished by wortmannin. CONCLUSIONS: PDT induced caspase-dependent apoptosis in CNV. These results suggest that PDT leads to dephosphorylation of Akt and subsequent activation of the caspase-dependent pathway. Understanding the intracellular signaling mechanisms of apoptosis in PDT may lead to more selective and effective treatment of CNV secondary to age-related macular degeneration.

Shimura M, Nakazawa T, Yasuda K, Shiono T, Nishida K. · Department of Ophthalmology, NTT East Japan Tohoku Hospital, 2-29-1, Yamato, Wakabayashi, Sendai, Miyagi 984-8560, Japan. · Br J Ophthalmol. · Pubmed #17077114 No free full text.

Abstract: AIM: To prospectively evaluate the efficacy of subtenon injection of triamcinolone acetonide (TA) before laser grid pattern photocoagulation (G-PC) for the treatment of diffuse diabetic macular oedema (DDME). METHODS: 42 eyes of 37 consecutive patients with DDME were studied. 1 week before G-PC, 21 eyes received TA subtenon injection, and the other eyes served as control. The clinical course of visual acuity (VA) and foveal thickness (FT) was monitored for up to 24 weeks after G-PC. Mean deviation (MD) of perimetry with 30-2 program on Humphrey Perimeter (Zeiss-Humphrey, Dublin, California, USA) was also measured. The average laser intensity was recorded. RESULTS: After TA injection, FT and VA were improved, and subsequent G-PC maintained the improvement for up to 24 weeks without recurrence of diffuse diabetic macular oedema. In contrast, G-PC without TA injection induced transient worsening of FT and VA, then both were gradually improved. At 24 weeks after G-PC, MD in the TA-injected eyes was better than those in control. The required laser intensity in TA-injected eyes was less than that for control. CONCLUSION: Subtenon injection of TA prior to G-PC allows for treatment with a lower intensity of laser spots and also prevents the decrease in central visual field sensitivity, all of which have clinical advantages for G-PC.

Shimura M, Yasuda K, Nakazawa T, Ota S, Tamai M. · Department of Ophthalmology, Tohoku University Graduate School of Medicine, Sendai, Miyagi, Japan. · Ophthalmic Surg Lasers Imaging. · Pubmed #15305550 No free full text.

Abstract: BACKGROUND AND OBJECTIVE: To determine the effectiveness of laser grid pattern photocoagulation to the macula but not the papillomacular bundle for the treatment of diffuse diabetic macular edema. PATIENTS AND METHODS: Thirty-five eyes of 23 patients with diffuse diabetic macular edema underwent laser grid photocoagulation excluding the papillomacular bundle area. Best-corrected visual acuity by Snellen chart, foveal thickness using a retinal mapping program by optical coherence tomography (OCT), and mean deviation sensitivity by Humphrey automated central perimetry were investigated before and 1, 3, and 6 months after the treatment. RESULTS: Six months after treatment, the visual acuity was improved by 2 or more lines in 16 eyes (43%) and the foveal thickness decreased in 32 eyes (91%). The mean deviation worsened in 34 eyes (97%). There was a significant correlation between the improvement of visual acuity and the initial mean deviation, suggesting that a better visual acuity would be expected with a preoperative mean deviation of approximately -20 dB. CONCLUSION: Grid pattern photocoagulation without treatment to the papillomacular bundle area was effective in treating diffuse diabetic macular edema, especially in eyes with an initial mean deviation showing moderate dysfunction.

Shimura M, Yasuda K, Nakazawa T, Kano T, Ohta S, Tamai M. · Department of Ophthalmology, Tohoku Graduate School of Medicine, Sendai, Japan. · Ophthalmology. · Pubmed #14644723 No free full text.

Abstract: PURPOSE: To investigate the alterations of macular thickness during and after panretinal photocoagulation (PRP) in patients with severe diabetic retinopathy and good vision, and to compare the outcomes of weekly and biweekly treatments. DESIGN: Prospective, comparative interventional case series. PARTICIPANTS: Thirty-six patients with severe nonproliferative diabetic retinopathy or non-high-risk proliferative diabetic retinopathy whose visual acuity was 20/20 or better before PRP. METHODS: Seventy-two eyes of 36 patients underwent scatter PRP in 4 sessions. The macular thickness was measured by optical coherence tomography. The photocoagulation sessions were performed weekly to one eye and biweekly to the other eye. Each eye was selected at random. MAIN OUTCOME MEASURES: Best-corrected visual acuity and macular thickness. RESULTS: Visual acuities were maintained in 89% of eyes with weekly treatments and 92% of eyes with biweekly treatments. Macular thickness was increased transiently in the central macula in both eyes, more in the weekly treated eyes, and then decreased to control levels in eyes treated biweekly but remained thickened in eyes treated weekly. CONCLUSION: For eyes with severe diabetic retinopathy and good vision, PRP with either weekly or biweekly treatment did not affect postoperative visual acuity. However, biweekly treatments allowed faster recovery of macular thickening after PRP than weekly treatments.