WALTER YUKIHIKO TAKAHASHI

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LIM/33 - Laboratório de Oftalmologia, Hospital das Clínicas, Faculdade de Medicina

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  • article 8 Citação(ões) na Scopus
    Short-term effects of intravitreal bevacizumab in contrast sensitivity of patients with diabetic macular edema and optimizing glycemic control
    (2019) MOTTA, Augusto A. L.; BONANOMI, Maria Teresa B. C.; FERRAZ, Daniel A.; PRETI, Rony C.; SOPHIE, Raafay; ABALEM, Maria F.; QUEIROZ, Marcia S.; PIMENTEL, Sergio L. G.; TAKAHASHI, Walter Y.; DAMICO, Francisco M.
    Aims: To analyze contrast sensitivity of intravitreal bevacizumab injections with optimizing glycemic control versus optimizing glycemic control (in combination with sham injections) in eyes with Diabetic Macular Edema (DME). Design: Prospective, interventional, masked, randomized controlled trial. Methods: Forty-one eyes of 34 patients with type 2 diabetes mellitus and DME with glycated hemoglobin (HbA1c) < 11% received either intravitreal bevacizumab injection (Group 1) or sham injection (Group 2) at 0 and 6 weeks along with optimizing glycemic control. Mean change in best-corrected visual acuity (BCVA), contrast sensitivity (CS), optical coherence tomography (OCT)-measured by central macular thickness (CMT) were compared and correlated at baseline, 2, 6 and 12 weeks. Results: The study showed a mean CS improved in group 1 from 1.14 +/- 0.36 logCS to 1.32 +/- 0.24 logCS and also in group 2 from 1.11 +/- 0.29 logCS to 1.18 +/- 0.29 logCS at 12 weeks (P = 0.12). CS and CMT promptly decreased in group 1 compared to group 2 at 2 weeks (Delta CS = 0.15 +/- 0.25 vs. 0.03 +/- 0.15 logCS; P = 0.04; Delta CMT = 116 +/- 115 vs. 17 +/- 71 mu m; P = 0.01). There was a mean reduction of approximately 0.5% in HbA1c levels in both groups at 12 weeks (P = 0.002). Conclusion: The use of bevacizumab in combination with optimizing glycemic control results in earlier improvement of contrast sensitivity in type 2 diabetes patients with DME. However, the optimizing glycemic control itself has shown also to be effective at 12 weeks.
  • article 32 Citação(ões) na Scopus
    OPTICAL COHERENCE TOMOGRAPHY ANALYSIS OF OUTER RETINAL TUBULATIONS Sequential Evolution and Pathophysiological Insights
    (2018) PRETI, Rony C.; GOVETTO, Andrea; AQUETA FILHO, Richard Geraldo; ZACHARIAS, Leandro Cabral; PIMENTEL, Sergio Gianotti; TAKAHASHI, Walter Y.; MONTEIRO, Mario L. R.; HUBSCHMAN, Jean Pierre; SARRAF, David
    Purpose: To describe the sequential evolution of outer retinal tubulations (ORTs) in patients diagnosed with choroidal neovascularization and/or retinal pigment epithelium atrophy. Methods: Retrospective evaluation of spectral domain optical coherence tomography of a consecutive cohort of patients with various retinal conditions. Results: We reviewed the clinical findings of 238 eyes of 119 consecutive patients (54 men and 65 women) with a mean age of 76.2 +/- 14.2 years (range: 57-90) and a mean follow-up of 3 +/- 1.6 years (range 1-7). Over the follow-up period, ORTs were diagnosed in 67 of 238 eyes (28.1%), 9 of which were imaged with sequential, eye-tracked spectral domain optical coherence tomography dating from the beginning of ORT formation. The presence of geographic atrophy and subretinal hyperreflective material at baseline were found to be risk factors for ORT development (P < 0.001 and P < 0.001, respectively). Outer retinal tubulations were divided into forming versus formed morphologies. The latter was comprised open and closed ORTs of which the open subtype was the most common. The formation of ORTs was significantly associated with microcystic macular lesions in the inner nuclear layer and the downward displacement of the outer plexiform layer, referred to as the outer plexiform layer subsidence sign (P < 0.001). Conclusion: Outer retinal tubulation is a frequent optical coherence tomography finding in eyes with choroidal neovascularization and geographic atrophy. Open ORTs with progressive scrolled edges and shortened diameter were significantly associated with microcystic macular lesions in the inner nuclear layer and the outer plexiform layer subsidence sign.
  • conferenceObject
    Intravitreal Ranibizumab Combined with Panretinal Photocoagulation in Patients with Treatment-Naive Proliferative Diabetic Retinopathy
    (2013) FERRAZ, Daniel; SOPHIE, Raafay; BITTENCOURT, Millena; PRETI, Rony; VAZQUEZ, Lisa; MOTTA, Augusto; HANOUT, Mostafa; SEPAH, Yasir; Quan Dong Nguyen; TAKAHASHI, Walter
  • article 2 Citação(ões) na Scopus
    Evaluation of contrast sensitivity in non-high-risk proliferative diabetic retinopathy treated with panretinal photocoagulation with and without intravitreal injections of ranibizumab
    (2022) RENTIYA, Zubir S.; FERRAZ, Daniel A.; HUTNIK, Robert; BAE, Junun; MACHADO, Cleide G.; MUCCIOLLI, Cristina; MOTTA, Augusto Alves L. da; RIBEIRO, Lucas Z.; GUAN, Zeyu; PRETI, Rony Carlos; TAKAHASHI, Walter Y.
    Purpose: To evaluate contrast sensitivity in non-high-risk, treatment-naive proliferative diabetic retinopathy patients treated with panretinal photocoagulation and intravitreal injections of ranibizumab) versus panretinal photocoagulation alone. Methods: Sixty eyes of 30 patients with bilateral proliferative diabetic retinopathy were randomized into two groups: one received panretinal photocoagulation and ranibizumab injections (study group), while the other received panretinal photocoagulation alone (control group). All eyes were treated with panretinal photocoagulation in three sessions according to the Early Treatment Diabetic Retinopathy Study guidelines. Contrast sensitivity measurements were performed under photopic conditions (85 cd/m(2)) with the Visual Contrast Test Sensitivity 6500 chart, allowing for the evaluation of five spatial frequencies with sine wave grating charts: 1.5, 3.0, 6.0, 12.0, and 18.0 cycles per degree (cpd). Outcomes were measured in contrast sensitivity threshold scores among and within groups, from baseline to 1, 3, and 6 months. Results: Fifty-eight eyes (28 in the study group and 30 in the control group) reached the study endpoint. A comparative analysis of changes in contrast sensitivity between the groups showed significant differences mainly in low frequencies as follows: at month 1 in 1.5 cpd (p=0.001) and 3.0 cpd (p=0.04); at month 3 in 1.5 cpd (p=0.016), and at month 6 in 1.5 cpd (p=0.001) and 3.0 cpd (p=0.026) in favor of the study group. Conclusions: In eyes of patients with non-high-risk proliferative diabetic retinopathy, panretinal photocoagulation treatment with ranibizumab appears to cause less damage to contrast sensitivity compared with panretinal photocoagulation treatment alone. Thus, our evaluation of contrast sensitivity may support the use of ranabizumab as an adjuvant to panretinal photocoagulation for the treatment of proliferative diabetic retinopathy.
  • article 4 Citação(ões) na Scopus
    IN VITRO EVIDENCE FOR MYCOPHENOLIC ACID DOSE-RELATED CYTOTOXICITY IN HUMAN RETINAL CELLS
    (2013) ZACHARIAS, Leandro C.; DAMICO, Francisco Max; KENNEY, Maria C.; GASPARIN, Fabio; ACQUESTA, Felipe B.; VENTURA, Dora F.; TAKAHASHI, Walter Y.; KUPPERMANN, Baruch D.
    Purpose: Mycophenolic acid (MPA) is an immunosuppressive agent that controls noninfectious uveitis. Intravitreal MPA delivery may be a potential adjuvant therapy in patients who have to discontinue steroid or immunosuppressive systemic therapy because of side effects. The aims of this study are to evaluate the in vitro effects of MPA over human retinal pigment epithelium (ARPE-19) and human Muller cells (MIO M-1). Methods: ARPE-19 cells and MIO M-1 cells were exposed to 25, 50, and 100 mu g/mL of MPA (Roche Bioscience, Palo Alto, CA) for 24 hours. Toxicity was evaluated by trypan blue dye-exclusion cell viability assay, caspase-3/7 apoptosis-related assay, and JC-1 mitochondrial membrane potential assay. Results: The MPA (25 mu g/mL and 50 mu g/mL) did not cause reduction in cell viability or significant change in caspase-3/7 activity in both cell lines tested. Mycophenolic acid (100 mg/mL) caused a significant decrease in cell viability (P < 0.01) and higher caspase-3/7 activity (P < 0.05) in both cell lines compared with untreated cells. The JC-1 mitochondrial membrane potential did not show statistically significant differences for both cell lines and all concentration tested when compared with untreated controls (P > 0.05). Conclusion: Intraocular delivery may be a potential alternative for the treatment of noninfectious uveitis, either by intravitreal injection or sustained-release drug-delivery systems, in doses of 50 mu g/mL or lower.
  • conferenceObject
    Infra-red photography retinal abnormalities and inner nuclear layer microcystic retinal degeneration in eyes with band atrophy of the optic nerve
    (2014) MONTEIRO, Mario L. R.; SOUSA, Rafael Miranda Miranda; FERRAZ, Daniel Araujo; RAJAGOPALAN, Nithya; SADIQ, Mohammad Ali; SEPAH, Yasir; Quan Dong Nguyen; TAKAHASHI, Walter Y.
  • article 8 Citação(ões) na Scopus
    The Effects of Commercially Available Preservative-Free FDA-Approved Triamcinolone (Triesence (R)) on Retinal Cells in Culture
    (2011) ZACHARIAS, Leandro Cabral; ESTRAGO-FRANCO, Maria Fernanda; RAMIREZ, Claudio; KENNEY, Maria Cristina; TAKAHASHI, Walter Y.; SEIGEL, Gail M.; KUPPERMANN, Baruch D.
    Purpose: To evaluate the effects of Triesence (R) (TRI), a new preservative-free triamcinolone approved by the U. S. Food and Drug Administration (FDA) for intraocular use, on human retina pigment epithelial (ARPE-19) and rat neurosensory (R28) cells in culture. Methods: ARPE-19 and R28 cell cultures were treated 24 h with 1,000, 500, 200, or 100 mu g/mL of crystalline (cTRI) or 1,000, 500, or 200 mu g/mL of solubilized (sTRI). TRI was solubilized by centrifuging the drug, discarding the supernatant containing the vehicle and then resuspending the drug pellet in an equivalent amount of Dimethyl sulfoxide to achieve the same concentration as the commercial preparation. Percentage of cell viability (CV) was evaluated by a trypan blue dye-exclusion assay. The mitochondrial membrane potential (Delta Psi m) was analyzed with the JC-1 assay. The caspase-3/7 activity was measured by a fluorochrome assay. Results: In the ARPE-19 cultures, the cTRI caused a decrease in CV at 1,000 mg/mL (13.03 +/- 6.51; P < 0.001), 500 mu g/mL (28.87 +/- 9.3; P < 0.001), 200 mu g/mL (54.93 +/- 5.61; P < 0.001), and 100 mu g/mL (82.53 +/- 0.65; P < 0.005) compared with the untreated controls (96.98 +/- 0.16). In R28 cultures, the cTRI treatment also reduced CV values significantly (P < 0.001) for the 1,000 mu g/mL (22.73 +/- 2.44), 500 mu g/mL (34.63 +/- 1.91), 200 mu g/mL (58.70 +/- 1.39), and 100 mu g/m (75.33 +/- 2.47) compared with the untreated controls (86.08 +/- 3.54). Once the TRI was solubilized (sTRI), the CV and Delta Psi m remained similar to the untreated controls for both ARPE-19 and R28 cells. The sTRI treatment with 1,000, 500, and 200 mu g/mL increased in caspase-3/7 activity in ARPE-19 cells (P < 0.01) and in R28 cells (P < 0.05) compared with dimethyl sulfoxide equivalent controls. Conclusion: The crystalline form of TRI (cTRI) can cause a significant decrease in CV to cultured retinal cells. Once the TRI is solubilized (sTRI), at the same concentrations, the cells remain viable with no decrease in CV or Delta Psi m. The sTRI can, however, increase caspase-3/7 activity, thus suggesting some degree of apoptosis.
  • article 17 Citação(ões) na Scopus
    Toxicity of High-Dose Intravitreal Adalimumab (Humira) in the Rabbit
    (2011) MANZANO, Roberta P. A.; PEYMAN, Gholam A.; CARVOUNIS, Petros E.; DAMICO, Francisco Max; AGUIAR, Renata Genaro; IOSHIMOTO, Gabriela L.; VENTURA, Dora Fix; CURSINO, Sylvia T.; TAKAHASHI, Walter
    Purpose: To evaluate the ocular toxicity of escalating doses of intravitreous adalimumab (Humira (R)) in the rabbit eye. Methods: Thirty New Zealand albino rabbits received intravitreous injections of 0.5mg (6 eyes), 1.0mg (6 eyes), 2.5mg (6 eyes), 5mg (6 eyes), and 10mg (6 eyes) adalimumab. Slit lamp biomicroscopy and fundoscopy were carried out at baseline, day 7, and day 14 after intravitreous injection, whereas electroretinography (ERG) was carried out at baseline and day 14. Animals were euthanized on day 14, and histopathological examination of the eyes was performed. Results: Slit lamp biomicroscopy and fundoscopy were normal in all eyes receiving doses up to 5mg. In the 10mg group, 3 of 6 eyes showed mild anterior chamber inflammatory reaction on day 7. Similarly, scotopic and photopic a- and b-wave ERG amplitudes at baseline and day 14 were similar in all groups up to 5mg, but there was a significant decrease in the photopic-wave ERG response in the 10mg group (P = 0.046). Finally, histopathology demonstrated no differences among eyes receiving balanced salt solution, 0.5, 1.0, 2.5, 5.0, or 10mg of adalimumab. Conclusions: Intravitreous adalimumab exhibited no associated ocular short-term toxicity in rabbit eyes up to the 5mg dose. In the 10mg group mild clinical findings and ERG amplitude reduction could reflect early toxicity.
  • article 9 Citação(ões) na Scopus
    Natural history of diabetic macular edema and factors predicting outcomes in sham-treated patients (MEAD study)
    (2019) YOON, Young Hee; BOYER, David S.; MATURI, Raj K.; BANDELLO, Francesco; BELFORT, Rubens; AUGUSTIN, Albert J.; LI, Xiao-Yan; BAI, Zhanying; HASHAD, Yehia; ABUJAMRA, Suel; ACTON, James; ALI, Fareed; ANTOSZYK, Andrew; AUGUSTIN, Albert J.; AWH, Carl C.; BARAK, Adiel; BARTZ-SCHMIDT, Karl Ulrich; BAUMAL, Caroline R.; BELFORT JR., Rubens; BHENDE, Muna; BOYER, David S.; BRIDGES JR., William Z.; BROWN, David M.; CARMICHAEL, Trevor; CARNEVALE, Ken; CASELLA, Antonio M.; CHANG, Tom; CHECHIK, Daniel; CHEN, San-Ni; CHONG, Lawrence P.; CHONG, Victor; CORWIN, Joel; CREUZOT-GARCHER, Catherine; CRUESS, Alan; DANIELL, Mark; AVILA, Marcos P. de; MORAES JR., Haroldo Vieira de; DEVENYI, Robert G.; DOFT, Bernard H.; DONALDSON, Mark; DREYER, Richard; ELIOTT, Dean; ENGEL, Harry M.; ERNEST, Jan; ESSMAN, Thomas F.; FALCONE, Philip M.; FEKRAT, Sharon; FERENCZ, Joseph R.; FERREIRA, Joao L.; FIGUEIRA, Joao; FISER, Ivan; FOSTER, Bradley; FOX, Gregory M.; FREEMAN, William R.; GARG, S. P.; GILLIES, Mark; GLASER, David; GOLDSTEIN, Burton G.; GOMES, Andre M. V.; GONDER, John R.; GOPAL, Lingam; GOUS, Petrus; GUPTA, Amod; GUPTA, Anurag; HALPERIN, Lawrence; HAN, Dennis; HARIPRASAD, Seenu M.; HOLZ, Frank G.; KAISER, Peter; KALVODOVA, Bohdana; KATZ, Barrett; KATZ, Randy S.; KECIK, Dariusz; KELLAWAY, Judianne; KLEMPERER, Itamar; KUPPERMANN, Baruch; LANZETTA, Paolo; LATTANZIO, Rosangela; LEE, Won-Ki; LEHR, John; LEYS, Monique; LOOSE, Isaac; LOTERY, Andrew; LU, Da-Wen; MCCARTNEY, Paul; MAJJI, Ajit B.; MARTINEZ, Jose A.; MASSIN, Pascale; MATURI, Raj K.; MENCHINI, Ugo; MENON, Geeta; MICHELS, Mark; MIDENA, Edoardo; MILLER JR., James; MITCHELL, Paul; MOISSEIEV, Joseph; MORSE, Lawrence; NAVARRO, Rafael; NEMETH, Janos; NEWLAND, Henry; NEWSOM, Richard; NICHOLS, John; ORELLANA, Juan; ORZALESI, Nicola; PARANHOS JR., Augusto; PARK, Robert; PARK, Susanna; PARODI, Maurizio Battaglia; PAVAN, Peter R.; PEACE, James; PEREZ-ORTIZ, Don J.; POLLACK, Ayala; RAMASWAMY, Kim; RATNAKARAM, Ramakrishna; RAVALICO, Giuseppe; REHAK, Jiri; REZAEI, Kourous; RIZZO, Stanislao; RODRIGUEZ-ALVIRA, Francisco J.; ROMANET, Jean-Paul; ROSE, Steven; ROSEN, Richard B.; ROSSETTI, Luca; RUIZ-MORENO, Jose Maria; SADDA, SriniVas; SALL, Kenneth; SANDNER, Dirk; SANZ, Alvaro Fernandez-Vega; SARTANI, Gil; SCHMICKLER, Stefanie; SCHWARTZ, Steven D.; SHARMA, Y. R.; SHEU, Shwu-Jiuan; SINGER, Michael; SIVAPRASAD, Sobha; SOUBRANE, Gisele; SOUCEK, Petr; SOUIED, Eric H.; STAURENGHI, Giovanni; STUDNICKA, Jan; SUAREZ-FIGUEROA, Marta; TAKAHASHI, Walter Y.; TOGNETTO, Daniele; TSAI, Patrick L.; II, Lawrence J. Ulanski; UY, Harvey S.; VARANO, Monica; VEITH, Miroslav; VICHA, Igor; VIOLA, Francesco; VISSER, Linda; WEINBERGER, Dov; WING, Glenn L.; WONG, Edmund; WONG, Tien Y.; WYLEGALA, Edward; YAN, Jiong; YOON, Young Hee; YOUNG, Lucy H.; YU, Hyeong G.; ZIMMER-GALLER, Ingrid E.
    Purpose To describe the natural history of diabetic macular edema (DME) with respect to best-corrected visual acuity (BCVA) and central retinal thickness (CRT) outcomes and to identify baseline patient characteristics and systemic factors associated with improvement or worsening of outcomes in sham-treated patients. Methods The study population was sham-treated patients (n = 350) in the 3-year MEAD registration study of dexamethasone intravitreal implant for treatment of DME. Patients had center-involved DME and received sham intravitreal injections in the study eye at >= 6-month intervals. Potential prognostic factors for outcomes were evaluated using multiple linear regression analysis. Results Visual and anatomic outcomes were poorer in patients who left the study early (n = 198) than in study completers (n = 152). Mean change in BCVA from baseline at the last visit with available data was + 0.9 letters; 37.5% of patients had no change in BCVA, 23.2% had gained > 10 letters, and 16.0% had lost > 10 letters. Older age and baseline diabetic retinopathy score > 6 were associated with worse BCVA outcomes; thicker baseline CRT and larger number of hypertension medications used were associated with larger reductions in CRT during the study. Conclusions BCVA and CRT outcomes were variable in this population of DME patients with generally good glycemic control. In DME patients without active treatment, older age and baseline diabetic retinopathy score > 6 were associated with less improvement in BCVA; thicker baseline CRT and a larger number of antihypertensive medications used predicted better improvement in CRT.
  • article 39 Citação(ões) na Scopus
    A RANDOMIZED CONTROLLED TRIAL OF PANRETINAL PHOTOCOAGULATION WITH AND WITHOUT INTRAVITREAL RANIBIZUMAB IN TREATMENT-NAIVE EYES WITH NON-HIGH-RISK PROLIFERATIVE DIABETIC RETINOPATHY
    (2015) FERRAZ, Daniel A.; VASQUEZ, Lisa M.; PRETI, Rony C.; MOTTA, Augusto; SOPHIE, Raafay; BITTENCOURT, Millena G.; SEPAH, Yasir J.; MONTEIRO, Mario L. R.; Quan Dong Nguyen; TAKAHASHI, Walter Yukihiko
    Purpose: To compare the efficacy of panretinal photocoagulation (PRP) and intravitreal ranibizumab injection with PRP alone in patients with treatment-naive bilateral non-high-risk proliferative diabetic retinopathy. Methods: Sixty eyes of 30 patients were randomized either to the study group (SG) receiving PRP plus 2 ranibizumab injections or to the control group (CG) receiving PRP alone. Mean change in best-corrected visual acuity and in optical coherence tomography were compared at baseline and 1, 3, and 6 months. Results: Best-corrected visual acuity was significantly better at 6 months in the SG; however, there was decrease in best-corrected visual acuity in the CG. Central macula thickness decreased significantly at 6 months in SG when compared with baseline (-47.6 mm, P < 0.001) and did not reveal significant difference in the CG. In eyes with diabetic macular edema, best-corrected visual acuity increased by 3.6 letters (P = 0.06) in the SG and decreased by 4.4 letters in the CG (P = 0.003). Central macula thickness decreased by 69.3 mm (P = 0.001) in the SG and decreased by 45.5 mm (P = 0.11) in the CG. Conclusion: Intravitreal ranibizumab in combination with PRP can be an effective treatment in eyes with non-high-risk proliferative diabetic retinopathy and diabetic macular edema.