LEANDRO CABRAL ZACHARIAS
Projetos de Pesquisa
Unidades Organizacionais
Instituto Central, Hospital das Clínicas, Faculdade de Medicina
LIM/33 - Laboratório de Oftalmologia, Hospital das Clínicas, Faculdade de Medicina
LIM/33 - Laboratório de Oftalmologia, Hospital das Clínicas, Faculdade de Medicina
13 resultados
Resultados de Busca
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- 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, DavidPurpose: 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.
- Effects of light on retinal pigment epithelial cells, neurosensory retinal cells and Muller cells treated with Brilliant Blue G(2015) MANSOOR, Saffar; SHARMA, Ashish; CACERES-DEL-CARPIO, Javier; ZACHARIAS, Leandro C.; PATIL, A. Jayaprakash; GUPTA, Navin; LIMB, G. Astrid; KENNEY, M. Cristina; KUPPERMANN, Baruch D.Background: The aim of this study is to evaluate the safety profile of Brilliant Blue G (BBG) with and without exposure to light (L) on three different retinal cell lines. Method: ARPE-19, R28 and MIO-M1 cells were treated with BBG: 0.125 mg/mL (0.5x clinical concentration), 0.25 mg/mL (1x) or 0.5 mg/mL (2x) with or without surgical illumination of halogen light exposure for 10 min, 15 min or 30 min. Cells were further cultured after 24 h and then analysed for cell viability, late stages of apoptosis and mitochondrial damage associated with early apoptosis using assays that measure trypan blue dye exclusion, increases in caspase-3/7 activity or changes in mitochondrial membrane potential (Delta Psi m), respectively. Result: All three cell lines that were exposed to BBG in the presence or absence of light exposure for 30 min were found to have cell viability and caspase-3/7 activity levels similar to the untreated cultures. The mitochondrial membrane potential (Delta Psi m) was decreased significantly at the 2x + L dose and 2x dose in all three retinal cell lines compared to their respective untreated control cells. At the lower doses of BBG, with or without exposure to light, the Delta Psi m values were similar to the untreated control cultures. Conclusion: Exposure to BBG dye concentrations that are used clinically (0.125 mg/mL and 0.25 mg/mL) in the presence up to 30 min of surgically equivalent light intensity is safe for retinal cells.
- ASSESSMENT OF THE DIFFERENCES IN PHARMACOKINETICS AND PHARMACODYNAMICS BETWEEN FOUR DISTINCT FORMULATIONS OF TRIAMCINOLONE ACETONIDE(2013) ZACHARIAS, Leandro C.; LIN, Ton; MIGON, Rafael; GHOSN, Corine; ORILLA, Werhner; FELDMANN, Barbara; RUIZ, Guadalupe; LI, Yong; BURKE, James; KUPPERMANN, Baruch D.Purpose: To compare the durability of Kenalog, Trivaris, Triesence, and compounding pharmacy preservative-free triamcinolone acetonide in pigmented rabbits with syneretic vitreous using direct visualization, pharmacodynamics, and pharmacokinetics. Methods: Twenty-five Dutch-belted rabbits were used. Pharmacokinetic experiment: Rabbits were intravitreally injected with one of four 4-mg triamcinolone acetonide formulations. Wide-field imaging was serially performed to document residual drug mass. Pharmacodynamics experiment: Four triamcinolone acetonide groups and one control group received intravitreal recombinant human vascular endothelial growth factor 165 every 2 weeks and were followed with fluorescein angiography to assess vascular endothelial growth factor retinal vasculopathy as a measure of residual steroid effect. Particle size of the formulations was measured with Mastersizer 2000. Results: Remaining triamcinolone acetonide mass after 19 weeks: 12,091 +/- 2,512 pixels for the Kenalog group, 1,307.36 +/- 695.57 for Trivaris, 5577 +/- 1477 for Triesence, and 1,535 +/- 329 for compounded preservative-free triamcinolone acetonide. Kenalog suppressed recombinant human vascular endothelial growth factor-induced retinopathy more effectively than the other triamcinolone acetonide groups at Week 39, the final time point assessed. Particle size (90th percentile) was 47 mu m for Kenalog, 26 mu m for Triesence, and 22 mu m for both compounded preservative-free triamcinolone acetonide and Trivaris. Conclusion: Triamcinolone acetonide formulations do not have the same pharmacokinetics/pharmacodynamics. Kenalog has the longest vitreous visibility and durability. Particle size appears to correlate with efficacy and durability. RETINA 33:522-531, 2013
- Intraocular pressure (IOP) after intravitreal dexamethasone implant (Ozurdex) amongst different geographic populations-GEODEX-IOP study(2020) SHARMA, Ashish; KUPPERMANN, Baruch D.; BANDELLO, Francesco; LANZETTA, Paolo; ZUR, Dinah; PARK, Sung Wook; YU, Hyeong Gon; SARAVANAN, V. R.; ZACHARIAS, Leandro Cabral; BARREIRA, Alan K.; IGLICKI, Matias; MIASSI, Fernando; VERITTI, Daniele; TSAO, Sean; MAKAM, Deepika; JAIN, Nidhee; LOEWENSTEIN, AnatPurpose To analyse the intraocular pressure rise after intravitreal dexamethasone implant (Ozurdex) amongst different geographic populations. Methods The medical charts of 294 dexamethasone implants between February 2011 and 2017 were reviewed retrospectively. South Asian (India), White (Europe, US and Israel) Latino (Argentina and Brazil) patient data was included in the study. Ocular hypertension (OHT) was defined as intraocular pressure of >25 mmHg or an increase of at least 10 mmHg from baseline. The main indications for treatment were diabetic macular edema (ME) (65.6%), retinal vein occlusion (26.5%), uveitis (7.8%). Results Amongst 294 intravitreal implants, ocular hypertension (>25 mmHg) was recorded in 0, 8 and 9.5% in White, Latino, and South Asian groups, respectively. However, IOP > 20 mmHg was recorded in 14%, 28% and 27% in White, Latino, and South Asian groups, respectively. Incidence of very high IOP (>35 mmHg) was lower in all geographical groups. It was 3% in Latino followed by 2% in South Asian group. Conclusion Latino and South Asian groups have higher IOP rise compared to White population. Most patients with elevated IOP fluctuate between 20-25 mmHg.
- Diagnostic ability of confocal near-infrared reflectance fundus imaging to detect retrograde microcystic maculopathy from chiasm compression. A comparative study with OCT findings(2021) MONTEIRO, Mario L. R.; SOUSA, Rafael M.; ARAUJO, Rafael B.; FERRAZ, Daniel; SADIQ, Mohammad A.; ZACHARIAS, Leandro C.; PRETI, Rony C.; CUNHA, Leonardo P.; NGUYEN, Quan D.Purpose To evaluate the ability of confocal near-infrared reflectance (NIR) to diagnose retrograde microcystic maculopathy (RMM) in eyes with temporal visual field (VF) loss and optic atrophy from chiasmal compression. To compare NIR findings with optical coherence tomography (OCT) findings in the same group of patients. Methods Thirty-four eyes (26 patients) with temporal VF loss from chiasmal compression and 41 healthy eyes (22 controls) underwent NIR fundus photography, and macular OCT scanning. VF loss was estimated and retinal layers thickness were measured on OCT. Two examiners blinded to the diagnosis randomly examined NIR images for the presence of hyporeflective abnormality (HA) and OCT scans for the presence of microcystic macular abnormalities (MMA). The total average and hemi-macular HA area and number of microcysts were determined. The groups were compared and the level of agreement was estimated. Results The OCT-measured macular retinal nerve fiber and ganglion cell layers were thinner and the inner nuclear layer was thicker in patients compared to controls. HA and MMA were detected in 22 and 12 patient eyes, respectively, and in 0 controls (p<0.001, both comparisons). HA was significantly more frequent than MMA in patients with optic atrophy, and agreement between HA and MMA (both total and hemi-macular) was fair (kappa range: 0.24-0.29). The mean HA area was significantly greater in the nasal than temporal hemi-macula. A re-analysis of the 14 eyes with discrepant findings allowed to confirm RMM in 20 eyes (20/34) indicating that OCT detected RMM in 12 and missed it in 8 eyes. On the other hand, NIR correctly detected 18 out of 20 eyes, overcalled 4 and missed 2. Conclusions RMM is a frequent finding in eyes with severe VF loss from long-standing chiasmal compression. NIR photography appears to be more sensitive than OCT for detecting RMM and may be useful as screening method for its presence.
- 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.
- Prevalence of Focal Inner, Middle, and Combined Retinal Thinning in Diabetic Patients and Its Relationship With Systemic and Ocular Parameters(2021) PRETI, Rony Carlos; IOVINO, Claudio; ABALEM, Maria Fernanda; GARCIA, Rafael; SANTOS, Helen Nazareth Veloso dos; SAKUNO, Gustavo; AU, Adrian; CUNHA, Leonardo Provetti; ZACHARIAS, Leandro Cabral; MONTEIRO, Mario Luiz Ribeiro; SADDA, Srinivas Reddy; SARRAF, DavidPurpose: To determine the prevalence of focal inner, middle, and combined inner/middle retinal thinning (FIRT, FMRT, and FCRT, respectively) in different stages of diabetic retinopathy (DR) without diabetic macular edema and to assess the relationship between such findings with ocular and systemic parameters. Methods: This was a cross-sectional, comparative study comprising healthy participants and diabetic patients with different stages of DR. Forty-nine horizontal macular B-scans from the selected eye were obtained using spectral-domain optical coherence tomography (SD-OCT) and analyzed for the presence of FIRT, FMRT, or FCRT and any relationship with systemic and ocular parameters. Focal retinal thinning (FRT) was subjectively defined as any evidence of inner and/or middle retinal thinning. Results: A total of 190 participants (52 healthy participants and 138 diabetic patients) were included. A higher prevalence of FRT was observed in eyes with advanced DR versus healthy eyes and versus diabetic eyes with no DR or mild DR. FIRT and FCRT were significantly greater in eyes with proliferative DR treated with pan-retinal photocoagulation, and FMRT was significantly more common in eyes with severe nonproliferative DR. FRT was significantly more common in patients with coronary artery disease and was positively correlated with diabetes duration, serum creatinine, and glycosylated hemoglobin and negatively correlated with age, estimated glomerular filtration rate, and visual acuity. Conclusions: FRT occurs in all stages of DR and is increasingly prevalent with increasing severity of DR. Translational Relevance: OCT identification of FRT may provide a surrogate biomarker of retinal and systemic disease in diabetic patients.
- Spontaneous macular hole closure after posterior vitreous detachment in an eye with hyperreflective OCT stress line(2020) PRETI, R.C.; ZACHARIAS, L.C.; CUNHA, L.P.; MONTEIRO, M.L.R.; SARRAF, D.Purpose: The aim of this report is to describe a patient who presented with a central hyper-reflective line (HRL) with spectral domain-optical coherence tomography (SD-OCT) after posterior vitreous detachment that evolved to full thickness macular hole (FTMH) with subsequent spontaneous resolution. Observations: A 59-year-old patient presented with a history of photopsia and floaters followed by the development of a central scotoma in the right eye (OD). The left eye (OS) was normal. On examination, visual acuity (VA) was 20/20- OD and 20/20 OS. Retinal examination OD was remarkable for a retinal tear, and SD-OCT demonstrated a central HRL. The patient underwent laser retinopexy to barricade the retinal tear. Sequential SD-OCT of the macula was performed and the patient eventually developed a small FTMH 8 months after the baseline presentation. VA was correspondingly reduced to 20/80 OD. Upon return after 4 months, the hole was completely resolved with improvement of VA to 20/20 OD. Conclusion: Vitreomacular traction (VMT) may lead to foveal dehiscence. This instability can be detected with SD-OCT as a vertical hyperreflective stress line that is a risk factor for progression to a FTMH. With release of VMT, FTMH can spontaneously close. © 2020
- 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.
- The Effect of Glycemia on Choroidal Thickness in Different Stages of Diabetic Retinopathy(2020) ABALEM, Maria Fernanda; VELOSO, Helen Nazareth Santos; GARCIA, Rafael; CHEN, Xing Dong; CARRICONDO, Pedro C.; ZACHARIAS, Leandro Cabral; PRETI, Rony C.Objective:The purpose of this study was to evaluate the influence of renal and glycemic parameters on choroidal thickness (CT) in patients with diabetes with and without diabetic retinopathy (DR).Methods:This cross-sectional study included patients with and without diabetes. Patients underwent comprehensive ocular examination. CT was obtained using spectral-domain optical coherence tomography (SD-OCT) with enhanced depth imaging (EDI) mode. Clinical parameters were body mass index, mean arterial pressure, glycated hemoglobin, fasting plasma glucose, estimated glomerular filtration rate, and capillary plasma glucose (CPG) a few minutes before EDI-SD-OCT.Results:The study included 275 participants: 42 with diabetes and no DR, 43 with mild nonproliferative diabetic retinopathy (NPDR), 46 with moderate NPDR, 39 with severe NPDR, 24 with proliferative diabetic retinopathy (PDR), 40 with previous panretinal photocoagulation (PRP) treatment for DR, and 41 without diabetes. The diabetic patients had thinner subfoveal CT than the nondiabetic participants (280.5 +/- 83.4 vs. 327.1 +/- 48.8 mu m,p< 0.001). After multivariable adjustment, CT was significantly correlated with age, DR stage, and CPG. In patients with mild and moderate NPDR, a higher level of CPG was associated with thicker CT. This relationship was not found in patients with PDR.Conclusion:CPG had the strongest correlation with CT in patients with NPDR (mild, moderate, and severe), but not in PDR and PRP PDR patients. Our study suggests that the glucose level at the time of the test should be aggregated to other systemic and ocular parameters, such as age and axial length, when studying the choroid using SD-OCT.