Papers by Sebastiao Cronemberger
American Journal of Ophthalmology, 2006
To correlate the retinal nerve fiber layer (RNFL) thickness and optic nerve head (ONH) parameters... more To correlate the retinal nerve fiber layer (RNFL) thickness and optic nerve head (ONH) parameters measured by optical coherence tomography (OCT) with central corneal thickness (CCT) measurements in patients with ocular hypertension (OHT). Observational cross-sectional study. setting: Tertiary care referral teaching institute. study population: Fifty-one eyes of 51 patients with OHT and 35 eyes of 35 normal subjects. Both groups were stratified into thin (CCT < or =555 microm) and thick (CCT >555 microm) cornea subsets. Ocular hypertensives were further stratified by CCT into < or =555 microm, 556 to 588 microm, and >588 microm subsets. observation procedure: RNFL thickness (average, superior average, and inferior average) and ONH parameters were measured by OCT. CCT was measured by ultrasonic pachymetry. main outcome measures: Correlation between CCT and OCT measurements of RNFL and ONH parameters. In the OHT group, CCT correlated significantly with all three RNFL measurements (Pearson's coefficient r = 0.412, 0.484, and 0.380, respectively) but with only four ONH parameters (cup-to-disk area ratio, cup area, rim area, and horizontally integrated rim width; r = -0.459, -0.283, 0.421, and 0.436, respectively). The RNFL in ocular hypertensives with CCT < or =555 microm was significantly thinner than in those with thick corneas (analysis of variance, post hoc Bonferroni comparisons, P < .001). RNFL thickness of normal subjects and ocular hypertensives with CCT >555 microm were similar. Ocular hypertensives with CCT < or =555 microm may represent patients who have either very early undetected glaucoma or an inherent structural predisposition to glaucomatous damage. This may in part explain the higher risk of these patients for progression to glaucoma.
Investigative Ophthalmology & Visual Science, Jun 11, 2015
Investigative Ophthalmology & Visual Science, Jun 16, 2013
The endothelium is a single layer of cells extending over the inner surface of Descemet's mem... more The endothelium is a single layer of cells extending over the inner surface of Descemet's membrane. Its sub cellular organization reflects that the endothelium is extremely active metabolically. It functions as a regulator of corneal water content. Endothelium cells are mitochondria-rich and represent an active metabolic pump that carries out this function in conjunction with the tear film. The cornea must remain relatively dehydrated to retain its transparency. If the water content of the ground substance increases significantly, the stroma will be- come swollen and opaque, and the two most important optical functions, transparency and refractive power, will be severely compromised. The cornea is transparent, but the mechanism whereby corneal transparency is maintained is not known. The factors believed to contribute to its clarity may be divided into two categories: (1) the physical arrangement of the fibers and cells, and (2) their state of hydration. Although many studies have been performed about corneal transparency, there are some gaps to be full field. We performed 50 experiments on corneal preparations of Sprague-Dawley rats and analyzed the presence or absence of electrical sign by recording its voltage variations through one two pore electrode connected to a Grass polygraph. This study aims to register and quantify the resting potential of endothelial cells, as well as bring an important contribution to the knowledge of the normal physiology of the corneal endothelial
Alterações conjuntivais induzidas por análogos de prostaglandinas e maleato de timolol: estudo hi... more Alterações conjuntivais induzidas por análogos de prostaglandinas e maleato de timolol: estudo histomorfométrico
Investigative Ophthalmology & Visual Science, May 1, 2004
Revista de Ciências Farmacêuticas Básica e Aplicada, 2020
The substance 4-Aminobenzamidine dihydrochloride (4-AD) is one of the degradation products of dim... more The substance 4-Aminobenzamidine dihydrochloride (4-AD) is one of the degradation products of diminazene aceturate and has demonstrated antiglaucomatous potential. Glaucoma is the second leading cause of blindness worldwide; thus, new therapeutic alternatives must be studied, for example, the molecule 4-AD vehiculated into polymeric inserts for prolonged release. The present work aims to develop and validate an analytical method to quantify 4-AD in pharmaceutical ophthalmic forms. A HPLC was used with UV-Vis detector, at 290 ƞm and ACE ® C18 column (125 × 4.6 mm, 5 μm), in which the mobile phase consists of phosphate buffer (pH 7.4) and triethylamine (30 mmol/L), under an isocratic flow of 1.0 mL/min. The retention time of 3.2 minutes was observed. The method was developed and validated in accordance with ANVISA recommendations and ICH guides. The linearity range was established between the concentrations 5 and 25 μg/mL (correlation coefficient r = 0.993). The accuracy, repeatability, and intermediate precision tests obtained a relative standard deviation less than or equal to 5%. In addition, the method was considered selective, exact. and robust, with pH being its critical factor. Therefore, the HPLC analysis method is robust and can be used to quantify 4-AD in pharmaceutical forms for ocular application.
Investigative Ophthalmology & Visual Science, Sep 26, 2016
BV UNIFESP: Teses e dissertaçõe
Arquivos Brasileiros De Oftalmologia, 1992
Revista do Colégio Brasileiro de Cirurgiões, Jul 30, 2018
Healing modulation in glaucoma surgery after application of subconjunctival triamcinolone acetate... more Healing modulation in glaucoma surgery after application of subconjunctival triamcinolone acetate alone or combined with mitomycin C: an experimetal study Hayana Marques do aragão rangel 1,2 ; Hévila TaMar roliM 2,3 ; Paula vidigal 4 ; ivana duval de araújo 5 ; sebasTião CroneMberger 1 Objetivo: estudar a eficácia e segurança do uso de acetato de triancinolona subconjuntival isolado ou em associação à mitomicina C como modulador da cicatrização de trabeculectomias em coelhos. Métodos: trinta coelhos machos, albinos, raça Nova Zelândia foram submetidos à trabeculectomia bilateralmente. Os animais foram divididos em quatro grupos experimentais com 15 olhos por grupo: controle, mitomicina C, acetato de triancinolona e acetato de triancinolona + mitomicina C. Tonometria de aplanação e análise clínica da bolha através do Sistema de Graduação de Moorfields foram obtidas no pós-operatório. Para a avaliação da cicatrização, procedeu-se à análise quantitativa do infiltrado inflamatório (polimorfonucleares) através da coloração Hematoxilina & Eosina e da proliferação vascular por imuno-histoquímica. Resultados: foi observada em todos os grupos diminuição significativa da pressão intraocular pós-operatória em relação à pré-operatória (p<0,001). Contudo, não houve diferença entre os grupos (p=0,186). O grupo acetato de triancinolona + mitomicina C apresentou melhores índices na altura máxima da bolha e na vascularização da área central da bolha (p=0,001); além disso, houve menor resposta inflamatória (p=0,001) e menor proliferação vascular (p=0,001) na fase intermediária do estudo em relação às monoterapias. Conclusão: a associação da mitomicina C ao acetato de triancinolona resultou numa ação sinérgica entre esses agentes, com bolhas mais amplas e difusas e menor infiltrado inflamatório e menor proliferação vascular em estágio intermediário do acompanhamento neste modelo animal.
Revista Brasileira De Oftalmologia, 2020
P rimary open-angle glaucoma (POAG) is an age-old disease that remains enigmatic. Millions of peo... more P rimary open-angle glaucoma (POAG) is an age-old disease that remains enigmatic. Millions of people worldwide still lose their sight due to POAG and the prediction is that, with longer life expectancy, more people will be diagnosed with it. (1) Over the years, glaucoma has undergone changes in concept, workup and treatment. Up to now, the concept of this disease is not consensual. (2) Would it be a brain disease? Initially, glaucoma was synonymous with elevated intraocular pressure (IOP). The elevated IOP would cause the excavation of the optic disc (glaucomatous excavation) (3) and visual field (VF) loss, characterizing the glaucoma triad. (2) Conceptual changes occurred in 1996 when glaucoma was defined as an optic neuropathy being the elevated IOP its main risk factor. (4) Since then, optic neuropathy and VF loss characterize the manifest glaucoma. However, some patients may have an elevated IOP without VF loss nor retinal nerve fiber layer (RNFL) loss-ocular hypertension (OH). (5) Others may present preperimetric glaucoma characterized by RNFL loss detected by optical coherence tomography (OCT) in the absence of VF loss. (6) It is surprising that elevated IOP, the only known modifiable condition, has been considered as the principal risk factor taking in view that, for avoiding glaucoma progression, the treatment is the IOP normalization even when IOP is statistically normal. It is a big mistake to think that the IOP level is important for POAG and normal tension glaucoma treatment, but at the same time, not as a criterion for its diagnosis. It is known that elevated IOP is the result of impairment of drainage of the aqueous humor (AH) independently of the type of glaucoma. Uncontrolled IOP causes glaucoma progression with irreversible and progressive loss of RNFL and VF. This implies that elevated IOP seems to be or is a fundamental part of the disease and needs a detailed investigation. Taking into consideration that IOP is a highly dynamic parameter with many influence factors, it is an absurd to manage glaucoma with single IOP measurement. The major challenge is to find out the target IOP for each preperimetric or glaucomatous patient. Workup The workup of glaucoma has also changed over time. New tonometers have appeared, but none of them has overcome the gold standard Goldmann applanation tonometer since 1957. (7) In 1997, the measurement of central corneal thickness (CCT) was introduced, but there is no algorithm that directly relates it to the value of IOP. (8,9) Also, the role of corneal hysteresis (CH) in glaucoma has not been fully elucidated. CH may be more significantly associated with glaucoma than CCT. (10) OCT and OCT angiography (OCTA) have been used in last decades. (11,12) Diniz-Filho et al. reported that "higher levels of IOP during follow-up were associated with faster rates of RNFL loss over time measured by SD OCT". (10) OCTA allows for simultaneous in vivo imaging of the morphology and vasculature of the eye. (12) IOP assessment The 24-hour IOP investigation still remains a challenge. It is performed for detecting IOP peaks but it is not performed by most ophthalmologists around the world because of expense and inconvenience. (12) Many provocative and functional tests have been used to diagnose early glaucoma. The water-drinking and ibopamine tests failed to diagnose early POAG because of high rates of false-positive and false-negative results. (13,14) Some authors have monitored 24-hour IOP with the SENSIMED Triggerfish contact lens, but the results are not convincing yet. (15) Corneal hysteresis (CH) and lamina cribrosa Although there are some controversies about CH in glaucoma, some authors reported that lower CH measurements were significantly associated with increased risk of developing glaucomatous visual field defects over time.(10) Studies using Swept-Source OCT (SS-OCT) have demonstrated that the lamina cribrosa is likely biomechanically active and that significant changes occur in glaucoma. (16) VF examination In the past, blue-yellow perimetry was performed for early glaucoma diagnosis. This technique was completely abandoned. (14) Frequency-doubling perimetry (FDP) has been less used than in thepast, presenting a tendency of abandon. (14) Nowadays, all scientific works use the 24-2 test VF. Recently, some authors have advised performing the 10-2 test could be essential for some glaucoma patients. (17) Other authors reported that further studies are needed to determine the potential advantages of the 10-2 test in relation to the 24-2. (18)
Journal of the Optical Society of America, Apr 1, 2019
This paper proposes a customized and versatile optical setup to evaluate the optical performance ... more This paper proposes a customized and versatile optical setup to evaluate the optical performance of different commercially available intraocular lenses (IOLs). The setup was used to measure the wavefront error induced by different IOL models, verifying and analyzing the magnitude of low- and high-order aberrations induced by currently available IOLs. Independent analyses included non-toric spherical and aspheric IOLs from three different manufacturers. Three different dioptric powers were tested: 15, 20, and 25 D from each model. Dioptric power, induced cylinder, and spherical aberration were measured in each tested lens. All lenses had dioptric power within the tolerated margin of error. Induced cylinder was also within the current standards and clinically irrelevant. Spherical aberration varied according to the analyzed dioptric power and to the IOL model. We reported on the importance of the plane where the spherical aberration is reported, IOL or cornea. All analyzed IOLs were within current standards for the dioptric power and induced cylinder. Spherical IOLs had higher spherical aberration measured at the IOL plane.
Investigative Ophthalmology & Visual Science, 2006
Current Drug Delivery, 2021
Introduction: The most common treatment for Primary Open-Angle Glaucoma (POAG) is the daily use o... more Introduction: The most common treatment for Primary Open-Angle Glaucoma (POAG) is the daily use of eye drops. Sustained-release drug delivery systems have been developed to improve patient adherence by achieving prolonged therapeutic drug concentrations in ocular target tissues while limiting systemic exposure. The purpose of this study is to compare the efficacy and safety of bimatoprost inserts with bimatoprost eye drops in patients with POAG and Ocular Hypertension (OH). Methods: We include OH and POAG patients aged between 40 and 75 years-old. Both OH and POAG patients had intraocular pressure (IOP) greater than 21 and ≤30 mmHg at 9:00 am without glaucoma medication and normal biomicroscopy. Five normal patients with IOP≤14 mmHg constitute the control group. A chitosan-based insert of bimatoprost was placed at the upper conjunctival fornix of the right eye. In the left eye, patients used one drop of LumiganTM daily at 10:00 pm. For statistical analysis, a two-way analysis of var...
Journal of Biomedical Materials Research Part A, 2020
A benzamidine derivative from diminazene was tested for a novel activity: treatment of primary op... more A benzamidine derivative from diminazene was tested for a novel activity: treatment of primary open‐angle glaucoma. This drug was incorporated into mucoadhesive polymeric inserts prepared using chitosan (Chs) and chondroitin sulfate (CS). Of current interest is the mucoadhesion, which increases the contact time with the ocular surface, resulting in improved bioavailability; also, the inserts are made to act as a prolonged release system. In the present work the inserts were prepared by the solvent casting method using different polymeric proportions (30:70, 50:50, 75:25% w/w Chs:CS and 100% Chs). Thermal analysis and infrared spectroscopy both demonstrated physical dispersion of the active drug. The most promising was the 50:50% Chs:CS which demonstrated that it was not fragile and has an in vitro release profile of up to 180 minutes. In addition, it presented greater adhesion strength in relation to the other formulations. These physicochemical results corroborate the in vivo tests...
Journal of Biomedical Materials Research Part B: Applied Biomaterials, 2020
The use of chitosan as a pharmaceutical excipient in the ocular field is already established. Nev... more The use of chitosan as a pharmaceutical excipient in the ocular field is already established. Nevertheless, some aspects related to its ocular administration, such as sterilization and excipient's pharmacokinetics, remain unclear. So, in this study, we evaluated those two relevant aspects, related to chitosan administration in eye. We used chitosan‐based ocular inserts (CI) as formulation model. CI were produced by solvent/casting method and sterilized by saturated steam. Sterilization was confirmed by direct inoculation of inserts in suitable microbiological growth media. Physicochemical characterization of inserts before and after sterilization was performed. Results suggested that, although steam sterilization changed the arrangement of the matrix, the heat and the humidity did not modify the structure of the main polymeric chain. Pharmacokinetics of CI radiolabeled with technetium‐99m (99mTc) was assessed by scintigraphic images and ex vivo biodistribution study, after ocula...
International Journal of Pharmaceutics, 2019
This is a PDF file of an article that has undergone enhancements after acceptance, such as the ad... more This is a PDF file of an article that has undergone enhancements after acceptance, such as the addition of a cover page and metadata, and formatting for readability, but it is not yet the definitive version of record. This version will undergo additional copyediting, typesetting and review before it is published in its final form, but we are providing this version to give early visibility of the article. Please note that, during the production process, errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.
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Papers by Sebastiao Cronemberger