Moxifloxacin releasing intraocular implant based on a cross-linked hyaluronic acid membrane.

Intraocular antibiotic delivery is an important technique to prevent bacterial infection after ophthalmic surgery, such as cataract surgery. Conventional drug delivery methods, such as antibiotic eye drops, have limitations for intraocular drug delivery due to the intrinsic barrier effect of the cornea. Therefore, frequent instillation of antibiotic eyedrops is necessary to reach a sufficient bactericidal concentration inside the eye. In this study, an intraocular implant, MXF-HA, that combines hyaluronic acid (HA) and moxifloxacin (MXF) was developed to increase the efficiency of intraocular drug delivery after surgery. MXF-HA is manufactured as a thin, transparent, yellow-tinted membrane. When inserted into the eye in a dry state, MXF-HA is naturally hydrated and settles in the eye, and the MXF contained therein is delivered by hydrolysis of the polymer over time. It was confirmed through in vivo experiments that MXF delivery was maintained in the anterior chamber of the eye at a concentration sufficient to inhibit Pseudomonas aeruginosa and Staphylococcus aureus for more than 5 days after implantation. These results suggest that MXF-HA can be utilized as a potential drug delivery method for the prevention and treatment of bacterial infections after ophthalmic surgery.

Offset of openings in optic nerve head canal at level of Bruch's membrane, anterior sclera, and lamina cribrosa.

We compared the central retinal vascular trunk (CRVT) position, as a surrogate of lamina cribrosa (LC) offset, with the anterior scleral opening (ASCO) offset from the Bruch's membrane opening (BMO). Based on the BMO-centered radial scans, the BMO and ASCO margins were demarcated, and each center was determined as the center of the best-fitted ellipse for each margin. The ASCO/BMO offset was defined as the offset between each center. Angular deviations and the extent of ASCO and CRVT offsets from the BMO center were compared directly. Incomplete demarcation of ASCO was found in 20%, which was associated with a larger BMO area and a larger ASCO offset from the BMO. The angular deviation of ASCO offset was associated with that of CRVT offset and that of the longest externally oblique border. The ASCO offset was smaller than the CRVT offset, and, unlike the CRVT offset, it was rarely deviated to the inferior side. The complete ASCO margin might not be demarcatable when determined on BMO-centered radial scans in the presence of an offset. Also, the ASCO, which reflects only the superficial scleral layer, might not reflect the LC position, because the LC might be shifted further from the ASCO.

Development of a novel hyaluronic acid membrane for the treatment of ocular surface diseases.

Ocular surface diseases (OSD) can cause serious visual deterioration and discomfort. Commercial artificial tear solution containing hyaluronic acid (HA) show excellent biocompatibility and unique viscoelastic characteristics. Here, we developed a novel HA membrane (HAM) by chemical crosslinking using 1,4-butanediol diglycidyl ether for the effective treatment of OSDs. The main purpose of HAMs is to provide sustained release of HA to modulate the wound healing response in OSDs. The safety and efficacy of HAMs were investigated using primary cultured human corneal epithelial cells and various OSD rabbit models. In the dry state, the HAM is firm, transparent, and easy to manipulate. When hydrated, it swells rapidly with high water retention and over 90% transmission of visible light. Human corneal epithelial cells and rabbit eyes showed no toxic response to HAM. Addition of HAMs to the culture medium enhanced human corneal epithelial cell viability and expression of cell proliferation markers. Investigation of HAM wound healing efficacy using mechanical or chemical corneal trauma and conjunctival surgery in rabbits revealed that application of HAMs to the ocular surface enhanced healing of corneal epithelium and reduced corneal limbal vascularization, opacity and conjunctival fibrosis. The therapeutic potential of HAMs in various OSDs was successfully demonstrated.

Effect of Nitric Oxide on Acanthamoeba castellanii.

Purpose: Acanthamoeba keratitis is a well-known intractable corneal infectious disease. We investigated the anti-Acanthamoeba effect of exogenous nitric oxide (NO). Methods: Acanthamoeba castellanii was axenically cultured and exposed to various concentrations of NO donors, such as sodium nitrite, sodium nitroprusside (SNP), and NO-releasing silica nanoparticles (coated in branched polyethylene imine, size:100 nm), for 1 to 7 days (sodium nitrite and SNP: 0, 0.1, 1, 10, 100, and 1000 µM; silica nanoparticles: 0, 6.25, 12.5, 25, 50, and 100 µg/mL). Human corneal epithelial cells (HCECs) were cultured and exposed to sodium nitrite, SNP (0, 0.1, 1, 10, 100, and 1000 µM), and silica nanoparticles for 1, 2, and 3 days. Results: Sodium nitrite and SNP showed a dose-dependent inhibitory effect on A. castellanii viability. A more prominent inhibitory effect was observed with SNP (less than 10% of organisms survived at 7-day culture with 1000 µM) compared with sodium nitrite. However, more cytotoxicity on HCEC was observed with SNP. NO-releasing silica nanoparticles were successfully internalized into the amoebic cytoplasm and accumulated in large vacuoles. Although blank silica nanoparticles had no inhibitory effect on A. castellanii viability, NO-releasing silica nanoparticles showed a dose-dependent amoebicidal effect. Furthermore, no cystic transformation of A. castellanii was observed under a phase contrast microscope or transmission electron microscope after exogenous NO treatment. Conclusions: Our results demonstrated the anti-Acanthamoeba effect of exogenous NO. This finding suggests that NO-releasing drug platforms, including nano-carriers, can be a promising therapeutic strategy for Acanthamoeba keratitis.

Effect of Nitric Oxide on Human Corneal Epithelial Cell Viability and Corneal Wound Healing.

Although the wound healing effects of nitric oxide (NO) are known, the mechanism by which NO modulates corneal wound healing remains unclear. In this study, we investigated the effect of exogenous NO donor (NaNO2) on corneal wound healing. We found that NaNO2 (0.1 µM to 100 µM) increased human corneal epithelial cell (HCEC) viability and migration. It also modulated the phosphorylation of mitogen-activated protein kinases (MAPKs) in a time- dependent manner in those HCECs. Further, p38 MAPK phosphorylation increased at 6 h and normalized at 24 h, while the phosphorylation of extracellular signal regulated kinase (ERK) was increased both at 6 h and 24 h. Topical treatment with NaNO2 (10 µM) enhanced corneal epithelial healing and decreased corneal opacity in murine corneal alkali burn model by modulating inflammatory cytokines. Our findings suggest that NO increased HCEC proliferation and migration via time-dependent MAPK activation and eventually enhanced corneal recovery from the alkali burn.

The Effect of Silica Nanoparticles on Human Corneal Epithelial Cells.

Ocular drug delivery is an interesting field in current research. Silica nanoparticles (SiNPs) are promising drug carriers for ophthalmic drug delivery. However, little is known about the toxicity of SiNPs on ocular surface cells such as human corneal epithelial cells (HCECs). In this study, we evaluated the cytotoxicity induced by 50, 100 and 150 nm sizes of SiNPs on cultured HCECs for up to 48 hours. SiNPs were up-taken by HCECs inside cytoplasmic vacuoles. Cellular reactive oxygen species generation was mildly elevated, dose dependently, with SiNPs, but no significant decrease of cellular viability was observed up to concentrations of 100 µg/ml for three different sized SiNPs. Western blot assays revealed that both cellular autophagy and mammalian target of rapamycin (mTOR) pathways were activated with the addition of SiNPs. Our findings suggested that 50, 100 and 150 nm sized SiNPs did not induce significant cytotoxicity in cultured HCECs.

Changes of the Macular Ganglion Cell-Inner Plexiform Layer Thickness after Cataract Surgery in Glaucoma Patients.

Purpose. To investigate the effect of uneventful cataract surgery on macular ganglion cell-inner plexiform layer (mGC-IPL) thickness in glaucoma patients. Methods. This retrospective study included 65 eyes of 65 subjects who underwent uneventful cataract surgery, including 13 glaucoma eyes and 52 normal eyes. Using spectral domain optical coherence tomography, the mGC-IPL thickness was measured and compared between glaucoma and normal eyes preoperatively as well as 1 month and 3 months postoperatively. Linear regression analysis was used to determine the factors associated with postoperative change in mGC-IPL thickness. Results. The mean mGC-IPL significantly increased in both groups 1 month and 3 months after surgery (all P values equal to or less than 0.001). The postoperative changes between groups were not significantly different (P = 0.171). In the multivariate regression analysis, preoperative mGC-IPL thickness showed a significant association with the change of average mGC-IPL thickness 1 month and 3 months after surgery (all P values < 0.001). Conclusions. The mean mGC-IPL thickness was increased after cataract surgery, and the postoperative mGC-IPL thickness changes were associated with preoperative mGC-IPL thickness in both groups and axial length in normal eye. The effects of cataract surgery on mean mGC-IPL thickness were not different in glaucomatous and normal eyes.

Anterior chamber configuration changes after cataract surgery in eyes with glaucoma.

PURPOSE: To evaluate changes in anterior chamber depth (ACD) and angle width induced by phacoemulsification and intraocular lens (IOL) implantation in eyes with glaucoma, using anterior segment optical coherence tomography (AS-OCT). METHODS: Eleven eyes of 11 patients with angle-closure glaucoma (ACG) and 12 eyes of 12 patients with open-angle glaucoma (OAG) underwent phacoemulsification and IOL implantation. Using AS-OCT, ACD and angle parameters were measured before and 2 days after surgery. Change in intraocular pressure (IOP) and number of ocular hypotensive drugs were evaluated. RESULTS: After surgery, central ACD and angle parameters increased significantly in eyes with glaucoma (p < 0.05). Prior to surgery, mean central ACD in the ACG group was approximately 1.0 mm smaller than that in the OAG group (p < 0.001). Post surgery, mean ACD of the ACG group was still significantly smaller than that of the OAG group. No significant differences were found in angle parameters between the ACG and OAG groups. In the ACG group, postoperative IOP at the final visit was significantly lower than preoperative IOP (p = 0.018) and there was no significant change in the number of ocular hypotensive medications used, although clinically, patients required fewer medications. In the OAG group, the IOP and number of ocular hypotensive drugs were almost unchanged after surgery. CONCLUSIONS: The ACD and angle width in eyes with glaucoma increased significantly after phacoemulsification and IOL implantation. Postoperative ACD significantly differed between the ACG and OAG groups, whereas angle parameters did not differ.

Changes in anterior chamber configuration after cataract surgery as measured by anterior segment optical coherence tomography.

PURPOSE: To evaluate the changes in anterior chamber depth (ACD) and angle width induced by phacoemulsification and intraocular lens (IOL) implantation in normal eyes using anterior segment optical coherence tomography (AS-OCT). METHODS: Forty-five eyes (45 patients) underwent AS-OCT imaging to evaluate anterior chamber configuration before and 2 days after phacoemulsification and IOL implantation. We analyzed the central ACD and angle width using different methods: anterior chamber angle (ACA), trabecular-iris angle (TIA), angle opening distance (AOD), and trabecular iris surface area (TISA) in the nasal and temporal quadrants. Comparison between preoperative and postoperative measurement was done using paired t-tests and each of the angle parameters was analyzed with Pearson correlation testing. Subgroup analyses according to the IOL and axial length were performed with a general multivariate linear model adjusted for age. RESULTS: Before surgery, the mean anterior chamber angle widths were 23.21 ± 6.70° in the nasal quadrant and 24.89 ± 7.66° in the temporal quadrant. The mean central ACD was 2.75 ± 0.43 mm. After phacoemulsification and IOL implantation, the anterior chamber angle width increased significantly to 35.16 ± 4.65° in the nasal quadrant (p = 0.001) and 36.03 ± 4.86° in the temporal quadrant (p = 0.001). Also, central ACD increased to 4.14 ± 0.31 mm (p = 0.001). AOD, TISA, and TIA increased significantly after cataract surgery and showed positive correlation with ACA. CONCLUSIONS: After cataract surgery, the ACD and angle width significantly increased in eyes with cataract. AS-OCT is a good method for obtaining quantitative data regarding anterior chamber configuration.

Ultrassonografia nas lesões do couro cabeludo pediátrico / Ultrasonography in pediatric scalp lesions

OBJETIVO: Apresentar os resultados do estudo ultrassonográfico de diferentes lesões do couro cabeludo em crianças de diversas faixas etárias, seguidos de breve discussão acerca da patologia, juntamente com revisão da literatura. MATERIAL E MÉTODO: Pacientes com idades entre 13 dias e 7 anos e 9 meses, submetidos a avaliação ultrassonográfica das lesões do couro cabeludo com transdutor linear de alta frequência (12 MHz) e avaliação com Doppler colorido. DISCUSSÃO: A ultrassonografia possibilitou o estudo anatômico detalhado e a caracterização das lesões do couro cabeludo, assim como seu padrão de fluxo sanguíneo ao Doppler colorido. CONCLUSÃO: A correta interpretação dos achados de imagem das lesões do couro cabeludo depende do conhecimento,pelo médico radiologista, das principais afecções existentes, dos mecanismos fisiopatológicos dadoença e da apresentação clínica do paciente, para que o diagnóstico seja estabelecido de formaprecoce e correta.

OBJECTIVE: To present the results of an ultrasound study of differentscalp lesions in children of different ages followed by brief discussion of pathology, along with review of literature. MATERIAL AND METHOD: Patients aged between 13 days and 7 years and 9 months underwent sonographic evaluation of lesions of the scalp with a linear, high frequency probe (12 MHz) and color Doppler evaluation. DISCUSSION: The ultrasound allowed a detailed anatomical study and characterization of lesions of the scalp, as well as its pattern of blood flow on color Doppler. CONCLUSION: The correct interpretation of imaging findings of lesions of the scalp depends on the knowledge, the radiologist, existing major diseases,the pathophysiological mechanisms of disease and clinical presentation so that the diagnosis is established early and correct.

Differential expression of stem cell markers and vascular endothelial growth factor in human retinoblastoma tissue.

PURPOSE: To investigate the relationship between vascular endothelial growth factor (VEGF) and the cancer stem cell-vascular niche complex in human retinoblastoma tissue. METHODS: Six human retinoblastoma specimens primarily enucleated for Reese-Ellsworth classification stage 5a were stained to detect cancer stem cell markers, including ABCG2 for the stem cell marker and MCM2 for the neural stem cell marker, as well as to detect VEGF for the angiogenic cytokine. Using immunofluorescence, the expression of these proteins was analyzed, and their relative locations noted. RESULTS: In non-neoplastic retina of tumor-bearing eyes, ABCG2 and MCM2 were sporadically expressed in the ganglion cell layer and the inner nuclear layer, whereas VEGF was sporadically expressed in inner retina where retinal vessels are abundantly distributed. In the tumor, ABCG2 was strongly expressed out of Wintersteiner rosettes, whereas MCM2 and VEGF were strongly stained in the rosettes. Interestingly, the outer portion of the rosettes was positive for MCM2, and the inner portion of the rosettes was positive for VEGF. CONCLUSIONS: Our data demonstrated that MCM2 and VEGF are strongly expressed in the rosettes of the tumor, which were far from the area of ABCG2-positive cells. Although VEGF might not directly contribute to the cancer stem cell-vascular niche complex, it could play some role in the differentiation of tumor cells to build up the rosettes.

Volumoso hidrocolpo em neonato: relato de caso / Newborn hydrocolpos secondary to congenital imperforate hymen: a case report

Os autores relatam um caso de hímen imperfurado congênito determinando volumoso hidrocolpo em recém-nascido. Esta anomalia é uma condição rara, pois a maioria dos casos de hímen imperfurado é diagnosticada na fase pré-púbere com o atraso da menarca. O objetivo deste relato é demonstrar os achados ultrassonográficos do hidrocolpo no recém-nato e realizar uma breve revisão de literatura sobre o assunto. É de fundamental importância nestes pacientes o rastreamento de outras malformações congênitas que podem estar associadas ao quadro.

The authors report a case of newborn hydrocolpos secondary to congenital imperforate hymen. This anomaly is a rare condition, since most cases of imperforate hymen are diagnosed in the prepubertal period with the delay of menarche. The objective of this report is to demonstrate ultrasound findings of newborn hydrocolpos and make a review of literature about it. It is vital to search other congenital malformations that may be associated.

Ultrasonographic findings in genitourinary tract malformations: a pictorial essay / Achados ultrassonográficos nas malformações do trato geniturinário: ensaio pictórico

Objective: To demonstrate didactically the different ultrasound findings of various congenital malformations of the genitourinary system. Methods: Twelve cases were retrospectively studied, comprising patients who presented with genitourinary tract malformations (with or without related symptoms), detected by ultrasound testing carried out with Phillips ATL / HDI - 5000 ultrasound equipment, during the period of August 2007 to June 2009 at the Imaging Department of the Hospital Israelita Albert Einstein. Results: Six patients were females and six were males, and ages varied from a few hours of life to 15 years and 9 months. All individuals were evaluated and accompanied by the Pediatric Radiology sector of the Hospital Israelita Albert Einstein. The study was carried out as follows: two cases of hydrocolpos, one of them a result of imperforate hymen and one a case a congenital stenosis of the ureteropyelic junction, one case of ureterocele, one case of bilateral double collection system, one case of horseshoe kidney, one case of Hutchs diverticulum, two cases of pelvic kidney, one of them with hydronephrosis, one case of multicystic dysplastic kidney, one case of polycystic kidney (adult form), and one case of congenital megaureter. Conclusions: The ultrasonographic study is a valuable method for the early identification, often in the uterus, of these and several other treatable anomalies of the genitourinary tract. Additionally, it also presents the advantage of not using ionizing radiation, which is very significant, especially in the pediatric age group.

Objetivo: Demonstrar de maneira didática os diferentes achados ultrassonográficos de diversas malformações congênitas do sistema geniturinário. Métodos: Foram estudados retrospectivamente 12 casos de pacientes que apresentavam malformações do trato geniturinário (com ou sem sintomas relacionados), detectados nos exames de ultrassonografia com aparelhos de ultrassom Phillips ATL / HDI - 5000, no período de agosto de 2007 a junho de 2009 no Departamento de Imagem do Hospital Israelita Albert Einstein. Resultados: Seis pacientes eram do sexo feminino e seis do sexo masculino, e as idades variaram entre algumas horas de vida até 15 anos e 9 meses. Todos foram avaliados e acompanhados pelo setor da radiologia pediátrica do Hospital Israelita Albert Einstein. Os casos estudados foram: dois casos de hidrocolpo um deles consequente a hímen imperfurado, um caso de estenose congênita da junção ureteropiélica, um caso de ureterocele, um caso de duplicidade do sistema coletor bilateral, um caso de rim em ferradura, um caso de divertículo de Hutch, dois casos de rim pélvico, um deles apresentando hidronefrose, um caso de rim displásico multicístico, um caso de rim policístico (forma adulta) e um caso de megaureter congênito. Conclusões: O estudo ultrassonográfico é um valioso método para a identificação precoce, muitas vezes intrauterina, dessas e de diversas outras anomalias do trato geniturinário passíveis de tratamento. Além disso, apresenta também a vantagem de não utilizar radiação ionizante, o que é de grande importância especialmente na faixa etária pediátrica.

Síndrome de Nutcracker: a aplicação da ultra-sonografia com dopler e relato de caso / Nutcracker syndrome: the application of ultrasonography with doppler and a case report

Neste artigo descrevemos o caso clínico de um paciente com síndrome de nutcracker (síndrome de quebra-nozes) diagnosticado por ultra-sonografia com Doppler e discutimos a aplicação e a importância deste método de imagem, bem como suas limitações.

In this article we describe the clinical case of a patient with nutcracker syndrome, diagnosed by ultrasonography with Doppler, and discuss the application and the importance of this method of image, as well its limitations.

Temporal and spatial patterns of glial differentiation in the surgically induced spinal open neural tube defect of chick embryos: astrocytic, radial glial and microglial differentiations.

INTRODUCTION: There are controversies over the pattern of glial differentiation in spinal open neural tube defect (ONTD) at the prenatal stage. A surgical model of ONTD allows a more precise comparison of glial differentiation between the ONTD and control groups than chemical and genetic models. MATERIALS AND METHODS: To investigate the influence of ONTDs on the patterns of glial differentiation, ONTDs were induced by surgery using Hamburger and Hamilton stage 18 or 19 chick embryos. The spinal cord tissues on postoperative days (POD) 5, 7, 10, and 14 were processed to observe astrocytic, radial glial, and microglial differentiations by glial fibrillary acid protein (GFAP), vimentin and ricinus communis agglutinin-I (RCA-I) stainings, respectively. Four embryos were assigned to subgroups of each POD. Control embryos ( n=4) were staged but the neural tubes were not incised. RESULTS: In the control group, GFAP positivity was shown faintly at the dorsal midline on embryonic day (E) 10 (corresponding to POD 7), in the ventral one-third of the white matter on E 13 and in the whole white matter on E 17. Embryos with ONTDs showed earlier and stronger GFAP positivity from POD 7-14, especially at the dorsal surface and the adjacent gray matter. In the control group, vimentin staining demonstrated a positive reaction at the midline with positivity in a faint, radial pattern on E 8 and E 10. This had all disappeared by E 13 and 17. In embryos with ONTDs, vimentin positivity was enhanced and persisted from POD 5-14. These findings were prominent along the dorsal surface of ONTDs. No difference in RCA-I staining was found between the control and ONTD groups. CONCLUSION: The results reveal that ONTD promotes astrocytic differentiation and prolongs expression of radial glial fibers, which seems to be a reaction to the damage caused by exposure of the spinal cord tissue to amniotic fluid.