Le virus de l'herpès simplex de sérotype 1 (HSV-1) est la plus grande cause de l’aveuglement infectieuse dans les pays développés. Les infections cornéennes à HSV-1 ont plusieurs conséquences, comme la difficulté à éliminer l'infection virale et l'inflammation provoquant une plus grande opacité de la cornée. Une infection cornéenne a montré qu'il y a colocalisation des cellules souches et les cellules amplificatrices transitoires avec le virus, mais le HSV-1 était toujours abondant dans le limbe de l'œil. Pour combattre le virus, anciennes publications ont montré que LL37, une cathélicidine humaine, peut réduire la charge virale. Le GF19, un fragment de LL37 modifié pour favoriser la perméabilité, a été capable de réduire la charge virale in vitro et ex vivo, avec la possibilité d'avoir des effets thérapeutique et préventif. Pour combattre les conséquences inflammatoires, un agoniste cannabinoïde CB2r impliqué dans la modulation de la neuroinflammation, TA-A001, a été testé. Des souris ayant reçu des brûlures alcalines pour induire l’inflammation et ils ont montré de meilleurs résultats cliniques avec le TA-A001 qu'avec le véhicule du médicament seul ou un corticostéroïde, la prednisolone. En conclusion, il apparaît que l’HSV-1 infecte rapidement le limbe, que le GF19 a pu réduire la charge virale, et que le TA-A001 a pu réduire l'inflammation en ayant peu d'effets secondaires. Une combinaison des traitements antiviraux et immunosuppresseurs administrés à la cornée pourrait être examinée plus pour combattre contre les infections à HSV-1 dans les yeux. / Herpes Simplex Virus serotype 1 (HSV-1) is the most common cause of infectious blindness in developed countries. Little is known about the early events in HSV-1 ocular infections since clinical symptoms often appear a week after infection. There are two significant consequences of HSV-1 corneal infection: the viral impacts of the disease and the inflammatory impacts. In mouse corneas, after HSV-1 infection, viruses localized in the limbal area of the cornea. However, there was no/little immunohistochemical co-localization with the stem cells or transient amplifying cells. Previous work has shown that LL37, a human cathelicidin, can reduce the viral burden. GF19, a fragment of LL37 with a modification to promote permeability, reduced viral loads in vitro and in ex vivo corneas. To combat the inflammatory consequences of HSV-1 infection, a cannabinoid CB2r agonist implicated in neuroinflammation modulation, TA-A001, was tested. Mice given alkali burns to induce inflammation showed better clinical results with TA-A001 than with the drug’s vehicle alone or a corticosteroid, prednisolone. In conclusion, it appears that HSV-1 quickly infects the limbus, GF19 was able to reduce viral burden, and CB2 agonists such as TA-A001 could reduce inflammation with few side effects. A combination of the anti-viral and immunosuppressant treatments could be a potential HSV-1 treatment.

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Yes / This paper outlined our method for developing polymer-linked contact lens type materials for rapid detection and differentiation of Gram-positive, Gram-negative bacteria and fungi in infected corneas. It can be applied to both model synthetic or ex-vivo corneal models and has been successfully trialed in an initial efficacy tested animal study. First a hydrogel substrate for the swab material is selected, we have demonstrated selective swabs using a glycerol monomethacrylate hydrogel. Alternatively any commercial material with carboxylic acid functional groups is suitable but risks nonspecific adhesion. This is then functionalised via use of N-hydroxysuccinimide reaction with amine groups on the specified highly branched polymer ligand (either individually gram negative, gram positive or fungal binding polymers or a combination of all three can be employed for desired sensing application). The hydrogel is then cut into swabs suitable for sampling, used, and then the presence of gram positive, game negative and fungi are disclosed by the sequential addition of dyes (fluorescent vancomycin, fluorescein isothiocyanate and calcofluor white). In summary this method presents: Method to produce glycerol monomethacrylate hydrogels to minimize nonspecific binding Methods of attaching pathogen binding highly branched polymers to produce selective hydrogel swabs Method for disclosing bound pathogens to this swab using sequential dye addition

O ceratocone é uma disfunção da córnea, que geralmente manifesta-se por meio de um astigmatismo irregular e de um alto grau de miopia. O estágio avançado da doença é a principal causa de indicação da cirurgia de transplante de córnea. Certamente, trata-se de uma condição complexa, com etiologia multifatorial: fatores genéticos e ambientais estão associados para a expressão fenotípica. A maioria dos casos vistos na prática clínica são não sindrômicos (cursam sem comorbidades) e isolados, mas há uma proporção considerável de casos familiares. Foi feito um levantamento bibliográfico das principais variantes associadas ou relacionadas à doença para auxiliar na investigação. O presente projeto teve por objetivo identificar uma possível variante causal, por meio de estudo de ligação de amplitude genômica (GWLS), de uma família brasileira com 15 afetados por ceratocone, após a extração de DNA e genotipagem das amostras por microarranjo de SNP. Também foi realizado o sequenciamento de exoma do probando, visando filtrar as variantes patogênicas candidatas a explicar a doença. Foram encontradas 123 variantes suspeitas no exoma do paciente avaliado por NGS. Adicionalmente, identificou-se 3 regiões com LOD Score >1 (1p35.2-p34.3; 2q32.3-q33.2; 3q23; 5q11.2-q13.2) e uma com LOD Score>2 (19p13.11-q12). A combinação das duas metodologias permitiu a identificação de três variantes, sendo uma delas provavelmente implicada na etiologia, ainda por validar. Duas outras variantes foram excluídas / Keratoconus is a dysfunction of the cornea, which usually manifests itself through irregular astigmatism and a high degree of myopia. The advanced stage of the disease is the leading cause of indication for corneal transplant surgery. Certainly, it is a complex condition with a multifactorial etiology: genetic and environmental factors acts together to the phenotypic expression. Most of the cases seen in clinical practice are non- syndromic (with no comorbidities) and isolated, but there is a considerable proportion of familial cases. A bibliographic survey of the main variants associated or related to the disease was made to suport the investigation. The present project aimed to identify a possible causal variant by genomic amplitude binding study (GWLS) of a Brazilian family with 15 affected by keratoconus, after DNA extraction and genotyping of the samples by SNP microarray. It was also performed one exome sequencing, aiming to filter out the pathogenic candidate variants from the proband to explain the disease. 123 suspected variants were found in the patient\'s exams evaluated by NGS. In addition, 3 regions with LOD Score> 1 (1p35.2-p34.3; 2q32.3-q33.2; 3q23; 5q11.2- q13.2) and one with LOD Score> 2 (19p13.11 -q12). The combination of the two methodologies allowed the identification of three variants, one of them probably implicated in the etiology, yet to be validated. Two other variants were excluded

O presente trabalho trata-se do desenvolvimento de um programa para de análise de imagens de topografia corneana de sistemas comerciais, para ser implementado no topógrafo corneano para Lâmpada de Fenda, em desenvolvimento no Laboratório de Instrumentação Oftálmica - EESC/USP e no Laboratório de Física Oftálmica - FMRP/USP. O programa foi desenvolvido em C++, utilizando a plataforma Windows, e fornece mapas axiais de topografia corneana. O programa foi testado em esferas de calibração e em olhos humanos, apresentando um fator de correlação de 0,9998 para as medidas em esferas e um erro inerente estimado em 3%. Os mapas de topografias axiais em olhos humanos foram comparados com os mapas gerados por sistemas comerciais e o padrão visual de forma e relevo estão em concordância. / This work is about a software for the analisys of corneal topography images provided by commercial available systems to be implemented in a corneal topographer for slit lamps under evelopment at Laboratório de Instrumentação Oftálmica . EESC/USP e no Laboratório de Física Oftálmica . FRMP/USP. The software was developed in Borland C++ Builder for Windows and provides the corneal topography axial maps. The software has been tested in calibration spheres and in human eyes, presenting a correlation factor of 0,9998 for the measurements performed in the spheres and an inherent error of 3%. The axial topographic maps form the exams performe in human eyes have been compared to the axial maps provided by the commercial available system and the visual pattern as well as the relief are in accordance.

INTRODUÇÃO: Comparar duas soluções viscoelásticas, ácido hialurônico 1,6%/sulfato de condroitina 4% (DisCoVisc®, Alcon Laboratórios, EUA) e hidroxipropilmetilcelulose 2% (HPMC, Ophthalmos, Brasil), com relação ao desempenho durante a facoemulsificação (FACO) e o implante de lente intraocular. MÉTODOS: Foi realizado um ensaio clínico randomizado, envolvendo 78 olhos (39 pacientes) submetidos à FACO bilateral, por um único cirurgião. Os pacientes foram randomizados para receber DisCoVisc ou HPMC no primeiro olho. O olho contralateral foi operado mais tarde recebendo a outra solução viscoelástica em todas as etapas da cirurgia. Examinadores mascarados realizaram as avaliações pré e pósoperatórias (5, 24 e 48 horas; 7 e 14 dias; 3 e 6 meses), incluindo a medida da pressão intraocular (PIO), espessura cornena central (ECC) e acuidade visual corrigida. A densidade endotelial foi realizada no pré-operatório e ao final do seguimento (6 meses). Variáveis intraoperatórias incluíram medidas da quantidade total de solução viscoelástica, tempo de ultrassom durante a FACO e tempo para a retirada completa da solução do olho. RESULTADOS: A densidade endotelial foi estatisticamente superior com DisCoVisc (2.214 ± 372 cel/mm2) do que com HPMC (2.032 ± 460 cel/mm2) ao final do seguimento (p = 0,001). Uma redução média de 7% e de 15%, respectivamente. Não houve diferença estatística entre as soluções viscoelásticas com relação a densidade da catarata (p = 0,363) e o tempo de ultrassom (p = 0,456). O tempo de aspiração da HPMC (0,22 ± 0,09 min) foi significativamente maior que o DisCoVisc (0,17 ± 0,06 min) (p = 0,001) e a quantidade de viscoelástico utilizada foi maior com a HPMC (1,35 ± 0,20 ml) do que com DisCoVisc (0,89 ± 0,11 ml) (p < 0,001). Não houve diferença estatisticamente significativa entre as soluções quanto a ECC e a PIO durante o seguimento. CONCLUSÕES: A densidade endotelial ao final do estudo foi significativamente maior com o uso de DisCoVisc, o que pode representar uma melhor proteção endotelial. Foi necessário uma menor quantidade de DisCoVisc e um tempo de aspiração menor durante a FACO com essa solução viscoelástica / INTRODUCTION: To compare two ophthalmic viscosurgical devices (OVDs), 1.6% hyaluronic acid/4% chondroitin sulfate (DisCoVisc®, Alcon Lab., USA) and 2% hydroxypropylmethylcellulose (HPMC, Ophthalmos, Brazil), in terms of their overall performance during phacoemulsification (PHACO) and intraocular lens implantation. METHODS: This prospective, randomized clinical trial comprised 78 eyes (39 patients) that underwent PHACO by the same surgeon. Patients were randomly assigned to receive DisCoVisc or HPMC on the first eye. The other eye was treated later and received the other OVD. Masked examiners measured intraocular pressure (IOP), central corneal thickness (CCT) and best-corrected visual acuity. The corneal endothelial cell density was measured at baseline and at 6 months postoperatively. Intraoperative variables include the total amount of the OVD, ultrasound and washout times. RESULTS: Corneal endothelial cell density was significantly higher with DisCoVisc (2.214 ± 372 cell/mm2) than HPMC (2.032 ± 460 cell/mm2) at the end of follow-up (p = 0.001). A mean reduction of 7% and 15%, respectively. There were no statistically significant differences between OVDs in terms of cataract density (p = 0.363) or ultrasound time (p = 0.456). Regarding washout time, it took longer to remove HPMC (0.22 ± 0.09 min) than DisCoVisc (0.17 ± 0.06 min) (p = 0.001), and the amount of viscoelastic material used was greater with HPMC (1.35 ± 0.20 ml) than DisCoVisc (0.89 ± 0.11 ml) (p < 0.001). There were no statistically significant differences between the two OVDs regarding CCT or IOP measurements at any point in time. CONCLUSION: The corneal endothelial cell loss was significantly less with DisCoVisc than HPMC, which can improve corneal endothelium protection. DisCoVisc was easier to remove after IOL implantation and fewer amounts were necessary during PHACO

Se ha estudiado la calidad óptica del ojo en función de la edad para entender mejor el envejecimiento del sistema visual humano. Se ha construido un sistema experimental de registro de imágenes, adaptado a un entorno clínico, para medir la función de transferencia (MTF) ocular, y se ha desarrollado un procedimiento computacional para obtener las aberraciones ópticas de la córnea. Se han realizado medidas en una población de 60 sujetos distribuidos en tres grupos de edad (20-30 años, 40-50 años y 60-70 años), y en un grupo de pacientes implantados con lente intraocular. La MTF media ocular empeora de cada grupo de edad al siguiente, y las aberraciones corneales tienden a aumentar. La calidad óptica del ojo humano se reduce progresivamente con la edad; la córnea es parcialmente responsable de esa reducción. La calidad óptica en pacientes con lente intraocular es similar a la media de los sujetos mayores normales. / The optical quality of the eye was studied as a function of age to better understand the aging process in the human visual system. An experimental imaging system, adapted to a clinical environment, was constructed to measure the ocular modulation transfer function (MTF). A computational procedure was developed to obtain the optical aberrations of the cornea. Measurements were performed in a population of 60 subjects within three age groups (20-30 years, 40-50 years, and 60-70 years), and in a group of 20 patients implanted with intraocular lenses. The average MTF declines as age increases from young to middle and older groups. Corneal aberrations tends to increase with age. Optical quality of the human eye progressively deteriorates with age. The cornea may partially explain the reduction of optical performance of the complete eye. The average image quality in patients with intraocular lenses was similar to the average of normal older subjects.

Ocular neovascularization (NV) associated with corneal NV, ischemic retinopathies and age-related macular degeneration is a leading cause of severe vision loss. While numerous contributing factors have been identified, the potential role of the CD36 scavenger receptor has been largely overlooked notwithstanding its crucial involvement in normal retinal function. Accordingly, the central aim of this work was to elucidate the contribution and regulation of CD36 during ocular NV using the cornea as a model. / Initial work investigating the role of CD36 10 maintaining corneal avascularity, an important feature of the normal cornea, revealed that genetic ablation of CD36 elicits age-related corneal NV. Subsequent studies using a pathophysiologically relevant model of inflammatory corneal NV showed constitutive expression of CD36 in the normal cornea with marked induction in the neovascularized cornea. Importantly, activation of CD36 suppressed and induced regression of corneal NV, effects that proceeded via concerted inhibition of VEGFA, JNK-1, and cJun. / Because hypoxia is a fundamental stimulus for angiogenesis, it was pertinent to explore the role and regulation of CD36 during hypoxia. We demonstrate that CD36 expression was significantly elevated in hypoxia-exposed corneal and retinal tissue and in hypoxic retinal pigment epithelial cells. Essential contributions of hypoxia-inducible factor (HIF)-1 and reactive oxygen species were also established. Functional consequences were depicted by augmentations in CD36 phagocytic and anti-angiogenic activities. / Collectively, data disclose CD36 as an important modulator of corneal avascularity and inflammatory corneal NV; this imparts several interesting avenues for future research on the involvement of CD36 in neovascular diseases of the eye. Novel data further identify CD36 as a hypoxia and HIF-1 regulated gene thus creating a framework for future elucidation of the regulatory aspects of this receptor.

Background: A mouse model of combined UVA/riboflavin irradiation to eliminate stromal cells and other antigen-presenting cells in the cornea provides the basis for a probably low risk of corneal transplantation. Methods: After abrasion of the epithelium, the central corneas of mouse eyes were treated with UVA/riboflavin in vitro. Histological studies of hematoxylin-eosin and immunohistochemical staining with caspase 3 were performed. Dissected mouse corneas were analyzed by Western blot. Results: Apoptotic cells were shown on the central corneal stroma; a cell-free zone was displayed in the cornea. Numbers of dead cells increased according to cultivation time. However, the endothelium survived due to the adjustment of the irradiation dose. Conclusions: A cell-free zone in the stroma of the mouse cornea was produced by UVA/riboflavin irradiation in vitro. The technique makes possible to prevent or reduce immunological reactions and the risk of graft rejection by pretreatment of the donor cornea, ultimately prolonging graft survival. / Dieser Beitrag ist mit Zustimmung des Rechteinhabers aufgrund einer (DFG-geförderten) Allianz- bzw. Nationallizenz frei zugänglich.

Portadores de diabetes parecem ter mais queixas de olho seco do que o resto da população. Acredita-se que isto possa estar associado a uma forma de neuropatia diabética expressa por uma redução na sensibilidade corneana desses pacientes. Nossos principais objetivos neste estudo foram avaliar a influência da diabetes melito tipo 2 na sensibilidade corneana central e verificar se há uma associação entre a sensibilidade corneana central e a síndrome do olho seco em indivíduos com a doença. Assim, 62 portadores de diabetes tipo 2 foram submetidos a um exame oftalmológico de rotina, a uma ceratoestesiometria e a testes específicos para avaliar olho seco e polineuropatia distal simétrica. Num outro grupo, 20 voluntários saudáveis tiveram seus olhos avaliados da mesma forma, exceto pela não realização dos testes específicos para disfunção lacrimal. Entre os indivíduos diabéticos avaliados, foram observados 53.2% com hipoestesia corneana, 54.2% com retinopatia diabética, 45.9% com polineuropatia distal simétrica e 51.6% com a síndrome do olho seco. Entre os principais achados, observamos associações significativas envolvendo: diabetes tipo 2 e hipoestesia corneana central, síndrome do olho seco e hipoestesia corneana central, produção lacrimal reflexa (avaliada pelo teste de Schirmer II) e sensibilidade corneana central e retinopatia diabética proliferativa e sensibilidade corneana central. Uma possível associação foi encontrada envolvendo síndrome do olho seco retinopatia diabética proliferativa. Os autores discutem os resultados obtidos e os mecanismos envolvidos. / Diabetes bearers seem to have more complaints of dry eye than the rest of the population. It`s believed that this fact might be associated to a kind of diabetes neuropathy wich is represented by a reduction in corneal sensibility of these patients. Our main target in this study was to evaluate the influence of type 2 diabetes mellitus in central corneal sensibility and to determine if there is an association among central corneal sensibility and the dry eye syndrome in individuals suffering of this disease. Therefore, 62 type 2 diabetic patients were submitted to an ophthalmological routine examination, to corneal esthesiometry and to specific tests to evaluate dry eye and peripheral polineurophaty. In other group, 20 healthy volunteers had their eyes evaluated in the same way, except for the non accomplishment of the specific tests for dry eye. Among the examined diabetic individuals, 53.2% had corneal hypoesthesia, 54.2% presented diabetic retinopathy, 45.9% presented periferal polineuropathy and 51.6% presented the dry eye syndrome. Among the main findings, we observed associations between: type 2 diabetes and central corneal hypoesthesia, dry eye syndrome and central corneal hypoesthesia, reflex tear production (evaluated by Schirmer 2 test) and central corneal esthesiometry and also between proliferative diabetic retinopathy and central corneal sensibility. A possible association was found involving dry eye syndrome and proliferative diabetic retinophaty. The authors discuss the results obtained and the involved mechanisms.