Stabilization in early adult-onset myopia with corneal refractive therapy

Purpose: To describe the stabilization of early adult-onset myopia in three university students after initiating orthokeratology treatment with corneal refractive therapy contact lenses. Methods: Three Caucasian early adult-onset progressing myopic subjects (1 male, 2 females) were fitted with corneal refractive therapy lenses to correct myopia between ?1.50 and ?2.50 D of sphere using Paragon CRT (Paragon Vision Sciences, Mesa, AZ)lenses for overnight orthokeratology. The pre-treatment refractive history from 2005 as well as refraction and axial length after treatment onset are reported over a period of 3 years between December 2009 and January 2013 with an additional year of follow-up after treatment discontinuation (January–December 2013). The peripheral refractive patterns and topographic changes are also reported individually. Results: Treatment was successful in all three subjects achieving uncorrected visual acuity of 20/20 or better monocularly. During a period of 3 years of follow-up the subjects did not experience progression in their refractive error, nor in their axial length (measured during the last 2 years of treatment and 1 year after discontinuation). Furthermore, the subjects recovered to their baseline refraction and did not progressed further over the following year after lens wear discontinuation. Conclusions: We cannot attribute a causative effect to the orthokeratology treatment alone as underlying mechanism for myopia stabilization in this 3 patients. However, the present report points to the possibility of stabilization of early adult-onset myopia progression in young adults using corneal refractive therapy treatment.

Hipertensão arterial entre funcionários de banco estatal no Rio de Janeiro. Hábitos de vida e tratamento

OBJETIVO: Estimar a freqüência de tratamento de hipertensão arterial e hábitos de vida relacionados à saúde, comparando-se hipertensos e não hipertensos. MÉTODOS: Estudo seccional em amostra sistemática de 1183 funcionários de banco estatal, no Rio de Janeiro, através de questionário autopreenchido. Medidas diretas da pressão arterial, peso e estatura foram tomadas em subamostra. Participantes informados por profissional de saúde, mais de uma vez, que eram hipertensos, foram classificados como hipertensos. RESULTADOS: Não houve diferença importante entre hipertensos e não hipertensos, quanto à prevalência de tabagismo, consumo de álcool e atividades físicas. Entre os hipertensos com sobrepeso/obesidade, a prática de dieta foi mais freqüente do que entre não hipertensos com sobrepeso/obesidade. Apenas 44,7% dos hipertensos estavam sob tratamento, condição associada à alta escolaridade, ser ex-fumante, ter sobrepeso/obesidade ou história familiar de doenças cerebrovasculares. CONCLUSÃO: A disponibilidade de serviços de saúde e o acesso à informação não foram suficientes para garantir o tratamento ou adoção de hábitos de vida que contribuem para o controle da pressão arterial, no conjunto dos hipertensos.

Effect of hormonal changes on corneal biomechanical properties and anterior segment ocular perameters

Dissertação de mestrado em Optometria Avançada

A gestão do desempenho como prática de implementação participada de um plano estratégico: o caso do Banco de Moçambique

Dissertação de Mestrado em Políticas Desenvolvimento dos Recursos Humanos

Banco de semillas y perturbación en pastizales de altitud (Pampa de Achala, Sierras de Córdoba)

El banco de semillas de las comunidades vegetales se define como el reservorio de semillas viables enterrados en el suelo y puede ser transitorio o permanente dependiendo del tiempo durante el cual las semillas se conservan viables. En general, los bancos de semillas permanentes caracterizan a sitios con perturbaciones impredecibles, como el pastoreo y el fuego. Ambas perturbaciones son típicas de los pastizales de la Pampa de Achala. El propósito de este proyecto es estudiar el tamaño y la composición de especies del banco de semillas bajo parches con diferente estructura y composición florística, originados principalmente por perturbación. Para ello, se realizarán muestreos de suelo en 4 tipos de vegetación que presentan un gradiente de perturbación, con réplicas adecuadas. Las muestras se analizarán mediante dos métodos: identificación y recuento de plántulas emergentes, colocando las muestras en condiciones adecuadas de germinación y recuento directo de semillas de las muestras de suelo. Los aspectos aplicados del problema son relevantes, por ejemplo, la predicción del desarrollo sucesional luego de las perturbaciones y el manejo y restauración de pastizales naturales y seminaturales.

Efecto del pastoreo y el fuego sobre la composición florística y el banco de semillas en un pastizal serrano

El presente proyecto intenta determinar los efectos que producen las dos perturbaciones más frecuentes en los pastizales de altura de las sierras de Córdoba, el pastoreo y el incendio post-invernal, sobre la estructura comunitaria y la composición del banco de semillas. Es conocido el efecto que producen las perturbaciones sobre las composición florística de comunidades de pastizal con diferentes historias de disturbio, pero no se conoce aún la repuesta de pastizales naturales a nivel de sus bancos de semillas, una de las principales fuentes de propágulos que asegura la regeneración de las especies. El conocimiento de las respuestas del banco de las semillas frente a perturbaciones permitirá predecir los cambios comunitarios y de esta manera encontrar un mejor equilibrio entre el manejo de los pastizales y la conservación de la diversidad. Objetivo general: * Determinar el efecto de perturbaciones comunitarias y sobre bancos de semillas en sistemas de pastizal natural. Objetivos específicos: * Determinar el efecto del pastoreo y del incendio post-invernal sobre la composición florística de la comunidad y sobre la composición del banco de semillas. * Determinar si existen efectos diferentes frente a ambos tipos de perturbación. * Determinar si existen diferencias entre la composición florística de la comunidad y la del banco de semillas bajo los diferentes tratamientos.

A corneal dystrophy associated with transforming growth factor beta-induced Gly623Asp mutation an amyloidogenic phenotype.

PURPOSE: To present the light and electron microscopic findings of a unique corneal dystrophy never before described in a German family carrying the Gly623Asp Mutation of the TGFBI gene with late clinical onset. DESIGN: Experimental study. PARTICIPANTS: Four affected and 6 nonaffected family members. METHODS: Slit-lamp examination, photographic documentation, and isolation of genomic DNA from peripheral blood leucocytes obtained from each family member examined. Exons 3, 4, 5, and 11 to 14 of the TGFBI gene were amplified and sequenced in these family members. Five corneal buttons of 3 affected siblings were excised at the time of penetrating keratoplasty. Light and electron microscopic examination were performed including immunohistochemistry with antibodies against keratoepithelin (KE) 2 and 15. MAIN OUTCOME MEASURES: Clinical and histologic characteristics of corneal opacification in affected patients and presence of coding region changes in the TGFBI gene. RESULTS: The specimens showed destructive changes in Bowman's layer and the adjacent stroma. Patchy Congo red-positive amyloid deposits were found within the epithelium in 1 cornea, in Bowman's layer and in the anterior stroma of all specimens also showing KE2, but not KE15, immunostaining. Electron microscopy revealed deposits mainly located in the anterior stroma and Bowman's layer and in small amounts in the basal area of some epithelial cells. The destroyed areas were strongly Alcian blue-positive, the Masson Trichrome stain proved mainly negative for the deposits. All affected but none of the unaffected family members had a heterozygous missense mutation in exon 14 of the TGFBI gene (G-->A transition at nucleotide 1915) replacing glycin by aspartic acid amino acid (Gly623Asp) at position 623 of the KE protein. CONCLUSIONS: In contrast with the patient carrying the Gly623Asp mutation of the TGFBI gene described by Afshari et al, our cases presented with Salzmann's nodular degeneration-like clinical features and their specimens contained KE2-positive amyloid. The reason for this now "meeting the expectation histologic phenotype" is unclear. The histologic findings emphasize that this is a unique corneal dystrophy, which shares no clinical characteristics with Reis-Bücklers' dystrophy and should be treated as a distinct entity. FINANCIAL DISCLOSURE(S): The authors have no proprietary or commercial interest in any materials discussed in this article.

Characterization of pip5k3 fleck corneal dystrophy-linked gene in zebrafish.

PIKfyve is a kinase encoded by pip5k3 involved in phosphatidylinositols (PdtIns) pathways. These lipids building cell membranes have structural functions and are involved in complex intracellular regulations. Mutations in human PIP5K3 are associated with François-Neetens mouchetée fleck corneal dystrophy [Li, S., Tiab, L., Jiao, X., Munier, F.L., Zografos, L., Frueh, B.E., Sergeev, Y., Smith, J., Rubin, B., Meallet, M.A., Forster, R.K., Hejtmancik, J.F., Schorderet, D.F., 2005. Mutations in PIP5K3 are associated with François-Neetens mouchetee fleck corneal dystrophy. Am. J. Hum. Genet. 77, 54-63]. We cloned the zebrafish pip5k3 and report its molecular characterization and expression pattern in adult fish as well as during development. The zebrafish PIKfyve was 70% similar to the human homologue. The gene encompassed 42 exons and presented four alternatively spliced variants. It had a widespread expression in the adult organs and was localized in specific cell types in the eye as the cornea, lens, ganglion cell layer, inner nuclear layer and outer limiting membrane. Pip5k3 transcripts were detected in early cleavage stage embryos. Then it was uniformly expressed at 10 somites, 18 somites and 24 hpf. Its expression was then restricted to the head region at 48 hpf, 72 hpf and 5 dpf and partial expression was found in somites at 72 hpf and 5 dpf. In situ on eye sections at 3 dpf showed a staining mainly in lens, outer limiting membrane, inner nuclear layer and ganglion cell layer. A similar expression pattern was found in the eye at 5 dpf. A temporal regulation of the spliced variants was observed at 1, 3 and 5 dpf and they were also found in the adult eye.

Nitrosative stress and corneal transplant endothelial cell death during acute graft rejection.

BACKGROUND: Nitrosative stress takes place in endothelial cells (EC) during corneal acute graft rejection. The purpose of this study was to evaluate the potential role of peroxynitrite on corneal EC death. METHODS: The effect of peroxynitrite was evaluated in vivo. Fifty, 250, and 500 microM in 1.5 microL of the natural or denatured peroxynitrite in 50 microM NaOH, 50 microM NaOH alone, or balanced salt solution were injected into the anterior chamber of rat eyes (n=3/group). Corneal toxic signs after injection were assessed by slit-lamp, in vivo confocal imaging, pachymetry, and EC count. The effect of peroxynitrite was also evaluated on nitrotyrosine and leucocyte elastase inhibitor/LDNase II immunohistochemistry. Human corneas were incubated with peroxynitrite and the effect on EC viability was evaluated. A specific inducible nitric oxide synthase inhibitor (iNOS) was administered systemically in rats undergoing allogeneic corneal graft rejection and the effect on EC was evaluated by EC count. RESULTS: Rat eyes receiving as little as 50 microM peroxynitrite showed a specific dose-dependent toxicity on EC. We observed an intense nitrotyrosine staining of human and rat EC exposed to peroxynitrite associated with leucocyte elastase inhibitor nuclear translocation, a noncaspase dependent apoptosis reaction. Specific inhibition of iNOS generation prevented EC death and enhanced EC survival of the grafted corneas. However, inhibition of iNOS did not have a significant influence on the incidence of graft rejection. CONCLUSION: Nitrosative stress during acute corneal graft rejection in rat eyes induces a noncaspase dependent apoptotic death in EC. Inhibition of nitric oxide production during the corneal graft rejection has protective effects on the corneal EC survival.

Estudio retrospectivo sobre cambios en la morfología corneal tras crosslinking

S'ha realitzat un estudi retrospectiu de 41 casos clínics de queratocon mesurant les variables abans i després de la intervenció (al primer mes postoperatori, als 3 mesos i als 6 mesos). El crosslinking corneal amb riboflavina i radiació ultraviolada sembla ser un procediment segur i efectiu, que ha assenyalat la parada a la progressió del queratocon, una reducció, encara que no estadísticament significativa de la curvatura corneal, de l'equivalent esfèric i de l'astigmatisme en ulleres a pacients que prèviament havien manifestat una progressió del queratocon. Conclusions que podem treure d'aquest estudi: 1) Es pot esperar una mínima millora de l'agudesa visual o una detecció la pèrdua d'aquesta en els casos de queratocon progressiu. Encara que aquesta millora no va ser estadísticament significativa. 2) No es demostra que el crosslinking freni la progressió del queratocon, però sí observem un augment de les mitjanes dels valors que ens indiquen el grau de duresa corneal comparant els valors abans de la intervenció, i als 3 i 6 mesos, encara que no hagi diferència estadísticament significativa. Podem constatar que el Crosslinking és una tècnica més que podem emprar en el tractament del queratocon. Possiblement el seu efecte en la visió no serà molt apreciable, però davant de casos amb alt risc de progressió pot ser factible el seu ús ja que no té efectes secundaris d'importància.

Expression of inducible nitric oxide synthase in bovine corneal endothelial cells and keratocytes in vitro after lipopolysaccharide and cytokines stimulation.

PURPOSE: To determine whether bovine corneal endothelial (BCE) cells and keratocytes express the inducible form of nitric oxide synthase (NOS) after exposure to cytokines and lipopolysaccharide (LPS), and to study the regulation of NOS by growth factors. METHODS: Cultures of bovine corneal endothelial cells and keratocytes were exposed to increasing concentrations of LPS, interferon-gamma (IFN-gamma), and tumor necrosis factor-alpha (TNF-alpha). At selected intervals after exposure, nitrite levels in the supernatants were evaluated by the Griess reaction. Total RNA was extracted from the cell cultures, and messenger RNA levels for inducible NOS (NOS-2) were measured by reverse transcription-polymerase chain reaction (RT-PCR). RESULTS: Exposure of BCE cells and keratocytes to LPS and IFN-gamma resulted in an increase of nitrite levels that was potentiate by the addition of TNF-alpha. Analysis by RT-PCR demonstrated that nitrite release was correlated to the expression of NOS-2 messenger RNA in BCE cells and keratocytes. Stereoselective inhibitors of NOS and cycloheximide inhibited LPS-IFN-gamma-induced nitrite release in both cells, whereas transforming growth factor-beta (TGF-beta) slightly potentiated it. Fibroblast growth factor-2 (FGF-2) inhibited LPS-IFN-gamma-induced nitrite release and NOS-2 messenger RNA accumulation in keratocytes but not in BCE cells. CONCLUSIONS: The results demonstrate that in vitro activation of keratocytes and BCE cells by LPS and cytokines induces NOS-2 expression and release of large amounts of NO. The high amounts of NO could be involved in inflammatory corneal diseases in vivo.

Aganirsen Antisense Oligonucleotide Eye Drops Inhibit Keratitis-Induced Corneal Neovascularization and Reduce Need for Transplantation: The I-CAN Study.

OBJECTIVE: Eye drops of aganirsen, an antisense oligonucleotide preventing insulin receptor substrate-1 expression, inhibited corneal neovascularization in a previous dose-finding phase II study. We aimed to confirm these results in a phase III study and investigated a potential clinical benefit on visual acuity (VA), quality of life (QoL), and need for transplantation. DESIGN: Multicenter, double-masked, randomized, placebo-controlled phase III study. PARTICIPANTS: Analysis of 69 patients with keratitis-related progressive corneal neovascularization randomized to aganirsen (34 patients) or placebo (35 patients). Patients applied aganirsen eye drops (86 μg/day/eye) or placebo twice daily for 90 days and were followed up to day 180. MAIN OUTCOME MEASURES: The primary end point was VA. Secondary end points included area of pathologic corneal neovascularization, need for transplantation, risk of graft rejection, and QoL. RESULTS: Although no significant differences in VA scores between groups were observed, aganirsen significantly reduced the relative corneal neovascularization area after 90 days by 26.20% (P = 0.014). This improvement persisted after 180 days (26.67%, P = 0.012). Aganirsen tended to lower the transplantation need in the intent-to-treat (ITT) population at day 180 (P = 0.087). In patients with viral keratitis and central neovascularization, a significant reduction in transplantation need was achieved (P = 0.048). No significant differences between groups were observed in the risk of graft rejection. However, aganirsen tended to decrease this risk in patients with traumatic/viral keratitis (P = 0.162) at day 90. The QoL analyses revealed a significant improvement with aganirsen in composite and near activity subscores (P = 0.039 and 0.026, respectively) at day 90 in the per protocol population. Ocular and treatment-related treatment-emergent adverse events (TEAEs) were reported in a lower percentage with aganirsen compared with placebo. Only 3 serious TEAEs (2 with aganirsen and 1 with placebo) were considered treatment-related. CONCLUSIONS: This first phase III study on a topical inhibitor of corneal angiogenesis showed that aganirsen eye drops significantly inhibited corneal neovascularization in patients with keratitis. The need for transplantation was significantly reduced in patients with viral keratitis and central neovascularization. Topical application of aganirsen was safe and well tolerated.