Minimally invasive microneedles for ocular drug delivery

Introduction: Anterior and posterior segment eye diseases are highly challenging to treat, due to the barrier properties and relative inaccessibility of the ocular tissues. Topical eye drops and systemically delivered treatments result in low bioavailability. Alternatively, direct injection of medication into the ocular tissues is clinically employed to overcome the barrier properties, but injections cause significant tissue damage and are associated with a number of untoward side effects and poor patient compliance. Microneedles (MNs) has been recently introduced as a minimally invasive means for localizing drug formulation within the target ocular tissues with greater precision and accuracy than the hypodermic needles.  Areas covered: This review article seeks to provide an overview of a range of challenges that are often faced to achieve efficient ocular drug levels within targeted tissue(s) of the eye. It also describes the problems encountered using conventional hypodermic needle-based ocular injections for anterior and posterior segment drug delivery. It discusses research carried out in the field of MNs, to date.
Expert opinion: MNs can aid in localization of drug delivery systems within the selected ocular tissue. And, hold the potential to revolutionize the way drug formulations are administered to the eye. However, the current limitations and challenges of MNs application warrant further research in this field to enable its widespread clinical application.  

Tuberculose ocular

Relato de quatro casos de tuberculose ocular presumida, com comprometimento do segmento posterior em três destes casos. Nos dois primeiros casos, relata-se comprometimento do segmento anterior do olho e antecedente de tuberculose, em um caso sistêmica e no outro ocular. No terceiro caso, paciente apresenta lesão coriorretiniana no olho esquerdo. No quarto caso, descrita lesão serpiginosa-like. Os pacientes evoluíram favoravelmente com o tratamento específico. As lesões oculares da tuberculose são diversas e devemos continuar atentos a esta enfermidade.

Prevalence of biomicroscopic findings in the anterior segment and ocular adnexa among schoolchildren in Natal/Brazil

Objective: To determine the prevalence of ocular findings of the external structures and anterior segment of the eye, detected by biomicroscopic examination in schoolchildren in Natal (RN) - Brazil. Methods: After previous random selection, 1,024 pupils from elementary and secondary public and private schools in the city of Natal were evaluated from March to June 2001. All were submitted to preestablished standard research norms, consisting of identification, demographic information, ophthalmologic biomicroscopic examination, with slit lamp, performed by ophthalmologists from the “Onofre Lopes” University Hospital. Results: Alterations of the conjunctival and palpebral conditions were the most prevalent (10.4% and 6.2% respectively). Follicles (4.2%) and papillae (3.0%) were the frequent conjunctival lesions, while blepharitis (3.5%) and meibomitis (1.1%) were the most detected abnormalities in the eyelids. Upon examining the cornea, iris, lens and anterior vitreous, the most encountered findings were nubecula (0.5%), papillary membrane reliquiae (0.5%), posterior capsula opacity (0.8%) and hyaloid arteria reliquiae (2.0%). Conclusion: The most prevalent findings affecting the external structures of the eye such as eyelids and conjunctiva, consisted of blepharitis followed by follicular reaction of the conjunctiva. The most prevalent abnormalities in the cornea, iris, lens and anterior vitreous were nubecula, papillary membrane reliquiae, posterior capsular opacity and hyaloid arteria reliquiae, in that order

Ocular Risk Factors for Exudative AMD: A Novel Semiautomated Grading System

Purpose. To evaluate the contribution of the ocular risk factors in the conversion of the fellow eye of patients with unilateral exudative AMD, using a novel semiautomated grading system. Materials and Methods. Single-center, retrospective study including 89 consecutive patients with unilateral exudative AMD and ≥3 years of followup. Baseline color fundus photographs were graded using an innovative grading software, RetmarkerAMD (Critical Health SA). Results. The follow-up period was 60.9 ± 31.3 months. The occurrence of CNV was confirmed in 42 eyes (47.2%). The cumulative incidence of CNV was 23.6% at 2 years, 33.7% at 3 years, 39.3% at 5 years, and 47.2% at 10 years, with a mean annual incidence of 12.0% (95% CI = 0.088-0.162). The absolute number of drusen in the central 1000 and 3000  μ m (P < 0.05) and the absolute number of drusen ≥125 µm in the central 3000 and 6000 µm (P < 0.05) proved to be significant risk factors for CNV. Conclusion. The use of quantitative variables in the determination of the OR of developing CNV allowed the establishment of significant risk factors for neovascularization. The long follow-up period and the innovative methodology reinforce the value of our results. This trial is registered with ClinicalTrials.gov NCT00801541.

An anti-TNF--α antibody mimetic to treat ocular inflammation

Infliximab is an antibody that neutralizes TNF-α and is used principally by systemic administration to treat many inflammatory disorders. We prepared the antibody mimetic Fab-PEG-Fab (FpFinfliximab) for direct intravitreal injection to assess whether such formulations have biological activity and potential utility for ocular use. FpFinfliximab was designed to address side effects caused by antibody degradation and the presence of the Fc region. Surface plasmon resonance analysis indicated that infliximab and FpFinfliximab maintained binding affinity for both human and murine recombinant TNF-α. No Fc mediated RPE cellular uptake was observed for FpFinfliximab. Both Infliximab and FpFinfliximab suppressed ocular inflammation by reducing the number of CD45+ infiltrate cells in the EAU mice model after a single intravitreal injection at the onset of peak disease. These results offer an opportunity to develop and formulate for ocular use, FpF molecules designed for single and potentially multiple targets using bi-specific FpFs.

Ocular manifestations of microcephaly with or without chorioretinopathy, lymphedema or intellectual disability (MCLID) syndrome associated with mutations in KIF11

Purpose Microcephaly with or without chorioretinopathy, lymphedema or intellectual disability (MCLID) is an autosomal dominant condition. Mutations in KIF11 have been found to be causative in approximately 75% of cases. This study describes the ocular phenotype in patients with confirmed KIF11 mutations. Methods Standard ophthalmic examination and investigation including visual acuity, refraction and fundus examination was carried out in all patients. Fundus autofluorescence imaging (FAF) was performed in three patients, and four patients underwent spectral domain optical coherence tomography (OCT). Flash electroretinography (ERG) was performed in seven patients, and five underwent additional pattern electroretinography (PERG). Results The patients ranged in age from 2 to 10 years. Most presented with visual acuity loss. Fundus examination revealed lacunae of chorioretinal atrophy. Pigmentary macular changes and optic disc pallor were present in three of seven patients. Fundus autofluorescence demonstrated hypoautofluorescence at the macula in two of three patients. The lacunae of chorioretinal atrophy were hypoautofluorescent. The OCT showed atrophic maculae in three of four patients. Follow-up in one patient showed no deterioration of the vision over a 9-year period. The lesions appear not to be progressive on the follow-up imaging. Electrophysiology showed generalized rod and cone dysfunction and severe macular dysfunction. Inner retinal dysfunction was evident in three of seven patients. Conclusions Patients with KIF11 mutations show a specific ocular phenotype with variable expressivity and intrafamilial variability. Macular atrophy and dysfunction have not been consistently documented before. The fundus lesions appear non-progressive. The findings assist in providing an accurate diagnosis and thus improving the management and follow-up of patients with this syndrome.

Prologo a las investigaciones dirigidas por el Dr. Adolf Zilch

La primera tarea de un Instituto nuevo que se dedica a la investigación científica pura dentro de un territorio poco conocido es elaborar un catálogo de las riquezas naturales que constituyen la fauna y la flora de dicho país. Por esta razón es la tarea básica de nuestro Instituto Tropical de Investigaciones Científicas de El Salvador investigar la fauna y flora un mapa geológico del país. Las clases de los vertebrados están terminadas o actualmente en trabajo, tenemos ya en nuestras manos los manuscritos acerca de las aves, anfibios y reptiles de El Salvador; actualmente se están estudiando los mamíferos un especialista en peces, la última clase de vertebrados, llegara a principios del año entrante. También diferentes grupos de los invertebrados, como por ejemplo los caracoles terrestres y varios grupos de insectos están ya investigados. En cuanto a la flora, se está elaborando una descripción de las especies de las catorce familias de la fanerógamas pentacíclicas, a las cuales pertenecen las orquídeas y las bromeliáceas. El trabajo de la fauna y flora tiene dos fines: describir las especies nuevas recién descubiertas y comprobar la presencia de las especies ya conocidas que hasta ahora no se habían descrito.

Instituto Tropical de Investigaciones Científicas de El Salvador

Desde su fundación en septiembre de 1950 hasta marzo de 1954 han trabajado en este Instituto 40investigadores originarios de cuatro países: Alemania 22, Estados Unidos de Norte América 13,Holanda 4 y Francia 1, quienes permanecieron en el país conduciendo sus trabajos por periodos que han variado desde 8 días hasta 18 meses permaneciendo durante 220 meses trabajando sobre botánica,zoología,hidrobiología,geología, geografía, meteorología, antropología y arqueología.Debido a la poca investigación hecha previamente, los investigadores gozaron de gran libertad para llevar a cabo sus estudios, evitando únicamente la duplicación de trabajos. Se han preferido sistemáticamente aquellas personas que tenían el respaldo necesario de las instituciones científicas de reconocida importancia y cuyos planos de trabajo estaban controlados por la misma previa aceptación por el Instituto Tropical.

Instituto Tropical de Investigaciones Científicas de El Salvador

El instituto tropical de Investigaciones científicas de la universidad de el salvador ha tenido la suerte de seguir gozando de la colaboración de varios países, Alemania, Estados Unidos de Norte América, Francia, Holanda y Japón, de los cuales ha recibido representantes de alginas Universidades para venir a El Salvador a continuar Investigaciones que se desarrollan de preferencia en los trópicos y sobre algunas de las cuales no ha habido hasta la fecha mucha literatura disponible. Este país no ha sido muy afortunado de gozar de muchas expediciones científicas. El Salvador presenta como muchos de los pueblos nuevos que se desarrollan en tierras viejas, una infinidad de problemas de adaptación que necesitan un conocimiento bastante exacto no solo del propio suelo en que se ha de desarrollar, sino también de las variantes biológicas de los seres que los pueblan. No cabe duda que los Investigadores venidos de otros lugares son más fuertemente impresionados por esas características, que aquellos individuos que habiendo vivido en ese medio ambiente por muchos años no son tan fuertemente sacudidos por cuadros que parecen extraños y algunas veces incongruentes a los ojos del forastero, quien ve en ellos un mayor estimulo para emprender su estudio

Ocular traumatology in children. A retrospective study

Obiective. This study assesses the descriptive epidemiology of children with eye injuries presenting to the Emergency Department of a non exclusive Paediatric University Hospital - First Division of Ophthalmology of “Sapienza” University of Rome - over a period of 12 years. Study Design. A retrospective long term study of 12 years. Participants. All paediatric patients (up to 14 years of age) presenting with ocular injuries and hospitalized. Methods. It was analyzed the incidence of the ocular trauma among males and females. The situation in which the trauma occurred, type of trauma (contusive or perforating), the presence of endo-bulbar foreign bodies, visual acuity outcome. Results. There were 203 patients who presented to the Emergency Department in the period examined. Contusive traumas were 130 (90 males, 40 females). The perforating trauma were 73 (63 males, 10 females). The presence of an endo-bulbar foreign body was registered in 10 patients. A detailed analysis of the causes of the trauma is therefore provided. We evidence that males were almost exclusively involved in sport traumas (60 males versus 2 females), and in second instance accidental trauma is almost equally divided between two genders. Conclusions. Our retrospective study presents the paediatric cases of a non exclusive Paediatric University Hospital where 3% of ocular traumas requiring hospitalization were in children. Therefore our data could be useful in order to bring about the necessary preventive measures to minimize paediatric eye injuries.