Purpose Primary Open Angle Glaucoma (POAG) is an important cause of irreversible visual loss in South Africa. POAG is asymptomatic, yet early detection and treatment can prevent visual loss. POAG has a genetic component, and identifying genetic risk factors could facilitate early detection as well as elucidate pathogenic mechanisms of the disease. POAG is more common in populations of African descent, but has been understudied in the context of POAG genetic risk factors in these populations. The purpose of this research was to identify genetic risk factors for POAG in black South Africans. Methods Self-identified black South African POAG patients and unaffected control participants were enrolled at St John Eye Hospital in Soweto. The study population was evaluated in case-control association studies for genetic risk factors in the following genomic regions: CDKN2B/CDKN2BAS-1, MYOC, TMCO1, CAV1/CAV2, CYP1B1, WDR36, COL1A1, COL1A2, COL5A1, COL8A2, ZNF469, SIX1/SIX6, ATOH7 and the chromosome 2p16 locus. The study was powered to detect moderate-sized genetic effects. Family members of participants identified with potentially pathogenic mutations in MYOC were counselled, screened for the mutations and clinically screened for glaucoma. Genotyping data from SNPs in TMCO1, CAV1/CAV2, CDKN2BAS-1 and SIX1/SIX6 that had also been genotyped in a West African and an African American population were compared with the South African data and the three datasets were combined to create a larger sample of individuals of African descent for association analyses. Results There were 247 POAG patients and 255 control participants enrolled in the study that were representative of the black population of South Africa. The POAG participants had advanced disease with more than half having severe visual impairment from the disease. Potentially pathogenic mutations in MYOC were identified in 4.2% of the POAG patients (Lys500Arg in 1.2%, Gly374Val in 0.9% and Tyr453del in 2.3%) and in 20% of the family members screened. The screening successfully identified individuals at high risk for future visual loss and enabled them to receive counselling and follow-up. Lys500Arg is a benign variant, whereas Gly374Val and Tyr453del are pathogenic. Tyr453del is incompletely penetrant. In the association studies, single SNPs in the COL1A1, ZNF469 and MYOC regions showed marginal associations with POAG, but the identified associations did not withstand correction for multiple testing. Ocular quantitative trait association analyses also yielded no significant associations after correction but a significant association was identified with type 2 diabetes mellitus and rs12522383 in WDR36. There was also a significant association identified with SNP rs10120688 in CDKN2BAS-1 and visual impairment in the African American dataset. Combining the three datasets of individuals of African descent increased the power to detect small genetic effects and identified suggestive associations with SNPs in TMCO1 and CAV1/CAV2. Conclusions Black South Africans with POAG may have a MYOC mutation that either causes or contributes to their risk for developing POAG in approximately 3.3%. MYOC mutation screening in affected families successfully demonstrated the value of genetic information in identifying and protecting individuals at risk for visual loss from glaucoma. The genetic risk associated with the candidate genes evaluated in this study and POAG in black South Africans, if such a risk exists, is a small risk. There is therefore a critical need for further genetic association studies in POAG in this significantly affected population to identify other genetic risk factors. This study has important implications for the management and counselling of black South African patients with POAG and their families.

No description available.

Las microemulsiones son dispersiones transparentes y termodinámicamente estables de dos fases inmiscibles entre sí que contienen cantidades apropiadas de tensioactivos y cosurfactantes, dando lugar a gotas de tamaño entre 10-100 nm. Tienen potencial aplicación como vehículos portadores de fármacos que presentan limitaciones debido a su baja solubilidad en agua, toxicidad o dificultad de permeación. Otras ventajas son: vida útil prolongada, aumento de solubilidad de moléculas hidrófilas y lipófilas, esterilización por filtración, liberación controlada de principios activos. En el presente trabajo de tesis se abordaron tres aplicaciones diferentes para las microemulsiones. POTENCIAL APLICACIÓN DE LAS MICROEMULSIONES DISEÑADAS SISTEMA PORTADOR DE FÄRMACOS A NIVEL OCULAR Acetazolamida (ACZ) es el inhibidor oral de la anhidrasa carbónica comúnmente utilizado en el tratamiento de glaucoma. Para obtener una disminución deseada de la presión intraocular deben emplearse grandes dosis orales de ACZ. Esto resulta en una amplia gama de efectos secundarios que podrían evitarse con el uso tópico del fármaco. Sin embargo, la escasa solubilidad acuosa y la baja permeabilidad corneal de ACZ limitan su biodisponibilidad a nivel ocular. Uno de los principales objetivos de esta tesis fué formular una microemulsión ocular de ACZ de alta eficacia terapéutica y efecto prolongado. Se prepararon tres sistemas aceite / agua, basados en geranio, geraniol, aceite esencial de citronella (fase oleosa), Cremophor El, Brij 35 y Tween 80 como tensioactivos. Se construyeron los correspondientes diagramas de fase pseudoternarios. La microemulsión basada en citronella mostró propiedades fisicoquímicas aceptables. Para todas las preparaciones se aplicó una versión modificada de la prueba de irritación ocular Draize que reveló que la fórmula de Citronella no era irritante. La evaluación biológica de las fórmulas comerciales y de la microemulsión en conejos albinos normotensos, nos orientó a seleccionar la formulación anteriormente mencionada basándonos en una eficacia terapéutica similar a dosis más bajas y un efecto más prolongado respecto de los productos convencionales, ofreciendo un tratamiento más intensivo del glaucoma. SISTEMAS AUTOCONSERVABLES Si bien los conservantes se agregan a los productos farmacéuticos para inhibir el crecimiento de microorganismos peligrosos, en formulas oftálmicas generan efectos indeseables. Se ha sugerido que las microemulsiones podrían autopreservarse. Asimismo, como los aceites esenciales son conocidos por sus propiedades antibacterianas, la hipótesis de trabajo estuvo orientada a verificar si la microemulsión de citronella tenía propiedades conservantes. Los resultados indicaron que el sistema inhibió el crecimiento de Staphyloccocus aureus, Mycobacterium gordonae, Candida albicans pero no el de Pseudomonas aeruginosa, por lo que la formula no es capaz de autopreservarse. CONTROL DE MOSQUITOS Las microemulsiones son atractivas como posibles productos insecticidas debido a la alta biodisponibilidad de las gotas de aceites esenciales larvicidas, atribuible al reducido tamaño particular. Se realizó un estudio para comparar el efecto biológico de la emulsión y la microemulsión o/w de aceite esencial de geranio y geraniol, sobre larvas de mosquito Culex pipiens pipiens. Los sistemas microemulsificados basados en geranio y los de geraniol produjeron un aumento notable de la actividad larvicida en comparación con las emulsiones correspondientes, siendo las nanoformulaciones basadas en geraniol más efectivas que las basadas en geranio. Sin embargo, se prefieren las microemulsiones de geranio debido a sus perfiles toxicológicos residuales. Estos sistemas podrían usarse en un programa de manejo integrado de plagas para Culex pipiens pipiens. / The microemulsions are clear and thermodinamically stable dispersions of inmiscible phases containing appropriate amounts of surfactants and cosurfactants, forming small droplets with diameters between 10 and 100 nm. They have potential use as delivery systems for many pharmaceuticals which are normally of limited use due to their low aqueous solubility, toxicity or low permeation. Other advantages are: extended shelf life, compatibility with hydrophilic and lipophilic drug molecules, ability to be sterilized by filtration, control of drug release. Three different applications of microemulsions were approached in this work of Thesis. POTENTIAL APPLICATION OF THE DESIGNED MICROEMULSIONS OCULAR DRUG DELIVERY SYSTEM: Acetazolamide (ACZ) is the most commonly oral anhydrase carbonic inhibitor used in the treatment of Glaucoma. To obtain the desired lowering of intraocular pression, large oral doses of ACZ are used resulting in a wide array of side effects. Side effects of ACZ could be avoided if ACZ was topically administered into the eyes. However, poor aqueous solubility and low corneal permeability of the drug limits its ocular bioavailability. The main objective of this work was to formulate an ACZ ocular microemulsion of high therapeutic efficacy and prolonged effect. Three oil/water systems, consisting of geranium, geraniol, and Citronella essential oils and Cremophor El, Brij 35 and Tween 80 as surfactants, were prepared and their pseudoternary-phase diagrams were obtained. Microemulsion made of Citronella, showed acceptable physicochemical properties. A modified version of Draize rabbit eye irritation test was carried out for all of the preparations and revealed citronella formulation was nonirritant. Biological evaluation of the microemulsion and commercial formulations on normotensive albino rabbits orientated us to select the microemulsion mentioned previously that it was the most effective, having a similar therapeutic efficacy, with a lower dose, and longer effect relative to a market product, offering more intensive treatment of glaucoma, compared to conventional eye drops. SELF PRESERVING SYSTEMS Antimicrobial preservatives are added to pharmaceuticals to inhibit the growth of dangerous microorganisms. However, the presence preservatives in ocular medications has undesirable effects. It has been suggested that microemulsions are self-preserving antimicrobials. As essential oils are known for their antimicrobial properties, the hypothesis of our work was testing if citronella microemulsion acts as a self-preserving system. The results indicated that citronella microemulsion inhibited the growth of Staphyloccocus aureus, Mycobacterium gordonae, Candida albicans but not Pseudomonas aeruginosa, so the system could not be considered as a self-preserved one. MOSQUITO CONTROL Microemulsions are attractive as potential insecticidal products due to high bioviability of the larvicidal essential oil drops, attributable to their small size. A laboratory study was conducted in order to compare the biological effect of emulsion and microemulsion of geranium and geraniol essential oils in water against Culex pipiens pipiens mosquito larvae. Microemulsified systems based on geranium and those on geraniol produced a notable increase of the larvicidal activity when compared with the corresponding emulsions, being nanoformulations based on geraniol more effective than geranium based ones. However, geranium microemulsions are preferred due to their residual toxicological profiles. The results indicate that these novel systems could be used in integrated pest management program for the Culex pipiens pipiens.

Yes / Blur is one of the most commonly reported visual symptoms of glaucoma, but it is not directly measured by current clinical tests. We aimed to investigate the effects of glaucoma on detection and discrimination of image blur. People with glaucoma, separated into two groups with (n=15) or without (n=17) central visual field defects measured by 10-2 perimetry, and an age-similar control group (n=18) participated. First, we measured contrast detection thresholds centrally using a 2-interval forced choice procedure. We then measured blur detection and discrimination thresholds for the same stimuli (reference blurs 0, 1 arcmin respectively) using a 2-alternative forced choice procedure under two contrast conditions; 4x individual detection threshold for the low contrast condition, 95% contrast for the high contrast condition. The stimulus was a horizontal edge bisecting a hard-edged circle of 4.5° diameter. Data were analysed by linear mixed modelling. Contrast detection thresholds for the glaucoma group with central visual field defects were raised by 0.014 ± 0.004 (mean ± SE, Michelson units) (p=0.002) and by 0.011 ± 0.004 (p=0.03) relative to control and glaucoma without central visual field defect groups respectively. Blur detection and discrimination thresholds were similar between groups, with small elevations in blur detection thresholds in the glaucoma groups not reaching statistical significance (detection p=0.29, discrimination p=0.91). The lower contrast level increased thresholds from the higher contrast level by 1.30 ± 0.10 arcmin (p<0.001) and 1.05 ± 0.096 arcmin (p<0.001) for blur detection and discrimination thresholds respectively. Early-moderate glaucoma resulted in only minimal elevations of blur detection thresholds that did not reach statistical significance in this study. Despite the prevalence of blur as a visual symptom of glaucoma, psychophysical measurements of blur detection or discrimination may not be good candidates for development as clinical tests for glaucoma / College of Optometrists PhD scholarship

published_or_final_version / abstract / Anatomy / Doctoral / Doctor of Philosophy

Antecedentes: El uso de la mitomicina C como coadyuvante intraoperatorio ha mejorado considerablemente el éxito de la cirugía de glaucoma. Sin embargo la concentración ideal y el tiempo de exposición de la mitomicina C es desconocido. Método: Estudio retrospectivo, comparativo observacional. 62 ojos de 62 pacientes con diagnostico de Glaucoma primario de ángulo abierto, edad (> 40 años), y pobre respuesta al tratamiento medico. 31 pacientes recibieron una sola aplicación intraoperatoria de mitomicina C (0.4 mg/ml por 3 minutos) ellos fueron emparejados con un grupo de 31 pacientes quienes recibieron una sola aplicación intraoperatoria de mitomicina C (0.4 mg/ml por 5 minutos), usando edad, PIO preoperatorio y postoperatoria, además de complicaciones como variables. Resultados: El porcentaje de éxito a los 12 meses fue de 80.62% para el grupo en que se aplicó mitomicina C por 3 minutos y de 93.54% para el grupo en que se aplicó mitomicina C por 5 minutos. No siendo significativa la diferencia (P = 0.130) Se presentaron complicaciones en 15 (48.38%) de los pacientes del grupo en que se aplico mitomicina C por 3 minutos y 4 (12.9%) pacientes en el grupo en que se aplico mitomicina C por 5 minutos, no siendo significativa la diferencia encontrada. En el grupo de 3 minutos se presentaron como complicaciones: hifema en 5 (16.1%), ampolla quística 2 (6.5%), fibrosis de la ampolla 3 (9.7%), hipotonía 2 (6.5%), desprendimiento de retina 1(3.2%), ampolla plana 2 (6.5%) pacientes. Mientras que en el grupo de 5 minutos, las complicaciones fueron, ampolla quística 1(3.2%), fibrosis de la ampolla 1 (3.2%) y ampolla plana en 2 (6.5%) pacientes. Conclusión: Estos resultados sugieren que la exposición intraoperatoria de 3 minutos de 0.4 mg/ml de mitomicina C es tan efectivo como la exposición de 5 minutos. Sin que el rango de complicaciones se altere.

Yu, Chak Yan Marco. / Thesis (Ph.D.)--Chinese University of Hong Kong, 2013. / Includes bibliographical references (leaves 153-178). / Electronic reproduction. Hong Kong : Chinese University of Hong Kong, [2012] System requirements: Adobe Acrobat Reader. Available via World Wide Web. / Abstract also in Chinese.

Man, Xiaofei. / Thesis (Ph.D.)--Chinese University of Hong Kong, 2013. / Includes bibliographical references (leaves 138-162). / Electronic reproduction. Hong Kong : Chinese University of Hong Kong, [2012] System requirements: Adobe Acrobat Reader. Available via World Wide Web. / Abstracts also in Chinese.

Dexamethasone (DEX) and triamcinolone acetonide (TA) are widely used in clinical practice for ocular anti-inflammation. The most common side effect of these two corticosteroids is the rise of intraocular pressure that leads to death of the retinal ganglion cells, a feature of POAG. We investigated the differential gene expression profiles induced by DEX and TA treatment in human trabecular meshwork (hTM) cells using microarray technology. A number of genes differentially expressed in hTM cells were identified under DEX and TA treatment, mainly involving in proteolysis, cell adhesion and acute phase response. Five genes (MYOC, GAS1, SENP1, ZNF343 and SOX30) were commonly differentially expressed in both DEX and TA treatment. It indicates that DEX and TA may share similar effect on hTM cells, which may associate with the onset of ocular hypertension. / In one Chinese juvenile onset POAG (JOAG) family with autosomal dominant inheritance, a novel locus at 15822-q24 (GLC1N) was identified using genome-wide scan, supported by clinical, linkage, and haplotype transmission data. The critical region covered a genetic distance of 16.6 Mb. To search for disease genes within this new JOAG locus, we screened NR2E3, SMAD6 and CLN6 for mutations. However, no mutations was found in the family members. We attempted a new gene-based SNPs genotyping approach to search for susceptibility genes to JOAG in this novel locus by using 97 unrelated JOAG patients and 99 unrelated control subjects. Significant association was identified in a set of 6 adjacent SNPs out of 122 gene-based SNPs. Among them, one non-synonymous SNP rs3743171 in the SLC24A1 gene was incompletely segregated in the JOAG family. Our findings indicate the mutation in other regions of SLC24A1 may be responsible for JOAG in this family, or another gene in this region may be the actual cause of glaucoma. / Primary open angle glaucoma (POAG) is a leading cause of visual impairment and blindness worldwide. Genetic factors play a major role in the etiology of POAG. This thesis describes our investigations of the POAG causative genes using genome-wide DNA scanning by linkage/association analysis and RNA level scanning by microarray technology. / Wang Danyi. / "September 2006." / Adviser: Calvin Chi Pui Pang. / Source: Dissertation Abstracts International, Volume: 68-08, Section: B, page: 5155. / Thesis (Ph.D.)--Chinese University of Hong Kong, 2006. / Includes bibliographical references (p. 139-181). / Electronic reproduction. Hong Kong : Chinese University of Hong Kong, [2012] System requirements: Adobe Acrobat Reader. Available via World Wide Web. / Electronic reproduction. [Ann Arbor, MI] : ProQuest Information and Learning, [200-] System requirements: Adobe Acrobat Reader. Available via World Wide Web. / Abstracts in English and Chinese. / School code: 1307.

Submitted by Ana Lúcia Torres (bfmhuap@gmail.com) on 2017-10-04T13:45:33Z No. of bitstreams: 2 license_rdf: 0 bytes, checksum: d41d8cd98f00b204e9800998ecf8427e (MD5) DISSERTAÇAO MARCELO JARCZUN KAC.pdf: 1310344 bytes, checksum: 894e8b8ff1bbb98f54524b2bf42cfdc9 (MD5) / Approved for entry into archive by Ana Lúcia Torres (bfmhuap@gmail.com) on 2017-10-04T13:45:45Z (GMT) No. of bitstreams: 2 license_rdf: 0 bytes, checksum: d41d8cd98f00b204e9800998ecf8427e (MD5) DISSERTAÇAO MARCELO JARCZUN KAC.pdf: 1310344 bytes, checksum: 894e8b8ff1bbb98f54524b2bf42cfdc9 (MD5) / Made available in DSpace on 2017-10-04T13:45:45Z (GMT). No. of bitstreams: 2 license_rdf: 0 bytes, checksum: d41d8cd98f00b204e9800998ecf8427e (MD5) DISSERTAÇAO MARCELO JARCZUN KAC.pdf: 1310344 bytes, checksum: 894e8b8ff1bbb98f54524b2bf42cfdc9 (MD5) Previous issue date: 2010 / Prefeitura da Cidade do Rio de Janeiro / Objetivo: Avaliar a amplitude de pulso ocular (APO) utilizando o tonômetro de contorno dinâmico (TCD) em pacientes com glaucoma primário de ângulo aberto (GPAA) assimétrico e pressão intra-ocular (PIO) assimétrica. Métodos: 48 pacientes (96 olhos) com GPAA assimétrico foram recrutados. Três medidas da PIO e da APO foram aferidas utilizando o TCD. Para o diagnóstico de assimetria eram necessárias uma diferença de perda de campo visual maior que 6 dB no índice “mean deviation” (MD), e uma diferença de 5 mmHg na PIO medida com o tonômetro de aplanação de Goldmann (TAG) entre o olho mais afetado e o contra-lateral. Todos os participantes se submeteram a um exame oftalmológico completo, incluindo paquimetria ultrassônica e ecobiometira. Os critérios de exclusão consistiram de: doenças ou cicatrizes corneanas, uso de medicação anti-glaucomatosa tópica ou sistêmica e cirurgia ocular prévia. Resultados: Não houve diferença com significância estatística (p = 0,142) entre o comprimento axial dos olhos do grupo melhor (22,95 +/- 0,91 mm) e pior (22,85 +/- 0,97 mm). Houve diferença estatisticamente significativa (p = 0,011) entre a espessura corneana central do grupo de olhos melhores (537,08 +/- 29,54 μm) e do grupo de olhos piores (534,40 +/- 29,87 μm). Os valores da APO do grupo de olhos melhores (3.32 +/- 1.14 mmHg) foram significativamente menores (p = 0,001) do que os obtidos no grupo de olhos piores (3,83 +/- 1,27 mmHg). Quando corrigimos as medidas de APO pela diferença de PIO entre os olhos houve uma perda da significância estatística entre os grupos (p = 0,996). Conclusão: A APO é semelhante entre os dois olhos de pacientes portadores de GPAA assimétrico com PIO assimétrica. De acordo com esses dados não há evidência de que a APO possa ter um papel no GPAA hipertensivo assimétrico / Aim: To evaluate ocular pulse amplitude (OPA) using the dynamic contour tonometer (DCT) in patients with asymmetric primary open-angle glaucoma (POAG) and asymmetric intra-ocular pressure (IOP). Methods: The participants consisted of 48 patients (96 eyes) with asymmetric POAG. Three measurements of IOP and OPA were taken using DCT. The diagnosis of asymmetry required a difference of glaucomatous visual field loss greater than 6 dB in the global index MD and a difference of 5 mmHg in IOP measured by Goldmann aplannation tonometry (GAT) between the more affected and the contra-lateral eye. All participants underwent full ophthalmologic clinical assessment including ultrasonic pachymetry and biometric measurements. Exclusion criteria were corneal diseases or scars, topical or systemic glaucomatous medications, and previous ocular surgery. Results: No difference (p = 0.142) was found between the axial length measurements of the better eyes group (22.95 +/- 0.91 mm) and worse eyes group (22.85 +/- 0.97 mm). There was a statistically significant difference (p = 0.011) between the central corneal thickness values of the better eyes group (537.08 +/- 29.54 μm) and worse eyes group (534.40 +/- 29.87 μm). The OPA values of the better eyes group (3.32 +/- 1.14 mmHg) were significantly lower (p = 0.001) than those obtained on worse eyes group (3.83 +/- 1.27 mmHg). When correcting the OPA readings by the IOP there was a loss of statistical difference between groups (p = 0.996). Conclusion: OPA is similar in both eyes of asymmetric hypertensive POAG patients with asymmetric IOP. According to this data there was no evidence that OPA could play a role in asymmetric hypertensive POAG