M.Med. Faculty of Health Sciences, University of the Witwatersrand, 2009 / Purpose To compare the outcomes of primary viscocanalostomy with trabeculectomy augmented with mitomycin C (MMC) in black South African patients with primary open-angle glaucoma (POAG). Method A prospective, randomized study was conducted over a four year period. Fifteen black South African patients with bilateral open-angle glaucoma requiring surgery that met the inclusion criteria and gave informed consent to participate in the trial were randomized to receive either a viscocanalostomy or a trabeculectomy with MMC in the first eye requiring surgery. The fellow eye then received the alternate procedure. Patients were followed up for two years postoperatively. Results There were no significant differences between the two surgical groups preoperatively. Twelve eyes in each group were followed for twenty-four months. In both groups the intraocular pressure (IOP) was significantly reduced post-operatively (p < 0.01) and the average number of medications used per eye was significantly reduced (p < 0.02). At twenty-four months, complete success (IOP less than or equal to 18mmHg without glaucoma medication and with no evidence of glaucoma progression) was seen in 75% of eyes undergoing trabeculectomy with MMC that completed the follow up, but in only 33% of eyes undergoing viscocanalostomy (p = 0.0498). Survival curves for both success and qualified success (IOP less than or equal to 18mmHg with glaucoma medications) in the two surgical procedures confirmed the superiority of trabeculectomy with MMC over viscocanalostomy. Conclusion Viscocanalostomy may offer some advantages because it is less invasive, but intraocular pressure control appears to be superior with trabeculectomy with MMC and this continues to be the filtering procedure of choice for the management of glaucoma in black South African patients.

Objetivo: Estudo comparativo da pressão intraocular (PIO) após agulhamento transconjuntival (ATC) com 5-fluoracil (5-FU) e tratamento clínico (TC) em olhos glaucomatosos com bolha encapsulada e PIO não controlada após trabeculectomia com mitomicina C (MMC), no final de 12 meses de seguimento. Desenho: Estudo prospectivo, randomizado, intervencionista. Participantes: 40 olhos de 39 pacientes com bolha encapsulada, desenvolvida em 5 meses ou menos, após trabeculectomia primária com mitomicina e PIO >= 20mmHg. Métodos: Os olhos foram randomizados para ATC com 5-FU e TC. Um máximo de dois ATC foi permitido no estudo. Todos os olhos foram acompanhados por 12 meses. O sucesso foi definido como PIO <= 18 mmHg e redução de 20% da PIO basal (sem medicações no grupo ATC). Resultados: A média da PIO em 12 meses de acompanhamento foi de 12,14 ± 2,80 mmHg no grupo do ATC e 15,13 ± 2,07 mmHg no grupo do TC (p = 0,004). 14 olhos (70%) foram considerados sucesso no grupo do ATC e 15 olhos (75%) no grupo do TC (p = 0,89). O número médio de agulhamentos foi de 1,35 ± 0,49 e a quantidade média de medicamentos foi de 2,15 ± 0,74. Conclusões: Houve uma taxa de sucesso semelhante nos olhos randomizados para ATC com 5-FU em comparação com TC em 12 meses de seguimento. No entanto, foi observada uma significativa menor média da PIO, após o ATC / Objective: To compare de efficacy of transconjuctival needling revision (TNR) with 5-fluorouracil (5-FU) and medical treatment (MT) in glaucomatous eyes with encapsulated bleb and uncontrolled intraocular pressure (IOP) after trabeculectomy with mitomycin C (MMC) at 12 months follow-up. Design: Prospective, randomized, interventional study. Participants: Forty eyes of 39 patients with encapsulated bleb developed in 5 months or less following primary trabeculectomy with mitomycin and IOP >= 20mmHg. Methods: Eyes were randomized to either TNR with 5-FU or MT. A maximum of two TNR was allowed in the study. All eyes were followed-up for 12 months. Success of treatment was defined as IOP <= 18mmHg and a 20% reduction from baseline (no medications in TNR group). Results: Mean IOP at 12 months follow-up was 12.14 ± 2.80 mmHg in the TNR group and 15.13 ± 2.07 mmHg in the MT group (p=0.004). Fourteen eyes (70%) were considered a success in the TNR group and 15 eyes (75%) in the MT group (p=0.89). The number of needling procedure was 1.35 ± 0.49 procedures and the number of medication was 2.15 ± 0.74 medications. Conclusions: We have demonstrated a similar success rates in eyes randomized to MT in comparison to TNR with 5-FU at the last follow-up. However, a significant lower mean IOP after TNR was observed

In the health-informatics and bio-medical domains, clinicians produce an enormous amount of data which can be complex and high in dimensionality. This scenario includes visual field data, which are used for managing the second leading cause of blindness in the world: glaucoma. Visual field data are the most common type of data collected to diagnose glaucoma in patients, and usually the data consist of 54 or 76 variables (which are referred to as visual field locations). Due to the large number of variables, the six nerve fiber bundles (6NFB), which is a collection of visual field locations in groups, are the standard clusters used in visual field data to represent the physiological traits of the retina. However, with regard to classification accuracy of the data, this research proposes a technique to find other significant spatial clusters of visual field with higher classification accuracy than the 6NFB. This thesis presents a novel clustering technique, namely, Simultaneous Modelling and Clustering (SMC). SMC performs clustering on data based on classification accuracy using heuristic search techniques. The method searches a collection of significant clusters of visual field locations that indicate visual field loss progression. The aim of this research is two-fold. Firstly, SMC algorithms are developed and tested on data to investigate the effectiveness and efficiency of the method using optimisation and classification methods. Secondly, a significant clustering arrangement of visual field, which highly interrelated visual field locations to represent progression of visual field loss with high classification accuracy, is searched to complement the 6NFB in diagnosis of glaucoma. A new clustering arrangement of visual field locations can be used by medical practitioners together with the 6NFB to complement each other in diagnosis of glaucoma in patients. This research conducts extensive experiment work on both visual field and simulated data to evaluate the proposed method. The results obtained suggest the proposed method appears to be an effective and efficient method in clustering visual field data and 3 improving classification accuracy. The key contributions of this work are the novel model-based clustering of visual field data, effective and efficient algorithms for SMC, practical knowledge of visual field data in the diagnosis of glaucoma and the presentation a generic framework for modelling and clustering which is highly applicable to many other dataset/model combinations.

Made available in DSpace on 2014-06-11T19:22:13Z (GMT). No. of bitstreams: 0 Previous issue date: 2010-02-26Bitstream added on 2014-06-13T20:28:22Z : No. of bitstreams: 1 addad_mt_me_botfm.pdf: 674800 bytes, checksum: 101691ff84e6e0c57b104e36c6ab28a2 (MD5) / Comparar pico e flutuação de pressão intra-ocular (PIO) entre curva tensional diária e teste de sobrecarga hídrica, detectar os horários de pico de PIO, comparar os valores da PIO nos horários das 6 horas da manhã deitado e sentado. 30 olhos direitos de 30 pacientes portadores de glaucoma primário de ângulo aberto (GPAA) ou hipertensão ocular (HO), foram submetidos à curva tensional diária de 24 horas (CTD) e teste de sobrecarga hídrica (TSH). Foram avaliados: pico (maior valor da PIO durante a CTD e TSH ) e flutuação (maior valor da PIO menos o menor valor da PIO durante o CTD e TSH). A PIO foi avaliada, com tonômetro de aplanação de Goldmann às 9, 12, 15, 18, 21, 24 e 6h, com paciente sentado. As medidas das 3 e 6 horas da manhã foram realizadas no leito com tonômetro de Perkins com o paciente em posição supina (deitado). Imediatamente após a medida no leito deitado, foi realizada outra medida das 6 horas com o paciente sentado. Para realização do TSH, os pacientes ingeriam 1 litro de água, em até 5 minutos. A PIO foi avaliada imediatamente antes e durante uma hora após a ingestão de água, com intervalos de 15 minutos entre as medidas. O TSH foi realizado logo após a avaliação da PIO às 6h da manhã. Foram calculados valores de média (M) e desvio padrão (s) para pico e flutuação e mediana (Md) e quartís (Q2) para flutuação em porcentagem (%). Para comparação de médias foi realizado o teste t de Student para amostras dependentes. Foi utilizado teste de Wilcoxon para comparação de medianas entre amostras dependentes. Para todas as análises foi considerado nível de significância p <0,05. A média dos valores de pico de PIO foi significativamente maior na CTD (20,39 ±1,03 mmHg) do que no TSH (17,37 ± 0,78 mmHg), p < 0,001. A média dos valores de flutuação também foi maior na CTD (10,17 ± 0,90) do que no TSH (5,0 ± 0,45), p < 0,001... / Comparing peak and fluctuation of intraocular pressure (IOP) between diurnal tension curve and water drinking test, detect the peak of IOP, compare the IOP at 6AM in supine and sitting position. 30 right eyes of 30 glaucoma patients with open angle glaucoma (OAG) or ocular hypertension (HO) were submitted to water drinking test (WDT) and diurnal tension curve (DTC). Were evaluated: peak (higher value of IOP observed during WDT and DTC), fluctuation (difference between highest and lowest value of IOP WDT and DTC). IOP was measured with applanation Goldmann tonometry at 9AM, 12AM, 3PM, 6PM, 9PM, 12PM and 6 AM, with the patient sitting. Measurements of 3AM and 6AM were made in bed with Perkins tonometer with the patient in the supine position. Immediately after the measure in supine position, another measure was done at 6AM, with the patient seated. The WDT involved ingestion of 1 liter of tap water in 5 minutes. IOP was measured immediately before and one hour after ingestion of water at intervals of 15 minutes between measurements. The WDT was performed immediately after the measure IOP at 6 AM. For comparison of means was performed Student's t test for dependent samples. Wilcoxon test was used to compare medians between dependent samples. The level of significance was considered p <0.05. The mean peak IOP was significantly higher in the DTC (20.39 ± 1.03 mmHg) than in TSH (17.37 ± 0.78 mmHg), p <0.001. The mean fluctuation was also higher in the DTC (10.17 ± 0.90) than in WDT (5.0 ± 0.45), p <0.001. The value of the fluctuation in the DTC percentile was 90.46% (70.00, 129.90) while the WDT was 35.42% (27.92, 56.95), p <0.001. The IOP of 6 AM showed a statistically significant when performed with the patient in supine position (17,47 mmHg) and sitting (14,30 mmHg) and was significantly higher with the patient in supine position. (p < 0,001). The WDT peak and underestimates of ... (Complete abstract click electronic access below)

Human eyes with exfoliation syndrome (XFS) exhibit a distinctive pattern of iris transillumination defects that are recapitulated in Lyst mutant mice carrying the beige allele. Here I present the identification and characterization of the B6-Lystbg-J mouse model of XFS, modifiers of Lyst mediated ocular phenotypes, mechanisms of intraocular pressure (IOP) pathology related to circadian rhythms, and mechanisms of iris transillumination defects in the B6-Lystbg-J mice. Clinical and histological analysis shows that the B6-Lystbg-J mice have multiple similarities to human XFS including: iris transillumination defects, production of an exfoliative-like material, and pronounced pigment dispersion. Despite these insults, Lyst mutation does not cause increased IOP or optic nerve damage within the context of a C57BL/6J genetic background. However, defects in the circadian rhythm regulation of IOP were identified. Sequence analysis identifies that the beige mutation is predicted to delete a single isoleucine from the WD40 domain of the LYST protein. I identified CSNK2B as a binding partner of LYST and showed that LYSTbg-J completely disrupts the interaction. CSNK2B function in regulating E-cadherin and β-catenin binding is subsequently disrupted. These results lead to a working hypothesis that aspects of the XFS phenotype involve LYST and CSNK2B pathways, likely influencing cell-cell adherens junctions. Epistasis experiments were used to test for genetic modifiers of Lyst, which demonstrated that albino Lyst mutant mice exhibited complete rescue of Lyst-dependent iris phenotypes. In a genetic background-driven approach, a DBA/2J strain of congenic mice was created. The DBA/2J background, which harbors multiple mutations influencing melanosomal-proteins, enhanced Lyst dependent iris phenotypes. Thus, both experimental approaches implicated melanosomes, a potential source of oxidative stress, as mechanistically contributory. Supporting a contributory role of oxidative damage, Lyst mutation resulted in genetic context sensitive changes in iris lipid hydroperoxide levels, being lowest in albino and highest in DBA/2J mice. These results identified an association between oxidative damage to lipid membranes and severity of Lyst-mediated phenotypes, uncovering a new mechanism contributing to pathophysiology involving LYST. In conclusion these results demonstrate that mutation of the Lyst gene can produce ocular features of human XFS and suggests that LYST or LYST-interacting genes may contribute to XFS.

Visual field testing, or perimetry, measures peripheral visual loss in eye diseases such as glaucoma. Rarebit Perimetry (RBP) is a new and novel perimetric method, introduced in 2002 by Lars Frisén (2002), with the aim of detecting low degrees of neural damage within the retina. / RBP is unlike conventional perimetric methods that measure levels of retinal sensitivity, but instead uses very bright (i.e. suprathreshold) and very small targets to detect tiny areas of absolute blindness within otherwise normal areas of vision. RBP thus claims to locate miniscule gaps in the receptive field matrix of neurons in the retina, with the assumption that dead neurons leave gaps in this matrix. The most useful application of this idea is to detect progressive eye disease in the earliest stages (Frisén, 2002). Current research shows that RBP correlates with other standard visual field tests (Brusini, Salvetat, et al., 2005; Frisén, 2003; Gedik, Akman, et al., 2007; Martin & Wanger, 2004), but may afford greater sensitivity by detecting very mild visual losses missed by other tests (Martin, Ley, et al., 2004; Martin & Nilsson, 2007; Nilsson, Wendt, et al., 2007). / To date, there are no studies that definitively test the theoretical basis of RBP, so in this thesis I aim to explore the proposed underlying mechanisms and assumptions of this test. In particular, the proposed mechanism of RBP leads to specific predictions as to how responses will alter when the luminances of the RBP targets are systematically decreased. I therefore compared RBP responses of mean hit rate as a function of target luminance and found results to be inconsistent with the proposed RBP mechanism. Mathematical simulations were performed to explore reasons for the differences between the two groups (Chapter Seven).

INTRODUCCIÓN El glaucoma es una neuropatía óptica progresiva multifactorial. Se observa una disminución de la capa de fibras nerviosas retinianas (CFNR) que puede ser medida mediante tomografía de coherencia óptica (OCT). Se ha realizado un estudio prospectivo de los cambios en el grosor de la CFNR en ojos de pacientes con glaucoma sometidos a cirugía combinada, facoemulsificación asociada a esclerotomía profunda no perforante. Estos cambios también se han comparado con los cambios de la CFNR en ojos no intervenidos. MATERIAL Y MÉTODOS Se incluyeron ojos de pacientes con glaucoma que se distribuyeron en dos grupos. Uno de los ojos se sometió a cirugía combinada y se incluyó como caso. El ojo contralateral se incluyó como control. A estos pacientes se les realizaron dos mediciones del grosor de la CFNR utilizando el OCT Cirrus® (Carl Zeiss Meditec Inc., Dublín, California, USA), una antes y otra un mínimo de dos meses después de la intervención. Los resultados se han analizado mediante la t de Student dado que son datos apareados y se ha aplicado la corrección de Bonferroni puesto que se realizan múltiples comparaciones. RESULTADOS Al comparar los ojos intervenidos de cirugía combinada con los no intervenidos, no se han observado cambios en el grosor de la CFNR que sean significativos. Tampoco existen diferencias significativas entre el grosor antes y después de la cirugía por lo que la OCT no ha demostrado utilidad en la monitorización del éxito o el fracaso de la cirugía combinada a corto plazo. Tampoco se ha determinado si la calidad de la imagen tiene un papel en el cambio de grosor de la CFNR entre tomografías. / INTRODUCTION Glaucoma is a progressive optic nerve disease, with multiple factors involved in its development. There is a thinning in the retinal nerve fiber layer (RNFL) that can be measured using the optic coherence tomography. We have done a prospective trial regarding the thickness of the nerve fiber layer in glaucoma patients who underwent combined surgery for both glaucoma and cataract. The changes in the RNFL have also been compared to those in glaucomatous eyes without surgery. MATERIALS AND METHODS The glaucoma patients included were divided in two groups. One of the eyes underwent combined surgery and was included as a case. The fellow eye was included as a control. In all patients, two measurements of the RNFL were obtained using OCT Cirrus® (Carl Zeiss Meditec Inc., Dublin, California, USA), one before surgery, the second one at least two months after the surgery. Results were analised using t Sudent, and Bonferroni correction was also used because of multiple analisis to the same sample was carried out. RESULTS We have not found significant changes in the RNFL thickness by comparing glaucomatous eyes that underwent surgery with those that did not. There are no significant differences between the thickness before and after the surgery, so OCT has not been proved to be useful in monitoring short-term success after combined surgery for glaucoma and cataract. It has not been possible either to determine whether the signal strength has a significant role in the changes in RNFL thickness between OCT.

El presente trabajo es una adaptación de la técnica quirúrgica de trabeculectomía para el tratamiento del glaucoma canino. Para tal fin se utilizaron 5 caninos de distintos sexos, razas y edades, con una historia clínica de glaucoma. Ellos fueron intervenidos en la Clínica de Animales Menores de la Facultad de Medicina Veterinaria de la Universidad Nacional Mayor de San Marcos, empleándose la técnica quirúrgica de trabeculectomía, la cual consiste en crear una nueva vía de drenaje del humor acuoso. En cada uno de los casos, se demostró que dicha técnica es una alternativa, rápida, poco costosa y confiable para el tratamiento resolutivo de esta patología. Con el fin de verificar su eficacia se realizaron evaluaciones oftalmológicas post-quirúrgicas. Los hallazgos mostraron en todos los casos una importante disminución de la presión intraocular. Al comparar las presiones intraoculares antes y después de la intervención quirúrgica se encontró una diferencia estadística significativa con un nivel de confiabilidad del 99%. Se concluye que la técnica quirúrgica de trabeculectomía puede ser usada en la resolución del aumento de la presión intraocular en caninos. / The present work in an adjustment of the surgical technique of trabeculectomy for the treatment of the canine glaucoma. To accomplish it, 5 canines of different sex, races and age, with clinical history of glaucoma were used. They were treated in the Clinic of Small Animals of the Faculty of Veterinary Medicine of the National University of San Marcos. The surgical technique of trabeculectomy permitted to find a new way of draining of the aqueous humor. In each of the cases, there was demonstrated that the technique is a quick, cheap and reliable alternative for treatment of this pathology. In order to verify its efficiency, postsurgical evaluations were done. In all the case the findings showed an important decrease of the intraocular pressure. When comparing the intraocular pressures before an after the surgical intervention. There was found a significative statistical difference, with 99% of reliance. It is concluded that the surgical technique of trabeculectomy can be used successfully in the treatment of the increase of he intraocular pressure in canine.

A polarization sensitive optical coherence tomography (PS-OCT) instrument is presented for the study of glaucoma. Glaucoma is the second leading cause of blindness worldwide and causes irreversible damage to the retina. This PS-OCT system was built to perform retinal imaging with a swept source laser providing a 28 kHz A-scan repetition rate. Thickness, phase retardation, birefringence and reflectance index measurements were taken from the primate eyes on a weekly or semi-weekly basis through the course of a 30 week study. Statistical analysis of these measurements indicates that the reflectance index is the earliest measured indicator of glaucomatous changes and a potential marker for early glaucoma diagnosis. / text

Acute glaucoma is an ocular emergency and sight -threatening disease which is caused by a sudden increase in intraocular ocular pressure (IOP) due to blockage of aqueous humor outflow. Acute glaucoma can result in permanent loss of visual acuity and visual field (VF). Prophylactic or therapeutic medicine is rare for acute glaucoma. In animal studies, a well-established model to investigate this acute IOP spike is by fluid infusion and adjustment of the fluid level to induce high IOP within a few seconds. However, there is no blockage of aqueous outflow and the increase in intraocular pressure is unrealistically rapid. To mimic the IOP profile in human acute glaucoma attack, we propose the use of an ophthalmic viscosurgical device (OVD), Healon 5 (AMO, Santa Ana, CA, USA) which is injected intracamerally to block aqueous outflow. The IOP is allowed to increase naturally inside the globe. We found that Healon 5 can induce an acute elevation in IOP with very similar characteristics to those observed in humans. For example, the IOP profile during the attack, changes in the anterior segment and retinal nerve fibre layer (RNFL) thinning are all consistent with findings in human acute angle closure glaucoma (AACG). We believed that our new model can more accurately reflect acute glaucoma than other animal models. Based on these findings we further tested the neuroprotective effect of Lycium barbarum polysaccharides (LBP) on retinal neurons against an acute rise in IOP (attack) with the new model. L. barbarum is an herb that has been used in Chinese medicine for thousands of years. The fruit of this plant is believed to be good for the health of the eyes. In our study we found that oral administration of LBP preceding an acute glaucoma attack can preserve the visual function of the animals despite the loss of neurons in the retinal ganglion cell layer (RGCL). L. barbarum intake seems to inhibit secondary cell death and progression of the disease. In conclusion, we had successfully established a new acute glaucoma attack animal model by intracameral injection of Healon 5. This model more closely resembles the condition observed in human acute glaucoma. We also found that LBP has a prophylactic neuroprotective effect against an acute glaucoma attack in animals. It can protect the visual function and possibly inhibit secondary cell death. Oral consumption of LBP as a health supplement may provide extra benefit to people who are at high risk of developing acute glaucoma, in addition to the protective effects of LBP against other diseases. / published_or_final_version / Anatomy / Master / Master of Philosophy