INTRODUÇÃO: A trabeculectomia é a técnica de eleição para o tratamento cirúrgico do glaucoma. Entretanto, estudos recentes têm demonstrado perda da eficácia e menor redução da pressão intra-ocular dos pacientes submetidos à cirurgia ao longo dos anos. Esta diminuição decorre do contínuo processo de cicatrização e proliferação de fibroblastos na superfície epiescleral na região da bolha filtrante. Com o objetivo de diminuir esta proliferação fibroblástica e a conseqüente perda de função da trabeculectomia, introduziu-se o uso de antimetabólicos como o 5-fluorouracil e a mitomicina C. O uso dos antimetabólicos, no entanto, com freqüência é acompanhado dos indesejáveis efeitos da filtração excessiva e hipotonia. O uso da membrana amniótica em oftalmologia remonta aos anos de 1940, quando vários autores relataram seus efeitos benéficos no tratamento de doenças da superfície ocular. Além de promover a epitelização de superfícies, a membrana amniótica também é inibidora da fibrose. O efeito inibidor da fibrose pela membrana amniótica é altamente desejável na modulação da cicatrização após a trabeculectomia. O objetivo deste estudo é comparar a eficácia e a segurança do uso da membrana amniótica na trabeculectomia no tratamento cirúrgico do glaucoma primário de ângulo aberto. MATERIAL E MÉTODOS: Foi realizado um estudo prospectivo aberto, aleatório, com grupos paralelos de tratamento. Sessenta e três pacientes com indicação de cirurgia para glaucoma foram selecionados e aleatoriamente divididos em 2 RESUMO grupos. O primeiro grupo foi submetido a trabeculectomia com o uso peroperatório da membrana amniótica (grupo estudo) e o segundo grupo foi submetido a trabeculectomia sem o uso da membrana amniótica (grupo controle), na seção de glaucoma do Departamento de Oftalmologia da Santa Casa de São Paulo. Foram avaliados os efeitos redutores da pressão intraocular, número de medicações, aparência da bolha filtrante e complicações. Todos os pacientes foram acompanhados por 12 meses. RESULTADOS: A média das pressões pré-operatórias foi de 25,19 ± 7,34 mmHg no grupo da membrana amniótica e 25,42 ± 7,71 mmHg no grupo controle. A média das pressões pós-operatórias foi de 13,13 ± 2,50 mmHg no grupo da membrana amniótica e 15,47 ± 2,92 mmHg no grupo controle, diferença estatisticamente significante no seguimento de 1 ano. Não foi encontrada diferença estatisticamente significante entre os grupos controle e estudo em relação ao número de medicações pré e pós-operatória. No final de 12 meses de seguimento, no grupo de estudo, dois entre 31 olhos (6,45%) apresentaram bolha plana e vascularizada, 14 olhos (45,16%) bolha elevada e pouco vascularizada e 15 olhos (48,38 %) bolha fina e avascular. No grupo controle sete entre 32 olhos (21,87%) apresentaram bolha plana vascularizada, 22 olhos (68,75%) bolha elevada e pouco vascularizada e três olhos (9,37%) bolha fina e avascular. Foi encontrada diferença estatisticamente significante entre os grupos estudo e controle quanto a distribuição dos tipos de bolha encontradas. As complicações observadas no grupo de estudo foram um olho com câmara anterior rasa (3,22%) e dois olhos que apresentaram bolha encapsulada (6,45%). No grupo controle, dois olhos apresentaram câmara anterior rasa (6,25%), um olho descolamento de coróide (3,12%) e dois olhos RESUMO com bolha encapsulada (6,25%). CONCLUSÃO: O presente estudo demonstrou que a trabeculectomia com membrana amniótica causou maior redução da pressão intra-ocular e aparência menos vascularizada das bolhas filtrantes. Mostrou-se uma técnica segura e com baixo índice de complicações. / INTRODUCTION: Trabeculectomy is the procedure of choice for the surgical treatment of glaucoma until nowadays. However, recent studies have demonstrated a loss of efficacy and minor reduction of intraocular pressure in patients who underwent surgery over the years. This loss of efficacy of the trabeculectomy is related to the continuous process of healing and fibroblastic proliferation in the episcleral surface inside the filtering bleb. The use of 5-fluorouracil or mitomycin-C can improve the results of trabeculectomy, but they have been associated with an increased incidence of postoperative complications, especially in primary trabeculectomies. The use of amniotic membrane in ophthalmology retraces back to 1940, when some authors showed its beneficial effect in treatment of ocular surface disorders. Amniotic membrane can promote epitelization of ocular surface and act as an inhibitor of fibrosis. The purpose of this study was to compare the safety and efficacy of human preserved amniotic membrane in the trabeculectomy for treatment of primary open angle glaucoma. METHODS: The study was a prospective, randomized clinical trial comparing primary trabeculectomy with amniotic membrane (study group) and without amniotic membrane (control group) in the treatment of the glaucoma. Intraocular pressure (IOP), number of glaucoma medication, appearance of the bleb and complications were compared between the two groups. Sixty-three patients were divided in the study group of 31 patientes and control group of 32 patients and were followed for a period of 12 months in the glaucoma section of Santa Casa de Sao Paulo. RESULTS: The mean pre-operative IOP was 25.19 ± 7.34 mmHg in the amniotic membrane group and 25.42 ± 7.71 mmHg in the control group. The difference of the mean postoperative IOP between groups was statistically significant; in the control group it was 15.47 ± 2.92 mmHg and in the study group 13.13± 2.50 mmHg at one year follow up. Postoperative number of medication decreased in both groups. Analysis shows at the end of 12-month follow-up period in the study group two of 31 eyes (6.45%) exhibited flat vascularized bleb, 14 eyes (45.16%) had elevated but not avascular blebs and 9 eyes (48.38%) showed thin, avascular blebs. In the control group seven of 32 eyes (21.87%) exhibited flat vascularized bleb, 22 eyes (68.75%) had elevated but not avascular blebs and three eyes (9.37%) showed a thin avascular bleb. Complications were: one eye (3.22%) presented with shallow anterior chamber after surgery and two eyes (6.45%) had encapsulated bleb in the study group; in the control group, two eyes (6.25%) presented shallow anterior chamber after surgery, one eye (3.12%) had coroidal detachment and two eyes (6.25%) developed encapsulated bleb. CONCLUSIONS: Trabeculectomy with amniotic membrane and standard trabeculectomy promote lower postoperative IOP and the results showed statistically significant difference between groups in postoperative IOP after one year follow-up. The procedure is safe with low rate of complications.

Glaucoma is a common cause of blindness worldwide, yet the etiology of the disease is unclear. A leading hypothesis is that elevated intraocular pressure (IOP) affects the biomechanical environment within the tissues of the optic nerve head (ONH), and that the altered biomechanical environment contributes to optic nerve damage and consequent loss of vision. The biomechanical environment of the ONH is strongly dependent on the biomechanical properties of sclera, particularly scleral stiffness. However there is significant variability in reported stiffness data for human sclera. Therefore, our research goal was to measure the stiffness of human sclera and incorporate this information into finite element models of the human eye to characterize and quantify the biomechanical environment within and around the optic nerve head region at different IOP levels. Human sclera adjacent to the optic nerve head showed highly nonlinear, nearly isotropic and heterogeneous stiffness which was found to be substantially lower than that previously assumed, particularly at lower levels of IOP. The products c*c1 and c*c2, measures of stiffness in the latitudinal and longitudinal directions from the Fung constitutive model, were 2.9 ± 2.0 MPa and 2.8 ± 1.9 MPa, respectively, and were not significantly different (two-sided t-test; p = 0.795). Scleral stiffness was not statistically different between left and right eyes of an individual (p = 0.952) and amongst the quadrants of an eye (p = 0.412 and p = 0.456 in latitudinal and longitudinal directions, respectively). Three stress-strain relationships consistent with the 5th, 50th and 95th percentiles of the measured scleral stiffness distribution were selected as representatives of compliant, median and stiff scleral properties and were implemented in a generic finite element model of the eye using a hyperelastic five-parameter Mooney-Rivlin material model. Models were solved for IOPs of 15, 25 and 50 mmHg. The magnitudes of strains at the optic nerve head region were substantial at even the lowest applied IOP (15 mmHg) and increased at elevated IOPs (e.g. the third principal strain in the compliant model reached as much as 5.25% in the lamina cribrosa at 15mmHg and 8.84% in the lamina cribrosa at 50 mmHg). Scleras that are “weak”, but still within the physiologic range, are predicted to lead to appreciably increased optic nerve head strains and could represent a risk factor for glaucomatous optic neuropathy. As IOP increased from 15 to 50 mmHg, principal strains in the model with a compliant sclera increased at a lower rate than in the model with a stiff sclera. We quantified the biomechanical environment within and around the optic nerve head region using a range of experimentally measured mechanical properties of sclera and at different IOPs. We showed that IOP-related strains within optic nerve head tissues can reach potentially biologically significant levels (capable of inducing a range of effects in glial cells) even at average levels of IOP and for typical human scleral biomechanical properties.

Background: Glaucoma is a chronic, progressive eye disease and the second cause of blindness in the world. To measure the patients’ perspective in randomised controlled trials (RCTs), patient-reported outcome measures (PROMs) are increasingly being used. However, the use of PROMs in glaucoma trials is low suggesting there may be a reluctance to use PROMs. Objectives: To explore three methodological challenges of using PROMs in RCTs in glaucoma: 1) PROM selection; 2) characterising glaucoma severity; and 3) interpreting PROM scores in terms of minimal important difference (MID). Methods: Vision PROMs used in glaucoma studies were identified and content validated using a systematic review approach and categorised by a new PROM taxonomy. Existing visual field staging systems (VFSSs) based on standard automated perimetry were systematically identified and quality assessed with a new tool developed for this review using a consensus method. The performance of four high quality visual field staging systems were evaluated and referenced against an experienced ophthalmologist in a diagnostic test accuracy study. A pilot study using the social comparison approach was undertaken to test the feasibility of an anchor-based approach in determining the MID of a vision PROM in a glaucoma population. Results: Thirty-three vision PROMs were identified and categorised, according to content into impairment, disability, status and satisfaction measures. Twenty-three VFSSs were identified but evaluation of quality assessment, particularly performance, was affected by poor VFSS reporting. The diagnostic accuracy study demonstrated suboptimal performance of the four highest quality staging systems. The pilot study to determine the MID for a vision PROM found the social comparison method to be a feasible approach in a glaucoma population. Conclusion: This thesis demonstrated how to select a PROM and identified difficulties with characterising glaucoma severity. Future research needs include development of robust methods for characterising glaucoma severity and full scale evaluation of MIDs in PROMs in glaucoma.

Topical medication is a standard treatment for glaucoma. However, frequent dosing makes the therapy inconvenient and patient unfriendly. There is a great need to develop new topical formulations that provide long lasting noninvasive drug release. In this thesis, novel clickable dendrimer hydrogels for anti-glaucoma drug delivery were synthesized and characterized. Polyamidoamine (PAMAM) dendrimers have been widely applied for drug delivery. The physical characteristics they possess include monodispersity, water solubility, encapsulation ability, and a large number of surface groups. Polycationic PAMAM dendrimer G3 was surface modified with alkyne-PEG5-acid and then reacted with polyethylene glycol bisazide (PEG-BA, 1100 gmol-1) through click chemistry to form a cross-linked hydrogel. The resulting hydrogels were characterized in terms of mechanical properties, swelling, structural morphology, pH-dependent degradation, anti-glaucoma drugs (brimonidine tartrate and timolol maleate) release and cytotoxicity. To fully explore PAMAM dendrimers to make clickable hydrogels, polyanionic PAMAM dendrimer G4.5 was also surface modified with propargylamine to possess alkyne groups and successfully formed a hydrogel with PEG-BA. The work conducted in the thesis shows that clickable dendrimer hydrogels were successfully developed and shown to possess desired properties for delivery of anti-glaucoma drugs.

MMed, Ophthalmology,Faculty of Health Sciences, University of the Witwatersrand, 2009 / Objectives To determine in a cohort of 69 African patients with large optic discs and large optic cups, that proportion of patients with physiologic cupping (normal eyes) misdiagnosed as glaucomatous. To evaluate the possible relationship between optic disc size and central corneal thickness. Design and method A case series of 69 patients with large discs (vertical disc height measuring 1.8mm) and large cups (vertical cup to disc ratio 0.6) was evaluated to determine what proportion had glaucoma and what proportion was normal. Patients categorized as normal were further evaluated to determine what proportion were previously misdiagnosed and treated for glaucoma. Patients with a suspected diagnosis of glaucoma, normal tension glaucoma or primary open angle glaucoma were recruited from the glaucoma clinic at St John Eye Hospital. Outcome measures included corrected vertical disc height (VDH), vertical cup to disc ratio (CDR), central corneal thickness (CCT), the relationship between VDH and vertical cup height, the relationship between VDH and CCT, adjusted intraocular pressure (A-IOP), retinal nerve fiber layer analysis and visual fields. vii Results Sixty-nine African patients (138 eyes) with large discs and large cups were evaluated. 41 (59%) were females and 28 (41%) were males. The mean age was 56 years. Of the 69 patients, 51 (74%) had physiologic cupping (normal eyes) and 18 (26%) patients were glaucomatous. Of the group of 51 patients with physiologic cupping, there were 9 patients who were previously misdiagnosed with glaucoma and who had received treatment. VDH ranged between 1.9 and 3.2mm (mean ±SD, 2.3±0.26mm). The distribution analysis of VDH measurements noted the largest cluster around 2.3mm. CCT ranged between 454μm and 618μm (mean±SD, 516±37μm). 107 (77.5%) of the 138 eyes had CCT < 544μm. Conclusion Large cup to disc ratio in relation to large disc size can be normal. It can be misdiagnosed as glaucomatous if objective retinal nerve fiber layer analysis is not carried out. In this study, 9 (18%) patients from a group of 51 patients with physiologic cupping were misdiagnosed as glaucomatous. There was no linear correlation between CCT and VDH in this study. Pearson’s correlation coefficient was 0.13. The majority (77.5%) of eyes had thin corneas (CCT < 544μm).

INTRODUÇÃO: O glaucoma de ângulo fechado é reconhecido como uma das principais causas de cegueira mundial. A iridotomia representa o tratamento de eleição nos casos com fechamento angular primário, entretanto, este procedimento pode não ser suficiente para proporcionar abertura do ângulo irido-corneano, controle da pressão intra-ocular (PIO) e estabilização do processo da lesão glaucomatosa. O presente estudo tem como objetivo avaliar a morfologia do segmento anterior do olho em uma amostra de pacientes brasileiros, e realizar uma comparação entre olhos normais (sem sinais de fechamento angular prévio) e olhos com ângulos oclusíveis, antes e após a realização da iridotomia. MÉTODOS: Realizou-se um estudo prospectivo observacional tipo caso-controle em pacientes da Clínica Oftalmológica do HC - FMUSP, onde 40 olhos com ângulos oclusíveis (grupo caso) e 27 olhos normais (grupo controle) foram examinados durante o período de agosto de 2003 a dezembro de 2004. Os pacientes do grupo controle foram pareados por idade, sexo e raça. Os exames de gonioscopia e biometria ultra-sônica foram utilizados para comparar os 27 olhos normais com os 40 olhos com ângulos oclusíveis, antes e após a realização da iridotomia. A biometria ultra-sônica mediu o comprimento axial do olho (CAX), a profundidade da câmara anterior (PCA) e o diâmetro ântero-posterior do cristalino (DAPC). Os 27 olhos do grupo controle foram comparados, através da biomicroscopia ultra-sônica, antes e após a iridotomia com os 31 olhos do grupo caso, que não apresentavam goniosinéquias no quadrante inferior. As imagens da UBM foram obtidas em cortes radiais sobre típicos processos ciliares, no claro e no escuro. A distância da abertura angular a 500?m do esporão escleral (DAA500), profundidade da câmara anterior (PCA-UBM), distância do trabeculado aos processos ciliares (DTPC), espessura da íris a 500?m do esporão escleral (EI500) e distância do esporão escleral à inserção da íris (linha X) foram medidas nas imagens da UBM obtidas às 6 horas. As freqüências de processos ciliares longos sem sulco ciliar e fechamento angular aposicional no escuro também foram determinadas nessas imagens. RESULTADOS: Os parâmetros morfológicos dos 27 olhos do grupo controle apresentaram diferenças significativas quando comparados com os 40 olhos do grupo caso. Os olhos normais apresentaram ângulo irido-corneano mais aberto, menor DAPC e maiores CAX e PCA. Nas imagens da UBM os 27 olhos normais apresentaram maior DAA500, PCA-UBM, linha X, e também, maior DTPC que os 31 olhos com ângulos oclusíveis (651 ± 119 ?m e 508 ± 116 ?m; p < 0.001); porém, a EI500 não apresentou diferença significativa entre os dois grupos. Após a realização da iridotomia foi observado uma abertura significativa do seio camerular, e uma diminuição da freqüência de fechamento angular aposicional nas imagens da UBM obtidas no escuro (28/31 para 16/31). Processos ciliares longos sem sulco ciliar foram observados em 61% (19/31) dos olhos do grupo caso após a iridotomia e em 33% (9/27) dos olhos do grupo controle. CONCLUSÃO: A presença de processos ciliares longos sem sulco ciliar foi um achado comum não somente nos olhos com ângulos oclusíveis como também nos olhos normais. No entanto, nos olhos do grupo caso, os processos ciliares estavam localizados, em média, numa posição mais anterior. Após a iridotomia, mais da metade dos olhos com ângulos oclusíveis continuaram apresentando fechamento angular aposicional na UBM. Os valores preditivos da presença de fechamento angular aposicional (associada ou não a processos ciliares longos sem sulco ciliar) na detecção de pacientes sob risco de apresentarem episódios de fechamento angular precisam ser avaliados em estudos futuros / Introduction: Angle closure glaucoma is emerging as one of the leading cause of worldwide blindness. Laser iridotomy (LI) has been proposed as first line therapy for patients with angle closure, however this procedure may not be effective opening the irido-corneal angle, controlling intra-ocular pressure (IOP) and halting glaucoma progression in all cases. Our study aimed to evaluate anterior segment morphology on a cohort of Brazilian patients comparing normal eyes (no signs of angle closure) to angle closure eyes before and after LI. Methods: In this prospective observational case control study, performed from August of 2003 to December of 2004, we evaluated 40 angle closure eyes and 27 normal control eyes with no signs of angle closure at clinical exam, paired by age, race and gender. We used gonioscopy and A-scan biometry to compare anterior segment morphology of 27 normal control eyes to 40 angle closure eyes of patients from our service, before and after LI. We also used ultrasound biomicroscopy (UBM) exam, to compare 27 normal control eyes to 31 of 40 angle closure eyes with no goniosynachiae at the inferior quadrant evaluated by gonioscopy, before and after LI. Immersion 50-MHz high-frequency ultrasound transducer was used to obtain UBM images in radial scans through a typical ciliary process, in both standard light and dark conditions. A-scan biometry measured axial length (AXL), anterior chamber depth (ACD) and lens thickness (LENS). The angle opening distance at 500?m from the scleral spur (AOD500), trabecular ciliary process distance (TCPD), iris thickness at 500?m and the distance from scleral spur to iris insertion (line X) were measured at UBM images obtained at the inferior quadrant. The frequency of appositional angle closure and the presence of long ciliary process with no ciliary sulcus were also evaluated at UBM images. Results: At gonioscopy and A-scan biometry exam, 27 normal eyes had a significant wider iridocorneal angle opening, a thinner LENS and a greater AXL, ACD than angle closure eyes. At UBM exam, 27 normal control eyes had an significant wider AOD500, line X and also, a longer TCPD than angle closure eyes (651 ± 119 ?m vs. 508 ± 116 ?m; p < 0.001); however no differences were observed in iris thickness between the two groups. After LI, we observed a significant irido-corneal angle opening and the number of angle closure eyes with UBM appositional angle closure in dark condition decreased from 28/31 to 16/31. A long ciliary processes with no ciliary sulcus were observed in 61% (19/31) of angle closure eyes after LI, and also in 33% (9/27) of normal control eyes. Conclusion: A long ciliary processes and absence of ciliary sulcus were a quite common finding not only in angle closure eyes, but also in normal control eyes. However, ciliary processes were located more anteriorly in angle closure eyes. On this cohort of Brazilian patients, more than half of studied eyes submitted to LI maintained UBM appositional angle closure. Whether this apposition with or without long ciliary process and absence of ciliary sulcus detected at UBM images after LI is associated to further goniosynachiae formation and/or loss of IOP control remains to be evaluated

Glaukom är än kronisk sjukdom i synnerven som medför synfältsdefekter, oftast i samband med förhöjt ögontryck. I västvärlden är glaukom den näst vanligaste orsaken till blindhet. Det uppskattas att mer än 60 miljoner människor i hela världen har glaukom och antalet väntas stiga till nästan 80 miljoner år 2020. Även om det finns flera orsaker till glaukom så finns det bara en orsak som kan behandlas, ögontrycket, som ska sänkas med hjälp av ögondroppar. För att kunna bromsa försämringen i patientens sjukdom så krävs det god medverkan av patienten, som noggrant behöver följa läkarens ordination. Trots allvarliga konsekvenser för synen finns det många brister i följsamheten. Syftet med denna uppsats är därför att beskriva faktorer som patienter med glaukom upplever påverkar deras följsamhet till den medicinska terapin. Som metod valdes en litteraturstudie. Åtta kvalitativa primärkällor valdes från databaserna PubMed och Cinahl. Resultatet presenterar fyra huvudteman, Att ha förståelse för sin sjukdomssituation, Att kombinera medicineringen med livet, Individuella förutsättningar och Att ha tillgång till vårdens resurser med tillhörande subteman. Det framkommer i studien att stor vikt ligger på information om sjukdomen och behandlingen. Kunskap om tilltagande försämring trots symtomfrihet samt vilka biverkningar medicineringen kan ge är en förutsättning för att patienten ska följa sin ordinerade terapi. Dessutom måste behandlingen kunna kombineras med patientens vardag för att möjliggöra för patienten att droppa regelbundet. Denna studie visar att flera faktorer ligger hos patienten själv men att även vårdpersonalen har möjlighet att påverka patientens följsamhet positivt. / Program: Fristående kurs

Thesis (M.S.)--Massachusetts Institute of Technology, Dept. of Mechanical Engineering, 1981. / MICROFICHE COPY AVAILABLE IN ARCHIVES AND ENGINEERING. / Bibliography: leaves 68-69. / by Mark Johnson. / M.S.

Thesis (M.S.)--Massachusetts Institute of Technology, Dept. of Mechanical Engineering, 1982. / MICROFICHE COPY AVAILABLE IN ARCHIVES AND ENGINEERING / Bibliography: leaves 48-50. / by Maura Elizabeth Donnelly. / M.S.

Orientador: Renée Laufer Amorim / Coorientador: José Luiz Laus / Banca: Juliany Quitzan Gomes / Banca: Alvio Isao Shiguematsu / Resumo: Não disponível / Abstract: Purpose: The aims of this study were to better understand the mechanism of cell death by apoptosis in a glaucoma model (ischemia / reperfusion) and evaluate the role of apoptosis in this model and if treatment with Sildenafil helps prevent apoptosis. Methods: 36 rats, from 4 to 6 months, males, Lewis and weighing ± 350g were divided in 5 groups: control group (6 animals) and for groups with ischemia / reperfusion (7 and 21 days), two groups consisting of ten animals treated with sildenafil and two groups of Five animals treated with placebo. Paracentesis of the anterior chamber with needle 30G coupled to saline (0.9%) was made and maintained for 60 minutes. Intraocular pressure was measured by rebound tonometer (Tonovet®). There was histological, morphometric by hematoxylin and eosin and, immunohistochemical staining and qRT-PCR analysis by Caspase-7, Caspase-6, Caspase-9, Tnf-r2, Fas-l, Bcl-2 and Bax. For statistic analysis we used ANOVA and t-test for morphometric analysis and, for immunohistochemistry and qRT-PCR, Fisher exact test was employed with a statistical significance level of p <0.05 Results: Histology and morphometric analysis, proved more changes in the untreated group compared to the treatment and control group. Analysis of immunohistochemistry and qRT-PCR observed the more significant expression in untreated eyes. Conclusion: Sildenafil apperead to be protective to ganglion cell apoptosis. Cell survival was evident in histology and morphometry. For immunohistochemistry and RT-PCR was observed protective effect in the apoptosis pathways with similar or below expression compared to the control / Mestre