Posterior capsule opacification (PCO) is a major component of secondary cataract, a complication of current cataract surgery practice. This iatrogenic condition occurs in virtually all pediatric cases and to a lesser extent in adults. PCO correlates with the development in the latter half of the 20th Century of extracapsular cataract extraction (ECCE). In these surgeries, the lens capsule is left intact. During ECCE surgery a circular capsulotomy opening is created in the anterior lens capsule, and the cataractous, proteinaceous lens is removed, often via ultrasonic lens liquefaction i.e. phacoemulsification. The posterior, equatorial and remaining anterior portions of the sac-like capsule are left intact, permitting the insertion of an artificial lens into the emptied capsule. However, cells from the monolayer of epithelium on the inner surface of the capsule often begin to proliferate and migrate onto the normally cell-free inner surface of the posterior capsule, and may obscure the central axis of vision. Subsequently, a second surgery is necessary to create a small capsulotomy in the centre of the posterior capsule, usually employing an Nd:YAG laser. However, up to 5% of patients who have capsulotomies may then develop further serious, vision-threatening complications such as macular edema and retinal detachments. This thesis reports the photodynamic therapy (PDT) conditions required to prevent lens epithelial (LE) cell de novo proliferation and migration onto posterior lens capsules in a euthanized rabbit surgical model in order to predict parameters required to prevent PCO in humans. Experiments with primary in vitro cultures of human LE cells have shown rapid delivery of the photosensitizer benzoporphyrin derivative monoacid ring A (BPD-MA) and efficient killing with low light doses of 690 nm red light. Additional studies have shown the efficacy of various viscous agents in protecting the comeal endothelium. During model phacoemulsification ECCE surgeries, the use of hyaluronate viscoelastic carriers addressed the need for containment necessary for localized delivery of photosensitizer in the emptied capsule. Long-term monitoring of PDT-treated rabbit lens capsules in vitro has demonstrated a phototoxic effect including complete cell kill in this surgical model employing the prophylactic use of PDT.

No description available.

An investigation of the spectral reflectance of the fundus in normals and patients with common eye diseases was carried out using a multi wavelength scanning laser ophthalmoscope (SLO). With a knowledge of the spectral properties of the principal ocular pigments in the fundus, the appearance of the retina and choroid is predictable in normal subjects. The optic disc has a characteristic dark appearance when viewed with the SLO, and reasons for this may include a filtering effect of the confocal aperture to reduce the return of scattered light to the detector. In patients with macular exudates these features have a high reflectance in green-yellow light. An image processing method has been developed to quantify exudates and this was applied to SLO images and digitised colour slides of the same patients. Results show similar performance of processing in both image types with high accuracy (90% sensitivity for 95% specificity). A similar experiment was carried out on patients with macular drusen. These structures are of lower intensity than exudates and may have less well-defined borders. Again performance of the image processing methods showed broadly similar performance when comparing SLO images and digitised colour slides (60 to 68% sensitivity for 95% specificity). A study was carried out to assess the ability of the SLO to image the fundus in patients with cataract using a range of wavelengths. In conclusion the SLO offers the ability to image the fundus at selected wavelengths to enhance the desired features under investigation. As a fundus camera, used to generate digital images, it is unlikely to offer significant improvements over commercially available digital imaging CCD cameras. However, the SLO has properties which are likely to make it an ideal instrument for reflectometry, angiography and fundus topography. These applications are discussed in the final chapter.

Cataract is the leading cause of blindness in the world and is defined by opacification of the normally transparent lens of the eye. The major avoidable cause of cataract is ultraviolet radiation (UVR), but no current strategies have been developed to prevent the onset of cataract. Apoptosis and internal and external antioxidant systems that inhibit apoptosis have been shown to play a significant role in cataractogenesis. The main purposes of this thesis were to study the time evolution of apoptosis, to develop the concept of a protection factor (PF), and to investigate the effect of thioltransferase (Grx1) and topical caffeine in UVR cataract development. Further, to elucidate pharmacokinetics and influence on iris diameter of topical caffeine. Sprague Dawley rats were exposed to UVR and TUNEL staining of the lens sections was analysed. Grx1+/+ and Grx1-/- mice were exposed to 5 sub-doses of UVR. Based on the difference of light scattering between Grx1+/+ and Grx1-/- mice, the concept of the PF was developed. Topical caffeine and a placebo were applied to the eyes of separate groups of Sprague Dawley rats that were exposed to sub-doses of UVR and protective effect was evaluated. Penetration of topical caffeine in Sprague Dawley rats to lens and blood was analysed by high performance liquid chromatography. Pupil diameter was measured in groups of unilaterally and bilaterally caffeine-treated ketamine/xylazine anesthetized Sprague Dawley rats. TUNEL-labeling peaked between 5 and 120 hours after UVR exposure. The PF of Grx1 was 1.3. Moreover, topically administered caffeine protected against UVR-induced cataract development with a PF of 1.23. Topical caffeine peaked at 30 min in the lens, increased up to 120 min in the blood and antagonized ketamine/xylazine-induced mydriasis. In conclusion, UVR induces apoptosis, which is evidenced by the peak of TUNEL-labeling at 24 hours after UVR exposure. The PF is an objective relative measure of protective properties that allows the comparison of different antioxidant systems and administered antioxidant substances. Grx1 and caffeine are protective against UVR-induced cataract. Topically administered caffeine penetrates to the lens and inhibits UVR-induced apoptosis. Additionally, a miotic effect of caffeine is described for the first time.

Purpose: The prevalence of diabetes (DM) is increasing globally with type 2 diabetes (T2DM) being primarily responsible for this alarming trend. Age and DM have been associated with an increased prevalence of AR cataract in earlier studies but T2DM has not been considered separately from type 1 diabetes. Furthermore, study results have been inconsistent in terms of whether nuclear sclerosis (NS), cortical cataract (CC) or posterior subcapsular (PSC) are specifically associated with DM. The purpose of this thesis was to provide Canadian data on these issues while considering the limitations found in earlier studies in terms of variable age group selection and cataract definition. Logistic regression analysis was extended beyond risk analysis to model the prevalence of AR cataract across the human age range. Finally, as statins are commonly prescribed for patients with T2DM, the impact of using this pharmaceutical on AR cataract prevalence was investigated. Methods: A file review of over 6397 clinic files was performed to create the Waterloo Eye Study (WatES) database. Abstracted data included patient age and sex, the presence of early to late AR cataract (NS, CC, PSC or related lens extraction-LE), systemic health diagnoses including a diagnosis of T2DM or type 1 diabetes, and any medication used. Data quality was looked at through repeatability with double-entry of files and calculation of missing data rates. Comparisons were done between the study population demographics (age and sex) and those available on the general population and representative Canadian optometric patients. Prevalence of AR cataract was determined for the entire study group and for yearly age-groups. The probability of AR cataract generated from logistic regression analysis was used to model the prevalence of AR cataract over the entire age range of patients. Similar functions were determined for T2DM and non-diabetic (ND) subgroups and then again after further subdividing them into patients who did and did not use statins. The age of 50% prevalence of AR cataract were determined for each of these functions. Distribution rates of mixed and uniform cataract were calculated and compared for the T2DM and ND subgroups. Age of first lens extraction and differences in LE rates were also determined for these groups. Multivariable logistic regression analysis was done to determine odds ratios (OR) for associations between variables (patient age, being female, having a diagnosis of T2DM, smoking, systemic hypertension, and statin use) and the outcome of AR cataracts or its subtypes. Results: Data abstraction repeatability was found to be high and missing data rates were found to be low. While significant differences existed between the demographics of the general population and this clinic population, the sex and age distributions were comparable to optometric practices in Canada. The overall prevalence of AR cataract, NS, CC,and PSC in this population was 35.3%, 28.8%, 9.9%, and 3.6% respectively. The yearly prevalence of AR cataract in this population was found to increase in a sigmoid trend over the course of the human age span that began to rise after 38 years of age and approached 100% by 75 years of age. When modelled into a probability of cataract function, 50% prevalence of AR cataract occurred at 56.6 years of age. T2DM was reported in 452 WatES patients; 97% of whom were over 38 years of age. The probability of 50% AR cataract, NS, and CC prevalence occurred almost four years earlier in the T2DM subgroup compared to those without diabetes. PSC was much less prevalent and did not reach 50% levels, but the age of 10% prevalence was eight year earlier in the T2DM group compared to the ND group. Patients with T2DM had more mixed cataract, a higher rate of LE and an earlier age of first LE than non-diabetics. Statin use was reported in 761 patients; 96% who were over 38 years of age. Statin use was 3.5 times more common in patients with T2DM compared to non-diabetics. When the diabetic subgroups were further subdivided by those who do and do not use statins, the age of 50% probability of AR cataracts was now almost eight years earlier in the T2DM patients using statins compared to the ND patients who did not. The probability functions were similar between T2DM patients not using statins and ND patients who did report statin use. Having a diagnosis of T2DM was significantly associated with early to late NS and CC when controlling for statin use, whereas statin use was significantly associated with NS and PSC when controlling for a diagnosis of T2DM. Conclusions: AR cataract, T2DM and statin use were prevalent conditions in this clinic population, especially over 38 years of age. Modelling the prevalence of AR cataract over a broad age range could assist predicting cataract in Canadian optometric patients. A diagnosis of T2DM resulted in an earlier development of all three cataract subtypes, resulting in increased rates of LE and mixed cataract. However, the association was only significant for NS and CC when controlling for statin use. Given the frequent use of statins in patients with T2DM, the significant association found between statin use and increased risk of AR cataract warrants further study.

Thesis (Ph.D.) -- McMaster University, 1998. / Includes bibliographical references (leaves 191-212). Also available via World Wide Web.

Thesis (Ph.D.)--University of Wollongong, 2004. / Typescript. Includes bibliographical references: leaf 171-192.

Thesis (Ph. D.) -- Lincoln University, 2008. / Also available via the World Wide Web.

Orientadores: Carlos Eduardo Leite Arieta, Mônica Barbosa de Melo / Tese (doutorado) - Universidade Estadual de Campinas, Faculdade de Ciências Médicas / Made available in DSpace on 2018-08-23T06:48:19Z (GMT). No. of bitstreams: 1 Figueiredo_EugenioSantanade_D.pdf: 3323342 bytes, checksum: 042b6873e6f41d4d3c640662d8944a96 (MD5) Previous issue date: 2013 / Resumo: A catarata congênita é a principal causa de cegueira reversível na infância, com prevalência de um a cinco casos por 10.000 nascidos vivos. A forma hereditária corresponde a 50% desses casos, sendo a forma de transmissão autossômica dominante a mais comum. As alterações genéticas podem determinar mudanças no funcionamento das proteínas do cristalino, tais como cristalinas, conexinas, proteínas de transporte de membrana e proteínas de citoesqueleto. As cataratas nucleares e lamelares são as formas mais comuns entre as opacidades congênitas, e as alterações nos genes que codificam as proteínas ?A-cristalina (CRYAA), ?C-cristalina (CRYGC) e ?D-cristalina (CRYGD) têm sido relacionados com esses tipos de catarata. O presente estudo teve como objetivo determinar as alterações estruturais nos genes CRYAA, CRYGC e CRYGD em pacientes com catarata congênita bilateral, formas nuclear e lamelar, do ambulatório de catarata congênita do Hospital das Clínicas da Faculdade de Ciências Médicas da Universidade Estadual de Campinas (UNICAMP). Foram investigadas dez famílias (69 indivíduos), incluindo os casos-índice e seus parentes em primeiro grau. As regiões de codificação e as junções intron/exon foram amplificadas a partir de ácido desoxirribonucleico (DNA) genômico e submetidas à sequenciamento automático. Este estudo identificou seis polimorfismos (SNP) e uma mutação nos três genes investigados (gene CRYAA - SNP D2D, Y18Y e G137G; gene CRYGC - SNP G41G e S119S; gene CRYGD - SNP R95R e mutação Y134C), sendo três deles inéditos na literatura (G137G, G41G e Y134C). No gene CRYGD, a inédita mutação Y134C mostrou-se potencialmente deletéria para o funcionamento da proteína ?D-cristalina / Abstract: Congenital cataract is the leading cause of reversible blindness in childhood, with a prevalence of one to five cases per 10,000 live births. The hereditary form corresponds to 50% of these cases. The most common mode of inheritance is autosomal dominant with high penetrance. Genetic abnormalities determine changes in lens proteins, such as crystallins, connexins, membrane transport proteins and cytoskeletal proteins. The nuclear and lamellar cataracts are the most common among congenital opacities. Abnormalities in ?A-crystallin (CRYAA), ?C-crystallin (CRYGC) and ?D-crystallin (CRYGD) genes have been associated with these phenotypes. The present study aimed to determine the structural alterations in CRYAA, CRYGC and CRYGD genes in patients with bilateral congenital cataract, nuclear and lamellar forms, evaluated at Hospital das Clínicas, Faculdade de Ciências Médicas, Universidade Estadual de Campinas (UNICAMP), Ambulatório de Catarata Congênita. We investigated ten families (69 individuals), including the probands and their first-degree relatives. Coding regions and intron/exon boundaries were amplified from genomic deoxyribonucleic acid (DNA) and directly sequenced. Six single-nucleotide polymorphisms (SNP) and one missense mutation were identified (CRYAA gene - SNP D2D, Y18Y and G137G; CRYGC gene - SNP G41G and S119S; CRYGD gene - SNP R95R and mutation Y134C), three of them unpublished (G137G, G41G and Y134C). In the CRYGD gene, the novel mutation Y134C proved to be potentially damaging for functioning of the ?D-crystallin protein / Doutorado / Oftalmologia / Doutor em Ciências Médicas

Orientadores: Rodrigo Pessoa Cavalcanti Lira, Carlos Eduardo Leite Arieta / Dissertação (mestrado) - Universidade Estadual de Campinas, Faculdade de Ciências Médicas / Made available in DSpace on 2018-08-19T07:57:39Z (GMT). No. of bitstreams: 1 Zanetti_FernandoRoberte_M.pdf: 5269678 bytes, checksum: 52bd5ded5d0f8194a3568da0d6fc7488 (MD5) Previous issue date: 2011 / Resumo: Introdução: Os Antiinflamatórios tópicos são utilizados comumente no tratamento da inflamação ocular e do edema macular cistóide relacionado a cirurgia de catarata. Tem sido sugerido o uso de antiinflamatórios antes da cirurgia, para conseguir uma melhor midriase intraoperatória. Foi relatado que quando midriase e maior do que 6 mm, a incidência de ruptura da cápsula posterior e reduzido pela metade. O objetivo deste estudo original foi comparar o efeito do uso pré-operatório do acetato de prednisolona, do cetorolaco de trometamina, do nepafenaco e de um placebo, na manutenção da midriase intra-operatória da cirurgia de catarata. Objetivo: Comparar o efeito do uso pré-operatório dos antiinflamatórios tópicos acetato de prednisolona 1%, nepafenaco 0.1% e cetorolaco de trometamina 0.4%, alem de um placebo, na manutenção da midriase intraoperatoria durante a cirurgia de catarata. Desenho: Ensaio clinico aleatorizado, mascarado, realizado em um único centro. Métodos: E um estudo composto por 140 pacientes submetidos a cirurgia de facoemulsificação de catarata. Os pacientes (35 voluntários por grupo) foram aleatorizados para receber o placebo (carboximetilcelulose de sódio 0,5%), acetato de prednisolona 1%, cetorolaco de trometamina 0,4% e o nepafenaco 0,1%. Os colírios eram administrados 3 vezes ao dia e iniciados 48 horas antes da cirurgia.. A medida do tamanho da pupila foi realizada pelo cirurgião usando um compasso nos seguintes momentos: antes da secção da córnea e ao final da cirurgia. O desfecho primário foi avaliar a eficácia de cada medicamento em inibir a miose intraoperatoria (pupilas > 6mm, no final da cirurgia). O desfecho secundário foi obter pupilas > 6mm no inicio da cirurgia. Resultados: O numero de pacientes no grupo da prednisolona (29/35), no grupo do nepafenaco (31/35) e no grupo do cetorolaco (30/35) com diâmetro pupilar > 6 mm foi maior do que no grupo placebo em relação a manutenção da midriase intraoperatoria (19/35 - P =. 003). Não houve diferença estatística entre o grupo da prednisolona, do nepafenaco e do cetorolaco na manutenção da midriase intraoperatória (P =. 791). Não houve complicações durante a cirurgia ou efeitos adversos relacionados com o uso pré-operatório do colírio. Conclusão: O uso pré-operatório da prednisolona, do cetorolaco e do nepafenaco foi eficaz na manutenção midriase intraoperatória quando comparado com o placebo / Abstract: Introduction: Topical anti-inflammatory drugs are commonly used in the management of ocular inflammation and cystoid macular edema related to cataract surgery. It has been suggested the use of anti-inflammatory drugs before surgery, to achieve better intraoperative mydriasis. It was reported that, when mydriasis is greater than 6 mm, the incidence of posterior capsule rupture is reduced by half. The objective of the original study was to compare the effect of preoperative use of topical anti-inflammatory prednisolone acetate, ketorolac tromethamine, nepafenac and placebo, in the maintenance of intraoperative mydriasis in cataract surgery. Purpose: To compare the effects of preoperative use of topical anti-inflammatory prednisolone acetate, ketorolac tromethamine, nepafenac and placebo, on the maintenance of intraoperative mydriasis during cataract surgery. Design: Randomized clinical trial, single-center and masked. Methods: This study comprised 140 patients scheduled for cataract surgery. Patients (35 in each group) were randomized to receive placebo, prednisolone acetate, ketorolac tromethamine 0.4 % or nepafenac. These eye drops were administered three times daily for the two days prior to surgery. The pupillary diameters were measured by the surgeon using a compass prior to the corneal section and at the end of surgery. The primary outcome was the number of patients with pupil > 6 mm at the end of the surgery; the secondary outcome was the number of patients with pupil > 6 mm at the beginning of the surgery. Results: All the patients achieved pupil > 6 mm at the beginning of the surgery. The number of patients in the prednisolone (29/35), nepafenac (31/35) and ketorolac (30/35) groups with pupil > 6 mm was greater than in the placebo group in the maintenance of intraoperative mydriasis (19/35 - P =.003 - Table 2). There was no statistical difference among the prednisolone, nepafenac and ketorolac groups in the maintenance of intraoperative mydriasis (P =.791). There were no complications during surgery or related to the preoperative use of the eye drops. Conclusion: Preoperative use of ketorolac, prednisolone and nepafenac was effective in maintaining intraoperative mydriasis when compared with placebo / Mestrado / Oftalmologia / Mestre em Ciências Médicas