This consecutive nonrandomized comparative interventional study was designed to examine the association between pars plana vitrectomy (PPV) with or without internal limiting membrane (ILM) peeling in the treatment of idiopathic macular holes (IMH). The ILM is the innermost layer of the retina. The macula is located within the retina, and is responsible for central vision. Although IMH manifests in a relatively small region within the retina, patients notice significant drops in visual acuity up to the 20/400 - 20/800 level (legally blind in the affected eye). In the literature, the anatomic success rate of macular hole surgery has been reported between 48% - 94%. To best treat idiopathic macular holes, it is imperative that physicians have access to the most up-to-date information regarding the treatment outcomes. This study included 55 eyes of 52 patients who received surgery at the Beth Israel Deaconess Medical Center for idiopathic macular holes between December 1999 and January 2015. Patients were non-randomly assigned to PPV with or without ILM peeling. Early patients did not receive ILM peeling, while more recent patients did. The primary endpoint measured was macular hole (MH) status as established by ocular coherence tomography (OCT) within 6 to 12 months of the vii procedure. 36 out of 39 (92.3%) eyes in the ILM peeling group had closed MH. In the comparison group without ILM peeling, 11 out of 16 (68.8%) eyes had closed MH. In comparison to the conventional PPV without ILM peeling, these findings suggest that PPV with ILM peeling is associated with a significantly higher anatomic success rate (OR, 5.45; [95% CI, 1.12 to 26.55]; P = 0.023). / 2018-06-16T00:00:00Z

Orientador: José Paulo Cabral de Vasconcellos / Tese (doutorado) - Universidade Estadual de Campinas, Faculdade de Ciências Médicas / Made available in DSpace on 2018-08-24T03:32:34Z (GMT). No. of bitstreams: 1 Medina_FlavioMacCord_D.pdf: 2571030 bytes, checksum: 442e6e86f7bd3a0d6fae088740a1e85e (MD5) Previous issue date: 2013 / Resumo: Introdução: O fator de complemento H (CFH) é um componente do sistema imunológico que possui ação imunomoduladora sobre a resposta inflamatória. A gravidade da degeneração macular relacionada à idade (DMRI) é determinada em parte por um estado inflamatório sustentado por atividade aberrante da via alternativa do complemento. As evidências na literatura da relação entre o polimorfismo Y402H do gene CFH e a resposta ao tratamento da DMRI exsudativa permanecem controversas. Objetivo: Avaliar a associação entre as variantes do polimorfismo Y402H do gene CFH e os efeitos funcional e morfológico a curto prazo, assim como a evolução a longo prazo, dos antiangiogênicos em pacientes com DMRI exsudativa. Métodos: Vinte e cinco pacientes recém diagnosticados com DMRI exsudativa foram avaliados em um estudo de curto prazo com acuidade visual medida pela tabela do ETDRS e espessura retiniana central por tomografia de coerência óptica (OCT) de alta resolução, submetidos a injeção intravítrea de bevacizumabe e prospectivamente reexaminados em 7 e 28 dias. Quarenta e seis pacientes previamente submetidos ao tratamento com antiangiogênicos tiveram seus prontuários e exames retrospectivamente avaliados em um estudo de longo prazo quanto às evoluções funcional e morfológica ao longo de um ano. Esses parâmetros foram comparados com o genótipo do CFH, cuja análise molecular do polimorfismo Y402H foi realizada por meio da reação em cadeia da polimerase (PCR) e sequenciamento direto. Resultados: No estudo de curto prazo, houve melhora da acuidade visual no dia 28 em relação ao valor inicial (D0 vs. D28) em todos os genótipos. Entretanto, no grupo homozigoto para o alelo de risco (CC), ocorreu diferença apenas no dia 28 em relação ao dia 7 (D7 vs. D28), enquanto nos grupos CT e TT, a acuidade visual melhorou mais precocemente, no dia 7 em relação ao valor inicial (D0 vs. D7). A espessura retiniana central apresentou redução nos grupos CT (D0 vs. D7 e D0 vs. D28) e TT (D0 vs. D28), enquanto não houve mudança significativa no grupo CC. No estudo de longo prazo, foi evidenciada melhora da acuidade visual ao longo de um ano de acompanhamento apenas no grupo de pacientes sem o alelo C, sem diferença significativa no grupo de pacientes com o alelo de risco. A espessura retiniana central apresentou redução nos genótipos CT e TT, enquanto que no grupo CC não houve significância. Número de injeções, persistência de atividade neovascular e percepção subjetiva de melhora não diferiram entre os genótipos. Conclusão: O perfil de genótipo do CFH parece influenciar o efeito funcional e morfológico da injeção intravítrea de bevacizumabe com uma ação mais precoce em pacientes sem o genótipo de risco. A presença do alelo de risco parece estar relacionada à ausência de melhora visual ao longo de um ano de tratamento com inibidores do VEGF. Esses resultados sugerem que o perfil do genótipo do CFH possa exercer efeito farmacogenético nesse grupo de pacientes brasileiros, influenciando negativamente a resposta ao tratamento da DMRI exsudativa com antiangiogênicos / Abstract: Introduction: The complement factor H (CFH) is a component of the immune system that has immunomodulatory action on the inflammatory response. The severity of age-related macular degeneration (AMD) is determined in part by an inflammatory state sustained by aberrant activity of the alternative complement pathway. Evidences in the literature of the relationship between the Y402H polymorphism of CFH gene and response to treatment of wet AMD remain controversial. Purpose: To evaluate the association between variants of the Y402H polymorphism of CFH gene polymorphism and the short-term functional and morphological effects, as well as long-term evolution, of antiangiogenic drugs in patients with exudative AMD. Methods: Twenty-five patients with newly diagnosed exudative AMD were evaluated in a short-term study with visual acuity on ETDRS chart and central retinal thickness measured with high resolution optical coherence tomography (OCT), underwent intravitreal injection of bevacizumab and were prospectively reviewed in 7 and 28 days. Forty-six patients previously submitted to treatment with VEGF inhibitors had their medical charts retrospectively evaluated in a long-term study about the functional and morphological evolutions over one year. These parameters were compared with the CFH genotype, whose molecular analysis of Y402H polymorphism was performed by polymerase chain reaction (PCR) and direct sequencing. Results: In the short-term study, there was improvement in visual acuity at day 28 compared to baseline (D0 vs. D28) in all genotypes. However, in the group homozygous for the risk allele (CC), differences occurred only on day 28 compared to day 7 (D7 vs. D28), while the CT and TT groups, visual acuity improved earlier in the day 7 compared the initial value (D0 vs. D7). The central retinal thickness decreased in groups CT (D0 vs. D7, D0 vs. D28) and TT (D0 vs. D28), while there was no significant change in group CC. In the long-term study, it was noticed improvement in visual acuity over one year of follow-up in the group of patients without the C allele and no significant difference in the group of patients with the risk allele. The central retinal thickness decreased in the CT and TT genotypes, whereas in the CC group the difference was not significant. Number of injections, persistent neovascular activity and subjective perception of improvement did not differ between genotypes. Conclusion: The profile of the CFH genotype seems to influence the functional and morphological effect of intravitreal injection of bevacizumab with an earlier action in patients without the risk genotype. The presence of the risk allele seems to be related to the lack of visual improvement over one year of treatment with inhibitors of VEGF. These results suggest that the profile of the CFH genotype may present pharmacogenetic effect in this group of Brazilian patients, negatively influencing the response to treatment of exudative AMD with antiangiogenic drugs / Doutorado / Oftalmologia / Doutor em Ciências Médicas

Orientador: Vital Paulino Costa / Dissertação (mestrado) - Universidade Estadual de Campinas, Faculdade de Ciências Médicas / Made available in DSpace on 2018-08-24T05:19:20Z (GMT). No. of bitstreams: 1 Santana_AlanaMendonca_M.pdf: 2805390 bytes, checksum: 9512111e988de78a1ffde9d9f877658b (MD5) Previous issue date: 2014 / Resumo: O objetivo deste trabalho foi investigar os efeitos das combinações fixas dos análogos de prostaglandinas com timolol sobre a barreira hematoaquosa, a espessura macular central e a pressão intraocular (PIO), em pacientes pseudofácicos com glaucoma primário de ângulo aberto. Neste ensaio clínico randomizado, com observador mascarado e duração de 6 meses, os pacientes foram tratados uma vez por dia (20:00 horas) com lubrificante (grupo controle) ou com a combinação fixa de maleato de timolol 0,5% e latanoprosta 0,005% (CFLT), maleato de timolol 0,5% e bimatoprosta 0,03% (CFBT) ou maleato de timolol 0,5% e travoprosta 0,004% (CFTT). Foi incluído no estudo apenas um olho de 61 pacientes: CFLT (n=16), CFBT (n=15), CFTT (n=15) e grupo controle (n=15). A barreira hematoaquosa foi avaliada por meio do &quot;laser flare meter¿ antes do início do uso das medicações e após 15 dias, 1,2,3,4,5 e 6 meses de tratamento. A PIO foi medida sempre às 9:00 horas, nas mesmas ocasiões. A espessura macular central foi avaliada por meio da tomografia de coerência óptica antes do uso das medicações, após 1 e 6 meses de tratamento ou na hipótese de piora da acuidade visual. Não houve aumento estatisticamente significante nos valores médios de &quot;flare¿ em comparação aos valores iniciais em todos os grupos (p>0,05) em todas as visitas, exceto no grupo CFTT no primeiro mês (p=0,0476) e no grupo CFLT (p=0,0129) no terceiro mês de seguimento. Não houve diferença estatisticamente significativante entre os valores médios de &quot;flare¿ entre os grupos durante o estudo (p>0,05). A média dos valores da espessura macular central aumentou significativamente nos grupos CFLT (p=0,012) e CFTT (p=0,0419) no primeiro mês de tratamento em relação aos valores iniciais. Não houve aumento estatisticamente significante nos valores médios da espessura macular central em relação aos valores iniciais em todos os grupos após 6 meses de tratamento (p>0,05) e não ocorreu diferença estatisticamente significante entre os grupos durante o estudo (p>0,05). A PIO média inicial foi significativamente menor no grupo controle (p=0,0000). Todas as combinações fixas reduziram significativamente a PIO em todas as visitas (P<0,0001), com efeito hipotensor semelhante entre si (p=0,816). Estes resultados indicam que o uso das combinações fixas de análogos de prostaglandinas com timolol não aumentou significativamente a média dos valores de &quot;flare¿ ou a média da espessura macular após 6 meses de tratamento nesta população / Abstract: The aim of this study was to investigate the effects of prostaglandin analogues and timolol fixed-combinations on the blood-aqueous barrier, central macular thickness and intraocular pressure (IOP) in pseudophakic patients with primary open angle glaucoma. In this randomized, masked-observer, 6-month clinical trial, patients were treated once daily (8 pm) with lubricant eye drops (control group), 0,5% timolol and 0,005% latanoprost fixed-combination (LTFC), 0,5% timolol and 0,03% bimatoprost fixed-combination (BTFC) or 0,5% timolol and 0,004% travoprost fixed-combination (TTFC). One eye of 61 patients were included in the study: LTFC (n=16), BTFC (n=15), TTFC (n=15) and control group (n=15). The blood-aqueous barrier status was assessed using the laser flare meter before the medications were started and after 15 days, 1, 2, 3, 4, 5 and 6 months of treatment. The IOP was measured always at 9 am, at the same intervals. The central macular thickness was evaluated with optical coherence tomography before medications were started, after 1 and 6 months of follow-up or if a patient showed decreased visual acuity at any time during follow-up. There was no significant increase in mean flare measurements from baseline in all groups (p>0.05) in all visits, except TTFC group at 1 month (p=0,0476) and LTFC group at 3 months (p=0,0129). There were no significant differences in mean flare values among the groups (p>0.05). Mean central macular thickness values were significantly higher in LTFC (p=0,012) and TTFC groups (p=0,0419) at 1 month of follow-up. There was no significant increase in mean central macular thickness values from baseline in all groups (p>0.05) after 6 months and no significant differences among the groups (p>0.05) during follow-up. At baseline, mean IOP was significantly lower in control group (p=0,0000). All fixed-combinations significantly reduced IOP in all follow-up visits, with similar lowering effect (p=0,816). These findings indicate that the use of prostaglandin analogues and timolol fixed-combinations didn't significantly increased mean flare values or mean central macular thicknes measurements after 6 months of follow-up in this population / Mestrado / Oftalmologia / Mestra em Ciências Médicas

京都大学 / 0048 / 新制・論文博士 / 博士(医学) / 乙第12917号 / 論医博第2092号 / 新制||医||1009(附属図書館) / 32127 / 京都大学大学院医学研究科医学専攻 / (主査)教授 河野 憲二, 教授 大森 治紀, 教授 渡邉 大 / 学位規則第4条第2項該当 / Doctor of Medical Science / Kyoto University / DFAM

Made available in DSpace on 2014-07-29T15:25:16Z (GMT). No. of bitstreams: 1 Tese Alan Ricardo Rassi.pdf: 1456250 bytes, checksum: c7e131ba3c1d15cc824df69f5c3dc3f6 (MD5) Previous issue date: 2011-10-08 / The objective of this study was to determine the levels of toxicity of two and three intravitreous injections of infliximab to the retina and choroid of albino rabbits by means of histological, electroretinographic and clinical ophthalmological tests. Twelve New Zealand albino rabbits (24 eyes) were used in the study. Each eye was given two (n=10) or three (n=10) serial intravitreous 2 mg injections of infliximab dissolved in 0.06 ml of saline, at monthly intervals. A separate group of rabbits (n=4 eyes) served as a control group. Ninety days after the first injection, the rabbits underwent electroretinographic and clinical ophthalmological tests. After being enucleated, the eyes underwent histological examination. No clinical ophthalmologic abnormalities were detected in the 24 eyes studied. The histological change noted was the presence of rare lymphocytes and eosinophiles in the posterior vitreous of four eyes subjected to two injections and six eyes subjected to three injections of infliximab, but it was not considered clinically significant. One clinically significant abnormality was found, a severe inflammatory reaction with vitreous exudates and ganglion cell edema in both eyes of a single rabbit, subjected to two to three injections of infliximab. The electroretinographic tests showed amplitudes that were on the average 12% smaller than those obtained before the treatment. However, there were no statistically significant differences when comparing amplitude or the implicit time between the pre and post-treatment electroretinographic findings, in all groups examined. Then, two and three intravitreous 2 mg injections of infliximab in eyes of rabbits at monthly intervals did not cause any changes after a 90-day follow-up, according to histological, electroretinographic tests and clinical ophthalmological evaluation. It was concluded that serial intravitreous infliximab doses to rabbits is a safe procedure. / O objetivo deste trabalho foi determinar os níveis de toxicidade de duas e três aplicações intravítreas de infliximabe na retina e coroide de coelhos albinos, por meio de exames clínicos oftalmológicos, eletrorretinográficos e histológicos. Foram utilizados doze coelhos albinos (24 olhos) da raça New Zealand. Cada olho recebeu duas (n=10 olhos) ou três (n=10 olhos) injeções intravítreas seriadas de 2 mg de infliximabe dissolvidos em 0,06 ml de solução salina, em intervalos mensais. Um grupo separado de olhos (n=4 olhos) serviu como controle. Noventa dias após a primeira injeção, os coelhos foram novamente submetidos a exames clínicos oftalmológicos e eletrorretinográfico e, após enucleados, os olhos foram submetidos a exame histológico. Nos 24 olhos estudados, não foram detectadas alterações clínicas oftalmológicas. A alteração histológica notada foi a presença de raros linfócitos e eosinófilos na região posterior do vítreo de quatro olhos submetidos a duas aplicações e de seis olhos que receberam três aplicações de infliximabe, mas sem significado clínico. Foi encontrada uma única alteração clinicamente significante, caracterizada como reação inflamatória grave, com presença de exsudatos vítreos nos dois olhos de um coelho, que foi submetido a duas e três aplicações de infliximabe. Os exames eletrorretinográficos mostraram amplitudes em média 12% menores do que aquelas obtidas antes do tratamento, porém sem diferenças estatisticamente significantes, comparando-se a amplitude ou o tempo implícito entre os achados eletrorretinográficos pré e pós-tratamento em todos os grupos examinados. Assim, duas e três aplicações intravítreas de infliximabe em olhos de coelhos em intervalos mensais, na dosagem de 2 mg, não provocaram alterações após seguimento de noventa dias, quer no exame histológico, na eletrorretinografia ou na avaliação clínica oftalmológica. Conclui-se que doses seriadas de infliximabe por via intravítrea em coelhos é um procedimento seguro.

Age-related macular degeneration (AMD) is the leading cause of vision loss in individuals aged 50 years and older and is estimated to affect as many as 11 million individuals in the United States. The purpose of this study was to examine the association between vitamin D and AMD disease progression. The life course epidemiology framework model was used to explore how vitamin D level as a risk factor may have an association to AMD disease through time. Data in the 2005-2008 National Health and Nutrition Examination Survey (NHANES) database were collected on vitamin D levels and identified stages of AMD level based on graded fundus eye exams from an available sample size of 5,604 participants. A quantitative cross-sectional study approach was used to address this gap in knowledge. A bivariate analysis was used to examine each independent variable (age, race/ethnicity, smoking status, and diabetes) to the dependent variable AMD from the 2005-2008 NHANES dataset. A multivariate logistic regression analysis was performed with AMD including each independent variable found to be significant. The findings from this study failed to suggest an association between vitamin D levels to AMD, with or without the covariates included in the model. There was not an association found between vitamin D level and presence of AMD. An association was found between age, smoking, and race to presence of AMD in each of the bivariate models. The findings from this study could be used for positive social change by encouraging medical and public health agencies to target screening programs at high-risk age, smoking, and race groups. There remains to be conflicting data in the literature. This study adds to the body of literature suggesting that higher levels of vitamin D are not necessarily beneficial as they pertains to AMD.

Age related macular degeneration (AMD) is the most common cause of irreversible vision loss in the elderly. At present, there are an estimated one million people in Canada with some form of AMD and this number is expected to double to two million by 2031. These estimates are sobering, and it is predicted that costs for treatment and care of individuals who suffer vision loss from AMD will have significant impact on the social and public health systems in Canada in the next two decades. There are treatments to slow the progression of vision loss, but unfortunately, there are currently no cures available for AMD. In order to develop effective second generation therapies and cures, further insights into how and why AMD develops are greatly needed. Recent studies have provided novel insights into the role of inflammation in the pathogenesis of AMD. Inflammation, or swelling of the retinal tissues, causes harmful processes that promote macular degeneration. The proposed studies will focus on the triggers of inflammation in the retina. It is hypothesized that macular degeneration may be slowed or stopped by eliminating the molecules that cause inflammation in the retina. This study will focus on amyloid beta (Aβ), a toxic molecule that has been implicated in retinal inflammation, and the role that it may play in gene expression of the retinal pigment epithelial cell. Amyloid beta is a well studied peptide in another age related disorder, Alzheimer’s disease. It is the major extracellular deposit in Alzheimer’s disease plaques, and has recently been discovered as a component of drusen, the hallmark extracellular deposits in the retina of patients with the ‘dry’ form of AMD. These studies will allow the development of new treatment regimens that target retinal inflammation and thus minimize the processes that ‘trigger’ the onset of macular degeneration.

OBJETIVOSEstudiar los resultados anatómicos y funcionales en la cirugía del agujero macular mediante disección de la membrana limitante interna (MLI) asistida o no con verde de indocianina (ICG). Valorar el efecto de la cirugía combinada en el agujero macular.DISEÑOEstudio prospectivo no randomizado.MÉTODOSe estudian ciento trece ojos de 94 pacientes con agujero macular idiopático, en estadio 3 y 4 que fueron intervenidos por un solo cirujano mediante vitrectomía con pelado de la MLI. Criterios de exclusión: cirugía vítrea o escleral previa, patología macular o retiniana, miopía mayor a -1D, ambliopía o atrofia papilar. En el grupo I, el pelado de la MLI fue asistido con 0,1ml de ICG diluido en ácido hialurónico (0.012mg/ml, 283 mOsm) durante un minuto. En el grupo II, el pelado se realizó sin uso de colorante. 71 casos se recogieron en el grupo I y 52 casos en el grupo II. Se usó taponador gaseoso de medio y largo plazo de reabsorción en todos los casos, con un decúbito mínimo de 7 días. Las exploraciones practicadas incluyen, examen funduscópico, presión intraocular, mejor agudeza visual corregida, resultados anatómicos y complicaciones.RESULTADOSEl seguimiento de la serie fue de 6 meses.El cierre anatómico a las 2 semanas de la cirugía, fue del 97,2% en el grupo I y del 81% en el grupo II con un acto quirúrgico (p=0.005). La cirugía combinada afecta al índice de cierre en los 6 meses de seguimiento, el 94% de los pacientes sin cirugía combinada cierran frente al 76,1% en aquellos a los que se les practica vitrectomía aislada (p=0.009). En el grupo I el índice de cierre con cirugía combinada fue del 86% vs. 100% en no combinada (p=0,021).En el grupo II el índice de cierre con cirugía combinada fue del 61% vs. 83% en no combinadas (p=0.159). Durante los seis meses de seguimiento, dos casos se reabrieron en el grupo I y tres en el grupo II, alcanzando un índice de cierre tras la segunda intervención del 94,4% en el grupo I y del 73,8% en el grupo II (p=0.003). La mejor agudeza visual corregida progresa de una media preoperatoria de 0.823 a una media de 0.525 en el grupo I y de 0.862 a 0.789 en el grupo II (p=0.009). La cirugía combinada, el tipo de taponador, la edad y el tiempo de evolución, no afectan de forma significativa en la mejoría de la agudeza visual. La incidencia de roturas retinianas intraoperatoriamente fue del 12% en el grupo I y del 2% en el grupo II (p=0.025). No encontramos diferencias significativas entre los dos grupos en cuanto a la presencia de complicaciones postoperatorias o alteraciones del epitelio pigmentario macular.CONCLUSIONESEl uso de ICG como adyuvante para el pelado de la MLI con la técnica de tinción utilizada, mejora el éxito anatómico en la cirugía del agujero macular, facilitando la técnica de pelado, preservando mejor la retina. La mejoría de agudeza visual es mayor en el grupo I. No hay diferencias significativas en cuanto a complicaciones postoperatorias entre los dos grupos. La cirugía combinada parece influir negativamente en el índice de cierre en la muestra y por grupo. / PURPOSETo report long-term anatomical and functional results after retinal internal limiting membrane (ILM) peeling assisted or not by indocyanine green for idiopathic macular hole.DESINGProspective, non randomized.METHODSOne hundred and thirteen (113) eyes of 94 patients with idiopathic, stages 3 and 4 macular holes that underwent pars plana vitrectomy with ILM peeling by one surgeon. Exclusion criteria: previous vitreal or escleral surgery, macular or retinal pathology, myopia >-1D, ambliopya or papilar atrophy. In group I, ILM peeling was assisted by 0,1ml of indocyanine green (ICG) diluited in hialuronic acid (0.012mg/ml, 283 mOsm) for one minute. In group II ILM peeling were not assisted by ICG. 71 cases belong to group I and 52 cases to group II. Medium to long-acting gas tamponade was used in all cases, and all patients were asked to head-down positioning for at least 7 days. Follow-up examinations included a clinical exam, intraocular presure, best corrected visual acuity, anatomic results and complications.RESULTSPatients were observed postoperatively for al least 6 months. Anatomic closure of the macular hole was a 97.2% in group I and 81% in group II by one surgical procedure, evaluated at 2 weeks postoperatively (p=0.005). Combined surgery affect the closure rate during the 6 months of follow-up, the 94% in patients without combined surgery, vs. 76.1% in patients with combined surgery(p=0.009). In group I the closure rate with combined surgery was 86% vs. 100% in no combined surgery (p=0.021). In group II the closure rate with combined surgery was 61% vs. 83% in no combined surgery (p=0.159). During 6 months of follow-up period, 2 cases reopened in group I and 3 in group II, getting a closure rate of 94.4% in group I and 73.8% in group II (p=0.003). Best corrected visual acuity improved from a median of 0.823 to a median of 0.525 in group I and from 0.862 to 0.789 in group II (p=0.009). Combined surgery, kind of tamponade, age and time of evolution, did not demostratesignificant effect in the improvement of visual acuity achieved. There were not postoperative complications attribuited to the use of our ICG dilution. The incidence or intraoperative retinal breaks was 12% in group I versus 2% in group II (p=0.025).CONCLUSIONSIntravitreal ICG-assisted ILM peeling with 0.1 ml of hialuronic acid dilution at 0.012mg/ml, 283 mOsm for 1 minute, improves anotomical succes in macular hole surgery, allows safer and easier removal of the inner limiting membrane. No unfavorable visual outcome or postoperative complications were obseved versus the no ICG group.

Ongoing efforts to quantify changes in quality of life attributable to low vision rehabilitation have focused on the utility of a single test instrument to measure this multidimensional concept. It is hypothesized that quality of life is best assessed using multiple instruments to capture some of its component facets, including functional status and psychosocial impact. Low vision devices have a predictably spontaneous impact on functional vision status, but associated psychosocial impact occurs with different magnitudes and over more protracted time intervals. The National Eye Institute Visual Function Questionnaire (NEI VFQ-25) measures the functional status of individuals in key vision areas that are associated with quality of life. The Psychosocial Impact of Assistive Devices Scale (PIADS) is an instrument that measures the psychosocial impact of assistive device intervention in three quality of life domains: competence, adaptability, and self-esteem. 68 participants were obtained from an ongoing parent study. These participants were recruited through the Low Vision Clinic at the University of Waterloo. They had a primary diagnosis of age-related macular degeneration (ARMD) and were obtaining a CCTV system for the first time. Assessments from the parent study used in this thesis included follow-up from 2 weeks, 1 month, 3 months, and 6 months post-adoption of the CCTV. The two tests administered were to measure functional vision status (NEI VFQ-25) and perceived psychosocial impact (PIADS), according the framework outlined by the Consortium for Assistive Technology Outcomes Research (CATOR). Multivariate repeated-measures ANVOA results confirmed that CCTV systems have an immediate and robust effect on the daily visual functioning of their users, and that this effect is stable over long periods of device use. The psychosocial impact of CCTV device use peaks in the shorter term and then seems to wane in the longer term for reasons that are not yet understood. The NEI VFQ-25 and the PIADS appear to have differential sensitivity to important influences on low vision rehabilitation outcomes. This project has demonstrated the value of longitudinal outcomes research in low vision rehabilitation. After obtaining a CCTV, visual function status remains static while psychosocial impact is dynamic during 6-months of follow-up.

Introduction Retinal vascular reactivity is impaired in patients with diabetes and is thought to be involved in the onset and progression of diabetic retinopathy (DR). Previous studies that have utilized hyperoxia to assess retinal vascular reactivity have been limited due to confounding factors associated with the administration of oxygen and have used a variety of different instruments to measure retinal blood flow. The influence of blood glucose at the time of blood flow assessment has also not been systemically investigated. The specific aims of each Chapter are as follows: Chapter 3: To compare three systems used to administer hyperoxia to human subjects. Chapter 4: To quantify the magnitude and timeline of change of retinal hemodynamic parameters induced by an isocapnic hyperoxic stimulus. Chapters 5, 6 and 7: To quantify the magnitude of change of retinal hemodynamic parameters induced by hyperoxia, hyperglycemia and combined hyperoxia / hyperglycemia, respectively, in groups of diabetic patients with no clinically visible, and mild-to-moderate, DR and in age-matched subjects without diabetes. Methods Chapter 3: Subjects breathed air followed by oxygen, or oxygen plus carbon dioxide using a non-rebreathing system, or air followed by oxygen using a sequential rebreathing system. The magnitude of change and variability of CO2 concentrations was compared between systems. Chapter 4: Baseline retinal blood flow data was acquired while the subjects breathed air using a sequential rebreathing system. An isocapnic hyperoxic stimulus was initiated and maintained for 20 minutes. Air was then re-administered for 10 minutes. Retinal blood flow measurements were acquired every minute over the course of the study. The magnitude of change of each hemodynamic parameter was determined by fitting individual data with a sigmoidal function. For Chapter 5, 6 and 7 diabetic patients with no clinically visible, and mild-to-moderate, DR were stratified into groups based upon their retinopathy status. Age-matched non-diabetic subjects were recruited as controls. Baseline retinal blood flow data was acquired while subjects breathed air. Retinal blood flow measurements were then acquired after exposure to (a) hyperoxia, (b) hyperglycemia and (c) combined hyperoxic / hyperglycemic stimuli. Change in hemodynamic parameters was compared between groups and correlated with objective measures of retinal edema. Results Chapter 3: The difference in group mean end-tidal CO2 levels between baseline and hyperoxia was significant for oxygen administration using a non-rebreathing system. The sequential rebreathing technique resulted in a significantly lower variability of individual CO2 levels than either of the other techniques. Chapter 4: An ~11% decrease of diameter, ~36% decrease of velocity and ~48% decrease of blood flow was observed in response to isocapnic hyperoxia in young, healthy subjects. A response time of 2.30±0.53 minutes and 2.62±0.54 minutes was observed for diameter and velocity, respectively. Chapter 5: Retinal blood velocity, flow, and WSR significantly decreased in response to isocapnic hyperoxia in all groups. The magnitude of the reduction of blood flow was significantly reduced with increasing severity of retinopathy. There was a significant relationship between baseline objective edema index values and retinal vascular reactivity. Chapter 6: A significant change in blood glucose level was observed for all groups. No significant change in any hemodynamic parameter was found in patients with diabetes and in age-matched subjects without diabetes. Chapter 7: Retinal blood velocity and flow significantly decreased in all groups in response to combined hyperoxic / hyperglycemic provocation. The vascular reactivity response was not significantly different across the groups. Conclusions Chapter 3: Control of CO2 is necessary to attain standardized, reproducible hyperoxic stimuli for the assessment of retinal vascular reactivity. Chapter 4: Arteriolar retinal vascular reactivity to isocapnic hyperoxic provocation occurs within a maximum of 4 minutes. Although there was a trend for diameter to respond before velocity, the response characteristics were not significantly different between diameter and velocity. Different response characteristics of the retinal vasculature to transmural pressure mediated autoregulation as opposed to metabolic mediated vascular reactivity are suggested. Chapter 5: The vascular reactivity response in terms of the reduction of blood flow relative to baseline was significant in all groups but the magnitude of the change in flow was significantly reduced with increasing severity of retinopathy. A loss of retinal vascular reactivity is indicated in patients with moderate DR without clinically evident diabetic macular edema (DME), and in patients with DME. Chapter 6: Unaltered retinal arteriolar blood flow was found 1 hour after glucose ingestion in patients with diabetes and in age-matched subjects without diabetes. These results do not support the theory that retinal blood flow is affected by an acute increase of blood glucose in diabetic patients and in subjects without diabetes. Chapter 7: The vascular reactivity response to a combined hyperoxic / hyperglycemic provocation produced a pronounced reduction in blood flow. Unlike the response to hyperoxia alone, the vascular reactivity response was not significantly different across the groups. This suggests that hyperglycemia may influence the retinal vascular reactivity response to hyperoxia.