Visual function degrades with increasing age, in absence of frank disease, and affects both photopic and scotopic sensitivity. The mechanisms underlying these impairments may be related to biological (e.g., neural, optical) and environmental (e.g., smoking, dietary) factors. Recent evidence suggests that visual function may be improved following retinal carotenoid supplementation, both, in healthy and diseased eyes. Retinal carotenoids accumulate within the retina to form the macular pigment (MP) - a biomarker of antioxidant status of the eye and retinal disease risk. The objectives of this thesis were manyfold. First, the extent of vision loss (particularly scotopic sensitivity) in healthy ageing was examined. The results of this investigation showed that dark adaptation recovery slows with increasing age despite no significant change in visual acuity or fundus appearance. The technique described had excellent repeatability and correlated well with previous research. The potential link between MP and dark adaptation was also examined. The results showed that macular pigment optical density (MPOD) was correlated with a specific parameter of dark adaptation (S2) - a sensitive marker of functional degradation in normal ageing and retinal disease. The main part of this thesis sought to investigate the effect of MP augmentation on visual function in a large group of observers aged between 50 and 90 years old. The baseline data from this clinical trial revealed very interesting findings with regards to unhealthy lifestyle behaviours, health status and statin use. Subjects taking statins were identified (n = 25) and matched with 25 participants not using statins for age and body mass index. It was found that statin users had a higher proportion of males, higher prevalence of current smoking status and poorer general health (e.g. hypertension, high cholesterol and heart disease). Statin users also had significantly reduced MPOD, prolonged photostress recovery time, and deficits in a number of dark adaptation parameters. In a separate analysis of the whole group (n= 74, mean age 65.51), smokers were found to have reduced MPOD, slower S2, higher prevalence of high cholesterol and lower fruit and vegetable intake. MPOD was also reduced among obese subjects. The impact of MP augmentation on visual function in normal older subjects was assessed (n = 74, mean age 65.51) in a 12 month, randomized, double-blind, placebo-controlled study. Active formulation consisted of 20 mg lutein combined with vitamins and minerals. Data were collected at baseline, 6 months and 12 months. The results showed that, despite a 24% MPOD increase in the active group, there were no significant differences between the two groups over the three visits for any of the visual parameters. Given the increasing size of the older adult population in developed countries, research aimed at slowing or reversing age-related declines in vision is much needed both from an economical and psycho-social perspective. The results of the studies presented in this thesis show that lifestyle, health status and certain medications can adversely affect visual function in normal ageing. MP augmentation, however, had no effect on visual function. Further research is warranted, particularly paying close attention to subjects engaging in several unhealthy lifestyle/dietary behaviours, statin users and those with low MPOD and suboptimal visual function.

The optical density of human macular pigment was measured for 50 observers ranging in age from 10 to 90 years. The psychophysical method required adjusting the radiance of a 1°, monochromatic light (400–550 nm) to minimize flicker (15 Hz) when presented in counterphase with a 460 nm standard. This test stimulus was presented superimposed on a broad-band, short-wave background. Macular pigment density was determined by comparing sensitivity under these conditions for the fovea, where macular pigment is maximal, and 5° temporally. This difference spectrum, measured for 12 observers, matched Wyszecki and Stiles's standard density spectrum for macular pigment. To study variation in macular pigment density for a larger group of observers, measurements were made at only selected spectral points (460, 500 and 550 nm). The mean optical density at 460 nm for the complete sample of 50 subjects was 0.39. Substantial individual differences in density were found (ca. 0.10–0.80), but this variation was not systematically related to age.

Face à la limite de la littérature sur l’impact de l’environnement notamment alimentaire dans le vieillissement oculaire liée en partie aux manques de données en population générale particulièrement la plus âgée en France, nous nous sommes intéressés dans un premier temps, aux relations entre l’alimentation, les xanthophylles plasmatiques et le pigment maculaire puis sa distribution spatiale et dans un second temps, au profil des acides gras et les signes de sécheresse oculaire chez les 1153 participants de l’étude Montrachet.Dans un premier temps, nous avons mis en évidence une augmentation de la concentration plasmatique de lutéine et zéaxanthine chez les personnes consommant fréquemment des courges et courgettes et ainsi, une augmentation de la densité optique du pigment maculaire chez les personnes âgées non-fumeurs ayant une concentration plasmatique élevée en lutéine. De plus, nous avons fourni des valeurs du pigment maculaires qui pourraient servir de référence en population générale pour des études épidémiologiques. Nos résultats sont très cohérents avec ceux des autres études épidémiologiques même si notre population est en moyenne plus âgée. Par ailleurs, nous avons montré que les signes de la sécheresse oculaire sont plus fréquents chez les personnes âgées ayant des concentrations plasmatiques faibles en acides gras polyinsaturés et saturés. Ainsi, nos résultats apportent des éléments nouveaux dans l’implication des acides gras dans le processus de la sécheresse oculaire.Enfin, ces travaux de thèse, viennent enrichir la littérature relative au pigment maculaire, sa densité, sa répartition spatiale et ses déterminants ainsi que les déterminants de la sécheresse oculaire. Cependant, compte tenu de caractère transversal de nos études, ces résultats permettent seulement d’émettre des hypothèses qui seront confirmées à l’aide d’études longitudinales et pourraient contribuer à conforter l’intérêt des interventions reposant sur des supplémentation en caroténoïdes xanthophylles. / Given the limits of the literature on the environmental nutritional impact in ocular aging witch is partially due to the lack of data in general population notably in French elderly, first, we were interested in the relationships of diet, plasma xanthophylls and macular pigment optical density as well as its spatial distribution and second of plasma fatty acids and dry eye disease signs in the 1153 Montrachet study participants.Firstly, we reported the high consumption of squash, the high plasma lutein and zeaxanthin levels and also the high plasma lutein level, the high macular pigment optical density level in nonsmokers subjects. In addition, the macular pigment values we provided in the study could be used as reference in population based study. Our results are very consistent with those found in other epidemiological studies even though our population is on average older. Secondly, we have shown that dry eye disease signs are more frequent in elderly subjects with low plasma polyunsaturated and saturated fatty acids level. Thus, our results provide new elements in the involvement of fatty acids in the process of dry eye disease.Finally, this work enriches the literature on macular pigment, its density, as well as its spatial distribution and its determinants as well as the determinants of dry eye disease. However, given the transversal nature of our studies, these results make only possible to formulate hypotheses that will be confirmed with longitudinal studies and could reinforce the interest of interventions based xanthophylls carotenoids supplementation in elderly.

The purpose of this research was to investigate detect and monitor laser-tissue interactions at threshold and potentially sub-threshold levels of injury. High resolution imaging modalities can provide a deeper understanding of candidate biomarkers disease and injury at the molecular, cellular, and tissue-levels which can be used to identify and diagnose early stages disease and damage. In addition, multi-scale and multi-modal imaging have also been used to identify inherent biomarkers of retinal disease and injury. Monitoring tissue changes can be mapped back to biological changes at the cellular and sub-cellular level. Diseases often alter tissue on the ultra-structural level yet retinal clinical diagnosis often monitor changes in tissue at the organ level. If injury and disease is detected and diagnosed during an “early” stage of development, treatments and drug interventions may prevent further spread of the pathology. Non-invasive imaging is expected to be a valuable tool for in vivo medical research as well as for the diagnosis and management of disease. In addition to developing new imaging tools and techniques to image the retina, the identification of inherent biomarkers of disease and health using diagnostic methods are almost equally as important. Using the inherent optical properties of retinal tissue, we can non- invasively quantify differences in the absorption and reflection of light to gauge the risk for visual disability or worse yet irreversible vision loss as a result of retinal disease and chronic light exposure. The research presented with in this dissertation is three separate studies aimed at identifying light injury and potential biomarkers indicating the risk of light mediated development of disease. / text

Age related macular degeneration (AMD) is one of the leading causes of blindness amongst the elderly. Macular pigment (MP) in the retina has been established to protect individuals against AMD. Improving levels of MP by diet or supplements is the constant quest of clinical practitioners and researchers, thus necessitating development of instruments capable of repeatable and reliable MP measurement. Cataract, a consequence of the rising opacity levels of the lens with age is one of the other major causes of blindness in the world. Mapcatsf, a LED-based microprocessor-controlled heterochromatic flicker photometer (HFP) using photopic vision is capable of measuring the levels of MP and the opacity of the lens in terms of optical density. Test-retest measurements conducted on 83 subjects were analyzed for repeatability in macular pigment optical density (MPOD) measurements. Reliability of the lens optical density (LOD) measurements were tested and compared with those obtained at absolute scotopic thresholds for 25 individuals. A supplement study with 32 individuals both in the young (50) age groups for 6 months further established Mapcatsf’s capacity to monitor changing levels of MP in individuals. As an overall outcome, high levels of repeatability and reliability were obtained in MPOD and LOD measurements establishing Mapcatsf as an instrument for use in clinical settings in the future.

Purpose: The main objective of the present study was the investigation of possible influence of lens opacification on macular pigment optical density (MPOD) measurements. Methods: 86 eyes of 64 patients (mean age 73.4(±8.3)years) were included in the study. MPOD was prospectively measured using one-wavelength reflection method (Visucam500, Carl Zeiss Meditec AG) before and after cataract extraction with implantation of a blue-light filtering intraocular lens (AlconSN60WF). The median of the maximum optical density (MaxOD) and the median of the mean optical density (MeanOD) measurements of macular pigment across the subject group were evaluated. Results: Statistically significant differences were noticed between pre-operative and post-operative measurements, the absolute values were generally lower after cataract extraction. The following median(lower/upper quartile) differences across the group were determined: MaxOD -33.8%(-46.2%/-19.1%), MeanOD -44.0%(-54.6%/-26.6%). Larger changes were observed in elderly patients (<70years of age: (n=25eyes) MaxOD -13.4%(-20.5%/3.6%), MeanOD -23.6%(-30.5%/-15.3%) versus patients ≥70years: (n=61eyes) MaxOD -40.5%(-53.2%/-30.1%), MeanOD -47.2%(-57.8%/-40.1%)) and in patients with progressed stage of cataract. MaxOD for lens opacification grade 1:(n=9eyes) -27.4%(-42.1%/-19.6%), 2:(n=26eyes) -35.0%(-44.2%/-25.3%), 3:(n=21eyes) -34.4%(-45.4%/-11.4%), 4:(n=25eyes) -32.6%(-53.2%/-6.4%) and 5:(n=5eyes) -53.5%(-61.7%/-38.7%) and MeanOD for cataract stage 1:(n=9eyes) -42.6%(-46.0%/-26.0%), 2:(n=26eyes) -44.1%(-51.8%/26.2%), 3:(n=21eyes) -45.7%(-54.7%/-24.7%), 4:(n=25eyes) -39.5%(-59.4%/-26.1%), 5:(n=5eyes) -57.0%(-66.1%/-51.4%). Conclusions: As established by comparison of pre- to post-operative measurements, cataract presented a strong effect on MPOD measured by one-wavelength reflection method. Particular care should therefore be taken when evaluating MPOD using this method in elderly patients with progressed stage of cataract. Future optimization of correcting parameters of scattered light and consideration of cataract influence may allow more precise evaluation of MPOD.

Submitted by Franciele Moreira (francielemoreyra@gmail.com) on 2017-09-26T15:36:47Z No. of bitstreams: 2 Dissertação - Letícia Pinto Coelho Jorge - 2017.pdf: 7825738 bytes, checksum: 4eca5b3a59512770f7384ddd353ddb59 (MD5) license_rdf: 0 bytes, checksum: d41d8cd98f00b204e9800998ecf8427e (MD5) / Approved for entry into archive by Luciana Ferreira (lucgeral@gmail.com) on 2017-09-27T11:21:13Z (GMT) No. of bitstreams: 2 Dissertação - Letícia Pinto Coelho Jorge - 2017.pdf: 7825738 bytes, checksum: 4eca5b3a59512770f7384ddd353ddb59 (MD5) license_rdf: 0 bytes, checksum: d41d8cd98f00b204e9800998ecf8427e (MD5) / Made available in DSpace on 2017-09-27T11:21:13Z (GMT). No. of bitstreams: 2 Dissertação - Letícia Pinto Coelho Jorge - 2017.pdf: 7825738 bytes, checksum: 4eca5b3a59512770f7384ddd353ddb59 (MD5) license_rdf: 0 bytes, checksum: d41d8cd98f00b204e9800998ecf8427e (MD5) Previous issue date: 2017-09-19 / Macula lutea is the region of the retina where the yellow pigments lutein and zeaxanthin are concentrated. Oxidative damage seems to be an important factor for exacerbation of several retinal diseases, such as age-related macular degeneration, and a protective role of macular pigment has been postulated. The quantitative study of macular pigment and its distribution are possible through the determination of macular pigment optical density (MPOD). The objective of this study was to determine the mean MPOD value in a sample of the Brazilian population and to evaluate the influence of sex, age, ethnicity, smoking history and refractive status on MPOD values in this sample. A cross-sectional study was performed. Forty-two healthy patients had both eyes photographed using Visucam 500 (Carl Zeiss Meditec, Jena, Germany) in combination with the MPOD module. Four variables were obtained: maximum MPOD, mean MPOD, MPOD volume and MPOD area. Demographic data and life habits were collected. The mean MPOD value in the studied population was 0.13 density unit ± 0.02. MPOD values were not influenced by gender, smoking history or refraction. MPOD values were significantly higher among black patients when compared to caucasians. There was a positive but low correlation between mean MPOD and age. / A mácula lútea é a região da retina onde se concentram os pigmentos amarelos luteína e zeaxantina. Acredita-se que eles sejam um fator de proteção para doenças atribuídas ao estresse oxidativo, como degeneração macular relacionada à idade. O estudo quantitativo do pigmento macular e sua distribuição são possíveis por meio da medida da densidade óptica de pigmento macular (MPOD). O objetivo deste trabalho foi determinar o valor médio de MPOD em uma amostra da população brasileira e avaliar a influência dos fatores sexo, idade, etnia, histórico de tabagismo e status refracional nos valores de MPOD nesta amostra. Foi realizado estudo tipo corte transversal. Quarenta e dois pacientes saudáveis tiveram ambos os olhos fotografados utilizando o Visucam 500 (Carl Zeiss Meditec, Jena, Alemanha) em combinação com o módulo MPOD. Quatro variáveis foram obtidas: MPOD máxima, MPOD média, volume de MPOD e área de MPOD. Foram colhidos dados demográficos e hábitos de vida. O valor médio de MPOD nesta amostra da população brasileira foi de 0,13 unidade de densidade ± 0,02. Os valores de MPOD não foram influenciados pelo sexo, histórico de tabagismo ou refração. Os valores de MPOD foram significativamente maiores entre os pacientes negros, quando comparados aos brancos. Encontrou-se uma correlação positiva, porém baixa, entre o valor de MPOD médio e a idade.

Purpose: The main objective of the present study was the investigation of possible influence of lens opacification on macular pigment optical density (MPOD) measurements. Methods: 86 eyes of 64 patients (mean age 73.4(±8.3)years) were included in the study. MPOD was prospectively measured using one-wavelength reflection method (Visucam500, Carl Zeiss Meditec AG) before and after cataract extraction with implantation of a blue-light filtering intraocular lens (AlconSN60WF). The median of the maximum optical density (MaxOD) and the median of the mean optical density (MeanOD) measurements of macular pigment across the subject group were evaluated. Results: Statistically significant differences were noticed between pre-operative and post-operative measurements, the absolute values were generally lower after cataract extraction. The following median(lower/upper quartile) differences across the group were determined: MaxOD -33.8%(-46.2%/-19.1%), MeanOD -44.0%(-54.6%/-26.6%). Larger changes were observed in elderly patients (<70years of age: (n=25eyes) MaxOD -13.4%(-20.5%/3.6%), MeanOD -23.6%(-30.5%/-15.3%) versus patients ≥70years: (n=61eyes) MaxOD -40.5%(-53.2%/-30.1%), MeanOD -47.2%(-57.8%/-40.1%)) and in patients with progressed stage of cataract. MaxOD for lens opacification grade 1:(n=9eyes) -27.4%(-42.1%/-19.6%), 2:(n=26eyes) -35.0%(-44.2%/-25.3%), 3:(n=21eyes) -34.4%(-45.4%/-11.4%), 4:(n=25eyes) -32.6%(-53.2%/-6.4%) and 5:(n=5eyes) -53.5%(-61.7%/-38.7%) and MeanOD for cataract stage 1:(n=9eyes) -42.6%(-46.0%/-26.0%), 2:(n=26eyes) -44.1%(-51.8%/26.2%), 3:(n=21eyes) -45.7%(-54.7%/-24.7%), 4:(n=25eyes) -39.5%(-59.4%/-26.1%), 5:(n=5eyes) -57.0%(-66.1%/-51.4%). Conclusions: As established by comparison of pre- to post-operative measurements, cataract presented a strong effect on MPOD measured by one-wavelength reflection method. Particular care should therefore be taken when evaluating MPOD using this method in elderly patients with progressed stage of cataract. Future optimization of correcting parameters of scattered light and consideration of cataract influence may allow more precise evaluation of MPOD.