Risk factors and biomarkers of age-related macular degeneration

A biomarker can be a substance or structure measured in body parts, fluids or products that can affect or predict disease incidence. As age-related macular degeneration (AMD) is the leading cause of blindness in the developed world, much research and effort has been invested in the identification of different biomarkers to predict disease incidence, identify at risk individuals, elucidate causative pathophysiological etiologies, guide screening, monitoring and treatment parameters, and predict disease outcomes. To date, a host of genetic, environmental, proteomic, and cellular targets have been identified as both risk factors and potential biomarkers for AMD. Despite this, their use has been confined to research settings and has not yet crossed into the clinical arena. A greater understanding of these factors and their use as potential biomarkers for AMD can guide future research and clinical practice. This article will discuss known risk factors and novel, potential biomarkers of AMD in addition to their application in both academic and clinical settings.

Effectiveness of Community versus Hospital Eye Service follow-up for patients with neovascular age-related macular degeneration with quiescent disease (ECHoES): a virtual non-inferiority trial

OBJECTIVES: To compare the ability of ophthalmologists versus optometrists to correctly classify retinal lesions due to neovascular age-related macular degeneration (nAMD).

DESIGN: Randomised balanced incomplete block trial. Optometrists in the community and ophthalmologists in the Hospital Eye Service classified lesions from vignettes comprising clinical information, colour fundus photographs and optical coherence tomographic images. Participants' classifications were validated against experts' classifications (reference standard).

SETTING: Internet-based application.

PARTICIPANTS: Ophthalmologists with experience in the age-related macular degeneration service; fully qualified optometrists not participating in nAMD shared care.

INTERVENTIONS: The trial emulated a conventional trial comparing optometrists' and ophthalmologists' decision-making, but vignettes, not patients, were assessed. Therefore, there were no interventions and the trial was virtual. Participants received training before assessing vignettes.

MAIN OUTCOME MEASURES: Primary outcome-correct classification of the activity status of a lesion based on a vignette, compared with a reference standard. Secondary outcomes-potentially sight-threatening errors, judgements about specific lesion components and participants' confidence in their decisions.

RESULTS: In total, 155 participants registered for the trial; 96 (48 in each group) completed all assessments and formed the analysis population. Optometrists and ophthalmologists achieved 1702/2016 (84.4%) and 1722/2016 (85.4%) correct classifications, respectively (OR 0.91, 95% CI 0.66 to 1.25; p=0.543). Optometrists' decision-making was non-inferior to ophthalmologists' with respect to the prespecified limit of 10% absolute difference (0.298 on the odds scale). Optometrists and ophthalmologists made similar numbers of sight-threatening errors (57/994 (5.7%) vs 62/994 (6.2%), OR 0.93, 95% CI 0.55 to 1.57; p=0.789). Ophthalmologists assessed lesion components as present less often than optometrists and were more confident about their classifications than optometrists.

CONCLUSIONS: Optometrists' ability to make nAMD retreatment decisions from vignettes is not inferior to ophthalmologists' ability. Shared care with optometrists monitoring quiescent nAMD lesions has the potential to reduce workload in hospitals.

TRIAL REGISTRATION NUMBER: ISRCTN07479761; pre-results registration.

Visual functioning and health-related quality of life in diabetic patients about to undergo anti-vascular endothelial growth factor treatment for sight-threatening macular edema

Purpose To examine patient-reported outcome (PRO) in a selected group of Swedish patients about to receive anti-vascular endothelial growth factor (VEGF) treatment for diabetic macular edema (DME). Material and methods In this cross-sectional study, 59 patients with diabetes mellitus, who regularly visited the outpatient eye-clinics, were included. Sociodemographic and clinical data were collected and the patients completed PRO measures before starting anti-VEGF treatment. PRO measures assessed eye-specific outcomes (NEI-VFQ-25) and generic health-related quality of life (SF-36). Results The participants consisted of 30 men and 29 women (mean age, 68.5 years); 54 (92 %) patients had type 2 diabetes; Five (9%) patients had moderate or severe visual impairment; 28 (47 %) were classified as having mild visual impairment. Some of the patients reported overall problems in their daily lives, such as with social relationships, as well as problems with impaired sight as a result of reduced distance vision. Conclusions Further studies are needed to investigate PRO factors related to low perceived general health in this patient population. It is important to increase our understanding of such underlying mechanisms to promote improvements in the quality of patient care.

Anti-VEGF treatment of patients with diabetic macular edema : Studies of visual acuity, macular edema and patient-reported outcomes

The aim of this thesis was to describe and evaluate visual acuity, macular edema and patientreported outcomes (PRO) following anti-VEGF treatment of diabetic macular edema (DME) patients in a real-world setting. Using a longitudinal study design, a cohort of DME patients was followed from baseline to 1 year after treatment start. Data were collected from two eye clinics at two county hospitals. Social background characteristics, medical data and PRO were measured before treatment initiation, at four month and after 1 year. A total of 57 patients completed the study. Mean age was 69 years and the sample was equally distributed regarding sex. At baseline, the patients described their general health as low. One year after treatment initiation, 30 patients had improved visual acuity and 27 patients had no improvement in visual acuity. The patients whose visual acuity improved reported an improvement in several subscales in patient-reported outcome measures (PROM), which was in contrast to the group that experienced a decline in visual acuity, where there was no improvement in PROM. Outcomes from the study can be useful for developing and providing relevant information and support to patients undergoing this treatment.

Patient-reported outcomes and visual acuity after 12 months of anti-VEGF-treatment for sight-threatening diabetic macular edema in a real world setting

Aims To examine objective visual acuity measured with ETDRS, retinal thickness (OCT), patient reported outcome and describe levels of glycated hemoglobin and its association with the effects on visual acuity in patients treated with anti-VEGF for visual impairment due to diabetic macular edema (DME) during 12 months in a real world setting. Methods In this cross-sectional study, 58 patients (29 females and 29 males; mean age, 68 years) with type 1 and type 2 diabetes diagnosed with DME were included. Medical data and two questionnaires were collected; an eye-specific (NEI VFQ-25) and a generic health-related quality of life questionnaire (SF-36) were used. Results The total patient group had significantly improved visual acuity and reduced retinal thickness at 4 months and remains at 12 months follow up. Thirty patients had significantly improved visual acuity, and 27 patients had no improved visual acuity at 12 months. The patients with improved visual acuity had significantly improved scores for NEI VFQ-25 subscales including general health, general vision, near activities, distance activities, and composite score, but no significant changes in scores were found in the group without improvements in visual acuity. Conclusions Our study revealed that anti-VEGF treatment improved visual acuity and central retinal thickness as well as patient-reported outcome in real world 12 months after treatment start.

Carotenoids and antioxidant enzymes as biomarkers of the impact of heavy metals in food chain

Antioxidant enzymes (catalase and peroxidase) and carotenoids (lutein and â-carotene) are often used as biomarkers of metal contamination of water and agricultural soils. In this study, the effects of heavy metals present in irrigation water on the aforementioned carotenoids of potatoes (Solanum tuberosum L.) and carrots (Daucus carota L.), cultivated in a greenhouse and irrigated with a water solution including different levels of Cr(VI) and Ni(II) were investigated. These results were compared to the levels of the same metabolites that had been assessed in market-available potato and carrot samples. The findings indicated that the levels of the examined metabolites on the treated with Cr and Ni samples, resemble the levels of the same parameters in the market samples, originating from polluted areas. Therefore, the antioxidant enzymes, catalase and peroxidase, and the carotenoids, lutein and â-carotene, could be handled as indicators of heavy metal pollution.

Use of time-resolved spectroscopy as a method to monitor carotenoids present in tomato extract obtained using ultrasound treatment

Introduction Compounds exhibiting antioxidant activity have received much interest in the food industry because of their potential health benefits. Carotenoids such as lycopene, which in the human diet mainly derives from tomatoes (Solanum lycopersicum), have attracted much attention in this aspect and the study of their extraction, processing and storage procedures is of importance. Optical techniques potentially offer advantageous non-invasive and specific methods to monitor them. Objectives To obtain both fluorescence and Raman information to ascertain if ultrasound assisted extraction from tomato pulp has a detrimental effect on lycopene. Method Use of time-resolved fluorescence spectroscopy to monitor carotenoids in a hexane extract obtained from tomato pulp with application of ultrasound treatment (583 kHz). The resultant spectra were a combination of scattering and fluorescence. Because of their different timescales, decay associated spectra could be used to separate fluorescence and Raman information. This simultaneous acquisition of two complementary techniques was coupled with a very high time-resolution fluorescence lifetime measurement of the lycopene. Results Spectroscopic data showed the presence of phytofluene and chlorophyll in addition to lycopene in the tomato extract. The time-resolved spectral measurement containing both fluorescence and Raman data, coupled with high resolution time-resolved measurements, where a lifetime of ~5 ps was attributed to lycopene, indicated lycopene appeared unaltered by ultrasound treatment. Detrimental changes were, however, observed in both chlorophyll and phytofluene contributions. Conclusion Extracted lycopene appeared unaffected by ultrasound treatment, while other constituents (chlorophyll and phytofluene) were degraded.

Estudio piloto sobre la función de sensibilidad al contraste y la calidad de vida relacionada con la salud en pacientes con degeneración macular relacionada con la edad

Tesis (Maestría en Ciencias de la Visión).-- Universidad de La Salle. Maestría en Ciencias de la Visión, 2014

Ability of Gordonia alkanivorans strain 1B for high added value carotenoids production

Currently, carotenoids are valuable bioactive molecules for several industries, such as chemical, pharmaceutical, food and cosmetics, due to their multiple benefits as natural colorants, antioxidants and vitamin precursors. Hence, the increasing interest on these high added-value products has led to the search of alternatives, more cost-effective and with better yields, towards their industrial production. Indeed, microbial metabolism offers a promising option for carotenoids production. Herein it is shown the potential of the dibenzothiophene desulfurizing bacterium Gordonia alkanivorans strain 1B as a high carotenoid-producer microorganism. The novel carotenoids, produced under different culture conditions, were extracted with DMSO and then further analyzed both through spectrophotometry and HPLC. When grown in glucose-sulfate-light, strain 1B was able of achieving 2015 g carotenoids per g DCW in shake-flask assays, with about 60% corresponding to lutein, canthaxanthin and astaxanthin. Further optimization studies open a new focus of research aiming to get a hyper pigment-producer strain that may be applied towards different industrial sectors.

Espesor macular medido con tomografía de coherencia óptica en ojos pseudoafáquicos con implante amarillo vs. transparente

Objetivo: Evaluar mediante tomografía de coherencia óptica (OCT) las variaciones de espesor macular producidas a lo largo del tiempo en ojos pseudoafáquicos implantados con una lente intraocular (LIO) transparente en comparación con sus respectivos ojos contralarerales implantados con LIO amarilla. Métodos: El espesor macular de 36 ojos de 18 sujetos fue evaluado mediante OCT. Los sujetos presentaban edades superiores a 65 años y habían sido intervenidos de cataratas en ambos ojos en 2 cirugías independientes. La principal característica de los individuos es que llevaban implantada una LIO con diferente absorción en cada ojo: transparente (absorbente de la radiación ultravioleta) y amarilla (con filtro adicional absorbente de las radiaciones violeta-azul del espectro visible). El espesor macular se evaluó en 2 sesiones separadas en el tiempo por un intervalo de tiempo de 5 años, mediante el sistema Stratus-OCT (protocolo fast macular thickness). Se analizaron estadísticamente las diferencias en la evolución del espesor macular entre ojos con diferente tipo de LIO. Resultados: Tras 5 años de seguimiento, se observó que los ojos implantados con LIO transparente manifestaban una reducción del espesor macular estadísticamente significativa, superior a la esperada por el aumento de la edad. Sin embargo, los ojos implantados con LIOs amarillas mantuvieron su espesor macular estable. La disminución del espesor macular promedio en ojos implantados con LIO transparente fue de 5 ± 8 μm (p = 0,02) y la reducción del espesor foveal fue de 10 ± 17 μm (p = 0,02). Conclusiones: Los cambios de espesor macular producidos en ojos implantados con una LIO amarilla difieren de los cambios manifestados en ojos con LIO transparente. Estas observaciones apuntan a un posible efecto protector de las LIOs amarillas contra los efectos dañinos de la luz en sujetos pseudoafáquicos. Sin embargo, estudios con un mayor tamaño muestral y mayor tiempo de seguimiento son necesarios para confirmar que la protección inducida por este tipo de LIO es clínicamente significativa.

Macular Thickness as a Potential Biomarker of Mild Alzheimer's Disease

Although several postmortem findings in the retina of patients with Alzheimer's disease (AD) are available, new biomarkers for early diagnosis and follow-up of AD are still lacking. It has been postulated that the defects in the retinal nerve fiber layer (RNFL) may be the earliest sign of AD, even before damage to the hippocampal region that affects memory. This fact may reflect retinal neuronal-ganglion cell death and axonal loss in the optic nerve in addition to aging.

Impaired Mesopic Visual Acuity in Eyes with Early Age-Related Macular Degeneration

Purpose.: To determine photopic and mesopic distance high-contrast visual acuity (HC-VA) and low-contrast visual acuity (LC-VA) in eyes with early age-related macular degeneration (AMD). Methods.: Measurements were made in 22 subjects with early AMD and 28 healthy control subjects. Inclusion criteria included a photopic HC-VA of 20/25 or better. Distance VA was measured using HC (96%) and LC (10%) Bailey-Lovie logMAR letter charts under photopic (85 cd/m2) and mesopic (0.1–0.2 cd/m2) luminance conditions. Results.: Mean mesopic distance HC-VA and LC-VA were significantly worse (0.1 logMAR and 0.28 logMAR, respectively) in the early AMD group than in the control group. Under mesopic conditions, the mean difference between LC-VA and HC-VA was significantly greater in the early AMD (0.45 logMAR) than the control group (0.27 logMAR). Mean differences between mesopic versus photopic HC-VA and mesopic versus photopic LC-VA were significantly greater in the early AMD than the control group (0.13 and 0.32 logMAR of difference between the means, respectively). Sensitivity and specificity were significantly greater for mesopic LC-VA than for mesopic HC-VA (Receiver Operating Characteristics, area under the curve [AUC], 0.94 ± 0.030 and 0.76 ± 0.067, respectively). AUC values for photopic HC-VA and LC-VA were below 0.70. Conclusions.: Visual acuity testing under low luminance conditions emerged as an optimal quantitative measure of retinal function in early AMD.