Age-Related Eye Disease Research Articles

Rare Dysfunctional Complement Factor I Genetic Variants and Progression to Advanced Age-Related Macular Degeneration.

To evaluate associations between rare dysfunctional complement factor I (CFI) genetic variant status and progression to advanced age-related macular degeneration (AAMD), geographic atrophy (GA), and neovascular disease (NV). Prospective, longitudinal study. Patients aged 55 to 80 years at baseline identifying as White with non-AAMD in 1 or both eyes at baseline were included. Follow-up grades were assigned as early, intermediate, or AAMD (GA or NV). CFI variants were categorized using genotyping and sequencing platforms. Analyses were performed using the Seddon Longitudinal Cohort Study (N=2116 subjects, 3901 eyes, and mean follow-up of 8.3 years) and the Age-Related Eye Disease Study (N=2837 subjects, 5200 eyes, and mean follow-up of 9.2 years). CFI rare variants associated with low serum factor I (FI) protein levels and decreased FI function (type 1), other AMD genetic variants, and demographic, behavioral, and ocular factors were evaluated. Generalized estimating equations methods were used to assess the association between CFI rare variants and progression, independent of other genetic variants and covariates. Progression to AAMD, GA, or NV. In the prospective cohort of 4953 subjects (9101 eyes with non-AAMD at baseline), 1% were type 1 rare CFI carriers. Over 12 years, progression to AAMD was 44% for carriers and 20% for noncarriers (P < 0.001), 30% of carriers versus 10% of noncarriers progressed to GA (P<0.001), and 18% of carriers compared with 11% of noncarriers progressed to NV (P=0.049). CFI carriers were more likely to have a family history of AMD (P for trend=0.035) and a higher baseline AMD grade (P<0.001). After adjusting for all covariates, CFI carrier status was associated with progression to GA (odds ratio [OR]=1.91; 95% confidence interval [CI]=1.03, 3.52) but not NV (OR=0.96). Higher body mass index was associated with progression among CFI carriers (body mass index ≥ 25 vs.<25; OR=5.8; 95% CI 1.5, 22.3) but not for noncarriers (OR=1.1; 95% CI=0.9, 1.3), with P_interaction=0.011. Results suggest that carriers of rare dysfunctional type 1 CFI variants are at higher risk for progression to AAMD with GA. Proprietary or commercial disclosure may be found after the references.

The Assessment of Acute Chorioretinal Changes Due to Intensive Physical Exercise in Senior Elite Athletes.

Regular physical exercise is known to lower the incidence of age-related eye diseases. We aimed to assess the acute chorioretinal alterations in older adults following intense physical strain. Seventeen senior elite athletes were recruited who underwent an aerobic exercise on a cycle ergometer and macular scanning by optical coherence tomography. A significant thinning of the entire retina was observed 1min after exercise, followed by a thickening at 5min, after which the thickness returned to baseline. This trend was similar in almost every single retinal layer, although a significant change was observed only in the inner retina. Choroidal thickness changes were neither significant nor did they correlate with the thickness changes of intraretinal layers. The mechanism of how these immediate retinal changes chronically impact age-related sight-threatening pathologies that, in turn, result in a substantially reduced quality of life warrants further investigation on nontrained older adults as well.

Biologically Guided Optimization of Test Target Location for Rod-mediated Dark Adaptation in Age-related Macular Degeneration: Alabama Study on Early Age-related Macular Degeneration 2 Baseline.

We evaluate the impact of test target location in assessing rod-mediated dark adaptation (RMDA) along the transition from normal aging to intermediate age-related macular degeneration (AMD). We consider whether RMDA slows because the test locations are near mechanisms leading to or resulting from high-risk extracellular deposits. Soft drusen cluster under the fovea and extend to the inner ring of the ETDRS grid where rods are sparse. Subretinal drusenoid deposits (SDDs) appear first in the outer superior subfield of the ETDRS grid where rod photoreceptors are maximal and spread toward the fovea without covering it. Cross-sectional. Adults ≥ 60 years with normal older maculas, early AMD, or intermediate AMD as defined by the Age-Related Eye Disease Study (AREDS) 9-step and Beckman grading systems. In 1 eye per participant, RMDA was assessed at 5° and at 12° in the superior retina. Subretinal drusenoid deposit presence was identified with multi-modal imaging. Rod intercept time (RIT) as a measure of RMDA rate at 5° and 12°. In 438 eyes of 438 persons, RIT was significantly longer (i.e., RMDA is slower) at 5° than at 12° for each AMD severity group. Differences among groups were bigger at 5° than at 12°. At 5°, SDD presence was associated with longer RIT as compared to SDD absence at early and intermediate AMD but not in normal eyes. At 12°, SDD presence was associated with longer RIT in intermediate AMD only, and not in normal or early AMD eyes. Findings were similar in eyes stratified by AREDS 9-step and Beckman systems. We probed RMDA in relation to current models of deposit-driven AMD progression organized around photoreceptor topography. In eyes with SDD, slowed RMDA occurs at 5° where these deposits typically do not appear until later in AMD. Even in eyes lacking detectable SDD, RMDA at 5° is slower than at 12°. The effect at 5° may be attributed to mechanisms associated with the accumulation of soft drusen and precursors under the macula lutea throughout adulthood. These data will facilitate the design of efficient clinical trials for interventions that aim to delay AMD progression.

Macular and Plasma Xanthophylls Are Higher in Age-related Macular Degeneration than in Normal Aging: Alabama Study on Early Age-related Macular Degeneration 2 Baseline.

Quantification of retinal xanthophyll carotenoids in eyes with and without age-related macular degeneration (AMD) via macular pigment optical volume (MPOV), a metric for xanthophyll abundance from dual wavelength autofluorescence, plus correlations to plasma levels, could clarify the role of lutein (L) and zeaxanthin (Z) in health, AMD progression, and supplementation strategies. Cross-sectional observational study (NCT04112667). Adults ≥ 60 years from a comprehensive ophthalmology clinic, with healthy maculas or maculas meeting fundus criteria for early or intermediate AMD. Macular health and supplement use was assessed by the Age-related Eye Disease Study (AREDS) 9-step scale and self-report, respectively. Macular pigment optical volume was measured from dual wavelength autofluorescence emissions (Spectralis, Heidelberg Engineering). Non-fasting blood draws were assayed for L and Z using high-performance liquid chromatography. Associations among plasma xanthophylls and MPOV were assessed adjusting for age. Age-related macular degeneration presence and severity, MPOV in fovea-centered regions of radius 2.0° and 9.0°; plasma L and Z (μM/ml). Of 809 eyes from 434 persons (89% aged 60-79, 61% female), 53.3% eyes were normal, 28.2% early AMD, and 18.5% intermediate AMD. Macular pigment optical volume 2° and 9° were similar in phakic and pseudophakic eyes, which were combined for analysis. Macular pigment optical volume 2° and 9° and plasma L and Z were higher in early AMD than normal and higher still in intermediate AMD (P<0.0001). For all participants, higher plasma L was correlated with higher MPOV 2° (Spearman correlation coefficient [Rs]=0.49; P < 0.0001). These correlations were significant (P<0.0001) but lower in normal (Rs=0.37) than early and intermediate AMD (Rs=0.52 and 0.51, respectively). Results were similar for MPOV 9°. Plasma Z, MPOV 2°, and MPOV 9° followed this same pattern of associations. Associations were not affected by supplement use or smoking status. A moderate positive correlation of MPOV with plasma L and Z comports with regulated xanthophyll bioavailability and a hypothesized role for xanthophyll transfer in soft drusen biology. An assumption that xanthophylls are low in AMD retina underlies supplementation strategies to reduce progression risk, which our data do not support. Whether higher xanthophyll levels in AMD are due to supplement use cannot be determined in this study.

DETECT: DEveloping and testing a model to identify preventive vision loss among older paTients in gEneral praCTice – protocol for a complex intervention in Denmark

IntroductionThe number of people living with visual impairment is increasing. Visual impairment causes loss in quality of life and reduce self-care abilities. The burden of disease is heavy for people...

Gene-level association analysis of bivariate ordinal traits with functional regressions.

In genetic studies, many phenotypes have multiple naturally ordered discrete values. The phenotypes can be correlated with each other. If multiple correlated ordinal traits are analyzed simultaneously, the power of analysis may increase significantly while the false positives can be controlled well. In this study, we propose bivariate functional ordinal linear regression (BFOLR) models using latent regressions with cumulative logit link or probit link to perform a gene-based analysis for bivariate ordinal traits and sequencing data. In the proposed BFOLR models, genetic variant data are viewed as stochastic functions of physical positions, and the genetic effects are treated as a function of physical positions. The BFOLR models take the correlation of the two ordinal traits into account via latent variables. The BFOLR models are built upon functional data analysis which can be revised to analyze the bivariate ordinal traits and high-dimension genetic data. The methods are flexible and can analyze three types of genetic data: (1) rare variants only, (2) common variants only, and (3) a combination of rare and common variants. Extensive simulation studies show that the likelihood ratio tests of the BFOLR models control type I errors well and have good power performance. The BFOLR models are applied to analyze Age-Related Eye Disease Studydata, in which two genes, CFH and ARMS2, are found to strongly associate with eye drusen size, drusen area, age-related macular degeneration (AMD) categories, and AMD severity scale.

Deep-GA-Net for Accurate and Explainable Detection of Geographic Atrophy on OCT Scans

To propose Deep-GA-Net, a 3-dimensional (3D) deep learning network with 3D attention layer, for the detection of geographic atrophy (GA) on spectral domain OCT (SD-OCT) scans, explain its decision making, and compare it with existing methods. Deep learning model development. Three hundred eleven participants from the Age-Related Eye Disease Study 2 Ancillary SD-OCT Study. A dataset of 1284 SD-OCT scans from 311 participants was used to develop Deep-GA-Net. Cross-validation was used to evaluate Deep-GA-Net, where each testing set contained no participant from the corresponding training set. En face heatmaps and important regions at the B-scan level were used to visualize theoutputs of Deep-GA-Net, and 3 ophthalmologists graded the presence or absence of GA in them to assess the explainability (i.e., understandability and interpretability) of its detections. Accuracy, area under receiver operating characteristic curve (AUC), area under precision-recall curve (APR). Compared with other networks, Deep-GA-Net achieved the best metrics, with accuracy of 0.93, AUC of 0.94, and APR of 0.91, and received the best gradings of 0.98 and 0.68 on the en face heatmap and B-scan grading tasks, respectively. Deep-GA-Net was able to detect GA accurately from SD-OCT scans. The visualizations of Deep-GA-Net were more explainable, as suggested by 3 ophthalmologists. The code and pretrained models are publicly available at https://github.com/ncbi/Deep-GA-Net. The author(s) have no proprietary or commercial interest in any materials discussed in this article.

Adherence of patients with age-related macular degeneration to AREDS 2-recommended nutritional supplements.

The Age-Related Eye Disease Study 2 (AREDS 2) proved the benefit of vitamin and mineral supplementation in preventing advanced age-related macular degeneration (AMD). AREDS 2 supplements are indicated for patients with either bilateral intermediate AMD (AREDS category 3) or unilateral neovascular AMD (AREDS category 4). The aims of this telephone survey were to identify the rate of adherence of patients to AREDS 2 supplements and the factors associated with non-compliance in these patient groups. A patient telephone survey was conducted in an Irish tertiary care hospital. Patients were identified by chart review, and their AREDS categorization was reconfirmed. A telephone consultation was conducted with each patient to assess their compliance with the micronutrient supplements. We identified 120 patients who met the AREDS criteria for supplementation. Of these, 103 patients were graded as category 4, and 17 patients were graded as category 3. Almost a fifth (18%) were current smokers. Under two-thirds (60%) of the patients were taking AREDS 2 supplements. Of the remainder, 83% of patients did not recall being advised of their benefit. The cost was cited by 10% of patients as a reason for non-compliance. The ophthalmologist not only has a duty of care to treat the neovascular complications of AMD, but they must also strive to improve patient compliance with AREDS supplements. The cessation of smoking needs to be actively promoted in order to stop preventable vision loss in patients with AMD.

Was gibt es Neues in der AMD-Landschaft?

As society ages, the importance of age-related eye diseases such as age-related macular degeneration (AMD) increases. The intravitreal treatment of neovascular AMD (nAMD), which accounts for about 10% of all AMD cases, revolutionized the world of ophthalmology about 15 years ago. This form of therapy, which can be used to treat - in addition to nAMD - other vascular retinal diseases, has led to a significant reduction in the incidence of vision loss and blindness caused by AMD and diabetes worldwide. Current developments in ophthalmology may shape the future of AMD treatment and include advancements in home-monitoring technologies like simpler, more cost-effective optical coherence tomography (OCT) devices, application of artificial intelligence for more detailed OCT, development and approval of novel therapeutics with longer-lasting effects on the eye or new mechanisms of action as well as new application systems using nanotechnological “Sustained-Delivery Systems” or suprachoroidal treatment with viral vectors for gene therapy. Overall, these exciting ongoing developments will change the treatment landscape in AMD and pave the way to increased quality of life for our elderly patients. Moreover, home monitoring technologies will ease the burden on our healthcare systems. At the same time, novel therapeutic options that require intravitreal surgical interventions may increase it.

Impact of major age-related eye disorders on health-related quality of life assessed by EQ-5D: a systematic review and meta-analysis.

This study is to quantitatively estimate the health-related quality of life (HRQOL) impact of major age-related eye diseases (AREDs) including cataract, glaucoma, age-related macular degeneration (AMD), and diabetic retinopathy (DR) assessed by the EuroQoL Five-Dimensional Questionnaire (EQ-5D). PubMed, Embase, Cochrane Library, and CINAHL were searched until October 20, 2022. Studies were included if they reported the EQ-5D health utility score (HUS) or visual analogue scale (VAS) score of both AREDs patients and healthy controls. The mean difference (MD) in HUS or VAS score between cases and controls and its 95% confidence interval (95%CI) were pooled using the random-effects model. We also performed sensitivity analysis using the leaving-one-out method and subgroup analyses by sample size and race. The prevalence in reporting any problems in the five EQ-5D dimensions was summarized and compared between cases and controls using the Chi-square test. Fifteen articles involving 30,491 participants were included in this review. Pooled estimates indicated reduced HUS in AMD patients (MD = -0.04, 95%CI -0.07, -0.01; P = 0.009), DR patients (MD = -0.03, 95%CI -0.05, -0.01; P = 0.01), and glaucoma patients (MD = -0.06, 95%CI -0.10, -0.01; P = 0.01), compared with the controls. Significantly lower EQ-5D VAS score was also observed in cataract patients (MD = -11.33, 95%CI -13.47, -9.18; P < 0.001) and DR patients (MD = -6.41, 95%CI -10.64, -2.18; P = 0.003). AREDs patients reported usual activities and anxiety/depression problems more frequently than the control group. Our findings confirmed the HRQOL impairment caused by major AREDs including AMD, cataract, DR, and glaucoma. High-quality studies with large sample sizes are warranted to further verify our results.

Effect of Correcting Peripheral Refractive Errors on Retinal Sensitivity in Younger and Older Healthy Adults.

Retinal sensitivity decreases with age and age-related eye diseases. Peripheral retinal sensitivity may also be compromised if the refractive correction is not optimized for peripheral vision. This study aimed to determine the impact of using a peripheral refractive correction on perimetric thresholds and the influence of age and spherical equivalent on this impact. We measured, in 10 younger (20 to 30 years) and 10 older (58 to 72 years) healthy subjects, perimetric thresholds for Goldmann size III stimulus in several test locations along the horizontal meridian of the visual field (eccentricity, 0, ±10, and ±25°), with default central refractive correction and with peripheral refractive corrections as measured with a Hartmann-Shack wavefront sensor. We used analysis of variance to determine the effect of age and spherical equivalent (between-subject variables) and eccentricity and correction method (central vs. eccentricity specific; within-subject variables) on retinal sensitivity. Retinal sensitivity was higher if the eyes were optimally corrected for the concerning test location (P = .008), and the effect of this peripheral correction differed between the younger and older subjects (interaction term between group and correction method: P = .02), primarily because of more myopia in the younger group (P = .003). The average improvement by applying peripheral corrections was 1.4 dB in the older subjects and 0.3 dB in the younger subjects. Peripheral optical correction has a variable impact on retinal sensitivity, and therefore, assessment of retinal sensitivity may be more accurate if peripheral defocus and astigmatism are corrected.

Protein-Mediated Carotenoid Delivery Suppresses the Photoinducible Oxidation of Lipofuscin in Retinal Pigment Epithelial Cells.

Lipofuscin of retinal pigment epithelium (RPE) cells is a complex heterogeneous system of chromophores which accumulates as granules during the cell's lifespan. Lipofuscin serves as a source of various cytotoxic effects linked with oxidative stress. Several age-related eye diseases such as macular degeneration of the retina, as well as some severe inherited eye pathologies, are accompanied by a significant increase in lipofuscin granule concentration. The accumulation of carotenoids in the RPE could provide an effective antioxidant protection against lipofuscin cytotoxic manifestations. Given the highly lipophilic nature of carotenoids, their targeted delivery to the vulnerable tissues can potentially be assisted by special proteins. In this study, we demonstrate how protein-mediated delivery of zeaxanthin using water-soluble Bombyx mori carotenoid-binding protein (BmCBP-ZEA) suppresses the photoinducible oxidative stress in RPE cells caused by irradiation of lipofuscin with intense white light. We implemented fluorescence lifetime imaging of the RPE cell culture ARPE-19 fed with lipofuscin granules and then irradiated by white light with and without the addition of BmCBP-ZEA. We demonstrate that after irradiation the mean fluorescence lifetime of lipofuscin significantly increases, while the presence of BmCBP-ZEA at 200 nM concentration suppresses the increase in the average lifetime of lipofuscin fluorescence, indicating an approx. 35% inhibition of the oxidative stress. This phenomenon serves as indirect yet important evidence of the efficiency of the protein-mediated carotenoid delivery into pigment epithelium cells.

Automation of Macular Degeneration Classification in the AREDS Dataset, Using a Novel Neural Network Design.

To create an ensemble of Convolutional Neural Networks (CNNs), capable of detecting and stratifying the risk of progressive age-related macular degeneration (AMD) from retinal photographs. Retrospective cohort study. Three individual CNNs are trained to accurately detect 1) advanced AMD, 2) drusen size and 3) the presence or otherwise of pigmentary abnormalities, from macular centered retinal images were developed. The CNNs were then arranged in a "cascading" architecture to calculate the Age-related Eye Disease Study (AREDS) Simplified 5-level risk Severity score (Risk Score 0 - Risk Score 4), for test images. The process was repeated creating a simplified binary "low risk" (Scores 0-2) and "high risk" (Risk Score 3-4) classification. There were a total of 188,006 images, of which 118,254 images were deemed gradable, representing 4591 patients, from the AREDS1 dataset. The gradable images were split into 50%/25%/25% ratios for training, validation and test purposes. The ability of the ensemble of CNNs using retinal images to predict an individual's risk of experiencing progression of their AMD based on the AREDS 5-step Simplified Severity Scale. When assessed against the 5-step Simplified Severity Scale, the results generated by the ensemble of CNN's achieved an accuracy of 80.43% (quadratic kappa 0.870). When assessed against a simplified binary (Low Risk/High Risk) classification, an accuracy of 98.08%, sensitivity of ≥85% and specificity of ≥99% was achieved. We have created an ensemble of neural networks, trained on the AREDS 1 dataset, that is able to accurately calculate an individual's score on the AREDS 5-step Simplified Severity Scale for AMD. If the results presented were replicated, then this ensemble of CNNs could be used as a screening tool that has the potential to significantly improve health outcomes by identifying asymptomatic individuals who would benefit from AREDS2 macular supplements.

Association Between Fatty Acid Intakes and Age-Related Macular Degeneration in a Japanese Population: JPHC-NEXT Eye Study

To determine the associations between fatty acid intakes and the prevalence of age-related macular degeneration (AMD) under a population-based cross-sectional study. Residents of Chikusei City aged ≥40 years underwent systemic and eye screening. AMD was graded according to a modified version of the Age-Related Eye Disease Study classification. Dietary intake was assessed using a food frequency questionnaire and was adjusted for total energy intake. Altogether, 10,788 eyes of 5394 participants, 2116 men (mean [standard deviation (SD)] age, 62.4 [9.4] years) and 3278 women (60.6 [9.5] years), were included. The mean daily total fat intakes were 52.8 g and 59.0 g in men and women, respectively. After adjustments for potential confounders, saturated fatty acid (SFA) intake was inversely associated with the prevalence of any AMD in men (for each energy-adjusted 1-SD increase: odds ratio [OR], 0.86; 95% confidence interval [CI], 0.74-1.00). Significant trends were found for decreasing odds ratios of AMD with increasing SFA, monounsaturated fatty acid (MUFA), and polyunsaturated fatty acid (PUFA) intake (P for trend = 0.02, 0.04, and 0.04, respectively). In women, only a significant association was observed between the second quartile of linolenic acid intake and the prevalence of any AMD (OR, 0.78; 95% CI, 0.62-0.99). We found an inverse association of SFA intake and a weak inverse association of MUFA and PUFA intakes with the prevalence of any AMD in a Japanese population. Adequate fatty acid intake may be necessary to prevent or decelerate AMD.

Risk Factors for Vision Loss among Nursing Home Residents: A Cross-Sectional Analysis

Approximately 2% of older adults currently live in nursing homes. It is important that the risks for vision loss be characterized to ensure appropriate vision care is provided for nursing home patients. Our objective was to evaluate the association of age-related eye diseases (AREDs) and multimorbidities with vision loss. Cross-sectional study. This is a cross-sectional analysis of comprehensive eye examination records for 7753 residents of 74 North Carolina nursing homes who were ≥65years of age at time of the initial patient visit. Complete data on vision and associated factors were included from the standardized Centers for Medicare and Medicaid Services eye examination. We defined vision impairment and blindness respectively as best-corrected visual acuity between 20/40 and 20/200, and 20/200 or worse. Clinical diagnoses of AREDs were defined by the attending clinician. Data were extracted from electronic health records, and all analyses were conducted in SAS v 9.4. We used descriptive statistics to summarize the resident characteristics and AREDs and logistic regression analysis to examine independent risk factors for vision impairment. A total of 7753 initial eye examination records with complete data were included in the analysis. Overall, 34% of the residents had normal vision, 43% had vision impairment, and 23% were blind. Among participants with various AREDs, the prevalence of vision impaired/blind ranged from 63% to 76%, while blindness ranged from 23% to 53%. We found correction of refractive error alone served to reduce vision impairment or blindness. Comprehensive eye examinations showed vision impairment and blindness affected 66% of nursing home residents, overall. This study substantiates the positive impact of comprehensive eye examinations to promote visual, systemic, and cognitive health and well-being and the need that eye care service be used to inform policy and practice to improve patient functioning and independence.

Validity and reliability of food frequency questionnaire used in age-related eye disease studies in Turkish adults.

The present study aimed to perform the validity and reliability study of the Food Frequency Questionnaire (FFQ) on the frequency of foods rich in antioxidant nutrients and used in Age-Related Eye Diseases (AREDs). In the first interview of the study, the first application of FFQ was carried out, and blank forms of Dietary Records (DRs) were given. For the validity of the FFQ, a total of 12 d (3 days * 4 weeks) of DR were taken. For the reliability of the FFQ, a test-retest application was made with an interval of 4 weeks. The daily intake means of antioxidant nutrients, omega 3 and total antioxidant capacity data obtained from both the FFQ and DR were calculated, and the concordance between the two methods was evaluated with the Pearson Correlation Coefficient (PCC) and Bland-Altman graphs. The present study was carried out at Ege University İzmir/Turkey, Department of Ophthalmology, Retina Unit. The study was conducted with individuals aged ≥50 years who suffered from Age-Related Macular Degeneration (n 100, 72⋅0 ± 8⋅03 years). The values obtained from the test-retest applications for FFQ reliability were the same. The nutrient intake means obtained from the FFQ were similar or significantly higher than DR (P < 0⋅05). In the Bland-Altman graphical approach, the nutrient data were within the limits of agreement, and the PCCs between the two methods were moderately related. Considered together, this FFQ is a suitable tool for determining the dietary intakes of antioxidant nutrients in the Turkish population.

A xanthophyll-derived apocarotenoid regulates carotenogenesis in tomato chromoplasts

Carotenoids possess important biological functions that make them essential components of the human diet. β-Carotene and some other carotenoids have vitamin A activity while lutein and zeaxanthin, typically referred to as the macular pigments, are involved in good vision and in delaying the onset of age-related eye diseases. In order to create a zeaxanthin-producing tomato fruit, two transgenic lines, one with a high β-carotene cyclase activity and the other with a high β-carotene hydroxylase activity, have been genetically crossed. Ripe fruits from the resulting progeny contained significant levels of violaxanthin, antheraxanthin, and xanthophyll esters. However, their zeaxanthin content was not as high as expected, and the total level of carotenoids was only 25% of the carotenoids found in ripe fruits of the comparator line. Targeted transcript analysis and apocarotenoids determinations indicated that transcriptional regulation of the pathway or degradation of synthesized carotenoids were not responsible for the low carotenoid content of hybrid fruits which instead appeared to result from a substantial reduction of carotenoid biosynthesis. Notably, the content of an unidentified hydroxylated cyclic (C13) apocarotenoid was 13 times higher in the hybrid fruits than in the control fruits. Furthermore, a GC-MS-based metabolite profiling demonstrated a perturbation of carotenogenesis in ripening hybrid fruits compatible with a block of the pathway. Moreover, carotenoid profiling on leaf, fruit, and petal samples from a set of experimental lines carrying the hp3 mutation, in combination with the two transgenes, indicated that the carotenoid biosynthesis in petal and fruit chromoplasts could be regulated. Altogether the data were consistent with the hypothesis of the regulation of the carotenoid pathway in tomato chromoplasts through a mechanism of feedback inhibition mediated by a xanthophyll-derived apocarotenoid. This chromoplast-specific post-transcriptional mechanism was disclosed in transgenic fruits of HU hybrid owing to the abnormal production of zeaxanthin and antheraxanthin, the more probable precursors of the apocarotenoid signal. A model describing the regulation of carotenoid pathway in tomato chromoplasts is presented.

Association of Dietary Nitrate and a Mediterranean Diet With Age-Related Macular Degeneration Among US Adults

Low dietary nitrate intake has previously been suggested to be a risk factor for age-related macular degeneration (AMD) progression; however, this finding has not been replicated in other cohorts or adjusted for dietary patterns. To determine whether there is an association between dietary nitrate intake and AMD progression. This cohort study analyzed data from the prospective Age-Related Eye Disease Study (AREDS) and AREDS2 randomized clinical trial cohorts and their extended follow-up studies, which were conducted in multicenter outpatient retinal practices. Participants in both trials had non-late AMD in at least 1 eye. Data were analyzed from March 1, 2020, to September 30, 2022. Dietary nitrate intake. Association between dietary nitrate intake and development of late AMD (neovascular AMD [nAMD] or geographic atrophy [GA]) or large drusen. The interactions of dietary patterns, with common at-risk single-nucleotide polymorphisms, were also assessed. In the combined AREDS/AREDS2 cohort of 7788 participants (4288 AREDS participants and 3610 AREDS2 participants [110 of whom participated in both studies]), there were 13 511 eligible eyes. The combined cohort comprised 4396 women (56%) and 3392 men (44%), and the combined mean (SD) age was 71.1 (6.6) years. Dietary nitrate intake was associated with a decreased risk of progression to late AMD in the combined AREDS/AREDS2 cohort (hazard ratio [HR], 0.77 [95% CI, 0.69-0.86] for quartile 4 vs quartile 1 of intake) and a decreased risk of GA (HR, 0.71 [95% CI, 0.61-0.83]) and nAMD (HR, 0.85 [95% CI, 0.73-0.99]). In AREDS, increased nitrate intake (quartile 4 vs quartile 1) was associated with a decreased risk of late AMD (HR, 0.77 [95% CI, 0.65-0.91]) and GA (HR, 0.80 [95% CI, 0.65-0.97]) but not nAMD; in AREDS2, there was no association between nitrate intake (quartile 4 vs quartile 1) and late AMD (HR, 0.90 [95% CI, 0.80-1.02]) or nAMD (HR, 0.93 [95% CI, 0.78-1.11]). There was a correlation between Mediterranean dietary patterns and dietary nitrate intake (r = 0.52, P < .001). The findings of this cohort study suggest that dietary nitrate intake was associated with lower AMD risk. However, this association disappeared after adjusting for Mediterranean dietary patterns. These results are subject to potential bias and are hypothesis-generating in nature; therefore, they are insufficient to support new clinical recommendations. Previously described associations between dietary nitrate intake and AMD may in fact represent overall dietary patterns. Further research is needed before dietary nitrate intake can be recommended as a therapy for AMD.

Assessment of Knowledge Regarding Cataract Among Saudi Adult Population in Assir Region, Saudi Arabia.

Cataract is the most prevalent age-related eye disease and the most curable cause of adult visual impairment. The aim of this study was to assess the cataract disease rate and knowledge regarding its definition, symptoms, risk factors, prognosis, and treatment. A community-based cross-sectional study of 600 randomly selected people aged 18 and up was conducted from May 2022 to August 2022, among adults.Participants were given an online survey via social media that included items testing their knowledge of cataracts. Study participants had a 3.4% cataract previous exposure rate.Four hundred forty-eight (75.9%) participants had good knowledge about cataracts. Participants with higher educational levels were more likely to correctly answer questions about different aspects of knowledge about cataracts. Future studies should focus on improving awareness about cataracts. Risk factors, complications, treatment options, complications of cataract surgery, and regular follow-ups should be explained to patients. Through routine eye checks, early detection and treatment of this condition will be better understood.

Assessing the quality of life in age-related macular degeneration patients: a cross-sectional study in Kazakhstan.

The goal of this study was to assess Vision-Related Quality of Life (VRQoL) in patients with Age-Related Macular Degeneration (AMD) and identify its significant predictors. 458 AMD patients from four eye clinics in three major cities of Kazakhstan were recruited for this study. Data were collected using a structured questionnaire on sociodemographic and visual information and the National Eye Institute-VisualFunction Questionnaire-39 (NEI-VFQ-39). The study sample included 181 male patients who were 64.9 years on average (SD±8.4), and 277 female patients who were 68.7 years on average (SD±10.7). The majority of patients had stage 2 (43.7%) or stage 3 (40.2%) AMD according to the Age-Related Eye Disease Study (AREDS) classification. The mean (SD) NEI-VFQ-39 total score was 58.0 (23.8), range (9.8 - 100). The multiple linear regression model showed that the VRQoL of AMD patients correlated with the AMD stage according to the AREDS classification, age of the patients, visual acuity, number of years since the AMD diagnosis, and the city of residence. AMD causes severe vision impairment and daily functioning problems, reducing the quality of life of patients. To diagnose and treat degenerative eye disorders at an early stage, it is essential to inform patients about regular ophthalmological checkups to diagnose and treat degenerative eye disorders at an early stage.