A Comprehensive Evaluation of Serum Iron Status Indicators in Patients with Age-Related Macular Degeneration.

Objectives: Iron is recognized as a significant contributor to oxidative damage, and its levels tend to rise with age, potentially worsening age-related diseases. The aim of this study was to investigate the role of serum iron metabolism markers in the pathogenesis of age-related macular degeneration (AMD). Methods: The files of all AMD patients in Kocaeli University School of Medicine between January 2017 and March 2020 were reviewed retrospectively. By examining the files of AMD patients who applied to the eye outpatient clinic on the same dates, those dry AMD (dAMD) and neovascular AMD (nAMD) were recorded. As a control group, the records of patients without any AMD findings were obtained from the files of all patients who visited the clinic during the same time period. All records were recorded for analysis, including a comprehensive ophthalmological examination, laboratory data of fasting blood tests, and an internal medicine outpatient examination. Results: Of the 164 participants, 50 were dAMD patients, 51 were nAMD patients, and 63 were patients non-AMD (control group). There was a significant difference between the groups' mean corpuscular volume (MCV), serum ferritin, and total iron-binding capacity (TIBC) (p<0.050). It was observed that the ferritin of those with AMD was significantly higher than the control group, whereas MCV and TIBC were found to be significantly lower (p<0.050). There was no significant difference in serum iron marker levels between nAMD and dAMD patients (p>0.05). Conclusion: Assessing serum iron status indicators during the routine monitoring of AMD may provide insights into the associated risk profile of the condition.

Exploring the comparative regressive effects of aflibercept and faricimab on pigment epithelial detachment.

BACKGROUND: This study aimed to compare the regressive effects of aflibercept and faricimab on pigment epithelial detachment (PED) in patients with neovascular age-related macular degeneration. METHODS: In total, 41 eyes of 40 patients diagnosed with type 1 macular neovascularization were retrospectively analyzed using multimodal imaging. Of these, 23 eyes were treated with intravitreal aflibercept injections (IVA group), and 18 eyes were treated with intravitreal faricimab (IVFa group), with 3 consecutive injections administered as loading dose therapy. Before treatment and at 1, 2, and 3 months after the first treatment, the maximum height (MH) and maximum diameter (MD) of the PED were measured using optical coherence tomography in each treatment group. RESULTS: In the IVA group, the MH at baseline (215 ± 177 µm) was reduced to 141 ± 150 (P = 0.06), 119 ± 150 (P < 0.01), and 107 ± 150 µm (P < 0.0001) at 1, 2, and 3 months after treatment, respectively. Similarly, in the IVFa group, the MH decreased from 240 ± 195 µm before treatment to 165 ± 170 µm (P = 0.24), 139 ± 142 µm (P < 0.05), and 117 ± 112 µm (P < 0.01) at 1, 2, and 3 months after treatment, respectively. The reduction at 2 and 3 months was significant in both treatments. The mean changes of MH from baseline were -108 ± 142 µm in the IVA group and -124 ± 112 µm in the IVFa group, with no significant difference (P = 0.21). In both groups, the MD did not regress significantly. CONCLUSIONS: The results suggested that the MH of the PED between the IVA and IVFa groups regressed similarly after each loading therapy.

Predictors of Disease Activity After Anti-VEGF Treatment for Neovascular Age-Related Macular Degeneration Using Real-World Data from the PROOF Study.

INTRODUCTION: The aim of this study was to investigate the predictive factors for persistent disease activity following anti-vascular endothelial growth factors (anti-VEGF) and their long-term effects in patients to be treated for neovascular age-related macular degeneration (nAMD) under real-world conditions. METHODS: Retrospective data analysis of the PROOF study, a multi-center real-world retrospective chart review conducted across Korea in patients with nAMD included treatment-naive patients with nAMD who received first anti-VEGF (ranibizumab, bevacizumab, or aflibercept) between January 2017 and March 2019 was performed. All 600 patients (cohort 1) had a minimum follow-up of 12 months of which 453 patients (cohort 2) were followed-up for 24 months from baseline. RESULTS: At month 12 after anti-VEGF therapy, 58.10% (95% confidence interval [CI]: 54.09, 62.12) of patients and at month 24, 66.02% of patients continued to have persistent retinal fluid. At both months 12 and 24, predictive factors for persistent disease activity were fibrovascular pigment epithelial detachments (PED) (P = 0.0494) and retinal fluid at month 3 after loading phase (P = 0.0082). The mean changes in visual acuity were + 6.2, + 10.1, and + 13.3 letters and in the central subfield thickness were - 79.1 µm, - 96.3 µm, and - 134.4 µm at 12 months from baseline, in the bevacizumab, aflibercept, and ranibizumab groups, respectively. CONCLUSIONS: The presence of retinal fluid after loading phase and fibrovascular PED were predictors of persistent disease activity after at least 1 year of anti-VEGF treatment.

Artificial Intelligence-Based Disease Activity Monitoring to Personalized Neovascular Age-Related Macular Degeneration Treatment: A Feasibility Study.

Purpose: To evaluate the performance of a disease activity (DA) model developed to detect DA in participants with neovascular age-related macular degeneration (nAMD). Design: Post hoc analysis. Participants: Patient dataset from the phase III HAWK and HARRIER (H&H) studies. Methods: An artificial intelligence (AI)-based DA model was developed to generate a DA score based on measurements of OCT images and other parameters collected from H&H study participants. Disease activity assessments were classified into 3 categories based on the extent of agreement between the DA model's scores and the H&H investigators' decisions: agreement ("easy"), disagreement ("noisy"), and close to the decision boundary ("difficult"). Then, a panel of 10 international retina specialists ("panelists") reviewed a sample of DA assessments of these 3 categories that contributed to the training of the final DA model. A panelists' majority vote on the reviewed cases was used to evaluate the accuracy, sensitivity, and specificity of the DA model. Main Outcome Measures: The DA model's performance in detecting DA compared with the DA assessments made by the investigators and panelists' majority vote. Results: A total of 4472 OCT DA assessments were used to develop the model; of these, panelists reviewed 425, categorized as "easy" (17.2%), "noisy" (20.5%), and "difficult" (62.4%). False-positive and false negative rates of the DA model's assessments decreased after changing the assessment in some cases reviewed by the panelists and retraining the DA model. Overall, the DA model achieved 80% accuracy. For "easy" cases, the DA model reached 96% accuracy and performed as well as the investigators (96% accuracy) and panelists (90% accuracy). For "noisy" cases, the DA model performed similarly to panelists and outperformed the investigators (84%, 86%, and 16% accuracies, respectively). The DA model also outperformed the investigators for "difficult" cases (74% and 53% accuracies, respectively) but underperformed the panelists (86% accuracy) owing to lower specificity. Subretinal and intraretinal fluids were the main clinical parameters driving the DA assessments made by the panelists. Conclusions: These results demonstrate the potential of using an AI-based DA model to optimize treatment decisions in the clinical setting and in detecting and monitoring DA in patients with nAMD. Financial Disclosures: Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

Association of rheumatoid arthritis with age-related macular degeneration in nationwide longitudinal cohort study.

Previous studies on the association between age-related macular degeneration (AMD) and rheumatoid arthritis (RA) have shown conflicting results. We sought to assess the association between AMD with/without visual disability (VD) and the risk of RA using National Health Insurance data in South Korea. In total, 3,537,293 individuals who underwent health checkups in 2009 were included and followed until 2019. Participants with VD were defined as those with loss of vision or a visual field defect as certified by the Ministry of Health and Welfare of Korea. Using multivariable adjusted Cox regression analysis, RA hazard ratios were estimated for control and AMD with/without VD groups. In total, 43,772 participants (1.24%) were diagnosed with RA. Individuals with AMD were at higher risk of RA compared to controls, regardless of the presence of VD (aHR 1.11; 95% CI 1.02-1.21). Among individuals with AMD, different risk levels of RA were observed between those without VD (aHR 1.13; 95% CI 1.03-1.21) and those with VD (aHR 0.90; 95% CI 0.64-1.27). AMD was associated with a higher risk of RA, which remained significant as a trend even after adjusting for lifestyle factors and comorbidities.

Protective effect of ghrelin in oxidative stress-induced age-related macular degeneration in vitro and in vivo.

Oxidative damage to human retinal pigment epithelial (RPE) cells is the main cause of age-related macular degeneration (AMD), in our previous work, we showed that ghrelin has an antioxidative effect on human lens epithelium (HLE) cells, however, the studies of using ghrelin in treating the degenerative diseases of the retina have rarely been reported. In this article, we assessed the effect of ghrelin on preventing oxidative stress induced by hydrogen peroxide (H2O2) in ARPE-19 cells and its mechanism. We observed that pretreatment with ghrelin protected ARPE-19 cells from H2O2-induced cell oxidative injuries and apoptosis responses. Furthermore, an oxidative stress-induced mouse model of AMD was established via injection of sodium iodate (NaIO3) to tail veins, and treatment with ghrelin preserved retinal function, and protected photoreceptors.

Neurosensory retina detachment combined with retinal pigment epithelium separation from the choroid in the course of dry macular degeneration - A case report.

of advanced diagnostic methods shed the light on the variable course of age-related macular degeneration (AMD). Despite establishing AMD classifications used in clinical practice, there are still forms of AMD that do not fit into these systems. The case report presents a rare evolution of non-neovascular form of AMD presenting at baseline as large soft drusen. Within the 5 years of observation one eye with such form of AMD transformed to retinal pigment epithelial detachment and subsequently simultaneous separation of the neurosensory retina and the choroid from the RPE. As a result, on the spectral domain optical coherence tomography scan, the case presented with lone line of the RPE neighbored by subretinal fluid from the inner side and choroidal excavation from the outside. Macular neovascularization was excluded at each timepoint of the follow-up. During 2.5 years of observation post the onset of RPE separation, the case remained stable with maintained visual acuity at 0.25 Snellen and lack of progression to wet form of AMD. Further observation is needed to fully assess the eye's potential for visual preservation in the long term.

Harnessing the potential of mesenchymal stem cells-derived exosomes in degenerative diseases.

Mesenchymal stem cells (MSCs) have gained attention as a promising therapeutic approach in both preclinical and clinical osteoarthritis (OA) settings. Various joint cell types, such as chondrocytes, synovial fibroblasts, osteoblasts, and tenocytes, can produce and release extracellular vesicles (EVs), which subsequently influence the biological activities of recipient cells. Recently, extracellular vesicles derived from mesenchymal stem cells (MSC-EVs) have shown the potential to modulate various physiological and pathological processes through the modulation of cellular differentiation, immune responses, and tissue repair. This review explores the roles and therapeutic potential of MSC-EVs in OA and rheumatoid arthritis, cardiovascular disease, age-related macular degeneration, Alzheimer's disease, and other degenerative diseases. Notably, we provide a comprehensive summary of exosome biogenesis, microRNA composition, mechanisms of intercellular transfer, and their evolving role in the highlight of exosome-based treatments in both preclinical and clinical avenues.

A lipidomic study on the lens epithelial cells of patients with age related cataracts.

Age related cataracts (ARC) represent the main reason for blindness globally. The lens epithelial cells (LECs) participate not only in the metabolism of many substances in the lens but also in maintaining lens transparency. This study used lipidomics to investigate the metabolic differences in LECs of ARC patients with different severity, aiming at identifying potential metabolic biomarkers of ARC. Patients diagnosed with ARC and underwent cataract surgery at Shanghai Tongren Hospital were selected to participate in this study, which were classified as mild ARC group and severe ARC group. During their cataract surgery, anterior lens capsules(LCs) containing LECs were obtained. The lipidomics of LECs were analyzed using the liquid chromatography­mass spectrometry (LC-MS). Potential pathways of lipids were searched for using databases such as the Kyoto Encyclopedia of Genes and Genomes (KEGG) and MetaboAnalyst platform. In LEC lipids, 26 lipids have been identified as potential biomarkers between mild ARC and severe ARC, with AUC values of 0.67-0.94. The pathway analysis results revealed that the Glycerophospholipid (GPL) metabolism was significantly influenced, indicating that these metabolic markers contribute significantly to regulating this pathway. The LEC metabolic spectrum demonstrates a proficient ability to differentiate between patients with varying levels of cataracts. Herein, we have successfully identified potential metabolic biomarkers and pathways that have proven to be valuable in enhancing our understanding of ARC pathogenesis. The finding has translational value for developing new cataract treatment methods in the future.

[Effectiveness and safety of brolucizumab in the treatment of neovascular age-related macular degeneration]. / Effektivnost' i bezopasnost' brolutsizumaba v lechenii neovaskulyarnoi vozrastnoi makulyarnoi degeneratsii.

PURPOSE: This study analyzes the effectiveness and safety of brolucizumab in the treatment of neovascular age-related macular degeneration (nAMD) in real clinical practice. MATERIAL AND METHODS: The study included patients with nAMD who received brolucizumab treatment and evaluated the changes in best-corrected visual acuity (BCVA), central retinal thickness (CRT), macular volume, as well as the number of injections and adverse events. RESULT: The group of previously treated patients included 28 subjects (28 eyes) that were switched to brolucizumab with a loading phase. By 12 months, BCVA changed from 0.43±0.29 to 0.33±0.27 LogMAR (p=0.11), CRT decreased from 281.5±58.2 to 239.9±45.6 µm (p=0.02). The group of previously untreated patients included 29 subjects (29 eyes). By 12 months, BCVA changed from 0.47±0.32 to 0.40±0.30 LogMAR (p=0.09), CRT decreased from 333.2±77.3 to 226.2±49.6 µm (p<0.001). Patients received 6.3±0.7 injections. In this group, baseline choroidal thickness showed a statistically significant correlation with final visual acuity (r=0.54; p<0.05) and CRT (r= -0.5; p<0.05). The group of previously treated patients switched without a loading phase included 18 patients (18 eyes). By 6 months, BCVA changed from 0.42±0.2 to 0.37±0.26 LogMAR (p=0.42). CRT remained stable at 285.6±56.9 µm (p=0.97). No adverse events related to intraocular inflammation were reported during the course of 385 injections. CONCLUSION: Brolucizumab therapy helps achieve significant anatomical and functional improvements in real clinical practice both in patients switched from previous treatments and in treatment-naïve patients. Greater baseline choroidal thickness may be associated with better anatomical and functional outcomes with brolucizumab treatment.

What are the age-related factors linked to aseptic revisions in constrained and unconstrained TKA as well as UKA? A register-based study from the German arthroplasty registry (EPRD).

PURPOSE: The implantation rate of total knee arthroplasties (TKA) is continuously growing. Aseptic problems are a major cause of revision. The aim of the following study was to determinate the incidence of aseptic revisions in primary knee arthroplasty as well as aseptic revision rates and influencing factors according to the patients' age and type of procedure. METHODS: Data collection was performed using the German Arthroplasty Registry. Influencing factors were analyzed according to the patients' age and type of procedure. Risk factors were calculated using multiple Log-rank test with the Holm's method. Incidence and comparison of aseptic revisions according to the patients' age and type of procedure were analyzed using Kaplan-Meier-estimates. Cox regression was applied to calculate the hazard ratio. RESULTS: Overall, 300,998 knee arthroplasties with 254,144 (84.4%) unconstrained TKA, 9,993 (3.3%) constrained TKA and 36,861 (12.3%) unicondylar knee arthroplasties (UKA) were analyzed. Patients younger than 65 years suffered a significantly higher aseptic revision rate than older patients (p < 0.0001). After one year, a revision rate of 1.1% was recorded for patients 65-74 years, 1.6% for patients under 65 years, and 1.3% for patients beyond 74 years. After seven years, patients younger than 65 years sustained in 5.0%, patients 65-74 years in 2.9% and patients beyond 74 years in 2.4% revision. In unconstrained TKA, an increased Elixhauser-score (HR = 1,75; HR = 1,54; HR = 1,7; p < 0,001) was a risk factor regardless the age. A TKA volume of 101-250 regardless the age (HR = 0,66; HR = 0,69; HR = 0,79) and > 250 under 75 years (< 65: HR = 0,72; 65-74: HR = 0,78; p = 0,001) were protective for aseptic revision. In UKA, male gender (HR = 0,81; HR = 0,72; HR = 0,57; p < 0,001), a UKA volume ≥ 51 for patients under 75 years (< 65: HR = 0,62; 65-74: HR = 0,59; p = 0,003) as well as cemented UKA for patients younger than 75 years (< 65: HR = 0,37; 65-74: HR = 0,37; p < 0,001) were detected as preventive factors. CONCLUSION: A significant increased rate of aseptic revisions was reported for patients younger than 65 years compared to older patients. An increased Elixhauser score was a risk factor, whereas male and a high volume of performed UKA or TKA could be identified as preventive factors. LEVEL OF EVIDENCE: III, cohort study.

Atrophic Macular Degeneration and Stem Cell Therapy: A Clinical Review.

Age-related macular degeneration (AMD) is one of the leading causes of visual loss in older patients. No effective drug is available for this pathology, but studies about therapy with stem cells replacing the damaged retinal cells with retinal pigment epithelium (RPE) were described. The documentation of AMD progression and the response to stem cell therapy have been performed by optical coherence tomography, microperimetry, and other diagnostic technologies.This chapter reports a clinical review of the most important clinical trials and protocols regarding the use of stem cells in AMD.

Unilateral percutaneous balloon kyphoplasty for thoracic osteoporotic vertebral compression fractures: A case report and literature review.

Background: Unilateral percutaneous balloon kyphoplasty (PBK) is increasingly utilized for the management of osteoporotic vertebral compression fractures (OVCFs). Its potential advantages include procedural simplicity, reduced tissue trauma, and minimal radiation exposure. Case Description: A 59-year-old female with osteoporosis presented with back pain but was neurologically intact 2 weeks after a fall. The magnetic resonance imaging documented a thoracic 12 vertebral compression fracture that was successfully treated with a unilateral PBK. Conclusion: Unilateral PBK appears promising for managing OVCFs in the aging population and offers rapid pain relief, vertebral height restoration, and functional improvement.

Temporal localization of upper extremity bilateral synergistic coordination using wearable accelerometers.

Background: The human upper extremity is characterized by inherent motor abundance, allowing a diverse array of tasks with agility and adaptability. Upper extremity functional limitations are a common sequela to Stroke, resulting in pronounced motor and sensory impairments in the contralesional arm. While many therapeutic interventions focus on rehabilitating the weaker arm, it is increasingly evident that it is necessary to consider bimanual coordination and motor control. Methods: Participants were recruited to two groups differing in age (Group 1 (n = 10): 23.4 ± 2.9 years, Group 2 (n = 10): 55.9 ± 10.6 years) for an exploratory study on the use of accelerometry to quantify bilateral coordination. Three tasks featuring coordinated reaching were selected to investigate the acceleration of the upper arm, forearm, and hand during activities of daily living (ADLs). Subjects were equipped with acceleration and inclination sensors on each upper arm, each forearm, and each hand. Data was segmented in MATLAB to assess inter-limb and intra-limb coordination. Inter-limb coordination was indicated through dissimilarity indices and temporal locations of congruous movement between upper arm, forearm, or hand segments of the right and left limbs. Intra-limb coordination was likewise assessed between upper arm-forearm, upper arm-hand, and forearm-hand segment pairs of the dominant limb. Findings: Acceleration data revealed task-specific movement features during the three distinct tasks. Groups demonstrated diminished similarity as task complexity increased. Groups differed significantly in the hand segments during the buttoning task, with Group 1 showing no coordination in the hand segments during buttoning, and strong coordination in reaching each button with the upper arm and forearm guiding extension. Group 2's dissimilarity scores and percentages of similarity indicated longer periods of inter-limb coordination, particularly towards movement completion. Group 1's dissimilarity scores and percentages of similarity indicated longer periods of intra-limb coordination, particularly in the coordination of the upper arm and forearm segments. Interpretation: The Expanding Procrustes methodology can be applied to compute objective coordination scores using accessible and highly accurate wearable acceleration sensors. The findings of task duration, angular velocity, and peak roll angle are supported by previous studies finding older individuals to present with slower movements, reduced movement stability, and a reduction of laterality between the limbs. The theory of a shift towards ambidexterity with age is supported by the finding of greater inter-limb coordination in the group of subjects above the age of thirty-five. The group below the age of thirty was found to demonstrate longer periods of intra-limb coordination, with upper arm and forearm coordination emerging as a possible explanation for the demonstrated greater stability.

Switch to faricimab after initial treatment with aflibercept in eyes with neovascular age-related macular degeneration.

PURPOSE: To investigate the efficacy and outcomes of switching neovascular age-related macular degeneration (nAMD) patients from aflibercept to faricimab, focusing on visual acuity, retinal fluid management, and treatment intervals. The primary aim was to assess the early outcomes in nAMD patients refractory to aflibercept and explore faricimab's potential as a longer-lasting therapeutic alternative. METHODS: A single-center retrospective study was conducted on 50 refractory nAMD patients at Cleveland Clinic Abu Dhabi from September 2022-May 2023. Patients were switched from aflibercept to faricimab, having met specific criteria for refractory nAMD. The study analyzed best-corrected visual acuity (BCVA), central subfield thickness (CST), and fluid changes post-switch, using Optical Coherence Tomography (OCT). RESULTS: After three faricimab injections, significant reductions in CST were observed, with a notable decrease in retinal fluid. The mean BCVA remained stable throughout the study period. Although there was a decrease in the maximum pigment epithelial detachment (PED) height, it was not statistically significant. Treatment intervals post-switch showed that the majority of patients maintained or extended their treatment intervals, with a significant proportion achieving resolution of intraretinal fluid (IRF) and subretinal fluid (SRF). CONCLUSIONS: Switching to faricimab from aflibercept in refractory nAMD patients led to significant improvements in retinal fluid management and CST, with stable BCVA outcomes. Faricimab presents a promising alternative for patients requiring frequent aflibercept injections, potentially offering a more manageable treatment regimen with extended dosing intervals. This study highlights the need for personalized therapeutic strategies in nAMD treatment, though further research is necessary to optimize treatment switches.

A potential biomarker for age-related macular degeneration disease: iris freckles.

BACKGRAUND: To determine the potential relationship between age-related macular degeneration and iris freckles. METHOD: In this case-control study, iris photographs of 300 eyes of 300 patients diagnosed with age-related macular degeneration and 300 eyes of 300 healthy volunteers were obtained with the help of a high-resolution mobile phone camera. The evaluated iris photographs were classified according to the Descriptive Iris Color Classification Scale. RESULTS: The average age of the AMD group is 73.05 ± 6.93, and the average age of the control group is 73.43 ± 5.72. (p = 0.124) While freckles were present in 200 (66.7%) of the patients in the AMD group, freckles were not observed in 100 patients (33.3%) of AMD group. While freckles were present in 142 (47.3%) of the patients in the control group, freckles were not observed in 158 of control group(52.7%). There was a significant difference in the presence of freckles between the two groups. (p < 0.001) The average number of freckles in the AMD group was 3.97 ± 3.07, and the number of freckles in the control group was 3.06 ± 2.55. (p = 0.001) CONCLUSION: We think that evaluation of iris details, especially the presence of iris freckles, should be used routinely in age-related macular degeneration screening. The risk of age-related macular degeneration can be predicted by evaluating iris details, which is an easy and inexpensive method.

Age-related changes in connected speech production: evidence from eye-tracking in the culturally adapted picture description task.

Purpose: Age-related changes in connected speech production remain a subject of debate, yielding inconsistent findings across various tasks and measures. This study aimed to investigate the effects of aging on picture description tasks using two types of pictures: a standardized picture (the Beach picture) and a culturally and linguistically modified picture tailored for Korean speakers (the Han River picture). Method: Twenty-four young adults and 22 older adults participated in two picture description tasks while their eye movements were recorded. Word-level linguistic variables were used to assess informativeness (Correct Information Units per minute) and productivity (noun and verb counts per utterance) of connected speech production. Eye-movement measures were employed to evaluate real-time cognitive processing associated with planning connected speech (pre-speech fixation counts and durations; eye fixations before the speech onset of each utterance). Results and conclusions: The findings revealed age-related declines in linguistic measures, with older adults exhibiting decreased CIUs per minute and smaller counts of nouns and verbs per utterance. Age-related changes in eye movement measures were evident in that older adults displayed longer pre-speech fixation durations. Unlike younger adults, older adults exhibited higher pre-speech fixation counts on the Han River picture compared to the Beach picture, suggesting cognitive challenges in performing the task that requires producing more words and detailed descriptions. These results suggest that aging is associated with reduced informativeness and productivity of connected speech, as well as a decline in cognitive processing efficiency.

Elevated concentrations of amyloid-ß oligomers and their proapoptotic effects on age-related cataract.

Recently, amyloid-ß oligomers (AßOs) have been studied as the primary pathogenic substances in Alzheimer's disease (AD). Our previous study revealed that the Aß expression level is closely related to ARC progression. Here, we demonstrated that the accumulation of AßOs in the lens epithelium of age-related cataract (ARC) patients increased during ARC progression and that this alteration was consistent with the changes in mitochondrial function, oxidative stress, and cellular apoptosis. In vitro, human lens epithelial cells (HLECs) treated with AßOs exhibited Ca2+ dyshomeostasis, impaired mitochondrial function, elevated oxidative stress levels, and increased apoptosis. Moreover, the proapoptotic effect of AßOs was alleviated after the uptake of mitochondrial Ca2+ was inhibited. These results establish that AßOs may promote HLEC apoptosis by inducing mitochondrial Ca2+ overload, thus preliminarily revealing the possible association between the accumulation of AßOs and other pathological processes in ARC.

Quantifying Changes on OCT in Eyes Receiving Treatment for Neovascular Age-Related Macular Degeneration.

Purpose: Application of artificial intelligence (AI) to macular OCT scans to segment and quantify volumetric change in anatomical and pathological features during intravitreal treatment for neovascular age-related macular degeneration (AMD). Design: Retrospective analysis of OCT images from the Moorfields Eye Hospital AMD Database. Participants: A total of 2115 eyes from 1801 patients starting anti-VEGF treatment between June 1, 2012, and June 30, 2017. Methods: The Moorfields Eye Hospital neovascular AMD database was queried for first and second eyes receiving anti-VEGF treatment and had an OCT scan at baseline and 12 months. Follow-up scans were input into the AI system and volumes of OCT variables were studied at different time points and compared with baseline volume groups. Cross-sectional comparisons between time points were conducted using Mann-Whitney U test. Main Outcome Measures: Volume outputs of the following variables were studied: intraretinal fluid, subretinal fluid, pigment epithelial detachment (PED), subretinal hyperreflective material (SHRM), hyperreflective foci, neurosensory retina, and retinal pigment epithelium. Results: Mean volumes of analyzed features decreased significantly from baseline to both 4 and 12 months, in both first-treated and second-treated eyes. Pathological features that reflect exudation, including pure fluid components (intraretinal fluid and subretinal fluid) and those with fluid and fibrovascular tissue (PED and SHRM), displayed similar responses to treatment over 12 months. Mean PED and SHRM volumes showed less pronounced but also substantial decreases over the first 2 months, reaching a plateau postloading phase, and minimal change to 12 months. Both neurosensory retina and retinal pigment epithelium volumes showed gradual reductions over time, and were not as substantial as exudative features. Conclusions: We report the results of a quantitative analysis of change in retinal segmented features over time, enabled by an AI segmentation system. Cross-sectional analysis at multiple time points demonstrated significant associations between baseline OCT-derived segmented features and the volume of biomarkers at follow-up. Demonstrating how certain OCT biomarkers progress with treatment and the impact of pretreatment retinal morphology on different structural volumes may provide novel insights into disease mechanisms and aid the personalization of care. Data will be made public for future studies. Financial Disclosures: Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

An in-depth understanding of the role and mechanisms of T cells in immune organ aging and age-related diseases.

T cells play a critical and irreplaceable role in maintaining overall health. However, their functions undergo alterations as individuals age. It is of utmost importance to comprehend the specific characteristics of T-cell aging, as this knowledge is crucial for gaining deeper insights into the pathogenesis of aging-related diseases and developing effective therapeutic strategies. In this review, we have thoroughly examined the existing studies on the characteristics of immune organ aging. Furthermore, we elucidated the changes and potential mechanisms that occur in T cells during the aging process. Additionally, we have discussed the latest research advancements pertaining to T-cell aging-related diseases. These findings provide a fresh perspective for the study of T cells in the context of aging.