Macular Degeneration Research Articles

Associations of mediterranean diet score and age-related macular degeneration in Korean elderly

BackgroundPrevious studies have reported associations between individual nutrients or specific foods and the risk of age-related macular degeneration (AMD). However, the relationship between overall dietary quality, specifically the alternative Mediterranean diet (aMED) score, and AMD remains unclear. Therefore, this study aimed to investigate the association between the aMED score, as an indicator of overall diet quality, and AMD in the Korean population.MethodsWe conducted a cross-sectional analysis using nationally representative samples of older adults aged ≥ 65 years (895 men and 1,191 women) from the Korea National Health and Nutrition Examination Survey (2017–2018). Food intake and the aMED score were estimated using 24-h recall. AMD was diagnosed by an ophthalmologist based on fundus photography. The associations of aMED score tertiles with AMD were determined using odds ratios (ORs) from multivariate logistic regressions.ResultsMultiple logistic regression analysis revealed a significantly negative association between the aMED score and AMD (adjusted ORs = 0.58; 95% confidence interval = 0.39–0.88; p-trend = 0.021) in older men after adjusting for confounding factors such as age, body mass index, family monthly income, current smoking, alcohol consumption, physical activity, chronic disease status, and energy intake. Notably, this association was exclusively observed in men, and no significant association was observed between the aMED score and AMD in women (adjusted OR = 0.88; 95% CI = 0.61–1.29; p-trend = 0.691).ConclusionsThis study’s findings suggest that a high aMED score may be associated with a reduced risk of AMD in older men. Future studies with larger sample sizes and a prospective or interventional design are required to enhance current understanding regarding the association between diet quality and AMD.

Incidence and progression of age-related macular degeneration among patients with and without obstructive sleep apnea: a national cohort study.

Obstructive sleep apnea (OSA) may increase the risk of age-related macular degeneration (AMD) due to repetitive oxygen deprivation or other mechanisms, though whether OSA increases the risk of AMD progression is unknown. We analyzed associations between OSA and AMD risk in the Taiwanese population. We identified patients diagnosed with OSA between 2000 and 2018 in the Taiwan National Health Insurance Research Database and used 1:1 propensity score matching on demographics and co-morbidities to create a non-OSA cohort. We used Cox proportional hazard modeling to investigate the risk of AMD and the risk of progression from nonexudative to exudative AMD in OSA versus non-OSA patients. A total of 66,869 OSA patients were matched with 66,869 non-OSA patients. The hazard ratio (HR) of AMD in the OSA cohort was 1.36 (95% confidence interval[CI]: 1.31-1.43, p<.0001). The HR for progression from nonexudative to exudative AMD for the OSA cohort was 0.94 (95%CI: 0.77-1.14, p=0.5073). OSA is associated with a higher risk of developing AMD. However, no increased risk of AMD progression is observed among people with OSA and existing non-exudative AMD.

Ghost vessels in the eye: Cell free choriocapillaris domains in atrophic age-related macular degeneration

The choriocapillaris is a dense vascular bed in the inner choroid that supplies the photoreceptor cells and retinal pigment epithelium (RPE). While loss of choriocapillaris density has been described in association with age-related macular degeneration (AMD), whether these changes are primary or secondary to RPE degenerative changes in AMD has been debated. In this study we characterized choriocapillaris loss by quantifying “ghost” vessels in a series of 99 human donor maculae labeled with the UEA-I lectin, and found significant increases in early-intermediate AMD and a greater difference in geographic atrophy in areas with intact RPE. Eyes were genotyped at the CFH Tyr402His locus, and those homozygous for the His allele showed significantly more ghost vessels than those with other genotypes. When only non-AMD eyes were evaluated, His homozygotes had increased ghost vessel density but this trend did not reach statistical significance. These results support the notion that choriocapillaris death often precedes RPE degeneration in AMD and that this loss is an important therapeutic consideration for AMD.

Precision Segmentation of Subretinal Fluids in OCT Using Multiscale Attention-Based U-Net Architecture.

This paper presents a deep-learning architecture for segmenting retinal fluids in patients with Diabetic Macular Oedema (DME) and Age-related Macular Degeneration (AMD). Accurate segmentation of multiple fluid types is critical for diagnosis and treatment planning, but existing techniques often struggle with precision. We propose an encoder-decoder network inspired by U-Net, processing enhanced OCT images and their edge maps. The encoder incorporates Residual and Inception modules with an autoencoder-based multiscale attention mechanism to extract detailed features. Our method shows superior performance across several datasets. On the RETOUCH dataset, the network achieved F1 Scores of 0.82 for intraretinal fluid (IRF), 0.93 for subretinal fluid (SRF), and 0.94 for pigment epithelial detachment (PED). The model also performed well on the OPTIMA and DUKE datasets, demonstrating high precision, recall, and F1 Scores. This architecture significantly enhances segmentation accuracy and edge precision, offering a valuable tool for diagnosing and managing retinal diseases. Its integration of dual-input processing, multiscale attention, and advanced encoder modules highlights its potential to improve clinical outcomes and advance retinal disease treatment.

Fluid Resolution Without Shortening Injection Interval During Subretinal Fluid-tolerating Treatment in Neovascular Age-related Macular Degeneration.

To investigate the incidence and factors associated with subretinal fluid(SRF) resolution during SRF-tolerating treatment in patients with neovascular age-related macular degeneration(AMD). This retrospective study included patients diagnosed with neovascular AMD who exhibited fovea-involving residual SRF persisting for at least 6 months during aflibercept treatment. Patients who showed SRF resolution despite maintaining the injection intervals were included in the resolution group, while those who exhibited persisting SRF throughout the study period were included in the non-resolution group. The incidence and associated factors of SRF resolution without reducing the injection interval were evaluated. Furthermore, the frequency of successfully extending the injection intervals while maintaining SRF resolution was identified. In total, 65 patients with neovascular AMD were included(32 and 33 in the resolution and non-resolution groups, respectively). When compared to the non-resolution group, the resolution group showed a lower mean height of SRF(67.7±33.4 vs 109.9±44.9 µm, P<0.001) and a lower maximum height of SRF(138.3±88.6 vs 176.2±76.9 µm, P=0.034). In multivariate analysis, the mean SRF height(P=0.001), maximum SRF height(P=0.006), and interval of anti-vascular endothelial growth factor injections(P=0.023) were significantly associated with the resolution of SRF. In the resolution group, 14 patients(43.8%) successfully expanded the injection interval. During SRF-tolerating treatment for neovascular AMD, a substantial proportion of patients exhibited resolution of fluid without shortening the injection interval. Patients with lesser residual SRF during treatment were more likely to achieve fluid resolution. Following SRF resolution, injection intervals can be extended in more than 40% of patients.

Regualtion of LAMTOR1 by Oxidative Stress in Retinal Pigment Epithelium: Implications for Age-Related Macular Degeneration Pathogenesis

Oxidative stress is a critical pathogenic factor for age-related macular degeneration (AMD). Autophagy serves as a mechanism to counteract oxidative stress. LAMTOR1 regulates mTORC1 activity by recruiting or disassembling it on the lysosome under the addition or deprivation of amino acids. This regulation inhibits or enhances autophagy. Our study investigates whether oxidative stress impacts LAMTOR1, thereby adapting to oxidative conditions. We employed oxidative stressors, menadione (VK3) and 4-hydroxynonenal (4-HNE), and observed a reduction of LAMTOR1 in both human and mouse retinal pigment epithelium (RPE) following short-term (1h) and prolonged exposures (24h). Nrf2 overexpression increased both lamtor1 mRNA and LAMTOR1 protein in the RPE. To determine if Nrf2 regulates lamtor1 transcription, we cloned the deletion mutants of the lamtor1 promoter into a luciferase reporter. Although the promoter contained antioxidant response elements, transcriptional activity depended on the interaction between Nrf2 and the constructs containing the transcriptional start site. Moreover, Nrf2-driven transcription was significantly reduced by an inhibitor of histone acetyltransferase, p300. Correspondingly, Nrf2 overexpression increased levels of acetylated histone3 and p300. The reduction in LAMTOR1 by 4-HNE was reversed by pepstatin A and NH4Cl which block lysosomal degradation. 4-HNE increased TFEB nuclear translocation which was reversed by LAMTOR1 overexpression. In vivo, LAMTOR1 levels decreased in the photoreceptor and RPE layers of NaIO3-injected mice, compared to PBS-injected controls. In conclusion, oxidative injury reduces LAMTOR1, predominantly through lysosomal degradation although Nrf2-mediated histone acetylation enhances lamtor1 transcription. This study reveals a previously unrecognized regulatory mechanism of lamtor1 by oxidative stress, suggesting a novel role for LAMTOR1 in the pathogenesis of AMD.

Complete retinal pigment epithelium and outer retinal atrophy: Is it really an end-stage atrophy?

Geographic atrophy (GA), a late manifestation of age-related macular degeneration (AMD), leads to irreversible vision loss. Early identification of precursor lesions, such as incomplete and complete retinal pigment epithelium and outer retinal atrophy (iRORA and cRORA), is crucial for predicting GA formation. The latter stage has been associated with irreversible and progressive changes, and the eventual development of a dense scotoma on the compromised area. We present an 80-year-old woman with AMD in both eyes, demonstrating progressive changes over a 2-year follow-up. While the right eye developed cRORA with vision decline, the left eye exhibited unexpected restoration of the outer retinal layers within the cRORA lesion. This finding challenges the notion of "end-stage atrophy" in GA development and highlights the potential reversibility of early atrophic lesions. Recognizing these dynamics has implications for the development of targeted therapies aimed at preserving vision in AMD's early stages.

Association of polymorphisms in the HTRA1 gene with myopia

PurposeTo evaluate the associations of single-nucleotide polymorphisms (SNPs) in the high-temperature requirement protease A 1 (HTRA1) gene with myopia.Methods25 SNPs in HTRA1 were selected, including 23 haplotype-tagging SNPs, SNP rs2142308...

Splice variant of retinal G-protein-coupled receptor deletion (RGR-d)-mediated dysregulation of autophagy increases the susceptibility to age-related macular degeneration-like defects.

The splice variant of retinal G-protein-coupled receptor deletion (RGR-d) is a persistent component of drusen and may be involved in the pathogenesis of dry age-related macular degeneration (AMD). Increasing evidence has demonstrated the critical role of autophagy in AMD. In this study, we investigated whether RGR-d disrupts autophagy in early dry AMD in vivo and in vitro. Fundus imaging and fluoroscopy were performed on RGR-d mice created by multiplex gene editing. The retina microstructure was evaluated by performing hematoxylin and eosin (H&amp;E) staining as well as transmission electron microscopy (TEM). Retinal function was assessed by full-field electroretinography (ERG). After lentivirus transfection and stimulation, the permeability, phagocytosis, and tight junctions of ARPE-19 cells were evaluated. Western blotting of ATG5, beclin-1, LC3II/I, and P62 was performed to detect the changes in autophagy pathways. Atrophy and patchy penetrating hyperfluorescent foci, consistent with early AMD-like defects, were observed in the fundus of 12-month-old RGR-d mice. H&amp;E staining of retinal tissues indicated thinning of each layer of the retinal structure. H&amp;E staining of retinal tissues indicated thinning of each layer of the retinal structure. TEM analysis showed some diffuse granular deposits. And the morphology of choroidal microvascular endothelial cells was degraded and distorted. The morphology of the photoreceptor outer segments showed structural damage and Bruch's membrane was thickened. ERG indicated that the photoreceptor of RGR-d mice were dysfunctional. Changes in autophagy-related protein expression were observed in the retinal pigment epithelium and retinal neuroepithelium, and autophagy regulation was decreased. Palmitic acid (PA) stimulation caused permeability, phagocytosis, and tight junction dysfunction in cells overexpressing RGR-d. Beclin-1 and LC3II/I expression levels were significantly decreased and that of P62 was elevated in RGR-d cells after PA stimulation. RGR-d disrupts the autophagy pathway, causing the development of an early AMD-like pathophysiology.

Foveal hyper-reflective vertical lines detected by optical coherence tomography: Imaging features, literature review and differential diagnoses.

To describe foveal hyper-reflective vertical lines (FVL) as a specific morphological finding on structural spectral-domain optical coherence tomography (SD-OCT) and discuss its differential diagnosis. Observational case series. Ten patients (10 eyes) with FVL were meticulously examined at the Ophthalmology Department, Shaare Zedek Medical Center, Jerusalem, Israel. Detailed analysis of SD-OCT findings, clinical records, and retinal imaging was conducted to establish correlations between FVL and various underlying conditions. We established the following list of settings, supported by the clinical context and ancillary investigations, in which SD-OCT displayed FVL: inflammation (1 eye), mechanical (1 eye), resorption of fluids of various origins (4 eyes), macular telangiectasia (1 eye), age-related macular degeneration (1 eye), diabetic retinopathy (1 eye) and scar (1 eye). FVL can be observed in various underlying conditions. Recognition of this pattern and formulation of an appropriate differential diagnosis is of interest for correctly diagnosing and treating patients whose structural OCT harbors this yet overlooked finding.

Serial intravitreal injections in age-related macular degeneration patients from the dry eye disease perspective: a cross-sectional study

BackgroundTo evaluate the effects of serial intravitreal injections (IVI) on the ocular surface and meibomian glands in patients with neovascular age-related macular degeneration (nAMD).MethodsPatients receiving anti-vascular endothelial growth factor (anti-VEGF) agent injections for unilateral nAMD were included. Untreated fellow eyes served as the control group. All participants followed a pre-IVI asepsis protocol with povidone-iodine (PI). Ocular surface diseases index (OSDI) questionnaire scores, first and average non-invasive tear break-up time (fNITBUT and avgNITBUT), Schirmer-1 test results, corneal staining score (according to Oxford scale), meibomian gland (MG) loss rates of lower and upper eyelids were recorded four weeks after the last IVI.ResultsForty-two nAMD patients with a mean age of 63.3 ± 19.4 were included in the study. The mean OSDI score was 20.3 and the median of IVI number was 9 (6–22). There were no statistically significant difference between treated and untreated fellow eyes regarding fNITBUT (5.6 vs. 4.5, p = 0.872), avgNITBUT (6.2 vs. 7.2, p = 0.968), Shirmer-1 results (7 vs. 7, p = 0.854), corneal staining (0.3 vs. 0.2, p = 0.341), lower and upper MG loss rate (29.3 vs. 28.4, p = 0.162, and 27.1 vs. 26.9, p = 0.476, respectively). Only significant correlation was observed between age with lower and upper MG loss rate (r:0.396, p = 0.042, and r:0.365, p = 0.047).ConclusionThe results of the present study demonstrated that serial IVI of anti-VEGF agents with PI asepsis is well tolerated by nAMD patients in terms of ocular surface, MG loss and DED measurements.

Artificial intelligence-based analysis of retinal fluid volume dynamics in neovascular age-related macular degeneration and association with vision and atrophy.

To characterise morphological changes in neovascular age-related macular degeneration (nAMD) during anti-angiogenic therapy and explore relationships with best-corrected visual acuity (BCVA) and development of macular atrophy (MA). Post-hoc analysis of the phase III HARBOR trial. SD-OCT scans from 1097 treatment-naïve nAMD eyes were analysed. Volumes of intraretinal cystoid fluid (ICF), subretinal hyperreflective material (SHRM), subretinal fluid (SRF), pigment epithelial detachment (PED) and cyst-free retinal volume (CFRV) were measured by deep-learning model. Volumes were analysed by treatment regimen, macular neovascularisation (MNV) subtypes and topographic location. Associations of volumetric features with BCVA and MA development were quantified at month 12/24. Differences in feature volume changes by treatment regimens and MNV subtypes were observed. Each additional 100 nanolitre unit (AHNU) of residual ICF, SHRM and CFRV at month 1 in the fovea was associated with deficits of 10.3, 7.3 and 12.2 letters at month 12. Baseline AHNUs of ICF, CFRV and PED were associated with increased odds of MA development at month 12 by 10%, 4% and 3%. While that of SRF was associated with a decrease in odds of 5%. Associations at month 24 were similar to those at month 12. Eyes with different MNV subtypes showed distinct trajectories of feature volume response to treatment. Higher baseline volumes of ICF or PED and lower baseline volume of SRF were associated with higher likelihoods of MA development over 24 months. Residual intraretinal fluid, including ICF and CFRV, along with SHRM were predictors of poor visual outcomes.

Adjusting for Glycemic Control in Assessing the Relationship Between Age-Related Macular Degeneration and Diabetic Retinopathy

Adjusting for Glycemic Control in Assessing the Relationship Between Age-Related Macular Degeneration and Diabetic Retinopathy

Faricimab versus bevacizumab for neovascular age-related macular degeneration: Cost analysis based on real-world data from the Swedish Macula Registry.

To analyse the impact on cost if faricimab is used as the first-line treatment for neovascular age-related macular degeneration (nAMD) compared to standard treatment with bevacizumab. Retrospective registry study including real-world data from the Swedish Macula Registry between 2017 and 2022. The observed number of injections and visits for bevacizumab during the first two years of treatment was used (n = 437 patients). Number of faricimab injections was obtained from published clinical trial data and unit costs mostly from publicly available Swedish sources. The provider cost included medication and visit cost and societal cost included additionally patient travel cost. Costs are presented in 2023 EUR. The incremental societal cost of faricimab was 277 EUR per patient compared to bevacizumab in the base case. Medication cost was higher (1516 EUR) while visit cost (-1183 EUR) and patient travel cost (-56 EUR) were lower due to longer injection intervals. Faricimab was of similar cost as bevacizumab for patients residing far from the clinic. The faricimab injection interval and the number of bevacizumab injections were major drivers of uncertainty in the results. Faricimab represents a cost-effective alternative to bevacizumab for patients with nAMD in Sweden. Its extended treatment interval is particularly beneficial for patients living far from clinics, and if the real-life faricimab injection interval extends beyond 12 weeks. Our findings emphasize faricimab's potential to free up healthcare staff to treat a larger patient population with existing clinic resources.

Review of type 3 macular neovascularization in age-related macular degeneration: no DRAMA (Deep Retinal Age-related Microvascular Anomalies).

Type 3 macular neovascularization (MNV) is a unique form of neovascular age-related macular degeneration (AMD) that presents distinct pathogenetic features, clinical manifestations, and prognostic considerations when compared to types 1 and 2 MNV. Insights gained from clinicopathological correlations, bridging in vivo examination techniques with ex vivo histological analysis, have significantly enhanced our comprehension of this MNV phenotype, shaped current management strategies and influenced future directions for therapeutics. The particularities of type 3 MNV, which may largely stem from its origin from the retinal vasculature, are critically important for predicting the disease course. Our current understanding suggests that type 3 MNV occurs in response to retinal pigment epithelium (RPE) disruption and photoreceptor loss when neovessels originating from the deep capillary plexus are accompanied by activated Müller glia as they infiltrate sub-retinal pigment epithelium basal laminar deposits. Dysregulation of angiogenic and angiostatic factors are thought to play a key role in its pathogenesis. The prognosis for type 3 MNV is likely bilateral involvement and progression towards macular atrophy. It may be imperative for practitioners to distinguish type 3 MNV from other mimicking pathologies such as intraretinal microvascular anomalies, which are also part of the type 3 disease spectrum. For instance, deep retinal age-related microvascular anomalies (DRAMA) may present with similar features on multimodal imaging yet may necessitate distinct management protocols. Distinguishing between these conditions may be vital for implementing tailored treatment regimens and improving patient outcomes in the diverse landscape of AMD phenotypes in the future.

An epidemiological survey of visual impairment in rural populations aged 30 and above: the Handan Eye Study

Objective: To investigate the changes in prevalence and causes of blindness and visual impairment over six years among rural populations aged 30 and above in Yongnian County, Handan City, Hebei Province, a pilot area in northern China for blindness prevention and treatment, and to study the incidence of common blinding eye diseases. Methods: This population-based prospective cohort study included a baseline survey conducted from 2006 to 2007 using stratified cluster sampling, targeting 6 830 Han Chinese individuals aged 30 and above, with a response rate of 90.4%, and a follow-up survey conducted from 2012 to 2013 with 5 394 participants, maintaining a response rate of 85.3%. Visual impairment was defined according to World Health Organization standards as visual acuity<20/60 but ≥20/400, and blindness as visual acuity<20/400. Age-and gender-standardized prevalence rates of blindness and visual impairment, along with their 95% confidence intervals (CI), were estimated. The six-year incidence rates of primary glaucoma, age-related macular degeneration, and myopic maculopathy, along with their 95%CI, were reported. Results: At baseline, the standardized prevalence of bilateral blindness in individuals aged 30 and above was 0.6% (41/6 799) for presenting visual acuity and 0.5% (31/6 799) for best-corrected visual acuity. These rates were higher than those found in the follow-up survey, 0.5% (27/5 293) and 0.3% (17/5 276). Conversely, the standardized prevalence of bilateral visual impairment increased from 4.7% (361/6 799) and 1.0% (85/6 799) at baseline to 6.5% (355/5 293) and 1.4% (74/5 276) at follow-up, respectively. The leading cause of bilateral blindness was cataract in both baseline (13/31, 41.9%) and follow-up (7/17) surveys. Other major causes included myopic retinal degeneration (5/31, 16.1% at baseline; 2/17 at follow-up), glaucoma (3/31, 9.7% at baseline; 2/17 at follow-up), and corneal opacity (3/31, 9.7% at baseline; 2/17 at follow-up). Over six years, the incidence rates for primary glaucoma, early and late age-related macular degeneration, and myopic maculopathy in individuals aged 35 and above were 1.6% (95%CI: 1.2%-1.9%), 4.2% (95%CI: 3.8%-4.7%), 0.2% (95%CI: 0.2%-0.3%), and 0.1% (95%CI: 0.0%-0.2%), respectively. Conclusions: The prevalence of bilateral blindness in the rural population of Yongnian County, Handan City, Hebei Province, decreased over six years due to blindness prevention and treatment efforts but remained higher than in urban areas. Meanwhile, the prevalence of bilateral visual impairment increased since the baseline survey. Cataracts continued to be the primary cause of blindness, followed by myopic retinal degeneration, glaucoma, and corneal opacity.

TdCoxSNN: Time-dependent Cox survival neural network for continuous-time dynamic prediction

Abstract The aim of dynamic prediction is to provide individualized risk predictions over time, which are updated as new data become available. In pursuit of constructing a dynamic prediction model for a progressive eye disorder, age-related macular degeneration (AMD), we propose a time-dependent Cox survival neural network (tdCoxSNN) to predict its progression using longitudinal fundus images. tdCoxSNN builds upon the time-dependent Cox model by utilizing a neural network to capture the nonlinear effect of time-dependent covariates on the survival outcome. Moreover, by concurrently integrating a convolutional neural network with the survival network, tdCoxSNN can directly take longitudinal images as input. We evaluate and compare our proposed method with joint modelling and landmarking approaches through extensive simulations. We applied the proposed approach to two real datasets. One is a large AMD study, the Age-Related Eye Disease Study, in which more than 50,000 fundus images were captured over a period of 12 years for more than 4,000 participants. Another is a public dataset of the primary biliary cirrhosis disease, where multiple laboratory tests were longitudinally collected to predict the time-to-liver transplant. Our approach demonstrates commendable predictive performance in both simulation studies and the analysis of the two real datasets.

Real-world six-month outcomes in patients switched to faricimab following partial response to anti-VEGF therapy for neovascular age-related macular degeneration and diabetic macular oedema.

Landmark studies reported on faricimab efficacy and safety predominantly in treatment naïve patients, but outcomes following switch from other anti-VEGF therapies are lacking. We evaluated patients switched to faricimab who hadpreviously shown a partial response to other anti-VEGF injections for neovascular age-related macular degeneration (nAMD) and diabetic macular oedema (DMO). Retrospective study at the Oxford Eye Hospital. Patients switched to faricimab from January to April 2023 with six months follow-up were identified via electronic medical records. A total of 116 patients (151 eyes) were included. In 88 patients with nAMD (107 eyes), mean visual acuity remained stable: 62±17 ETDRS letters at baseline; 62±18 at six months (p > 0.05). Central subfield thickness (CST) reduced from 294 ± 73 μm to 270 ± 53 μm (p < 0.05) at six months. Subretinal or intraretinal fluid was present in 102 eyes (95%) at baseline and 75 eyes (70%) at follow-up (p < 0.05). Pigment epithelial detachment height decreased from 233 ± 134 μm to 188 ± 147 μm (p < 0.05). Mean treatment interval increased by 1.7 weeks (p < 0.05) and was extended in 61 eyes (57%) at six months. In 28 patients with DMO (44 eyes), visual acuity remained stable: 69 ± 15 letters at baseline; 70±15 at six months (p > 0.05). CST reduced from 355 ± 87 μm to 317 ± 82 μm (p < 0.05). Mean treatment interval increased by 1.4 weeks (p < 0.05) and was extended in 21 eyes (46%) by six months. Switching to faricimab in treatment resistant eyes led to improved anatomical response and extended treatment interval in a significant proportion of patients. Ongoing review of real-world data will inform longer-term outcomes of safety and effectiveness.

Ophthalmic Use of Targeted Biologics in the Management of Intraocular Diseases: Current and Emerging Therapies.

Monoclonal antibodies (mAbs) have demonstrated substantial potential in the treatment of intraocular diseases. This review aimed to comprehensively evaluate the applications, efficacy, and safety of mAbs in the management of intraocular conditions. A comprehensive literature search was conducted in major medical databases through July 2024. Relevant studies on monoclonal antibodies for intraocular diseases were included. Two independent researchers screened the literature, extracted data, and assessed study quality. Cost-effectiveness analyses were also reviewed. Anti-vascular endothelial growth factor (VEGF) antibodies, such as bevacizumab, ranibizumab, and aflibercept, showed significant therapeutic effects in neovascular age-related macular degeneration (NVAMD), diabetic macular edema (DME), and retinal vein occlusion (RVO). Tumor necrosis factor-alpha (TNF-α) inhibitors demonstrated promising results in treating noninfectious uveitis. Complement system-targeted therapies like pegcetacoplan offered new options for geographic atrophy. Anti-VEGF antibodies showed potential in managing retinopathy of prematurity (ROP). However, challenges persist, including high costs, potential drug resistance, and limited long-term safety data in certain scenarios. Monoclonal antibodies are vital for treating intraocular diseases, but continuous innovation and rigorous clinical evaluation are essential. Future research should focus on developing novel delivery systems, exploring combination therapies, conducting long-term follow-up studies, and investigating personalized treatment strategies to provide safer, more effective, and cost-effective therapeutic solutions.

Proteomics Analysis on the Effects of Oxidative Stress and Antioxidants on Proteins Involved in Sterol Transport and Metabolism in Human Telomerase Transcriptase-Overexpressing-Retinal Pigment Epithelium Cells.

Age-related macular degeneration (AMD) is the most prevalent ocular disease in the elderly, resulting in blindness. Oxidative stress plays a role in retinal pigment epithelium (RPE) pathology observed in AMD. Tocopherols are potent antioxidants that prevent cellular oxidative damage and have been shown to upregulate the expression of cellular antioxidant proteins. Here, we determined whether oxidative stress and tocopherols, using either normal cellular conditions or conditions of sublethal cellular oxidative stress, alter the expression of proteins mediating sterol uptake, transport, and metabolism. Human telomerase transcriptase-overexpressing RPE cells (hTERT-RPE) were used to identify differential expression of proteins resulting from treatments. We utilized a proteomics strategy to identify protein expression changes in treated cells. After the identification and organization of data, we divided the identified proteins into groups related to biological function: cellular sterol uptake, sterol transport and sterol metabolism. Exposure of cells to conditions of oxidative stress and exposure to tocopherols led to similar protein expression changes within these three groups, suggesting that α-tocopherol (αT) and γ-tocopherol (γT) can regulate the expression of sterol uptake, transport and metabolic proteins in RPE cells. These data suggest that proteins involved in sterol transport and metabolism may be important for RPE adaptation to oxidative stress, and these proteins represent potential therapeutic targets.