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To analyze the associations between development of age-related macular degeneration (AMD) and regular use of aspirin or non-aspirin non-steroidal anti-inflammatory drugs (NA-NSAIDs). We retrospectively recruited individuals who received ≥28-day prescriptions of aspirin or NA-NSAIDs exclusively between 2008 and 2017 in one tertiary center as regular users. Non-regular users were free from regular use of any anti-inflammatory drugs and were matched to regular users in terms of age, sex, and visit date at a ratio of 1–4:1. The aspirin cohort included 36,771 regular users and 110,808 matched non-regular users, while the NA-NSAID cohort included 59,569 regular users and 179,732 matched non-regular users. Stratified multivariate Cox regression analyses with adjustment for systemic confounding factors were performed for the development of AMD and neovascular AMD. In the aspirin cohort, the adjusted hazard ratios of aspirin use for AMD in the whole cohort, individuals without cardiovascular diseases (CVDs), and those with CVDs were 0.664, 0.618, and 0.702, respectively (P < 0.0001 for all), while those of aspirin use for neovascular AMD were 0.486, 0.313, and 0.584 (P < 0.05 for all), respectively. In the NA-NSAID cohort, regular use of NA-NSAIDs was associated with a decreased risk of AMD (hazard ratio = 0.823, P < 0.0001) and neovascular AMD (hazard ratio = 0.720, P = 0.040) only in people without arthritis. Regular use of aspirin or NA-NSAIDs had protective effects on AMD and neovascular AMD. The effect of aspirin was observed in all patients, while the effect of NA-NSAIDs was observed only in people without arthritis. [ABSTRACT FROM AUTHOR]

Inflammation is involved in the pathogenesis of cataract, age-related macular degeneration (AMD), and possibly open-angle glaucoma (OAG). We assessed whether the inflammatory potential of diet (quantified using the dietary inflammatory index; DII) affects the incidence of these common blinding age-related eye diseases. Serum inflammation markers were investigated as possible mediators. Participants aged >45 years were selected from the prospective, population-based Rotterdam Study. From 1991 onwards, every 4–5 years, participants underwent extensive eye examinations. At baseline, blood samples and dietary data (using food frequency questionnaires) were collected. The DII was adapted based on the data available. Of the 7436 participants free of eye diseases at baseline, 4036 developed incident eye diseases during follow-up (cataract = 2895, early-intermediate AMD = 891, late AMD = 81, OAG = 169). The adapted DII (aDII) ranged from −4.26 (i.e., anti-inflammatory) to 4.53 (i.e., pro-inflammatory). A higher aDII was significantly associated with increased inflammation. A higher neutrophil-lymphocyte ratio (NLR) was associated with an increased risk of cataract and AMD. Additionally, complement component 3c (C3c) and systemic immune-inflammation index (SII) were associated with increased risks of cataract and late AMD, respectively. Every point increase in the aDII was associated with a 9% increased risk of cataract (Odds ratio [95% confidence interval]: 1.09 [1.04–1.14]). The NLR and C3c partly mediated this association. We also identified associations of the aDII with risk of AMD (early-intermediate AMD, OR [95% CI]: 1.11 [1.03–1.19]; late AMD, OR [95% CI]: 1.24 [1.02–1.53]). The NLR partly mediated these associations. The aDII was not associated with OAG. A pro-inflammatory diet was associated with increased risks of cataract and AMD. Particularly the NLR, a marker of subclinical inflammation, appears to be implicated. These findings are relevant for patients with AMD and substantiate the current recommendations to strive for a healthy lifestyle to prevent blindness. [ABSTRACT FROM AUTHOR]

Retinal vascular diseases such as neovascular age-related macular degeneration (nAMD) are the leading cause of blindness worldwide. They can be treated with intravitreal injections of anti-vascular endothelial growth factor (anti-VEGF) agents by inhibiting VEGF which is a major agent of abnormal blood vessel growth. However, because of drug's short half-life, clinical treatment often requires monthly repeated intravitreal injections, causing treatment burden and undertreatment. Among various kinds of drug carriers, in situ forming hydrogels have been studied as potential intravitreal drug carriers for the high drug loading, easy injection, controlled drug release, and protection of encapsulated drugs from the environment. However, gelation time, crosslinking degree, and drug release patterns following injection of a liquid that will be subsequently gelled in situ are susceptible to be hindered by dilution of the hydrogel precursor solution with body fluids (e.g. , blood or vitreous). Here, we report an injectable pre-crosslinked hydrogel rod to overcome the limitations of in situ forming hydrogels and to extend intravitreal half-life of anti-VEGF for reducing intraocular injection frequency. Hydrogel rods can be simply prepared using in situ forming hydrogels, and injectable using a designed rod injector. The adjustable crosslinking degree of hydrogel rods easily controlled bevacizumab release profiles in a sustained manner. Compared with in situ forming hydrogels, hydrogel rods effectively reduced initial burst release, and showed sustained release with long-term drug efficacy in vitro. From the 4-month in vivo pharmacokinetic analysis, following the intravitreal injection of hydrogel rods, the half-life of bevacizumab in the vitreous and retina was significantly extended, and drug elimination to aqueous humor was effectively reduced. Finally, intraocular stability, degradation, and inflammatory response of hydrogel rods were evaluated. We expect that the hydrogel rod can be a potential drug delivery system for the treatment of nAMD and other conditions that need long-term and local sustained drug administration. Herein, we report an injectable pre-crosslinked hydrogel rod based on an in situ forming hydrogel to achieve intravitreal long-acting anti-VEGF delivery to reduce injection frequency and improve the long-term visual outcomes of patients with retinal vascular diseases. Hydrogel rods were readily prepared using removable molds and injected using customized injectors. Compared to the in situ forming hydrogel, hydrogel rods showed significantly reduced initial burst release, controllable release profiles for several months, physical stability, and a long-acting anti-angiogenic effect. Animal studies demonstrated that the hydrogel rods dramatically prolonged the intraocular drug half-life while significantly reducing drug elimination for up to four months. Moreover, the biodegradability and safety of the hydrogel rods suggest their suitability as an advanced intravitreal DDS for treating retinal vascular diseases. [Display omitted] [ABSTRACT FROM AUTHOR]

• Crystalline retinopathy characterized by reflective crystal deposits in the macula. • Crystalline retinopathy is a biomarker of several pathological systemic conditions. • We introduced deep learning + fundus photography to detect crystalline retinopathy. • Multistage CycleGAN + combined CutMix provides synthetic pathological fundus photographs with crystalline retinopathy. • The diverse synthetic pathological fundus photographs can improve diagnostics. Crystalline retinopathy is characterized by reflective crystal deposits in the macula and is caused by various systemic conditions including hereditary, toxic, and embolic etiologies. Herein, we introduce a novel application of deep learning with a multistage generative adversarial network (GAN) to detect crystalline retinopathy using fundus photography. The dataset comprised major classes (healthy retina, diabetic retinopathy, exudative age-related macular degeneration, and drusen) and a crystalline retinopathy class (minor set). To overcome the limited data on crystalline retinopathy, we proposed a novel multistage GAN framework. The GAN was retrained after CutMix combination by inputting the GAN-generated synthetic data as new inputs to the original training data. After the multistage CycleGAN augmented the data for crystalline retinopathy, we built a deep-learning classifier model for detection. Using the multistage CycleGAN facilitated realistic fundus photography synthesis with the characteristic features of retinal crystalline deposits. The proposed method outperformed typical transfer learning, prototypical networks, and knowledge distillation for both multiclass and binary classifications. The final model achieved an area under the curve of the receiver operating characteristics of 0.962 for internal validation and 0.987 for external validation for the detection of crystalline retinopathy. We introduced a deep learning approach for detecting crystalline retinopathy, a potential biomarker of underlying systemic pathological conditions. Our approach enables realistic pathological image synthesis and more accurate prediction of crystalline retinopathy, an essential but minor retinal condition. [ABSTRACT FROM AUTHOR]

Choroidal neovascularization (CNV) is the main cause of vision loss in patients with wet age-related macular degeneration (AMD). Currently, treatment of these conditions requires repeated intravitreal injections, which may lead to complications such as infection and hemorrhage. So, we have developed a noninvasive method for treating CNV with nanoparticles, namely, Angiopoietin1-anti CD105-PLGA nanoparticles (AAP NPs), which targets the CNV to enhance drug accumulation at the site. These nanoparticles, with PLGA as a carrier, can slowly release encapsulated Angiopoietin 1 (Ang 1) and target the choroidal neovascularization marker CD105 to enhance drug accumulation, increases vascular endothelial cadherin (VE-cadherin) expression between vascular endothelial cells, effectively reduce neovascularization leakage and inhibit Angiopoietin 2(Ang 2) secretion by endothelial cells. In a rat model of laser-induced CNV, intravenous injection of AAP NPs exerted a good therapeutic effect in reducing CNV leakage and area. In short, these synthetic AAP NPs provide an effective alternative treatment for AMD and meet the urgent need for noninvasive treatment in neovascular ophthalmopathy. This work describes the synthesis, injection-mediated delivery, in vitro and in vivo efficacy of targeted nanoparticles with encapsulated Ang1; via these nanoparticles, the drug can be targeted to choroidal neovascularization lesions for continuous treatment. The release of Ang1 can effectively reduce neovascularization leakage, maintain vascular stability, and inhibit Ang2 secretion and inflammation. This study provides a new approach for the treatment of wet age-related macular degeneration. [Display omitted] [ABSTRACT FROM AUTHOR]

We report the case of a 14-year-old girl with ocular toxoplasmosis presenting with severe panuveitis with anterior segment involvement, moderate vitreous haze, focal retinochoroiditis, extensive retinal periphlebitis, and macular bacillary layer detachment. Toxoplasmosis treatment was complicated by Stevens-Johnson syndrome, which developed 8 days after starting trimethoprim-sulfamethoxazole. [ABSTRACT FROM AUTHOR]

This work aimed to evaluate the performance of deep learning algorithms for an automated differentiation between polypoidal choroidal vasculopathy (PCV) and wet age-related macular degeneration (wet-AMD) by optical coherence tomography (OCT) images of macula. The automated classification model was developed with the self-supervised learning technique and was analyzed for the model performance. It learned visual representations from unlabeled data prior to fitting with labeled data. This technique was shown to provide desirable performance based only on a small proportion of labeled data. The final ensemble model trained with this technique with selected parameters yielded promising performance. Particularly, the proposed model provided 0.71 AUC with 0.67 sensitivity and 0.8 specificity on test set which were better than the traditional supervised learning models used as baseline approached in this study. [ABSTRACT FROM AUTHOR]

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Background: The RENOWNED study investigated the treatment patterns, real-world effectiveness and safety of ranibizumab in Taiwanese patients with neovascular age-related macular degeneration (nAMD) treated with ranibizumab 0.5 mg in accordance with the first reimbursement scheme effective from 2012 to 2014.Methods: This study was a Phase IV, 12-month, open-label, prospective, observational study conducted in Taiwan. Patients with visual impairment due to nAMD initiating treatment with ranibizumab 0.5 mg were included. The primary endpoint was mean change in best-corrected visual acuity (BCVA) from Baseline at Month 3.Results: Overall, 202 patients with nAMD were included. Mean (standard deviation [SD]) BCVA Early Treatment Diabetic Retinopathy Study letters improved from Baseline (49.6 [21.5] letters) at Month 3 (+4.9 [11.8], P < 0.0001), and at Month 12 (+3.5 [14.1], P = 0.0043). The proportion of patients with nAMD who lost ≥5 letters at Months 3 and 12 was 13.6% (n = 27) and 26.6% (n = 37), respectively. Mean (SD) central retinal thickness decreased from Baseline (320.1 [127.2] μm) with a mean reduction of 49.1 (107.3) μm at Month 3 (P < 0.0001), but was not significant at Month 12 with a mean reduction of 11.6 (115.6) μm (P = 0.2861). Mean (SD) number of ranibizumab injections over 12 months was 3.1 (1.0). A mean treatment interval of 109.5 days was observed between the third and fourth injections. After limited reimbursed ranibizumab injections, 43.8% patients received other treatments. The safety findings are consistent with previous studies.Conclusion: Ranibizumab 0.5 mg treatment for 12 months under real-world settings improved visual outcomes in Taiwanese patients with nAMD. [ABSTRACT FROM AUTHOR]

Retinal diseases significantly contribute to the global burden of visual impairment and blindness. The occurrence of retinal diseases is often accompanied by destruction of the blood‒retinal barrier, a vital physiological structure responsible for maintaining the stability of the retinal microenvironment. However, detailed summaries of the factors damage the blood‒retinal barrier and treatment methods involving natural plant medications are lacking. To comprehensively summarize and analyze the protective effects of active substances in natural plant medications on damage to the blood-retina barrier that occurs when retinal illnesses, particularly diabetic retinopathy, and examine their medicinal value and future development prospects. In this study, we searched for studies published in the ScienceDirect, PubMed, and Web of Science databases. The keywords used included natural plant medications, plants, natural herbs, blood retinal barrier, retinal diseases, diabetic retinopathy, age-related macular degeneration, and uveitis. Chinese herbal compound articles, non-English articles, warning journals, and duplicates were excluded from the analysis. The blood‒retinal barrier is susceptible to high glucose, aging, immune responses, and other factors that destroy retinal homeostasis, resulting in pathological changes such as apoptosis and increased vascular permeability. Existing studies have shown that the active compounds or extracts of many natural plants have the effect of repairing blood-retinal barrier dysfunction. Notably, berberine, puerarin, and Lycium barbarum polysaccharides exhibited remarkable therapeutic effects. Additionally, curcumin, astragaloside IV, hesperidin, resveratrol, ginsenoside Rb1, luteolin, and Panax notoginseng saponins can effectively protect the blood‒retinal barrier by interfering with distinct pathways. The active ingredients found in natural plant medications primarily repair the blood‒retinal barrier by modulating pathological factors such as oxidative stress, inflammation, pyroptosis, and autophagy, thereby alleviating retinal diseases. This review summarizes a series of plant extracts and plant active compounds that can treat retinal diseases by preventing and treating blood‒retinal barrier damage and provides reference for the research of new drugs for treating retinal diseases. [ABSTRACT FROM AUTHOR]

• The pathogenesis of AMD is related to oxidative stress, chronic Inflammation, and neovascularization. • Bioactive products from herbal medicines and functional foods may help AMD patients by alleviating oxidative stress, treating chronic inflammation, and slowing the development of new blood vessels. • Research is needed to understand the effects, safety and efficacy in investigating the translational potential of NP- Bench to bedside. • Mutiple new methods can be used in NP-related drug investigation. • Natural plant products may represent a promising direction for the development of novel drugs in the treatment of AMD. Age-related macular degeneration (AMD) is a chronic retinal disease that significantly influences the vision of the elderly. There is no effective treatment and prevention method. The pathogenic process behind AMD is complex, including oxidative stress, inflammation, and neovascularization. It has been demonstrated that several natural products can be used to manage AMD, but systematic summaries are lacking. PubMed, Web of Science, and ClinicalTrials.gov were searched using the keywords "Biological Products" AND "Macular Degeneration" for studies published within the last decade until May 2023 to summarize the latest findings on the prevention and treatment of age-related macular degeneration through the herbal medicines and functional foods. The eligible studies were screened, and the relevant information about the therapeutic action and mechanism of natural products used to treat AMD was extracted. Our findings demonstrate that natural substances, including retinol, phenols, and other natural products, prevent the development of new blood vessels and protect the retina from oxidative stress in cells and animal models. However, they have barely been examined in clinical studies. Natural products could be highly prospective candidate drugs used to treat AMD, and further preclinical and clinical research is required to validate it to control the disease. [Display omitted] [ABSTRACT FROM AUTHOR]

• Sulfuric acid proves to be the most efficient for the acid hydrolysis of molasses. • An optimal hydrolysis was observed at a concentration of 0.15 M sulfuric acid. • Heterotrophic cultivation of C. sorokiniana MB-1-M12 was achieved using molasses. • Using 10 g/L reducing sugars yield 2.57 g/L biomass and 2.1 mg/g lutein content. • The process fulfills the objective of waste recycling and reutilization. Lutein is a xanthophyll carotenoid commonly found in photosynthetic organisms, such as microalgae and plants. It serves as a photosynthetic accessory pigment and possesses antioxidant properties. Lutein is recognized for its prophylactic use in preventing Age-Related Macular Degeneration (AMD) and is widely employed in health supplements. The demand for lutein is steadily increasing. This study utilized Chlorella sorokiniana MB-1-M12 for heterotrophic growth and lutein production, employing molasses as a model of food industrial waste as an alternative carbon source. Molasses was hydrolyzed using acids, and the optimal hydrolysis conditions were determined by varying the types and concentrations of the acids. The resulting hydrolysate, which contains reducing sugars, was then recovered and used to support the heterotrophic growth of C. sorokiniana MB-1-M12 for lutein production. The best efficiency in molasses hydrolysis was achieved using 0.15 M sulfuric acid, resulting in a maximum sugar recovery of 0.721 gs of reducing sugar per gram of molasses. When the molasses hydrolysate reached a sugar concentration of 10 g/L, it yielded a biomass of 2.57 g/L and a lutein content of 2.1 mg/g. These findings indicate that molasses can effectively serve as a substitute for glucose as a carbon source, although it cannot provide all the essential micronutrients required for biomass growth. Consequently, the addition of nutrients in BG-11 medium became necessary. This study successfully demonstrates the upcycling of waste resources, such as molasses, into a high-value product like lutein, all achieved in a cost-effective and resource-efficient manner. [ABSTRACT FROM AUTHOR]

• Our study overcomes the limitations of manual estimations by employing AI to precisely measure the choroidal vascular layer thickness in patients with wet AMD. This novel, AI-based auto-measurement method is accurate, efficient, and detailed. It will provide valuable insights into the pathology of choroidal changes in wet AMD. To facilitate the assessment of choroid vascular layer thickness in patients with wet age-related macular degeneration (AMD) using artificial intelligence (AI). We included 194 patients with wet AMD and 225 healthy participants. Choroid images were obtained using swept-source optical coherence tomography. The average Sattler layer-choriocapillaris complex thickness (SLCCT), Haller layer thickness (HLT), and choroidal thickness (CT) were auto-measured at 7 regions centered around the foveola using AI and subsequently compared between the 2 groups. Results: The SLCCT was lower in the AMD group than in the control group (P < 0.05). The HLT was significantly higher in the AMD group than in the control group at the Tparafovea and T-perifovea in the total population (P < 0.05) and in the ≤70-year subgroup (P < 0.05). The CT was higher in the AMD group than in the control group, particularly at the N-perifovea, T-perifovea, and T-parafovea in the ≤70-year subgroup; Interestingly, it was lower in the AMD group than in the control group at the Nparafovea, N-fovea, foveola, and T-fovea in the >70-year subgroup (P < 0.05). This novel AI-based auto-measurement was more accurate, efficient, and detailed than manual measurements. SLCCT thinning was observed in wet AMD; however, CT changes depended on the interaction between HLT compensatory thickening and SLCCT thinning. [ABSTRACT FROM AUTHOR]

We report the case of an 8-year-old boy who presented with an optic disk pit and subsequently developed optic disk pit maculopathy, consisting of cystoid retinal edema in the peripapillary space and in the papillomacular bundle, which slowly and spontaneously resolved without intervention. [ABSTRACT FROM AUTHOR]

Although dysregulated cholesterol metabolism predisposes aging tissues to inflammation and a plethora of diseases, the underlying molecular mechanism remains poorly defined. Here, we show that metabolic and genotoxic stresses, convergently acting through liver X nuclear receptor, upregulate CD38 to promote lysosomal cholesterol efflux, leading to nicotinamide adenine dinucleotide (NAD+) depletion in macrophages. Cholesterol-mediated NAD+ depletion induces macrophage senescence, promoting key features of age-related macular degeneration (AMD), including subretinal lipid deposition and neurodegeneration. NAD+ augmentation reverses cellular senescence and macrophage dysfunction, preventing the development of AMD phenotype. Genetic and pharmacological senolysis protect against the development of AMD and neurodegeneration. Subretinal administration of healthy macrophages promotes the clearance of senescent macrophages, reversing the AMD disease burden. Thus, NAD+ deficit induced by excess intracellular cholesterol is the converging mechanism of macrophage senescence and a causal process underlying age-related neurodegeneration. [Display omitted] • Cholesterol promotes macrophage senescence by NAD+ depletion via LXR/CD38 signaling • Senescent macrophages accumulate in the subretinal space in AMD model mice • NAD+ augmentation and senolytics can suppress subretinal drusenoid deposits • Cell-mediated clearance has the capacity to remove subretinal deposits Terao et al. demonstrated how dysregulated cholesterol metabolism drives macrophage senescence and the development of subretinal drusenoid deposits in mice. LXR/CD38 signaling activated by cholesterol reduces NAD+ availability and promotes macrophage senescence. Senolytic agents targeting NAD+ decline and senescent macrophages are a potential therapeutic option against early AMD. [ABSTRACT FROM AUTHOR]

• The ensemble U-Net training is done by PFPO that is formed by merging PO with FPA. • Detection of AMD is carried out by means of DMN, where DMN is trained using PFPO. • The layers are segmented in layer segmentation phase by utilizing ensemble U-Net. Age-related Macular Degeneration (AMD) is the eye state, which influences most elder people. An accurate cause of AMD is yet not understood fully, but it is referred to as multi-factorial with increasing age as the most reliable factor. Thus, AMD prevalence is increasing owing to the aged population in the community. Hence, earlier AMD detection is required to avoid vision loss in the elderly. The detection of AMD in earlier stages at most perils of development permits more appropriate treatment and protection. Even though, arranging a complete eye examination for detection of AMD in the elderly is challenging and laborious. Hence, this research introduces the Political Flower Pollination Optimizer_Deep Maxout network (PFPO_DMN) for AMD detection. Here, median filter is used to pre-process the OCT images. The layers in considered input optical coherence tomography (OCT) images are segmented in the layer segmentation phase utilizing ensemble U-Net. The ensemble U-Net training is accomplished by employing PFPO which is formed by amalgamating the Political Optimizer (PO) with the flower pollination algorithm (FPA). After that, feature extraction is done including texture features, reflectivity, statistical features, thickness and curvature. Lastly, AMD detection is performed using DMN, where DMN is trained by PFPO and hence, detected output is obtained. Furthermore, PFPO_DMN achieved high specificity, sensitivity and accuracy values about 91.6%, 92.9% and 92%. [ABSTRACT FROM AUTHOR]

To analyze the prevalence of dry and wet age-related macular degeneration (AMD) in patients with diabetes, hypertension and hyperlipidemia, and to analyze the risk factors for AMD. A population-based cross-sectional epidemiologic study was conducted involving 14,440 individuals. We assessed the prevalence of dry and wet AMD in diabetic and non-diabetic subjects and analyzed the risk factors for AMD. The prevalence of wet AMD in diabetic and non-diabetic patients was 0.3% and 0.5%, respectively, and the prevalence of dry AMD was 17% and 16.4%, respectively. The prevalence of wet AMD in healthy, hypertensive, hyperlipidemic, and hypertensive/hyperlipidemic populations was 0.5%, 0.3%, 0.2%, and 0.7%, respectively. The prevalence of dry AMD in healthy, hypertensive, hyperlipidemic, and hypertensive/hyperlipidemic populations was 16.6%, 16.2%, 15.2%, and 17.2%, respectively. Age, sex, body mass index, and use of hypoglycemic drugs or lowering blood pressure drugs were corrected in the risk factor analysis of AMD. Diabetes, diabetes/hypertension, diabetes/hyperlipidemia, and diabetes/hypertension/hyperlipidemia were analyzed. None of the factors analyzed in the current study increased the risk for the onset of AMD. There was no significant difference in the prevalence of wet and dry AMD among diabetic and non-diabetic subjects. Similarly, there was no significant difference in the prevalence of wet and dry AMD among subjects with hypertension and hyperlipidemia. Diabetes co-existing with hypertension and hyperlipidemia were not shown to be risk factors for the onset of dry AMD. [ABSTRACT FROM AUTHOR]

Retinal pigment epithelial (RPE) is primarily impaired in age-related macular degeneration (AMD), leading to progressive loss of photoreceptors and sometimes choroidal neovascularization (CNV). mTOR has been proposed as a promising therapeutic target, while the usage of its specific inhibitor, rapamycin, was greatly limited. To mediate the mTOR pathway in the retina by a noninvasive approach, we developed novel biomimetic nanocomplexes where rapamycin-loaded nanoparticles were coated with cell membrane derived from macrophages (termed as MRaNPs). Taking advantage of the macrophage-inherited property, intravenous injection of MRaNPs exhibited significantly enhanced accumulation in the CNV lesions, thereby increasing the local concentration of rapamycin. Consequently, MRaNPs effectively downregulated the mTOR pathway and attenuate angiogenesis in the eye. Particularly, MRaNPs also efficiently activated autophagy in the RPE, which was acknowledged to rescue RPE in response to deleterious stimuli. Overall, we design and prepare macrophage-disguised rapamycin nanocarriers and demonstrate the therapeutic advantages of employing biomimetic cell membrane materials for treatment of AMD. Macrophage-disguised nanoparticles are fabricated so as to deliver rapamycin to choroidal neovascularization lesions in the eye. The intravenous administration of the formulation addresses the issue of current therapeutic strategies that rely on the invasive intravitreal injection. [Display omitted] [ABSTRACT FROM AUTHOR]

Retinal disease is one of the diseases that cause visual symptoms or loss of vision in humans. This disease can affect the choroid, which severely affects vision. Optical coherence tomography (OCT) images are usually used to detect retinal disease. OCT is an imaging technique that takes high-resolution slices of retinal images. It takes time for experts to examine and interpret the OCT images. Experts need to take advantage of technological capabilities to make this process faster and more accurate. Three datasets were used in this study. Dataset #1 (UCSD dataset) consists of choroidal neovascularization (CNV), diabetic macular edema (DME), drusen, and normal OCT image types. Dataset #2 (Duke dataset) and Dataset #3 consist of age-related macular degeneration (AMD), DME, and normal OCT image types. An artificial intelligence based hybrid approach was proposed for retinal disease detection. In the proposed approach, class-based activations were extracted for each model with nine transfer learning models using the dataset. Next, the dominant activations were selected from the model-based activations of each class using the slime mold algorithm (SMA) and the selected activations were classified using the softmax method. The overall accuracy obtained in classification is as follows: 99.60% for dataset 1, 99.89% for dataset #2 and 97.49% for dataset #3. In this study, it was found that the proposed approach contributes to the performance of transfer learning models. [ABSTRACT FROM AUTHOR]

Deep learning applications for assessing medical images are limited because the datasets are often small and imbalanced. The use of synthetic data has been proposed in the literature, but neither a robust comparison of the different methods nor generalizability has been reported. Our approach integrates a retinal image quality assessment model and StyleGAN2 architecture to enhance Age-related Macular Degeneration (AMD) detection capabilities and improve generalizability. This work compares ten different Generative Adversarial Network (GAN) architectures to generate synthetic eye-fundus images with and without AMD. We combined subsets of three public databases (iChallenge-AMD, ODIR-2019, and RIADD) to form a single training and test set. We employed the STARE dataset for external validation, ensuring a comprehensive assessment of the proposed approach. The results show that StyleGAN2 reached the lowest Fréchet Inception Distance (166.17), and clinicians could not accurately differentiate between real and synthetic images. ResNet-18 architecture obtained the best performance with 85% accuracy and outperformed the two human experts (80% and 75%) in detecting AMD fundus images. The accuracy rates were 82.8% for the test set and 81.3% for the STARE dataset, demonstrating the model's generalizability. The proposed methodology for synthetic medical image generation has been validated for robustness and accuracy, with free access to its code for further research and development in this field. [ABSTRACT FROM AUTHOR]

• Incomplete retinal pigment epithelium and outer retinal atrophy (iRORA) is a term that can. • Be used to describe atrophy whether or not there is choroidal neovascularization present. • Thinning of the outer nuclear layer (ONL) is one criterion for iRORA. • ONL changes are also seen in some patients treated with anti-VEGF medications. • Aflibercept therapy in neovascular AMD may lead to ONL thinning. There has been some concern that anti-vascular growth factor treatment accelerates the development of macular atrophy in eyes with neovascular age-related macular degeneration. During the treatment with aflibercept, the thickness of choroid may decrease. This may lead to photoreceptor death. The rod cells are more susceptible to atrophic changes than cones during the disease. We aimed to find any thickness changes in the perifoveal outer nuclear layer, where the highest density of rods is found, during the aflibercept intravitreal injection therapy. Retrospectively, forty-two patients who were treated for age-related macular degeneration with choroidal neovascularization were included in the study. After the first three loading doses, intravitreal injections were repeated every two months. Outer nuclear layer thicknesses were measured 2000 µm away from the center of the fovea with OCT, at a total of 20 points, located at 180 and 90°. The mean of these measurements was obtained before the treatment and 1 year after the therapy. Results were compared by using the Wilcoxon Rank Test. The mean visual acuity was 1,11±0,287 logMAR at the beginning and increased to 0,53±0,32 LogMAR after. Perifoveal thickness was significantly reduced when compared with the thickness before the treatment (p = 0.039, p < 0.05). This result was also significantly lower than the control group thicknesses (p = 0.035, p < 0.05). Anti-VEGFs can cause loss of phagocytic functions of RPE. The mechanism of the observed thinning of the ONL may be described as follows: VEGF emitted by the RPE normally helps to maintain the choriocapillaris. Thus, injecting an anti-VEGF intravitreally causes RPE atrophy, which leads to a decrease in the choroidal vascular index. This in turn causes first the rods, and later the cones, that are part of the outer nuclear layer, to start to die and disappear, hence the thinning of this layer. As aflibercept consists of parts of the extracellular domain of both the VEGFR1 and VEGFR2 receptors, that are held together by a human IgG1 backbone, this makes the binding of aflibercept to VEGF-A and VEGF-B stronger as compared to the binding of the previously used ranibizumab or bevacizumab (by nearly a factor 100 in the case of the most abundant isoform VEGF-A 165). Besides, aflibercept also binds very well to placental growth factor (PIGF), which is also associated with several ocular diseases. [ABSTRACT FROM AUTHOR]

Humans are exposed to cadmium and lead in various regions of the world daily due to industrial development and climate change. Increasing numbers of preclinical and clinical studies indicate that heavy metals, such as cadmium and lead, play a role in the pathogenesis of eye diseases. Excessive exposure to heavy metals such as cadmium and lead can increase the risk of impaired vision. Therefore, it is essential to better characterize the role of these non-essential metals in disease etiology and progression. This article discusses the potential role of cadmium and lead in the development of age-related eye diseases, including age-related macular degeneration, cataracts, and glaucoma. Furthermore, we discuss how cadmium and lead affect ocular cells and provide an overview of putative pathological mechanisms associated with their propensity to damage the eye. [ABSTRACT FROM AUTHOR]

Soot is a prevalent aerosol found both indoors and outdoors that has several sources, such as natural (e.g., wildfires), civilian (e.g., cooking), or military (e.g., burn pit operation). Additionally, within the sources, factors that influence the physicochemical properties of the soot include combustion temperature, oxygen availability, and fuel type. Being able to reproduce soot in the laboratory and systematically assess its toxicity is important in the pursuit of elucidating pathologies associated with its exposure. Of the organs of interest, we targeted the eye given the scant attention received. Yet, air pollution constituents such as soot have been linked to diseases such as age-related macular degeneration and proliferative vitreoretinopathy. We developed a bench-scale system to synthesize different types of soot, that is, soot with a systematically varied physical attributes or chemical composition. We used common analytical techniques to probe such properties, and used statistical analyses to correlate them with toxicity in vitro using ARPE-19 cells. Within the range of flame conditions studied, we find that soot toxicity increases with increasing oxygen concentration in fuel-rich premixed flames, and weakly increases with decreasing flame temperature. Additionally, soot particles produced in premixed flames are generally smaller in size, exhibit a lesser fractal structure, and are considerably more toxic to ARPE-19 cells than soot particles produced in non-premixed flames. [Display omitted] • Incipient (immature) soot is more toxic compared to mature soot. • Dose-dependent toxicity presented by both chemiluminescence and colorimetry assays. • Evidence of epithelial-mesenchymal transitions upon soot exposure is presented. • Results suggest soot morphology affects toxicity; surface functionality does not. [ABSTRACT FROM AUTHOR]

[Display omitted] The most frequent cause of blindness in industrialized nations is age-related macular degeneration (AMD), particularly in persons over 60. In recent years in this field, three key factors have led to an increase in the workload of experts and the healthcare system: 1) population aging worldwide prevalence, 2) AMD's chronic nature, and 3) more widespread usage of the retinal optical coherence tomography (OCT) imaging technology. The establishment of fully automated diagnosis systems has recently been made possible by recent developments in the deep learning field. The main objective of the research is to develop a new deep learning-based model using OCT images. The performance for classification and segmentation of retinal diseases is improved by the proposed model through effectively capturing inter-scale features and combining these features using convolutional blocks. Then, we classify volumetric OCT images via a new deep learning-based model. For multi-class classification and segmentation of ocular diseases, the OCT scans of the human eye are used in this research to demonstrate a Deep Learning Network (DL-Net) model by automatically recognizing normal, diabetic macular edema (DME), choroidal neovascularization (CNV), AMD, and drusen images. This research introduces the Modified ResNet-50 approach and Image Processing for multiple OCT image classification. This research presents an efficient diagnostic technique for image segmentation based on a Bi-LSTM-based deep recurrent convolutional neural network (DRCNN). The modified SqueezeNet model analyzes the volumetric segmentation of OCT images. The volumetric publicly available datasets are used to analyze the proposed model. The proposed multi-scale structure model outperforms several well-known OCT classification and segmentation frameworks. 99.76% accuracy is achieved by the proposed model respectively. In healthcare settings, the proposed methodology can be used as a diagnostic instrument to help medical experts make better-diagnosing decisions, as shown by the encouraging proposed architecture's qualitative evaluations and quantitative results by generating a confusion matrix. [ABSTRACT FROM AUTHOR]

Neovascular age-related macular degeneration (nAMD) is a leading cause of irreversible vision loss. The present consensus provides suggestions on diagnosis, evaluation, treatment, and follow-up strategies for nAMD from a panel of 11 practicing ophthalmologists. The experts suggest that the baseline visit for nAMD management should include a comprehensive ophthalmologic examination via a multimodal approach consisting of visual and anatomical evaluation. Patients diagnosed with nAMD should be subjected to treatment with the goal of maintaining visual function while diminishing anatomical disease activity and minimizing treatment burden. Currently, anti-VEGF therapy is the main treatment strategy for nAMD, and evaluation involving comprehensive ophthalmologic examination within 1 month of completion of the loading phase comprising three monthly injections is recommended to guide subsequent management. Either a treat-and-extend or pro re nata regimen can be considered for the maintenance phase of anti-VEGF therapy, and the regimen should be chosen and adjusted according to disease activity, reimbursement criteria, financial burden, and patient preferences. In the event of inactive nAMD or poor treatment outcomes, after thorough evaluation and patient education, anti-VEGF therapy may be stopped. The consensus provides practical nAMD management guidelines for ophthalmologists and fellow healthcare professionals. [ABSTRACT FROM AUTHOR]

Epidemiologic studies are inconsistent regarding the association of dietary omega-3 polyunsaturated fatty acids (PUFA) and/or fish intake with risk of age-related macular degeneration (AMD) incidence and progression. The objective was to determine these associations by conducting a meta-analysis of available studies. Three electronic databases were searched for studies that quantified dietary omega-3 PUFA and/or fish intake from inception to December 2020 without language restriction. Three investigators independently assessed for inclusion and extracted data. Study-specific risk estimates were combined using random-effects model. Potential dose–response associations were explored with the use of generalized least-squares trend estimation. 21 studies were included in the meta-analysis. Higher dietary intakes of omega-3 PUFA was significantly associated with 14% (relative risk [RR]: 0.86, 95% confidence interval [CI]: 0.77, 0.96) and 29% (RR: 0.71, 95% CI: 0.55, 0.91) lower risk of early and late AMD, respectively. The dose–response analysis showed a 6% and 22% decrease in the risk of early and late AMD for each additional 1 g/d omega-3 PUFA intake. For individual omega-3 PUFA, the intake of eicosapentaenoic acid and docosahexaenoic acid was inversely associated with lower AMD risk, whereas no association was found for the alpha-linolenic acid. Consistent inverse associations were also found between fish intake and AMD. The pooled RRs comparing extreme categories of fish intake were 0.79 (95% CI: 0.70, 0.90) and 0.71 (95% CI: 0.60, 0.85) for early and late AMD risk, respectively. Every 15 g/d of fish consumption was associated with 13% and 14% lower early and late AMD. In addition, fish intake was associated with a significantly reduced risk of AMD progression (RR: 0.73, 95% CI: 0.53, 1.00). A high intake of dietary omega-3 PUFA or fish was associated with a reduced risk of developing of AMD, which further supports that consumption of omega-3 PUFA-rich foods may be a new avenue nutritional approach to preventing AMD. [ABSTRACT FROM AUTHOR]

To determine the efficacy of prisms when used for redirection of incoming images towards the preferred reinal loci (PRLs) for restitution of potential visual acuity (PVA) in low vision cases with age-related macular degeneration (AMD). Retrospective comparative interventional case series review. Low vision rehabilitation (LVR) protocol used included best corrected visual acuity (BCVA), PVA, topographic PRL identification and use of prisms to produce image redirection to the presumed PRL. The primary outcome measure selected for analysis was BCVA for viewing distance targets after use of yoke prisms. Image relocation with prisms in patients with AMD resulted in significantly better BCVA levels (t 32 = 8.57, p < 0.0001) in the better eye. Distance BCVA levels achieved were almost identical to PVA levels (t 32 = 0.415, p < 0.681) (y= -0.136 + 1.195x, r = 0.8333, p < 0.001). Use of yoke prisms for image redirection towards a peripheral identifiable PRL may result in PVA restitution in most cases. [ABSTRACT FROM AUTHOR]

Age-related macular degeneration (AMD) is a typical fundus disease that affects the central vision of elderly people. It causes difficulties in everyday activities such as reading and recognizing faces. AMD can progress slowly or rapidly, and it leads to severe vision loss if left untreated. Therefore, early detection and diagnosis of AMD are crucial to prevent or delay vision impairment in the elderly. To handle this requirement, researchers are exploring deep learning-based models as an AI tool to assist ophthalmologist in AMD diagnosis. However, conducting an appropriate deep learning model for the AMD classification is challenging and cost-intensive. This research aims to evaluate the efficacy of various deep learning models for obtaining the best performance results when identifying AMD disease using retinal images. To meet this objective, the retinal images from the Department of Ophthalmology, the King Chulalongkorn Memorial Hospital, Thailand were collected for transfer learning and other publicly available datasets for testing. Then, seven deep learning models VGG19, Xception, DenseNet201, EfficientNetB7, InceptionV3, NASNetLarge, and ResNet152V2 were chosen to training for the 2-labels (Normal vs. AMD) and the 3-labels (Normal vs. Dry AMD vs. Wet AMD) classifications. From the experimental results, the DenseNet201 model with Dense block in its structure showed the best efficacy in both 2-labels and 3-labels AMD classifications since its performance always include in the Top-3 models accuracy and generalization performance measured by total accuracy and total F1-Score, respectively. Furthermore, the accuracy performance of deep learning models in Top-3 are comparable with the performance of retinal specialist. These results contribute consolidated knowledge to the process of implementation effective deep learning as production that detects AMD automatically in the clinical and enhance the quality of healthcare service. • DenseNet201 is the most effective model for 2-labels & 3-labels AMD classification. • Top-3 models for 2-labels classification are EfficientNetB7, Xception & DenseNet201. • Top-3 models for 3-labels classification are DenseNet201, ResNet152V2 & InceptionV3. [ABSTRACT FROM AUTHOR]

An 18-year-old female lost the majority of her central vision over the course of three months in 1959. Medical records from 1960 indicate visual acuities (VA) of less than 20/400 for both eyes corresponding to legal blindness. On fundus examination of the eye there were dense yellowish-white areas of atrophy in each fovea and the individual was diagnosed with juvenile macular degeneration (JMD). In 1971, another examination recorded her uncorrected VA as finger counting on the right and hand motion on the left. She was diagnosed with macular degeneration (MD) and declared legally blind. In 1972, having been blind for over 12 years, the individual reportedly regained her vision instantaneously after receiving proximal-intercessory-prayer (PIP). Subsequent medical records document repeated substantial improvement; including uncorrected VA of 20/100 in each eye in 1974 and corrected VAs of 20/30 to 20/40 were recorded from 2001 to 2017. To date, her eyesight has remained intact for forty-seven years. [ABSTRACT FROM AUTHOR]

The standard-of-care treatment for age-related macular degeneration (AMD) and diabetic macular edema (DME) includes inhibiting blood vessel proliferation and reducing macular edema or swelling using anti–vascular endothelial growth factor therapies, such as ranibizumab and aflibercept. To conduct a cost-minimization analysis of ranibizumab and aflibercept for treating Saudi patients with visual impairment owing to AMD or DME. Cost minimization was analyzed assuming that ranibizumab and aflibercept have equivalent clinical effectiveness. The third-party payer's perspective was used in several clinical scenarios. The base-case scenario was DME cases followed monthly using a protocol-specific follow-up. In scenario 1, AMD cases followed a treat-and-extend protocol over 2 years. In scenario 2, AMD cases followed the PRN (pro re nata) regimen over 2 years. In scenario 3, DME cases followed the PRN regimen for 1 year only. Aflibercept yielded cost savings of 25.75%, 31.54%, 51.30%, and 9.28% compared with ranibizumab for the base case, scenario 1, scenario 2, and scenario 3, respectively, which supports the premise that aflibercept is more cost saving than ranibizumab. From the third-party payer perspective, aflibercept is a cost-containment option that provides substantial savings over ranibizumab for treating Saudi patients with AMD or DME. [ABSTRACT FROM AUTHOR]

Polypoidal choroidal vasculopathy (PCV) is a prevalent retinal disease predominantly occurs in Asians that shares some similarities seen in neovascular age-related macular degeneration. Recent large multicenter clinical trials on intravitreal anti-vascular endothelial growth factor (VEGF) agents and photodynamic therapy (PDT) have shed lights on the management of PCV. The Taiwan National Health Insurance had granted limited anti-VEGF agents and PDT for patients with PCV after the approval of required data submission, especially fundus angiography, optical coherence tomography, and visual acuity. In order to best utilize these limited resources for the patients, an expert meeting was held to provide updated Taiwan consensus recommendations for the management of PCV, including initial therapy selection, assessment of treatment response, re-treatment/rescue treatment, and determination of treatment extension/follow-up schedule. An algorithm for treatment allocation under both initial and re-treatment setting was proposed. Further mechanistic and clinical studies are required to investigate the prognostic factors and optimal treatment protocols that will improve healthcare quality and reduce burden of disease and treatment for patients with PCV. [ABSTRACT FROM AUTHOR]

A naturally rich source of lutein and zeaxanthin are eggs. There is scarce epidemiological data on the temporal association between total egg consumption and age-related macular degeneration (AMD) incidence. We aimed to establish the prospective and independent association between consumption of eggs with the incidence of AMD over a 15-year follow-up. In this population-based cohort study of 3,654 participants aged 49 + years examined at baseline, 2034 participants had complete information on baseline egg consumption and AMD signs over 15 years. AMD was determined from retinal photographs. Egg consumption was assessed using a semi-quantitative food-frequency questionnaire. Total egg intake was calculated through summing up intakes in all forms e.g. boiled, poached, fried, scrambled and/or omelette. We summarized total egg consumption into the following categories: ≤1 egg/week; 2–4 eggs/week; 5–6 eggs/week; and ≥1 egg/day. At baseline, participants who consumed 2–4 eggs/week compared to those who consumed ≤1 egg/week (reference group) had reduced risk of incident late-stage AMD after 15 years: multivariable-adjusted odds ratio, OR, 0.51 (95% confidence intervals, CI, 0.28–0.92). Participants who consumed 2–4 eggs/week versus ≤1 egg/week at baseline had 62% reduced risk of developing neovascular AMD. Among those whose AMD onset was at or before the 10-year follow-up, consumption of 2–4 and 5–6 eggs/week was associated with 54% and 65% reduced risk of incident late AMD, respectively. When analyzed as a dichotomized variable, participants who consumed >1 egg/week versus ≤1 egg/week at baseline, had 46% reduced risk of developing late-stage AMD 15 years later: multivariable-adjusted OR 0.54 (95% CI 0.3–0.90). Non-significant associations were observed between egg consumption and incident early AMD. Our findings suggest that moderate consumption of eggs significantly reduces the risk of developing incident late-stage AMD over 15 years. [ABSTRACT FROM AUTHOR]

Increased Connexin43 hemichannel opening is associated with inflammasome pathway activation and inflammation in a range of pathologies including ocular disorders, such as age-related macular degeneration (AMD) and diabetic retinopathy (DR). In this study, the effect on retinal function and morphology of clinically safe doses of orally delivered tonabersat, a small molecule connexin hemichannel blocker, was investigated in the light-damaged retina animal model of dry AMD and in a spontaneous rat model of DR. Clinical parameters (fundus imaging, optical coherence tomography (OCT), and electroretinography) and inflammatory markers (immunohistochemistry for Iba-1 microglial marker, astrocyte marker glial fibrillary acidic protein, and Connexin43 protein expression) were assessed. Tonabersat treatment reduced inflammation in the retina in parallel with preservation of retinal photoreceptor function when assessed up to 3 months post light damage in the dry AMD model. In the DR model, clinical signs, including the presence of aneurysms confirmed using Evans blue dye perfusion, were reduced after daily tonabersat treatment for 2 weeks. Inflammation was also reduced and retinal electrical function restored. Tonabersat regulates assembly of the inflammasome (NLRP3) through Connexin43 hemichannel block, with the potential to reduce inflammation, restore vascular integrity and improve anatomical along with some functional outcomes in retinal disease. [ABSTRACT FROM AUTHOR]

• Autologous RPE and choroid translocation are promising for patients with vision loss due to AMD.°Various follow-up methods are currently available to monitor the viability of RPE and choroid grafts and the leading ones are indocyanine green angiography(ICGA), fundus autofluorescence(FAF) and fundus fluorescein angiography (FFA).° We use these imaging methods in early and late postoperative periods to reduce the complications of graft tissue and to preserve vision. To investigate the functional and anatomical results of autologous retinal pigment epithelial(RPE) cells and choroidal translocation after removal of the subfoveal choroidal neovascular membrane(CNVM) in patients with exudative age-related macular degeneration(AMD). To monitor the viability of choroidal patch with indocyanine green angiography(ICGA) and fundus autofluorescence(FAF) This study was conducted as a retrospective, interventional case series, and evaluation of 8 patients ;4 patients had large (> 1 disk diameter) subfoveal choroidal membranes, 3 with massive subretinal hemorrhage and 1 case with suprachoroidal hemorrhage(SCH) + rhegmatogenous retinal detachment(RRD). After removal of the CNVM, the autologous full-thickness patch of the RPE, bruch's membrane, choriocapillaris, and choroid was excised from the midperiphery and placed under the macula. At the 1 st month, 3rd month, 6th month and final examination, color fundus pictures and optical coherence tomography (OCT) were performed by preferred fixation of the OCT-light. Visual test with the early treatment of diabetic retinopathy study(ETDRS), OCT imaging with fixation, scanning with laser ophthalmoscopy autofluorescence, and ICGA were performed to evaluate the viability of choroidal patch at each visits. This study was carried out in 8 patients with a mean follow-up of 14.12 ± 8.16 (range 7-30 months) months. The mean age was 73 ± 7.17(range, 60-80 years) years. Pre-operative visual acuity ranged from hand motion (HM) (20/2000) to light perception (LP)(20/20000). Post-operative vision ranged from HM (20/2000) to 0.15(20/125). In 6 patients, autofluorescence was reflected in FAF imaging and lipofuscin activity was evaluated as viable. Post-operative subretinal hemorrhage was encountered in 1 (12.5%) patient and it also resolved spontaneously. There was a statistically significant increase in visual acuity at the postoperative final visit compared to baseline. (p = 0.027) After removal of the CNVM, translocation of a full-thickness patch with the autologous peripheral RPE and choroid can be performed at the macula, resulted in survival and functional graft for 6 months and moreover, hereby viability of the choroid and RPE patch were monitored by imaging methods such as FAF and ICGA. [ABSTRACT FROM AUTHOR]

Leading causes of vision loss include neovascular age-related macular degeneration (NVAMD) and macular edema (ME), which both require frequent intravitreal injections for treatment. A safe, poly(lactic-co-glycolic acid) (PLGA)-based biodegradable polymeric microparticle (MP) delivery system was developed that encapsulates and protects a biomimetic peptide from degradation, allows sustained intraocular release through polymer hydrolysis, and demonstrates a prolonged anti-angiogenic effect in vivo in three different NVAMD animal models (a laser-induced choroidal neovascularization mouse model, a rho VEGF transgenic mouse model, and a Tet/opsin/VEGF transgenic mouse model) following intravitreal administration. The role of copolymer composition and microparticle shape was explored and 85:15 lactide-to-glycolide PLGA formed into ellipsoidal microparticles was found to be effective at inhibiting neovascularization for at least 16 weeks in vivo. Treatments were found to not only inhibit the growth of neovascularization, but also to cause regression of the neovasculature, reduce vascular leakage, and prevent exudative retinal detachment. These particulate devices are promising for the sustained release of biologics in the eye and may be useful for treating retinal diseases. Devastating retinal diseases cause blindness in millions of people around the world. Current protein-based treatments have insufficient efficacy for many patients and also necessitate frequent intravitreal injections. Here, we demonstrate a new treatment consisting of a peptide encapsulated in biodegradable microparticles. We explore the effects of copolymer composition and physical shape of polymeric microparticles and find that both modulate peptide release. Efficacy of the treatment was validated in three different mouse models and the lead formulation was determined to be effective long-term, for at least 16 weeks in vivo , following a single injection. Treatments inhibited and regressed neovascularization as well as reduced vascular leakage. Anisotropic polymeric microparticles are promising for the sustained release of biologics in the eye. [ABSTRACT FROM AUTHOR]

Despite the significant impact of retinal diseases such as wet age-related macular degeneration (wAMD) and diabetic macular edema (DME), there is a limited understanding of how these conditions are managed in Central and Eastern Europe (CEE). To provide a comprehensive overview of the clinical and economic burden of wAMD and DME in CEE and the status quo associated with their management. A narrative literature review was undertaken to identify existing data on wAMD and DME, including epidemiology, economic burden, clinical guidelines, and available and reimbursed treatments. Data were collected from relevant sources such as PubMed, ophthalmology associations, national statistical offices, and government agency websites; practical viewpoints were provided by local ophthalmologists and healthcare economics experts in CEE. Epidemiological data on wAMD and DME are limited in CEE, and intercountry comparison is difficult because of differences in data collection methodologies. There are effective treatment options for wAMD and DME, and international guidelines advocate the use of intravitreal anti-vascular endothelial growth factor injections as first-line therapy. Local expert organizations broadly support these recommendations; nevertheless, no clinical practice guidelines exist on the treatment of wAMD and DME in CEE. Access to and reimbursement of anti-vascular endothelial growth factor agents vary significantly in the region and, as a result, many patients remain untreated or inadequately treated. There is an urgent need for the creation of a wAMD/DME treatment program in CEE to ensure that patients have timely access to the most appropriate treatments. • The prevalence of wet age-related macular degeneration (wAMD) and diabetic macular edema (DME) is increasing because of aging populations and the increase in the number of diabetes cases. These diseases pose a significant global economic and clinical burden, potentially leading to vision loss and having a negative impact on patients' quality of life. Although effective pharmacological treatments are widely available, access to these agents in the Central and Eastern European (CEE) region is not aligned with other regions. • AMD alone is responsible for 19.5% and 15.9% of all blindness cases reported in Eastern Europe and Central Europe, respectively. Despite the high impact of retinal diseases such as wAMD and DME, there is a limited understanding of how healthcare systems in the CEE countries are managing these patients. This review provides a comprehensive overview of the status quo associated with wAMD and DME management in the CEE region, their clinical and economic burden, and how the CEE region compares with other countries in terms of approval and reimbursement policies. The authors also provide a critical assessment of access barriers and the limitations associated with wAMD and DME management in the CEE region. • This article provides the first comprehensive review of the clinical and economic impact of wAMD and DME in the CEE region. A group of experts provides a critical appraisal of how the diseases have an impact on the CEE countries and how healthcare systems are currently managing wAMD and DME. The authors identify gaps and limitations in the current approach, but also provide examples of how other healthcare systems and clinical organizations have successfully addressed the management of wAMD and DME. [ABSTRACT FROM AUTHOR]

Objective: To review the current literature on psychosocial and psychological interventions to prevent and treat depression and anxiety in patients with age-related macular degeneration (AMD).Methods: The authors conducted a systematic review of literature evaluating psychosocial and psychological interventions for depression and anxiety in patients with AMD. Primary searches of PubMed, Cochrane library, EMBASE, Global Health, Web of Science, EBSCO, and Science Direct were conducted to include all articles published up to April 21, 2018.Results: Of a total of 398 citations retrieved, the authors selected 12 eligible studies published between 2002 and 2016. The authors found nine randomized controlled trials (RCT), and three non-randomized intervention (NRI) studies. RCT studies suggested that interventions using group self-management techniques and individual behavioral activation plus low vision rehabilitation can be effective to treat and prevent depression in patients with AMD, and one study suggested that a stepped-care intervention using cognitive-behavioral techniques can be effective to manage anxiety and depression over time. NRI studies highlighted a positive effect of self-help and emotion-focused interventions to reduce depression.Conclusion: Clinical practice with patients with AMD can rely on some tailored cognitive-behavioral therapeutic protocols to improve patients' mental health, but further clinical trials will generate the necessary evidence-based knowledge to improve those therapeutic techniques and offer additional tailored interventions for patients with AMD. [ABSTRACT FROM AUTHOR]

Our goal is to construct a high-performance model that generates two types of fundus disease images for both Diabetic Retinopathy (DR) and Age-Related Macular degeneration (AMD) that have different symptoms for each severity for overcoming the lack of labeled data and data imbalance problems that hinder to build a model based on deep learning. To this end, we propose a framework named FundusGAN for building fundus image generators in semi-supervised learning. First, a semantic coarse lesion mask as a guidance mask is exploited to express disease and severity information more accurately to generate a final fundus image by adopting a coarse-to-fine strategy. Second, the disease-feature matching loss is proposed to learn the abundant features of the two diseases by employing the unlabeled datasets and is able to generate the initial symptoms of two fundus diseases accurately. We demonstrate the effectiveness of the proposed FundusGAN in comparison with carefully tuned baselines and state-of-the-art DR fundus image generation model and finally achieve 0.9174, and 0.8254 f1-score for DR and AMD, respectively. • FundusGAN synthesizes fundus image for ophthalmic diseases, tackling data challenges. • Semantic lesion mask guides severity identification in coarse-to-fine approach. • Disease-feature matching loss enhances early-stage fundus generation. [ABSTRACT FROM AUTHOR]

• Reticular pseudedrusen have a significant effect on choroidal structure. • Reticular pseudedrusen induces choroidal thinning. • Reticular pseudedrusen diminish choroidal flow. This study aimed to compare choroidal thickness, total choroidal area (TCA), luminal area (LA), stromal area (SA) and choroidal vascularity index (CVI) in patients with reticular pseudodrusen (RPD) and drusen. A total of 100 eyes of 100 patients with non-neovascular age related macular degeneration (AMD) with five or more medium drusen (63–125 µm) and RPD in two or more quadrants were recruited to the study. 48 eyes of 48 patients with RPD were assigned as Group 1 and 52 eyes of 52 patients with drusen were assigned as Group 2. 40 right eyes of 40 healthy subjects were included as controls. Patients with neovascular AMD or advanced non-neovascular AMD were excluded from the study. After a detailed ophthalmic examination, infrared reflectance images and OCT with enhanced depth imaging mode was obtained from all patients. TCA, SA, LA and CVI were calculated using the Image J program. The data were analyzed for statistics using SPSS software. The female/male ratio was 56/44 in the patient groups and 20/20 in the control group. The mean age was 73.63±6.14 (61–91) years for Group 1 and 69.43± 6.97 (59–87) years for Group 2 (p =0.005). The mean age of Group 3 patients was 71.14±8.17 (60–79) years and was statistically similar to Groups 1 and 2 (p =0.09 and p =0.12, respectively). Choroidal thickness, TCA, SA and LA were significantly lower in Group 1 (p <0.001). CVI and foveal thicknesses were not significantly different between Group 1 and 2 (p =0.214 and p =0.384 respectively). CVI was significantly lower in Group 3 (p <0.01). RPD was most commonly seen in the superior quadrant followed by temporal, nasal, and inferior quadrants. TCA, SA and LA, which reflect choroidal vasculature, were decreased in patients with RPD. These parameters can help evaluate the pathophysiology of the disease. [ABSTRACT FROM AUTHOR]

[Display omitted] • Antioxidative effects of Lycii Fructus on Müller glia cells during AMD. • Mechanism of Lycii Fructus on relieving apoptosis of Müller cells was explored. • The aqueous extracts of Lycii Fructus protect Müller glia from oxidative injury. • Mechanism of Lycii Fructus protect Müller glia via Nrf2/HO-1 signaling pathway. Lycii Fructus (LF) is a medicinal-edible homology material frequently used for treating age-related macular degeneration (AMD) in Chinese medicine. Abundant of literatures verified the retina protection effect of LF on AMD-like animal models. However, previous studies on LF attenuating retinal damage mainly focused on its protection effect on pigment epithelial cells and optic ganglion cells while few reports on Müller cells. In the current study, we found that LF extracts attenuated oxidation damages and inhibited cell apoptosis of retina on a mouse retinal injury model induced by sodium iodate. LF extracts also increased expressions of Müller cell biomarker glutamine synthetase of eyeballs of model mice, which indicated that LF extract protected Müller cell from oxidation injury induced by sodium iodate. In Müller cell MIO-M1 cultures, LF also significantly inhibited cellular apoptosis induced by NaIO 3 by regulating Nrf2/HO-1 signaling pathway and the aqueous extracts exerted better active tendency than ethanol extracts. These data implied that the antioxidant effect of LF on protecting Müller cell might contribute to its retina repair function, thereby providing more scientific evidences for the development of LF as an alternative therapy or preventive measures for AMD. [ABSTRACT FROM AUTHOR]

Age-related macular degeneration (AMD) is a common retinal degenerative disorder among older individuals. Amyloid deposits, a hallmark of cerebral amyloid angiopathy (CAA), may be involved in the pathogenesis of AMD. Since amyloid deposits may contribute to the development of both AMD and CAA, we hypothesized that patients with AMD have a higher prevalence of CAA. To compare the prevalence of CAA in patients with or without AMD matched for age. We conducted a cross-sectional, 1:1 age-matched, case-control study of patients ≥40 years of age at the Mayo Clinic who had undergone both retinal optical coherence tomography and brain MRI from 2011 to 2015. Primary dependent variables were probable CAA, superficial siderosis, and lobar and deep cerebral microbleeds (CMBs). The relationship between AMD and CAA was assessed using multivariable logistic regression and was compared across AMD severity (none vs early vs late AMD). Our analysis included 256 age-matched pairs (AMD 126, no AMD 130). Of those with AMD, 79 (30.9%) had early AMD and 47 (19.4%) had late AMD. The mean age was 75±9 years, and there was no significant difference in vascular risk factors between groups. Patients with AMD had a higher prevalence of CAA (16.7% vs 10.0%, p=0.116) and superficial siderosis (15.1% vs 6.2%, p=0.020), but not deep CMB (5.2% vs 6.2%, p=0.426), compared to those without AMD. After adjusting for covariates, having late AMD was associated with increased odds of CAA (OR 2.83, 95% CI 1.10-7.27, p=0.031) and superficial siderosis (OR 3.40, 95%CI 1.20-9.65, p=0.022), but not deep CMB (OR 0.7, 95%CI 0.14-3.51, p=0.669). AMD was associated with CAA and superficial siderosis but not deep CMB, consistent with the hypothesis that amyloid deposits play a role in the development of AMD. Prospective studies are needed to determine if features of AMD may serve as biomarkers for the early diagnosis of CAA. [ABSTRACT FROM AUTHOR]

Highlights • Novel method for differentiation of adipose derived stem cells into RPE cells. • Generation of adult RPE cells in vitro with high efficiency and no cell death. • Electron microscopic feature of tight junction in adjacent RPE cells. • Presentation of apical microvilli on top of RPE cells in electron microscope. Abstract Background The induction of retinal pigmented epithelium cells (RPE) is one of the most important objectives in research focused on treating retinal degenerative diseases. The present study aims to differentiate human adipose stem cells (hADSCs) into RPE cells for replacement therapies in cases of retinal degenerative diseases. Methods Lipoaspirate-derived human adipose stem cells (LA-hADSCs) were obtained from abdominal samples and examined by immunocytochemistry for the expression of mesenchymal adipose stem cell markers. RPE cells were also obtained from human samples and cultured to be used as control after being examined for the expression of their designated markers. hADSCs differentiated into RPE cells after 80 days using chemical inducers in one steps. The differentiated cells were then compared to control cells in marker expression. The differentiated cells were also examined under a scanning electron microscope for the presence of apical microvilli and cell connection. Results Cultured hADSCs at the fourth passage was shown to express the surface markers CD90 (98 ± 2%), CD11b (96 ± 3%), and CD105 (95 ± 4%). The RPE cells obtained from human samples expressed the marker RPE65 quite well. 80 days after differentiation, the previously hADSCs expressed both RPE65 (100%) and CRALBP (96 ± 1%) and were thus significantly similar to the RPE cells obtained from human samples. Morphologically, differentiated cells appeared to have epithelial and cytoplasmic pigment granules. Observations using a scanning electron microscope recorded clear connections among the differentiated RPE cells and revealed apical microvilli. Conclusion Human adipose stem cells can differentiate into retinal pigmented epithelium cells, which can be used in cell replacement therapy for degenerative diseases including age-related macular degeneration (AMD) as well as retinitis pigmentosa (RP). [ABSTRACT FROM AUTHOR]

Population-based and interventional studies have shown that elevated zinc levels can reduce the progression to advanced age-related macular degeneration. The objective of this study was to assess whether elevated extracellular zinc has a direct effect on retinal pigment epithelial cells (RPE), by examining the phenotype and molecular characteristics of increased extracellular zinc on human primary RPE cells. Monolayers of human foetal primary RPE cells were grown on culture inserts and maintained in medium supplemented with increasing total concentrations of zinc (0, 75, 100, 125 and 150 μM) for up to 4 weeks. Changes in cell viability and differentiation as well as expression and secretion of proteins were investigated. RPE cells developed a confluent monolayer with cobblestone morphology and transepithelial resistance (TER) >200 Ω*cm 2 within 4 weeks. There was a zinc concentration-dependent increase in TER and pigmentation, with the largest effects being achieved by the addition of 125 μM zinc to the culture medium, corresponding to 3.4 nM available (free) zinc levels. The cells responded to addition of zinc by significantly increasing the expression of Retinoid Isomerohydrolase (RPE65) gene; cell pigmentation; Premelanosome Protein (PMEL17) immunoreactivity; and secretion of proteins including Apolipoprotein E (APOE), Complement Factor H (CFH), and High-Temperature Requirement A Serine Peptidase 1 (HTRA1) without an effect on cell viability. This study shows that elevated extracellular zinc levels have a significant and direct effect on differentiation and function of the RPE cells in culture, which may explain, at least in part, the positive effects seen in clinical settings. The results also highlight that determining and controlling of available, as opposed to total added, zinc will be essential to be able to compare results obtained in different laboratories. [ABSTRACT FROM AUTHOR]

Background: The majority of research performed to date has examined the effects of commonly known antioxidants such as vitamins C, E, and A and carotenoids on age-related macular degeneration (AMD) risk and progression. To date, there is limited research on promising phytochemicals with antioxidant and antiinflammatory properties, including flavonoids. Objective: In this exploratory study, we aimed to assess the independent associations between dietary intake of total flavonoids and common flavonoid classes with the prevalence and 15-y incidence of AMD. Design: In this population-based cohort study, 2856 adults aged ≥49 y at baseline and 2037 followed up 15 y later were included in prevalence and incidence analyses, respectively. Dietary intake was assessed by using a semiquantitative food-frequency questionnaire (FFQ). Estimates of the flavonoid content of foods in the FFQ were assessed by using the USDA Flavonoid, Isoflavone, and Proanthocyanidin databases. AMD was assessed from retinal photographs. Results: In cross-sectional analysis, each 1-SD increase in total overall flavonoid intake was associated with a reduced likelihood of any AMD (multivariable-adjusted OR: 0.76; 95% CI: 0.58, 0.99). Each 1-SD increase in dietary intake of total flavonols and total flavanones was associated with reduced odds of the prevalence of any AMD [multivariable-adjusted OR (95% CI): 0.75 (0.58, 0.97) and 0.77 (0.60, 0.99), respectively]. A marginally significant trend (P = 0.05) was observed between increasing the intake of total flavanone and hesperidin (from the first to the fourth quartile) and reduced likelihood of incident late AMD, after multivariable adjustment. Participants who reported ≥1 serving of oranges/d compared with those who never consumed oranges at baseline had a reduced risk of late AMD 15 y later (multivariable-adjusted OR: 0.39; 95% CI: 0.18, 0.85). Conclusions: Our findings suggest an independent and protective association between dietary intake of flavonoids and the likelihood of having AMD. [ABSTRACT FROM AUTHOR]

Retinal pigment epithelium (RPE) dysfunction and choroidal neovascularization (CNV) are predominant features of age-related macular degeneration (AMD), with an unclear mechanism. Herein, we show that RNA demethylase α-ketoglutarate-dependent dioxygenase alkB homolog 5 (ALKBH5) is up-regulated in AMD. In RPE cells, ALKBH5 overexpression associates with depolarization, oxidative stress, disturbed autophagy, irregular lipid homeostasis, and elevated VEGF-A secretion, which subsequently promotes proliferation, migration, and tube formation of vascular endothelial cells. Consistently, ALKBH5 overexpression in mice RPE correlates with various pathological phenotypes, including visual impairments, RPE anomalies, choroidal neovascularization (CNV), and interrupted retinal homeostasis. Mechanistically, ALKBH5 regulates retinal features through its demethylation activity. It targets PIK3C2B and regulates the AKT/mTOR signaling pathway with YTHDF2 as the N6-methyladenosine reader. IOX1, an ALKBH5 inhibitor, suppresses hypoxia-induced RPE dysfunction and CNV progression. Collectively, we demonstrate that ALKBH5 induces RPE dysfunction and CNV progression in AMD via PIK3C2B-mediated activation of the AKT/mTOR pathway. Pharmacological inhibitors of ALKBH5, like IOX1, are promising therapeutic options for AMD. [Display omitted] • ALKBH5 is up-regulated in clinical AMD specimens, hypoxic RPE cells, and CNV mice • ALKBH5 triggers oxidative stress, disturbed autophagy, and irregular lipid homeostasis in RPE • ALKBH5 overexpression in mice RPE disturbed retinal homeostasis and promoted CNV progression • ALKBH5 modulates PIK3C2B mRNA stability as an m6A eraser with YTHDF2 as the reader Sun et al. demonstrate that the N6-methyladenosine demethylase ALKBH5 induces RPE dysfunction and CNV progression in AMD via PIK3C2B-mediated activation of the AKT/mTOR pathway. They also reveal IOX1, an ALKBH5 inhibitor, as a pharmacological option for AMD. They offer insights into the molecular mechanism and therapeutic strategies for AMD. [ABSTRACT FROM AUTHOR]

Subretinal fibrosis (SF) accounts for vision loss in patients with neovascular age-related macular degeneration (nAMD) even treated with adequate intravitreal injection of anti-vascular endothelial growth factor (anti-VEGF) drugs. Currently, there is no treatment available to prevent or treat SF caused by nAMD. This study aims to investigate the potential effects of luteolin on SF and epithelial-mesenchymal transition (EMT) as well as the underlying molecular pathways both in vivo and in vitro. Seven-week-old male C57BL/6J mice were employed to establish laser-induced choroidal neovascularization (CNV) and SF. One day after the laser induction, luteolin was administered intravitreally. SF and CNV were assessed with the immunolabeling of collagen type I (collagen I) and isolectin B4 (IB4), respectively. RPE65 and α-SMA colocalization in the lesions was used to evaluate the extent of EMT in retinal pigment epithelial (RPE) cells by using immunofluorescence. In vitro , luteolin was administered to TGFβ1-treated primary human RPE (phRPE) cells. RT-qPCR, Western blot and immunofluorescence were employed to evaluate the change of EMT-related molecules, epithelial markers, and relevant signaling pathways. The functional changes associated with EMT were investigated using the scratch assay, Transwell migration assay, and collagen gel contraction assay. CCK-8 was used to determine the cell viability of phRPE cells. On day 7 and 14 after laser induction in mice, intravitreal injection of luteolin dramatically decreased the immunolabeled sizes of both collagen I and IB4, as well as the amount of colocalized double immunostaining of α-SMA and RPE65 in laser-induced SF lesions. In vitro , TGFβ1-treated phRPE cells demonstrated increased cell migration and contraction capacity, accompanied with considerable overexpression of fibronectin, α-SMA, N-cadherin and vimentin, as well as downregulation of E-cadherin and ZO-1. The above changes were largely inhibited by luteolin co-incubation. Mechanistically, luteolin could evidently decrease the phosphorylation of Smad2/3, whereas increase the phosphorylation of YAP in TGFβ1-treated phRPE cells. This study demonstrates that luteolin exhibits the anti-fibrotic effect in a laser-induced mouse model by inhibiting EMT of RPE cells via deactivating Smad2/3 and YAP signaling, which provides a potential natural compound for the prevention and treatment of SF and fibrosis-related diseases. [Display omitted] [ABSTRACT FROM AUTHOR]

The neovascular form of age-related macular degeneration (nvAMD) is the leading cause of blindness in the elderly population. Vascular endothelial growth factor (VEGF) plays a crucial role in choroidal neovascularization (CNV), and anti-VEGF therapy is recommended as first-line therapy for nvAMD. However, many patients do not radically benefit from this therapy. Epidemiological data suggest that physical exercise is beneficial for many human diseases, including nvAMD. Yet, its protective mechanism and therapeutic potential remain unknown. Here, using clinical samples and mouse models, we found that exercise reduced CNV and enhanced anti-angiogenic therapy efficacy by inhibiting AIM2 inflammasome activation. Furthermore, transfusion of serum from exercised mice transferred the protective effects to sedentary mice. Proteomic data revealed that exercise promoted the release of adiponectin, an anti-inflammatory adipokine from adipose tissue into the circulation, which reduced ROS-mediated DNA damage and suppressed AIM2 inflammasome activation in myeloid cells of CNV eyes through AMPK-p47phox pathway. Simultaneous targeting AIM2 inflammasome product IL-1β and VEGF produced a synergistic effect for treating choroidal neovascularization. Collectively, this study highlights the therapeutic potential of an exercise-AMD axis and uncovers the AIM2 inflammasome and its product IL-1β as potential targets for treating nvAMD patients and enhancing the efficacy of anti-VEGF monotherapy. [Display omitted] • High physical activity levels correlate with improved lesion recovery in AMD patients. • Adiponectin is necessary for the protective effect of exercise on CNV. • AIM2 deficiency improves CNV progression in mice. • Adiponectin suppresses AIM2 activation by reducing p47-mediated ROS production. [ABSTRACT FROM AUTHOR]

• A new framework of dual guidance networks for the close-related tasks of AMD-associated OCT image classification and segmentation. • A complementary mask guided convolutional neural network is proposed to perform the classification of OCT images, where the auxiliary task of lesion segmentation is introduced and the resulting segmentation mask is used in a complementary form to guide the extraction of classification features. • A class activation map guided UNet is proposed to achieve automatic segmentation of AMD lesions, where the CAM from classification is fused into the features at each layer to guide the segmentation task. Age-related macular degeneration (AMD) is one of the main causes of visual impairment in elderly people, with drusen and choroidal neovascularization (CNV) being two characterizing types of lesions. Based on optical coherence tomography (OCT), image classification can be used in AMD diagnosis, while image segmentation is necessary for quantitative assessment of the lesion area. In this paper, we propose a deep learning framework exploiting dual guidance between the two tasks. Firstly, a complementary mask guided convolutional neural network (CM-CNN) is proposed to perform classification of OCT B-scans with drusen or CNV from normal ones, where the guiding mask is generated by the auxiliary segmentation task. Secondly, a class activation map guided UNet (CAM-UNet) is proposed to achieve segmentation of drusen and CNV lesions, using CAM output from the CM-CNN. Tested on a subset of the public UCSD dataset, and compared with five classification networks, four segmentation networks, and three multi-task networks, the proposed dual guidance network has achieved higher accuracy both in classification and segmentation. The classification accuracy reaches 96.93% and the Dice coefficient for segmentation reaches 77.51%. Results on an extra dataset for detection of macular edema and segmentation of retinal fluids further show the generalizability of the proposed model. [ABSTRACT FROM AUTHOR]

[Display omitted] • Roles of oxidative stress on Age-related Macular Degeneration (AMD). • Plant carotenoids reduce AMD based on in vitro , in vivo and clinical trials. • Carotenoid benefits determined by treatment duration, body weight and exposure. Age-related macular degeneration (AMD) is a chronic disease leading to blindness in older adults and poses a significant economic burden to the healthcare system. The macula is regularly exposed to light, oxidative and inflammatory stress which play a central role in AMD pathogenesis. Lutein, zeaxanthin and their isomer meso -zeaxanthin are carotenoids from plants accumulating in the human macula that scavenge light, and reduce oxidation and inflammation. This review of relevant cellular, animal and human clinical trials investigated the benefits of the plant carotenoids, as a preventative and therapeutic treatment for AMD. Factors influencing the protective effects of the carotenoids were dependent on dose and treatment duration that could be important for translational applications leading to visual improvement in AMD patients. The application of carotenoid supplementation was discussed to provide non-invasive alternatives for the prevention and treatment of AMD. [ABSTRACT FROM AUTHOR]

The pandemic of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), the virus responsible for coronavirus disease 2019 (COVID-19), has brought with it many changes in the way with live, work, and socialise. One such change is an increase in the use of videoconferencing for communication with friends, family and work colleagues, and doing presentations, while physically distancing. We demonstrate an increase in the use of ring lights during the pandemic, and argue that this increased exposure to blue light may lead to a growing burden of macular degeneration in coming years. [ABSTRACT FROM AUTHOR]