Stages Of Age-related Macular Degeneration Research Articles

Photoreceptor assessment in age-related macular degeneration.

Clinical trials investigating drugs for various stages of age-related macular degeneration (AMD) are actively underway and there is a strong interest in outcomes that demonstrate a structure-function-correlation. The ellipsoid zone (EZ), a crucial anatomical feature affected in this disease, has emerged as a strong contender. There is significant interest in evaluating EZ metrics on Optical Coherence Tomography (OCT), such as integrity and reflectivity, as disruption of this photoreceptor-rich layer may indicate disease progression. Loss of photoreceptor integrity in the junctional zone of geographic atrophy (GA) has been shown to exceed the areas of retinal pigment epithelial (RPE) atrophy, thus predicting future GA expansion. Furthermore, reduced visual acuity and retinal sensitivity have been correlated with loss of EZ integrity, underscoring a structure-function relationship. Photoreceptor integrity has also recently been acknowledged by the Food and Drug Administration (FDA), supporting its use as a primary endpoint in clinical trials investigating treatments for GA. However, the segmentation of this EZ still poses challenges. Continuous enhancements in OCT resolution and advancements in automated segmentation algorithms contribute to improved assessment of the EZ, strengthening its potential as an imaging biomarker for assessing photoreceptor function. It remains to be seen whether the EZ will serve as a surrogate marker for intermediate AMD. This article aims to provide an overview of the current understanding and knowledge of the EZ, while addressing ongoing challenges encountered in its assessment and interpretation.

Applying low levels of strain to model nascent phenomenon of retinal pathologies.

Age-related macular degeneration (AMD) is a leading cause of vision loss in aging populations. A better understanding of the mechanisms of the disease, especially at early stages, could elucidate new treatment targets. One characteristic of AMD is strain on the retinal pigment epithelium (RPE), a crucial layer of the retina. This strain can be caused by physical phenomena like waste aggregation underneath the RPE, drusen formation, or leaky blood vessels that infiltrate the retina during choroidal neovascularization (CNV). It is not well understood how strain affects RPE cell function. Most models generate equibiaxial strain or higher levels of strain that are not representative of early stages of AMD. To overcome these issues, we engineered a device to cause controlled, low amounts of localized, radial strain (maximum ∼1.4%). This strain level is more mimetic to what occurs during aging or at the beginning of physical disruptions experienced during AMD. To evaluate how RPE cells respond to this physical stimulus, primary porcine RPE cells were exposed to low levels of strain applied by our custom-made device. Cell secretions and genetic expression were analyzed to determine how proteins linked to drusen and CNV are affected. The results indicate that this low amount of strain does not immediately initiate angiogenesis but causes changes in mRNA expression of amyloid precursor protein (APP), which plays a role in retinal health and drusen accumulation. This research offers insight into AMD progression as well as the health of other organs, including the brain.

Levodopa is associated with reduced development of new-onset geographic atrophy in patients with age-related macular degeneration.

Geographic atrophy (GA) is a significant cause of vision loss in patients with age-related macular degeneration (AMD). Current treatments are limited to anti-complement drugs, which have limited efficacy to delay progression with significant risk of complications. Levodopa (L-DOPA) is a byproduct of melanin synthesis that is associated with reduced development of neovascular AMD. In this study, we determined if L-DOPA was associated with a reduced likelihood of new-onset GA. We performed a retrospective analysis in the Vestrum Health Retina Database. We included eyes with non-neovascular AMD without GA and 1-5years of follow-up. Eyes were divided into two groups. Exposed to L-DOPA before or on the date of non-neovascular AMD without GA diagnosis, and eyes not exposed to L-DOPA. We extracted age, sex, AREDS2 status, dry AMD stage, smoking history, and conversion rate to GA at years 1 through 5. Propensity score matching was used to match L-DOPA and control groups. Cox proportional hazard regression, adjusting for age, sex, AMD severity, AREDS2 use, smoking status, and L-DOPA use was employed to calculate hazard ratios for new-onset GA detection. We identified 112,089 control and 844 L-DOPA exposed eyes with non-neovascular AMD without GA. After propensity score matching, 2532 control and 844 L-DOPA exposed eyes remained that were well-matched for age, sex, AMD severity, AREDS2 use, and smoking status. We found that L-DOPA exposure was associated with a significantly reduced likelihood (HR = 0.68, 95% CI: 0.48-0.95, P = 0.025) of new-onset GA detection. L-DOPA use was associated with reduced detection of new-onset GA.

Longitudinal Changes in Choroidal Thickness and Choroidal Vascularity Index in Age-Related Macular Degeneration

Introduction: The aim of the study was to investigate the rate of choroidal thinning and Choroidal Vascularity Index (CVI) changes over time in eyes with different stages of age-related macular degeneration (AMD) and control eyes. Methods: Retrospective longitudinal study of 105 eyes with different stages of AMD: non-advanced (n = 46), exudative (n = 28), central complete retinal pigment epithelium and outer retinal atrophy (cRORA) (n = 5) and healthy eyes (n = 26). We evaluated choroidal thickness (CT) and CVI at baseline and during 2–4 years of follow-up. After adjustment for age and sex, we estimated the rate of change per year of CT and CVI in each group. We also performed logistic regression to analyze the relationship between baseline CT and CVI with AMD progression. Results: The mean age of the included patients was 77.1 years with a mean follow-up of 3.36 years. Healthy eyes had higher baseline CT and CVI values compared to eyes with AMD. Exudative AMD showed a significant annual decrease in subfoveal CT (−5.1% per year vs. −3.5% in controls) and in the temporal and nasal sectors (−5.3% and −6.3%). CVI decreased during follow-up in all study groups, most in eyes with central cRORA (−1.09% per year). Conclusion: CVI and CT values are reduced in eyes with AMD compared to healthy eyes. Eyes with exudative AMD have the highest annual rate of choroidal thinning, while CVI decreases most in eyes with central cRORA. CT and CVI may aid in a further stratification of AMD progression risk.

Complement proteins and complement regulatory proteins are associated with age-related macular degeneration stage and treatment response

BackgroundDysregulation of the complement system is involved in development of age-related macular degeneration (AMD). The complement cascade is regulated by membrane bound complement regulatory proteins (Cregs) on mononuclear leukocytes among others. This study aims to investigate systemic complement proteins and Cregs in AMD stages and their association with treatment response in neovascular AMD (nAMD).MethodsIn this clinical prospective study, treatment-naïve patients with nAMD, intermediate AMD (iAMD) and healthy controls were recruited and systemic complement proteins C3, C3a and C5a were investigated with electrochemiluminescence immunoassays, and Creg expression (CD35, CD46 and CD59) on T cells (CD4 + and CD8+) and monocytes (classical, intermediate and non-classical) investigated with flow cytometry. Treatment response in nAMD patients was evaluated after loading dose and after one year, and categorized as good, partial or poor. Complement proteins and Creg expression levels were compared between healthy controls, iAMD and nAMD, as well as between good, partial and poor nAMD treatment response groups. Polymorphisms in the CFH and ARMS2 genes were analyzed and compared to complement proteins and Creg expression levels in nAMD patients.ResultsOne hundred patients with nAMD, 34 patients with iAMD and 61 healthy controls were included. 94 nAMD patients completed the 1-year follow-up. Distribution of treatment response in nAMD was 61 (65%) good, 26 (28%) partial, and 7 (7%) poor responders. The distribution of 1-year treatment response was 50 (53%) good, 33 (36%) partial, and 11 (11%) poor responders. The concentrations of systemic C3, C3a, and the C3a/C3-ratio were significantly increased in patients with nAMD compared to healthy controls (P < 0.001, P = 0.002, and P = 0.035, respectively). Systemic C3 was also increased in iAMD compared to healthy controls (P = 0.031). The proportion of CD46 + CD4 + T cells and CD59 + intermediate monocytes were significantly decreased in patients with nAMD compared to healthy controls (P = 0.018 and P = 0.042, respectively). The post-loading dose partial treatment response group had significantly lower concentrations of C3a and C5a compared to the good response group (P = 0.005 and P = 0.042, respectively). The proportion of CD35 + monocytes was significantly lower in the 1-year partial response group compared to the 1-year good response group (P = 0.039). High-risk CFH genotypes in nAMD patients was associated with increased C3a, C3a/C3-ratio, and expression levels of CD35 + CD8 + T cells and CD46 + classical monocytes, while expression level of CD46 + non-classical monocytes was decreased.ConclusionElevated concentrations of systemic complement proteins were found in patients with iAMD and nAMD. Decreased Creg expression levels were found in patients with nAMD. Partially responding nAMD patients had a dysregulated complement system and Cregs compared to good responders.

Immunocorrective effects of Tricor fenofibrate in the treatment of the early and intermediate stages of age-related macular degeneration

Age-related macular degeneration (AMD) is the leading cause of irreversible visual impairment, blindness and disability in the elderly. Treatment of end-stage AMD is extremely limited and requires invasive interventions. Currently, there is an active search for remedies aimed at preventing the degenerative process in the retina in the early stages of the disease. AMD is a multifactorial pathology, has common mechanisms with diseases associated with aging, metabolic shifts and hemodynamic disorders. The study of the effects of drugs already used to correct these disorders in the general clinic may also be of interest to ophthalmologists. The aim of the work was to study the dynamics of inflammatory markers of activation of the vascular endothelium and cytokines of the immune response in the tear fluid (TF) of patients with initial and intermediate stages of AMD against the background of the use of Tricor fenofibrate. 65 people were examined, divided into three groups according to the AREDS classification: group I – 20 people with early AMD (AREDS2), group II – 16 patients with intermediate AMD (AREDS3), 29 healthy elderly people without ophthalmopathology entered the age control group (AREDS1 – risk group). Patients of groups I and II received Tricor at a dose of 145 mg once a day for 9 months. Tear fluid (TF) was taken twice: before and immediately after the completion of the course of treatment. The determination of sICAM-1, sVCAM-1, sE-, sP-selectin and MCP-1/CCL2 in CS was performed by flow cytometry using a self-constructed multiplex panel from compatible simplex test kits Human FlowCytomixTM Simplex (Bender MedSystem GmbH, Germany); IL-1β, IL-2 IL-6 TNFα was determined within the framework of the Human Flow CytomixTM 15 Flex system (Bender MedSystem GmbH, Germany). Data processing was performed in the FlowCytomix Pro v 6.0 package (Bender Med Systems GmbH, Germany). According to the results of the study, a significant effect of Tricor fenofibrate was found on the initially high levels of local production of IL-1β, IL-2, IL-6, MCP-1/CCL2 and sICAM-1 in the AREDS2 group, which indicated a direct anti-inflammatory, vasoprotective effect in the treatment of the initial stage of AMD; a similar effect of the drug, but less pronounced, noted in the AREDS3 group. The ophthalmological examination data also indicated stabilization of visual functions and the clinical picture of the fundus, improvement of intraocular blood circulation in patients of the main groups. Thus, the use of Tricor can help prevent the degenerative process in the retina in the early stages of AMD development.

Dynamics of clinical and immunological parameters in retinal pigment epithelium transplantation in the context of combined immunosuppressive therapy in the rabbit model of retinal degeneration

Progressive damage of the retinal pigment epithelium (RPE) underlies the pathogenesis of degenerative retinal diseases such as: age-related macular degeneration (AMD), Stargardt’s disease, retinitis pigmentosa, Best’s disease and others. This group of diseases led by AMD leads to irreversible loss of visual functions, blindness and disability. The possibilities of therapy of late stages of AMD are extremely limited. The most promising approach to replace the damaged retinal pigment epithelium appears to be transplantation of RPE cells derived from induced pluripotent stem cells (iPSC-RPE) into the subretinal space (SRS). Despite immune privilege in the SRS, transplantation of xenogeneic cellular material causes severe inflammation in the posterior segment of the eye and leads to graft rejection in an in vivo experiment in the absence of immunosuppression. The solution to the problem of tissue incompatibility in this case can be the use of combined immunosuppressive therapy (CIT), aimed, on the one hand, at suppression of local inflammation (in the eye) and, on the other hand, at suppression of the systemic transplantation immune response. The aim of the study: clinical and immunological analysis of the results of transplantation of IPSC-RPE suspension on the background of CIT, including single intravitreal intraoperative administration of kenalog and further systemic application of mycophenolate mofetil (MMF), in the model of RPE atrophy in rabbits. Standard and specialized ophthalmological examination was performed at early and distant terms after the intervention in order to clinically assess the posttransplantation process. To analyze the immune status, vitreous humor (VH) and blood serum (BS) of rabbits of the experimental groups were collected. The concentrations of TGF-β1, TGF-β2, and IL-2 were determined in the biomaterial using solid-phase enzyme immunoassay. According to the results of the study, subretinal transplantation of IPSC-RPE, performed against the background of combination of single intravitreal intraoperative administration of kenalog and systemic application of MMF, is a safe method, which provides preservation of the retina and other adjacent structures of the eye and allows to prevent rejection of xenogenic material during its transplantation both in a healthy eye and with pre-formed RPE atrophy, which opens perspectives for full testing of biological effects realized by IPSC-RPE.

Retinal pigment epithelium-specific ablation of GPx4 in adult mice recapitulates key features of geographic atrophy in age-related macular degeneration.

Age-related macular degeneration (AMD) is a leading cause of irreversible vision loss in the elderly population, particularly the late-stage of dry AMD known as geographic atrophy (GA), lacks effective treatment options. Genetic mouse models of AMD have revealed the significance of impaired lipid metabolism and anti-oxidative capacity in early/intermediate stage of AMD, but remains unclear in GA that severely damages visual function. Here, to investigate the potential relevance of peroxidized lipids in RPE for late-stage dry AMD, GPx4fl/fl mice underwent subretinal injections of RPE-specific AAV-Cre vector or control AAV vector. RPE-specific GPx4 deficiency led to rapid RPE degeneration resembling key features of late-stage dry AMD, including preceding loss of RPE cell polarity, accumulation of acrolein, malondialdehyde, and 4-hydroxynonenal, photoreceptor loss, lipofuscin-laden subretinal melanophage infiltration, and complement activation. Treatment with α-tocopherol and ferrostatin-1 mitigated RPE degeneration, and shrunk mitochondria were observed in GPx4 deficient mice, suggesting involvement of ferroptosis. Unexpectedly, necrostatin-1s, an inhibitor of necroptosis, also ameliorated RPE degeneration, and activation of RIP3 and MLKL along with inactivation of caspase-8 was observed, indicating crosstalk between ferroptosis and necroptosis pathways. Our findings shed light on the intricate mechanisms underlying RPE degeneration in AMD and highlight GPx4/lipid peroxidation as potential therapeutic targets. RPE-specific ablation of GPx4 in mice provides a valuable tool for further elucidating the interplay between lipid peroxidation, cell death pathways, and AMD pathogenesis, offering new insights for preclinical research and therapeutic development targeting GA.

Dry age-related macular degeneration classification from optical coherence tomography images based on ensemble deep learning architecture.

Dry age-related macular degeneration (AMD) is a retinal disease, which has been the third leading cause of vision loss. But current AMD classification technologies did not focus on the classification of early stage. This study aimed to develop a deep learning architecture to improve the classification accuracy of dry AMD, through the analysis of optical coherence tomography (OCT) images. We put forward an ensemble deep learning architecture which integrated four different convolution neural networks including ResNet50, EfficientNetB4, MobileNetV3 and Xception. All networks were pre-trained and fine-tuned. Then diverse convolution neural networks were combined. To classify OCT images, the proposed architecture was trained on the dataset from Shenyang Aier Excellence Hospital. The number of original images was 4,096 from 1,310 patients. After rotation and flipping operations, the dataset consisting of 16,384 retinal OCT images could be established. Evaluation and comparison obtained from three-fold cross-validation were used to show the advantage of the proposed architecture. Four metrics were applied to compare the performance of each base model. Moreover, different combination strategies were also compared to validate the merit of the proposed architecture. The results demonstrated that the proposed architecture could categorize various stages of AMD. Moreover, the proposed network could improve the classification performance of nascent geographic atrophy (nGA). In this article, an ensemble deep learning was proposed to classify dry AMD progression stages. The performance of the proposed architecture produced promising classification results which showed its advantage to provide global diagnosis for early AMD screening. The classification performance demonstrated its potential for individualized treatment plans for patients with AMD.

Evaluating the persistence of large choroidal hypertransmission defects using SS-OCT imaging

In age-related macular degeneration (AMD), large choroidal hypertransmission defects (hyperTDs) are identified on en face optical coherence tomography (OCT) images as bright lesions measuring at least 250 μm in greatest linear dimension (GLD). These choroidal hyperTDs arise from focal attenuation or loss of the retinal pigment epithelium (RPE). We previously reported that once large hyperTDs formed, they were likely to persist compared with smaller lesions that were more likely to be transient. Due to their relative persistence, these large persistent choroidal hyperTDs are a point-of-no-return in the progression of intermediate AMD to the late stage of atrophic AMD. Moreover, the onset of these large choroidal hyperTDs can serve as a clinical trial endpoint when studying therapies that might slow disease progression from intermediate AMD to late atrophic AMD. To confirm the persistence of these large choroidal hyperTDs, we studied an independent dataset of AMD eyes enrolled in an ongoing prospective swept-source OCT (SS-OCT) natural history study to determine their overall persistence. We identified a total of 202 eyes with large choroidal hyperTDs containing 1725 hyperTDs followed for an average of 46.6 months. Of the 1725 large hyperTDs, we found that 1718 (99.6%) persisted while only 7 hyperTDs (0.4%) were non-persistent. Of the 7 non-persistent large hyperTDs in 6 eyes, their average GLD at baseline was 385 μm. Of the large hyperTDs ranging in size between 250 and 300 μm when first detected, only one was not persistent with a baseline GLD of 283 μm. In 6 of the non-persistent hyperTDs, the loss of a detectable large hyperTD was due to the accumulation of hyperreflective material along the retinal pigment epithelium (RPE) and in the retina over the area where the hyperTD was located. This hyperreflective material is thought to represent the migration and aggregation of RPE cells into this focal region where the choroidal hyperTD arose due to attenuated or lost RPE.

Prevalence of Age-related Macular Degeneration among Elderly Bulgarian Population

Age-related macular degeneration (AMD) is the leading cause of blindness worldwide in an older patient population with the highest risk of disease development in individuals older than 65 years. This study aims to estimate the prevalence of AMD and its stages among the elderly population of Sofia city. An observational study among elderly Sofia citizens, held as prophylactic ophthalmological examinations was performed. The participants underwent full ophthalmic examination including autorefractometry, noncontact tonometry, best-corrected visual acuity measurement, biomicroscopy, and indirect ophthalmoscopy through a dilated pupil. Optical coherent tomography was performed in cases with difficulties to determine the stage of AMD or when the visual acuity did not correspond to the ophthalmoscopy findings. All participants were asked to fill in informed consent and a specifically structured questionnaire based on the modified Wolffson LVQOL questionnaire that was previously used in the study in Eastern Bulgaria (in 2014 by Nencheva). Overall 700 patients, with a median age of 74 years (69 to 96 years) met the inclusion criteria and were enrolled in the study. The prevalence of AMD, early, intermediate and late AMD was estimated as 26.1%, 14%, 6.6%, and 5.6%, respectively. Age was strongly associated with the prevalence of AMD and its stages. The ageing of the population in Bulgaria and worldwide and the large proportion of elderly persons, affected by AMD, emphasize the necessity of regular ophthalmological examinations of that part of the population. The timely diagnosis and treatment are very important for diminishing of blindness and visual impairment.

A cost-minimization analysis of anti-VEGFs for the treatment of neovascular age-related macular degeneration in the Netherlands.

Age-related macular degeneration (AMD) is the main cause of severe vision loss globally. Neovascular AMD (nAMD) is an advanced stage of AMD treated with anti-vascular endothelial growth factors (anti-VEGFs). Although anti-VEGF treatment is effective, the frequent intravitreal injections place a burden on patients, (in)formal caregivers, and clinics. This study assesses the health-economic impact of anti-VEGF agents with lower injection frequency that have the potential to reduce treatment burden and compares it to the standard of care. We developed a cost-minimization model to evaluate the direct medical costs associated with first-line unilateral anti-VEGF treatment across a 3-year time horizon in the Netherlands. The analysis compared aflibercept 8mg, aflibercept 2mg, bevacizumab, faricimab, and ranibizumab. Our model adopted a treat-and-extend (T&E) regimen for aflibercept 2mg, bevacizumab, and ranibizumab. For aflibercept 8mg, a flexible regimen that was extendable up to 24weeks was applied, while faricimab followed a flexible regimen that was extendable up to 16weeks. Additionally, since list prices may vary from net prices, we calculated the break-even price for each anti-VEGF in comparison to bevacizumab, which is the recommended first-line treatment due to its low medication price. Based on list prices, aflibercept 8mg led to the lowest treatment costs (€16,251 per patient over a 3-year time horizon), closely followed by bevacizumab (€17,616 per patient over a 3-year time horizon). Ranibizumab led to the highest per-patient costs (€31,746 over a 3-year time horizon). For bevacizumab, most costs were attributable to administration, while for the other anti-VEGFs, most were attributable to medication. Aflibercept 8mg is cost-saving compared to bevacizumab at their medication prices at the time of writing. Aflibercept 2mg, faricimab, and ranibizumab should be priced below €488, €591, and €75, respectively. To be cost-equal to bevacizumab with current list prices, anti-VEGFs should be administered with a maximum of 12.7 to 13.8 injections over a 3-year time horizon. According to the injection frequency observed in clinical trials, aflibercept 8mg would be the anti-VEGF that generates the lowest per-patient healthcare costs for the treatment of nAMD in the Netherlands after a treatment period of three years. Our study indicates that anti-VEGF drugs with a lower injection frequency might provide a cost-saving solution to the increasing burden of anti-VEGF treatment on the healthcare system.

Choriocapillaris in Age-Related Macular Degeneration.

Age-related macular degeneration (AMD) is a multifactorial disease characterized by progressive alterations of different retinal structures ultimately leading to vision loss. Among these, the choriocapillaris (CC) has been found to be affected in different stages of AMD. In this review we provide a discussion on the different stages of AMD, focusing particularly on the alterations involving the CC. This has been possible thanks to the introduction of optical coherence tomography-angiography, a recently developed imaging technique which allows the detection of blood flow in choroidal vessels. Therefore, the aim of this review is to provide a description of the various alterations involving the CC in the different stages of AMD.

Developing an image-based grading scale for peripheral drusen to investigate associations of peripheral drusen type with age-related macular degeneration

Age-related macular degeneration (AMD) is a leading cause of blindness. It is associated with peripheral drusen which has not been categorized. We investigated peripheral drusen to validate an image grading system and to understand possible associations between peripheral drusen and AMD. We collated clinical data, ultra-widefield (UWF) pseudocolor fundus images and Spectral-Domain Optical Coherence Tomography (SD-OCT) scans from consecutive retinal patients. SD-OCT scans were used to determine AMD stage. A masked retinal specialist recorded the types of peripheral drusen observed in UWF images. Eyes whose UWF images did not pass quality screening and those without AMD and peripheral drusen were excluded from the study. Statistical tests were utilized to determine the validity of our grading system and associations of peripheral drusen with AMD. A total of 481 eyes (283 subjects) were included in the study (mean age 73.1 ± 1.2years, 64.3% female). Interobserver and test–retest statistical analyses to evaluate the UWF image grading system resulted in Cohen’s Kappa 0.649 (p < 0.001) and 0.922 (p < 0.001) respectively. A total of 284 (59.0%), 28 (5.8%), 15 (3.1%), 22 (4.6%), 4 (0.8%), 39 (8.1%), and 32 (6.7%) eyes had hard, soft, reticular, cuticular, atrophic, mixed drusen, and mixed drusen and atrophy respectively in at least one peripheral retinal quadrant. Hard peripheral drusen was significantly associated with the presence of AMD (p = 0.010). Peripheral drusen types were variably seen in retinal patients with and without AMD. We validated a peripheral drusen grading system and provided an image library to assist in the identification of peripheral drusen. Our study found an association between peripheral hard drusen and an AMD diagnosis but did not find a link between peripheral drusen and severity of AMD.

Hyperautofluorescent material inside areas of macular atrophy may reveal non-lipofuscin fluorophores in late stage AMD.

To characterize fundus autofluorescence (FAF) in complete (cRORA) and incomplete retinal pigment epithelium and outer retinal atrophy (iRORA) by fluorescence lifetime imaging ophthalmology (FLIO). Overall, 98 macular atrophy (MA) lesions in 42 eyes of 37 age-related macular degeneration (AMD) patients (mean age: 80.9 ± 5.8 years), 25 of them classified as iRORA and 73 as cRORA by OCT, were investigated by FLIO in a short (SSC: 498-560 nm) and a long wavelength channel (LSC: 560-720 nm). Differences of FAF lifetimes and peak emission wavelength (PEW) between atrophic lesions and intact retinal pigment epithelium (RPE) in the outer ring of the ETDRS grid were considered. FAF lifetimes in MA were longer and PEW were significantly (p < 0.001) shorter than in intact RPE by 112 ± 78 ps (SSC), 91 ± 64 ps (LSC), 27 ± 18 nm (PEW) in iRORA and by 227 ± 112 ps (SSC), 167 ± 81 ps (LSC), and 54 ± 17 nm (PEW) in cRORA. 37% of iRORA and 24% of cRORA were hyperautofluorescent in SSC. Persistent sub-RPE-BL material in MA was newly found as a hyperautofluorescent entity with lifetimes considerably longer than that of drusen and RPE. Despite RPE and, thus, lipofuscin are greatly absent in MA, considerable FAF, preferably at short wavelengths, was found in those lesions. Drusen, persistent sub-RPE-BL material, basal laminar deposits, persistent activated RPE, and sclera were identified as putative sources of this fluorescence. FLIO can help to characterize respective fluorophores.

Metadata-enhanced contrastive learning from retinal optical coherence tomography images

Deep learning has potential to automate screening, monitoring and grading of disease in medical images. Pretraining with contrastive learning enables models to extract robust and generalisable features from natural image datasets, facilitating label-efficient downstream image analysis. However, the direct application of conventional contrastive methods to medical datasets introduces two domain-specific issues. Firstly, several image transformations which have been shown to be crucial for effective contrastive learning do not translate from the natural image to the medical image domain. Secondly, the assumption made by conventional methods, that any two images are dissimilar, is systematically misleading in medical datasets depicting the same anatomy and disease. This is exacerbated in longitudinal image datasets that repeatedly image the same patient cohort to monitor their disease progression over time. In this paper we tackle these issues by extending conventional contrastive frameworks with a novel metadata-enhanced strategy. Our approach employs widely available patient metadata to approximate the true set of inter-image contrastive relationships. To this end we employ records for patient identity, eye position (i.e. left or right) and time series information. In experiments using two large longitudinal datasets containing 170,427 retinal optical coherence tomography (OCT) images of 7912 patients with age-related macular degeneration (AMD), we evaluate the utility of using metadata to incorporate the temporal dynamics of disease progression into pretraining. Our metadata-enhanced approach outperforms both standard contrastive methods and a retinal image foundation model in five out of six image-level downstream tasks related to AMD. We find benefits in both a low-data and high-data regime across tasks ranging from AMD stage and type classification to prediction of visual acuity. Due to its modularity, our method can be quickly and cost-effectively tested to establish the potential benefits of including available metadata in contrastive pretraining.

A deep learning LSTM-based approach for AMD classification using OCT images

Age-related macular degeneration (AMD) is an age-related, persistent, painless eye disease that impairs central vision. The central area (macula) of the retina, located at the back of the eye, sustains damage that is the cause of loss of vision. The early detection of AMD can increase the probability of treatment and prevent vision loss. The AMD can be classified into dry and wet AMD based on the absence of neovascularization. This study introduces a new methodology for the classification of AMD using optical coherence tomography (OCT) retinal images. The proposed methodology is based on three stages. The first stage is the data preparation stage for resizing and normalizing the used images. The second stage is the image processing stage for enhancing the image quality as contrast and resolution these enhancements have been checked by the weighted peak signal-to-noise ratio (WPSNR) methodology. The third stage is the deep feature extraction and classification stage, which consists of two sub-models. The first model is MobileNet V1 which has been used as a deep feature extractor. The second model is LSTM (long short-term memory), fed with deep features to classify the AMD stages. A multi-classification with six separate trials has been employed with the proposed methodology, and compared with other models like DenseNet201 and InceptionV3. The proposed model has been tested on a sample of benchmark data with 4005 grayscale images labeled into three classes. The proposed methodology has achieved an accuracy of 98.85%, a sensitivity of 99.09%, and a specificity of 99.1%. To ensure the effectiveness of the proposed methodology, a comparative analysis has been established with previous approaches in the related field, and the results demonstrated the superiority of the proposed system in AMD multi-classification.

The role of nutritional factors in transitioning between early, mid, and late stages of age-related macular degeneration: prospective longitudinal analysis

BackgroundTransitions between different stages of age-related macular degeneration (AMD) are not completely captured by traditional survival models with an end point of advanced AMD. ObjectivesThis study aimed to explore the transitions from early and intermediate AMD to higher non-advanced and advanced stages and determine the contributions of nutritional factors to these outcomes. MethodsEyes with early or intermediate AMD at baseline, classified according to the Age-Related Eye Disease Study severity scale, were included in this prospective longitudinal analysis. Foods and the biologically active nutrients associated with AMD [green leafy vegetables, fish, lutein/zeaxanthin (LZ), and ω-3 (n–3) fatty acids] were determined by a baseline food frequency questionnaire. Progression was defined as eyes transitioning to higher severity groups including non-advanced and advanced stages over 5 years, confirmed at 2 consecutive visits. Cox proportional hazards models for foods and nutrients were analyzed adjusting for demographics, lifestyle, baseline macular status, a family history of AMD, caloric intake, and genetic risk. ResultsAmong 2697 eyes, 616 (23%) progressed to higher severity groups. In the food group model, higher intake of green leafy vegetables reduced incidence of transitions {hazard ratio [HR] (≥2.7 servings/wk compared with none): 0.75; 95% confidence interval [CI]: 0.59, 0.96; P = 0.02}. Higher fish intake was also protective [HR (≥ two 4-ounce servings/wk compared with <2): 0.79; 95% CI: 0.65, 0.95; P = 0.01]. In the nutrient model, LZ intake was protective [HR (≥2 mg/d compared with <2): 0.76; 95% CI: 0.60, 0.96; P = 0.02]. Higher intake of ω-3 fatty acids also tended to be beneficial [HR (≥0.7 g/wk compared with <0.7): 0.85; 95% CI: 0.71, 1.01; P = 0.06]. ConclusionsIncreased consumption of green leafy vegetables, LZ, and fish nutritionally rich in ω-3 fatty acids during the initial stages of AMD may reduce rates of progression to higher severity of this debilitating disease.This trial was registered at clinicaltrials.gov as NCT00594672.

Hyper transmission Defects in Early Stages of Age-Related Macular Degeneration (AMD)

Hyper transmission Defects in Early Stages of Age-Related Macular Degeneration (AMD)

Summary of the Therapeutic Options for Patients with Dry and Neovascular AMD.

Age-related macular degeneration (AMD) is the leading cause of irreversible blindness worldwide and a severe medical and social problem. The steadily increasing number of patients is related to the aging of the population. So far, many factors affecting the development of AMD have been identified, which can be divided into non-modifiable, including genetic factors, age, and sex, and modifiable or environmental factors, such as smoking, poor diet, and hypertension. Early stages of age-related macular degeneration are characterized by fundus drusen and abnormalities in the retinal pigment epithelium. In late stages, geographic atrophy and choroidal neovascularization (CNV) are observed. The treatment of AMD, especially its advanced forms, is very challenging. Intensive research has made it possible to treat advanced stages of the dry form of AMD with pegcetacoplan and avacincaptad pegol, new drugs approved for use in the US. Pegcetacoplan targets the C3 and avacincaptad pegol targets the C5, the pivotal proteins of the complement cascade. The drugs are administered by intravitreal injection. The gold standard for neovascular AMD (nAMD) consists of intravitreal injections of anti-vascular endothelial growth factor (anti-VEGF) drugs such as bevacizumab, ranibizumab, aflibercept, brolucizumab, and faricimab. Treatment can be administered according to the fixed, pro-re-nata, and treat-and-extend regimens. The latter seems to have the best effect on improving visual acuity (VA) and the maximum therapeutic benefit. The search continues for the best ways to deliver intravitreal drugs. Current methods include sustained-release implants and hydrogel platforms for drug release, while the most promising future pathways for treating dry and nAMD are stem cell and gene therapy.