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Introduction: Photobiomodulation (PBM) has become a promising approach for slowing the progression of early and intermediate dry age-related macular degeneration (dAMD) to advanced AMD. This technique uses light to penetrate tissues and activate molecules that influence biochemical reactions and cellular metabolism. This preliminary analysis is aimed at assessing the safety, tolerability, and short-term effectiveness of the EYE-LIGHT®PBM treatment device in patients with dAMD. Methods: The EYE-LIGHT® device employs two wavelengths, 590 nm (yellow) and 630 nm (red), in both continuous and pulsed modes. Patients over 50 years of age with a diagnosis of dAMD in any AREDS (Age-Related Eye Disease Study) category were randomly assigned to either the treatment group or the sham group. The treatment plan consisted of an initial cycle of two sessions per week for 4 weeks. Safety, tolerability, and compliance outcomes, along with functional and anatomical outcomes, were assessed at the end of the fourth month. Results: This preliminary analysis included data from 76 patients (152 eyes). All patients were fully compliant with treatment sessions, and only one fifth of patients treated with PBM reported mild ocular adverse events, highlighting exceptional results in terms of tolerability and adherence. Changes in best-corrected visual acuity (BCVA) from baseline to month 4 differed significantly between the sham and PBM-treated groups, favoring the latter, with a higher proportion achieving a gain of five or more letters post-treatment (8.9% vs. 20.3%, respectively; p = 0.043). No significant differences in central subfield thickness (CST) were observed between the two groups over the 4-month period. The study also found a statistically significant disparity in mean drusen volume changes from baseline to month 4 between the groups in favor of patients treated with PBM (p = 0.013). Conclusion: These preliminary results indicate that PBM treatment using the EYE-LIGHT® system is safe and well tolerated among patients with dAMD. Furthermore, both functional and anatomical data support the treatment's short-term efficacy. Trial Registration: ClinicalTrials.gov identifier NCT06046118. [ABSTRACT FROM AUTHOR]

Age‐related macular degeneration (AMD) is an emerging cause of blindness in aged people worldwide. One of the key signs of AMD is the degeneration of the retinal pigment epithelium (RPE), which is indispensable for the maintenance of the adjacent photoreceptors. Because of impaired energy metabolism resulting from constant light exposure, hypoxia, and oxidative stress, accumulation of drusen in AMD‐affected eyes is observed. Drusen contain damaged cellular proteins, lipoprotein particles, lipids and carbohydrates and they are related to impaired protein clearance, inflammation, and extracellular matrix modification. When autophagy, a major cellular proteostasis pathway, is impaired, the accumulations of intracellular lipofuscin and extracellular drusen are detected. As these aggregates grow over time, they finally cause the disorganisation and destruction of the RPE and photoreceptors leading to visual loss. In this review, the role of autophagy in drusen biogenesis is discussed since impairment in removing cellular waste in RPE cells plays a key role in AMD progression. In the future, means which improve intracellular clearance might be of use in AMD therapy to slow the progression of drusen formation. [ABSTRACT FROM AUTHOR]

Classification and identification of eye diseases using Optical Coherence Tomography (OCT) has been a challenging task and a trending research area in recent years. Accurate classification and detection of different diseases are crucial for effective care management and improving vision outcomes. Current detection methods fall into two main categories: traditional methods and deep learning-based approaches. Traditional approaches rely on machine learning for feature extraction, while deep learning methods utilize data-driven classification model training. In recent years, Deep Learning (DL) and Machine Learning (ML) algorithms have become essential tools, particularly in medical image classification, and are widely used to classify and identify various diseases. However, due to the high spatial similarities in OCT images, accurate classification remains a challenging task. In this paper, we introduce a novel model called "OCTNet" that integrates a deep learning model combining InceptionV3 with a modified multi-scale attention-based spatial attention block to enhance model performance. OCTNet employs an InceptionV3 backbone with a fusion of dual attention modules to construct the proposed architecture. The InceptionV3 model generates rich features from images, capturing both local and global aspects, which are then enhanced by utilizing the modified multi-scale spatial attention block, resulting in a significantly improved feature map. To evaluate the model's performance, we utilized two state-of-the-art (SOTA) datasets that include images of normal cases, Choroidal Neovascularization (CNV), Drusen, and Diabetic Macular Edema (DME). Through experimentation and simulation, the proposed OCTNet improves the classification accuracy of the InceptionV3 model by 1.3%, yielding higher accuracy than other SOTA models. We also performed an ablation study to demonstrate the effectiveness of the proposed method. The model achieved an overall average accuracy of 99.50% and 99.65% with two different OCT datasets. [ABSTRACT FROM AUTHOR]

Purpose: To examine age‐related macular degeneration (AMD) and retinal pigment epithelium (RPE)–Bruch's membrane (BrM) complex volume associations in monozygotic twin pairs. Methods: In this study, 106 elderly twins (53 twin pairs) from the Finnish Twin Cohort study were recruited. Each participant underwent dilated 35‐degree digital colour fundus photography (CFP), and spectral domain optical coherence tomography (OCT) and replied to a structured study questionnaire. The CFPs were graded according to the Age‐Related Eye Disease Study (AREDS) classification. The OCT images were segmented and volumetric data of the RPE‐BrM complex volume was calculated with the Orion™ software. The worse eye according to AREDS classification was used for the analysis. Results: Twenty‐nine (55%) of the twin pairs were discordant with regard to AREDS classification. Fourteen (26%) pairs were discordant with one twin participant having AMD (AREDS 2–4) and the other being unaffected (AREDS 1). Four (8%) pairs had one twin participant with intermediate or late AMD (AREDS 3–4) versus the other being unaffected (AREDS 1). The within‐pair polychoric correlation for AREDS was 0.605 (95% confidence interval 0.418–0.792). In multivariate analysis intermediate and late AMD as well as age associated with RPE‐BrM complex volume. RPE‐BrM complex volume showed a within twin pair correlation, r = 0.430 (95% confidence interval 0.172–0.688, p < 0.01). Conclusion: A substantial proportion of monozygotic twin pairs are discordant with regard to age‐related macular degeneration phenotype. RPE‐BrM complex volume associated with age and intermediate and late AMD. [ABSTRACT FROM AUTHOR]

Image preprocessing is a method to transform raw image data into clean image data. The objective of preprocessing is to improve the image data by suppressing undesired distortions. Enhancement of some image features which are relevant for further processing of image and analysis task is also done in preprocessing. Screening and diagnosis of various eye diseases like diabetic retinopathy, Choroidal Neovascularization(CNV), DRUSEN, etc. are possible using digital retinal images. This paper aims to provide a better understanding and knowledge of the computer algorithms used for retinal image preprocessing. In this paper, various image preprocessing techniques are incorporated such as color correction, color space selection, noise reduction, and contrast enhancement on retinal images. Retinal blood vessels are better seen in Green color space instead of Red or Blue color space. Noise reduction through Block matching and 3D(BM3D) techniques show a significant result as compared to Total Variation Filter (TVF) and Bilateral Filter (BLF). Contrast enhancement through Contrast Limited Adaptive Histogram Equalization (CLAHE) outperforms Global Equalization (GE) or Adaptive Histogram Equalization (AHE). Evaluation parameters such as Mean square error, Peak Signal Noise ratio, Structured similarity index measures, and Normalized root mean square error values for BM3D noise filtering are 0.0029, 25.3370, 0.6839 and 0.0998 respectively which shows that BM3D outperforms the others. [ABSTRACT FROM AUTHOR]

Abstract Introduction Photobiomodulation (PBM) has become a promising approach for slowing the progression of early and intermediate dry age-related macular degeneration (dAMD) to advanced AMD. This technique uses light to penetrate tissues and activate molecules that influence biochemical reactions and cellular metabolism. This preliminary analysis is aimed at assessing the safety, tolerability, and short-term effectiveness of the EYE-LIGHT®PBM treatment device in patients with dAMD. Methods The EYE-LIGHT® device employs two wavelengths, 590 nm (yellow) and 630 nm (red), in both continuous and pulsed modes. Patients over 50 years of age with a diagnosis of dAMD in any AREDS (Age-Related Eye Disease Study) category were randomly assigned to either the treatment group or the sham group. The treatment plan consisted of an initial cycle of two sessions per week for 4 weeks. Safety, tolerability, and compliance outcomes, along with functional and anatomical outcomes, were assessed at the end of the fourth month. Results This preliminary analysis included data from 76 patients (152 eyes). All patients were fully compliant with treatment sessions, and only one fifth of patients treated with PBM reported mild ocular adverse events, highlighting exceptional results in terms of tolerability and adherence. Changes in best-corrected visual acuity (BCVA) from baseline to month 4 differed significantly between the sham and PBM-treated groups, favoring the latter, with a higher proportion achieving a gain of five or more letters post-treatment (8.9% vs. 20.3%, respectively; p = 0.043). No significant differences in central subfield thickness (CST) were observed between the two groups over the 4-month period. The study also found a statistically significant disparity in mean drusen volume changes from baseline to month 4 between the groups in favor of patients treated with PBM (p = 0.013). Conclusion These preliminary results indicate that PBM treatment using the EYE-LIGHT® system is safe and well tolerated among patients with dAMD. Furthermore, both functional and anatomical data support the treatment’s short-term efficacy. Trial Registration ClinicalTrials.gov identifier NCT06046118.

PurposeChoroidal vascular changes occur with normal aging and age-related macular degeneration (AMD). Here, we evaluate choroidal thickness and vascularity in aged rhesus macaques to better understand the choroid's role in this nonhuman primate model of AMD.MethodsWe analyzed optical coherence tomography (OCT) images of 244 eyes from 122 rhesus macaques (aged 4-32 years) to measure choroidal thickness (CT) and choroidal vascularity index (CVI). Drusen number, size, and volume were measured by semiautomated annotation and segmentation of OCT images. We performed regression analyses to determine any association of CT or CVI with age, sex, and axial length and to determine if the presence and volume of soft drusen impacted these choroidal parameters.ResultsIn rhesus macaques, subfoveal CT decreased with age at 3.2 µm/y (R2 = 0.481, P < 0.001), while CVI decreased at 0.66% per year (R2 = 0.257, P < 0.001). Eyes with soft drusen exhibited thicker choroid (179.9 ± 17.5 µm vs. 162.0 ± 27.9 µm, P < 0.001) and higher CVI (0.612 ± 0.051 vs. 0.577 ± 0.093, P = 0.005) than age-matched control animals. Neither CT or CVI appeared to be associated with drusen number, size, or volume in this cohort. However, some drusen in macaques were associated with underlying choroidal vessel enlargement resembling pachydrusen in human patients with AMD.ConclusionsChanges in the choroidal vasculature in rhesus macaques resemble choroidal changes in human aging, but eyes with drusen exhibit choroidal thickening, increased vascularity, and phenotypic characteristics of pachydrusen observed in some patients with AMD.

The increasing development of Deep Learning mechanism allowed ones to create semi-fully or fully automated diagnosis software solutions for medical imaging diagnosis. The convolutional neural networks are widely applied for central retinal diseases classification based on OCT images. The main aim of this study is to propose a new network, Deep CNN-GRU for classification of early-stage and end-stages macular diseases as age-related macular degeneration and diabetic macular edema (DME). Three types of disorders have been taken into consideration: drusen, choroidal neovascularization (CNV), DME, alongside with normal cases. The created automatic tool was verified on the well-known Labelled Optical Coherence Tomography (OCT) dataset. For the classifier evaluation the following measures were calculated: accuracy, precision, recall, and F1 score. Based on these values, it can be stated that the use of a GRU layer directly connected to a convolutional network plays a pivotal role in improving previously achieved results. Additionally, the proposed tool was compared with the state-of-the-art of deep learning studies performed on the Labelled OCT dataset. The Deep CNN-GRU network achieved high performance, reaching up to 98.90% accuracy. The obtained results of classification performance place the tool as one of the top solutions for diagnosing retinal diseases, both early and late stage. [ABSTRACT FROM AUTHOR]

Abstract 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

Introduction: We aim to report the clinical course of a patient with pachychoroidopathy who experienced regression of subfoveal drusen during cholesterol treatment using PCSK9 inhibitors. Case Presentation: A 62-year-old woman who was visually asymptomatic complained of recent visual loss in the left eye (OS). She was diagnosed with foveal pachydrusen (OS) that had remained stable for 10 years. Three months after starting cholesterol treatment with a PCSK9 inhibitor, the latest class of lipid-lowering medication, her vision improved in parallel with gradual regression of material deposited beneath the retinal pigment epithelium (RPE). Recurrence of drusen was observed after discontinuing the drug. Conclusions: Use of PCSK9 inhibitors may improve the retina’s lipid homeostasis by increasing the number of RPE-LDL receptors and partly contribute to the improvement of ocular phenotypes associated with dysfunctional RPE in pachychoroidopathy.

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. [ABSTRACT FROM AUTHOR]

Introduction: We aim to report the clinical course of a patient with pachychoroidopathy who experienced regression of subfoveal drusen during cholesterol treatment using PCSK9 inhibitors. Case Presentation: A 62-year-old woman who was visually asymptomatic complained of recent visual loss in the left eye (OS). She was diagnosed with foveal pachydrusen (OS) that had remained stable for 10 years. Three months after starting cholesterol treatment with a PCSK9 inhibitor, the latest class of lipid-lowering medication, her vision improved in parallel with gradual regression of material deposited beneath the retinal pigment epithelium (RPE). Recurrence of drusen was observed after discontinuing the drug. Conclusions: Use of PCSK9 inhibitors may improve the retina’s lipid homeostasis by increasing the number of RPE-LDL receptors and partly contribute to the improvement of ocular phenotypes associated with dysfunctional RPE in pachychoroidopathy. [ABSTRACT FROM AUTHOR]

Purpose: To examine histological characteristics and differences between drusen beneath the retinal pigment epithelium (small hard drusen) located in the macula and located in the parapapillary region. Methods: We histomorphometrically examined human eyes enucleated due to uveal melanomas or secondary angle-closure glaucoma. Results: The study included 106 eyes (age, 62.6 ± 15.2 years) with macular drusen (n = 7 globes) or parapapillary drusen (n = 29 eyes) and 70 eyes without drusen. In all drusen, periodic-acid-Schiff-positive material was located between the RPE basal membrane and the inner collagenous layer of Bruch's membrane (BM). Macular drusen as compared with parapapillary drusen had lower height (15.2 ± 10.1 µm versus 34.3 ± 19.8 µm; P = 0.003), while both groups did not differ significantly in basal drusen width (74.0 ± 36.3 µm versus 108.7 ± 101.0 µm; P = 0.95). Eyes with macular drusen and eyes without drusen did not differ significantly in BM thickness (2.74 ± 0.44 µm versus 2.55 ± 0.88 µm; P = 0.57) or in RPE cell density (35.4 ± 10.4 cells/480 µm versus 32.8 ± 7.5 cells/480 µm; P = 0.53), neither in the drusen region nor in the drusen vicinity, while BM thickness (4.60 ± 1.490 µm; P < 0.001) and RPE cell density (56.9 ± 26.8 cells/480 µm; P = 0.005) were higher at the parapapillary drusen. Eyes with macular drusen, eyes with parapapillary drusen, and eyes without drusen did not differ significantly in choriocapillaris density (all P > 0.10) and thickness (all P > 0.35). Limitations of the study, among others, were a small number and size of drusen examined, diseases leading to enucleation, lack of serial sections, limited resolution of light microscopy, and enucleation-related and histological preparation-associated artefacts. Conclusions: The findings of this study, also taking into account its methodological limitations, suggest that macular drusen and parapapillary drusen shared the morphological feature of periodic-acid-Schiff-positive material between the RPE basal membrane and BM and that they did not vary significantly in choriocapillaris thickness and density. RPE cell density and BM thickness were higher in parapapillary drusen than in macular drusen. [ABSTRACT FROM AUTHOR]

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Background: Drusen and drusenoid deposits are a hallmark of age-related macular degeneration (AMD). Nowadays, a multimodal retinal imaging approach enables the detection of these deposits. However, quantitative data on subretinal drusenoid deposits (SDDs) are still missing. Here, we compare the capability of en-face drusen and SDD area detection in eyes with non-exudative AMD using conventional imaging modalities versus Retro mode imaging. We also quantitatively assess the topographic distribution of drusen and SDDs. Methods: In total, 120 eyes of 90 subjects (mean age ± standard deviation = 74.6 ± 8.6 years) were included. Coherent en-face drusen and SDD areas were measured via near-infrared reflectance, green (G-) and blue (B-) fundus autofluorescence (AF), and Retro mode imaging. Drusen phenotypes were classified by correlating en-face drusen areas using structural high-resolution spectral domain optical coherence tomography. The topographic distribution of drusen was analyzed according to a modified ETDRS (Early Treatment of Diabetic Retinopathy Study) grid. Intraclass correlation coefficient (ICC) analysis was applied to determine the inter-reader agreement in the SDD en-face area assessment. Results: The largest coherent en-face drusen area was found using Retro mode imaging with a mean area of 105.2 ± 45.9 mm2 (deviated left mode (DL)) and 105.4 ± 45.5 mm2 (deviated right mode (DR)). The smallest en-face drusen areas were determined by GAF (50.9 ± 42.6 mm2) and BAF imaging (49.1 ± 42.9 mm2) (p < 0.001). The inter-reader agreement for SDD en-face areas ranged from 0.93 (DR) to 0.70 (BAF). The topographic analysis revealed the highest number of SDDs in the superior peripheral retina, whereas sub-retinal pigment epithelium drusen were mostly found in the perifoveal retina. Retro mode imaging further enabled the detection of the earliest SDD stages. Conclusions: Retro mode imaging allows for a detailed detection of drusen phenotypes. While hundreds/thousands of SDDs can be present in one eye, the impact of SDD number or volume on AMD progression still needs to be evaluated. However, this new imaging modality can add important knowledge on drusen development and the pathophysiology of AMD. [ABSTRACT FROM AUTHOR]

One of the major causes of vision impairment among elderly people in developed nations is age-related macular degeneration (AMD). The distinctive features of AMD are the accumulation of extracellular deposits called drusen and the gradual deterioration of photoreceptors and nearby tissues in the macula. AMD is a complex and multifaceted disease influenced by several factors such as aging, environmental risk factors, and a person's genetic susceptibility to the condition. The interaction among these factors leads to the initiation and advancement of AMD, where genetic predisposition plays a crucial role. With the advent of high-throughput genotyping technologies, many novel genetic loci associated with AMD have been identified, enhancing our knowledge of its genetic architecture. The common genetic variants linked to AMD are found on chromosome 1q32 (in the complement factor H gene) and 10q26 (age-related maculopathy susceptibility 2 and high-temperature requirement A serine peptidase 1 genes) loci, along with several other risk variants. This review summarizes the common genetic variants of complement pathways, lipid metabolism, and extracellular matrix proteins associated with AMD risk, highlighting the intricate pathways contributing to AMD pathogenesis. Knowledge of the genetic underpinnings of AMD will allow for the future development of personalized diagnostics and targeted therapeutic interventions, paving the way for more effective management of AMD and improved outcomes for affected individuals. [ABSTRACT FROM AUTHOR]

Purpose: To understand the spatial relationship between local rod-mediated visual function and reticular pseudodrusen (RPD) in eyes with large drusen. Design: Retrospective cross-sectional study. Participants: One eye with large drusen (>125 μm) each from 91 individuals with intermediate age-related macular degeneration, with and without RPD. Methods: All participants underwent dark adaptation testing using a dark-adapted chromatic perimeter, where visual sensitivities were measured over 30 minutes of dark adaptation after photobleach. The rod intercept time (RIT; a measure of dynamic rod function) and pointwise sensitivity difference (PWSD; a relative measure of rod- compared with cone-mediated function) was determined at multiple retinal locations, and their association with the overall (central 20° × 20° region) and local (2° diameter region centered on the location tested) extent of RPD and drusen (quantified using multimodal imaging) was examined. Main Outcome Measures: Association between overall and local extent of RPD and drusen with RIT and PWSD at each retinal location tested. Results: In a multivariable analysis, delayed RIT was associated with an increasing overall (P < 0.001), but not local (P = 0.884), extent of RPD. In contrast, the increasing local (P < 0.001), but not overall (P = 0.475), extent of drusen was associated with delayed RIT. Furthermore, only an increasing overall extent of RPD (P < 0.001) was associated with reduced PWSD (or worse rod compared with cone function), but not the local extent of RPD and drusen, or overall extent of drusen (P ≥ 0.344). Conclusions: Local rod-mediated function was associated with the overall, rather than local, extent of RPD in eyes with large drusen, suggesting that there may be widespread pathologic changes in eyes with RPD that account for this. Financial Disclosure(s): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

Abstract Artificial intelligence (AI) has emerged as a transformative technology across various fields, and its applications in the medical domain, particularly in ophthalmology, has gained significant attention. The vast amount of high-resolution image data, such as optical coherence tomography (OCT) images, has been a driving force behind AI growth in this field. Age-related macular degeneration (AMD) is one of the leading causes for blindness in the world, affecting approximately 196 million people worldwide in 2020. Multimodal imaging has been for a long time the gold standard for diagnosing patients with AMD, however, currently treatment and follow-up in routine disease management are mainly driven by OCT imaging. AI-based algorithms have by their precision, reproducibility and speed, the potential to reliably quantify biomarkers, predict disease progression and assist treatment decisions in clinical routine as well as academic studies. This review paper aims to provide a summary of the current state of AI in AMD, focusing on its applications, challenges, and prospects.

Age-related macular degeneration (AMD) affects millions of individuals worldwide and is a leading cause of blindness in the elderly. In dry AMD, lipoproteinaceous deposits called drusen accumulate between the retinal pigment epithelium (RPE) and Bruch’s membrane, leading to impairment of oxygen and nutrient trafficking to the neural retina, and degeneration of the overlying photoreceptor cells. Owing to key differences in human and animal ocular anatomy and the slowly progressing nature of the disease, AMD is not easily modeled in vivo. In this study, we further characterize a “drusen-in-a-dish” primary porcine RPE model system by employing vital lipid staining to monitor sub-RPE deposition over time in monolayers of cells cultured on porous transwell membranes. We demonstrate for the first time using a semi-automated image analysis pipeline that the number and size of sub-RPE deposits increases gradually but significantly over time and confirm that sub-RPE deposits grown in culture immunostain positive for multiple known components found in human drusen. As a result, we propose that drusen-in-a-dish cell culture models represent a high-throughput and cost-scalable alternative to animal models in which to study the pathobiology of drusen accumulation and may serve as useful tools for screening novel therapeutics aimed at treating dry AMD.

ObjectiveTo investigate the confounding effect of nonexudative age-related macular degeneration (AMD), specifically drusen and outer retinal atrophy, on the architecture and automated segmentation of the inner retinal layers as measured with OCT.DesignObservational cross-sectional study.SubjectsTwo hundred sixty-three consecutive eyes with nonexudative AMD were identified through a retrospective chart review. Exclusion criteria were a diagnosis of glaucoma or glaucoma suspect, other retinal pathology affecting the macula, axial length > 26.5 mm or spherical equivalent less than -6 diopters, any other optic nerve or neurologic disorders, or poor image quality.MethodsDrusen were automatically segmented on macular OCT B-scans with a publicly available and validated deep learning approach. Automated segmentation of the inner plexiform layer (IPL)/inner nuclear layer (INL) boundary was carried out with the device's proprietary software.Main outcome measuresQuality of segmentation of the IPL/INL boundary as a function of drusen size and presence of inner retinal layer displacement in the area of macular pathology (drusen or atrophy).ResultsOne hundred twenty-five eyes (65 patients) met the inclusion criteria. Drusen size varied between 16 and 272 μm (mean, 118 μm). Automated segmentation had a 22% chance of failure if the drusen height was between 145 and 185 μm and was most likely to fail with drusen heights above 185 μm. When drusen height was normalized by total retinal thickness, segmentation failed 36% of the time when the drusen to total retinal thickness ratio was 0.45 or above. Images were likely to show displacement of inner retinal layers with drusen heights above 176 μm and a normalized drusen height ratio of 0.5 or higher. Eighty-seven percent of images with outer retinal atrophy displayed incorrect segmentation.ConclusionsOuter retinal diseases can alter the retinal topography and affect the segmentation accuracy of the inner retinal layers. Large drusen may cause segmentation error and compression of the inner macular layers. Geographic atrophy confounds automated segmentation in a high proportion of eyes. Clinicians should be cognizant of the effects of outer retinal disease on the inner retinal layer measurements when interpreting the results of macular OCT imaging in patients with glaucoma.

Drusen are one of the most characteristic pathologies of precursor lesion of age-related macular degeneration (AMD). Drusen comprise a yellowish white substance that accumulates typically under the retinal pigment epithelium (RPE), and their constituents are lipids, complement, amyloid, crystallin, and others. In the past, many researchers have focused on drusen and tried to elucidate the pathophysiology of AMD because they believed that disease progression from early AMD to advanced AMD might be based on drusen or drusen might cause AMD. In fact, it is well established that drusen are the hallmark of precursor lesion of AMD and a major risk factor for AMD progression mainly based on their size and number. However, the existence of advanced AMD without drusen has long been recognized. For example, polypoidal choroidal vasculopathy (PCV), which comprises the majority of AMD cases in Asians, often lacks drusen. Thus, there is the possibility that drusen might be no more than a biomarker of AMD and not a cause of AMD. Now is the time to reconsider the relationship between AMD and drusen. In this review, we focus on early AMD pathogenesis based on basic research from the perspective of cholesterol metabolism and hypoxic response in the retina, and we discuss the role of drusen. [ABSTRACT FROM AUTHOR]

The intricate parallels in structure and function between the human retina and the central nervous system designate the retina as a prospective avenue for understanding brain-related processes. This review extensively explores the shared physiopathological mechanisms connecting age-related macular degeneration (AMD) and proteinopathies, with a specific focus on tauopathies. The pivotal involvement of oxidative stress and cellular senescence emerges as key drivers of pathogenesis in both conditions. Uncovering these shared elements not only has the potential to enhance our understanding of intricate neurodegenerative diseases but also sets the stage for pioneering therapeutic approaches in AMD. [ABSTRACT FROM AUTHOR]

Artificial intelligence (AI) has emerged as a transformative technology across various fields, and its applications in the medical domain, particularly in ophthalmology, has gained significant attention. The vast amount of high-resolution image data, such as optical coherence tomography (OCT) images, has been a driving force behind AI growth in this field. Age-related macular degeneration (AMD) is one of the leading causes for blindness in the world, affecting approximately 196 million people worldwide in 2020. Multimodal imaging has been for a long time the gold standard for diagnosing patients with AMD, however, currently treatment and follow-up in routine disease management are mainly driven by OCT imaging. AI-based algorithms have by their precision, reproducibility and speed, the potential to reliably quantify biomarkers, predict disease progression and assist treatment decisions in clinical routine as well as academic studies. This review paper aims to provide a summary of the current state of AI in AMD, focusing on its applications, challenges, and prospects. [ABSTRACT FROM AUTHOR]

This study provides a comprehensive and extensive review of the use of deep learning techniques in diagnosing a variety of retinal diseases, such as Drusen, choroidal neovascularization (CNV), and diabetic macular edema (DME) using optical coherence tomography images (OCT). The research reviews the different models used in this field and evaluates their effectiveness, robustness, and reliability in distinguishing and diagnosing retinal diseases with high accuracy. The research analyzes the most effective and most widely used models in this field, focusing on the results achieved in terms of accuracy and reliability, highlighting the methods that showed the best performance in diagnosis, and improving and developing them in the future to achieve better results. The specialized data sets used to train and test these models are also reviewed, with an assessment of their role and importance in promoting and supporting scientific research in this field. Furthermore, the paper discusses recent advances in research that have been achieved in recent years. In addition, the research addresses current research gaps and challenges facing researchers and provides a comprehensive vision of future work that can contribute to the further development of this field. One of the topics that the research aims for is the importance of using deep learning techniques in the medical field to enhance the accuracy and speed of diagnosis. The research concludes by providing recommendations on future directions that research in this field can take, with the aim of achieving sustainable progress and improving the quality of healthcare for patients with retinal diseases using deep learning techniques. [ABSTRACT FROM AUTHOR]

Advanced forms of age‐related macular degeneration (AMD), characterised by atrophic and neovascular changes, are a leading cause of vision loss in the elderly population worldwide. Prior to the development of advanced AMD, a myriad of risk factors from the early and intermediate stages of AMD have been published in the scientific literature over the last years. The ability to precisely recognise structural and anatomical changes in the ageing macula, altogether with the understanding of the individual risk implications of each one of them is key for an accurate and personalised diagnostic assessment. The present review aims to summarise updated evidence of the relative risk conferred by diverse macular signs, commonly seen on optical coherence tomography, in terms of progression to geographic atrophy or macular neovascularization. This information may also serve as a basis for tailored follow‐up monitoring visits. [ABSTRACT FROM AUTHOR]

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Age-Related Macular Degeneration (AMD) is a highly prevalent form of retinal disease amongst Western communities over 50 years of age. A hallmark of AMD pathogenesis is the accumulation of drusen underneath the retinal pigment epithelium (RPE), a biological process also observable in vitro. The accumulation of drusen has been shown to predict the progression to advanced AMD, making accurate characterisation of drusen in vitro models valuable in disease modelling and drug development. More recently, deposits above the RPE in the subretinal space, called reticular pseudodrusen (RPD) have been recognized as a sub-phenotype of AMD. While in vitro imaging techniques allow for the immunostaining of drusen-like deposits, quantification of these deposits often requires slow, low throughput manual counting of images. This further lends itself to issues including sampling biases, while ignoring critical data parameters including volume and precise localization. To overcome these issues, we developed a semi-automated pipeline for quantifying the presence of drusen-like deposits in vitro, using RPE cultures derived from patient-specific induced pluripotent stem cells (iPSCs). Using high-throughput confocal microscopy, together with three-dimensional reconstruction, we developed an imaging and analysis pipeline that quantifies the number of drusen-like deposits, and accurately and reproducibly provides the location and composition of these deposits. Extending its utility, this pipeline can determine whether the drusen-like deposits locate to the apical or basal surface of RPE cells. Here, we validate the utility of this pipeline in the quantification of drusen-like deposits in six iPSCs lines derived from patients with AMD, following their differentiation into RPE cells. This pipeline provides a valuable tool for the in vitro modelling of AMD and other retinal disease, and is amenable to mid and high throughput screenings.

Background: Researchers need to find informative age-related macular degeneration (AMD) criteria which could be used for developing expert systems for the prediction of the course of the disease. Purpose: To evaluate risk factors of AMD progression on the basis of clinical and ophthalmological characteristics in patients of the Ukrainian population. Material and Methods: Totally, 302 eyes (152 patients) with AMD were included in the study. The stage of AMD was determined based on the Age-related Eye Disease Study (AREDS) guidelines. Median patient age (95% confidence interval (CI)) was 71.18 (69.47 – 72.89) years, most (82.9%) patients were of 60 – 85 years, and the percentage of women was 59.9%. Visual acuity, best-corrected visual acuity (BCVA), numbers of small, intermediate and large drusen, presence of retinal pigment epithelium (RPE) changes, subretinal neovascular membranes (SNM), and geographic RPE atrophy were assessed at baseline and at 1 year and 2 years. Statistical analyses were conducted using MedStat and MedCalc v.15.1 (MedCalc Software bvba, Ostende, Belgium) and EZR v.1.64 software (R Foundation for Statistical Computing, Austria). Results: There was a slow but statistically significant reduction in median BCVA (interquartile range (IQR)) from 0.4 (0.1–0.85) at baseline to 0.325 (0.1 – 0.8) (p < 0.001) at 2 years. Over the first year and over the second year, the frequency of RPE changes increased by 6.3% and 10.9%, respectively (p < 0.001), the frequency of SNM detection increased by 13.3% and 21.2%, respectively (p < 0.001), and the frequency of geographic atrophy detection, by 5.7% and 8.0%, respectively (p < 0.001). A multivariate logistic regression model was developed to select four covariates for the risk of AMD progression (the male gender, BCVA, number of small drusen and AREDS category at baseline). The BCVA was negatively associated (р = 0.026; OR = 0.12; 95% CI, 0.03 – 0.60), whereas the number of small drusen was positively associated with the risk of AMD progression (р = 0.009; OR = 1.02; 95% CI, 1.00–1.04). The risk of AMD progression was the highest for eyes with the AREDS category 2 (63.0%, 95% CI, 48.7% – 75.7 %), and the lowest for eyes with the AREDS category 3 (41.2 %, 95% CI, 29.4% – 53.8%, р = 0.049). Conclusion: First, over 24 months, we observed a slow but statistically significant reduction in visual acuity, with an increase in the frequency of RPE changes and detection of SNM and geographic atrophy. Second, a multivariate logistic regression model was developed to select four covariates for the risk of AMD progression (the male gender, BCVA, number of small drusen and AREDS category at baseline). The BCVA was negatively associated, whereas the number of small drusen was positively associated with the risk of AMD progression. Finally, the risk of AMD progression was the highest for eyes with the AREDS category 2, and the lowest for eyes with the AREDS category 3.

Abstract Introduction This study aimed to compare the integrity of the hyperreflective layer of the inner choroid in eyes with and without drusen. Methods Swept-source optical coherence tomography images of patients with drusen and normal controls were reviewed. Using a line plot of ImageJ, choroidal reflectivity was measured at the subfovea, and the integrity of the hyperreflective layer of the inner choroid was determined. Results In total, 63 eyes with drusen and 30 control eyes without drusen were included. The integrity of the hyperreflective layer of the inner choroid was preserved in 81.0% of eyes with drusen and 93.3% of normal controls. The proportion of eyes with the hyperreflective layer did not differ between eyes with and without drusen. Of the 63 subjects with drusen, this hyperreflective layer was observed in all 28 eyes (100%) with pachydrusen but only in 68.6% of the 35 eyes with soft drusen, and its prevalence was significantly different (P = 0.001). Conclusion The prevalence of the hyperreflective layer between the choriocapillaris and medium or large choroidal vessels in eyes with soft drusen differed from that in eyes with pachydrusen. These findings support the suggestion that changes within the choroidal stroma may be involved in the pathogenesis of age-related macular degeneration.

Classification and identification of eye diseases using Optical Coherence Tomography (OCT) has been a challenging task and a trending research area in recent years. Accurate classification and detection of different diseases are crucial for effective care management and improving vision outcomes. Current detection methods fall into two main categories: traditional methods and deep learning-based approaches. Traditional approaches rely on machine learning for feature extraction, while deep learning methods utilize data-driven classification model training. In recent years, Deep Learning (DL) and Machine Learning (ML) algorithms have become essential tools, particularly in medical image classification, and are widely used to classify and identify various diseases. However, due to the high spatial similarities in OCT images, accurate classification remains a challenging task. In this paper, we introduce a novel model called “OCTNet” that integrates a deep learning model combining InceptionV3 with a modified multi-scale attention-based spatial attention block to enhance model performance. OCTNet employs an InceptionV3 backbone with a fusion of dual attention modules to construct the proposed architecture. The InceptionV3 model generates rich features from images, capturing both local and global aspects, which are then enhanced by utilizing the modified multi-scale spatial attention block, resulting in a significantly improved feature map. To evaluate the model’s performance, we utilized two state-of-the-art (SOTA) datasets that include images of normal cases, Choroidal Neovascularization (CNV), Drusen, and Diabetic Macular Edema (DME). Through experimentation and simulation, the proposed OCTNet improves the classification accuracy of the InceptionV3 model by 1.3%, yielding higher accuracy than other SOTA models. We also performed an ablation study to demonstrate the effectiveness of the proposed method. The model achieved an overall average accuracy of 99.50% and 99.65% with two different OCT datasets.

Introduction: This study aimed to compare the integrity of the hyperreflective layer of the inner choroid in eyes with and without drusen. Methods: Swept-source optical coherence tomography images of patients with drusen and normal controls were reviewed. Using a line plot of ImageJ, choroidal reflectivity was measured at the subfovea, and the integrity of the hyperreflective layer of the inner choroid was determined. Results: In total, 63 eyes with drusen and 30 control eyes without drusen were included. The integrity of the hyperreflective layer of the inner choroid was preserved in 81.0% of eyes with drusen and 93.3% of normal controls. The proportion of eyes with the hyperreflective layer did not differ between eyes with and without drusen. Of the 63 subjects with drusen, this hyperreflective layer was observed in all 28 eyes (100%) with pachydrusen but only in 68.6% of the 35 eyes with soft drusen, and its prevalence was significantly different (P = 0.001). Conclusion: The prevalence of the hyperreflective layer between the choriocapillaris and medium or large choroidal vessels in eyes with soft drusen differed from that in eyes with pachydrusen. These findings support the suggestion that changes within the choroidal stroma may be involved in the pathogenesis of age-related macular degeneration. [ABSTRACT FROM AUTHOR]

Globally age‐related macular degeneration (AMD) is a leading cause of blindness with a significant impact on quality of life. Geographic atrophy (GA) is the atrophic late form of AMD and its prevalence increases markedly with age with around 1 in 5 persons aged 85 and above having GA in at least one eye. Bilateral GA leads to severe visual impairment thus posing a significant burden on patients, careers and health providers. The incidence and prevalence of GA varies across different geographic regions, with the highest rates in those of European ancestry. Although heterogeneity in definitions of GA and reporting strategy can explain some of the discrepancies, the data overall are consistent in showing a lower prevalence in other ethnicities such as those of Asian heritage. This is at present unexplained but thought to be due to the existence of protective factors such as differences in eye pigmentation, diet, environmental exposures and genetic variability. This review covers key aspects of the prevalence and incidence of the ocular precursor features of GA (large drusen, pigmentary abnormalities and reticular pseudo‐drusen), the late stage of GA and factors that have been known to be associated with modifying risk including systemic, demographic, environment, genetic and ocular. Understanding the global epidemiology scenario is crucial for the prevention of and management of patients with GA. [ABSTRACT FROM AUTHOR]

Background: Photobiomodulation (PBM) relies on the pathophysiological mechanism whereby red to near-infrared light can target mitochondrial activity and promote ATP synthesis. Preclinical and clinical studies have shown promising results in treating intermediate age-related macular degeneration (AMD), since PBM can produce photochemical reactions in endogenous retinal chromophores. Currently, PBM is approved by the Food and Drug Administration and by the European Medicines Agency for the treatment of intermediate AMD. This narrative review aimed to evaluate the available evidence on the effectiveness and safety of PBM in treating intermediate AMD. Methods: A comprehensive search was conducted using the PubMed database, employing the keywords "photobiomodulation" and "age-related macular degeneration." All English-language studies published up to June 2023 were reviewed, and the search was expanded to include relevant references from selected articles. The included publications were analyzed for this review. Results: The available studies on PBM in AMD demonstrated promising but inconsistent results. PBM showed potential in improving best-corrected visual acuity (BCVA) and contrast sensitivity (CS) in patients with AMD. Some studies also suggested a reduction in AMD lesions, such as drusen volume. However, the long-term efficacy and optimal treatment parameters of PBM in AMD remained to be fully determined due to the limitations of the available studies. These included variations in irradiation techniques, wavelengths, exposure times, and treatment sessions, making it challenging to generalize the effectiveness of PBM. Furthermore, the lack of accurate classification of AMD phenotypes in the available studies hindered the understanding of which phenotypes could truly benefit from this treatment. Finally, the strength of evidence varied among studies, with limited sample sizes, unpublished results, and only three randomized sham-controlled trials. Conclusions: Currently, the effectiveness of PBM in promoting drusen resorption or preventing progression to advanced forms of AMD, as observed in the cited studies, remains uncertain. [ABSTRACT FROM AUTHOR]

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

Purpose: An algorithm developed to obtain drusen area and volume measurements using swept-source OCT angiography (SS-OCTA) scans was tested on spectral-domain OCT angiography (SD-OCTA) scans. Design: Retrospective study. Participants: Forty pairs of scans from 27 eyes with intermediate age-related macular degeneration and drusen. Methods: Patients underwent both SD-OCTA and SS-OCTA imaging at the same visit using the 6 mm × 6 mm OCTA scan patterns. Using the same algorithm, we obtained drusen area and volume measurements within both 3 mm and 5 mm fovea-centered circles. Paired 2-sample t-tests were performed along with Pearson’s correlation tests. Main Outcome Measures: Mean square root (sqrt) drusen area and cube root (cbrt) drusen volume within the 3 mm and 5 mm fovea-centered circles. Results: Mean sqrt drusen area values from SD-OCTA and SS-OCTA scans were 1.57 (standard deviation [SD] 0.57) mm and 1.49 (SD 0.58) mm in the 3 mm circle and 1.88 (SD 0.59) mm and 1.76 (SD 0.58) mm in the 5 mm circle, respectively. Mean cbrt drusen volume measurements were 0.54 (SD 0.19) mm and 0.51 (SD 0.20) mm in the 3 mm circle, and 0.60 (SD 0.17) mm and 0.57 (SD 0.17) mm in the 5 mm circle. Small differences in area and volume measurements were found (all P 0.97; all P

The intricate parallels in structure and function between the human retina and the central nervous system designate the retina as a prospective avenue for understanding brain-related processes. This review extensively explores the shared physiopathological mechanisms connecting age-related macular degeneration (AMD) and proteinopathies, with a specific focus on tauopathies. The pivotal involvement of oxidative stress and cellular senescence emerges as key drivers of pathogenesis in both conditions. Uncovering these shared elements not only has the potential to enhance our understanding of intricate neurodegenerative diseases but also sets the stage for pioneering therapeutic approaches in AMD.

AIM: To assess the agreement of optical coherence tomography (OCT) algorithm-based retinal pigment epithelium –Bruch's membrane complex volume (RBV) with fundus photograph-based age-related macular degeneration (AMD) grading. METHODS: Digital color fundus photographs (CFPs) and spectral domain OCT images were acquired from 96 elderly subjects. CFPs were graded according to Age-Related Eye Disease Study (AREDS) classification. OCT image segmentation and RBV data calculation were done with OrionTM software. Univariate and multivariate analyses were performed to find out whether AMD lesion features associated with higher RBVs. RESULTS: RBV correlated with AMD grading (rs=0.338, P=0.001), the correlation was slightly stronger in early AMD (n=52; rs=0.432, P=0.001). RBV was higher in subjects with early AMD compared with those with no AMD lesions evident in fundus photographs (1.05±0.20 vs 0.96±0.13 mm3, P=0.023). In multivariate analysis higher RBVs were associated significantly with higher total drusen (β=0.388, P=0.027) and pigmentation areas (β=0.319, P=0.020) in fundus photographs, whereas depigmentation area (β=-0.295, P=0.015) associated with lower RBV. CONCLUSION: RBV correlate with AMD grading status, with a stronger association in patients with moderate, non-late AMD grades. This effect is driven mostly by lesions with drusen or pigmentation. Lesions with depigmentation tend to have lower values. RBV is more comprehensive measurement of the key area of AMD pathogenesis, compared to sole drusen volume analysis. RBV measurements are independent on grader variations and offer a possibility to quantify early and middle grade AMD lesions in a research setting, but may not substitute fundus photograph-based grading in the whole range of AMD spectrum.

Objectives:To compare the clinical findings and multimodal imaging of pediatric patients diagnosed with papilledema and pseudopapilledema with those of healthy individuals.Materials and Methods:Ninety children (0.05). The average, nasal, and temporal RNFL thicknesses were significantly higher in the pseudopapilledema group compared with the controls (p

Abstract Background Photobiomodulation (PBM) relies on the pathophysiological mechanism whereby red to near-infrared light can target mitochondrial activity and promote ATP synthesis. Preclinical and clinical studies have shown promising results in treating intermediate age-related macular degeneration (AMD), since PBM can produce photochemical reactions in endogenous retinal chromophores. Currently, PBM is approved by the Food and Drug Administration and by the European Medicines Agency for the treatment of intermediate AMD. This narrative review aimed to evaluate the available evidence on the effectiveness and safety of PBM in treating intermediate AMD. Methods A comprehensive search was conducted using the PubMed database, employing the keywords “photobiomodulation” and “age-related macular degeneration.” All English-language studies published up to June 2023 were reviewed, and the search was expanded to include relevant references from selected articles. The included publications were analyzed for this review. Results The available studies on PBM in AMD demonstrated promising but inconsistent results. PBM showed potential in improving best-corrected visual acuity (BCVA) and contrast sensitivity (CS) in patients with AMD. Some studies also suggested a reduction in AMD lesions, such as drusen volume. However, the long-term efficacy and optimal treatment parameters of PBM in AMD remained to be fully determined due to the limitations of the available studies. These included variations in irradiation techniques, wavelengths, exposure times, and treatment sessions, making it challenging to generalize the effectiveness of PBM. Furthermore, the lack of accurate classification of AMD phenotypes in the available studies hindered the understanding of which phenotypes could truly benefit from this treatment. Finally, the strength of evidence varied among studies, with limited sample sizes, unpublished results, and only three randomized sham-controlled trials. Conclusions Currently, the effectiveness of PBM in promoting drusen resorption or preventing progression to advanced forms of AMD, as observed in the cited studies, remains uncertain.

The letter to the editor discusses the LIGHTSITE II clinical study on the efficacy of photobiomodulation (PBM) in patients with non-exudative age-related macular degeneration (AMD). The authors express concerns about the study's limitations, including a small sample size, heterogeneity in the treatment and control groups, and incorrect positioning of OCT segmentation lines. They also question the interpretation of the results regarding best corrected visual acuity and the effect of PBM on geographic atrophy. The authors emphasize the need for high standards in clinical trials and express skepticism about the evidence presented in the LIGHTSITE II study. [Extracted from the article]

Geographic atrophy (GA) is an advanced stage of age-related macular degeneration (AMD) that leads to gradual and permanent vision loss. GA is characterized by the loss of photoreceptor cells and retinal pigment epithelium (RPE), leading to distinct atrophic patches in the macula, which tends to increase with time. Patients with geographic atrophy often experience a gradual and painless loss of central vision, resulting in difficulty reading, recognizing faces, or performing activities that require detailed vision. The primary risk factor for the development of geographic atrophy is advanced age; however, other risk factors, such as family history, smoking, and certain genetic variations, are also associated with AMD. Diagnosis is usually based on a comprehensive eye examination, including imaging tests such as fundus photography, optical coherence tomography (OCT), and fluorescein angiography. Numerous clinical trials are underway, targeting identified molecular pathways associated with GA that are promising. Recent approvals of Syfovre and Izervay by the FDA for the treatment of GA provide hope to affected patients. Administration of these drugs resulted in slowing the rate of progression of the disease. Though these products provide treatment benefits to the patients, they do not offer a cure for geographic atrophy and are limited in efficacy. Considering these safety concerns and limited treatment benefits, there is still a significant need for therapeutics with improved efficacy, safety profiles, and better patient compliance. This comprehensive review discusses pathophysiology, currently approved products, their limitations, and potential future treatment strategies for GA.

Purpose: To determine the interreader agreement for reticular pseudodrusen (RPD) assessment on combined infrared reflectance (IR) and OCT imaging in the early stages of age-related macular degeneration across a range of different criteria to define their presence. Design: Interreader agreement study. Participants: Twelve readers from 6 reading centers. Methods: All readers evaluated 100 eyes from individuals with bilateral large drusen for the following: (1) the presence of RPD across a range of different criteria and (2) the number of Stage 2 or 3 RPD lesions (from 0 to ≥ 5 lesions) on an entire OCT volume scan and on a selected OCT B-scan. Supportive information was available from the corresponding IR image. Main Outcome Measures: Interreader agreement, as assessed by Gwet’s first-order agreement coefficient (AC1). Results: When evaluating an entire OCT volume scan, there was substantial interreader agreement for the presence of any RPD, any or ≥ 5 Stage 2 or 3 lesions, and ≥ 5 definite lesions on en face IR images corresponding to Stage 2 or 3 lesions (AC1 = 0.60–0.72). On selected OCT B-scans, there was also moderate-to-substantial agreement for the presence of any RPD, any or ≥ 5 Stage 2 or 3 lesions (AC1 = 0.58–0.65) and increasing levels of agreement with increasing RPD stage (AC1 = 0.08, 0.56, 0.78, and 0.99 for the presence of any Stage 1, 2, 3, and 4 lesions, respectively). There was substantial agreement regarding the number of Stage 2 or 3 lesions on an entire OCT volume scan (AC1 = 0.68), but only fair agreement for this evaluation on selected B-scans (AC1 = 0.30). Conclusions: There was generally substantial or near-substantial—but not near-perfect—agreement for assessing the presence of RPD on entire OCT volume scans or selected B-scans across a range of differing RPD criteria. These findings underscore how interreader variability would likely contribute to the variability of findings related to the clinical associations of RPD. The low levels of agreement for assessing RPD number on OCT B-scans underscore the likely challenges of quantifying RPD extent with manual grading. Financial Disclosure(s): Proprietary or commercial disclosure may be found after the references.