Dry Age-related Macular Degeneration Research Articles

Retrospective analysis of the progression of early dry age-related macular degeneration in patients receiving versus not receiving a multi-component nutraceutical for four years

Purpose: To retrospectively analyze the optical coherence tomography (OCT) changes in retinal morphology and progression in these changes in patients with early dry age-related macular degeneration (AMD) receiving versus not receiving a multi-component nutraceutical daily for four years. Material and Methods: We retrospectively analyzed disease progression in 52 patients (98 eyes) with early dry AMD who had been regularly followed up for four years. Group 1 was comprised of 24 patients (98 eyes) who had been receiving vitamin and mineral tablets containing the AREDS2 formulation plus resveratrol and vitamin D daily for four years. Group 2 was comprised of 28 patients (53 eyes) who had not been receiving any nutritional supplement. Retinal morphology was assessed by OCT and OCT angiography. Results: In group 1, best-corrected visual acuity (BCVA) did not change after completion of the 4-year observation period compared to baseline (0.6 ± 02, p = 0.72). In group 2, BCVA was 0.6 ± 0.2 at baseline and decreased to 0.2 ± 0.2 in four years (p ≤ 0.001). In patients with a low to moderate risk of progression in groups 1 and 2, the four-year progression rate was 15.4% and 45.4%, respectively, which corresponds to an annual progression rate of 3.8% and 11.3%, respectively. In patients with a high risk of progression in groups 1 and 2, the four-year progression rate was 26.3% and 80%, respectively, which corresponds to an annual progression rate of 6.5% and 20%, respectively. Patients who had early dry AMD eyes with a low to moderate risk of progression (and a high risk of progression) at baseline and were not taking the nutritional supplement, had 4.58 greater odds (95% CI, 1.291 – 16.267; р = 0.018) [and 11.2 greater odds (95% CI, 2.505 – 50.081; р = 0.0016)] of having AMD progression than those receiving the nutritional supplement daily for four years. Conclusion: A regular intake of tablets containing the AREDS2 formulation plus resveratrol and vitamin D slows the progression of early dry AMD, especially in eyes with a high risk of disease progression, and contributes to the preservation of visual function.

A novel lipophenol quercetin derivative to prevent macular degeneration: Intravenous and oral formulations for preclinical pharmacological evaluation

Drugs with properties against oxidative and carbonyl stresses are potential candidates to prevent dry age-related macular degeneration (Dry-AMD) and inherited Stargardt disease (STGD1). Previous studies have demonstrated the capacity of a new lipophenol drug: 3-O-DHA-7-O-isopropyl-quercetin (Q-IP-DHA) to protect ARPE19 and primary rat RPE cells respectively from A2E toxicity and under oxidative and carbonyl stress conditions. In this study, first, a new methodology has been developed to access gram scale of Q-IP-DHA. After classification of the lipophenol as BCS Class IV according to physico-chemical and biopharmaceutical properties, an intravenous formulation with micelles (M) and an oral formulation using lipid nanocapsules (LNC) were developed. M were formed with Kolliphor® HS 15 and saline solution 0.9 % (mean size of 16 nm, drug loading of 95 %). The oral formulation was optimized and successfully allowed the formation of LNC (25 nm, 96 %). The evaluation of the therapeutic potency of Q-IP-DHA was performed after IV administration of micelles loaded with Q-IP-DHA (M−Q−IP−DHA) at 30 mg/kg and after oral administration of LNC loaded with Q-IP-DHA (LNC-Q-IP-DHA) at 100 mg/kg in mice. Results demonstrated photoreceptor protection after induction of retinal degeneration by acute light stress making Q-IP-DHA a promising preventive candidate against dry-AMD and STGD1.

Eyedrop delivery of therapeutic proteins with zwitterionic polymers to treat dry age-related macular degeneration

In clinics, therapeutic proteins are commonly used to treat retinal diseases through intraocular injection, the treatment which suffers from rather low patient compliance. Topical administration (e.g. eye-drops) of large molecule drugs remains a major challenge due to the presence of various barriers in the eye. In this study, zwitterion-grafted chitosan (CS-ZW) was developed and then self-assembled with protein therapeutics including adalimumab (ADA) or catalase (CAT) for the treatment of dry age-related macular degeneration (dAMD) via topical eyedrops. Since CS-ZW can cross the mucus layer and open the tight junctions between epithelial cells, their delivered therapeutic proteins can be shuttled across the ocular barriers to reach the diseased site in the fundus. CS-ZW/ADA eyedrops delivering ADA to bind TNF-α in the fundus achieved a similar therapeutic effect to intravitreal ADA injection in a mouse dAMD model. In addition, the therapeutic effect was further improved by combining eyedrop formulations of CS-ZW/ADA and CS-ZW/CAT, the latter of which can clear reactive oxygen species (ROS) in the lesion to further assist dAMD treatment. Our work provides a simple and effective delivery vehicle that can non-invasively treat fundus diseases such as dAMD, showing potential advantages in reducing side effects associated with intraocular injection and improving patient compliance.

Human Pluripotent Stem Cells Derived Endothelial Cells Repair Choroidal Ischemia.

Choroidal atrophy is a common fundus pathological change closely related to the development of age-related macular degeneration (AMD), retinitis pigmentosa, and pathological myopia. Studies suggest that choroidal endothelial cells (CECs) that form the choriocapillaris vessels are the first cells lost in choroidal atrophy. It is found that endothelial cells derived from human pluripotent stem cells (hPSC-ECs) through the MESP1+ mesodermal progenitor stage express CECs-specific markers and can integrate into choriocapillaris. Single-cell RNA-seq (scRNA-seq) studies show that hPSC-ECs upregulate angiogenesis and immune-modulatory and neural protective genes after interacting with ex vivo ischemic choroid. In a rat model of choroidal ischemia (CI), transplantation of hPSC-ECs into the suprachoroidal space increases choroid thickness and vasculature density. Close-up examination shows that engrafted hPSC-ECs integrate with all layers of rat choroidal vessels and last 90 days. Remarkably, EC transplantation improves the visual function of CI rats. The work demonstrates that hPSC-ECs can be used to repair choroidal ischemia in the animal model, which may lead to a new therapy to alleviate choroidal atrophy implicated in dry AMD, pathological myopia, and other ocular diseases.

Multi-Wavelength Photobiomodulation Ameliorates Sodium Iodate-Induced Age-Related Macular Degeneration in Rats.

Age-related macular degeneration (AMD) is a global health challenge. AMD causes visual impairment and blindness, particularly in older individuals. This multifaceted disease progresses through various stages, from asymptomatic dry to advanced wet AMD, driven by various factors including inflammation and oxidative stress. Current treatments are effective mainly for wet AMD; the therapeutic options for dry AMD are limited. Photobiomodulation (PBM) using low-energy light in the red-to-near-infrared range is a promising treatment for retinal diseases. This study investigated the effects of multi-wavelength PBM (680, 780, and 830 nm) on sodium iodate-induced oxidatively damaged retinal tissue. In an in vivo rat model of AMD induced by sodium iodate, multi-wavelength PBM effectively protected the retinal layers, reduced retinal apoptosis, and prevented rod bipolar cell depletion. Furthermore, PBM inhibited photoreceptor degeneration and reduced retinal pigment epithelium toxicity. These results suggest that multi-wavelength PBM may be a useful therapeutic strategy for AMD, mitigating oxidative stress, preserving retinal integrity, and preventing apoptosis.

Recent Advances in Imaging Macular Atrophy for Late-Stage Age-Related Macular Degeneration.

Age-related macular degeneration (AMD) is a leading cause of blindness worldwide. In late-stage AMD, geographic atrophy (GA) of dry AMD or choroidal neovascularization (CNV) of neovascular AMD eventually results in macular atrophy (MA), leading to significant visual loss. Despite the development of innovative therapies, there are currently no established effective treatments for MA. As a result, early detection of MA is critical in identifying later central macular involvement throughout time. Accurate and early diagnosis is achieved through a combination of clinical examination and imaging techniques. Our review of the literature depicts advances in retinal imaging to identify biomarkers of progression and risk factors for late AMD. Imaging methods like fundus photography; dye-based angiography; fundus autofluorescence (FAF); near-infrared reflectance (NIR); optical coherence tomography (OCT); and optical coherence tomography angiography (OCTA) can be used to detect and monitor the progression of retinal atrophy. These evolving diverse imaging modalities optimize detection of pathologic anatomy and measurement of visual function; they may also contribute to the understanding of underlying mechanistic pathways, particularly the underlying MA changes in late AMD.

Pathologic vs. protective roles of hypoxia-inducible factor 1 in RPE and photoreceptors in wet vs. dry age-related macular degeneration.

It has previously been reported that antioxidant vitamins can help reduce the risk of vision loss associated with progression to advanced age-related macular degeneration (AMD), a leading cause of visual impairment among the elderly. Nonetheless, how oxidative stress contributes to the development of choroidal neovascularization (CNV) in some AMD patients and geographic atrophy (GA) in others is poorly understood. Here, we provide evidence demonstrating that oxidative stress cooperates with hypoxia to synergistically stimulate the accumulation of hypoxia-inducible factor (HIF)-1α in the retinal pigment epithelium (RPE), resulting in increased expression of the HIF-1-dependent angiogenic mediators that promote CNV. HIF-1 inhibition blocked the expression of these angiogenic mediators and prevented CNV development in an animal model of ocular oxidative stress, demonstrating the pathological role of HIF-1 in response to oxidative stress stimulation in neovascular AMD. While human-induced pluripotent stem cell (hiPSC)-derived RPE monolayers exposed to chemical oxidants resulted in disorganization and disruption of their normal architecture, RPE cells proved remarkably resistant to oxidative stress. Conversely, equivalent doses of chemical oxidants resulted in apoptosis of hiPSC-derived retinal photoreceptors. Pharmacologic inhibition of HIF-1 in the mouse retina enhanced-while HIF-1 augmentation reduced-photoreceptor apoptosis in two mouse models for oxidative stress, consistent with a protective role for HIF-1 in photoreceptors in patients with advanced dry AMD. Collectively, these results suggest that in patients with AMD, increased expression of HIF-1α in RPE exposed to oxidative stress promotes the development of CNV, but inadequate HIF-1α expression in photoreceptors contributes to the development of GA.

Invited Session II: Retinal remodeling and regeneration: Developing autologous iPSC-RPE therapy for the treatment of AMD patients.

Age-related macular degeneration (AMD) is one the leading causes of vision loss in older people in the Western world. The disease is caused by degeneration of the retinal pigment epithelium (RPE) monolayer that supports photoreceptors. We used induced pluripotent stem cells (iPSC) to develop an autologous cell replacement therapy for treating dry AMD patients. Patients' blood cells were reprogrammed into iPSCs and differentiated iPSCs into RPE cells using a protocol developed in our lab. RPE cells were matured on a biodegradable polylactic co-glycolic acid (PLGA) scaffold for five weeks. Quality control assays confirmed the iPSC-RPE patch's purity, maturity, and functionality. Pre-clinical studies in rats and pigs demonstrated the safety and efficacy of iPSC-RPE-patch. Immune-compromised rats transplanted with a 0.5 mm iPSC-RPE patch showed no signs of tumor formation after nine months, confirming the safety profile. We laser-injured the RPE monolayer in the visual streak of pig eyes and, after 48 hours, transplanted the patch. Optical coherence tomography (OCT) confirmed the integration of the patch. A multi-focal electroretinogram (ERG) showed that the retinal layers' electric response was much higher than the lasered area without the implant. We started a phase I/IIa trial for an autologous iPSC-RPE patch to treat AMD. This ongoing trial will test the safety, feasibility, and integration of the iPSC-RPE patch in 12 AMD patients.

Investigating the Spatiotemporal Summation of Perimetric Stimuli in Dry Age-Related Macular Degeneration.

To measure achromatic spatial, temporal, and spatiotemporal summation in dry age-related macular degeneration (AMD) compared to healthy controls under conditions of photopic gaze-contingent perimetry. Twenty participants with dry AMD (mean age, 74.6 years) and 20 healthy controls (mean age, 67.8 years) performed custom, gaze-contingent perimetry tests. An area-modulation test generated localized estimates of Ricco's area (RA) at 2.5° and 5° eccentricities along the 0°, 90°, 180°, and 270° meridians. Contrast thresholds were measured at the same test locations for stimuli of six durations (3.7-190.4 ms) with a Goldmann III stimulus (GIII, 0.43°) and RA-scaled stimuli. The upper limit (critical duration) of complete temporal summation (using the GIII stimulus) and spatiotemporal summation (using the RA stimuli) was estimated using iterative two-phase regression analysis. Median (interquartile range [IQR]) RA estimates were significantly larger in AMD participants (2.5°: 0.21 [0.09-0.41] deg2; 5°: 0.32 [0.15-0.65 deg2]) compared to healthy controls (2.5°: 0.08 [0.05-0.13] deg2; 5°: 0.15 [0.08-0.22] deg2) at all test locations (all P < 0.05). No significant difference in median critical duration was found in AMD participants with the GIII stimulus (19.6 [9.9-30.4] ms) and RA-scaled stimuli (22.9 [13.9-40.3] ms) compared to healthy controls (GIII: 17.0 [11.3-24.0] ms; RA-scaled: 22.4 [14.3-33.1] ms) at all test locations (all P > 0.05). Spatial summation is altered in dry AMD, without commensurate changes in temporal summation. The sensitivity of perimetry to AMD may be improved by utilizing stimuli that probe alterations in spatial summation in the disease.

Melatonin protects photoreceptor cells against ferroptosis in dry AMD disorder by inhibiting GSK-3B/Fyn-dependent Nrf2 nuclear translocation

BackgroundFerroptosis is a type of non-apoptotic cell death that relies on iron ions and reactive oxygen species to induce lipid peroxidation. This study aimed to determine whether ferroptosis exists in the pathogenesis of dry age-related macular degeneration (AMD) and to confirm that melatonin (MLT) suppresses the photoreceptor cell ferroptosis signaling pathway. MethodsWe exposed 661W cells to sodium iodate (NaIO3) in vitro and treated them with different concentrations of MLT. In vivo, C57BL/6 mice were given a single caudal vein injection of NaIO3, followed by an intraperitoneal injection of MLT, and eyeballs were taken for subsequent trials. ResultsWe found that NaIO3 could induce photoreceptor cell death and lipid peroxide accumulation, and result in changes in the expression of ferroptosis-related factors and iron maintenance proteins, which were treated by MLT. We further demonstrated that MLT can block Fyn-dependent Nrf2 nuclear translocation by suppressing the GSK-3β signaling pathway. In addition, the therapeutic effect of MLT was significantly inhibited when Nrf2 was silenced. ConclusionsOur findings provide a novel insight that NaIO3 induces photoreceptor cell ferroptosis in dry AMD and suggest that MLT has therapeutic effects by suppressing GSK-3β/Fyn-dependent Nrf2 nuclear translocation.

Deep learning model for automatic differentiation of EMAP from AMD in macular atrophy

To create a deep learning (DL) classifier pre-trained on fundus autofluorescence (FAF) images that can assist the clinician in distinguishing age-related geographic atrophy from extensive macular atrophy and pseudodrusen-like appearance (EMAP). Patients with complete outer retinal and retinal pigment epithelium atrophy secondary to either EMAP (EMAP Group) or to dry age related macular degeneration (AMD group) were retrospectively selected. Fovea-centered posterior pole (30° × 30°) and 55° × 55° degree-field-of-view FAF images of sufficiently high quality were collected and used to train two different deep learning (DL) classifiers based on ResNet-101 design. Testing was performed on a set of images coming from a different center. A total of 300 patients were recruited, 135 belonging to EMAP group and 165 belonging to AMD group. The 30° × 30° FAF based DL classifier showed a sensitivity of 84.6% and a specificity of 85.3% for the diagnosis of EMAP. The 55° × 55° FAF based DL classifier showed a sensitivity of 90% and a specificity of 84.6%, a performance that was significantly higher than that of the 30° × 30° classifer (p = 0.037). Artificial intelligence can accurately distinguish between atrophy caused by AMD or by EMAP on FAF images. Its performance are improved using wide field acquisitions.

Long‐Lasting Stabilization and Improvement of Dry Age‐Related Macular Degeneration by a High Oral Taurine Dose

Purpose: To examine the therapeutic potential of the amino acid taurine in the non‐ neovascular or ∙dry” form of Age‐Related Macular Degeneration (AMD), one of the main causes of vision loss in the elderly, which still lacks effective treatments. Taurine is the most abundant amino acid in the retina and exerts trophic and neuroprotective actions in cellular and animal models. Likewise, a recent Science paper indicates that taurine deficiency is a driver of aging and that taurine supplementation may be an effective treatment for age‐related diseases. Case Description: A dry AMD patient (F.A., male, 62‐yr old) presented a Snellen best corrected visual acuity of 0.15 on the Right Eye (RE) and 0.2 on the Left Eye (LE) in June 2013, together with central retina atrophy and reduction of central macular thickness to 144 µm (RE) and 159 µn (LE) (OCT analysis; Topcon 3D OCT1000). Oral taurine intake (600 mg t.i.d.) arrested macular degeneration over a 5.5‐yr period and moderately improved visual acuity and macular thickness after doubling the dose from 1.8 g/day to 3.6 g/day in December 2018. This improvement remained stable until last control visit in January 2023. Conclusion: Taurine may have disease‐modifying properties in dry AMD at the dose used. The present observations add to existing literature to foster proof‐of‐concept clinical trials using a high oral dose of taurine for the treatment of AMD.

Linking Adiponectin and Its Receptors to Age-Related Macular Degeneration (AMD).

In recent years, there has been a captivating focus of interest in elucidating the intricate crosstalk between adiponectin (APN), a versatile fat-associated adipokine and ocular pathologies. Unveiling the intricate relationship between adipocytokine APN and its receptors (AdipoRs) with aging eye disorders has emerged as a fascinating frontier in medical research. This review article delves into this connection, illuminating the hidden influence of APN on retinal health. This comprehensive review critically examines the latest findings and breakthroughs that underscore the pivotal roles of APN/AdipoRs signaling in maintaining ocular homeostasis and protecting against eye ailments. Here, we meticulously explore the intriguing mechanisms by which APN protein influences retinal function and overall visual acuity. Drawing from an extensive array of cutting-edge studies, the article highlights APN's multifaceted functions, ranging from anti-inflammatory properties and oxidative stress reduction to angiogenic regulation within retinal and macula tissues. The involvement of APN/AdipoRs in mediating these effects opens up novel avenues for potential therapeutic interventions targeting prevalent aging eye conditions. Moreover, this review unravels the interplay between APN signaling pathways and age-related macular degeneration (AMD). The single-cell RNA-seq results validate the expression of both the receptor isoforms (AdipoR1/R2) in retinal cells. The transcriptomic analysis showed lower expression of AdipoR1/2 in dry AMD pathogenesis compared to healthy subjects. The inhibitory adiponectin peptide (APN1) demonstrated over 75% suppression of CNV, whereas the control peptide did not exert any inhibitory effect on choroidal neovascularization (CNV). The elucidation of these relationships fosters a deeper understanding of adipose tissue's profound influence on ocular health, presenting new prospects for personalized treatments and preventative measures. Because APN1 inhibits CNV and leakage, it can be used to treat human AMD, although the possibility to treat human AMD is in the early stage and more clinical research is needed. In conclusion, this review provides a captivating journey into the enthralling world of APN, intertwining the realms of adipose biology and ophthalmology in aging.

Association of NLRPs with pathogenesis of dry age-related macular degeneration.

Age-related macular degeneration (AMD) is the leading cause of blindness in the elderly population, and Dry AMD is the most common clinical subtype. However, effective measures for the early diagnosis and treatment of dry AMD have not been proposed. In recent years, NOD-like receptors (NLRs) have received attention in the study of AMD as an important class of pattern recognition receptors. We attempted to elucidate the pathogenesis of NLRs in dry AMD from the perspective of chronic inflammation. This study involved 13 patients with dry AMD, 10 age- and sex-matched normal population without any history of disease and 8 patients with wet AMD as controls. Using RT-qPCR, the mRNA expression levels of NLRs in peripheral blood peripheral blood mononuclear cells (PBMCs) were compared to analyze the statistical differences in the expression contents among the three populations. The relative RNA expression of nucleotide-binding oligomerization-like receptor protein 12 (NLRP12) with negative regulation of inflammation was significantly lower in dry AMD patients than in normal people and wet AMD patients. And NLRX1, which also has an anti-inflammatory effect, was lower in dry AMD patients than in wet AMD patients. However, NLRP3 with proinflammatory effect was significantly expressed in wet AMD. The significant decrease in NLRP12 in dry AMD may become a breakthrough in the study of dry AMD and systemic chronic inflammatory response. However, NLRP3 may have a more important role in wet AMD.

Complement factor H Y402H polymorphism results in diminishing CD4+ T cells and increasing C-reactive protein in plasma

Age-related macular degeneration (AMD) is a common cause of visual loss among the elderly. Genetic variants in the gene encoding complement factor H (CFH) have been identified as an AMD susceptibility gene, however, the mechanistic link is debated. Here, we investigated the link between the CFH Y402H genotype and low-grade inflammation. We recruited 153 healthy individuals, 84 participants with dry stages of AMD, and 148 participants with neovascular AMD. All participants were subjected to detailed retinal examination, and interview regarding comorbidities and lifestyle. Blood samples were analyzed for level of C-Reactive Protein (CRP), white blood cell differential count, and stained with fluorescent antibodies to differentiate CD4+ and CD8+ T cells. CFH Y402H genotyping was performed using an allele-specific polymerase chain reaction genotyping assay. Splenocytes from young and aged wild type and Cfh null mutant C57BL/6J mice were examined for CD4+ and CD8+ T cells. Healthy individuals with the CFH Y402H at-risk polymorphism HH had higher levels of CRP and lower proportions of CD4+ T cells compared to persons with the YH or YY polymorphism (P = 0.037, Chi-square). Healthy individuals with the HH polymorphism displayed lower proportions of CD4+ T cells with ageing (P < 0.01, one-way ANOVA), whereas both young and aged Cfh null mutant mice displayed lower proportions of CD4+ T cells (P < 0.001 and P < 0.05; unpaired t test). Participants with dry AMD and the HH polymorphism had similarly lower proportions of CD4+ T cells (P = 0.024, one-way ANOVA), but no difference in CRP-levels. In the neovascular stage of AMD, there was no difference in proportion of CD4+ cells or CRP levels according to genotype. The risk-associated CFH genotype is associated with an age-related decrease in proportion of CD4+ T cells and increased levels of CRP in healthy individuals. This indicates that decreased complement regulation results in extensive changes in innate and adaptive immune compartments that precede development of AMD.

Complete resolution of subretinal fluid of the fellow eye following aflibercept injection in wet AMD

Abstract Purpose: To present a case of a patient with bilateral wet age-related macular degeneration (AMD) who was unilaterally treated with intravitreal aflibercept injections (IAIs) and the disease status in the fellow eye ameliorated after an IAI. Methods: Retrospective case report. Results: A 72-year-old woman was diagnosed with wet and dry AMD in her right (OD) and left (OS) eye, respectively. In OD, treatment strategy comprised 3 monthly IAIs, followed by re-injections according-to-need, while optical coherence tomography (OCT) scans were performed before IAIs. One month after the second IAI, subretinal fluid developed in OS. One week later, an IAI was applied in OD; two days later the disease status in OS was assessed by fluorescein angiography and OCT. Surprisingly, in OS subretinal fluid completely resolved and fluorescein angiography did not detect leakage, highlighting the absence of an active choroidal neovascularization. The short interval between IAI and the resolution of exudative phenomena in the other eye is suggestive of a beneficial effect in the contralateral eye. Conclusion: Herein we showed that an IAI had an effect to the fellow untreated eye. Our observation is consistent with active aflibercept in the systemic circulation. To the best of our knowledge, no other report in literature has demonstrated this effect of aflibercept in wet AMD.

Co-cultivation of primary porcine RPE cells and neuroretina induces inflammation: a potential inflammatory AMD-model

One common aspect in the pathology of many retinal diseases like age-related macular degeneration (AMD) is the death of retinal pigment epithelium (RPE) cells. RPE cells are essential for photoreceptor survival as they recycle and remove compounds of the visual cycle and secrete protective cytokines. Studying RPE cells is crucial to improve our understanding of retinal pathologies, yet only a few retinal ex vivo models include them or do so only indirectly. Besides the positive effects in indirect co-cultivation models, also a slight inflammation was observed. In this study we developed an ex vivo model consisting of a primary porcine RPE monolayer directly co-cultured with porcine retinal organ cultures, to investigate and simulate inflammatory retinal diseases, such as (dry) AMD. The direct co-cultivation resulted in immune reactivity (enhanced expression of pro-inflammatory cytokines e.g., IL-1β, IL-6,IL-8) and cell death. These effects were evaluated for the retinal explant as well as for the RPE-monolayer to further understand the complex interactions between these two compartments. Taken together, this ex vivo model can be used to study inflammatory retinal diseases like AMD as well as the rejection observed after RPE-transplantation.

Telehealth improves follow-up and monitoring of age-related macular degeneration during the COVID-19 pandemic.

To prevent vision loss, it is important to monitor patients with age-related macular degeneration (AMD) for the development of choroidal neovascularization. The coronavirus disease 2019 (COVID-19) pandemic caused many patients to miss or delay visits. To offset those gaps in care, providers utilized telehealth (TH) to evaluate patients for symptoms of disease progression and provide health education on the importance of continuous monitoring. This study evaluates the impact of TH encounters on the rate of return for recommended in-person examinations for 1103 patients with non-neovascular (dry) AMD seen in an outpatient ophthalmology clinic in 2019 and due for return evaluation after the outbreak of COVID-19 in 2020. Logistic regression analysis was used to identify demographic, clinical, and sociomedical factors associated with TH utilization and in-person return. 422 patients (38%) utilized TH during the study period. Patients who completed a TH encounter were more likely to return for an in-person examination as compared with those who did not receive TH (OR: 1.8, CI 95%: 1.4-2.3, P < 0.001). Completing a TH visit was associated with the detection of new wet AMD (OR: 3.3, 95% CI 1.04-10.6, P = 0.043), as well as with an earlier return for those patients who were found to have disease progression (62 ± 54days vs. 100 ± 57days, P = 0.049). Completing a TH visit increased the rate at which patients with dry AMD returned for recommended in-person eye examinations. In many cases, this permitted the earlier detection of wet AMD, which is linked with achieving better outcomes.

Activation of Lysosomal Function Ameliorates Amyloid-β-Induced Tight Junction Disruption in the Retinal Pigment Epithelium.

Accumulation of pathogenic amyloid-β disrupts the tight junction of retinal pigment epithelium (RPE), one of its senescence-like structural alterations. In the clearance of amyloid-β, the autophagy-lysosome pathway plays the crucial role. In this context, mammalian target of rapamycin (mTOR) inhibits the process of autophagy and lysosomal degradation, acting as a potential therapeutic target for age-associated disorders. However, efficacy of targeting mTOR to treat age-related macular degeneration remains largely elusive. Here, we validated the therapeutic efficacy of the mTOR inhibitors, Torin and PP242, in clearing amyloid-β by inducing the autophagy-lysosome pathway in a mouse model with pathogenic amyloid-β with tight junction disruption of RPE, which is evident in dry age-related macular degeneration. High concentration of amyloid-β oligomers induced autophagy-lysosome pathway impairment accompanied by the accumulation of p62 and decreased lysosomal activity in RPE cells. However, Torin and PP242 treatment restored the lysosomal activity via activation of LAMP2 and facilitated the clearance of amyloid-β in vitro and in vivo. Furthermore, clearance of amyloid-β by Torin and PP242 ameliorated the tight junction disruption of RPE in vivo. Overall, our findings suggest mTOR inhibition as a new therapeutic strategy for the restoration of tight junctions in age-related macular degeneration.

Deep Learning Approach for Age-related Macular Degeneration Detection Using Retinal Images: Efficacy Evaluation of Different Deep Learning Models

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