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Journal of Clinical Medicine Jun 2024The aim of this study is to report short-term outcomes after the shortening of the treatment interval to 4 weeks with a treat-and-extend (TAE) regimen (Si4w) of...
The aim of this study is to report short-term outcomes after the shortening of the treatment interval to 4 weeks with a treat-and-extend (TAE) regimen (Si4w) of aflibercept in patients with refractory neovascular age-related macular degeneration (nAMD). This retrospective study included 34 patients given aflibercept with a TAE regimen of a minimum of a 4-week interval when they had a limited response to bimonthly aflibercept. The best-corrected visual acuity (BCVA) and central macular thickness (CMT) were compared before and after Si4w. The resolution of subretinal and intraretinal fluid before and after Si4w was also examined. The risk factors associated with persistent fluid were analyzed. The average treatment duration until initiation of Si4w was 57.82 ± 28.59 months, with an average of 23.64 ± 12.40 injections administered. The BCVA was not significantly improved after Si4w. The CMT decreased significantly from 427.91 ± 125.74 μm to 336.38 ± 121.67 μm at the third visit ( < 0.001). Eighteen eyes (52.9%) showed complete resolution, and twenty-three eyes (67.6%) experienced complete resolution at least once during the three visits. The duration of fluid before Si4w was significantly associated with complete resolution ( = 0.011). Si4w of aflibercept showed satisfactory anatomical outcomes with complete resolution of fluid in patients with a limited response to bimonthly aflibercept injections, and should be considered as a useful treatment option.
PubMed: 38930032
DOI: 10.3390/jcm13123503 -
Journal of Clinical Medicine Jun 2024: This study aimed to assess the effectiveness of bi-monthly brolucimumab treatment in patients with neovascular age-related macular degeneration (nAMD) refractory to...
: This study aimed to assess the effectiveness of bi-monthly brolucimumab treatment in patients with neovascular age-related macular degeneration (nAMD) refractory to monthly aflibercept treatment. : A retrospective chart review included 32 eyes of patients with refractory nAMD who switched from monthly intravitreal aflibercept treatment to bi-monthly intravitreal brolucizumab treatment. This study evaluated changes in visual acuity (VA), intraretinal fluid (IRF), subretinal fluid (SRF), pigment epithelial detachment (PED), and central macular thickness (CMT), at specific times as follows: baseline before switching (T0), 2 months after switching (T1), 4 months after switching (T2), and 6 months after switching (T3). : The mean best-corrected visual acuity (BCVA) did not significantly change across all time points (0.52 ± 0.12, 0.48 ± 0.27, 0.48 ± 0.28, and 0.50 ± 0.27 logarithms of the minimum angle of resolution in T0, T1, T2, and T3, respectively). CMT significantly decreased after additional brolucizumab injections compared to the baseline (218.2 ± 48.6 and 207.9 ± 49.8 μm, respectively; = 0.001). The PED height also significantly decreased from 251.0 ± 165.4 to 154.4 ± 115.65 μm ( < 0.001), with complete resolution in nine patients (28%). The mean subfoveal choroidal thickness (SFCT) before brolucizumab treatment was 262.8 ± 79.7 μm, which decreased to 233.0 ± 71.2 μm ( = 0.001) after the first injection. The final SFCT also significantly decreased after additional brolucizumab injections compared to the baseline SFCT ( = 0.012). : Bi-monthly brolucizumab treatment proves effective for patients refractory to monthly fixed aflibercept, resulting in positive anatomical changes without significant deterioration in visual acuity. This approach provides a promising prognosis while reducing the treatment burden on refractory patients.
PubMed: 38929964
DOI: 10.3390/jcm13123434 -
Journal of Personalized Medicine Jun 2024The majority of neurodegenerative eye disorders occur with aging and significantly impair quality of life. Age-related macular degeneration (AMD) is the third most... (Review)
Review
The majority of neurodegenerative eye disorders occur with aging and significantly impair quality of life. Age-related macular degeneration (AMD) is the third most common cause of visual impairment and blindness worldwide. One of the most important elements in the pathophysiology of neurodegenerative eye disease is certainly oxidative stress, with neuroinflammation and ocular ischemia which may also be significant factors. Antioxidants, either by food or oral supplementation, may be able to mitigate the deleterious effects of reactive oxygen species that build as a result of oxidative stress, ischemia, and inflammation. Over the past few decades, a number of research works examining the potential adjuvant impact of antioxidants in AMD have been published. In fact, there is not only more and more interest in already known molecules but also in new molecules that can help clinicians in the management of this complex multifactorial disease, such as astaxanthin and melatonin. However, while some studies showed encouraging outcomes, others were conflicting. In addition, more and more attention is also being paid to nutrition, considered a pivotal key point, especially to prevent AMD. For this reason, the purpose of this review is to analyze the main antioxidant molecules currently used as oral supplements for AMD treatment, as well as the role of diet and food intake in this ocular disease, to better understand how all these factors can improve the clinical management of AMD patients.
PubMed: 38929874
DOI: 10.3390/jpm14060653 -
Life (Basel, Switzerland) May 2024The escalating prevalence of retinal diseases-notably, age-related macular degeneration and hereditary retinal disorders-poses an intimidating challenge to ophthalmic... (Review)
Review
The escalating prevalence of retinal diseases-notably, age-related macular degeneration and hereditary retinal disorders-poses an intimidating challenge to ophthalmic medicine, often culminating in irreversible vision loss. Current treatments are limited and often fail to address the underlying loss of retinal cells. This paper explores the potential of stem-cell-based therapies as a promising avenue for retinal regeneration. We review the latest advancements in stem cell technology, focusing on embryonic stem cells (ESCs), pluripotent stem cells (PSCs), and mesenchymal stem cells (MSCs), and their ability to differentiate into retinal cell types. We discuss the challenges in stem cell transplantation, such as immune rejection, integration into the host retina, and functional recovery. Previous and ongoing clinical trials are examined to highlight the therapeutic efficacy and safety of these novel treatments. Additionally, we address the ethical considerations and regulatory frameworks governing stem cell research. Our analysis suggests that while stem-cell-based therapies offer a groundbreaking approach to treating retinal diseases, further research is needed to ensure long-term safety and to optimize therapeutic outcomes. This review summarizes the clinical evidence of stem cell therapy and current limitations in utilizing stem cells for retinal degeneration, such as age-related macular degeneration, retinitis pigmentosa, and Stargardt's disease.
PubMed: 38929652
DOI: 10.3390/life14060668 -
Medicina (Kaunas, Lithuania) Jun 2024: Age-related macular degeneration (AMD) is a complex and multifactorial condition that can lead to permanent vision loss once it progresses to the neovascular exudative... (Review)
Review
: Age-related macular degeneration (AMD) is a complex and multifactorial condition that can lead to permanent vision loss once it progresses to the neovascular exudative stage. This review aims to summarize the use of deep learning in neovascular AMD. : Pubmed search. : Deep learning has demonstrated effectiveness in analyzing structural OCT images in patients with neovascular AMD. This review outlines the role of deep learning in identifying and measuring biomarkers linked to an elevated risk of transitioning to the neovascular form of AMD. Additionally, deep learning techniques can quantify critical OCT features associated with neovascular AMD, which have prognostic implications for these patients. Incorporating deep learning into the assessment of neovascular AMD eyes holds promise for enhancing clinical management strategies for affected individuals. : Several studies have demonstrated effectiveness of deep learning in assessing neovascular AMD patients and this has a promising role in the assessment of these patients.
Topics: Humans; Deep Learning; Macular Degeneration; Tomography, Optical Coherence
PubMed: 38929607
DOI: 10.3390/medicina60060990 -
Medicina (Kaunas, Lithuania) Jun 2024The complement cascade is a vital system in the human body's defense against pathogens. During the natural aging process, it has been observed that this system is... (Review)
Review
The complement cascade is a vital system in the human body's defense against pathogens. During the natural aging process, it has been observed that this system is imperative for ensuring the integrity and homeostasis of the retina. While this system is critical for proper host defense and retinal integrity, it has also been found that dysregulation of this system may lead to certain retinal pathologies, including geographic atrophy and diabetic retinopathy. Targeting components of the complement system for retinal diseases has been an area of interest, and in vivo, ex vivo, and clinical trials have been conducted in this area. Following clinical trials, medications targeting the complement system for retinal disease have also become available. In this manuscript, we discuss the pathophysiology of complement dysfunction in the retina and specific pathologies. We then describe the results of cellular, animal, and clinical studies targeting the complement system for retinal diseases. We then provide an overview of complement inhibitors that have been approved by the Food and Drug Administration (FDA) for geographic atrophy. The complement system in retinal diseases continues to serve as an emerging therapeutic target, and further research in this field will provide additional insights into the mechanisms and considerations for treatment of retinal pathologies.
Topics: Humans; Retinal Diseases; Complement System Proteins; Animals; Complement Inactivating Agents; Diabetic Retinopathy; Retina
PubMed: 38929562
DOI: 10.3390/medicina60060945 -
Antioxidants (Basel, Switzerland) May 2024This study aims to investigate the role of microRNA let-7f in the dysfunction and degeneration of retinal pigment epithelium (RPE) cells through the induction of...
This study aims to investigate the role of microRNA let-7f in the dysfunction and degeneration of retinal pigment epithelium (RPE) cells through the induction of senescence and oxidative stress. Furthermore, we explore whether let-7f inhibition can protect these cells against sodium iodate (SI)-induced oxidative stress. Oxidative stress and let-7f expression are reciprocally regulated in retinal pigment epithelial cells. Overexpression of let-7f in ARPE-19 cells induced oxidative stress as demonstrated by increased reactive oxygen species (ROS) production as well as senescence. Inhibition of let-7f successfully protected RPE cells from the detrimental effects induced by SI. In addition, let-7f overexpression induced RPE cellular dysfunction by diminishing their migratory capabilities and reducing the phagocytosis of porcine photoreceptor outer segments (POS). Results were further confirmed in vivo by intravitreal injections of SI and let-7f antagomir in C57BL/6 mice. Our results provide strong evidence that let-7f is implicated in the dysfunction of RPE cells through the induction of senescence and oxidative injury. These findings may help to uncover novel and relevant processes in the pathogenesis of dry AMD.
PubMed: 38929085
DOI: 10.3390/antiox13060646 -
International Journal of Molecular... Jun 2024Age-related macular degeneration (AMD) is a chronic disease, which often develops in older people, but this is not the rule. AMD pathogenesis changes include the... (Review)
Review
Age-related macular degeneration (AMD) is a chronic disease, which often develops in older people, but this is not the rule. AMD pathogenesis changes include the anatomical and functional complex. As a result of damage, it occurs, in the retina and macula, among other areas. These changes may lead to partial or total loss of vision. This disease can occur in two clinical forms, i.e., dry (progression is slowly and gradually) and exudative (wet, progression is acute and severe), which usually started as dry form. A coexistence of both forms is possible. AMD etiology is not fully understood. Extensive genetic studies have shown that this disease is multifactorial and that genetic determinants, along with environmental and metabolic-functional factors, are important risk factors. This article reviews the impact of heavy metals, macro- and microelements, and genetic factors on the development of AMD. We present the current state of knowledge about the influence of environmental factors and genetic determinants on the progression of AMD in the confrontation with our own research conducted on the Polish population from Kuyavian-Pomeranian and Lubusz Regions. Our research is concentrated on showing how polluted environments of large agglomerations affects the development of AMD. In addition to confirming heavy metal accumulation, the growth of risk of acute phase factors and polymorphism in the genetic material in AMD development, it will also help in the detection of new markers of this disease. This will lead to a better understanding of the etiology of AMD and will help to establish prevention and early treatment.
Topics: Humans; Macular Degeneration; Risk Factors; Genetic Predisposition to Disease; Metals, Heavy; Environmental Exposure; Immunogenetics
PubMed: 38928273
DOI: 10.3390/ijms25126567 -
International Journal of Molecular... Jun 2024Age-related macular degeneration (AMD) is strictly linked to chronic oxidative stress, inflammation, loss of epithelial barrier integrity, and often with abnormal new...
Vitamin D and Sulforaphane Decrease Inflammatory Oxidative Stress and Restore the Markers of Epithelial Integrity in an In Vitro Model of Age-Related Macular Degeneration.
Age-related macular degeneration (AMD) is strictly linked to chronic oxidative stress, inflammation, loss of epithelial barrier integrity, and often with abnormal new blood vessel development. In this study, the retinal epithelial cell line ARPE-19 was treated with pro-inflammatory transforming growth factor-beta (TGF-β) to investigate the activity of vitamin D (VD) and sulforaphane (SF) in abating the consequences of oxidative stress and inflammation. The administration of VD and SF lowered reactive oxygen species (ROS) levels, and abated the related expression of the pro-inflammatory cytokines interleukin-6 and interleukin-8 induced by TGF-β. We evaluated mitochondrial respiration as a source of ROS production, and we discovered that the increased transcription of respiratory elements triggered by TGF-β was prevented by VD and SF. In this model of inflamed epithelium, the treatment with VD and SF also reduced the secretion of VEGF, a key angiogenic factor, and restored the markers of epithelial integrity. Remarkably, all the observed biological effects were potentiated by the co-stimulation with the two compounds and were not mediated by VD receptor expression but rather by the ERK 1/2 pathway. Altogether, the results of this study reveal the powerful synergistic anti-inflammatory activity of SF and VD and lay the foundation for future clinical assessment of their efficacy in AMD.
Topics: Humans; Macular Degeneration; Isothiocyanates; Oxidative Stress; Sulfoxides; Vitamin D; Reactive Oxygen Species; Cell Line; Vascular Endothelial Growth Factor A; Inflammation; Retinal Pigment Epithelium; Epithelial Cells; Transforming Growth Factor beta; Biomarkers; Interleukin-8
PubMed: 38928111
DOI: 10.3390/ijms25126404 -
Bioengineering (Basel, Switzerland) Jun 2024Ultra-widefield (UWF) retinal imaging stands as a pivotal modality for detecting major eye diseases such as diabetic retinopathy and retinal detachment. However, UWF...
Ultra-widefield (UWF) retinal imaging stands as a pivotal modality for detecting major eye diseases such as diabetic retinopathy and retinal detachment. However, UWF exhibits a well-documented limitation in terms of low resolution and artifacts in the macular area, thereby constraining its clinical diagnostic accuracy, particularly for macular diseases like age-related macular degeneration. Conventional supervised super-resolution techniques aim to address this limitation by enhancing the resolution of the macular region through the utilization of meticulously paired and aligned fundus image ground truths. However, obtaining such refined paired ground truths is a formidable challenge. To tackle this issue, we propose an unpaired, degradation-aware, super-resolution technique for enhancing UWF retinal images. Our approach leverages recent advancements in deep learning: specifically, by employing generative adversarial networks and attention mechanisms. Notably, our method excels at enhancing and super-resolving UWF images without relying on paired, clean ground truths. Through extensive experimentation and evaluation, we demonstrate that our approach not only produces visually pleasing results but also establishes state-of-the-art performance in enhancing and super-resolving UWF retinal images. We anticipate that our method will contribute to improving the accuracy of clinical assessments and treatments, ultimately leading to better patient outcomes.
PubMed: 38927804
DOI: 10.3390/bioengineering11060568