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Romanian Journal of Ophthalmology 2023One of the fields of medicine in which artificial intelligence techniques have made progress is ophthalmology. Artificial intelligence (A.I.) applications for preventing... (Review)
Review
One of the fields of medicine in which artificial intelligence techniques have made progress is ophthalmology. Artificial intelligence (A.I.) applications for preventing vision loss in eye illnesses have developed quickly. Artificial intelligence uses computer programs to execute various activities while mimicking human thought. Machine learning techniques are frequently utilized in the field of ophthalmology. Ophthalmology holds great promise for advancing artificial intelligence, thanks to various digital methods like optical coherence tomography (OCT) and visual field testing. Artificial intelligence has been used in ophthalmology to treat eye conditions impairing vision, including macular holes (M.H.), age-related macular degeneration (AMD), diabetic retinopathy, glaucoma, and cataracts. The more common occurrence of these diseases has led to artificial intelligence development. It is important to get annual screenings to detect eye diseases such as glaucoma, diabetic retinopathy, and age-related macular degeneration. These conditions can cause decreased visual acuity, and it is necessary to identify any changes or progression in the disease to receive appropriate treatment. Numerous studies have been conducted based on artificial intelligence using different algorithms to improve and simplify current medical practice and for early detection of eye diseases to prevent vision loss. AI = artificial intelligence, AMD = age-related macular degeneration, ANN = artificial neural networks, AAO = American Academy of Ophthalmology, CNN = convolutional neural network, DL = deep learning, DVP = deep vascular plexus, FDA = Food and Drug Administration, GCL = ganglion cell layer, IDP = Iowa Detection Program, ML = Machine learning techniques, MH = macular holes, MTANN = massive training of the artificial neural network, NLP = natural language processing methods, OCT = optical coherence tomography, RBS = Radial Basis Function, RNFL = nerve fiber layer, ROP = Retinopathy of Prematurity, SAP = standard automated perimetry, SVP = Superficial vascular plexus, U.S. = United States, VEGF = vascular endothelial growth factor.
Topics: Infant, Newborn; Humans; Artificial Intelligence; Ophthalmology; Diabetic Retinopathy; Vascular Endothelial Growth Factor A; Retinal Perforations; Glaucoma; Macular Degeneration
PubMed: 37876505
DOI: 10.22336/rjo.2023.37 -
JAMA Ophthalmology Jul 2023Aflibercept biosimilars can expand available treatment options in retinal diseases and have the potential to improve patient access to safe and effective therapy. (Randomized Controlled Trial)
Randomized Controlled Trial
IMPORTANCE
Aflibercept biosimilars can expand available treatment options in retinal diseases and have the potential to improve patient access to safe and effective therapy.
OBJECTIVE
To establish equivalence in efficacy and similarity in safety, pharmacokinetics, and immunogenicity of SB15 and reference aflibercept (AFL) in neovascular age-related macular degeneration (nAMD).
DESIGN, SETTING, AND PARTICIPANTS
This was a randomized double-masked parallel group phase 3 trial conducted at 56 centers in 10 countries from June 2020 to March 2022, including follow-up through 56 weeks. Of 549 screened participants, 449 participants 50 years and older with treatment-naive nAMD were included and randomly assigned to SB15 (n = 224) or AFL (n = 225). Key exclusion criteria included considerable scarring, fibrosis, atrophy, and hemorrhage. This report includes results up to the end of the parallel group period at week 32. Of the 449 randomized participants, 438 (97.6%) completed week 32 follow-up.
INTERVENTION
Participants were randomized 1:1 to receive 2 mg of SB15 or AFL every 4 weeks for the first 12 weeks (3 injections), followed by dosing every 8 weeks up to week 48, with final assessments at week 56.
MAIN OUTCOMES AND MEASURES
The primary end point was the change in best-corrected visual acuity (BCVA) from baseline to week 8 with predefined equivalence margins of -3 letters to 3 letters. Other key end points were changes in BCVA and central subfield thickness up to week 32, safety, pharmacokinetics, and immunogenicity.
RESULTS
The mean (SD) age among the 449 included participants was 74.0 (8.1) years, and 250 participants (55.7%) were female. Baseline demographic characteristics and most disease characteristics were comparable between treatment groups. The least squares mean change in BCVA from baseline to week 8 in the SB15 group was equivalent to that in the AFL group (6.7 letters vs 6.6 letters, respectively; difference, 0.1 letters; 95% CI, -1.3 to 1.4). Comparable efficacy between treatment groups was maintained up to week 32 (least squares mean change from baseline in BCVA: SB15, 7.6 letters vs AFL, 6.5 letters; least squares mean change from baseline in central subfield thickness: SB15, -110.4 μm vs AFL, -115.7 μm). No clinically relevant differences were observed in the incidence of treatment-emergent adverse events (TEAEs) (SB15, 107/224 [47.8%] vs AFL, 98/224 [43.8%]) and ocular TEAEs in the study eye (SB15, 41/224 [18.3%] vs AFL, 28/224 [12.5%]). The serum concentration profiles and cumulative incidences of overall antidrug antibody positive participants were comparable.
CONCLUSIONS AND RELEVANCE
In this phase 3 randomized clinical trial, SB15 and AFL showed equivalent efficacy and comparable safety, pharmacokinetics, and immunogenicity in participants with nAMD.
TRIAL REGISTRATION
ClinicalTrials.gov Identifier: NCT04450329.
Topics: Humans; Female; Aged; Male; Angiogenesis Inhibitors; Biosimilar Pharmaceuticals; Treatment Outcome; Visual Acuity; Intravitreal Injections; Receptors, Vascular Endothelial Growth Factor; Recombinant Fusion Proteins; Macular Degeneration; Wet Macular Degeneration; Ranibizumab
PubMed: 37289448
DOI: 10.1001/jamaophthalmol.2023.2260 -
Autophagy Oct 2023Age-related macular degeneration (AMD) is the leading cause of irreversible blindness among the elderly, and there is currently no clinical treatment targeting the...
Age-related macular degeneration (AMD) is the leading cause of irreversible blindness among the elderly, and there is currently no clinical treatment targeting the primary impairment of AMD. The earliest clinical hallmark of AMD is drusen, which are yellowish spots mainly composed of lipid droplets (LDs) accumulated under the retinal pigment epithelium (RPE). However, the potential pathogenic role of this excessive LD accumulation in AMD is yet to be determined, partially due to a lack of chemical tools to manipulate LDs specifically. Here, we employed our recently developed Lipid Droplets·AuTophagy Tethering Compounds (LD∙ATTECs) to degrade LDs and to evaluate its consequence on the AMD-like phenotypes in apoe (apolipoprotein E; B6/JGpt-Apoe/Gpt) mouse model. apoe mice fed with high-fat diet (apoe-HFD) exhibited excessive LD accumulation in the retina, particularly with AMD-like phenotypes including RPE degeneration, Bruch's membrane (BrM) thickening, drusen-like deposits, and photoreceptor dysfunction. LD·ATTEC treatment significantly cleared LDs in RPE/choroidal tissues without perturbing lipid synthesis-related proteins and rescued RPE degeneration and photoreceptor dysfunction in apoe-HFD mice. This observation implied a causal relationship between LD accumulation and AMD-relevant phenotypes. Mechanically, the apoe-HFD mice exhibited elevated oxidative stress and inflammatory signals, both of which were mitigated by the LD·ATTEC treatment. Collectively, this study demonstrated that LD accumulation was a trigger for the process of AMD and provided entry points for the treatment of the initial insult of AMD by degrading LDs. AMD: age-related macular degeneration; : apolipoprotein E; ATTECs: autophagy-tethering compounds; BODIPY: boron-dipyrromethene; BrM: Bruch's membrane; ERG: electroretinogram; HFD: high-fat diet; LD·ATTECs: Lipid Droplets·AuTophagy Tethering Compounds; LDs: lipid droplets; OA: oleic acid; OPL: outer plexiform layer; ROS: reactive oxygen species; RPE: retinal pigment epithelium.
Topics: Mice; Animals; Lipid Droplets; Autophagy; Macular Degeneration; Retinal Pigment Epithelium; Apolipoproteins E; Phenotype; Apolipoproteins
PubMed: 37266932
DOI: 10.1080/15548627.2023.2220540 -
The British Journal of Ophthalmology Mar 2024Stargardt macular dystrophy (Stargardt disease; STGD1; OMIM 248200) is the most prevalent inherited macular dystrophy. STGD1 is an autosomal recessive disorder caused by... (Review)
Review
Stargardt macular dystrophy (Stargardt disease; STGD1; OMIM 248200) is the most prevalent inherited macular dystrophy. STGD1 is an autosomal recessive disorder caused by multiple pathogenic sequence variants in the large gene (OMIM 601691). Major advances in understanding both the clinical and molecular features, as well as the underlying pathophysiology, have culminated in many completed, ongoing and planned human clinical trials of novel therapies.The aims of this concise review are to describe (1) the detailed phenotypic and genotypic characteristics of the disease, multimodal imaging findings, natural history of the disease, and pathogenesis, (2) the multiple avenues of research and therapeutic intervention, including pharmacological, cellular therapies and diverse types of genetic therapies that have either been investigated or are under investigation and (3) the exciting novel therapeutic approaches on the translational horizon that aim to treat STGD1 by replacing the entire 6.8 kb open reading frame.
Topics: Humans; Stargardt Disease; Phenotype; Mutation; Macular Degeneration; Genotype; ATP-Binding Cassette Transporters
PubMed: 37940365
DOI: 10.1136/bjo-2022-323071 -
Retina (Philadelphia, Pa.) Mar 2024The LIGHTSITE III study evaluated multiwavelength photobiomodulation (PBM) therapy in nonexudative (dry) age-related macular degeneration (AMD) using the LumiThera... (Randomized Controlled Trial)
Randomized Controlled Trial
LIGHTSITE III: 13-Month Efficacy and Safety Evaluation of Multiwavelength Photobiomodulation in Nonexudative (Dry) Age-Related Macular Degeneration Using the Lumithera Valeda Light Delivery System.
PURPOSE
The LIGHTSITE III study evaluated multiwavelength photobiomodulation (PBM) therapy in nonexudative (dry) age-related macular degeneration (AMD) using the LumiThera Valeda Light Delivery System.
METHODS
LIGHTSITE III is a randomized, controlled trial to assess the safety and effectiveness of PBM in dry AMD. Subjects were given multiwavelength PBM (590, 660, and 850 nm) or Sham treatment delivered in a series of nine sessions over 3 to 5 weeks every four months over 24 months. Subjects were assessed for efficacy and safety outcomes. Data from the 13-month analysis are presented in this report.
RESULTS
A total of 100 subjects (148 eyes) with dry AMD were randomized. LIGHTSITE III met the primary efficacy best-corrected visual acuity endpoint with a significant difference between PBM (n = 91 eyes) and Sham (n = 54 eyes) groups (Between group difference: 2.4 letters (SE 1.15), CI: -4.7 to -0.1, P = 0.02) (PBM alone: 5.4 letters (SE 0.96), CI: 3.5 to 7.3, P < 0.0001; Sham alone: 3.0 letters (SE 1.13), CI: 0.7-5.2, P < 0.0001). The PBM group showed a significant decrease in new onset geographic atrophy ( P = 0.024, Fisher exact test, odds ratio 9.4). A favorable safety profile was observed.
CONCLUSION
LIGHTSITE III provides a prospective, randomized, controlled trial showing improved clinical and anatomical outcomes in intermediate dry AMD following PBM therapy.
Topics: Humans; Low-Level Light Therapy; Prospective Studies; Visual Acuity; Macular Degeneration; Eye; Geographic Atrophy
PubMed: 37972955
DOI: 10.1097/IAE.0000000000003980 -
International Journal of Molecular... Aug 2023The human microbiota refers to a large variety of microorganisms (bacteria, viruses, and fungi) that live in different human body sites, including the gut, oral cavity,... (Review)
Review
The human microbiota refers to a large variety of microorganisms (bacteria, viruses, and fungi) that live in different human body sites, including the gut, oral cavity, skin, and eyes. In particular, the presence of an ocular surface microbiota with a crucial role in maintaining ocular surface homeostasis by preventing colonization from pathogen species has been recently demonstrated. Moreover, recent studies underline a potential association between gut microbiota (GM) and ocular health. In this respect, some evidence supports the existence of a gut-eye axis involved in the pathogenesis of several ocular diseases, including age-related macular degeneration, uveitis, diabetic retinopathy, dry eye, and glaucoma. Therefore, understanding the link between the GM and these ocular disorders might be useful for the development of new therapeutic approaches, such as probiotics, prebiotics, symbiotics, or faecal microbiota transplantation through which the GM could be modulated, thus allowing better management of these diseases.
Topics: Humans; Eye; Face; Glaucoma; Macular Degeneration; Diabetic Retinopathy
PubMed: 37686143
DOI: 10.3390/ijms241713338 -
Metabolism: Clinical and Experimental Jul 2023The neovascular form of age-related macular degeneration (nvAMD) is the leading cause of blindness in the elderly population. Vascular endothelial growth factor (VEGF)...
The neovascular form of age-related macular degeneration (nvAMD) is the leading cause of blindness in the elderly population. Vascular endothelial growth factor (VEGF) plays a crucial role in choroidal neovascularization (CNV), and anti-VEGF therapy is recommended as first-line therapy for nvAMD. However, many patients do not radically benefit from this therapy. Epidemiological data suggest that physical exercise is beneficial for many human diseases, including nvAMD. Yet, its protective mechanism and therapeutic potential remain unknown. Here, using clinical samples and mouse models, we found that exercise reduced CNV and enhanced anti-angiogenic therapy efficacy by inhibiting AIM2 inflammasome activation. Furthermore, transfusion of serum from exercised mice transferred the protective effects to sedentary mice. Proteomic data revealed that exercise promoted the release of adiponectin, an anti-inflammatory adipokine from adipose tissue into the circulation, which reduced ROS-mediated DNA damage and suppressed AIM2 inflammasome activation in myeloid cells of CNV eyes through AMPK-p47phox pathway. Simultaneous targeting AIM2 inflammasome product IL-1β and VEGF produced a synergistic effect for treating choroidal neovascularization. Collectively, this study highlights the therapeutic potential of an exercise-AMD axis and uncovers the AIM2 inflammasome and its product IL-1β as potential targets for treating nvAMD patients and enhancing the efficacy of anti-VEGF monotherapy.
Topics: Aged; Humans; Mice; Animals; Inflammasomes; Vascular Endothelial Growth Factor A; Proteomics; Choroidal Neovascularization; Myeloid Cells; Macular Degeneration; DNA-Binding Proteins
PubMed: 37150437
DOI: 10.1016/j.metabol.2023.155584 -
Nature Communications Sep 2023Neovascular age-related macular degeneration (nAMD), along with its clinical subtype known as polypoidal choroidal vasculopathy (PCV), are among the leading causes of...
Neovascular age-related macular degeneration (nAMD), along with its clinical subtype known as polypoidal choroidal vasculopathy (PCV), are among the leading causes of vision loss in elderly Asians. In a genome-wide association study (GWAS) comprising 3,128 nAMD (1,555 PCV and 1,573 typical nAMD), and 5,493 controls of East Asian ancestry, we identify twelve loci, of which four are novel ([Formula: see text]). Substantial genetic sharing between PCV and typical nAMD is noted (r = 0.666), whereas collagen extracellular matrix and fibrosis-related pathways are more pronounced for PCV. Whole-exome sequencing in 259 PCV patients revealed functional rare variants burden in collagen type I alpha 1 chain gene (COL1A1; [Formula: see text]) and potential enrichment of functional rare mutations at AMD-associated loci. At the GATA binding protein 5 (GATA5) locus, the most significant GWAS novel loci, the expressions of genes including laminin subunit alpha 5 (Lama5), mitochondrial ribosome associated GTPase 2 (Mtg2), and collagen type IX alpha 3 chain (Col9A3), are significantly induced during retinal angiogenesis and subretinal fibrosis in murine models. Furthermore, retinoic acid increased the expression of LAMA5 and MTG2 in vitro. Taken together, our data provide insights into the genetic basis of AMD pathogenesis in the Asian population.
Topics: Aged; Animals; Humans; Mice; Asian; East Asian People; Extracellular Matrix; Genome-Wide Association Study; Macular Degeneration; Polypoidal Choroidal Vasculopathy; Disease Models, Animal
PubMed: 37696869
DOI: 10.1038/s41467-023-41256-z -
Revisiting Retinal Degeneration Hallmarks: Insights from Molecular Markers and Therapy Perspectives.International Journal of Molecular... Aug 2023Visual impairment and blindness are a growing public health problem as they reduce the life quality of millions of people. The management and treatment of these diseases... (Review)
Review
Visual impairment and blindness are a growing public health problem as they reduce the life quality of millions of people. The management and treatment of these diseases represent scientific and therapeutic challenges because different cellular and molecular actors involved in the pathophysiology are still being identified. Visual system components, particularly retinal cells, are extremely sensitive to genetic or metabolic alterations, and immune responses activated by local insults contribute to biological events, culminating in vision loss and irreversible blindness. Several ocular diseases are linked to retinal cell loss, and some of them, such as retinitis pigmentosa, age-related macular degeneration, glaucoma, and diabetic retinopathy, are characterized by pathophysiological hallmarks that represent possibilities to study and develop novel treatments for retinal cell degeneration. Here, we present a compilation of revisited information on retinal degeneration, including pathophysiological and molecular features and biochemical hallmarks, and possible research directions for novel treatments to assist as a guide for innovative research. The knowledge expansion upon the mechanistic bases of the pathobiology of eye diseases, including information on complex interactions of genetic predisposition, chronic inflammation, and environmental and aging-related factors, will prompt the identification of new therapeutic strategies.
Topics: Humans; Retinal Degeneration; Macular Degeneration; Retinitis Pigmentosa; Biomarkers; Blindness; Retina
PubMed: 37685886
DOI: 10.3390/ijms241713079 -
Investigative Ophthalmology & Visual... Nov 2023The purpose of this study was to describe the presence of choroidal hyper-reflective foci (HRF) on optical coherence tomography (OCT) in patients with geographic atrophy...
PURPOSE
The purpose of this study was to describe the presence of choroidal hyper-reflective foci (HRF) on optical coherence tomography (OCT) in patients with geographic atrophy (GA). The relationship between the presence and quantity of choroidal HRF and other clinical and imaging factors was also investigated.
METHODS
A total of 40 participants (40 eyes) with GA and age-related macular degeneration (AMD) were retrospectively analyzed. OCT images were reviewed for the presence, characteristics, and localization of choroidal HRF. The amount of choroidal HRF was quantified in different choroidal layers by two different (i.e. threshold reflectivity and manual counting) methodologies. The primary outcome was to describe and quantify choroidal HRF and correlate them with GA lesion size.
RESULTS
Structural OCT images showed that all patients had multiple hyper-reflective deposits in different layers of the choroid. These hyper-reflective deposits in the choroid were located near Bruch's membrane or the edges of the blood vessels, particularly in the Sattler's layer, and none were observed inside the vessels. Choroidal HRF exhibited variable size and shape and varying effects on the posterior signal, including shadowing or hypertransmission. Mean ± SD number of choroidal HRF per B-scan was 21.5 ± 15.4 using the threshold reflectivity methodology and 25.1 ± 16.0 using the manual counting methodology. A significant correlation between the untransformed GA size and number of HRF was found, considering both quantitative strategies.
CONCLUSIONS
Hyper-reflective dots in the choroid of subjects with GA may be readily identified with structural OCT. These HRF might represent a natural component of the choroid that becomes more visible due to the absence of the retinal pigment epithelium.
Topics: Humans; Geographic Atrophy; Retrospective Studies; Choroid; Macular Degeneration; Bruch Membrane; Retinal Pigment Epithelium; Tomography, Optical Coherence; Fluorescein Angiography
PubMed: 37922157
DOI: 10.1167/iovs.64.14.5