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Femtosecond Laser Pulse Ablation of Sub-Cellular Drusen-Like Deposits
摘要： Age-related macular degeneration (AMD) is a condition affecting the retina and is the leading cause of vision loss. Dry AMD is caused by the accumulation of lipid deposits called drusen, which form under the retina. This work demonstrates, for the first time, the removal of drusen-like deposits underneath ARPE-19 cell layers using femtosecond laser pulses. A novel cell culture model was created in response to the limited access to primary cell lines and the absence of animal models that recapitulate all aspects of AMD. In the cell culture model, deposits were identified with fluorescent stains specific to known deposit constituents. Trains of sub-10 femtosecond laser pulses from a Ti:Sapphire laser were used to successfully ablate the deposits without causing damage to surrounding cells. this drusen removal method can be used as a potential treatment for dry-stage AMD.
关键词： drusen,ARPE-19,laser ablation,age-related macular degeneration,femtosecond laser
更新于2025-09-12 10:27:22
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Evaluation of Retinal Pigment Epithelium and Choroidal Neovascularization in Rats Using Laser-Scanning Optical-Resolution Photoacoustic Microscopy
摘要： Purpose: To demonstrate the value of the laser-scanning optical-resolution (LSOR)-photoacoustic (PA) microscopy (PAM) system and the conventional multimodal imaging techniques in the evaluation of laser-induced retinal injury and choroidal neovascularization (CNV) in rats. Methods: Different degrees of retinal injury were induced using laser photocoagulation. We compared the LSOR-PAM system with conventional imaging techniques in evaluating retinal injury with or without CNV. Six additional rats, treated with an anti-VEGF antibody or immunoglobulin G immediately after photocoagulation, were imaged 7 and 14 days after injection, and CNV lesion areas were compared. Results: In the retinal injury model, fundus autofluorescence showed well-defined hyperreflection, while the lesion displayed abundant PA signals demonstrating nonuniform melanin distribution in retinal pigment epithelium (RPE). RPE was detected with higher contrast in the PAM B-scan image than optical coherence tomography (OCT). Additionally, the CNV lesion was present with multiple PA signal intensi- ties which distinctly characterized the location and area of CNV as found in fundus fluorescein angiography. Further- more, the decreased PA signals extending from the CNV le- sion were similar to those of the vascular bud in ex vivo im- aging, which was invisible in other in vivo images. When treated with anti-VEGF agents, statistically significant differ- ences can be demonstrated by PAM similar to other mo- dalities. Conclusions: LSOR-PAM can detect the melanin distribution of RPE in laser-induced retinal injury and CNV in rats. PAM imaging provides a potential new tool to evalu- ate the vitality and functionality of RPE in vivo as well as to monitor the development and treatment of CNV.
关键词： Age-related macular degeneration,Retinal pigment epithelium,Multimodal imaging,Photoacoustic microscopy,Choroidal neovascularization
更新于2025-09-12 10:27:22
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A DOUBLE-MASKED, RANDOMIZED, SHAM-CONTROLLED, SINGLE-CENTER STUDY WITH PHOTOBIOMODULATION FOR THE TREATMENT OF DRY AGE-RELATED MACULAR DEGENERATION
摘要： The LIGHTSITE I study investigated the efficacy and safety of photobiomodulation (PBM) treatment in subjects with dry age-related macular degeneration. Thirty subjects (46 eyes) were treated with the Valeda Light Delivery System, wherein subjects underwent two series of treatments (3· per week for 3–4 weeks) over 1 year. Outcome measures included best-corrected visual acuity, contrast sensitivity, microperimetry, central drusen volume and drusen thickness, and quality of life assessments. Photobiomodulation-treated subjects showed a best-corrected visual acuity mean letter score gain of 4 letters immediately after each treatment series at Month 1 (M1) and Month 7 (M7). Approximately 50% of PBM-treated subjects showed improvement of $5 letters versus 13.6% in sham-treated subjects at M1. High responding subjects ($5-letter improvement) in the PBM-treated group showed a gain of 8 letters after initial treatment (P , 0.01) and exhibited earlier stages of age-related macular degeneration disease. Statistically significant improvements in contrast sensitivity, central drusen volume, central drusen thickness, and quality of life were observed (P , 0.05). No device-related adverse events were reported. Photobiomodulation treatment statistically improved clinical and anatomical outcomes with more robust benefits observed in subjects with earlier stages of dry age-related macular degeneration. Repeated PBM treatments are necessary to maintain benefits. These pilot findings support previous reports and suggest the utility of PBM as a safe and effective therapy in subjects with dry age-related macular degeneration.
关键词： contrast sensitivity,best-corrected visual acuity,light-emitting diode,vision loss,low-level light therapy,mitochondria,photobiomodulation,dry age-related macular degeneration,drusen
更新于2025-09-12 10:27:22
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Secondary and Exploratory Outcomes of the Subthreshold Nanosecond Laser Intervention Randomized Trial in Age-Related Macular Degeneration: A LEAD Study Report
摘要： To evaluate the secondary and exploratory outcomes of the Laser Intervention in Early Stages of Age-Related Macular Degeneration (LEAD) study, a 36-month trial of a subthreshold nanosecond laser (SNL) treatment for slowing the progression to late age-related macular degeneration (AMD) in its early stages.
关键词： LEAD study,age-related macular degeneration,subthreshold nanosecond laser,secondary outcomes,exploratory outcomes
更新于2025-09-11 14:15:04
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Promiscuous Chemokine Antagonist (BKT130) Suppresses Laser-Induced Choroidal Neovascularization by Inhibition of Monocyte Recruitment
摘要： Background. Age-related macular degeneration (AMD), the most common cause of blindness in the developed world, usually affects individuals older than 60 years of age. The majority of visual loss in this disease is attributable to the development of choroidal neovascularization (CNV). Mononuclear phagocytes, including monocytes and their tissue descendants, macrophages, have long been implicated in the pathogenesis of neovascular AMD (nvAMD). Current therapies for nvAMD are based on targeting vascular endothelial growth factor (VEGF). This study is aimed at assessing if perturbation of chemokine signaling and mononuclear cell recruitment may serve as novel complementary therapeutic targets for nvAMD. Methods. A promiscuous chemokine antagonist (BKT130), aflibercept treatment, or combined BKT130+aflibercept treatment was tested in an in vivo laser-induced model of choroidal neovascularization (LI-CNV) and in an ex vivo choroidal sprouting assay (CSA). Quantification of CD11b+ cell in the CNV area was performed, and mRNA levels of genes implicated in CNV growth were measured in the retina and RPE-choroid. Results. BKT130 reduced the CNV area and recruitment of CD11b+ cells by 30-35%. No effect of BKT130 on macrophages’ proangiogenic phenotype was demonstrated ex vivo, but a lower VEGFA and CCR2 expression was found in the RPE-choroid and a lower expression of TNFα and NOS1 was found in both RPE-choroid and retinal tissues in the LI-CNV model under treatment with BKT130. Conclusions. Targeting monocyte recruitment via perturbation of chemokine signaling can reduce the size of experimental CNV and should be evaluated as a potential novel therapeutic modality for nvAMD.
关键词： Age-related macular degeneration,monocyte recruitment,VEGF,choroidal neovascularization,chemokine antagonist
更新于2025-09-11 14:15:04
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Behavioural responses to a photovoltaic subretinal prosthesis implanted in non-human primates
摘要： Retinal dystrophies and age-related macular degeneration related to photoreceptor degeneration can cause blindness. In blind patients, although the electrical activation of the residual retinal circuit can provide useful artificial visual perception, the resolutions of current retinal prostheses have been limited either by large electrodes or small numbers of pixels. Here we report the evaluation, in three awake non-human primates, of a previously reported near-infrared-light-sensitive photovoltaic subretinal prosthesis. We show that multipixel stimulation of the prosthesis within radiation safety limits enabled eye tracking in the animals, that they responded to stimulations directed at the implant with repeated saccades and that the implant-induced responses were present two years after device implantation. Our findings pave the way for the clinical evaluation of the prosthesis in patients affected by dry atrophic age-related macular degeneration.
关键词： artificial visual perception,non-human primates,photovoltaic subretinal prosthesis,age-related macular degeneration,retinal prostheses
更新于2025-09-11 14:15:04
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Longitudinal Assessment of Progressive Retinal Pigment Epithelium Disruption in a 26 Year Old A MultiSpectral Imaging Case Study
摘要： Background: Progressive retinal pigment epithelium (RPE) disruption in the absence of drusen or visual disturbances in young people is rarely reported in the literature, except for cases of juvenile macular degenerative diseases, pattern dystrophies or white dot syndromes. In age-related macular degeneration (AMD), RPE disruption typically does not become manifest clinically before age 55. This case report presents a young, healthy 26 year old Caucasian male with asymptomatic progressive RPE disruption in the absence of drusen, as detected by multi-spectral imaging (MSI) technology. Methods: A 26 year old Caucasian male was followed for progressive changes in RPE atrophy and melanin clumping over three visits in a three year period. His dilated fundus examination, fundus photography and optical coherence tomography were within normal limits. Long wavelength MSI revealed progressive RPE changes in the form of RPE atrophy and melanin clumping. MSI fundus auto-fluorescence (FAF) showed corresponding hyperautofluorescence and hypoautofluorescence in the left. Findings: Macular RPE changes can result from phototoxic effects and vary by ethnicity. Functional biomarkers to determine the risk of future vision loss with AMD are frequently sought and include complement factor H and Age-Related Maculopathy Susceptibility 2. FAF, for example is highly indicative of RPE dysfunction and progression. Long wavelength MSI, 620 nm to 740 nm, enhances visualization of the RPE, more specifically atrophy and melanin clumping, which may be indicative of asymptomatic progressive early AMD or retinal dystrophies. Conclusion: This case shows a longitudinal example of progressive RPE disruption in a 26 year old male. This is only one example, but multiple cases of RPE disruption in young people exist. Using MSI to further investigate RPE disruption and progression in a young population may provide a potential biomarker for early AMD, photo toxicity or other retinal dystrophies and degenerations.
关键词： Retinal Pigment Epithelium,Fundus Autofluorescence,Age-related Macular Degeneration,Multi-Spectral Imaging,Progressive retinal pigment epithelium disruption
更新于2025-09-11 14:15:04
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Photobiomodulation for the treatment of retinal diseases: a review
摘要： Photobiomodulation (PBM), also known as low level laser therapy, has recently risen to the attention of the ophthalmology community as a promising new approach to treat a variety of retinal conditions including age-related macular degeneration, retinopathy of prematurity, diabetic retinopathy, Leber's hereditary optic neuropathy, amblyopia, methanol-induced retinal damage, and possibly others. This review evaluates the existing research pertaining to PBM applications in the retina, with a focus on the mechanisms of action and clinical outcomes. All available literature until April 2015 was reviewed using PubMed and the following keywords: 'photobiomodulation AND retina', 'low level light therapy AND retina', 'low level laser therapy AND retina', and 'FR/NIR therapy AND retina'. In addition, the relevant references listed within the papers identified through PubMed were incorporated. The literature supports the conclusion that the low-cost and non-invasive nature of PBM, coupled with the first promising clinical reports and the numerous preclinical-studies in animal models, make PBM well-poised to become an important player in the treatment of a wide range of retinal disorders. Nevertheless, large-scale clinical trials will be necessary to establish the PBM therapeutic ranges for the various retinal diseases, as well as to gain a deeper understanding of its mechanisms of action.
关键词： low level laser therapy,age-related macular degeneration,retinopathy of prematurity,photobiomodulation,retinal degeneration,amblyopia,far-red to near-infrared,methanol toxicity,retinitis pigmentosa
更新于2025-09-10 09:29:36
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LONG-TERM VISUAL OUTCOMES AND CLINICAL FEATURES AFTER ANTI–VASCULAR ENDOTHELIAL GROWTH FACTOR INJECTION–RELATED ENDOPHTHALMITIS
摘要： Purpose: To determine long-term visual outcomes in patients who developed endophthalmitis after intravitreal anti–vascular endothelial growth factor injections and to correlate visual outcomes with clinical features. Methods: This is a retrospective, multicenter, consecutive case series of patients diagnosed with anti–vascular endothelial growth factor injection–related endophthalmitis who were treated at Mid Atlantic Retina, the Retina Service of Wills Eye Hospital, Philadelphia, PA, and the University of Southern California Roski Eye Institute, Los Angeles, CA. Patients were included if they had at least 1 year of follow-up. Primary outcome was to evaluate long-term visual outcomes up to 5 years of follow-up. The secondary outcome was to determine clinical features (e.g., culture results) that may predict long-term visual acuity outcomes. Results: A total of 56 cases of endophthalmitis from 168,247 anti–vascular endothelial growth factor injections were identi?ed (0.033%, 1/3,004 injections), from which 51 eyes met inclusion criteria. Mean follow-up period was 3.3 years (median 4 years; range 1–5 years). A total of 24 patients (47%) reached a maximum ?nal follow-up of 5 years. Mean Snellen visual acuity at the causative injection visit was 20/102 and decreased to counting ?ngers at diagnosis (P , 0.001). At 6-month follow-up, mean visual acuity improved to 20/644 (P , 0.001) and remained stable up to 5 years (20/480, P = 0.003) follow-up compared with diagnosis. At the ?nal follow-up, 20 eyes had visual acuity that returned to within one line of baseline visual acuity (visual recovery group), whereas 31 patients’ visual acuity was at least one line worse than initial visual acuity (visual deterioration group). The cultures for the visual recovery group were more likely to grow coagulase-negative Staphylococcus, whereas the visual deterioration group primarily grew Streptococcus species, Staphylococcus aureus, and Enterococcus faecalis (P = 0.002, comparing organisms isolated in the visual recovery and deterioration group). Conclusion: Visual outcomes after anti–vascular endothelial growth factor injection– related endophthalmitis seem to reach peak improvement by 6 months and remain stable up to a median of 4-year follow-up. Patients who develop culture-negative endophthalmitis or endophthalmitis secondary to coagulase-negative Staphylococcus are more likely to regain baseline visual acuity compared with cases secondary to Streptococcus species.
关键词： bevacizumab,anti-vascular endothelial growth factor,diabetic macular edema,intravitreal injection,endophthalmitis,a?ibercept,long-term,ranibizumab,neovascular age-related macular degeneration,retinal vein occlusion
更新于2025-09-10 09:29:36
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[IEEE 2018 40th Annual International Conference of the IEEE Engineering in Medicine and Biology Society (EMBC) - Honolulu, HI, USA (2018.7.18-2018.7.21)] 2018 40th Annual International Conference of the IEEE Engineering in Medicine and Biology Society (EMBC) - OCT Fluid Segmentation using Graph Shortest Path and Convolutional Neural Network <sup>*</sup>
摘要： Diagnosis and monitoring of retina diseases related to pathologies such as accumulated fluid can be performed using optical coherence tomography (OCT). OCT acquires a series of 2D slices (Bscans). This work presents a fully-automated method based on graph shortest path algorithms and convolutional neural network (CNN) to segment and detect three types of fluid including sub-retinal fluid (SRF), intra-retinal fluid (IRF) and pigment epithelium detachment (PED) in OCT Bscans of subjects with age-related macular degeneration (AMD) and retinal vein occlusion (RVO) or diabetic retinopathy. The proposed method achieves an average dice coefficient of 76.44%, 92.25% and 82.14% in Cirrus, Spectralis and Topcon datasets, respectively. The effectiveness of the proposed methods was also demonstrated in segmenting fluid in OCT images from the 2017 Retouch challenge.
关键词： optical coherence tomography,retinal vein occlusion,fluid segmentation,graph shortest path,convolutional neural network,age-related macular degeneration
更新于2025-09-10 09:29:36