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BMC Ophthalmology Jun 2024Glaucoma is a worldwide eye disease that can cause irreversible vision loss. Early detection of glaucoma is important to reduce vision loss, and retinal fundus image...
BACKGROUND
Glaucoma is a worldwide eye disease that can cause irreversible vision loss. Early detection of glaucoma is important to reduce vision loss, and retinal fundus image examination is one of the most commonly used solutions for glaucoma diagnosis due to its low cost. Clinically, the cup-disc ratio of fundus images is an important indicator for glaucoma diagnosis. In recent years, there have been an increasing number of algorithms for segmentation and recognition of the optic disc (OD) and optic cup (OC), but these algorithms generally have poor universality, segmentation performance, and segmentation accuracy.
METHODS
By improving the YOLOv8 algorithm for segmentation of OD and OC. Firstly, a set of algorithms was designed to adapt the REFUGE dataset's result images to the input format of the YOLOv8 algorithm. Secondly, in order to improve segmentation performance, the network structure of YOLOv8 was improved, including adding a ROI (Region of Interest) module, modifying the bounding box regression loss function from CIOU to Focal-EIoU. Finally, by training and testing the REFUGE dataset, the improved YOLOv8 algorithm was evaluated.
RESULTS
The experimental results show that the improved YOLOv8 algorithm achieves good segmentation performance on the REFUGE dataset. In the OD and OC segmentation tests, the F1 score is 0.999.
CONCLUSIONS
We improved the YOLOv8 algorithm and applied the improved model to the segmentation task of OD and OC in fundus images. The results show that our improved model is far superior to the mainstream U-Net model in terms of training speed, segmentation performance, and segmentation accuracy.
Topics: Optic Disk; Humans; Algorithms; Fundus Oculi; Glaucoma
PubMed: 38943095
DOI: 10.1186/s12886-024-03532-4 -
Scientific Reports Jun 2024To evaluate the protective effect of gallic acid on the optic nerve by studying the inhibitory effect of gallic acid on oxidative stress in retinal ganglion cells. 100...
To evaluate the protective effect of gallic acid on the optic nerve by studying the inhibitory effect of gallic acid on oxidative stress in retinal ganglion cells. 100 male SD rats were randomly divided into four groups: normal control group, simple high IOP group, 0.5% gallic acid experimental group, and 1% gallic acid experimental group. HE staining, immunofluorescence, DHE staining, Western blot, and q-PCR were used to observe the antioxidant effect of gallic acid on the retina of acute ocular hypertension rats. HE staining of the retina of SD rats confirmed that the nucleus of RGCs was clear, the thickness of the RNFL was regular in the normal control group, and the nucleus of RGCs was ruptured and lysed in the simple high intraocular pressure (IOP) group and the gallic acid group, and the thickness of the RNFL was significantly thickened, but the thickness of the RNFL in the gallic acid group was significantly reduced compared with that in the simple high IOP group (p < 0.05). DHE staining showed that ROS content in the simple high IOP group was significantly increased compared with the normal control group, and ROS content was significantly decreased after the application of gallic acid (p < 0.05). Immunofluorescence staining with Brn-3a antibody confirmed that the number of RGCs was significantly reduced in the simple high IOP group compared with the normal control group, whereas after application of gallic acid, the number of RGCs was significantly more in the gallic acid group than in the simple high IOP group (p < 0.05). Western Blot and q-PCR confirmed that hypoxia-inducing factor 1α (HIF-1α) protein content and transcription level were significantly increased in the retinal tissue of the simple high IOP group, and gallic acid could inhibit HIF-1α protein content (p < 0.05) and reduce transcription factor level (p < 0.05). Gallic acid exerts a protective effect on RGC by inhibiting oxidative stress in rats with acute IOP elevation.
Topics: Gallic Acid; Animals; Retinal Ganglion Cells; Antioxidants; Male; Rats; Rats, Sprague-Dawley; Disease Models, Animal; Glaucoma; Oxidative Stress; Reactive Oxygen Species; Hypoxia-Inducible Factor 1, alpha Subunit; Intraocular Pressure; Ocular Hypertension
PubMed: 38942959
DOI: 10.1038/s41598-024-65965-7 -
Scientific Reports Jun 2024This study aimed to investigate the effect of orbital wall decompression surgery and reduction of proptosis on the choroidal vascularity index (CVI) and subfoveal...
This study aimed to investigate the effect of orbital wall decompression surgery and reduction of proptosis on the choroidal vascularity index (CVI) and subfoveal choroidal thickness (SFCT) in patients with thyroid eye disease (TED). Fifty-one eyes from 38 patients with controlled TED and proptosis were enrolled in this study. The majority of the patients (50.9%) had a clinical activity score (CAS) of zero, and none had a CAS greater than 2. The patients underwent a complete baseline ophthalmologic examination, and their choroidal profile alterations were monitored using enhanced depth imaging optical coherence tomography (EDI-OCT) before and during the three months after surgery. Changes in SFCT, luminance area (LA), total choroidal area (TCA), and the choroidal vascularity index (CVI) were measured as the ratio of LA to TCA in EDI-OCT images. The participants had an average age of 46.47 years, and 22 were female (57.9%). The SFCT of the patients exhibited a significant reduction over the follow-up period, decreasing from 388 ± 103 to 355 ± 95 µm in the first month (p < 0.001) and further decreasing to 342 ± 109 µm by the third month compared to baseline (p < 0.001). The CVI exhibited a drop from 0.685 ± 0.037 at baseline to 0.682 ± 0.035 and 0.675 ± 0.030 at 1 and 3 months post-surgery, respectively. However, these changes were not statistically significant, indicating comparable decreases in both LA and TCA. There was a significant correlation between improved proptosis and reduction in SFCT (p < 0.001) but not with CVI (p = 0.171). In conclusion, during the three months of follow-up following orbital wall decompression, CVI did not change, while SFCT reduced significantly. Additionally, SFCT was significantly correlated with proptosis reduction, whereas CVI was not.
Topics: Humans; Female; Male; Middle Aged; Decompression, Surgical; Graves Ophthalmopathy; Choroid; Tomography, Optical Coherence; Adult; Orbit; Exophthalmos; Aged; Treatment Outcome
PubMed: 38942805
DOI: 10.1038/s41598-024-65884-7 -
Cell Death Discovery Jun 2024This study assesses the neuroprotective potential of CPP-P1, a conjugate of an anti-apoptotic peptain-1 (P1) and a cell-penetrating peptide (CPP) in in vitro, in vivo,...
This study assesses the neuroprotective potential of CPP-P1, a conjugate of an anti-apoptotic peptain-1 (P1) and a cell-penetrating peptide (CPP) in in vitro, in vivo, and ex vivo glaucoma models. Primary retinal ganglion cells (RGCs) were subjected to either neurotrophic factor (NF) deprivation for 48 h or endothelin-3 (ET-3) treatment for 24 h and received either CPP-P1 or vehicle. RGC survival was analyzed using a Live/Dead assay. Axotomized human retinal explants were treated with CPP-P1 or vehicle for seven days, stained with RGC marker RBPMS, and RGC survival was analyzed. Brown Norway (BN) rats with elevated intraocular pressure (IOP) received weekly intravitreal injections of CPP-P1 or vehicle for six weeks. RGC function was evaluated using a pattern electroretinogram (PERG). RGC and axonal damage were also assessed. RGCs from ocular hypertensive rats treated with CPP-P1 or vehicle for seven days were isolated for transcriptomic analysis. RGCs subjected to 48 h of NF deprivation were used for qPCR target confirmation. NF deprivation led to a significant loss of RGCs, which was markedly reduced by CPP-P1 treatment. CPP-P1 also decreased ET-3-mediated RGC death. In ex vivo human retinal explants, CPP-P1 decreased RGC loss. IOP elevation resulted in significant RGC loss in mid-peripheral and peripheral retinas compared to that in naive rats, which was significantly reduced by CPP-P1 treatment. PERG amplitude decline in IOP-elevated rats was mitigated by CPP-P1 treatment. Following IOP elevation in BN rats, the transcriptomic analysis showed over 6,000 differentially expressed genes in the CPP-P1 group compared to the vehicle-treated group. Upregulated pathways included CREB signaling and synaptogenesis. A significant increase in Creb1 mRNA and elevated phosphorylated Creb were observed in CPP-P1-treated RGCs. Our study showed that CPP-P1 is neuroprotective through CREB signaling enhancement in several settings that mimic glaucomatous conditions. The findings from this study are significant as they address the pressing need for the development of efficacious therapeutic strategies to maintain RGC viability and functionality associated with glaucoma.
PubMed: 38942762
DOI: 10.1038/s41420-024-02070-8 -
PAM-flexible Engineered FnCas9 variants for robust and ultra-precise genome editing and diagnostics.Nature Communications Jun 2024The clinical success of CRISPR therapies hinges on the safety and efficacy of Cas proteins. The Cas9 from Francisella novicida (FnCas9) is highly precise, with a...
The clinical success of CRISPR therapies hinges on the safety and efficacy of Cas proteins. The Cas9 from Francisella novicida (FnCas9) is highly precise, with a negligible affinity for mismatched substrates, but its low cellular targeting efficiency limits therapeutic use. Here, we rationally engineer the protein to develop enhanced FnCas9 (enFnCas9) variants and broaden their accessibility across human genomic sites by ~3.5-fold. The enFnCas9 proteins with single mismatch specificity expanded the target range of FnCas9-based CRISPR diagnostics to detect the pathogenic DNA signatures. They outperform Streptococcus pyogenes Cas9 (SpCas9) and its engineered derivatives in on-target editing efficiency, knock-in rates, and off-target specificity. enFnCas9 can be combined with extended gRNAs for robust base editing at sites which are inaccessible to PAM-constrained canonical base editors. Finally, we demonstrate an RPE65 mutation correction in a Leber congenital amaurosis 2 (LCA2) patient-specific iPSC line using enFnCas9 adenine base editor, highlighting its therapeutic utility.
Topics: Humans; Gene Editing; CRISPR-Associated Protein 9; CRISPR-Cas Systems; Francisella; Bacterial Proteins; Leber Congenital Amaurosis; Streptococcus pyogenes; HEK293 Cells; Mutation; RNA, Guide, CRISPR-Cas Systems; Protein Engineering; Genome, Human
PubMed: 38942756
DOI: 10.1038/s41467-024-49233-w -
Ophthalmology. Retina Jun 2024To demonstrate the therapeutic similarity of CT-P42 compared to reference aflibercept (Eylea®) in adult patients with diabetic macular edema (DME).
OBJECTIVE
To demonstrate the therapeutic similarity of CT-P42 compared to reference aflibercept (Eylea®) in adult patients with diabetic macular edema (DME).
DESIGN
Randomized, active-controlled, double-masked, Phase III clinical trial PARTICIPANTS: Patients with a diagnosis of either type 1 or 2 diabetes mellitus (DM) with DME involving the center of the macula.
METHODS
Patients were randomized (1:1) to receive either CT-P42 or reference aflibercept (2 mg/0.05 mL) by intravitreal injection every 4 weeks (5 doses) then every 8 weeks (4 doses) in the main study period. Results up to Week 24 are reported herein.
MAIN OUTCOME MEASURES
The primary endpoint was mean change from baseline at Week 8 in best corrected visual acuity (BCVA) using the Early Treatment Diabetic Retinopathy Study (ETDRS) chart. Equivalence between CT-P42 and reference aflibercept was to be concluded if the two-sided 95% confidence interval (CI) (global assumptions) and two-sided 90% CI (US Food and Drug Administration [FDA] assumptions) for the treatment difference fell entirely within the equivalence margin of ±3 letters, as assessed in the full analysis set.
RESULTS
Overall, 348 patients were randomized (CT-P42: 173; reference aflibercept: 175). BCVA improved from baseline to Week 8 in both groups, with a least squares mean (standard error) improvement of 9.43 (0.798) and 8.85 (0.775) letters in the CT-P42 and reference aflibercept groups, respectively. The estimated between-group treatment difference was 0.58 letters, with the CIs within the pre-defined equivalence margin of ±3 letters (95% CI -0.73, 1.88 [global]; 90% CI -0.52, 1.67 [FDA]). Through Week 24, other efficacy results for the two groups, in terms of change in BCVA and retinal central subfield thickness, as well as ETDRS Diabetic Retinopathy Severity Scale score, supported therapeutic similarity. Pharmacokinetics, usability, safety (including the proportions of patients experiencing at least one treatment-emergent adverse event [CT-P42: 50.3%; reference aflibercept: 53.7%]), and immunogenicity were also comparable between groups.
CONCLUSIONS
This study in patients with DME demonstrated equivalence between CT-P42 and reference aflibercept (2 mg/0.05 mL) in terms of efficacy, with similar pharmacokinetic, usability, safety, and immunogenicity profiles.
PubMed: 38942386
DOI: 10.1016/j.oret.2024.06.013 -
Journal of AAPOS : the Official... Jun 2024Terminal deletions of chromosome 3q are associated with a heterogenous clinical phenotype, which includes growth restriction, developmental delay, and intellectual...
Terminal deletions of chromosome 3q are associated with a heterogenous clinical phenotype, which includes growth restriction, developmental delay, and intellectual disability. However, little has been published on the ophthalmic impacts of chromosome 3q deletions. We report a 9-year-old boy with a 1.4 megabase deletion of 3q27.1q27.2 whose ocular morbidities included retinal detachment in one eye, vitreous hemorrhage in the other eye, and foveal hypoplasia in both eyes that required acute care and continuous ophthalmologic follow-up.
PubMed: 38942230
DOI: 10.1016/j.jaapos.2024.103960 -
American Journal of Ophthalmology Jun 2024Pan-retinal photocoagulation (PRP) is the mainstay of treatment for proliferative diabetic retinopathy (PDR), reducing the risk of severe vision loss. Pain poses a... (Review)
Review
PURPOSE
Pan-retinal photocoagulation (PRP) is the mainstay of treatment for proliferative diabetic retinopathy (PDR), reducing the risk of severe vision loss. Pain poses a potential obstacle to effective laser delivery and patient compliance. Therefore, implementing pain relief strategies can enhance both treatment efficacy and patient comfort.
DESIGN
A systematic review and meta-analysis.
METHODS
We conducted a systematic review and meta-analysis according to PRISMA guidelines. The PubMed, Embase and Cochrane Central Register of Controlled Trials databases were searched for randomized controlled trials (RCTs) that enrolled patients undergoing PRP due to DR and compared analgesics or non-steroidal anti-inflammatory drugs (NSAID) to placebo. Pain was evaluated with the visual analogue scale. The version 2 of the Cochrane Collaboration's Risk of Bias in Randomized Controlled Trials tool and its version for crossover trials were used to assess the risk of bias. The Grading of Recommendations, Assessment, Development, and Evaluation tool was used to measure the certainty of evidence.
RESULTS
A total of 13 studies were included, comprising 1404 eyes from RCTs, nine of which were crossover. Patients who were administered analgesia reported a significantly lower pain sensitivity compared to those who received placebo (Standardized mean difference [SMD] -0.38; 95% confidence interval [CI] -0.58, -0.17; P<0.01; I=69%). Subgroup analysis of systemic administration of analgesics/NSAIDs (metamizole, Entonox, acetaminophen, ibuprofen, caffeine, mefenamic acid, intramuscular ketorolac tromethamine, and potassium diclofenac) also showed a statistically significant reduction in pain when compared to placebo (SMD -0.28; 95% CI -0.50, -0.07; P<0.01; I=43%). Exclusive eye drops administration (ketorolac tromethamine 0.5% and sodium diclofenac 0.1%) also showed a significant difference in pain sensitivity (SMD -0.46; 95% CI -0.88, -0.05; I=83%), however with a more significant heterogeneity.
CONCLUSION
The results of this meta-analysis including over 1000 patients demonstrated that the use of analgesics significantly reduced pain sensitivity during PRP, and systemic analgesia is potentially better than topical administration when compared to placebo.
PubMed: 38942228
DOI: 10.1016/j.ajo.2024.06.018 -
Experimental Eye Research Jun 2024Over the past twenty years, ocular gene therapy has primarily focused on addressing diseases linked to various genetic factors. The eye is an ideal candidate for gene... (Review)
Review
Over the past twenty years, ocular gene therapy has primarily focused on addressing diseases linked to various genetic factors. The eye is an ideal candidate for gene therapy due to its unique characteristics, such as easy accessibility and the ability to target both corneal and retinal conditions, including retinitis pigmentosa (RP), Leber congenital amaurosis (LCA), age-related macular degeneration (AMD), and Stargardt disease. Currently, literature documents 33 clinical trials in this field, with the most promising results emerging from trials focused on LCA. These successes have catalyzed further research into other ocular conditions such as glaucoma, AMD, RP, and choroideremia. The effectiveness of gene therapy relies on the efficient delivery of genetic material to specific cells, ensuring sustained and optimal gene expression over time. Viral vectors have been widely used for this purpose, although concerns about potential risks such as immune reactions and genetic mutations have led to the development of non-viral vector systems. Preliminary laboratory research and clinical investigations have shown a connection between vector dosage and the intensity of immune response and inflammation in the eye. The method of administration significantly influences these reactions, with subretinal delivery resulting in a milder humoral response compared to the intravitreal route. This review discusses various ophthalmic diseases, including both corneal and retinal conditions, and their underlying mechanisms, highlighting recent advances and applications in ocular gene therapies.
PubMed: 38942133
DOI: 10.1016/j.exer.2024.109983 -
Survey of Ophthalmology Jun 2024Cystoid macular edema (CME) is a sight-threatening condition often associated with inflammatory and diabetic diseases. Early detection is crucial to prevent irreversible... (Review)
Review
Cystoid macular edema (CME) is a sight-threatening condition often associated with inflammatory and diabetic diseases. Early detection is crucial to prevent irreversible vision loss. Artificial intelligence (AI) has shown promise in automating CME diagnosis through optical coherence tomography (OCT) imaging, but its utility needs critical evaluation. This systematic review assesses the application of AI to diagnosis CME, specifically focusing on disorders like postoperative CME (Irvine Gass syndrome) and retinitis pigmentosa without obvious vasculopathy, using OCT imaging. A comprehensive search was conducted across 6 databases (PubMed, Scopus, Web of Science, Wiley, ScienceDirect, and IEEE) from 2018 to November, 2023. Twenty-three articles met the inclusion criteria and were selected for in-depth analysis. We evaluate AI's role in CME diagnosis and its performance in "detection", "classification" and "segmentation" of OCT retinal images. We found that convolutional neural network (CNN)-based methods consistently outperformed other machine learning techniques, achieving an average accuracy of over 96% in detecting and identifying CME from OCT images. Despite certain limitations such as dataset size and ethical concerns, the synergy between AI and OCT, particularly through CNNs, holds promise for significantly advancing CME diagnostics.
PubMed: 38942125
DOI: 10.1016/j.survophthal.2024.06.005