OBJECTIVE

To assess the diagnostic accuracy of point-of-care screening using Medios™ Artificial Intelligence (AI) in the diagnosis of diabetic retinopathy (DR).

This is a multi-center, cross-sectional, instrument validation study among adult Filipinos with Type 2 diabetes seen at Endocrine specialty clinics from May to November 2021. Retinal images were captured by a minimally trained nurse using the Remedio Fundus on Phone (FOP). Images were interpreted separately by the Medios™ AI and three retina specialists. The primary outcome measure is the accuracy of Medios™™ AI in diagnosing DR compared to retina specialists’ findings using sensitivity and specificity, predictive values, and likelihood ratios.

A total of 182 subjects with Type 2 diabetes were included in the study. The sensitivity and specificity of the Medios™ AI in diagnosing any DR were 73.68% (95%CI, 57.99-85.03) and 83.74% (95%CI, 79.35-87.35), respectively, compared with the retinal specialists’ findings using the same images. The positive and negative predictive values were 34.57% (95%CI, 25.12-45.41) and 96.47% (95%CI, 93.62-98.07). The positive and negative likelihood ratios were 4.53 (95%CI, 4.26 4.82) and 0.31 (95%CI, 0.26-0.38). The overall diagnostic accuracy of Medios™ AI in detecting DR was 82.69% (95%CI, 78.47-86.23).

The Medios™ AI system showed acceptable diagnostic accuracy when used as a point-of-care screening tool in detecting DR among patients with Type 2 diabetes seen at Endocrine specialty clinics. This technology can be a useful screening tool for endocrinologists as it is relatively inexpensive, safe, and easily performed. It can also shorten the lead time from screening to referral and intervention.

This paper summarizes Professor SUN Yuanzheng's academic thought and clinical experience in treating diabetic retinopathy (DR) with yuan-primary and luo-connecting meridian-regulating acupuncture. Professor SUN considers that the fundamental cause of DR lies in visceral dysfunction, with stagnation in the ocular collateral vessels and impairment of the mysterious orifices being the core pathogenesis. He proposes the treatment model of "regulating viscera, unblocking ocular collaterals, and opening mysterious orifices" based on yuan-primary and luo-connecting meridian-regulating acupuncture. Yuan-primary and luo-connecting points are used to balance qi, blood, yin, and yang of the viscera. Baihui (GV20) is stimulated with transcranial repetitive acupuncture to activate the yang qi of the governor vessel and invigorate qi in the twelve meridians, improving systemic microcirculation. Combining this with stimulation of ocular areas, Fengchi (GB20), and periocular points, the stasis in the ocular collaterals are cleared and the mysterious orifices are unblocked, addressing both the root and manifestations of DR.
Humans ; Diabetic Retinopathy/physiopathology* ; Acupuncture Therapy/history* ; Meridians ; Acupuncture Points ; Qi

Ginsenoside Rg_2(GRg2) is a triterpenoid compound found in Panax notoginseng. This study explored its effects and mechanisms on diabetic retinopathy and angiogenesis. The study employed endothelial cell models induced by glucose or vascular endothelial growth factor(VEGF), the chorioallantoic membrane(CAM) model, the oxygen-induced retinopathy(OIR) mouse model, and the db/db mouse model to evaluate the therapeutic effects of GRg2 on diabetic retinopathy and angiogenesis. Transwell assays and endothelial tube formation experiments were conducted to assess cell migration and tube formation, while vascular area measurements were applied to detect angiogenesis. The impact of GRg2 on the retinal structure and function of db/db mice was evaluated through retinal thickness and electroretinogram(ERG) analyses. The study investigated the mechanisms of GRg2 by analyzing the activation of Yes-associated protein(YAP) and Toll-like receptors(TLRs) pathways. The results indicated that GRg2 significantly reduced cell migration numbers and tube formation lengths in vitro. In the CAM model, GRg2 exhibited a dose-dependent decrease in the vascular area ratio. In the OIR model, GRg2 notably decreased the avascular and neovascular areas, ameliorating retinal structural disarray. In the db/db mouse model, GRg2 increased the total retinal thickness and enhanced the amplitudes of the a-wave, b-wave, and oscillatory potentials(OPs) in the ERG, improving retinal structural disarray. Transcriptomic analysis revealed that the TLR signaling pathway was significantly down-regulated following YAP knockdown, with PCR results consistent with the transcriptome sequencing findings. Concurrently, GRg2 downregulated the expression of Toll-like receptor 4(TLR4), TNF receptor-associated factor 6(TRAF6), and nuclear factor-kappaB(NF-κB) proteins in high-glucose-induced endothelial cells. Collectively, GRg2 inhibits cell migration and tube formation and significantly reduces angiogenesis in CAM and OIR models, improving retinal structure and function in db/db mice, with its pharmacological mechanism likely involving the down-regulation of YAP expression.
Animals ; Ginsenosides/pharmacology* ; Diabetic Retinopathy/physiopathology* ; Mice ; YAP-Signaling Proteins ; Humans ; Male ; Signal Transduction/drug effects* ; Cell Movement/drug effects* ; Adaptor Proteins, Signal Transducing/genetics* ; Mice, Inbred C57BL ; Neovascularization, Pathologic/metabolism* ; Drugs, Chinese Herbal/administration & dosage* ; Panax notoginseng/chemistry* ; Endothelial Cells/metabolism* ; Transcription Factors/genetics* ; Angiogenesis

Diabetic retinopathy is a common blinding complication in diabetic patients. Compared with conventional fundus color photography, fundus fluorescein angiography can dynamically display retinal vessel permeability changes, offering unique advantages in detecting early small lesions such as microaneurysms. However, existing intelligent diagnostic research on diabetic retinopathy images primarily focuses on fundus color photography, with relatively insufficient research on complex lesion recognition in fluorescein angiography images. This study proposed an adaptive multi-label classification model (D-LAM) to improve the recognition accuracy of small lesions by constructing a category-adaptive mapping module, a label-specific decoding module, and an innovative loss function. Experimental results on a self-built dataset demonstrated that the model achieved a mean average precision of 96.27%, a category F1-score of 91.21%, and an overall F1-score of 94.58%, with particularly outstanding performance in recognizing small lesions such as microaneurysms (AP = 1.00), significantly outperforming existing methods. The research provides reliable technical support for clinical diagnosis of diabetic retinopathy based on fluorescein angiography.
Diabetic Retinopathy/diagnostic imaging* ; Humans ; Fluorescein Angiography ; Microaneurysm/diagnostic imaging* ; Retinal Vessels ; Algorithms

Diabetic retinopathy, a prevalent and vision-threatening microvascular complication of diabetes mellitus, is the leading cause of blindness among middle-aged and elderly individuals. Natural diterpenoids isolated from Siegesbeckia pubescens demonstrate potent anti-inflammatory properties. This study aimed to identify novel bioactive diterpenoids from S. pubescens and investigate their effects on oxidative stress and inflammatory responses in diabetic retinopathy, both in vitro and in vivo. Three new ent-pimarane-type diterpenoids (1-3) and six known compounds (4-9) were isolated from the aerial parts of S. pubescens. Their structures were elucidated through spectroscopic data interpretation, and absolute configurations were determined by comparing calculated and experimental electronic circular dichroism (ECD) spectra. Among these compounds, 14β,16-epoxy-ent-3β,15α,19-trihydroxypimar-7-ene (5) exhibited the most potent protective effect against high glucose and interleukin-1β (IL-1β)-stimulated human retinal endothelial cells. Mechanistically, compound 5 promoted endothelial cell survival while ameliorating oxidative stress and inflammatory response in diabetic retinopathy, both in vivo and in vitro. These findings not only suggest that diterpenoids such as compound 5 are important anti-inflammatory constituents in S. pubescens, but also indicate that compound 5 may serve as a lead compound for preventing or treating vascular complications associated with diabetic retinopathy.
Diabetic Retinopathy/metabolism* ; Humans ; Oxidative Stress/drug effects* ; Animals ; Diterpenes, Kaurane/administration & dosage* ; Asteraceae/chemistry* ; Male ; Endothelial Cells/drug effects* ; Abietanes/administration & dosage* ; Molecular Structure ; Mice ; Anti-Inflammatory Agents/chemistry* ; Plant Extracts/chemistry* ; Mice, Inbred C57BL

OBJECTIVE: To establish and validate a novel diabetic retinopathy (DR) risk-prediction model using a whole-exome sequencing (WES)-based machine learning (ML) method. METHODS: WES was performed to identify potential single nucleotide polymorphism (SNP) or mutation sites in a DR pedigree comprising 10 members. A prediction model was established and validated in a cohort of 420 type 2 diabetic patients based on both genetic and demographic features. The contribution of each feature was assessed using Shapley Additive explanation analysis. The efficacies of the models with and without SNP were compared. RESULTS: WES revealed that seven SNPs/mutations ( rs116911833 in TRIM7, 1997T>C in LRBA, 1643T>C in PRMT10, rs117858678 in C9orf152, rs201922794 in CLDN25, rs146694895 in SH3GLB2, and rs201407189 in FANCC) were associated with DR. Notably, the model including rs146694895 and rs201407189 achieved better performance in predicting DR (accuracy: 80.2%; sensitivity: 83.3%; specificity: 76.7%; area under the receiver operating characteristic curve [AUC]: 80.0%) than the model without these SNPs (accuracy: 79.4%; sensitivity: 80.3%; specificity: 78.3%; AUC: 79.3%). CONCLUSION Novel SNP sites associated with DR were identified in the DR pedigree. Inclusion of rs146694895 and rs201407189 significantly enhanced the performance of the ML-based DR prediction model.
Diabetic Retinopathy/diagnosis* ; Humans ; Machine Learning ; Male ; Female ; Polymorphism, Single Nucleotide ; Middle Aged ; Exome Sequencing ; Aged ; Adult ; Pedigree ; Diabetes Mellitus, Type 2/complications* ; Genetic Predisposition to Disease ; Mutation

OBJECTIVE

To determine if dilated smartphone photography with a 3D-printed adaptor for a fundus lens can be an alternative screening tool for diabetic retinopathy.

This was a single-center, prospective, comparative study of 102 eyes of patients with diabetes mellitus. DR screening was performed using binocular indirect ophthalmoscopy (BIO) as the reference standard, alongside two imaging modalities: a traditional fundus camera and a smartphone equipped with a 3D-printed adaptor. Coded images were evaluated by three masked retina specialists. Sensitivity, specificity, predictive values, and likelihood ratios were calculated for both imaging modalities.

DR gradings of both imaging modalities were compared to BIO and showed very good agreement (κ 0.94-0.96 95% CI 0.93-0.99). Both have high levels of interobserver reliability (kappa value 0.88-0.92 95% CI 0.84-0.96) and intraobserver reliability (kappa value 0.85-1.00 95% CI 0.64-1.00). Smartphone and Visucam 500 images can detect presence of DR with a sensitivity of 93.9% (95% CI 83.1-98.7) and 91.8% (95% CI 80.4- 97.7); and a specificity of 90.6% (95% CI 79.3-96.9) and 92.5% (95% CI 81.8-97.9), respectively, as well as the presence of vision threatening DR with a sensitivity of 100% (95% CI 91.2-100) and specificity of 85.5% (95% CI 74.2-93.1). Image quality was similar between the two imaging modalities (P=1.00).

Smartphone-based imaging with an attached 3D-printed adaptor offers high sensitivity and reliability comparable to a traditional fundus camera, and can be used an alternative for DR screening.

OBJECTIVES: Long noncoding RNAs (lncRNA) play important roles in the pathological processes of angiogenesis-related diseases such as cancer and diabetic retinopathy. This study aims to identify global research trends and hotspots in the field of lncRNAs in angiogenesis-related diseases and to explore future research directions. METHODS: Relevant literature published between 2012 and 2022 was retrieved from the Web of Science Core Collection (WoSCC). A total of 1 516 articles on lncRNAs and angiogenesis-related diseases were included for bibliometric analysis. CiteSpace and VOSviewer were used to analyze publication countries, institutions, journals, authors, co-cited references, and key words. RESULTS: The number of publications in this field has shown a steadily increasing trend from 2012 to 2022, peaking in 2021. China has the highest number of publications, while the United States ranked highest in centrality. Nanjing Medical University was the most prolific institution. Liu Y was the most productive author, while Wang Y ranked first in co-citation frequency. Cell was the most frequently cited journal. The latest terms of burst key words were vascular remodeling, dysfunction, heart, target, suppress, and pulmonary arterial hypertension. CONCLUSIONS From 2012 to 2022, research on lncRNAs in angiogenesis-related diseases has grown significantly. China leads in publication volume, while the United States holds the most academic influence. Emerging research hotspots such as vascular remodeling and dysfunction point to key directions for future research.
Bibliometrics ; RNA, Long Noncoding/genetics* ; Humans ; Neovascularization, Pathologic/genetics* ; Neoplasms/genetics* ; Diabetic Retinopathy/genetics* ; Biomedical Research/trends* ; China ; Angiogenesis

Humans ; Diabetic Retinopathy/pathology* ; Retina ; Diabetes Mellitus

Objective To investigate the neuroprotective effect of methylene blue on diabetic retinopathy in rats. Methods Thirty SD rats were randomly divided into blank, control and experimental groups. The control and experimental groups were induced with diabetes by streptozotocin (STZ) intraperitoneal injection. After 6 weeks of successful modeling, the experimental group received intravitreal injection of methylene blue at a dose of [0.2 mg/(kg.d)], while the control group received an equal amount of dimethyl sulfoxide (DMSO) intravitreal injection, both continuously injected for 7 days. ELISA was used to detect the levels of retinal superoxide dismutase (SOD), 8-iso-prostaglandin F2alpha (iPF2α) and interleukin-1β (IL-1β) in rats. Western blot analysis was used to detect the expression of retinal extracellular signal-regulated kinase 1/2 phosphorylation (p-ERK1/2) and phosphorylated protein kinase B (p-AKT), and PAS staining was used to detect retinal morphological changes. Results Compared with the blank group rats, the retinal SOD activity in the control and experimental group rats was significantly reduced. iPF2α, IL-1β and p-ERK1/2 level increased, while p-AKT level decreased. Compared with the control group, the SOD activity of the experimental group rats increased. iPF2α and IL-1β level went down, while p-ERK1/2 and p-AKT level went up significantly. The overall thickness of the retinal layer and the number of retinal ganglion cells were significantly reduced. Conclusion Methylene blue improves diabetic retinopathy in rats by reducing retinal oxidative stress and enhancing ERK1/2 and AKT phosphorylation.
Rats ; Animals ; Diabetic Retinopathy/metabolism* ; Proto-Oncogene Proteins c-akt/metabolism* ; Mitogen-Activated Protein Kinase 3/metabolism* ; Interleukin-1beta/metabolism* ; Methylene Blue/pharmacology* ; Phosphorylation ; Rats, Sprague-Dawley ; MAP Kinase Signaling System ; Diabetes Mellitus, Experimental/drug therapy* ; Superoxide Dismutase/metabolism*