Haidong Zou’s research while affiliated with Tongji University and other places

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Publications (266)


Short-Chain Fatty Acids Are Potential Biomarkers of Immune Regulation in Diabetic Retinopathy
  • Article

June 2025

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8 Reads

Investigative Opthalmology & Visual Science

Xinran Qin

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Yi Xu

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Haidong Zou


Comparison of the difference in astigmatism parameters between the two groups with sufficient/insufficient sleep A, box plot depicting the relationship between insufficient sleep and cylinder power. B, box plot depicting the relationship between insufficient sleep and J0t. C, box plot depicting the relationship between insufficient sleep and J0a. D, box plot depicting the relationship between insufficient sleep and J0i. J0, horizontal or vertical vectors of the cylinder
Association between insufficient sleep and astigmatism in preschool children
  • Article
  • Publisher preview available

February 2025

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25 Reads

European Journal of Pediatrics

The aim of this study is to examine the association between insufficient sleep and astigmatism, as well as its related refractive components, in preschool children. Preschool children aged 3 to 6 from two kindergartens in Shanghai participated in this study. Non-cycloplegic refraction was assessed using an auto-refractor (Topcon KR-800, Tokyo, Japan), and biometric parameters were measured with the IOL Master 700 (Carl Zeiss, Jena, Germany). Sleep duration and lifestyle information were collected via questionnaires. Total Astigmatism (TA), Anterior Corneal Astigmatism (ACA), Internal Astigmatism (IA), and Compensation Factor (CF) were calculated from vector components J0 and J45. A total of 451 preschool children (55% males, mean age 5.20 ± 0.84 years) were included, with 5.8% experiencing astigmatism. Insufficient sleep was associated with higher astigmatism prevalence (OR = 2.932, 95% CI: 1.121 to 7.669) and increased cylinder power (β = 0.155, 95% CI: 0.024 to 0.286). Total sleep duration showed an inverse association with cylinder power (β = -0.049, 95% CI: -0.092 to -0.007). Insufficient sleep correlated significantly with J0t (β = 0.123, 95% CI: 0.032—0.215) and J0i (β = 0.170, 95% CI: 0.072—0.269), and CF0 (Adjusted OR = 1.731, 95% CI: 1.005 – 2.981). Sleep duration was also significantly associated with J0t, J0i and CF0. Insufficient sleep is significantly associated with astigmatism in preschool children, primarily through internal astigmatism. These findings emphasize the need for vision screening in children with insufficient sleep to identify and address refractive issues early. What is Known: • Refractive errors, including astigmatism, are common in preschool children and influenced by both environmental and genetic factors. • Insufficient sleep is significantly associated with refractive errors, particularly myopia, and is known to affect visual health and ocular conditions. What is New: • Insufficient sleep is significantly associated with astigmatism in preschool children. • This association may primarily stem from internal compensation mechanisms.

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The cross‐sectional and en face segmentation of optical coherence tomography images, (a) Early Treatment of Diabetic Retinopathy Study (ETDRS) grids centered in the fovea: central ring (d = 1 mm), inner macular ring (d = 3 mm), outer macular ring (d = 6 mm). (b) ETDRS grids centered in the optic nerve head: central ring (d = 1 mm), inner disc ring (d = 3 mm), outer disc ring (d = 6 mm). (c) Macular retinal thickness (from inner limiting membrane to the interface between photoreceptor outer segment and retinal pigment epithelium). (d) Peripapillary retinal thickness (from inner limiting membrane to the interface between photoreceptor outer segment and retinal pigment epithelium) The cup area was excluded. (e) Macular Choroidal thickness (from Bruch's membrane to the choroid‐scleral interface). (f) Peripapillary choroidal thickness (from Bruch's membrane to the choroid‐scleral interface). The cup area was excluded.
Three‐year retinal and choroidal thickness change rate around the optic disc and macula among subjects developing diabetic retinopathy (DR), type‐1 diabetics without DR (non‐DR) and healthy controls. The colour scale indicates the rate of retinal and choroidal thickness changes in each region from baseline over 3‐year follow‐up period.
Association between the onset of diabetic retinopathy and thickness changes in the retina and choroid of children with type 1 diabetes: A three‐year longitudinal study

January 2025

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12 Reads

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1 Citation

Purpose To explore the longitudinal changes in retinal and choroidal thickness and their relation with the onset of type 1 diabetes mellitus (T1DM) in children. Methods Thirty‐eight children with T1DM and 71 healthy controls were included in this 3‐year longitudinal study. Ophthalmic and systemic examinations were conducted on each participant. Retinal and choroidal thickness were measured by optical coherence tomography. Baseline values and changes in retinal and choroidal thickness were compared with DR onset, diabetics without DR and healthy controls. Logistic regression was used to explore the association with DR development. Results Six children developed DR during the follow‐up period (15.79%) and five of them developed microaneurysms in the parapapillary temporal quadrant. During follow‐up, greater retinal thickening occurred in subjects with DR compared with diabetic participants without DR (p = 0.03) and healthy controls (p = 0.02) in the parapapillary outer temporal section. Compared with the control group, greater retinal thickening was observed in DR subjects in the averaged parapapillary outer ring (p = 0.01), the macular inner temporal section (p = 0.03) and several macular sections (all p < 0.05). Additionally, greater retinal thickening was observed in several parapapillary regions in non‐DR T1DM participants compared with healthy controls (all p < 0.05). The thickness change in the outer temporal parapapillary section was independently associated with DR onset (OR = 1.33, 95% CI 1.01–1.73, p = 0.04). Conclusion Children with T1DM showed a significant or a trend of increasing retinal and choroidal thickness compared with normal controls over a 3‐year period. The change of retinal thickness in the parapapillary outer temporal section was associated with the development of DR in children with T1DM, suggesting that it could serve as a biomarker for predicting and screening DR in these individuals.



Fig. 2. The architecture of our Cross-Fundus Transformer (CFT) for DR grading. It consists Transformer encoders, linear projection layers, Cross-Fundus Attention (CFA) module, classifier layer and MLP heads.
Cross-Fundus Transformer for Multi-modal Diabetic Retinopathy Grading with Cataract

November 2024

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8 Reads

Diabetic retinopathy (DR) is a leading cause of blindness worldwide and a common complication of diabetes. As two different imaging tools for DR grading, color fundus photography (CFP) and infrared fundus photography (IFP) are highly-correlated and complementary in clinical applications. To the best of our knowledge, this is the first study that explores a novel multi-modal deep learning framework to fuse the information from CFP and IFP towards more accurate DR grading. Specifically, we construct a dual-stream architecture Cross-Fundus Transformer (CFT) to fuse the ViT-based features of two fundus image modalities. In particular, a meticulously engineered Cross-Fundus Attention (CFA) module is introduced to capture the correspondence between CFP and IFP images. Moreover, we adopt both the single-modality and multi-modality supervisions to maximize the overall performance for DR grading. Extensive experiments on a clinical dataset consisting of 1,713 pairs of multi-modal fundus images demonstrate the superiority of our proposed method. Our code will be released for public access.


Gut microbiome profiling in the cross-sectional study. A Illustration for the study designs. B Principal coordinates analysis (PCoA) to visualize Bray–Curtis distance–based beta diversity. C Bar plot of on the relative abundances of the phyla. D Bar plots to indicate the differential genera between the DR and DM groups. E PCoA to depict KEGG orthologue-based beta diversity. F Pathway enrichment analysis on the differentially expressed microbial genes
Microbial signatures predict DR development. A Heatmap to show co-abundance groups of bacteria at the genus level and their abundance. Participants in the cross-sectional study were classified into four clusters, A to D, based on their taxonomic profiles. B AUC of random forest classifiers was used to discriminate DR based on 16S genus-level KEGG orthologue-level, and combined data. Each dot represents an AUC value of a random-forest classifier using a given number of selected features as predictor variables. The number of predictive variables selected from the datasets increases with the x-axis. C Receiver operating characteristic curve with the highest AUC value obtained by selected features from the combined datasheet. D Variable importance plot to indicate the predictive value of each selected features within the combined datasheet
DR-related microbiota associated with PBMC transcriptomics. A Gene set enrichment analysis on the differential expressed genes (DEGs) between the DR and DM groups to summarize the pathway enrichment. B Heatmap to show the correlation between the DEGs and the relative abundances of discriminatory genera for DR. C Gene Ontology pathway analysis on the genes correlated with discriminatory genera
Gut microbiota predict retinopathy in patients with diabetes: A longitudinal cohort study

October 2024

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20 Reads

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9 Citations

Applied Microbiology and Biotechnology

The gut microbiota has emerged as an independent risk factor for diabetes and its complications. This research aimed to delve into the intricate relationship between the gut microbiome and diabetic retinopathy (DR) through a dual approach of cross-sectional and prospective cohort studies. In our cross-sectional study cross-sectional investigation involving ninety-nine individuals with diabetes, distinct microbial signatures associated with DR were identified. Specifically, gut microbiome profiling revealed decreased levels of Butyricicoccus and Ruminococcus torques group, alongside upregulated methanogenesis pathways among DR patients. These individuals concurrently exhibited lower concentrations of short-chain fatty acids in their plasma. Leveraging machine learning models, including random forest classifiers, we constructed a panel of microbial genera and genes that robustly differentiated DR cases. Importantly, these genera also demonstrated significant correlations with dietary patterns and the molecular profiles of peripheral blood mononuclear cells. Building upon these findings, our prospective cohort study followed 62 diabetes patients over a 2-year period to assess the predictive value of these microbial markers. The results underlined the panel’s efficacy in predicting DR incidence. By stratifying patients based on the predictive genera and metabolites identified in the cross-sectional phase, we established significant associations between reduced levels of Butyricicoccus, plasma acetate, and increased susceptibility to DR. This investigation not only deepens our understanding of how gut microbiota influences DR but also underscores the potential of microbial markers as early indicators of disease risk. These insights hold promise for developing targeted interventions aimed at mitigating the impact of diabetic complications. Key points • Microbial signatures are differed in diabetic patients with and without retinopathy • DR-related taxa are linked to dietary habits and transcriptomic profiles • Lower abundances of Butyricicoccus and acetate were prospectively associated with DR


Distribution map of participants’ residential locations and long-term PM2.5 concentrations (2013–2017).
Subgroup analysis of the association between PM2.5 and optic disc parameters. The estimates represent the regression coefficient of a 10 μg/m³ increase in PM2.5 on (a) vCDR, (b) vDD, and (c) vCD. They were calculated for each subgroup using linear regression adjusting for gender, age, gender, body mass index, duration of diabetes, fasting blood glucose, and blood pressure. vCDR, vertical cup-to-disc ratio; vDD, vertical disc diameter; vCD, vertical cup diameter; CI: confidence interval.
Baseline optic disc diameter and exposure levels to PM 2.5 , O 3 , and NO 2 from 2013 to 2017.
Increments in optic disc diameter associated with 10 µg/m 3 increase in PM 2.5 .
Sensitivity analyses of alternative PM 2.5 exposure levels using 1-year, 2-year, and 3-year averages.
PM2.5 Exposure as a Risk Factor for Optic Nerve Health in Type 2 Diabetes Mellitus

October 2024

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18 Reads

(1) Objective: This study investigated the relationship between long-term particulate matter (PM2.5) exposure and optic disc parameters—vertical cup-to-disc ratio (vCDR), vertical optic disc diameter (vDD), and vertical optic cup diameter (vCD)—in patients with type 2 diabetes mellitus (T2DM). (2) Methods: A cross-sectional analysis was conducted using data from 65,750 T2DM patients in the 2017–2018 Shanghai Cohort Study of Diabetic Eye Disease (SCODE). Optic disc parameters were extracted from fundus images, and PM2.5 exposure was estimated using a random forest model incorporating satellite and meteorological data. Multivariate linear regression models were applied, adjusting for confounders including age, gender, body mass index, blood pressure, glucose, time of T2DM duration, smoking, drinking, and physical exercise. (3) Results: A 10 μg/m³ increase in PM2.5 exposure was associated with significant reductions in vCDR (−0.008), vDD (−42.547 μm), and vCD (−30.517 μm) (all p-values < 0.001). These associations persisted after sensitivity analyses and adjustments for other pollutants like O3 and NO2. (4) Conclusions: Long-term PM2.5 exposure is associated with detrimental changes in optic disc parameters in patients with T2DM, suggesting possible optic nerve atrophy. Considering the close relationship between the optic nerve and the central nervous system, these findings may also reflect broader neurodegenerative processes.


Flowchart of the study participants included in the cross-sectional analysis
SCODE: the Shanghai Cohort Study of Diabetic Eye Disease; DR: diabetic retinopathy
The measurement area and retinal arterioles and venules automatically identified and extracted
Outcomes of subgroup analyses for the impact of insulin use on the prevalence of DR
The ORs for the use of insulin on the prevalence of DR were calculated for each subgroup using logistic regression models adjusting for gender, age, gender, duration of diabetes, body mass index, blood pressure, fasting blood glucose, HbA1c, smoking, and alcohol use based on the IPTW analyses
DR: diabetic retinopathy; IPTW: inverse probability treatment weighted; DM: diabetes mellitus; BMI: body mass index; BP: blood pressure
The influence of insulin on diabetic retinopathy and retinal vessel parameters in diabetes

September 2024

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14 Reads

Diabetology & Metabolic Syndrome

Aim To investigate the associations between insulin use and diabetic retinopathy (DR), and retinal vascular parameters in type 2 diabetes (T2DM). Methods A total of 6,374 T2DM patients, consisting of 2,231 patients receiving insulin alone and 4143 patients without any hypoglycemic medication, were included in cross-sectional analyses. Among those without DR at baseline, 791 patients were followed for three years in longitudinal analyses. Fundus photography was taken to diagnose DR and calculate central retinal arteriolar equivalent (CRAE), central retinal venular equivalent (CRVE), arteriolar-to-venular ratio (AVR), and vascular tortuosity. Inverse probability treatment-weighted analyses were performed. Results After adjusting for gender, age, body mass index, blood pressure, blood glucose, T2DM duration, smoking, and alcohol use, insulin users showed a higher risk of DR (odds ratio (OR) = 2.27, 95% confidence interval (95%CI) = 2.08–2.48, P < 0.001), larger CRVE (β = 3.92, 95%CI = 2.46–5.37, P < 0.001), smaller AVR (β=-0.0083, 95%CI=-0.0121- -0.0046, P < 0.001), and larger vascular curvature (β = 0.19, 95%CI = 0.05–0.33, P = 0.008). After 3 years, insulin users had a higher risk of developing DR (OR = 1.94; 95% CI = 1.37–2.73, P = 0.002), and greater change in CRVE (β = 3.92, 95%CI = 0.96–6.88, P = 0.009). Conclusions The impact of insulin on the retinal microvasculature provides support for linking insulin to the increased risk of DR, as well as cardiovascular events in T2DM.


ROC curve for DR plotted by 12‐HETE levels in the 143 patients with T2DM in the previous cross‐sectional study. The AUC was 0.836 (p < 0.0001).
12‐HETE induces inflammation and leukocyte adhesion in HRMECs in a GPR31‐dependent manner. (A) GPR31 protein expression levels in HRMECs after shRNA transfection measured by Western blot. NC, Negative control; shRNA fragments expressed without homology to the target gene sequence; sh‐GAP, shRNA for GAPDH; sh#1, #2, #3, and #4 are four candidate shRNA plasmid vectors designed to knock down GPR31. (B and C) Distribution and comparison of the mRNA expression levels of inflammatory cytokines IL‐6 and IL‐8 as well as adhesion molecules ICAM‐1 and VCAM‐1 among GPR31‐knockdown HRMECs with or without 12‐HETE treatment. (D) Representative photomicrographs and statistical histogram of fluorescence quantification of adherent leukocytes (labeled with green fluorescence dye) among the four groups. n = 6 per group. RFU, relative fluorescence unit. *p < .05, **p < .01, ***p < .001.
12‐HETE activates the p38 MAPK signaling pathway in HRMECs in a GPR31‐dependent way. (A) The phosphorylation levels of p38 and ERK1/2 in HRMEC at different time points after 12‐HETE treatment measured by Western blot. (B) Phosphorylated and total p38 levels in GPR31‐knockdown HRMECs with or without 12‐HETE treatment. n = 6 per group. ***p < .001.
12‐HETE/GPR31 induces inflammation and leukocyte adhesion in HRMECs through the p38 MAPK signaling pathway. (A and B) Distribution and comparison of the mRNA expression levels of IL‐6, IL‐8, ICAM‐1, and VCAM‐1 among four groups of HRMECs treated with 12‐HETE or vehicle in the presence or absence of SB202190. n = 9 per group. (C) Representative photomicrographs and statistical histogram of fluorescence quantification of adherent leukocytes (labeled with green fluorescence dye) among the four groups of HRMECs with or without 12‐HETE and SB202190 treatment. n = 6 per group. RFU, relative fluorescence unit. *p < .05, **p < .01, ***p < .001.
The elevated retinal 12‐HETE in mice with diabetes induced by HFD promoted retinopathy. (A and B) Distribution and comparison of 12‐HETE and GPR31 mRNA expression levels in the retinas of the three mouse groups. n = 7–8 mice per group. (C) Distribution and comparison of the mRNA expression levels of IL‐1β, IL‐6, ICAM‐1, and VCAM‐1 in the retinas of the three mouse groups. n = 7–8 mice per group. (D) Spearman correlation analysis of 12‐HETE and GPR31 gene expression levels with mRNA expression levels of inflammatory cytokines and adhesion molecules in the mouse retinas. The r values are represented by the numbers in the cells and the gradient colors, where blue indicates positive correlations. *p < .05, **p < .01, ***p < .001.
12‐HETE/GPR31 induces endothelial dysfunction in diabetic retinopathy

September 2024

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8 Reads

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1 Citation

12‐hydroxyeicosatetraenoic acid (12‐HETE), a major metabolite of arachidonic acid, is converted by 12/15‐lipoxygenase and implicated in diabetic retinopathy (DR). Our previous study demonstrated a positive correlation between 12‐HETE and the prevalence of DR. However, reasons for the increased production of 12‐HETE are unclear, and the underlying mechanisms through which 12‐HETE promotes DR are unknown. This study aimed to elucidate the correlation between 12‐HETE and DR onset, investigate potential mechanisms through which 12‐HETE promotes DR, and seek explanations for the increased production of 12‐HETE in diabetes. We conducted a prospective cohort study, which revealed that higher serum 12‐HETE levels could induce DR. Additionally, G protein‐coupled receptor 31 (GPR31), a high‐affinity receptor for 12‐HETE, was expressed in human retinal microvascular endothelial cells (HRMECs). 12‐HETE/GPR31‐mediated HRMEC inflammation occurred via the p38 MAPK pathway. 12‐HETE levels were significantly higher in the retina of mice with high‐fat diet (HFD)‐ and streptozotocin (STZ)‐induced diabetes than in those with only STZ‐induced diabetes and healthy controls. They were positively correlated with the levels of inflammatory cytokines in the retina, indicating that HFD could induce increased 12‐HETE synthesis in patients with diabetes in addition to hyperglycemia. Conclusively, 12‐HETE is a potential risk factor for DR. The 12‐HETE/GPR31 axis plays a crucial role in HRMEC dysfunction and could be a novel target for DR prevention and control. Nevertheless, further research is warranted to provide comprehensive insights into the complex underlying mechanisms of 12‐HETE in DR.


Citations (73)


... Previous studies investigating choroidal thickness in T1DM patients have reported conflicting results. Some have found increased thickness in patients without DR or with mild DR [19,20,21,22,23], while others reported significant thinning [24,25,26,27]. Aksoy et al. [19] demonstrated increased choroidal vascularity index in T1DM patients without DR, suggesting early choroidal involvement. ...

Reference:

New marker for the detection of pre-retinopathy in patients with type 1 diabetes mellitus: systemic immuno-inflammation index
Association between the onset of diabetic retinopathy and thickness changes in the retina and choroid of children with type 1 diabetes: A three‐year longitudinal study

... It is important to highlight that, in a dysbiotic state, metabolic homeostasis is also disrupted, with a decrease in key metabolites such as SCFAs, potentially compromising gut barrier integrity and amplifying inflammatory cascades [115]. As demonstrated by Qin et al. [116], patients with diabetic retinopathy (DR) exhibit specific microbial signatures, including reduced abundance of Butyricicoccus and Ruminococcus torques, along with lower plasma SCFA levels. Machine learning models using these microbial and genomic features have shown predictive value for DR onset, linking dietary patterns and peripheral immune profiles to dysbiosis-driven pathogenesis. ...

Gut microbiota predict retinopathy in patients with diabetes: A longitudinal cohort study

Applied Microbiology and Biotechnology

... In this context, the recent reports that there is a role for 12-LOX and its product 12-HETE, a pro-inflammatory molecule, in the pathogenesis of DR are interesting [81][82][83]. It is likely that 12-HETE can be converted to LXA4, though this has not been reported so far. ...

12‐HETE/GPR31 induces endothelial dysfunction in diabetic retinopathy

... Increasing outdoor time can also significantly mitigate the factors contributing to myopia development in school-aged children (39,40), potentially due to factors like light exposure, peripheral vision, vitamin D levels, and circadian rhythms (41). Sleep deprivation has been linked to myopia progression, particularly with a significant correlation to changes in axial length (42). The American Academy of Sleep Medicine recommends 9 to 12 h of sleep for children aged 6 to 12 years (43). ...

Effects of Insufficient Sleep on Myopia in Children: A Systematic Review and Meta-Analysis

... The allure of screens, particularly through social media, streaming platforms, and video games, often delays sleep onset and disrupts overall sleep quality. Excessive screen exposure, especially before bedtime, interferes with natural circadian rhythms through blue light exposure, further entrenching the cycle of insufficient sleep [5]. ...

Sleep onset time as a mediator in the association between screen exposure and aging: a cross-sectional study

GeroScience

... Research in children suggested that the minimum single exposure outdoor time should be at least 15 minutes, with an intensity reaching 2000 lx. 37 In addition to its direct effects on the eyes, variations in the lighting environment can affect indirectly through changes in the circadian rhythm. 62 The eyes have their own biological rhythm, and when this is disrupted, secretion of dopamine and melatonin can affect the regulation of ocular growth, leading to abnormal axial elongation and the development of myopia. ...

Smartwatch Measures of Outdoor Exposure and Myopia in Children
  • Citing Article
  • August 2024

JAMA Network Open

... Computer vision has demonstrated transformative potential across various applications, including image security [1], anomaly detection [2], visualization technology [3], etc., particularly in medical image analysis, where computer vision assists clinicians in disease prediction [4,5], diagnosis [6] and prognosis [7] through fundamental tasks such Qian 1 as classification [8,9] and segmentation [10,11] alongside visualization technology. Among them, tissue semantic segmentation is one of the important foundational tasks, aiming to accurately identify and delineate pathological tissue regions for more intuitive and quantitative lesion assessment. ...

A deep learning system for myopia onset prediction and intervention effectiveness evaluation in children

npj Digital Medicine

... Various interventions, including pharmacological approaches like low-dose atropine [3], optical devices such as orthokeratology [4,5], peripheral defocus lenses [6], and lifestyle modifications like increased outdoor time [7], have been explored to slow the progression of myopia. Recently, RLRL therapy has emerged as a novel non-invasive approach to myopia control, gaining attention for its potential to slow axial elongation [8][9][10][11][12]. ...

Repeated Low-Level Red-Light Therapy for Myopia Control in High Myopia Children and Adolescents: A Randomized Clinical Trial
  • Citing Article
  • June 2024

Ophthalmology

... Building on RETFound's success in clinical settings, another study demonstrates its real-world utility by developing a RETFound-enhanced DL model for community-based eye disease screening [31]. Trained on challenging real-world images from Shanghai community screenings, the model achieved 15% higher sensitivity and specificity compared to commercial models while showing superior generalization versus traditional AI approaches. ...

RETFound-enhanced community-based fundus disease screening: real-world evidence and decision curve analysis

npj Digital Medicine