Dan Cao

Aims To evaluate whether predominantly peripheral lesions (PPLs) and other imaging biomarkers on ultra-widefield (UWF) photography can predict the progression of diabetic retinopathy (DR) in a multiethnic Asian cohort. Methods This was a prospective, longitudinal cohort study involving 282 participants (528 eyes) with diabetes and either no DR or non-proliferative DR, recruited from the Singapore National Eye Centre between July 2017 and May 2021. Participants underwent annual UWF colour fundus photography and systemic evaluations over a 2-year period. Images were graded at a centralised reading centre. An automated lesion detection algorithm was used for objective quantification of microaneurysms and retinal haemorrhages. Multivariate regression analysis was conducted to identify independent predictors of DR progression, adjusting for systemic and ocular risk factors. The primary outcome was DR progression, defined as a ≥2 step worsening on the Diabetic Retinopathy Severity Scale or development of proliferative DR within 2 years. Results The 2-year progression rate of DR was 9.85%. Independent predictors of progression included increased peripheral retinal haemorrhage density (OR=3.09; 95% CI 1.03 to 9.22; p=0.044), presence of PPLs (OR=4.00; 95% CI 1.07 to 15.0; p=0.040) and higher baseline diastolic blood pressure (OR=1.04; 95% CI 1.01 to 1.08; p=0.015). Eyes with PPLs had a 1.6-fold higher risk of progression compared with eyes with predominantly central lesions (15.3% vs 9.3%). Conclusion Peripheral biomarkers on UWF imaging, including peripheral retinal haemorrhage density and PPLs, are independent predictors of DR progression. These findings support the clinical utility of peripheral retinal assessment and automated artificial intelligence-based imaging tools in DR risk stratification and management.

Preoperative anti-vascular endothelial growth factor (VEGF) therapy in proliferative diabetic retinopathy (PDR) may exacerbate fibrovascular contraction, posing significant challenges. This study aims to characterize proteo-metabolomic changes induced by anti-VEGF therapy, validate key candidates on orthogonal analytical platforms, and provide functional evidence for the lead molecule. Aqueous humor from 25 patients with PDR with simple vitreous hemorrhage (VH; n = 13) or VH with tractional retinal detachment (VH + TRD; n = 12) underwent data-independent acquisition (DIA) proteomics and widely targeted metabolomics before and 7 days after intravitreal aflibercept. Molecules altered in both cross-sectional and longitudinal comparisons were classified as "aggravation-type" or "improvement-type." Aggravation-type molecules were validated by parallel reaction monitoring/selected reaction monitoring (PRM/SRM) in an independent cohort (cataract controls, n = 10; simple VH, n = 5; VH + TRD, n = 5), and GALNS was functionally assessed by siRNA knockdown in fibroblasts. Intersection analysis identified 38 molecules (5 proteins and 33 metabolites): 35 improvement-type and 3 aggravation-type (CAST, GALNS, and 3-hydroxypropanoic acid [3-HPA]). Independent validation using PRM proteomics and SRM metabolomics confirmed that only GALNS was robustly validated across both cross-sectional (P = 0.016) and longitudinal (P = 0.049) comparisons, whereas CAST and 3-HPA did not reach statistical significance in validation. GALNS exhibited a biphasic pattern-elevated in PDR relative to cataract controls yet depleted in VH + TRD and further declined post-treatment. GALNS knockdown in fibroblasts upregulated α-SMA and collagen I, accelerated migration, and enhanced contractility. This multi-omics study, reinforced by independent validation, reveals GALNS depletion as a potential pro-fibrotic molecule following anti-VEGF therapy in PDR, offering a promising candidate for perioperative risk stratification. CAST and 3-HPA remain exploratory candidates requiring validation in larger cohorts.

While ultra-widefield fluorescein angiography (UWF-FA) is essential for evaluating retinal vascular pathology in diabetic retinopathy (DR), its invasive nature limits its clinical application. This study aimed to develop and evaluate UWFDR-GAN, a generative adversarial network (GAN) framework for translating ultra-widefield color fundus photography (UWF-CFP) into UWF-FA specifically for DR patients. A total of 270 paired UWF-CFP and UWF-FA images were collected from patients with DR, comprising 73 pairs of mild non-proliferative diabetic retinopathy (NPDR), 47 pairs of moderate NPDR, 82 pairs of severe NPDR, and 68 pairs of proliferative diabetic retinopathy (PDR). We first employed a self-supervised keypoint detection framework for precise cross-modal image registration. The generation network incorporated discrete wavelet transform/inverse transform (DWT/IDWT) to preserve high-frequency details and a Swin Transformer-based multi-scale discriminator to enhance structural realism. We quantitatively compared the performance of our model against several state-of-the-art methods, including pix2pix, pix2pixHD, and UWAFA-GAN, using objective evaluation metrics: the Multi-Scale Structural Similarity Index Measure (MS-SSIM), Peak Signal-to-Noise Ratio (PSNR), Fréchet Inception Distance (FID), and Inception Score (IS). UWFDR-GAN achieved the best quantitative performance (MS-SSIM: 0.7214; PSNR: 20.00; FID: 77.48; IS: 1.0123), outperforming all comparison models. Qualitatively, it preserved global vascular architecture and demonstrated superior reconstruction of DR-specific lesions, particularly neovascularization and non-perfusion areas. UWFDR-GAN provided a non-invasive ultra-widefield vascular assessment solution for clinical DR management, demonstrating potential to reduce reliance on invasive fluorescein imaging.

Introduction Persistent diabetic macular edema (DME) with inadequate responsiveness to conventional inhibitors of vascular endothelial growth factor (VEGF) has caused significant vision loss and substantial treatment burdens. Brolucizumab is a new-generation anti-VEGF agent with better anatomical efficacy and prolonged duration of action. This single-centre, open-label, single-arm design clinical trial aims to evaluate the efficacy and safety of intravitreal brolucizumab 6 mg in Chinese subjects with persistent DME. Methods and analysis A total of 52 adult subjects with persistent DME will be recruited from Guangdong Provincial People’s Hospital. All study eyes will receive three consecutive 6 mg brolucizumab injections at intervals of 6 weeks. Disease activity assessment (DAA) will be arranged at week 18, and if disease activity is detected, subjects will continue with dosing of brolucizumab every 6 weeks (at weeks 18 and 24). Otherwise, the dosing will be adjusted to every 12 weeks (at week 24). The primary endpoints will be the proportion of patients with central subfield thickness (CST) Ethics and dissemination This study has been approved by the Ethics Review Committee of Guangdong Provincial People’s Hospital (KY2024-319). This study will be conducted in accordance with the ethical principles that have their origin in the Declaration of Helsinki and that are consistent with the ICH E6 guidelines for Good Clinical Practice and the applicable regulatory requirements. The study results will be submitted to a peer-reviewed journal and presented at both local and international congresses. Trial registration number NCT06498050.

Corneal refractive laser surgery is widely used to correct myopia and astigmatism due to its safety and effectiveness. However, postoperative changes in corneal biomechanics, such as corneal ectasia, can occur, necessitating a deeper understanding of these changes. Finite Element Analysis has shown promise in predicting surgical outcomes based on corneal biomechanics. Devices like the Ocular Response Analyser (ORA) and Corvis ST provide noninvasive ways to measure corneal biomechanics, aiding in the assessment of corneal behavior post-surgery. Young's modulus and tangent modulus are crucial parameters for describing corneal elasticity, but there is limited data on the changes in tangent modulus following Femtosecond Laser-Assisted LASIK (FS-LASIK) in humans. This study aimed to investigate the effect of FS-LASIK on the corneal tangent modulus using a novel corneal indentation device (CID). The study sought to explore changes in corneal tangent modulus after FS-LASIK, taking into account central corneal thickness (CCT) and corneal radius, to enhance our understanding of the biomechanical changes induced by this surgical procedure. Sixty-six patients (66 eyes) underwent FS-LASIK, resulting in significant changes in CCT, corneal radius, and Goldmann intraocular pressure (GAT IOP) 6 months post-surgery (△CCT = − 88 ± 31 µm, △corneal radius = 0.81 ± 0.30 mm, △GAT IOP = − 3.2 ± 2.4 mmHg, p < 0.001) 6 months after surgery. However, corneal stiffness did not significantly change (△ = − 0.002 ± 0.011, p < 0.2). The corneal tangent modulus showed a significant increase post-surgery (△ = 0.263 ± 0.146, p < 0.001), exhibiting a negative correlation with CCT (r = − 0.68, P < 0.001) and a positive correlation with corneal radius (r = 0.71, P < 0.001). For each 1 mm increase in corneal radius, there was a 0.23 MPa increase in corneal modulus, and for every 100 µm reduction in corneal thickness, there was a 0.14 MPa increase in corneal modulus. The corneal tangent modulus, influenced by corneal radius and CCT, increased significantly following FS-LASIK. This study highlights the biomechanical changes induced by FS-LASIK, with implications for understanding corneal behavior post-surgery and its potential impact on patient outcomes.

Background: There are diverse etiologies of serous retinal detachment (SRD), and hypoalbuminemia is one of the rare causes of it. We report a case of bilateral SRD attributed to decreased serum albumin level caused by systemic lupus erythematosus (SLE). Case presentation: A 28-year-old female with no significant past medical history presented with bilateral palpebral edema for 10 days and blurred vision for 3 days. Optical coherence tomography demonstrated subretinal fluid in both eyes; fluorescein angiography revealed multiple hyperfluorescent spots with late leakage and pooling. Extensive serological and systemic examinations showed a slight decrease in serum albumin level with no other notable abnormalities. With the suspected diagnosis of Vogt-Koyanagi-Harada disease, the patient received high-dose intravenous corticosteroid therapy without any improvement. However significant clinical improvement was achieved after albumin supplementation and corticosteroid dose tapering. The decrease in albumin levels in this patient was ultimately found to be due to protein-losing enteropathy (PLE) caused by SLE. Conclusions: This case presented a rare cause of bilateral SRD associated with hypoalbuminemia induced by SLE related PLE. The report revealed that ocular involvements such as palpebral edema and SRD can be the initial manifestations of SLE rather than common lupus retinopathy. It emphasized the values of ocular manifestations as a clue for prompt diagnosis and management of systemic conditions.

Objective: Diabetic macular edema (DME) is the leading cause of visual impairment in patients with diabetes mellitus (DM). The goal of early detection has not yet achieved due to a lack of fast and convenient methods. Therefore, we aim to develop and validate a prediction model to identify DME in patients with type 2 diabetes mellitus (T2DM) using easily accessible systemic variables, which can be applied to an ophthalmologist-independent scenario. Methods: In this four-center, observational study, a total of 1994 T2DM patients who underwent routine diabetic retinopathy screening were enrolled, and their information on ophthalmic and systemic conditions was collected. Forward stepwise multivariable logistic regression was performed to identify risk factors of DME. Machine learning and MLR (multivariable logistic regression) were both used to establish prediction models. The prediction models were trained with 1300 patients and prospectively validated with 104 patients from Guangdong Provincial People’s Hospital (GDPH). A total of 175 patients from Zhujiang Hospital (ZJH), 115 patients from the First Affiliated Hospital of Kunming Medical University (FAHKMU), and 100 patients from People’s Hospital of JiangMen (PHJM) were used as external validation sets. Area under the receiver operating characteristic curve (AUC), accuracy (ACC), sensitivity, and specificity were used to evaluate the performance in DME prediction. Results: The risk of DME was significantly associated with duration of DM, diastolic blood pressure, hematocrit, glycosylated hemoglobin, and urine albumin-to-creatinine ratio stage. The MLR model using these five risk factors was selected as the final prediction model due to its better performance than the machine learning models using all variables. The AUC, ACC, sensitivity, and specificity were 0.80, 0.69, 0.80, and 0.67 in the internal validation, and 0.82, 0.54, 1.00, and 0.48 in prospective validation, respectively. In external validation, the AUC, ACC, sensitivity and specificity were 0.84, 0.68, 0.90 and 0.60 in ZJH, 0.89, 0.77, 1.00 and 0.72 in FAHKMU, and 0.80, 0.67, 0.75, and 0.65 in PHJM, respectively. Conclusion: The MLR model is a simple, rapid, and reliable tool for early detection of DME in individuals with T2DM without the needs of specialized ophthalmologic examinations.

Purpose To explore variations in systemic and ocular parameters among patients with diabetes, both with and without diabetic peripheral neuropathy (DPN) and to identify sensitive indicators for DPN diagnosis. Methods Ninty-five patients with type 2 diabetes mellitus (T2DM) were involved in this cross-sectional study, including 49 without DPN and 46 with DPN. Ocular parameters were obtained using optical coherence tomography angiography (OCTA) and corneal confocal microscopy (CCM). Result Patients with DPN presented with significantly higher HbA1c (p < 0.05) and glycated albumin (GA, p < 0.01) levels, increased prevalence of diabetic retinopathy (DR, p < 0.05), and lower serum albumin (ALB, p < 0.01) and red blood cell (RBC, p < 0.05) levels. Ocular assessments revealed reduced corneal nerve fiber length (CNFL, p < 0.001) and enlarged foveal avascular zone (FAZ) area (p < 0.05) in DPN group. Logistic regression analysis indicated a significant association of presence of DR, RBC, GA, ALB, CNFL and DPN (p < 0.05, respectively). In the binary logistic regression for DPN risk, all three models including the presence of DR and CNFL exhibited the area under the curve (AUC) exceeding 0.8. Conclusion The study establishes a strong correlation between ocular parameters and DPN, highlighting CCM's role in early diagnosis. Combining systemic and ocular indicators improves DPN risk assessment and early management.

A 27-year-old male patient presented with a complaint of 2 years of gradual vision loss in his left eye. His best-corrected visual acuity was logMAR 1.30 (approximate Snellen equivalent, 20/400) OS. Dilated fundus examination revealed a macula-off inferotemporal retinal detachment (RD) in the left eye. Two oval cystoid abnormalities were seen at the 3-o’clock and 4-o’clock meridian near the equator, and a retinal hole was visualized near the equator at approximately the 4-o’clock meridian (Figure, A). The patient was diagnosed with a chronic rhegmatogenous RD with retinal cystoid abnormalities. Ultra-widefield swept-source optical coherence tomography (BM-400K BMizar; TowardPi Medical Technology) showed the cavity of the retinal cystoid abnormalities, which were connected like a pair of sunglasses (Figure, B). Retinal cystoid abnormalities can be indicators of chronic RD, typically resolving after surgical management of the RD. Identify all potential conflicts of interest that might be relevant to your comment. Conflicts of interest comprise financial interests, activities, and relationships within the past 3 years including but not limited to employment, affiliation, grants or funding, consultancies, honoraria or payment, speaker's bureaus, stock ownership or options, expert testimony, royalties, donation of medical equipment, or patents planned, pending, or issued. Err on the side of full disclosure. If you have no conflicts of interest, check "No potential conflicts of interest" in the box below. The information will be posted with your response. Not all submitted comments are published. Please see our commenting policy for details.