To assess the cost-effectiveness of faricimab vs. other anti-vascular endothelial growth factor (anti-VEGF) drugs for treatment of neovascular age-related macular degeneration (nAMD) and diabetic macular edema (DME) in Japan, while considering societal burden associated with treatment.

A Markov model for cost-effectiveness analysis of anti-VEGF treatment in patients with nAMD and DME was applied based on cost and utility value data from Japan. Faricimab administered through a treat-and-extend (T&E) regimen was compared with ranibizumab administered pro re nata (PRN) and T&E, aflibercept T&E, brolucizumab T&E, and best supportive care (BSC). Further to treatment costs (public payer perspective), the societal burden (societal perspective), including costs of travel, informal care, and productivity, was assessed.

In treatment of nAMD, lifetime quality-adjusted life years (QALYs) gained were highest with faricimab (faricimab T&E: 6.92, ranibizumab PRN: 6.88, ranibizumab T&E: 6.91, aflibercept T&E: 6.89, brolucizumab T&E: 6.89, BSC: 5.99). From the public payer perspective, the lifetime total cost for faricimab T&E was lower than those for ranibizumab (PRN, T&E) and brolucizumab (T&E), comparable to aflibercept T&E, and higher than BSC (incremental costs: 158,385 and 6,475,511 JPY, respectively). As a result, faricimab was cost-effective or dominant in the treatment of nAMD, excluding BSC. From the societal perspective, faricimab was dominant against all comparators in nAMD. In treatment of DME, QALYs gained were highest with faricimab (faricimab T&E: 8.51, ranibizumab PRN: 8.17, aflibercept PRN: 8.36, ranibizumab T&E: 8.13, BSC: 5.16). From both the public payer and societal perspectives, faricimab was dominant against all comparators in DME.

When societal burdens were considered, faricimab was dominant in both nAMD and DME against all comparators, suggesting that the extended dosing interval associated with faricimab treatment may alleviate societal burdens and consequently improve patient outcomes.

Inflammation is a crucial aspect of the pathophysiology of diabetic retinopathy (DR). Polymerase delta-interacting protein 2 (Poldip2) has been linked to inflammation in various disorders, but its role in DR remains unclear. This study aims to elucidate the underlying mechanisms of Poldip2 in DR.

Transmission Electron Microscopy (TEM) revealed significant mitophagy reduction due to the accumulation of damaged mitochondria in the retinas of Streptozotocin (STZ)-induced diabetic Sprague Dawley (SD) rats. In vivo, AAV9-Poldip2-shRNA was administered to STZ-induced DR rats, partially restoring mitophagy. Microglia (BV2) cells cultured in high glucose (HG) conditions exhibited similar behavior. Likewise, BV2 received Poldip2-siRNA treatment to further explore the regulatory mechanism of Poldip2.

In vivo, Poldip2 was significantly elevated alongside VEGFR and SQSTM1/P62, while mitophagy markers were inhibited. Under HG conditions, BV2 secret large amounts of pro-inflammatory factors. Human Retinal Microvascular Endothelial Cells (HRMECs) were significantly affected by these HG-cultured BV2, leading to angiogenesis. Notably, Poldip2 knockdown significantly increased Pink1 by preventing its ubiquitination-mediated degradation, thereby enhancing mitophagy and reducing retinal inflammation.

Our findings suggest that Poldip2 contributes to DR by promoting Pink1 degradation, which inhibits mitophagy and leads to inflammation. Targeting Poldip2 may offer a novel therapeutic strategy for DR.

Oxidative stress-induced ocular dysfunctions are a significant global health concern. Glutathione (GSH), an abundant antioxidant in tears, can serve as an index for oxidative stress (OS). A coumarin-based fluorescent probe named CCAE was synthesized for GSH monitoring, functioning through structural changes via Michael's addition with GSH and elimination by H2O2, which restores the conjugation structure to assess the severity of OS-induced ocular diseases. CCAE demonstrated a high sensitivity with a detection limit (LOD) of 0.12 mM and reversibility for 15 cycles. A wearable contact lens sensor was developed featuring a microfluidic lens patterned with a 365 nm pulsed laser, requiring 6 μL of tears. CCAE was encapsulated in citric acid-crosslinked poly(vinyl alcohol) film and embedded in poly((hydroxyethyl)methacrylate-co-ethylene glycol)/polyvinylpyrrolidone (poly(HEMA-co-EG)/PVP) lenses. A customized smartphone readout device enabled quantitative GSH readings for point-of-care applications. Tested on an ex vivo porcine anterior eye model, the sensor achieved an LOD of 0.204 mM, within a detection range of 0.62-1.17 mM and 0.13-0.73 mM under mild and severe OS conditions respectively. The sensors maintained operational stability for 2 days and storage stability for 1 week. This reversible GSH contact lens sensor offers a unique platform for diagnosing and monitoring OS-related ocular conditions at point-of-care settings.

Researchers have explored choroidal features in the eyes of diabetic patients without clinically visible diabetic retinopathy (DM-NoDR) employing optical coherence tomography angiography (OCTA); however, the results are controversial. We systematically searched PubMed, Embase, and Ovid databases for OCTA studies comparing choroidal parameters between DM-NoDR eyes and healthy controls or nonproliferative diabetic retinopathy (NPDR) eyes. Outcomes included choriocapillaris (CC) perfusion density (PD), flow area (FA), and flow deficits (FD). 36 studies were finally included in the quantitative meta-analysis, involving 1908 DM-NoDR eyes, 792 NPDR eyes, and 1391 healthy control eyes. DM-NoDR eyes had significantly lower CC PD in the foveal region (P = 0.0005) and superior parafoveal region (P = 0.003) than healthy control eyes, but no significant difference was found in other parafoveal subregions (P > 0.05). DM-NoDR eyes were also associated with increased CC FD (P < 0.00001) and decreased CC FA (P < 0.0001) in whole OCTA images with a 3 × 3 mm2 field of view (FOV). Compared with all-stage NPDR eyes, DM-NoDR eyes had higher CC PD in the foveal region (P < 0.0001), parafoveal region (P < 0.00001), and the whole OCTA images with a 6 × 6 mm2 FOV (P < 0.00001). Early choroidal microvascular changes may precede clinically visible DR and can be detected early using OCTA in DM-NoDR eyes.

The aim of the study was to estimate the prevalence of diagnosed vision problems and to examine the association of single and multiple chronic conditions with vision problems among middle-aged and older adults in India.

The study utilized data from the Longitudinal Ageing Study in India (LASI) Wave 1, (2017-18). Descriptive statistics along with bivariate and multivariable analyses were conducted to achieve the study objectives.

The prevalence of diagnosed vision problems in the sampled population was 48.2%. The older adults (60+ years) (55.3%) had shown a greater prevalence of vision problems than the middle-aged individuals (41%). Among chronic conditions, hypertension, diabetes, chronic lung diseases, chronic heart diseases, bone related diseases, psychiatric disorders, and high cholesterol were significantly associated with vision problems in the case of both middle-aged and older adults. Furthermore, odds of experiencing vision problems according to the presence of multimorbidity were higher in the middle-aged population [adjusted odds ratio (AOR) = 1.986; confidence interval (CI):1.855-2.126] than in the older population [AOR = 1.746; CI:1.644-1.854].

Middle-aged and older adults with chronic illnesses and multimorbidity were at greater risk of vision problems. Due to the high prevalence of vision problem, interventions aimed at prevention or early detection are warranted.

Diabetic retinopathy (DR) is a leading cause of vision loss, with early detection challenging due to asymptomatic progression and limited predictive tools. To address this, we aimed to develop and validate a risk nomogram for DR prediction in type 2 diabetes patients.

In this retrospective cohort study of 70,073 patients with type 2 diabetes admitted from 2013 to 2019, 2,585 patients were included after exclusions. Patients were randomly assigned to derivation (2/3) and validation (1/3) sets. The prediction model was derived using Cox proportional hazards regression. A nomogram was developed and evaluated for discriminatory capacity and calibration accuracy.

Among 2585 participants (mean age 59 years), 220 (8.5 %) developed retinopathy over a median follow-up of 34 months. We identified key predictors: glycated haemoglobin A1c, serum urea, and diabetes duration. Predictive models for 1-, 3-, and 5-year retinopathy-free survival were constructed and presented as a nomogram, demonstrating good discriminatory power (AUC: 0.941, 0.886, 0.594 in derivation; 0.747, 0.736, 0.670 in validation). Calibration plots further corroborated the improved fit for 3- and 5-year models.

The proposed model shows promise for guiding early interventions and improving outcomes. Further external validation is needed to confirm its applicability across diverse populations.

Nanomedicine offers a promising avenue for improving retinal drug delivery, effectively addressing challenges associated with ocular diseases like age-related macular degeneration and diabetic retinopathy. Nanoparticles, with their submicron size and customisable surface properties, enable enhanced permeability and retention within retinal tissues, supporting sustained drug release and minimising systemic side effects. Nanostructured scaffolds further provide a supportive environment for retinal cell growth and tissue regeneration, crucial for treating degenerative conditions. Additionally, advanced nanodevices facilitate real-time monitoring and controlled drug release, marking significant progress in retinal therapy. This study reviews recent advancements in nanomedicine for retinal drug delivery, critically analysing design innovations, therapeutic benefits, and limitations of these systems. By advancing nanotechnology integration in ocular therapies, this field holds strong potential for overcoming current barriers, ultimately improving patient outcomes and quality of life.

Our aim was to detect early structural and functional changes in the macular capillaries using optical coherence tomography angiography during the course of type 1 or 2 diabetes mellitus.

In this cross-sectional study, individuals with type 1 diabetes (n=143) or type 2 diabetes (n=197) from the German Diabetes Study (ClinicalTrials.gov registration no. NCT01055093) underwent clinical examination and cluster analysis to identify phenotype-based diabetes subtypes, using BMI, age, HbA1c, homoeostasis model estimates and islet autoantibodies. Colour fundus photography, optical coherence tomography and optical coherence tomography angiography were performed within the first year of diabetes diagnosis (baseline) and at 5 year intervals up to year 10. Age- and sex-adjusted participants served as control participants (n=105). Perfusion density, vessel density, presence of retinal microaneurysms in superficial, intermediate and deep capillary plexus (SCP, ICP, DCP), choriocapillaris flow deficit density (CC FD) and the foveal avascular zone (FAZ) of the macula as well as retinal layer thickness, visual acuity and contrast sensitivity were analysed.

Perfusion density and vessel density of SCP were already reduced at baseline in type 2 diabetes (expected difference compared with control participants: -0.0071, p=0.0276, expected difference: -0.0034, p=0.0184, respectively), especially in participants with severe insulin-deficient and mild obesity-related diabetes. At year 10 only perfusion density of the SCP and DCP was reduced in both type 1 and 2 diabetes (p=0.0365, p=0.0062, respectively). The FAZ was enlarged and the CC FD within the first year increased in type 1 (p=0.0327, p=0.0474, respectively) and more markedly in type 2 diabetes (p=0.0006, p<0.0001). The occurrence of microaneurysms in SCP and DCP was significant at year 5 (p=0.0209, p=0.0279, respectively) and year 10 (p=0.0220, p=0.0007). Presence of microaneurysms in SCP and DCP was associated with decreases in perfusion density and vessel density in both SCP and ICP. Furthermore, microaneurysms were associated with decreased ganglion cell layer and inner plexiform layer thickness.

Type 2 diabetes already reduces macular perfusion SCP at time of clinical diagnosis, while long-standing diabetes affects both SCP and DCP. The FAZ of the SCP and the CC FD are early indicators of diabetic alterations, with more pronounced changes observed in type 2 diabetes. Microaneurysms in the macular plexus are associated with a decrease of ganglion cell layer and inner plexiform layer. Subclinical microangiopathy occurs prior to manifestation of diabetic retinopathy, disease-related visual acuity impairment or inner retinal layer thinning.

Diabetes mellitus (DM) increases the risk of vascular complications, and retinal vasculature imaging serves as a valuable indicator of both microvascular and macrovascular health. Moreover, artificial intelligence (AI)-enabled systems developed for high-throughput detection of diabetic retinopathy (DR) using digitized retinal images have become clinically adopted. This study reviews AI applications using retinal images for DM-related complications, highlighting advancements beyond DR screening, diagnosis, and prognosis, and addresses implementation challenges, such as ethics, data privacy, equitable access, and explainability.

We conducted a thorough literature search across several databases, including PubMed, Scopus, and Web of Science, focusing on studies involving diabetes, the retina, and artificial intelligence. We reviewed the original research based on their methodology, AI algorithms, data processing techniques, and validation procedures to ensure a detailed analysis of AI applications in diabetic retinal imaging.

Retinal images can be used to diagnose DM complications including DR, neuropathy, nephropathy, and atherosclerotic cardiovascular disease, as well as to predict the risk of cardiovascular events. Beyond DR screening, AI integration also offers significant potential to address the challenges in the comprehensive care of patients with DM.

With the ability to evaluate the patient's health status in relation to DM complications as well as risk prognostication of future cardiovascular complications, AI-assisted retinal image analysis has the potential to become a central tool for modern personalized medicine in patients with DM.

Diabetic retinopathy (DR), the prevalence of which continues to rise, is one of the most common causes of vision loss worldwide. Experimental and clinical research in recent years has contributed to a better understanding of the pathogenesis of DR, which is complex and results from many interrelated processes leading to abnormal permeability and occlusion of the retinal vasculature, with ischemia and subsequent neovascularization. According to the absence or presence of neovascularization, DR is divided into two main forms: nonproliferative and proliferative DR. From nonproliferative to proliferative disease, diabetic macular edema (DME) can develop anywhere along the spectrum. As the majority of diabetics have no ophthalmologic symptoms, screening plays an important role in preventing the development of retinal disease. Specific treatment options beyond metabolic risk factor control, including intravitreal administration of anti-vascular endothelial growth factor (VEGF) agents or corticosteroids, laser photocoagulation, and vitreous surgery, are effective approaches for ocular diabetic complications.

This study was to investigate the potential association between vitamin D receptor(VDR) gene polymorphisms and the risk of diabetic retinopathy(DR) in the Uygur population in China, focusing on four specific VDR gene single nucleotide polymorphisms(SNPs) as candidate SNPs.

The study genotyped a total of 151 DR patients and 130 healthy controls from the Uygur population using the single-base terminal extension (SNaPshot) method for four VDR gene SNPs: rs1544410, rs7975232, rs2228570, and rs731236. Hardy-Weinberg equilibrium was assessed using the χ2 test. Genotype frequencies were determined by directly counting the genotypes and correlating them with population data. The χ2 test was utilized to compare allele and genotype frequencies between patients and controls.

Compared to the healthy control group, the study observed a significantly higher frequency of the "TT" genotype at rs1544410 in the DR group. Additionally, within the non-proliferative diabetic retinopathy (NPDR) group, a significantly higher frequency of the "AA" genotype at rs7975232 was noted. No significant differences were found in the comparison of all haplotypes between patients and controls.

The study concluded that the rs1544410 polymorphism is associated with DR, and the rs7975232 polymorphism is associated with susceptibility to NPDR in the Uygur population in China.

Individuals with a psychiatric disease have been reported to have structural variations in the retina, but how this affects retinal disease risk and vision loss is poorly understood. This study evaluated the risk of retinal disease and visual impairment in individuals with psychiatric disorders.

An exploratory retrospective cohort study was conducted through a federated health research network that aggregates de-identified EHR data of over 95 million individuals across 50 healthcare organizations. Individuals ages 50-89 were identified for schizophrenia, bipolar disorder (BD), major depressive disorder (MDD), retinal disease, and visual impairment defined by vision loss or blindness using ICD-10 codes. Individuals were propensity score matched (PSM) on age, sex, race, ethnicity, hypertension, diabetes, and dyslipidaemias. Risk ratio calculation and statistical analyses were conducted through the network's analytics tool utilizing 95% confidence intervals.

After PSM, the schizophrenia cohort had 160,414 matched individuals (average age 65), 391,440 in the BD cohort (64), and 1,962,380 in the MDD cohort (67). A recorded diagnosis of schizophrenia was associated with a decreased likelihood of having a retinal disease diagnosis, while recorded diagnoses of BD and MDD were associated with an increased likelihood. Across all psychiatric disorders, individuals with a retinal disease diagnosis had an increased risk of visual impairment compared to individuals with a retinal disease alone.

Recorded diagnoses of BD and MDD were associated with an increased likelihood of having a retinal disease diagnosis. Across all psychiatric disorders, individuals with a concurrent retinal disease were more likely to have a visual impairment diagnosis.

The renin-angiotensin-aldosterone system (RAAS) plays a fundamental role in regulating blood pressure and fluid homeostasis through key effectors such as angiotensin II and aldosterone. These agents and their receptors have become crucial molecular targets in several cardiovascular and renal diseases. Over the past few decades, a growing body of evidence has revealed the presence of RAAS components in ocular structures, suggesting a tissue-specific RAAS within the eye. Building on this knowledge, studies have indicated that the ocular RAAS plays a significant role in the pathogenesis of various eye diseases. An impaired and overactivated RAAS contributes to the development of severe and widespread disorders affecting both the anterior and posterior segments of the eye. In this context, the current work aims to delve into the pivotal molecular pathways involving the RAAS, with an in-depth exploration of the ocular pathophysiology. It focuses on the relationship between overactivation of the RAAS and oxidative stress, as well as the exacerbation of neovascularization and inflammatory processes. The objective is to provide an updated and comprehensive understanding of the role of the RAAS in ophthalmological diseases, highlighting the therapeutic potential of RAAS modulators and discussing the controversies and challenges in this area of research.

This study explores the potential of calcium dobesilate combined with intravitreal ranibizumab injections to reduce the treatment frequency in patients with DME-induced visual impairment and observes the clinical outcomes.

In this investigation involving 90 DME patients, a comparative analysis was conducted between a group treated with both ranibizumab injections and calcium dobesilate capsules (45 patients) and a control group receiving only the injections (45 patients). Treatment was monthly for 3 months, then adjusted as needed, with a follow-up at 12 months focusing on injection frequency, BCVA scores, and CMT to assess both treatment efficacy and safety.

In the 12-month trial, subjects receiving a new combination therapy experienced fewer required intravitreal injections (average 4.73) compared to those on standard monotherapy (average 6.02), showing a significant reduction (p < 0.05). Final assessments revealed substantial improvements in best corrected visual acuity (BCVA) and central macular thickness (CMT) for both groups from baseline (p < 0.05). The experimental group notably showed greater enhancements in BCVA and CMT, highlighting the superior effectiveness of the combination therapy in managing DME symptoms with reduced treatment frequency.

Combination therapy with calcium dobesilate and ranibizumab decreased the frequency of intravitreal injections and led to greater improvements in BCVA and CMT compared to ranibizumab alone over 12 months. Both treatments were well-tolerated, with the combination therapy demonstrating a favorable safety profile.

Diabetic retinopathy (DR) is a severe microvascular complication of diabetes and a leading cause of vision impairment in diabetic patients. The accumulation of apoptotic cells and inflammation are key pathological mechanisms in DR. The Mer tyrosine kinase (MerTK) receptor plays a critical role in maintaining retinal homeostasis. Proteolytic cleavage of MerTK by disintegrin and metalloproteinase-17 (ADAM17) disrupts MerTK-dependent clearance of apoptotic cells and diminishes its anti-inflammatory effects. Therefore, reducing the cleavage activity ADAM17's and promoting MerTK-dependent anti-inflammatory effects may represent potent strategy to alleviate DR.

The DR mouse model was established using streptozotocin (STZ), and a high-glucose (HG)-induced in vitro model was developed using human retinal pigment epithelial (ARPE-19) cells. Relevant signaling molecules were analyzed through western blotting and immunohistochemistry.

Hyperglycemia promoted the accumulation of apoptotic cells and disrupted retinal microvascular growth. In both vivo and vitro model, MerTK expression was significantly reduced, while ADAM17 phosphorylation levels were markedly increased. In STZ-treated mice, protein disulfide isomerase (PDI) secretion initially rose but subsequently declined, whereas PDI secretion decreased under HG conditions. We then utilized paeoniflorin to increase the expression of this endogenous inhibitor of ADAM17. Results showed that paeoniflorin upregulated PDI production, suppressed ADAM17 expression, and enhanced MerTK phosphorylation in the eye tissues of STZ-induced mice. Additionally, paeoniflorin elevated the expression of suppressor of cytokine signaling 3 (SOCS3) and decreased the level of matrix metalloproteinase 9 (MMP9) both in vivo and in vitro.

Paeoniflorin may alleviate diabetic retinopathy by suppressing inflammation through modulation of the PDI/ADAM17/MerTK signaling pathway.

Despite current screening models, enhanced imaging modalities, and treatment regimens, diabetic retinopathy (DR) remains one of the leading causes of vision loss in working age adults. DR can result in irreversible structural and functional retinal damage, leading to visual impairment and reduced quality of life. Given potentially irreversible photoreceptor damage, diagnosis and treatment at the earliest stages will provide the best opportunity to avoid visual disturbances or retinopathy progression. We will review herein the current structural imaging methods used for DR assessment and their capability of detecting DR in the first stages of disease. Imaging tools, such as fundus photography, optical coherence tomography, fundus fluorescein angiography, optical coherence tomography angiography and adaptive optics-assisted imaging will be reviewed. Finally, we describe the future of DR screening programmes and the introduction of artificial intelligence as an innovative approach to detecting subtle changes in the diabetic retina. CLINICAL TRIAL REGISTRATION NUMBER: N/A.

To evaluate the efficacy and safety of Qiming Granule as an early treatment for patients with nerve injury associated with non-proliferative diabetic retinopathy (NPDR).

This was a multicenter, randomized, non-inferiority, active-controlled clinical trial. Patients with NPDR complicated with nerve injury, regardless of whether they presented with fundus abnormalities, were randomly assigned in a 1:1 ratio via a randomized number table to orally receive either 4.5 g of Qiming Granule or 0.5 g of calcium dobesilate (CaD), both 3 times daily for 24 weeks. The primary endpoints were changes in retinal nerve fiber layer (RNFL) thickness and foveal avascular zone (FAZ) area from baseline to week 24. The secondary endpoints included changes in RNFL thickness and FAZ area from baseline to week 12, and visual function questionnaire (NEI-VFQ-25) and health survey questionnaire (SF-36 scale), CM syndrome element scale score and the rates of abnormal full-field electroretinogram (ERG), abnormal dilated fundus, and abnormal visual acuity at treatment of weeks 12 and 24. Adverse drug reactions (ADRs) were detected.

A total of 82 patients were enrolled in the study. Changes in RNFL thickness from baseline to week 24 in the Qiming Granule and CaD groups were -1.53 ± 9.88 µm and -4.61 ± 9.23 µm, respectively (a difference of 3.08 µm [97.5% CI: -2.11 to 8.25]). Changes in FAZ area from baseline to week 24 were -0.08 ± 0.39 mm2 and 0.01 ± 0.05 mm2, respectively (a difference of -0.09 mm2 [97.5% CI: -0.26 to 0.08]). Non-inferiority was achieved for both primary endpoints. There were no significant differences between the two groups in secondary endpoints, including changes in RNFL thickness and FAZ area from baseline to week 12, rates of abnormal ERG, dilated fundus, and visual acuity results at weeks 12 and 24, as well as NEI-VFQ-25, SF-36 scale, and CM syndrome element scale scores at week 24. ADRs were detected in 4 (9.76%) and 1 (2.44%) patients in the Qiming Granule and CaD groups, respectively. No serious ADRs occurred.

Qiming Granule demonstrates non-inferiority in terms of efficacy and safety as an early treatment for nerve injury associated with NPDR. (Registration No. ISRCTN39825773).

By utilizing widefield swept-source optical coherence tomography angiography (WSS-OCTA) to quantify choroidal vascular density (VD) in order to identify early fundus changes in diabetic patients and to predict the progression of diabetic retinopathy (DR). A total of 101 eyes, including patients with type 2 diabetes mellitus and controls, were included in the cross-sectional study. Diabetic patients were stratified into three groups based on disease severity: non-DR (NDR), nonproliferative DR (NPDR), and proliferative DR (PDR). Fundus images obtained through WSS-OCTA were segmented into nine 2 mm × 2 mm regions centered on the macula: supratemporal (ST), superior (S), supranasal (SN), temporal (T), central macular area (C), nasal (N), inferotemporal (IT), inferior (I), and inferonasal (IN). Changes in choroidal VD in the choriocapillaris (CC) and mid-large choroidal vasculature (MLCV) layers were evaluated in each region among patients with DR. Additionally, the diagnostic value of choroidal VD in distinguishing different stages of DR was assessed using the area under the receiver operating characteristic (ROC) curve. In comparison to the NDR group, the VD of MLCV (S) was found to decrease significantly in the NPDR group. Furthermore, the VD of CC (S) was significantly lower in the PDR group compared to the NPDR group. The VD of MLCV (IN) demonstrated potential in distinguishing between healthy eyes and those with NDR. Additionally, the VD of CC (SN) and MLCV (S, SN, C, I) showed relatively high area under the curve (AUC) values in discriminating between NDR and NPDR. Lastly, the VD of CC (S) exhibited good diagnostic accuracy in distinguishing between NPDR and PDR patients. As DR advances, MLCV and CC are sequentially compromised to varying degrees. In clinical diagnosis, the VD of the IN region in the MLCV layer serves as a more sensitive early imaging biomarker for detecting preclinical DR, while a decrease in the VD of the S region in the CC layer indicates the onset of PDR.

Ocular drug delivery is a significant challenge due to the intricate anatomy of the eye and the various physiological barriers. Conventional therapeutic approaches, while effective to some extent, often fall short in effectively targeting ocular diseases, resulting in suboptimal therapeutic outcomes due to factors such as poor ocular bioavailability, frequent dosing requirements, systemic side effects, and limited penetration through ocular barriers. This review elucidates the eye's intricate anatomy and physiology, prevalent ocular diseases, traditional therapeutic modalities, and the inherent pharmacokinetic and pharmacodynamic limitations associated with these modalities. Subsequently, it delves into nanotechnology-based solutions, presenting breakthroughs in nanoformulations such as nanocrystals, liposomes, dendrimers, and nanoemulsions that have demonstrated enhanced drug stability, controlled release, and deeper ocular penetration. Additionally, it explores a range of nanosized carriers, including nano-structured lipid carriers, hydrogels, nanogels, nanoenzymes, microparticles, conjugates, exosomes, nanosuspensions, viral vectors, and polymeric nanoparticles, and their applications. Unique insights include emerging innovations such as nanowafers and transcorneal iontophoresis, which indicate paradigm shifts in non-invasive ocular drug delivery. Furthermore, it sheds light on the advantages and limitations of these nanotechnology-based platforms in addressing the challenges of ocular drug delivery. Though nano-based drug delivery systems are drawing increasing attention due to their potential to enhance bioavailability and therapeutic efficacy, the review ends up emphasizing the imperative need for further research to drive innovation and improve patient outcomes in ophthalmology.

Diabetic retinopathy (DR), a complication of type 2 diabetes mellitus (T2DM), is typically asymptomatic in its early stages. Diagnosis typically relies on routine fundoscopy for the clinical detection of microvascular abnormalities. However, permanent retinal damage may occur well before clinical signs are appreciable. In the early stages of DR, the retina undergoes distinct epigenetic changes, including DNA methylation and histone modifications. Recent evidence supports unique epigenetic 'signatures' in patients with DR compared to non-diabetic controls. These DNA 'signature' sequences may be specific to the retina and may circulate in peripheral blood in the form of cell-free DNA (cfDNA). In this review, we explore the literature and clinical application of cfDNA sampling as an early, non-invasive, accessible assessment tool for early DR detection. First, we summarize the known epigenetic signatures of DR. Next, we review current sequencing technologies used for cfDNA detection, such as magnetic bead-based enrichment, next-generation sequencing, and bisulfite sequencing. Finally, we outline the current research limitations and emerging areas of study which aim to improve the clinical utility of cfDNA for DR evaluation.

To utilize a convolutional neural network (CNN) to predict the response of treatment-naïve diabetic macular edema (DME) to a single injection of anti-vascular endothelial growth factor (anti-VEGF) with data from optical coherence tomography (OCT).

Retrospective study performed via chart review.

Setting: This was a single-center study performed at the Storm Eye Institute, Medical University of South Carolina.

Patients with a new diagnosis of DME who underwent intravitreal (IVT) anti-VEGF injections were eligible for inclusion, provided they had a baseline OCT scan at the time of diagnosis and a 1-month follow-up OCT scan after the first anti-VEGF injection. Exclusion criteria included prior treatment with anti-VEGF, lack of required OCT scans, coexistent macular degeneration, and macular edema due to other retinal diseases. Seventy-three (73) eyes from 53 patients were included.

The OCT scan from the baseline visit was compared to the follow-up OCT scan approximately 1 month after the first anti-VEGF injection to determine change in central subfield thickness (delta CST). The delta CST was fed into the CNN as a label to train the system to predict treatment response from only the baseline OCT scan.

CNN prediction of treatment response to anti-VEGF. Treatment response was defined as a CST reduction of 10 µm or more.

Based on delta CST from 2 OCT scans, 57 eyes were responders and 16 eyes were non-responders to the initial anti-VEGF injection. Analyzing only the baseline OCT scan for each eye, the trained CNN demonstrated an area under the curve (AUC) of 0.81. At the reported operating point, the CNN correctly identified 45 of the 57 responder eyes (i.e., recall of 78.9%) and 11 of the 16 non-responder eyes (i.e., specificity of 68.8%).

The results of this study demonstrate the potential of a CNN to predict the response of treatment-naïve DME to a single injection of anti-VEGF therapy. NOTE: Publication of this article is sponsored by the American Ophthalmological Society.

Localized oxidative stress plays a key role in the development of retinal degenerative diseases, with diabetic retinopathy (DR) being one of them, contributing significantly to this vision-threatening complication of diabetes. Increased oxidative burden leads to dysfunction across various retinal cell types, including vascular endothelial cells, neurons, glial cells and pericytes. Importantly, even after achieving normalized glycemia, the detrimental effects of oxidative stress persist. Nonetheless, growing data highlights the therapeutic potential of antioxidants in safeguarding vision. However, extensive clinical trials using traditional antioxidants have produced mixed results. Therefore, probucol, known for its ability to limit vascular oxidative stress, decrease superoxide generation, and improve endogenous antioxidant activity, is a promising candidate explored in this review. In addition to describing probucol, this review will explore novel therapeutic formulation strategies by incorporating bile acid into probucol-loaded nanoparticles to enhance drug delivery to the posterior segment of the eye for more effective management of DR. The integration of bio-nanotechnology with probucol and bile acids represents a promising avenue for developing effective therapies for DR, addressing the limitations of traditional antioxidant treatments.

Neurodegeneration is a common endpoint of various blinding retinal diseases. Yet, despite exciting advances in disease treatment, there continues to exist a critical need for the development of neuroprotective strategies to prevent retinal cell death. Here, we summarize the recent advances in neuroprotective strategies.

From laboratory deciphering of the mechanisms involved in disease, many novel neuroprotective strategies have emerged and are currently under investigation for the treatment of various retinal and ocular diseases such as inherited retinal degeneration, retinal detachment, diabetic retinopathy, age-related macular degeneration, macular telangiectasia type 2, and glaucoma. These strategies include gene therapies, Fas inhibition, and targeting inflammatory, metabolic and reduction-oxidation abnormalities. Interestingly, investigation of several treatments across different diseases suggests shared neuroprotection mechanisms that can be targeted regardless of the particular disease.

Retinal neuroprotection can improve treatment of different retinal diseases. Fortunately, the current landscape, with a plethora of novel neuroprotective therapies, portends a better future for patients.

Existing deep learning (DL) algorithms lack the capability to accurately identify patients in immediate need of treatment for proliferative diabetic retinopathy (PDR). We aimed to develop a DL segmentation model to detect active PDR in six-field retinal images by the annotation of new retinal vessels and preretinal hemorrhages.

We identified six-field retinal images classified at level 4 of the International Clinical Diabetic Retinopathy Disease Severity Scale collected at the Island of Funen from 2009 to 2019 as part of the Danish screening program for diabetic retinopathy (DR). A certified grader (grader 1) manually dichotomized the images into active or inactive PDR, and the images were then reassessed by two independent certified graders. In cases of disagreement, the final classification decision was made in collaboration between grader 1 and one of the secondary graders. Overall, 637 images were classified as active PDR. We then applied our pre-established DL segmentation model to annotate nine lesion types before training the algorithm. The segmentations of new vessels and preretinal hemorrhages were corrected for any inaccuracies before training the DL algorithm. After the classification and pre-segmentation phases the images were divided into training (70%), validation (10%), and testing (20%) datasets. We added 301 images with inactive PDR to the testing dataset.

We included 637 images of active PDR and 301 images of inactive PDR from 199 individuals. The training dataset had 1381 new vessel and preretinal hemorrhage lesions, while the validation dataset had 123 lesions and the testing dataset 374 lesions. The DL system demonstrated a sensitivity of 90% and a specificity of 70% for annotation-assisted classification of active PDR. The negative predictive value was 94%, while the positive predictive value was 57%.

Our DL segmentation model achieved excellent sensitivity and acceptable specificity in distinguishing active from inactive PDR.

Since its beginnings in the 1970s, telemedicine has advanced extensively. Telemedicine is now more accessible and powerful than ever thanks to developments in medical imaging, Internet accessibility, advancements in telecommunications infrastructure, exponential growth in computing power, and related computer-aided diagnoses. This is especially true in the field of ophthalmology. With the COVID 19 pandemic serving as a catalyst for the widespread adoption and acceptance of teleophthalmology, new models of healthcare provision integrating telemedicine are needed to meet the challenges of the modern world. The demand for ophthalmic services is growing globally due to population growth, aging, and a shortage of ophthalmologists. In this review, we discuss the development and use of telemedicine in the field of ophthalmology and shed light on the benefits and drawbacks of teleophthalmology.

To evaluate the acceptability, applicability, and cost-utility of AI-powered portable fundus cameras for diabetic retinopathy (DR) screening in Hong Kong, providing a viable alternative screening solution for resource-limited areas.

This pragmatic trial conducted in an optometric clinic and two optical shops. A self-testing system was used, integrating a portable fundus camera and AI software that automatically identified DR. Three months following the screening, selected participants were invited to complete an open-ended questionnaire.

A total of 316 subjects participated, with age of 60.80 ± 8.30 years. The success rate of the self-testing system without active assistance was 89 %. Among 61 subjects who completed follow-up interview, a majority agreed that the system and report were easy to follow and understand (85.3 % and 75.4 %). The satisfaction rate was 64 %, and the willingness to use again was 80 %. The AI screening showed a cost saving of 6312.92 USD per QALY, while the adjusted AI model saved 18639. AI screening and adjusted model outperformed traditional screening (Net Monetary Benefit 367,863.31 and 354,904.76 vs 339,919.83 USD).

The AI-powered portable fundus camera demonstrated high acceptability and applicability in real-world settings, suggesting that AI screening could be a viable alternative in resource-limited settings.

To determine the frequency of eye screening during pregnancy for people with pre-existing diabetes, and to examine what factors were associated with screening.

Using linked real-world population-level data in Ontario, Canada, we identified all livebirths to people with pre-existing diabetes between April 2015 and March 2020, and determined the proportion who had an eye screening examination during pregnancy. The associations between screening uptake and a variety of sociodemographic, clinical and health service variables were examined.

Of 6,708 pregnancies among people with pre-existing diabetes, 1,256 (18.7 %) had an eye screening examination within the first trimester and 3,045 (45.4 %) had eye screening at any time during pregnancy. The highest eye screening rates were seen among those with prior retinopathy treatment, with longer diabetes duration, and on the insulin pump program. People who received care from an endocrinologist in the first 180 days of pregnancy were far more likely to have an eye examination.

Uptake of eye screening in the first trimester among people with pre-existing diabetes was extremely low, despite the risk of worsening and sight-threatening retinopathy during pregnancy. Even by the end of pregnancy, fewer than one-half of patients had received eye screening.

Retinal diseases are a leading cause of vision loss, affecting millions of people worldwide. Current treatment options are based on invasive methods such as intravitreal injections. Therefore, there is a need for alternative therapeutic strategies that are both effective and more patient-friendly.

Topical drug delivery has gained attention as a preferred noninvasive approach, although it is hindered by several ocular barriers. Cyclodextrin (CD)-based nanoparticles have emerged as a promising strategy to overcome these limitations by enhancing drug permeability in the posterior segment of the eye. This review discusses the potential of CDs as enabling pharmaceutical excipients, their role in improving ocular drug bioavailability, and provides examples of CD-based eye drop formulations currently under development or undergoing clinical trials. Also, the role of CDs as active pharmaceutical agents in ophthalmology is discussed.

CD-based nanoparticle eye drops present a promising solution and have shown clinical success. CDs are approved pharmaceutical excipients for eye drop formulations and can act as active pharmaceutical ingredients for the treatment of inherent retinal diseases. Future innovations in hybrid CD-based delivery systems and integration of novel therapeutic compounds could provide more efficient and targeted treatment options for retinal diseases.

BackgroundDiabetic retinopathy (DR), the primary retinal vascular consequence of diabetes mellitus (DM) among people of working age worldwide, is the primary cause of vision impairment and blindness. Despite increasing understanding of the prevalence of DM as a significant public health concern in China, the world's most populous developing nation, there is much to discover about the epidemiology of DR.ObjectiveThis work uses a systematic review and meta-analysis to determine the total prevalence of diabetic retinopathy (DR) in China.MethodsUsing common keywords, we looked up published research on the prevalence of DR in diabetic patients using Google Scholar, PubMed, and Scopus from their founding until 2023. Using random effects models, pooled estimates of DR prevalence and the associated 95% confidence intervals (CI) were computed. Fifteen articles covering 4837 patients with different forms of diabetes were analyzed. The Egger tests refuted the publication bias assumption for the prevalence of DR (P = 0.825, P = 0.057, respectively). Significant heterogeneity was seen in the prevalence of DR (P < 0.01, I2 = 92% and τ2 = 0.0082), PDR (P < 0.01, I2 = 97% and τ2 = 0.0072), and NPDR (P < 0.01, I2 = 84% and τ2 = 0.0039), according to the results of I2 and τ2 statistics.ResultsThe combined prevalence of PDR was 24% (95% CI: 19-28), NPDR was 31% (95% CI: 27-35), and DR was 55% (95% CI: 63-71).Conclusions: In summary, DR's prevalence appears slightly higher than that of other studies, with a greater incidence of NPDR. This study emphasises the need for DR screening and treatment in individuals with diabetes.

Given how the diagnosis and management of many ocular and, most specifically, retinal diseases heavily rely on various imaging modalities, the introduction of artificial intelligence (AI) into this field has been a logical, inevitable, and successful development in recent decades. The field of retinal diseases has practically become a showcase for the use of AI in medicine. In this article, after providing a short overview of the most relevant retinal diseases and their socioeconomic impact, we highlight various aspects of how AI can be applied in research, diagnosis, and disease management and how this is expected to alter patient flows, affecting also health care professionals beyond ophthalmologists.

To evaluate the capability of artificial intelligence (AI) in screening for diabetic retinopathy (DR) utilizing digital retinography captured by non-mydriatic (NM) ≥45° cameras, focusing on diagnosis accuracy, effectiveness, and clinical safety.

We performed an overview of systematic reviews (SRs) up to May 2023 in Medline, Embase, CINAHL, and Web of Science. We used AMSTAR-2 tool to assess the reliability of each SR. We reported meta-analysis estimates or ranges of diagnostic performance figures.

Out of 1336 records, ten SRs were selected, most deemed low or critically low quality. Eight primary studies were included in at least five of the ten SRs and 125 in less than five SRs. No SR reported efficacy, effectiveness, or safety outcomes. The sensitivity and specificity for referable DR were 68-100% and 20-100%, respectively, with an AUROC range of 88 to 99%. For detecting DR at any stage, sensitivity was 79-100%, and specificity was 50-100%, with an AUROC range of 93 to 98%.

AI demonstrates strong diagnostic potential for DR screening using NM cameras, with adequate sensitivity but variable specificity. While AI is increasingly integrated into routine practice, this overview highlights significant heterogeneity in AI models and the cameras used. Additionally, our study enlightens the low quality of existing systematic reviews and the significant challenge of integrating the rapidly growing volume of emerging evidence in this field. Policymakers should carefully evaluate AI tools in specific contexts, and future research must generate updated high-quality evidence to optimize their application and improve patient outcomes.

Diabetes mellitus is a known risk factor for corneal epithelial defects (CEDs) after pars plana vitrectomy (PPV), but it is unclear if diabetes severity or specific diabetic risk factors are associated with an increased risk of CED. The purpose of this retrospective cohort study was to identify factors associated with CED and healing time in association with diabetes severity in diabetic patients following PPV. The electronic health record database at University of Florida in Gainesville was queried to identify patients who underwent PPV for retinal detachment (RD) between April 2016 and April 2022. Patient charts were reviewed for clinical data including type of diabetes (if present), diabetes duration and severity, and associated diabetic comorbidities. The main outcome measures included presence of a CED within one month postoperatively, treatment of CED if present, and CED healing time. A total of 637 patients were analyzed, with a total of 243 eyes (26.5%) that belonged to diabetic patients. The diabetic patients were further separated into a proliferative diabetic retinopathy (PDR) group and a nonproliferative diabetic retinopathy (NPDR) group. Diabetes was associated with the development of an initial CED (p=0.040), consistent with existing literature. There was not a significant difference in CED risk when comparing NPDR and PDR patients, although PDR patients tended to have more severe long-term outcomes with persistent corneal epithelial defects (PCEDs). This suggests that PDR patients may still require closer monitoring and earlier intervention for postoperative CED following PPV, as compared to the NPDR patient population.

To elucidate the association between dietary iron intake and diabetic retinopathy (DR) in type 2 diabetes (T2D) patients.

Participants from the National Health and Nutrition Examination Survey (NHANES) 2005-2008 aged over 40 years with T2D were included. Dietary iron intake was estimated from standardised questionnaires. The presence of DR and vision-threatening DR (VTDR) was determined through retinal imaging. We used logistic regression to assess the relationship between iron intake and DR, and restricted cubic splines to reveal nonlinear links.

The study enrolled 1172 T2D adults. We found significant nonlinear associations between dietary iron intake and DR among females (P = 0.023), but not in males (P = 0.490). Compared with the lowest quartile of iron intake, the third quartile (13.2-18.1 mg/d) yielded significantly lower odds of developing DR (odds ratio [OR], 0.59; 95% CI, 0.39-0.90) and VTDR (OR, 0.42; 95% CI, 0.19-0.94). Stratified logistic analyses showed that medium-high iron intake was associated with lower risks of DR in females (OR, 0.44; 95% CI, 0.24-0.81), non-Hispanic Blacks (OR, 0.38; 95% CI, 0.17-0.85), and individuals with obesity (OR, 0.45; 95% CI, 0.25-0.82), high HbA1c (OR, 0.56; 95% CI, 0.34-0.93), long diabetes duration (OR, 0.40; 95% CI, 0.21-0.76) or low blood haemoglobin (OR, 0.17; 95% CI, 0.05-0.60).

Dietary iron intake was nonlinearly negatively associated with the prevalence of DR and VTDR, showing protective effect against retinopathy of medium-high iron intake in T2D patients. Such associations significantly vary by multiple factors such as age, ethnicity, obesity and glycaemic control.

It has been reported that hemoglobin (Hb) levels are negatively associated with the prevalence of diabetic retinopathy (DR). This study aims to investigate the relationship between Hb levels and DR prevalence among highlanders, who exhibit elevated Hb levels as an adaptive response to hypoxia.

This cross-sectional, hospital-based study utilized data from 645 Tibetan male patients with type 2 diabetes (T2D) between 2018 and 2020. Patients were divided into two groups based on Hb level (group 1: 12.0 ≤ Hb < 16.0 g/dL; group 2: Hb ≥ 16.0 g/dL). DR was diagnosed based on fundus photographs and fundus fluorescein angiography.

Among the study participants, 140 were diagnosed with DR. An inverse relationship was observed between Hb levels and the prevalence of DR. Each 1.0-g/dL increase in Hb concentration was associated with an 18% reduction in the prevalence of DR (95% confidence interval [CI]: 0.71-0.95). Multiple logistic regression analysis confirmed that patients with higher Hb levels had an adds ratio of 0.48 (95% CI, 0.29-0.79) for DR after adjusting for confounders, compared to those with lower Hb levels.

Our findings indicate that the inverse relationship between Hb levels and DR prevalence observed in lowland populations is also applicable to high-altitude individuals.

Diabetic retinopathy (DR) is characterized by progressive retinal vascular damage that ultimately causes vision loss. The prognostic nutritional index (PNI), which integrates albumin and lymphocytes, serves as an indicator of an individual's inflammatory response, nutritional condition, and immune system function. This research aimed to explore the possible association between PNI and DR. This was a cross-sectional study utilizing data from the National Health and Nutrition Examination Survey (NHANES) between 2001 and 2018. Weighted logistic regression analyses were employed to assess the relationship between PNI and DR prevalence. A total of 4791 adults aged 20 years and older were included in the analysis. Results indicated a statistically significant negative correlation between PNI and DR prevalence. In the fully adjusted model, a one-unit rise in PNI corresponded to a 7% reduction in the probability of DR prevalence. Quartile analysis consistently indicated that individuals in the highest PNI quartile had notably lower odds of DR prevalence compared to those in the lowest quartile. Additionally, smooth curve fitting suggested a nonlinear relationship between PNI and DR. Subgroup analysis reinforced the strength of the inverse association between PNI and DR (all p for interaction > 0.05). This nationally representative study demonstrated a significant inverse relationship between PNI levels and DR prevalence among diabetic adults in the United States. Our findings emphasize the potential role of maintaining optimal PNI values in preventing the development of DR.

Diabetic retinopathy (DR) is the common cause of diabetic vascular complications and it causes blindness. Until now, there are still some patients with DR who lack effective treatment. Tripartite motif containing 44 (TRIM44) has been shown to play a significant role in endothelial cells. However, the role of TRIM44 in DR remains unknown.

Diabetes was induced in rats through the administration of an intraperitoneal injection of 65 mg/kg of streptozotocin (STZ). Rat retinal microvascular endothelial cells (RMECs) were subjected to stimulation under high glucose (HG) conditions. A thorough proteomic investigation and bioinformatic analysis were performed to identify the differentially expressed proteins (DEPs) in rat RMECs after blocking TRIM44. A dual luciferase reporter assay was employed to assess the luciferase activity of TRIM44.

TRIM44 was highly expressed in the retinal tissues of rats with diabetes and HG-induced RMECs. In vivo assays suggested that TRIM44 silencing improved the pathological alterations of DR rats as demonstrated by the downregulated expression of isolectin-B4 and VEGFA, along with a decrease in acellular capillaries within the retinal tissues. Knockdown of TRIM44 markedly reduced cell viability, proliferation, migration, invasion, and angiogenesis in HG-evoked RMECs. Mechanistically, TRIM44 was demonstrated to be activated transcriptionally by KLF transcription factor 9 (KLF9), a known facilitator of angiogenesis in DR. In HG-induced cells, the loss of TRIM44 resulted in the reverse of the endothelial cell function caused by KLF9 overexpression. After the comprehensive analysis, 64 upregulated and 38 downregulated DEPs were screened out for a series of functional enrichment analyses.

Collectively, this study demonstrates that TRIM44 knockdown suppressed diabetes-induced retinal vascular dysfunction in DR.

To investigate the relationship between Thioredoxin (Trx), Thioredoxin interacting protein (Txnip), and the severity of diabetic retinopathy (DR).

The study involved a total of 101 eyes, comprising of 31 healthy controls, 24 diabetic patients with no clinically detectable retinopathy (NDR group), 26 patients with non-proliferative DR (NPDR group), and 20 patients with proliferative DR (PDR group), including 62 males and 49 females, average aged 61.65 ± 9.4. Retinal morphology was evaluated using spectral domain optical coherence tomography (SD-OCT), while retinal function was assessed using full-field electroretinogram (ffERG) to record the amplitudes and implicit time. The correlation between serum Trx, Txnip, and DR was analyzed using Spearman correlation analysis.

In the early stage of DR, there was no significant difference in macular retinal thickness between groups; in the PDR group, there was a significant increase compared to both the NDR and control groups, particularly in the central fovea (p < 0.0001). Additionally, the amplitude and implicit time of oscillatory potentials exhibited a significant difference between the NDR and control groups at an early stage of DR (p < 0.001). Furthermore, the amplitude of rod and cone ERG decreased significantly in the early stage of DR, while the implicit time began to decline in the NPDR stage. The serum levels of Trx and Txnip exhibited a positive correlation with the progression of DR (r = 0.851, 0.762). Conversely, a negative correlation was observed between the serum levels of Trx and Txnip and the amplitudes of ERG, while a positive correlation was observed with the implicit time of ERG.

The serum levels of Trx and Txnip exhibit a positive correlation with retinopathy associated with type 2 diabetes mellitus (T2DM), and thus may be utilized as a potential target for the timely diagnosis and treatment of DR.

This study investigated the potential of serum disease-specific immunoglobulin G (DSIgG) crystallizable fragment (Fc) N-glycosylation as a diagnostic biomarker for the identification of nonproliferative and proliferative diabetic retinopathy (DR). A total of 160 patients were enrolled and categorized into three groups according to clinical diagnosis: non-diabetic retinopathy (NDR, n = 47); nonproliferative diabetic retinopathy (NPDR, n = 51); and proliferative diabetic retinopathy (PDR, n = 62). Gel electrophoresis was performed to separate IgG from morning fasting blood samples and polyaniline magnetic nanomaterials (Fe3O4@PANI) were used to enrich IgG N-glycopeptides from tryptic digestion. Matrix-assisted laser desorption ionization time-of-flight mass spectrometry (MALDI ToF MS) was used to detect the IgG N-glycopeptides. Nine DSIgG N-glycopeptide ratios were significantly different among NDR, NPDR, and PDR groups. There are six glycopeptide ratios available to classify mild, moderate, and severe NPDR. Moreover, four glycopeptide ratios could identify patients with or without diabetic macular edema (DME). The prediction model exhibited good discriminatory performance in distinguishing patients with DR or NDR (AUC = 0.8347), NPDR or PDR (AUC = 0.7002), mild/moderate or severe NPDR (AUC = 0.8059), and with or without DME (AUC = 0.7846). DSIgG Fc N-glycosylation ratios were closely associated with different stages of DR and may be used as potential biomarkers for the early diagnosis of NDR, NPDR, and PDR.

Two of the microvascular complications in type 2 diabetes (T2D) are diabetic retinopathy (DR), which is the most common cause of non-traumatic blindness, and diabetic kidney disease (DKD); the latter generally requires renal replacement therapy. The aim of the present study was to determine the frequency of polymorphisms of Tumor Necrosis Factor-α, interleukin-6, and interleukin-10 (TNF-α, IL-10, and IL-6), as well as to describe the clinical and laboratory characteristics of T2D association with these microvascular complications.

This study included 203 patients with T2D, of which 102 had microvascular complications: 95 with DR, 50 with DKD, and 15 with diabetic neuropathy (the latter were not included in the statistical analysis); those with T2D without confirmed microvascular complications were considered as controls. Clinical and laboratory data were collected from the patient's medical records. Polymorphism typing of TNF-α rs361525 and rs1800629 and IL-10 rs1800872 and rs1800871 were obtained using MALDI-TOF MS. IL-10 rs1800896 and IL-6 rs1800795 were typed using a quantitative real-time polymerase chain reaction.

The results of age, HbA1c, fasting glucose, and arterial hypertension are significantly associated in every group. The TNF-α rs1800629A allele and TNF-α rs1800629G/A genotype were associated with microvascular complications and DR. For IL-10-rs1800896, all the models were associated in DKD. The TNF-α rs361525-rs1800629GA haplotype was associated with microvascular complications and DR, while the IL-10 haplotype, rs1800872-rs1800871-rs1800896 GGC, showed susceptibility in every group.

Our results show the contributions of the variants of these cytokines to these microvascular complications, but more studies are required to reach relevant conclusions.

Screening for diabetic retinopathy has been shown to reduce the risk of sight loss in people with diabetes, because of early detection and treatment of sight-threatening disease. There is long-standing interest in the possibility of automating parts of this process through artificial intelligence, commonly known as automated retinal imaging analysis software (ARIAS). A number of such products are now on the market. In the UK, Scotland has used a rules-based autograder since 2011, but the diabetic eye screening programmes in the rest of the UK rely solely on human graders. With more sophisticated machine learning-based ARIAS now available and greater challenges in terms of human grader capacity, in 2019 the UK's National Screening Committee (NSC) was asked to consider the modification of diabetic eye screening in England with ARIAS. Following up on a review of ARIAS research highlighting the strengths and limitations of existing evidence, the NSC here sets out their considerations for evaluating evidence to support the introduction of ARIAS into the diabetic eye screening programme.

Diabetes mellitus, a chronic metabolic disorder affecting millions worldwide, is associated with microvascular complications, including diabetic retinopathy (DR) and periodontitis. Understanding their interrelationship is crucial for comprehensive patient care.

This systematic review and meta-analysis aim to investigate the association between DR and periodontitis in patients with Type 1 and Type 2 diabetes.

Using the PECO framework, we searched PubMed/MEDLINE, Scopus, EMBASE, Google Scholar, and Web of Science databases (Inception to April 2023) for studies on the association between DR and periodontitis. Ten studies (n = 1828 participants), including observational and cross-sectional studies, met the inclusion criteria. We conducted qualitative synthesis, risk of bias analysis using the ROBINS-E tool, Grading of Recommendations, Assessment, Development, and Evaluations assessment (GRADE), and random-effects meta-analysis.

Eight studies found a significant association between severe periodontitis (pocket depth ≥5 mm) and DR, while two found no association. Meta-analysis of 843 participants showed diabetics with periodontitis had 4.48 times higher odds (95% confidence interval: 1.67-12.07, P = .003) of developing retinopathy compared to diabetics without periodontitis. High heterogeneity was observed (I2 = 86%). Subgroup analysis by diabetes type showed no significant difference. The overall GRADE level of evidence was very low.

While most included studies suggest an association between severe periodontitis and increased DR risk, the overall certainty of evidence is low. These findings highlight the potential importance of periodontal health in diabetic patients. High-quality longitudinal studies with adequate control of confounders are required to determine if periodontitis contributes to the progression of DR or if the conditions are merely coincidentally related.