Search Results (272)

Background/Objectives: Diabetic retinopathy (DR) is a major microvascular complication of type 2 diabetes (T2D) and a leading cause of visual impairment. The relationships among Mediterranean diet adherence, dietary components, DR, and vision-related quality of life remain incompletely defined. This cross-sectional study evaluated Mediterranean Diet Score (MDS) as the primary dietary endpoint, individual MDS components as secondary endpoints, and micronutrient intakes as exploratory endpoints. Methods: In this single-centre study, 129 subjects with long-standing T2D were classified as no DR (NDR; n = 85), non-proliferative DR (NPDR; n = 36), or proliferative DR (PDR; n = 8). Dietary intake was assessed using a food frequency questionnaire and vision-related quality of life using the NEI-VFQ-25. Results: Subjects with DR had longer diabetes duration than those without DR (18 vs. 16 years, p < 0.01). Overall MDS did not differ by DR status, indicating a null finding for the primary dietary endpoint. In secondary analyses, lower legume consumption was observed among participants with DR and was associated with higher odds of DR in multivariable models. Participants with PDR showed poorer vision-related quality of life, although this finding was limited by the small PDR subgroup and high NEI-VFQ-25 scores in other groups. Exploratory analyses suggested associations between selected micronutrient intakes and NEI-VFQ-25 domains. Conclusions: Overall Mediterranean diet adherence was not associated with DR status. Secondary and exploratory findings should be considered hypothesis-generating and require confirmation in prospective studies. Full article

Background/Objectives: Diabetic retinopathy (DR) is one of the most common microvascular complications in type 2 diabetes mellitus (T2DM), in which oxidative stress, inflammation and angiogenic pathways are associated with the development and progression beyond glycemic control. Serum trace element levels (Cu, Zn, Fe, Mg, Cr, Mn, Cd, and Se), antioxidant enzyme activities (superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px)) were measured in patients with T2DM, with and without DR, as well as in healthy controls, and their associations with the presence and severity of DR were evaluated. Methods: 61 T2DM patients, 27 healthy controls. Patients with T2DM were classified into T2DM without DR (n = 30) and T2DM with DR (n = 31). Non-proliferative DR (NPDR, n = 19) and proliferative DR (PDR, n = 12) were classified as the T2DM with DR group. Inductively coupled plasma–mass spectrometry (ICP-MS) was used to quantify serum trace elements. SOD and GSH-Px activities were measured using colorimetric assays. Results: Significant differences were observed in trace element levels and antioxidant enzyme activities among the study groups (p < 0.001 to 0.05). The DR subgroup had lower levels of Cr, Cu and Se compared to the T2DM without DR group; Cd, Zn and Mn were also higher in the T2DM with DR than in the T2DM without DR group. Fe levels were significantly higher in the PDR subgroup than in the T2DM without DR group (p < 0.001). The PDR group showed greater declines of Cr, Cu and GSH-Px compared to NPDR while higher values for Mn, Fe, and Zn were obtained (p < 0.001). Several biomarkers remained significantly associated with DR after adjustment for metabolic variables. Correlation analysis between trace elements, and antioxidant enzymes showed significant associations. Conclusions: Trace element imbalance, and reduced antioxidant enzyme activities may contribute to the development and progression of DR in T2DM. These findings suggest that oxidative stress and micronutrient imbalance may be linked to DR-related biochemical alterations. Full article

Background/Objectives: Observational studies have reported comorbidity between diabetic retinopathy (DR) and physical frailty, but their genetic interplay remains incompletely understood. This study evaluated shared genetic architecture and potential causal relationships between DR severity and frailty-related phenotypes (FRPs). Methods: GWAS summary statistics were analyzed for four DR phenotypes (broad DR, background DR [BDR], severe non-proliferative DR, and proliferative DR [PDR]) and six FRPs, including frailty index (FI), appendicular lean mass, handgrip strength (HGS), and walking pace (UWP). Global and local genetic correlations were estimated using LDSC, HDL, and LAVA. Causality was assessed using bidirectional Mendelian randomization (MR) and latent causal variable (LCV) analyses. Biological mechanisms were investigated using partitioned heritability, cross-trait meta-analysis, Bayesian colocalization, tissue and cell enrichment, prioritization (MAGMA/TWAS), and 3D chromatin annotation. Results: BDR and PDR showed positive genetic correlations with FI and negative correlations with UWP. Local genetic correlation analyses identified 82 significant regions, including signals on chromosome 6. MR supported a directional effect in which genetic liability to DR was associated with higher FI and lower HGS, with no evidence of reverse causation. LCV indicated partial genetic causality within a shared polygenic architecture. Cross-trait meta-analysis and colocalization highlighted the MHC region, prioritizing C2, AIF1, NOTCH4, and EHMT2. Additional non-MHC loci included the BCL2L15 gene cluster and TERF1. Conclusions: DR and frailty share genetic determinants involving neurovascular, metabolic, and immune-inflammatory pathways, supporting an association between DR liability and frailty-related decline. Future longitudinal and functional studies are needed to validate these findings and assess candidate pleiotropic genes. Full article

Purpose: We investigated the association between age and retinal microvasculature parameters as measured by optical coherence tomography angiography (OCTA) and the modifying effect of diabetes status on this association. Methods: In this serial, cross-sectional study, 3 × 3 mm² macular OCTA images were obtained from healthy adults and adults with diabetes mellitus (DM) with no diabetic retinopathy (DR) or with mild non-proliferative DR (NPDR). The parameters analyzed included foveal avascular zone (FAZ) area and perimeter, vessel density (VD), vessel length density (VLD), and flow index (FI) of the superficial capillary plexus (SCP) and deep capillary plexus (DCP). The associations between OCTA parameters and age were explored using multivariable linear regression models. Results: For the included 1855 patients (1855 eyes) (49% male; mean age: 55 years), the results were as follows: no diabetes (N = 217), DM no DR (N = 1352), and mild NPDR (N = 286). Increasing age was significantly associated with decreased SCP and DCP VD and VLD in the diabetic and non-diabetic groups. The slope of association between SCP and DCP FI and age in the diabetic patients was significantly different than that in the control patients. Conclusions: The strength of the association between aging and OCTA parameters differed significantly between the controls and those with early retinopathy, pointing to a potentially altered retinal vascular homeostasis secondary to diabetic pathophysiology. This finding offers insight into the early pathological biomarkers of DR and may guide early DR management for patients based on personalized risk scores. Full article

Background: Intraocular surgery on patients with an irreversibly blind fellow eye carries high risks, often causing treatment delays due to patient and surgeon hesitation. Existing data beyond cataracts are scarce. This study aims to evaluate the clinical profiles, prognosis, and economic value of diverse surgeries in this monocular population to guide clinical decision-making and optimize blindness prevention strategies. Methods: This retrospective study included 308 patients with a pre-existing blind fellow eye who underwent primary inpatient intraocular surgery under a standardized clinical protocol between June 2021 and June 2025. Baseline demographics, bilateral etiologies, visual outcomes, postoperative complications, and average cost-effectiveness ratios (ACERs) were analyzed. Postoperative outcomes were evaluated for patients with at least 6 months of follow-up. Results: The primary surgical indications were cataract (51.3%), proliferative diabetic retinopathy (PDR, 19.5%), glaucoma (15.9%), and rhegmatogenous retinal detachment (RRD, 7.5%). Notably, 49.4% of patients exhibited identical blinding etiologies bilaterally. Among patients completing the 6-month follow-up (n = 109), overall mean BCVA significantly improved from 1.36 ± 0.77 to 0.73 ± 0.65 logMAR (p < 0.001). The cataract group achieved the greatest visual improvement and the lowest ACER. Despite surgical complexity and higher complication rates, PDR and RRD interventions achieved visual improvement in over 60% of cases. Conclusions: Despite high clinical stakes, timely surgery in monocular patients yields substantial visual and economic benefits. The notable disease symmetry highlights a critical window for early intervention, emphasizing the need for public health strategies that prioritize screening progressive bilateral diseases. Full article

Background/Objectives: This retrospective cohort study compared hospitalization and follow-up rates in patients with newly diagnosed proliferative diabetic retinopathy (PDR) versus those without prior diabetic retinopathy (DR) screening. Methods: Using TriNetX, a global electronic health record database, 57,964 patients aged ≥ 40 years with type 2 diabetes and newly diagnosed PDR without diabetic macular edema (DME) requiring panretinal photocoagulation or intravitreal injection were included. Patients were stratified based on the presence or absence of prior DR screening in the last 5 years and balanced using propensity score matching (PSM). Primary outcomes included 30-, 60-, and 90-day hospitalization rates and repeat ophthalmic follow-up as estimated using repeat PDR diagnosis codes and repeat retinal imaging codes, including OCT, fundus photography, and fluorescein angiography. Results: Of 57,964 patients, 25,003 had no prior DR screening and 32,961 had prior DR screening. After matching, 19,316 patients were included per cohort. Patients without known DR screening had significantly higher hospitalization rates at 30 days (RR = 1.78, 95% CI 1.67–1.89), 60 days (RR = 1.59, 95% CI 1.51–1.67), and 90 days (RR = 1.51, 95% CI 1.44–1.58), and lower repeat ophthalmic visits by PDR codes at 30 days (RR = 0.458, 95% CI 0.440–0.476), 60 days (RR = 0.450, 95% CI 0.437–0.463) and 90 days (RR = 0.420, 95% CI 0.408–0.432) or by repeat retinal imaging codes at 30 days (RR = 0.450, 95% CI 0.423–0.478), 60 days (RR = 0.394, 95% CI 0.377–0.411), and 90 days (RR = 0.381, 95% CI 0.366–0.396) (all p < 0.0001). Conclusions: Absence of known prior DR screening in PDR patients is associated with higher hospitalization risk and reduced ophthalmic follow-up, suggesting that a lack of screening indicates broader gaps in healthcare engagement and disease control. Tailored strategies are needed to prevent vision loss as well as systemic complications. Full article

Purpose: The aim of this study is to describe a slit-modified 23-gauge infusion trocar designed to enable early postoperative hypotony-free sclerotomy closure by allowing scleral suturing prior to complete trocar removal, and to report initial clinical outcomes in eyes with proliferative diabetic retinopathy with or without vitreous hemorrhage (PDR + H and PDR). Methods: A standard 23-gauge metallic (titanium) trocar was modified by creating a longitudinal slit that permitted passage of a suture needle while the trocar remained partially engaged within the scleral tunnel. At the end of pars plana vitrectomy, a transscleral suture was placed through the slit with the knot prepared prior to trocar removal, followed by simultaneous trocar extraction and suture tightening. Eighteen consecutive patients undergoing vitrectomy for PDR (fourteen with vitreous hemorrhage [PDR + H]; four without) were included. Intraocular pressure (IOP) was recorded preoperatively, immediately after sclerotomy closure (postoperative baseline), and at 8 and 24 h postoperatively. The study was designed as an exploratory pilot feasibility and safety evaluation of a slit-modified infusion trocar in 23-gauge vitrectomy. The primary outcomes were postoperative IOP stability and wound leakage. Secondary outcomes included early hypotony, postoperative hemorrhage, choroidal effusion, and the need for additional suturing. Results: All procedures were completed without intraoperative complications. The mean IOP was 14.83 ± 2.50 mmHg preoperatively, 13.33 ± 1.53 mmHg immediately after closure, 14.17 ± 3.01 mmHg at 8 h, and 15.17 ± 1.79 mmHg at 24 h. No cases of wound leakage or early postoperative hypotony were observed in either subgroup. One eye exhibited a transient IOP increase at 8 h; no choroidal effusion, postoperative hemorrhage, or need for secondary suturing occurred. Endotamponade consisted of balanced salt solution (BSS) in eight eyes, SF6 in seven eyes, silicone oil in two eyes, and air in one eye. Conclusions: The slit-modified infusion trocar enables secure, hypotony-free closure of the infusion sclerotomy by eliminating the open-wound interval during trocar removal. This simple biomedical device modification provides stable early postoperative IOP across different tamponade agents and appears safe and feasible in high-risk eyes with PDR. Full article

Background/Objectives: Diabetic retinopathy (DR) is a major microvascular complication of type 1 diabetes mellitus (T1DM) and remains an important cause of preventable visual impairment. Region-specific data on the incidence and clinical predictors of DR among patients with T1DM in Saudi Arabia remain limited. This study aimed to determine the incidence of DR and identify associated demographic and systemic risk factors among patients with T1DM at a tertiary care center in Riyadh, Saudi Arabia. Methods: This retrospective cohort study included 449 patients with T1DM aged ≥9 years who were followed at King Abdulaziz Medical City, Riyadh, between 2015 and 2025. Patients were selected using a consecutive non-probability sampling technique. Data were extracted from the BESTCare 2.0A electronic medical record system and supplemented, when required, by phone-based interviews to verify selected clinical and demographic variables. Patients were classified as controls without DR or cases with DR, including non-vision-threatening DR and vision-threatening DR (VTDR), according to the International Clinical Diabetic Retinopathy Severity Scale. Multivariable logistic regression, Cox proportional hazards models, and temporal trend analysis were performed, with statistical significance set at p < 0.05. Results: The overall incidence rate of DR was 92.66 per 1000 person-years, with similar rates among males and females. In multivariable logistic regression, older age at T1DM diagnosis, longer diabetes duration, hypertension, hyperlipidemia, and albuminuria were independently associated with DR. Mean HbA1c and HbA1c variability were not independently associated with DR after adjustment. In Cox regression, older age at T1DM diagnosis was associated with higher hazards of both DR and VTDR, while hypertension was associated with VTDR. Among patients with DR, younger age at T1DM diagnosis was associated with higher odds of proliferative disease in exploratory severity analysis. Conclusions: DR was common among patients with T1DM in this tertiary-care cohort and was mainly associated with disease duration, age at diagnosis, and systemic vascular comorbidities. These findings support the importance of routine ophthalmologic screening and integrated management of systemic risk factors in patients with T1DM. Full article

Diabetic retinopathy (DR) is a leading cause of vision impairment and permanent blindness worldwide, requiring accurate and automated systems for multi-grade severity classification. However, standard Convolutional Neural Networks (CNNs) often struggle to capture fine, high-frequency microvascular patterns critical for diagnosis. This study proposes a Robust Intelligent CNN Model (RICNN) that integrates Gabor-based feature extraction with deep learning to improve DR classification. Specifically, Gabor filters are applied during preprocessing to extract orientation- and frequency-sensitive texture features, which are transformed into feature maps and concatenated with CNN feature representations at the fully connected layer (feature-level fusion). The model also incorporates the Synthetic Minority Oversampling Technique (SMOTE) for data balancing and the Adam optimizer for efficient convergence. This integration enhances sensitivity to microvascular structures such as microaneurysms and hemorrhages. The proposed RICNN was evaluated on the Messidor dataset (1200 images) across four severity levels: Mild, Moderate, Severe, and Proliferative DR. The model achieved an accuracy of 89%, a precision of 88.75%, a recall of 89%, and an F1-score of 89%, with AUCs of 97% for Severe DR and 99% for Proliferative DR. Comparative analysis confirms that the proposed texture-aware Gabor enhancement significantly outperforms LBP and Color Histogram approaches, indicating its potential for reliable clinical decision support. Full article

Background/Objective: In late adulthood, the increasing prevalence of diabetes overlaps with the highest prevalence of postural instability. A cross-sectional study was designed to explore the combined influence of age, gender, history of COVID-19 quadriceps strength, and Body Mass Index (B.M.I.) on the postural stability of adults with/without diabetes, under a variety of sensory conditions. Methods: A total of 263 adults aged 21 to 82 years old accepted to participate, 99 with and 164 without diabetes. They had no history of vestibular/otology/neurology/autoimmune/orthopedic disease or proliferative retinopathy/severe renal dysfunction/traumatic injury. After clinical and vestibular evaluations, postural sway was recorded on hard/soft surface, eyes open/closed, and without/with 30° neck extension. Bivariate analysis and repeated measures multivariate analysis of covariance were performed with 0.05 significance. Results: In the two groups, two thirds of the participants had excess weight and almost half had history of COVID-19. Overall conditions, gender and diabetes were the main factors contributing to sway area (multiple R = 0.28–0.31, p ≤ 0.001) and to sway length (multiple R = 0.34–0.47, p ≤ 0.00001). Compared to adults without diabetes, in those with diabetes, the age was not related to sway measurements; with contribution to sway from history of COVID-19 and quadriceps strength, and decreased contribution of the study variables to both the anterior–posterior position of the center of pressure and ankle movement (velocity as a function of the anterior–posterior position of the center of pressure) (p > 0.05). Conclusions: Diabetes may interfere with the influence of individual cofactors contributing to postural sway, including decreased influence of age and reduced ankle movement. A history of mild–moderate COVID-19 may have influence on postural control in varied sensory conditions. Full article

Diabetic retinopathy (DR), recognized as a progressive neurovascular and microvascular complication of diabetes, remains one of the leading causes of visual disability worldwide, within the context of a sustained increase in ophthalmic diseases and retinal vascular disorders that compromise vision. This study aimed to characterize the progression of diabetic retinopathy in a streptozotocin (STZ)-induced Wistar rat model. A single dose of 65 mg/kg body weight was administered, with follow-up periods at 2, 4, 8, and 10 weeks, compared to healthy controls. STZ-induced rats exhibited reduced weight gain compared to the control group. They also showed markedly variable hyperglycemia, with glucose concentrations ranging from 250 to 530 mg/dL. Histological analysis of retinal tissue at week 4 revealed early signs of vascular compromise, including early indications of a microenvironment conducive to neovascularization and edema. By week 8, retinal damage had progressed to hemorrhage, persistent edema, and layer-specific vascular disruption. At week 10, intensified neovascularization and exacerbated edema indicated advanced microvascular deterioration. Immunofluorescence analysis demonstrated a temporal accumulation of CD8⁺ T cells in the retina, correlating with photoreceptor degeneration. The coordinated dynamics of CD4⁺ and CD8⁺ T cells suggested transient immune activation during STZ-induced retinal degeneration. Gene expression profiling revealed a proinflammatory and pro-oxidative retinal microenvironment, characterized by the overexpression of angiogenic pathways and proliferative signals. Simultaneously, the antioxidant response appeared partially impaired. Collectively, these findings provide mechanistic perspective on the multifactorial nature of diabetic retinopathy. Oxidative stress, inflammation, and angiogenesis converge to disrupt retinal homeostasis. This experimental model may serve as a reliable platform for future studies aimed at elucidating disease pathophysiology, identifying novel therapeutic targets, and evaluating emerging ophthalmic antidiabetic interventions. Full article

Background/Objectives: Magnesium is an intracellular cation that plays important roles in metabolism and insulin signaling. The evidence of association between magnesium levels and diabetic retinopathy is limited by small study effects. Therefore, this systematic review and meta-analysis aim to update the current evidence. Methods: A comprehensive search of PubMed, ScienceDirect, Google Scholar, and Scopus was conducted from database inception to January 2026 to identify studies examining magnesium levels and diabetic retinopathy. The pooled standardized mean difference in magnesium levels between type 2 diabetic patients with retinopathy and those without retinopathy was estimated using the “meta” package in R software. Results: We included seventeen studies which assessed magnesium levels in 1100 patients with diabetic retinopathy and 1132 diabetic controls without retinopathy. The random-effects model indicated significantly lower magnesium levels in patients with diabetic retinopathy compared to diabetic controls [SMD = −1.19, 95% CI (−1.68; −0.70); p < 0.0001; I² = 95%]. Sensitivity analysis retained all studies, and no evidence of publication bias was detected. Subgroup analyses demonstrated consistent findings across geographic regions (Asian versus non-Asian), study designs (case–control versus cross-sectional), and magnesium assay methods except enzymatic method. Meta-regression analysis revealed that year of publication (coefficient = 0.061; p = 0.009) and non-Asian studies (coefficient = 2.376; p = 0.001) were positively associated with the pooled effect size, while the NOS quality score was inversely associated (coefficient = −0.709; p = 0.035). The magnesium levels were significantly lower in patients with proliferative diabetic retinopathy compared with those with non-proliferative diabetic retinopathy using a fixed effect model [SMD = −1.41, (95% CI: −1.83; −1.00); p < 0.01; I² = 32%; Cochran’s Q statistic (Q = 1.46, p < 0.23)]. The certainty of the generated evidence is rated as low certainty. Conclusions: This systematic review and meta-analysis conclude that magnesium levels are significantly lower in patients with diabetic retinopathy than in diabetic controls without retinopathy. A potential association between hypomagnesemia and the development of diabetic retinopathy in individuals with type 2 diabetes is suggested; therefore, the clinician may check and adjust magnesium levels in patients with type 2 diabetes mellitus. Full article

Background/Objectives: Optical coherence tomography angiography (OCTA) enables noninvasive quantitative assessment of the retinal microvasculature and is widely used in diabetic retinopathy (DR). However, OCTA-derived metrics are highly dependent on post-processing techniques, particularly vessel binarization. This study aimed to compare local and global binarization methods applied after Frangi filtering for vessel enhancement in parafoveal vessel density analysis. Methods: This cross-sectional study included 69 participants: 17 healthy controls and 52 diabetic patients, classified as the following: no DR (n = 14), non-proliferative DR (NPDR, n = 18), or proliferative DR (PDR, n = 20). All subjects underwent comprehensive ophthalmological examination and OCTA imaging of the superficial capillary plexus using a Topcon OCTA system. Images were processed using a custom MATLAB protocol. Following Frangi filtering, five binarization methods were applied: three local (Phansalkar, local Otsu, adaptive mean) and two global (global mean and global Otsu). Parafoveal vessel density was quantified within the four inner quadrants of the ETDRS grid. Results: Statistically significant differences in vessel density were consistently observed between PDR group and both the control and no DR groups across all local binarization methods. Among global methods, only global Otsu thresholding detected a significant difference between PDR and control. The most robust differences were predominantly identified in the nasal and inferior quadrants. Conclusions: Local adaptive binarization methods demonstrated superior sensitivity and structural preservation for parafoveal vessel density analysis in DR. Global methods showed limited discriminative capability. These findings support the preferential use of local adaptive techniques for reliable OCTA-based vascular assessment in diabetic retinopathy. Full article

Diabetic retinopathy (DR) is one of the most common microvascular complications of diabetes and can lead to severe visual impairment. Based on disease severity, DR is classified into no clinically apparent diabetic retinopathy (NDR), non-proliferative diabetic retinopathy (NPDR), and proliferative diabetic retinopathy (PDR). Although nearly all retinal cell types are involved in DR progression, the dominant cell populations and their pathophysiological changes at each stage remain unclear. By integrating bulk and single-cell transcriptomic data from human and mouse retinas, this study revealed the following: (1) In the NDR stage, photoreceptors exhibit significant changes in ribosomal pathways. (2) In the NPDR stage, endothelial cells and pericytes show marked transcriptional alterations, accompanied by enhanced LAMININ signaling in cell-cell communication. (3) At the PDR stage, neural and glial cells are extensively involved in disease progression, with notable changes in ANGPTL signaling. Additionally, this study observed DR-specific subtypes of endothelial cells and pericytes and potentially identifies gene signatures in macroglia cells that correlate with disease duration. The altered expression of several key genes in early diabetic retina was confirmed by qPCR. These findings may offer a comprehensive view of the cellular and molecular landscape underlying DR and may suggest potential targets. Full article

Background/Objectives: This study aimed to evaluate the autoregulatory capacity of optic nerve head (ONH) tissue blood flow in response to intraocular pressure (IOP) fluctuations during vitrectomy in patients with proliferative diabetic retinopathy (PDR). We hypothesized that impaired autoregulation of ONH tissue blood flow in response to intraoperative IOP fluctuations could contribute to subsequent ONH atrophy and the development of visual field defects in PDR patients following vitrectomy. Methods: We included five eyes from five patients with PDR (mean age 70.6 ± 9.0 years) undergoing 25-gauge pars plana vitrectomy. ONH tissue blood flow was quantitatively assessed using intraoperative laser speckle flowgraphy. Mean blur rate in the tissue area (MT), an indicator of ONH tissue blood flow, was measured at baseline (infusion pressure 0 mmHg), during sustained elevation to 25 mmHg (at 5 and 10 min), and 1 min after return to baseline (11 min). IOP was modulated using the IOP Control system of the Constellation platform. Results: Elevation of IOP to 25 mmHg significantly reduced ONH tissue blood flow, with MT decreasing by 29% at 10 min compared with baseline (p < 0.05, Dunn’s multiple comparisons test). After IOP returned to baseline, MT significantly recovered compared with the 10 min measurement (p < 0.05) and returned to levels not significantly different from baseline (p > 0.05). Conclusions: MT decreases during intraoperative IOP elevation in PDR undergoing vitrectomy, but recovers after the return to baseline pressure, suggesting preserved short-term autoregulatory capacity. Careful IOP management during vitrectomy remains important in eyes with PDR. Full article