Editorial: Prevention and Treatment Advancements in Diabetic Retinopathy

Tomislav Bulum^1,2*Tomislav Jukić^1,3Domagoj Ivastinovic⁴MAYANK CHOUBEY⁵Miroslav Stamenkovic⁶Martina Tomić²

• ¹Medical School University of Zagreb, Zagreb, Croatia
• ²Klinicka bolnica Merkur Sveucilisna klinika za dijabetes endokrinologiju i bolesti metabolizma Vuk Vrhovac, Zagreb, Croatia
• ³Klinicki bolnicki centar Zagreb, Zagreb, Croatia
• ⁴Medizinische Universitat Graz, Graz, Austria
• ⁵New York University Long Island School of Medicine, Mineola, United States
• ⁶Klinicko-bolnicki centar Zvezdara, Belgrade, Serbia

Diabetes is a global pandemic with almost 600 million adults living with diabetes in 2024 [1,2]. High blood glucose levels have harmful effects on small vessels and neuroretinal structures, leading to the development of diabetic retinopathy (DR), a microvascular complication of diabetes, which is currently a leading cause of preventable blindness in working-age adults [3]. While the majority of patients with diabetes will develop DR, it is important to stress that about 10% of them will develop vision-threatening forms of DR, such as proliferative DR (PDR) and diabetic macular edema (DME) [4]. While there is a trend of decreasing the incidence of the most severe forms of DR in developed countries, the risk of vision-threatening forms of DR is still high, and the overall prevalence of DR is increasing due to the global diabetes epidemic [5]. In light of these considerations, further action is required to minimize the burden of vision loss and disability among individuals with diabetes. This Research Topic, therefore, highlights current developments and recent progress in the understanding and management of DR and DME, bringing together 18 original research articles, 5 narrative reviews, and 3 systematic reviews.Chen et al. investigated the association between serum selenium levels and DR and collected data from 645 adults through the National Health and Nutrition Examination Survey (NHANES) between 2011 and 2016. While there was no statistically significant linear association between serum selenium levels and the probability of developing DR, a U-shaped relationship was observed. The incidence of DR is elevated in individuals with serum selenium levels that are either higher or lower than the optimal range, suggesting that selenium supplementation should be balanced to avoid excessive intake.In addition to selenium, vitamin D has been reported to be involved in DR pathogenesis, but results have been inconsistent. He et al. explore the relationship between vitamin D level and the risk of DR in 535 adult patients with type 2 diabetes mellitus (T2DM). The results suggest that males, but not females, with DR had significantly lower vitamin D levels and a higher proportion of severe vitamin D deficiency than those without DR. In addition, total testosterone levels were significantly lower in males with DR. The findings indicate a sexspecific association between serum vitamin D levels and the risk of DR in T2DM. A significant inverse relationship was observed exclusively in men, potentially driven by a substantial decline in total testosterone levels.Since emerging evidence suggests a potential association between depression and DR, Li et al. investigate the relationship between depression and DR using nationally representative data from the National Health and Nutrition Examination Survey (NHANES, 2011-2020).Depression was assessed using the PHQ-9, and among 1,653 participants, the weighted DR prevalence was 18.91%. Depression was independently associated with higher DR risk. These findings underscore the importance of an integrated approach that addresses both mental health and metabolic regulation in individuals with diabetes. Targeted management of depressive symptoms may help mitigate the burden of DR and enhance overall quality of life. Decision curve analysis supported its clinical usefulness over a wide range of risk thresholds.Overall, the model offers a practical, scalable tool for early referable DR risk stratification in both community and ophthalmic settings. Triglyceride-glucose index (TyG). Data from 3,750 patients were analyzed, and SHapley Additive exPlanations (SHAP) analysis identified TyG, insulin therapy, HbA1c, diabetes duration, and HDL as key predictors, with HDL protective. This model highlights TyG as a cost-effective, practical alternative to traditional insulin resistance measures, such as HOMA-IR, enabling accessible DR risk stratification in primary care.In addition, a systematic review and meta-analysis from Amirashov et al. examined the association between the TyG and DR. Sixteen observational studies involving over 33,000 participants were included. Higher TyG levels were associated with increased DR risk, particularly when analyzed as a continuous variable. However, substantial heterogeneity and potential publication bias were observed, especially in categorical analyses. Subgroup and meta-regression analyses identified male proportion as a key source of heterogeneity. These findings suggest a possible link between TyG and DR, though inconsistent thresholds and bias limit immediate clinical application. She et al. investigated the association between the albumin-to-neutrophil-lymphocyte ratio (ANLR), a marker of nutritional and inflammatory status, and DR using NHANES data Glucagon-like peptide-1 (GLP-1) receptor agonists are now a fundamental class of drugs used in the treatment of T2DM because of their cardiorenoprotective properties and weight-reducing effects [6]. However, their impact on DR appear to be neutral, or in some cases, even harmful [7]. A systematic review and meta-analysis from Alwafi et al. aimed to clarify the association between GLP-1 receptor agonist use and the development or progression of DR. Thirty-nine studies were reviewed, with 23 included in the meta-analysis. Overall, GLP-1 receptor agonist use was not significantly associated with DR risk compared with other therapies. Subgroup analyses by study design, sample size, and risk of bias yielded consistent non-significant results, with a modest trend toward reduced risk in randomized trials.The collective evidence presented in this Research Topic provides a comprehensive overview of recent advances in research on DR and DME in T2DM and emphasizes the need to improve our understanding and management of these vision-threatening complications."