Autism spectrum-related symptoms and clinical ASD diagnoses in children and adolescents with classical galactosemia: a descriptive clinical cohort study.

Diabetic retinopathy (DR), of which diabetic macular edema (DME) is the principal vision-threatening manifestation, affects approximately 30% to 40% of all individuals with diabetes () and represents a leading cause of vision impairment in the working-age population globally (). With the escalating global prevalence of diabetes mellitus, projected to affect 783 million people by 2045, the clinical burden of DME is expanding at an unprecedented rate (). In China, DR represents a critical public health burden, with significant regional disparities in prevalence, screening coverage, and access to management (). The development of DME is a complex process primarily driven by chronic hyperglycemia, which induces microvascular damage and promotes disease progression through multiple interacting metabolic pathways (). Prolonged diabetes duration and poorly controlled glycated hemoglobin (HbA1c) are well-established systemic risk factors that accelerate the transition from non-proliferative retinopathy to vision-threatening macular edema (). The core pathophysiology of DME involves the breakdown of the blood-retinal barrier (BRB) (). Chronic high glucose levels trigger the overexpression of vascular endothelial growth factor (VEGF), which leads to increased vascular permeability and the subsequent accumulation of intraretinal and subretinal fluid (). Consequently, intravitreal injection of anti-VEGF agents has been established as the first-line therapeutic strategy (, ). Landmark RCTs, including Protocol T, which established the comparative efficacy among anti-VEGF agents (), and the VIVID/VISTA studies, which demonstrated the superiority of anti-VEGF therapy over laser photocoagulation in both functional and anatomical outcomes (), have fundamentally shifted the treatment paradigm for DME. Specifically, the VIVID and VISTA trials demonstrated that intravitreal aflibercept led to significant and durable gains in BCVA—with mean BCVA gains ranging from 10.3 to 11.7 letters across both studies and both dosing regimens—and robust reductions in central subfield thickness that were sustained through 148 weeks, regardless of baseline edema severity (). Complementing these global findings, the SAILING study in China has provided localized evidence for the efficacy of Conbercept, a domestically developed decoy receptor (). Unlike traditional monoclonal antibodies, Conbercept is a recombinant fusion protein that incorporates the second immunoglobulin (Ig) domain of VEGF receptor 1 (VEGFR-1) and the third and fourth Ig domains of VEGFR-2. This unique molecular configuration enables it to bind with higher affinity to all isoforms of VEGF-A, VEGF-B, and placental growth factor (PlGF). The SAILING study confirmed that Conbercept administered as needed (PRN) resulted in a mean BCVA improvement of 8.2 letters at 12 months, significantly outperforming laser therapy and reinforcing its role as a pivotal first-line intervention in the Chinese clinical setting (). However, a critical gap remains in the real-world management of DME. Despite regular treatment, a substantial proportion of patients exhibit an inadequate anatomical response to anti-VEGF agents; real-world survival analyses indicate that undesirable treatment outcomes develop in approximately 50% of DME patients within 2.3 years of initiating therapy (). These “non-responders” often experience persistent macular thickening, and structural disorganization of the retinal inner layers has been shown to predict progressive and potentially irreversible visual acuity decline (). While ocular biomarkers—such as the integrity of the inner segment–outer segment junction and the presence of epiretinal membranes—have been extensively investigated as predictors of anti-VEGF response (), existing evidence regarding the impact of systemic risk factors on anatomical outcomes remains inconsistent and inconclusive. Many studies are further limited by small sample sizes, a lack of standardized response definitions, or the failure to account for the correlation between bilateral eyes in statistical modeling, all of which hinder the translation of findings into actionable clinical guidelines ().