Background: Diabetic macular edema (DME) is the leading cause of vision impairment in diabetic patients, with intravitreal anti-vascular endothelial growth factor (anti-VEGF) injections being the first-line therapy. However, one-third of patients exhibit persistent DME despite treatment, suggesting additional pathogenic factors. This study aimed to evaluate the predictive value of complete blood count (CBC)-based inflammation indexes and optical coherence tomography (OCT) parameters in determining early anti-VEGF treatment effectiveness in DME. Methods: One hundred and four naïve patients with DME, treated with 0.05 mL of intravitreal aflibercept were retrospectively analyzed. Blood parameters analyzed included neutrophil-to-lymphocyte ratio (NLR), monocyte-to-lymphocyte ratio (MLR), platelet-to-lymphocyte ratio (PLR), and systemic immune-inflammation index (SII). Baseline OCT biomarkers included subretinal fluid (SRF), intraretinal cysts (IRC), hyperreflective retinal spots (HRS), and disorganization of retinal inner layers (DRIL). Treatment response was defined as a minimum 10% reduction in central macular thickness (CMT) at one month post-injection. Results: NLR, MLR, PLR, and SII were significantly higher in non-responders (p < 0.001), but their predictive value was fair, with an area under the ROC curve ranging between 0.704 (MLR) and 0.788 (SII). A multivariate model including SII, initial CMT, and the presence of IRC showed an excellent prediction value for early anatomical response (AUC ROC of 0.911). At the same time, lower PLR, DRIL, SRF, and the absence of HRF were correlated with early gain in BCVA. Conclusions: CBC-derived inflammation indices and OCT biomarkers have prognostic value in predicting early response to anti-VEGF therapy in DME in terms of functional and anatomical outcomes. These findings could help identify poor responders and guide personalized treatment strategies.

Background/Objectives: Diabetic macular edema (DME) are major causes of visual impairment worldwide, with vascular endothelial growth factor (VEGF) playing a central role in disease pathogenesis. Intravitreal anti-VEGF therapy is the current standard of care for center-involving DME. Methods: This narrative review summarizes and compares the pharmacological properties, clinical efficacy, safety, and real-world performance of aflibercept and brolucizumab in the treatment of DME, based on randomized controlled trials and observational studies published between 2014 and 2025. Results: Both agents demonstrate significant improvements in visual acuity and retinal anatomy. Brolucizumab has shown non-inferior visual outcomes and, in several studies, greater reductions in central retinal thickness with the potential for extended dosing intervals, suggesting reduced treatment burden. However, post-marketing data have identified an increased risk of intraocular inflammation, including retinal vasculitis and retinal vascular occlusion, associated with brolucizumab, which has influenced its clinical use. Conclusions: Both aflibercept and brolucizumab are effective anti-VEGF therapies for diabetic macular edema, but they differ in durability and safety considerations. Aflibercept remains a reliable first-line option for many patients, while brolucizumab may be considered in carefully selected cases where treatment burden is a priority. Individualized treatment selection based on clinical characteristics, patient preferences, and safety considerations is essential for optimizing long-term outcomes.

Background and Clinical Significance: Bilateral carotid-cavernous fistulas are rare clinical entities characterized by heterogeneous clinical presentations and variable outcomes. Case presentation: We report the case of a 69-year-old woman with a three-month history of progressive bilateral conjunctival hyperemia, proptosis, intermittent diplopia, and a left eye abduction deficit. Her systemic history included long-standing arterial hypertension and previous thyroidectomy with stable substitutive therapy. Comprehensive ophthalmologic, neurologic, and endocrine evaluations excluded more common causes of orbital congestion, including thyroid eye disease, orbital cellulitis, cavernous sinus thrombosis, and idiopathic orbital inflammation. The patient denied any history of recent trauma. Digital subtraction angiography (DSA) confirmed a bilateral, low-flow, indirect Barrow type D carotid–cavernous fistula (CCF) supplied by dural branches of both the internal and external carotid arteries, with marked reflux into dilated superior ophthalmic veins. DSA was essential, as prior CT and MRI studies did not identify any vascular abnormalities. The patient was scheduled for transvenous embolization; however, during the follow-up she noted gradual improvement in her condition. Repeat pre-procedural angiography performed approximately two months later demonstrated complete spontaneous closure of all shunts, accompanied by full clinical resolution. Conclusions: Owing to the exceptional rarity of bilateral indirect CCFs and the added occurrence of spontaneous closure, this case expands the limited existing literature and emphasizes the diagnostic challenges and the need for individualized treatment timing supported by multidisciplinary evaluation in low-flow dural carotid–cavernous fistulas.