Anti‐VEGF and steroid combination therapy relative to anti‐VEGF mono therapy for the treatment of refractory DME: A systematic review of efficacy and meta‐analysis of safety

Abstract

The aim of the study was to determine the efficacy and safety of combined anti‐VEGF and steroid therapy in treatment refractory DME patients. We conducted a systematic review and meta‐analysis of peer‐reviewed articles reporting on visual, anatomical and adverse outcomes to compare the efficacy and safety of combined intravitreal anti‐VEGF/steroids versus anti‐VEGF monotherapy for refractory DME. Seven studies (4 RCTs and 3 observational studies) reporting on 452 eyes were included. Our systematic review showed that combination therapy is significantly more effective for anatomical outcomes in the treatment of resistant DME compared to anti‐VEGF monotherapy in six studies. Two studies found that addition of intravitreal steroids promoted faster visual improvement, but not significantly better final visual outcomes compared to anti‐VEGF monotherapy. Combination therapy was associated with a higher incidence of IOP‐related adverse events (RR = 0.10, 95% CI = [0.02, 0.42], p = 0.002) and cataract‐related adverse events (RR = 0.10, 95% CI = [0.01, 0.71], p = 0.02). Our systematic review and meta‐analysis of seven studies and 452 eyes revealed that combination therapy of anti‐VEGF and steroid intravitreal drugs in the management of treatment refractory DME resulted in superior anatomical outcomes in all but one study. Combination therapy led to superior short‐term visual outcomes in two studies, while others reported no difference between treatment groups. Meta‐analysis revealed that combination therapy was associated with more adverse events. Future research should provide guidance on the standard definitions for treatment resistance and therapeutic alternatives for DME patients with sub‐optimal response to anti‐VEGF treatment.

Effects of vitrectomy combined with internal limiting membrane peeling in patients with diabetic macular edema

“…Chronic hyperglycemia activates four classical oxidative stress pathways – the polyol pathway, increased advanced glycation end products, activation of protein kinase, and the hexosamine pathway. All these pathways result in retinal hypoxia, an increase in the concentration of reactive oxygen species, aggravated inflammatory response, and the up-regulation of various inflammatory and oxidative factors within the pathway; this ultimately destroys the blood-retinal barrier, resulting in augmented vascular osmolality[ 11 ]. Hyperglycemia also leads to a decrease in retinal blood flow, reduced oxygen levels, and increased autoregulatory response of retinal arterioles, resulting in dilation of the retinal capillaries and venules.…”

Correlation between Topographic Vessel Density and Retinal Thickness Changes in Patients with Diabetic Macular Edema Treated with Anti-VEGF Therapy: Is It a Suitable OCTA Biomarker?

“…The prompt identification of the risk factors that can predict treatment success or failure is mandatory for reducing costs and patient burden. Traditionally, non-responders in clinical trial settings have been defined in relation to their response to treatment (less than three lines of visual gain, CST over 350 µm, or a reduction of less than 20% after six anti-VEGF injections), with the vascular changes often being relegated to having a secondary role due to the difficulty in acquiring routine vascular network measurements [43]. However, the evaluation of MAs pre-and post-anti-EGF therapy may have clinical implications for decision making.…”

Anti-angiogenic and antioxidant effects of axitinib in human retinal endothelial cells: implications in diabetic retinopathy

“…DR progresses from non-proliferative to proliferative stage, the latter characterized by abnormal retinal vessel growth, which causes macular edema, that if not treated can lead to retinal detachment and then irreversible vision loss. Intravitreal anti-vascular endothelial growth factor (anti-VEGF) agents (bevacizumab, ranibizumab, aflibercept) are the standard of care for treatment of diabetic macular edema (DME) ( Hatamnejad et al, 2024 ), but recently also brolucizumab and faricimab have been approved for DME treatment ( Montesel et al, 2021 ; Wong et al, 2023 ). In some cases, also intravitreal steroids, such as dexamethasone and triamcinolone acetonide are indicated to treat DME ( Bucolo et al, 2015 ; Bucolo et al, 2018 ).…”

“…In some cases, also intravitreal steroids, such as dexamethasone and triamcinolone acetonide are indicated to treat DME ( Bucolo et al, 2015 ; Bucolo et al, 2018 ). Besides these mentioned pharmacological treatments, several unmet medical needs affect diabetic retinopathy management: burden of care due to high cost and invasive intravitreal treatments, poor adherence, and 40%–50% of cases refractory to current approved pharmacological interventions ( Hatamnejad et al, 2024 ; Mandava et al, 2024 ). In this perspective in search of alternatives to intravitreal anti-VEGF agents, we focused our study on axitinib, a tyrosine kinase inhibitor (TKI).…”