Central retinal vein occlusion (CRVO) causes macular edema and subsequent vision loss and is common in people with diseases such as arteriosclerosis and hypertension. Various treatments for CRVO-associated macular edema have been trialed, including laser photocoagulation, with unsatisfactory results. However, when the important pathogenic role of vascular endothelial growth factor (VEGF) in macular edema was identified, the treatment of CRVO was revolutionized by anti-VEGF therapy. However, despite the success of intraocular injection of anti-VEGF agents in many patients with CRVO, some patients continue to suffer from refractory or recurring edema. In addition, the expression of inflammatory cytokines increases over time, causing more severe inflammation and a condition that is increasingly resistant to anti-VEGF therapy. This indicates that the pathogenesis of macular edema in CRVO is more complex than originally thought and may involve factors or cytokines associated with inflammation and ischemia other than VEGF. CRVO is also associated with leukocyte abnormalities and a gradual reduction in retinal blood flow velocity, which increase the likelihood of it developing from the nonischemic type into the more severe ischemic type; in turn, this results in excessive VEGF expression and subsequent neovascular glaucoma. Here, we review the role of different factors and cytokines involved in CRVO pathogenesis and propose a mechanism that holds promise for the development of novel therapies.

Purpose: The purpose of this study was to evaluate the effectiveness of intravitreal bevacizumab (IVB) on the reduction of diffuse diabetic macular edema in patients with different optical coherence tomography patterns. Design: Prospective interventional case series. Methods: One hundred and forty-three eyes with diffuse diabetic macular edema, without a history of any previous treatment, were classified according to their optical coherence tomography patterns: sponge-like diffuse retinal thickening (SDRT) (n = 50), cystoid macular edema (CME) (n = 38), serous retinal detachment (SRD) (n = 25), and the combination of all patterns (FULL: n = 30). All the participants received a single dose (1.25 mg in 0.05 mL) of IVB. The foveal thickness obtained with optical coherence tomography images and logarithm of the minimum angle of resolution visual acuity were assessed before receiving IVB and subsequently every 2 weeks for 12 weeks. Results: After IVB, the foveal thickness in all the groups was reduced but the reduction ratio in the SDRT (29.6 ± 15.6%) and CME (27.1 ± 20.5%) groups was significantly greater than in the SRD group (16.4 ± 17.7%) (P < 0.001). Similarly, improvement of visual acuity in the SDRT (−0.21 ± 0.16) and CME (−0.17 ± 0.24) groups was significantly greater than in the SRD (−0.12 ± 0.15) and FULL (−0.11 ± 0.13) (P = 0.047) groups. Interestingly, the efficacy of IVB for regression of diffuse diabetic macular edema was dependent on the duration of diabetes in the SDRT and CME groups but not in the SRD or FULL groups. Conclusion: The effectiveness of IVB on diffuse diabetic macular edema was dependent on the optical coherence tomography pattern (SDRT ≥ CME >> SRD), indicating that vascular endothelial growth factor plays a critical role in the pathogenesis of SDRT and CME, and was greater in patients having diabetes for a shorter duration of time.

Diabetic macular edema (DME) is a critical complication of diabetic retinopathy, a condition that arises from the breakdown of the blood–retinal barrier and the consequent increase in vascular permeability. Over the years, attempts have been made to treat DME by various approaches, including laser photocoagulation, steroid triamcinolone acetonide, and vitrectomy. However, treatment was unsatisfactory until research identified vascular endothelial growth factor (VEGF) as a factor in the pathogenesis of DME. Intraocular anti-VEGF agents show good efficacy in DME. Nevertheless, in some patients the condition recurs or becomes resistant to treatment, suggesting that other factors may be involved. Because inflammation and retinal hypoxia are seen in DME, research has examined the potential role of cytokines and other inflammatory mediators. In this review, we provide an overview of this research and describe feedback mechanisms that may represent a target for novel treatments.

To evaluate the effectiveness of intravitreal triamcinolone acetonide (IVTA) on the reduction of diffuse diabetic macular edema with different optical coherence tomographic patterns. One hundred and thirty-five eyes with diffuse diabetic macular edema without any treatment that had received a single dose (4 mg in 0.1 mL) of IVTA were retrospectively examined. Each preoperative macular optical coherence tomographic image was classified according to its appearance as follows: sponge-like diffuse retinal thickening, cystoid macular edema (CME), and serous retinal detachment (SRD). Central macular thickness with optical coherence tomographic images and visual acuity with a logarithm of the minimum angle of resolution chart were assessed at 3 months postoperatively. Of 135 eligible eyes, 49 eyes were identified as having only sponge-like diffuse retinal thickening, 45 eyes with CME, and 26 eyes with SRD. Of those 135 eyes, 15 eyes exhibited the combination of all types of diffuse diabetic macular edema, defined as FULL. After IVTA, central macular thickness was reduced to 31.0 ± 15.9% in the sponge-like diffuse retinal thickening, 40.7 ± 14.2% in the CME, 23.4 ± 15.0% in the SRD, and 25.8 ± 14.8% in the FULL group (P < 0.001; one-factor analysis of variance), while improvement in logarithm of the minimum angle of resolution visual acuity was −0.26 ± 0.21 in the sponge-like diffuse retinal thickening, −0.32 ± 0.20 in the CME, −0.17 ± 0.20 in the SRD, and −0.14 ± 0.22 in the FULL group (P = 0.018; one-factor analysis of variance). The effectiveness of IVTA on diffuse diabetic macular edema was dependent on the optical coherence tomographic pattern, and IVTA was found to be more effective in patients with CME, while IVTA was less effective in those with SRD.