Complications of BRVO include macular edema, retinal neovascularization, macroaneurysmal formation, maculopathy, retinal telangiectasia, retinal detachment, and vitreous hemorrhage[12]. ME is the major cause of vision impairment and metamorphopsia. The main purpose of all treatments is the resolution of the macular edema to maintain central visual acuity[13, 14]. It has been found that the level of VEGF in the vitreous body of BRVO eyes is higher than normal eyes, which may leads to neovascularization and ME. VEGF is a vascular permeability factor that plays a pivotal role in neovascularization. Conbercept can inhibit VEGF and placental growth factor competitively, inhibit angiogenesis and treating ME[15]. Intravitreal injections of anti-VEGF have become first-line treatment for symptomatic ME from BRVO. Many studies have reported that early Intravitreal injections treatment can improve visual outcome[16]. In our study, IVC therapy and IVC combined with Laser therapy significantly improved mean VA and reduced the mean CMT for recurrent ME secondary to BRVO. The combination treatment had a significant effect on reducing CMT and improving BCVA. But compared with IVC, it does not show great advantages. A prospective clinical trial indicated fixed monthly IVC over 3 months demonstrated a generally favorable safety and tolerability profile in the treatment of macular edema due to BRVO[8].
However, recurrence may occur if the IVC treatment has stopped. IVC therapy need multiple injections over periods of months to years. More importantly, multiple injections may causes some adverse effects. Such as endophthalmitis, cataract, retinal detachment, and intraocular hemorrhage. In addition, although IVC therapy is much cheaper than other anti-VEGF, it also has brought a certain economic burden for many patients.
Currently, laser photocoagulation is used for ME in patients with BRVO who are adverse reactions to intravitreal therapy or unable to pay high medical costs. Laser photocoagulation is a noninvasive and conventional treatment for BRVO. The research results about effectiveness of laser therapy for BRVO are different. Branch Vein Occlusion Study confirmed the efficacy of grid laser photocoagulation for treating macular edema due to BRVO in 1984[2]. More than a decade after that, this method become the standard treatment for BRVO. A review published in Cochrane included five studies conducted in Europe and North America. Among the five studies, one RCT with moderate-quality evidence supports the use of grid laser photocoagulation to treat macular edema following BRVO, and other evidence show intravitreal anti-vascular endothelial growth factor (VEGF) is not better than macular grid laser photocoagulation in BRVO[17]. A randomized clinical trial demonstrated that grid laser treatment is helpful in improving visual acuity in eyes with ME[18],but the results achieved are modest. Furthermore, one study on murine retina showed that VEGF protein level is found to increase a few days after laser treatment and then start to decrease in mouse eyes[19].So the laser treatment seems did not benefit in BCVA and resolution of edema. Most of the current studies still support vitreous injection. This may be due to that it is difficult to perform effective coagulation when macular edema is severe. But IVC treatment reduced the CMT allowed us to perform grid photocoagulation more safely. In our study, combination treatment reduced foveal thickness effectively, but there is no obvious advantage than IVC therapy. Considering the potential side effects of laser photocoagulation, we suggest that IVC without additional treatment be used for recurrent macular edema.
In this study, IVC alone and the combination therapy was performed to macular edema recurred.In the 9-month followed up period, 52.4% of patients need ≥ 5 injections. There was no significant difference between the two groups. Depending on the site of the arteriovenous crossing, BRVO was divided into 3 main groups: major BRVO, HSRVO, and macular BRVO[12]. There was no macular BRVO has been found in our study. But we observed the treatment of HSRVO, number of IVC treatments in combination group is fewer than treatment with IVC alone. HSRVO is characterized by an occlusive process involving a hemiretina. The Central Vein Occlusion Study Group reported that grid photocoagulation can reduce CMT in eyes with RVO. Based on the current findings, laser photocoagulation seems has the auxiliary effect of reducing the macular edema associated with HSRVO. However, it is difficult to draw reliable conclusions because the number of cases is too small. Previous studies about intravitreal injection of bevacizumab have shown that additional grid laser photocoagulation has a substantial effect on reducing recurrent macular edema[20]. Based on the current results, we consider that IVC with or without retinal photocoagulation can effectively improve the visual acuity and reduce the CMT of patients. And the effect of this combination therapy on visual recovery and reduce the CMT is limited. But when it is difficult to perform repeated IVC or patients with financial difficulties, we can consider grid photocoagulation combined with IVC therapy.
There are a few limitations to this study. First, this was a retrospective study and small sample size. Then, we did not have a control group of patients who did not undergo any treatment. Furthermore, the follow-up duration is relatively short. The results in this study need to be further verified using large number of samples by a multicenter randomized clinical trial.
In conclusion, conbercept with or without retinal photocoagulation can effectively improve the visual acuity and reduce the CMT. We only suggest that combination therapy be used for recurrent macular edema associated with HSRVO or when it is difficult to perform repeated IVC.
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