branch retinal vein occlusion ( brvo ) is a common sight - threatening retinal vascular disorder , in which macular edema is the main cause of visual impairment . retinal ischemia after vascular occlusion can cause both vitreous and aqueous vascular endothelial growth factor ( vegf ) elevation [ 2 , 3 ] . increased vegf results in higher vascular permeability and associated macular edema in patients with brvo . intravitreal injections of anti - vegf , such as bevacizumab ( avastin , genentech inc . , south san francisco , ca , usa ) and aflibercept ( eylea , regeneron pharmaceuticals , inc . , tarrytown , ny , usa , and bayer pharma ag , berlin , germany ) , can effectively lower intraocular level of vegf and reduce vascular permeability related to macular edema in brvo [ 414 ] . herein , we performed a head - to - head comparison of efficacy after intravitreal bevacizumab and aflibercept treatments for macular edema following brvo . to our knowledge , this is the first paper associated with the issue after reviewing the literature . we conformed to the declaration of helsinki to accomplish this study . from august 2012 to september 2015 , 104 eyes of 104 patients with macular edema secondary to perfused brvo were retrospectively reviewed . the patients did not have prior trauma , intravitreal injections , retinal or macular laser , or ocular surgery except uneventful phacoemulsification . no patient had history of thromboembolic events , known coagulation abnormalities or current use of anticoagulative medication other than aspirin , or other major systemic diseases . all the patients did not have any intravitreal anti - vegf , macular laser , or other associated treatments . the patients with perfused brvo were diagnosed with retinal nonperfusion area less than 10 disc diameters by fundus fluorescein angiography ( trc - nw7sf , topcon , tokyo , japan ) . macular edema was defined as macular leakage on fundus fluorescein angiography and central foveal thickness ( cft ) more than 300  m detected by spectral - domain optical coherence tomography ( rtvue , optovue , san francisco , usa ) with macular pathologies including cystoid changes , diffuse thickening , and submacular fluid , using 6 radial line scans through the fovea in all patients . baseline best - corrected visual acuity ( bcva ) in snellen chart ( converting into logmar and edtrs letters for statistical comparison ) , intraocular pressure via pneumotonometer ( ct-80 , topcon , tokyo , japan ) , and biomicroscope of anterior segment were examined in all the patients . once the patients were diagnosed with macular edema secondary to brvo , intravitreal bevacizumab or aflibercept was administered within one week without accompanying macular laser or future laser rescue . the procedures were performed at far eastern memorial hospital by one surgeon ( wang jk ) . after detailed explanation of risks , benefits , and off - label use of these medications , all the participants signed the informed consents before the intravitreal injections . between august 2012 and february 2014 , 54 consecutive cases received prn intravitreal bevacizumab 1.25  mg/0.05  ml treatment . between march 2014 and september 2015 , 50 consecutive patients were treated by prn intravitreal aflibercept 2  mg/0.05  ml . following topical anesthesia and disinfection of eyelid and conjunctiva , aflibercept or bevacizumab was injected into the vitreous cavity using a 30-gauge needle inserted through the inferotemporal pars plana , 3.5  mm posterior to the limbus . the patient was instructed to instill one drop of 0.3% norfloxacin into the injected eye four times daily for one week . all the patients were followed up monthly for at least 12 months , with anterior segment and fundus examination and bcva , cft , and intraocular pressure measurement . the follow - up sd - oct scans used the baseline scan as a reference . retreatment was based on findings of optical coherence tomography including cft more than 300  m , or there were persistent or recurrent macular cysts or submacular fluid that affected the visual acuity even if cft is less than 300  m . the intragroup changes in cft and bcva were compared with wilcoxon signed rank test and the between - group numerical difference compared with wilcoxon rank sum test . one month after the first intravitreal aflibercept , mean bcva significantly improved from baseline 0.77  logmar ( equal to 46.1 letters ) to 0.43  logmar ( 62.3 letters ) ( p = 0.0007 ) ( figure 1 ) . the baseline mean cft was 470.2  m , which significantly decreases 1 month after the first aflibercept injection to 254.2  m ( p < 0.0001 ) ( figure 2 ) . from month 2 to month 11 , all time points in cft and bcva were significantly different from baseline data ( p < 0.01 ) ( figures 1 and 2 ) . at month 12 in aflibercept group , mean bcva significantly improved to 0.29  logmar ( 70.2 letters ) , significantly better than baseline bcva ( p < 0.0001 ) , with mean change of 0.48  logmar ( + 24.1 letters ) ( figure 1 ) . at month 12 in aflibercept group , mean cft significantly decreased to 241.9  m ( p < 0.0001 ) , with mean change of 228.3  m ( figure 2 ) . the baseline mean bcva was 0.72  logmar ( 48.9 letters ) , which significantly improved 1 month after the first bevacizumab injection to 0.50  logmar ( 60.1 letters ) ( p = 0.0002 ) ( figure 1 ) . the mean cft 1 month after the first intravitreal bevacizumab ( 268.3  m ) significantly improved compared with the mean cft at baseline ( 459.4  m ) ( p < 0.0001 ) ( figure 2 ) . from month 2 to month 11 , all time points in cft and bcva were significantly different from baseline data ( p < 0.01 ) ( figures 1 and 2 ) . at month 12 in bevacizumab group , mean bcva significantly improved to 0.31  logmar ( 69.5 letters ) , significantly better than baseline bcva ( p < 0.0001 ) , with mean change of 0.41  logmar ( + 21.1 letters ) ( figure 1 ) . at month 12 in bevacizumab group , mean cft significantly decreased to 252.7  m ( p < 0.0001 ) , with mean change of 212.8  m ( figure 2 ) . there was no statistical difference between two groups in baseline data , including age , gender , lens status , incidence of patients with diabetes , presenting bcva and cft , and duration of symptoms ( p > 0.05 ) ( table 1 ) . at all time points from month 2 to month 11 , cft and bcva were not significantly different between aflibercept and bevacizumab groups ( p > 0.05 ) . there was also no significant difference between two groups in final anatomical and functional outcome at month 12 , including final bcva , mean visual gains , final cft , and mean cft changes ( p > 0.05 ) ( table 2 ) . nearly two - thirds of the patients in both groups had final bcva equal to or more than 20/40 and visual gains more than 3 lines from baseline to month 12 ( table 2 ) . only less than 10% of the patients in both groups lost bcva equal to or more than one line 12 months after the first injection ( table 2 ) . mean injection number of aflibercept was 2.12 , comparable with that of bevacizumab ( 2.22 ) during 12-month period ( p = 0.11 ) . in aflibercept group , 22 ( 44% ) eyes required no additional injection except the baseline injections . in bevacizumab group , 22 ( 40.7% ) eyes required no additional injection except the baseline injections . there were no episodes of endophthalmitis , retinal detachment , vitreous hemorrhage , or elevated intraocular pressure . the most common side effect was local hyperemia or subconjunctival hemorrhage at the site of injection . macular grid laser photocoagulation was the standard of care for macular edema in perfused brvo according to results of the branch vein occlusion study . however , the visual improvement following macular laser was limited , with mean improvement of 1.33 lines of vision at the 3-year primary end point . anti - vegf intraocular injection has been shown to be a new promising treatment modality , which results in noticeable functional and anatomical improvement . bevacizumab is a full - length recombinant humanized monoclonal antibody directed against the vegf - a . intravitreal bevacizumab is employed to lower the intraocular vegf level , effectively reducing macular edema in patients with brvo . the pan american collaborative retina study group used intravitreal bevacizumab in prn regimen to treat 63 patients with macular edema following brvo . the 2-year results demonstrated that bevacizumab 1.25  mg injection resulted in a gain of 3.8 lines . decreased macular thickness was found , without accompanying serious ocular and systemic adverse events . hikichi and coauthors performed prn intravitreal bevacizumab for 89 eyes with macular edema in brvo . the 2-year results showed that injections resulted in visual gains of 0.30  logmar and subsided macular edema . ahn and colleagues performed prn intravitreal bevacizumab for 69 eyes and three monthly prn injections for 26 eyes with macular edema in brvo . the 6-month results revealed functional and anatomical improvement in both groups , and there was no significant difference between two groups in final visual acuity . injection number was far less in prn only regimen ( mean 1.8 ) than in three - loading and prn group ( mean 3.4 ) . intravitreal bevacizumab demonstrated superior ability than conventional macular grid laser for treating macular edema in brvo . russo and associates compared the efficacy of intravitreal bevacizumab and macular grid laser for patients with macular edema secondary to brvo in a randomized study . the one - year outcome demonstrated that bevacizumab injections had better visual gains and reduction of macular thickness than macular laser . leitritz and coauthors performed a prospective crossover study to compare the efficacy of intravitreal bevacizumab and macular grid laser for patients with macular edema associated with brvo . the one - year outcome demonstrated that bevacizumab injections had superior visual improvement than macular laser . hayashi and colleagues compared the efficacy of intravitreal bevacizumab alone and injections combined with macular grid laser for patients with macular edema in brvo . the one - year outcome demonstrated that macular laser did not have adding effect for bevacizumab injections , neither prolonging the bevacizumab effect nor bettering visual outcome in combined treatment . in this study , the patients with macular edema associated with brvo gained 4.1 lines after one - year prn intravitreal bevacizumab injections . the visual results were similar to prior studies , from 2.9- to 3.8-line visual improvement after one - year prn bevacizumab treatment [ 5 , 7 , 13 , 14 ] . there were 52.8% of patients with visual gain equal to or more than 3 lines at month 12 , comparable to the outcome of previous trials ( from 48% to 80% ) [ 5 , 7 , 10 , 13 , 14 ] . the percentage of bevacizumab - treated patients who had at least 20/40 in bcva was 66.6% at month 12 , similar to results of prior studies after one - year prn bevacizumab management ( from 55 to 67% ) [ 5 , 10 ] . the mean injection number was 2.22 in one year in this study , comparable to the results of preceding articles requiring 1.9 to 2.6 injections of prn bevacizumab within one year [ 5 , 7 , 13 ] . aflibercept is a decoy receptor fusion protein , composed of the second domain of human vegf receptor 1 and the third domain of vegf receptor 2 , which are fused to the fc domain of human igg1 . aflibercept can downregulate vegf - a , vegf - b , and placental growth factor , which are synergistic for pathologic angiogenesis . intravitreal aflibercept was noted to lower the intraocular vegf level in patients with neovascular age - related macular degeneration . the vibrant study , a randomized controlled trial , was conducted in north america and japan . the study demonstrated the efficacy of intravitreal aflibercept 2  mg over the macular grid laser for 183 patients with macular edema associated with brvo . the 6-month results showed that the aflibercept group gained mean of 17.0 letters , significantly better than the laser group having only mean 6.9-letter improvement . the proportion of eyes that gained more than 15 letters from baseline at week 24 was 52.7% . decrease of macular thickness was more prominent in the aflibercept group than in the laser group , without accompanying serious ocular and systemic adverse events . in this study , we had 19.2-letter visual gain in the first 6 months of prn aflibercept injections , compared to the results of vibrant study which had 17-letter improvement . there were 61.1% of patients having at least 15-letter gain after 6-month aflibercept treatment , similar to 52.7% in vibrant study . we only used mean 1.33 aflibercept injections in the first 6 months , compared to 6 injections in the vibrant study . the binding affinity of vegf for this drug is higher than for ranibizumab and bevacizumab . aflibercept displays a prolonged vegf inhibition in comparison with the other vegf - antagonists ranibizumab and bevacizumab in retinal pigment epithelium / choroid organ cultures . aflibercept also demonstrates better safety than bevacizumab in vitro associated with mitochondria exocytosis . in a randomized controlled trial , the authors concluded that aflibercept was more effective than bevacizumab for visual improvement in diabetic patients with poor baseline vision , but comparable efficacy in both pharmaceutical agents for better baseline vision . both medications showed similar safety profiles and injection number during one - year follow - up . to our knowledge , there is no publication comparing clinical outcome of aflibercept and bevacizumab for patients with macular edema secondary to brvo . in the present study , aflibercept had comparable efficacy , injection number , and safety as bevacizumab for patients with macular edema associated with brvo . a large prospective randomized study can further confirm the difference to treat macular edema in brvo in longer follow - up period . in summary , intravitreal aflibercept and bevacizumab had similar efficacy and duration of treatment for macular edema associated with brvo during 12-month period .
fifty - two eyes of 52 patients with treatment - nave macular edema associated with perfused branch retinal vein occlusion were retrospectively reviewed . 
 twenty - seven cases received prn intravitreal bevacizumab , and 25 cases were treated by prn intravitreal aflibercept with monthly follow - ups for 12 months . 
 both aflibercept and bevacizumab were effective in reduction of macular thickness and improvement of visual acuity for the participants . 
 both antivascular endothelial growth factor agents had similar efficacy and duration of treatment for these eyes with macular edema secondary to branch retinal vein occlusion during a 12-month period . 
 no serious systemic or ocular adverse events were reported .