***TASK*** the task is to summarize an input biomedical literature in six sentences 
    ***INPUT*** the input is a biomedical literature 
    ***OUTPUT*** the output is the summary of an input biomedical literature in six sentences 
    ***DOCUMENTATION*** 
    ***EXAMPLES*** 
    Input: PURPOSE The role of vascular endothelial growth factor ( VEGF ) in diabetic macular edema ( DME ) was tested with ranibizumab , a specific antagonist of VEGF . DESIGN A nonr and omized clinical trial . METHODS Ten patients with chronic DME received intraocular injections of 0.5 mg of ranibizumab at baseline and at one , two , four , and six months . The primary outcome was change in foveal thickness between baseline and seven months , and the secondary outcome measures were changes from baseline in visual acuity and macular volume . RESULTS Mean values at baseline were 503 microm for foveal thickness , 9.22 mm3 for macular volume , and 28.1 letters ( 20/80 ) read on an Early Treatment Diabetic Retinopathy Study ( ETDRS ) visual acuity chart . At seven months ( one month after the fifth injection ) , the mean foveal thickness was 257 microm , which was a reduction of 246 microm ( 85 % of the excess foveal thickness present at baseline ; P = .005 by Wilcoxon signed-rank test for likelihood that this change is due to ranibizumab rather than chance ) . The macular volume was 7.47 mm3 , which was a reduction of 1.75 mm3 ( 77 % of the excess macular volume at baseline ; P = .009 ) . Mean visual acuity was 40.4 letters ( 20/40 ) , which was an improvement of 12.3 letters ( P = .005 ) . The injections were well-tolerated with no ocular or systemic adverse events . CONCLUSION Intraocular injections of ranibizumab significantly reduced foveal thickness and improved visual acuity in 10 patients with DME , which demonstrated that VEGF is an important therapeutic target for DME . A r and omized , controlled , double-masked trial is needed to test whether intraocular injections of ranibizumab provide long-term benefit to patients with DME Purpose To report 1-year visual and anatomic outcomes of a prospect i ve , double-masked r and omised clinical trial comparing bevacizumab with ranibizumab for the treatment of age-related macular degeneration ( AMD ) . Methods Patients who met inclusion criteria were r and omised 2 : 1 to bevacizumab or ranibizumab .  All subjects and investigators ( except for the pharmacist responsible for study assignments ) were masked to treatment arms . Visual acuity was taken on Early Treatment Diabetic Retinopathy Study chart . Patients were given either bevacizumab or ranibizumab every month for the first 3 months , followed by an optical coherence tomography-guided , variable-dosing treatment schedule . Main outcomes measured included visual acuity , foveal thickness , and total number of injections over the 1-year treatment period . Results In total , 15 patients received bevacizumab and 7 patients received ranibizumab .  The average pre-operative visual acuity was 34.9 letters in the bevacizumab group , and 32.7 letters in the ranibizumab group . At 1-year follow-up , mean vision was 42.5 letters in the bevacizumab group , and 39.0 letters in the ranibizumab group . Two-tailed t-test failed to showed statistical significance between the two groups ( P=0.5 ) . Patients in the bevacizumab group underwent an average of eight injections , whereas patients in the ranibizumab group underwent a mean of four injections ( P=0.001 ) . Conclusion The 1-year outcomes of a prospect i ve , double-masked , r and omised clinical trial comparing bevacizumab with ranibizumab failed to show a difference in visual and anatomic outcomes between the two treatments for choroidal neovascularisation in AMD . Total injections given over the treatment period were significantly different between the two groups . Further studies with larger sample sizes are warranted OBJECTIVE To describe effects of ranibizumab and bevacizumab when administered monthly or as needed for 2 years and to describe the impact of switching to as-needed treatment after 1 year of monthly treatment . DESIGN Multicenter , r and omized clinical trial . PARTICIPANTS Patients ( n = 1107 ) who were followed up during year 2 among 1185 patients with neovascular age-related macular degeneration who were enrolled in the clinical trial . INTERVENTIONS At enrollment , patients were assigned to 4 treatment groups defined by drug ( ranibizumab or bevacizumab ) and dosing regimen ( monthly or as needed ) . At 1 year , patients initially assigned to monthly treatment were reassigned r and omly to monthly or as-needed treatment , without changing the drug assignment . MAIN OUTCOME MEASURES Mean change in visual acuity . RESULTS Among patients following the same regimen for 2 years , mean gain in visual acuity was similar for both drugs ( bevacizumab-ranibizumab difference , -1.4 letters ; 95 % confidence interval [ CI ] , -3.7 to 0.8 ; P = 0.21 ) . Mean gain was greater for monthly than for as-needed treatment ( difference , -2.4 letters ; 95 % CI , -4.8 to -0.1 ; P = 0.046 ) . The proportion without fluid ranged from 13.9 % in the bevacizumab-as-needed group to 45.5 % in the ranibizumab monthly group ( drug , P = 0.0003 ; regimen , P < 0.0001 ) . Switching from monthly to as-needed treatment result ed in greater mean decrease in vision during year 2 ( -2.2 letters ; P = 0.03 ) and a lower proportion without fluid ( -19 % ; P < 0.0001 ) . Rates of death and arteriothrombotic events were similar for both drugs ( P > 0.60 ) . The proportion of patients with 1 or more systemic serious adverse events was higher with bevacizumab than ranibizumab ( 39.9 % vs. 31.7 % ; adjusted risk ratio , 1.30 ; 95 % CI , 1.07 - 1.57 ; P = 0.009 ) . Most of the excess events have not been associated previously with systemic therapy targeting vascular endothelial growth factor ( VEGF ) . CONCLUSIONS Ranibizumab and bevacizumab had similar effects on visual acuity over a 2-year period . Treatment as needed result ed in less gain in visual acuity , whether instituted at enrollment or after 1 year of monthly treatment . There were no differences between drugs in rates of death or arteriothrombotic events . The interpretation of the persistence of higher rates of serious adverse events with bevacizumab is uncertain because of the lack of specificity to conditions associated with inhibition of VEGF PURPOSE To report the findings at 1 year of a study comparing repeated intravitreal bevacizumab ( ivB ) and modified Early Treatment of Diabetic Retinopathy Study ( ETDRS ) macular laser therapy ( MLT ) in patients with persistent clinical ly significant diabetic macular edema ( CSME ) . DESIGN Prospect i ve , r and omized , masked , single-center , 2-year , 2-arm clinical trial . PARTICIPANTS A total of 80 eyes of 80 patients with center-involving CSME and at least 1 prior MLT . METHODS Subjects were r and omized to either ivB ( 6 weekly ; minimum of 3 injections and maximum of 9 injections in the first 12 months ) or MLT ( 4 monthly ; minimum of 1 treatment and maximum of 4 treatments in the first 12 months ) . MAIN OUTCOME MEASURES The primary end point was the difference in ETDRS best-corrected visual acuity ( BCVA ) at 12 months between the bevacizumab and laser arms . RESULTS The baseline mean ETDRS BCVA was 55.7+/-9.7 ( range 34 - 69 ) in the bevacizumab group and 54.6+/-8.6 ( range 36 - 68 ) in the laser arm . The mean ETDRS BCVA at 12 months was 61.3+/-10.4 ( range 34 - 79 ) in the bevacizumab group and 50.0+/-16.6 ( range 8 - 76 ) in the laser arm ( P = 0.0006 ) . Furthermore , the bevacizumab group gained a median of 8 ETDRS letters , whereas the laser group lost a median of 0.5 ETDRS letters ( P = 0.0002 ) . The odds of gaining > or = 10 ETDRS letters over 12 months were 5.1 times greater in the bevacizumab group than in the laser group ( adjusted odds ratio , 5.1 ; 95 % confidence interval , 1.3 - 19.7 ; P = 0.019 ) . At 12 months , central macular thickness decreased from 507+/-145 microm ( range 281 - 900 microm ) at baseline to 378+/-134 microm ( range 167 - 699 microm ) ( P<0.001 ) in the ivB group , whereas it decreased to a lesser extent in the laser group , from 481+/-121 microm ( range 279 - 844 microm ) to 413+/-135 microm ( range 170 - 708 microm ) ( P = 0.02 ) . The median number of injections was 9 ( interquartile range [ IQR ] 8 - 9 ) in the ivB group , and the median number of laser treatments was 3 ( IQR 2 - 4 ) in the MLT group . CONCLUSIONS The study provides evidence to support the use of bevacizumab in patients with center-involving CSME without advanced macular ischemia OBJECTIVES To compare ranibizumab with focal/grid laser or a combination of both in diabetic macular edema ( DME ) . DESIGN Prospect i ve , r and omized , interventional , multicenter clinical trial . PARTICIPANTS A total of 126 patients with DME . METHODS Subjects were r and omized 1:1:1 to receive 0.5 mg of ranibizumab at baseline and months 1 , 3 , and 5 ( group 1 , 42 patients ) , focal/grid laser photocoagulation at baseline and month 3 if needed ( group 2 , 42 patients ) , or a combination of 0.5 mg of ranibizumab and focal/grid laser at baseline and month 3 ( group 3 , 42 patients ) . MAIN OUTCOME MEASURES The primary end point was the change from baseline in best-corrected visual acuity ( BCVA ) at month 6 . RESULTS At month 6 , the mean gain in BCVA was significantly greater in group 1 ( + 7.24 letters , P = 0.01 , analysis of variance ) compared with group 2 ( -0.43 letters ) , and group 3 ( + 3.80 letters ) was not statistically different from groups 1 or 2 . For patients with data available at 6 months , improvement of 3 lines or more occurred in 8 of 37 ( 22 % ) in group 1 compared with 0 of 38 ( 0 % ) in group 2 ( P = 0.002 , Fisher exact test ) and 3 of 40 ( 8 % ) in group 3 . Excess foveal thickness was reduced by 50 % , 33 % , and 45 % in groups 1 , 2 , and 3 , respectively . CONCLUSIONS During a span of 6 months , ranibizumab injections by the current protocol had a significantly better visual outcome than focal/grid laser treatment in patients with DME PURPOSE To evaluate the efficacy and safety of ranibizumab administered monthly for three months and then quarterly in patients with subfoveal choroidal neovascularization ( CNV ) secondary to age-related macular degeneration ( AMD ) . DESIGN Phase IIIb , multicenter , r and omized , double-masked , sham injection-controlled trial in patients with predominantly or minimally classic or occult with no classic CNV lesions . METHODS Patients were r and omized 1:1:1 to 0.3 mg ranibizumab ( n = 60 ) , 0.5 mg ranibizumab ( n = 61 ) , or sham ( n = 63 ) treatment groups . The primary efficacy endpoint was mean change from baseline visual acuity ( VA ) at month 12 . RESULTS Mean changes from baseline VA at 12 months were -16.3 , -1.6 , and -0.2 letters for the sham , 0.3 mg , and 0.5 mg groups , respectively ( P < or = .0001 , each ranibizumab dose vs sham ) . Ranibizumab arrested CNV growth and reduced leakage from CNV . However , the treatment effect declined in the ranibizumab groups during quarterly dosing ( e.g. , at three months the mean changes from baseline VA had been gains of 2.9 and 4.3 letters for the 0.3 mg and 0.5 mg doses , respectively ) . Results of subgroups analyses of mean change from baseline VA at 1 
    Output:
    
Anti-VEGF mAbs did not significantly increase overall mortality , cardiovascular mortality , stroke , myocardial infa rct ion , VTEs , or hypertension .