***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 To evaluate intravitreal aflibercept injections ( IAI ; also called VEGF Trap-Eye ) for patients with macular edema secondary to central retinal vein occlusion ( CRVO ) . DESIGN R and omized controlled trial . METHODS This multicenter study r and omized 189 patients ( 1 eye/patient ) with macular edema secondary to CRVO to receive 6 monthly injections of either 2 mg intravitreal aflibercept ( IAI 2Q4 ) ( n = 115 ) or sham ( n = 74 ) . From week 24 to week 52 , all patients received 2 mg intravitreal aflibercept as needed ( IAI 2Q4 + PRN and sham + IAI PRN ) according to retreatment criteria . The primary endpoint was the proportion of patients who gained ≥15 ETDRS letters from baseline at week 24 . Additional endpoints included visual , anatomic , and quality -of-life NEI VFQ-25 outcomes at weeks 24 and 52 . RESULTS At week 24 , 56.1 % of IAI 2Q4 patients gained ≥15 letters from baseline compared with 12.3 % of sham patients ( P < .001 ) . At week 52 , 55.3 % of IAI 2Q4 + PRN patients gained ≥15 letters compared with 30.1 % of sham + IAI PRN patients ( P < .001 ) . At week 52 , IAI 2Q4 + PRN patients gained a mean of 16.2 letters of vision vs 3.8 letters for sham + IAI PRN ( P < .001 ) . The most common adverse events for both groups were conjunctival hemorrhage , eye pain , reduced visual acuity , and increased intraocular pressure . CONCLUSIONS Monthly injections of 2 mg intravitreal aflibercept for patients with macular edema secondary to CRVO result ed in a statistically significant improvement in visual acuity at week 24 , which was largely maintained through week 52 with intravitreal aflibercept PRN dosing . Intravitreal aflibercept injection was generally well tolerated The introduction of anti-vascular endothelial growth factor ( anti-VEGF ) drugs to ophthalmology over the past 7 years has revolutionised the treatment of exudative age-related macular degeneration ( AMD ) and holds great promise for diabetic macular oedema , branch and central retinal vein occlusions , and retinopathy of prematurity . Each of the three available drugs ( pegaptanib , bevacizumab and ranibizumab ) was eagerly embraced by surgeons , but the subsequent clinical results have been mixed , and the regulatory hurdles , particularly those regarding off-label use of bevacizumab , have been challenging . Into this mix enters aflibercept ( VEGF Trap-eye ( VTE ) ; Eylea , Regeneron , Tarrytown , New York , USA ) , for which the US Food and Drug Administration granted approval for the treatment of subfoveal choroidal neovascularisation due to AMD on 18 November 2011 . In contrast to the antibody-based VEGF binding strategy used by ranibizumab and bevacizumab , the VTE incorporates the second binding domain of the VEGFR-1 receptor and the third domain of the VEGFR-2 receptor.1 By fusing these extracellular protein sequences to the Fc segment of a human IgG backbone , in a manner similar to the rheumatoid arthritis drug etanercept , developers have created a chimeric protein with a very high VEGF binding affinity ( Kd≈1 pM).2 Like ranibizumab and bevacizumab , the VTE binds all isomers of the VEGF-A family , and although the clinical significance of this is not yet known , it also binds VEGF-B and placental growth factor . The approval application draws on the strengths of two concurrent AMD trials : the VIEW 1 trial , which enrolled 1217 patients in North American centres , and the VIEW 2 trial , which enrolled 1240 patients in South American , European , Asian and Australian centres . Each trial r and omised patients among four treatment arms : monthly 0.5 mg VTE , monthly or bimonthly 2 mg VTE , and monthly Flaws in the design , conduct , analysis , and reporting of r and omised trials can cause the effect of an intervention to be underestimated or overestimated . The Cochrane Collaboration ’s tool for assessing risk of bias aims to make the process clearer and more OBJECTIVE To evaluate interobserver agreement between investigator and Reading Center classification of retinal vein occlusion . DESIGN The St and ard Care versus COrticosteroid in REtinal Vein Occlusion ( SCORE ) Study includes 2 multicenter phase 3 r and omized clinical trials evaluating the efficacy and safety of intravitreal triamcinolone : one involves participants with central retinal vein occlusion ( CRVO ) and one for participants with branch retinal vein occlusion ( BRVO ) . Eyes with hemiretinal vein occlusion ( HRVO ) were classified as BRVO . PARTICIPANTS A total of 682 SCORE Study participants , including 271 with CRVO and 411 with BRVO . METHODS Participants were enrolled in each trial on the basis of investigator classification of retinal vein occlusion . Definitions of CRVO , BRVO , and HRVO based on clinical findings were specified in the study protocol . At baseline , 7-field color stereoscopic fundus photographs of the study eye of each participant were forwarded to the University of Wisconsin Fundus Photograph Reading Center ( Reading Center ) for evaluation . MAIN OUTCOME MEASURES Percent agreement and kappa statistics comparing investigator and Reading Center classification of retinal vein occlusion type . RESULTS With HRVO categorized as BRVO ( consistent with the SCORE Study design ) , there was 98.0 % agreement between investigator and Reading Center classification ( 641/654 eyes ; kappa = 0.96 ; 95 % confidence interval , 0.94 - 0.98 ) . Disagreements were fairly evenly divided between classification of an eye as CRVO by the investigator and as BRVO by the Reading Center ( 7/13 disagreements ) and vice versa ( 6 disagreements ) . When all 3 disease categories ( CRVO , BRVO , and HRVO ) were compared , there was 92.2 % agreement ( 603/654 ; unweighted kappa = 0.86 ; 95 % confidence interval , 0.83 - 0.90 ) . Most disagreements ( 38/51 , or 74.5 % ) were between BRVO and HRVO , with 9 between CRVO and BRVO , and 4 between HRVO and CRVO . In univariate analyses , baseline factors significantly associated with disagreement include larger area of capillary loss and black race ; black race was the only significant factor in a multivariate analysis . CONCLUSIONS Investigator and Reading Center agreement was excellent in the SCORE Study ; disease classification would have been altered in only 13 eyes ( 2.0 % ) had Reading Center eligibility been required . Interobserver agreement was least for classification between BRVO and HRVO OBJECTIVE To investigate baseline factors associated with visual acuity and central retinal thickness outcomes in patients with macular edema secondary to retinal vein occlusion in the St and ard Care versus COrticosteroid for REtinal Vein Occlusion ( SCORE ) Study . DESIGN Two multicenter , r and omized clinical trials : one evaluating participants with central retinal vein occlusion ( CRVO ) and one evaluating participants with branch retinal vein occlusion ( BRVO ) . PARTICIPANTS Participants with follow-up data of 1 year or more , including 238 with CRVO and 367 with BRVO . METHODS Visual acuity was measured by the electronic Early Treatment Diabetic Retinopathy Study ( E-ETDRS ) method , and central retinal thickness  was measured by optical coherence tomography ( OCT ) . Regression analysis related these outcomes to 20 baseline measures . Multiple P values were adjusted to control the false discovery rate . MAIN OUTCOME MEASURES Outcome measures of visual acuity letter score included absolute change from baseline , a gain of ≥ 15 from baseline , and a loss of ≥ 15 from baseline . Outcome measures of center point thickness included absolute change from baseline , a measurement of ≤ 250 μm , and a measurement of ≥ 500 μm . Outcomes were assessed at 1 and 2 years . RESULTS For CRVO and BRVO , younger age was associated with improved visual acuity and central retinal thickness outcomes . For CRVO , triamcinolone treatment and less severe anatomic abnormalities of the retina ( center point thickness and areas of retinal hemorrhage , thickening , and fluorescein leakage ) were predictive of better visual acuity outcomes . For BRVO , no history of coronary artery disease was predictive of improved visual acuity outcomes . For center point thickness outcomes , shorter duration of macular edema was associated with improvement in both disease entities . For CRVO , higher baseline visual acuity letter score was predictive of favorable OCT outcomes . For BRVO , lower baseline visual acuity letter score , presence of dense macular hemorrhage , and no prior grid photocoagulation were predictive of favorable OCT outcomes . CONCLUSIONS Several factors were predictive of better visual acuity outcomes and more favorable OCT outcomes , including younger age and shorter duration of macular edema , respectively . These factors may assist clinicians in predicting disease course for patients with CRVO and BRVO OBJECTIVE To investigate the relationship between baseline center point retinal thickness measured by optical coherence tomography ( OCT ) and best-corrected visual acuity in eyes with macular edema associated with retinal vein occlusion and to investigate other factors associated with baseline visual acuity letter score . DESIGN The St and ard Care versus COrticosteroid for REtinal Vein Occlusion ( SCORE ) Study includes 2 multicenter , r and omized clinical trials : one evaluating participants with central retinal vein occlusion ( CRVO ) and the other evaluating participants with branch retinal vein occlusion ( BRVO ) . PARTICIPANTS After omitting 17 participants with missing or unreliable OCT measurements , analyses proceeded with 665 enrolled SCORE Study participants ( 665 eyes ) , including 262 with CRVO and 403 with BRVO . METHODS At baseline , center point thickness was measured by OCT ( Stratus OCT 3 [ n=663 ] and OCT2 [ n=2 ] ; Carl Zeiss Meditech , Dublin , CA ) , and visual acuity was measured by the electronic Early Treatment Diabetic Retinopathy Study ( E-ETDRS ) methodology . MAIN OUTCOME MEASURES Center point thickness and best-corrected E-ETDRS visual acuity letter score . RESULTS The correlation coefficient for the association between baseline OCT-measured center point thickness and best-corrected E-ETDRS visual acuity letter score is -0.27 ( 95 % confidence limit : -0.38 to -0.16 ) for participants in the CRVO trial and -0.28 ( 95 % confidence limit : -0.37 to -0.19 ) in the BRVO trial . Regression modeling estimated the following decrease in baseline visual acuity letter score for every 100-microm increase in OCT-measured center point thickness : 1.7 letters ( P=0.0007 ) for CRVO and 1.9 letters ( P<0.0001 ) for BRVO . On the basis of multivariate regression models , baseline factors significantly associated ( P<0.05 , after adjusting for multiple testing ) with baseline visual acuity letter score include age and duration of macular edema for CRVO participants and center point thickness and presence of cystoid spaces for BRVO participants . CONCLUSIONS The correlation between OCT-measured center point thickness and visual acuity letter score is modest . OCT-measured center point thickness represents a useful tool for the detection and monitoring of macular edema in retinal vein occlusion , but it can not reliably substitute for visual acuity measurements PURPOSE Assess the 12-month efficacy and safety of intraocular injections of 0.3 mg or 0.5 mg ranibizumab in patients with macular edema after central retinal vein occlusion ( CRVO ) . DESIGN Prospect i ve , r and omized , sham injection-controlled , double-masked , multicenter clinical trial . PARTICIPANTS We included 392 patients with macular edema after CRVO . METHODS Eligible patients were r and omized 1:1:1 to receive 6 monthly intraocular injections of 0.3 mg or 0.5 mg of ranibizumab or sham injections . After 6 months , all patients with BCVA ≤20/40 or central subfield thickness ≥250 μm could receive ranibizumab . MAIN OUTCOME MEASURES Mean change from baseline best-corrected visual acuity ( BCVA ) letter score at month 12 , additional parameters of visual function , central foveal thickness ( CFT ) , and other anatomic changes were assessed . RESULTS Mean ( 95 % confidence interval ) change from baseline BCVA letter score at month 12 was 13.9 ( 11.2 - 16.5 ) and 13.9 ( 11.5 - 16.4 ) in the 0.3 mg and 0.5 mg groups , respectively , and 7.3 ( 4.5 - 10.0 ) in the sh 
    Output:
    
Results for pegaptanib and dexamethasone were mixed .
Steroids were associated with cataract formation and increased intraocular pressure .
No overall increase in adverse events was found with bevacizumab , ranibizumab , aflibercept or pegaptanib compared with control .
There was no head-to-head evidence .
CONCLUSIONS AND IMPLICATION S OF KEY FINDINGS Bevacizumab , ranibizumab , aflibercept and triamcinolone appear to be effective in treating  macular oedema secondary to CRVO .