***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 the effect of three intravitreal injections of bevacizumab ( IVB ) alone or combined with triamcinolone ( IVT ) in the first injection for treatment of refractory diabetic macular edema ( DME ) . Methods In this prospect i ve , placebo-controlled , r and omized clinical trial , 115 eyes of 101 patients with refractory DME were included . Subjects were r and omly assigned to one of the three study arms : 1 ) three injections of IVB ( 1.25 mg/0.05 ml ) at 6-week intervals , 2 ) combined IVB and IVT ( 1.25 mg/0.05 ml and 2 mg/0.05 ml respectively ) followed by two injections of IVB at 6-week intervals , and 3 ) sham injection ( control group ) . The primary outcome measure was change in central macular thickness ( CMT ) . Secondary outcome measures were change in best-corrected logMAR visual acuity ( BCVA ) and incidence of potential adverse events . Results Central macular thickness was reduced significantly in both the IVB and IVB/IVT groups . At week 24 , CMT change compared to the baseline was −95.7 μm ( 95 % CI , −172.2 to −19.26 ) in the IVB group , −92.1 μm ( 95 % CI , −154.4 to −29.7 ) in the IVB/IVT group , and 34.9 μm ( 95 % CI , 7.9 to 61.9 ) in the control group . There was a significant difference between the IVB and control groups ( P = 0.012 ) and between the IVB/IVT and control groups ( P = 0.022 ) . Improvement of BCVA was initiated at weeks 6 and 12 in the IVB/IVT and IVB groups respectively . In terms of BCVA change compared to the baseline at 24 weeks , the differences between the IVB and control groups ( P = 0.01 ) and also between the IVB/IVT and control groups ( P = 0.006 ) were significant . No significant differences were detected in the changes of CMT and BCVA between the IVB and IVB/IVT groups ( P = 0.99 ) . Anterior chamber reaction was noticed in eight ( 19.5 % ) and seven ( 18.9 % ) eyes respectively in the IVB and IVB/IVT groups the day after injection , and it resolved with no sequel . Elevation of IOP occurred in three eyes ( 8.1 % ) in the IVB/IVT group . Conclusion Three consecutive intravitreal injections of bevacizumab had a beneficial effect on refractory DME in terms of CMT reduction and BCVA improvement . Addition of triamcinolone in the first injection seemed to induce earlier visual improvement ; however , it did not show any significant additive effect later during follow-up OBJECTIVE To evaluate the safety and efficacy of intravitreal ranibizumab in a large population of subjects with neovascular age-related macular degeneration ( AMD ) . DESIGN Twelve-month r and omized ( cohort 1 ) or open-label ( cohort 2 ) multicenter clinical trial . PARTICIPANTS A total of 4300 subjects with angiographically determined subfoveal choroidal neovascularization ( CNV ) secondary to AMD . METHODS Cohort 1 subjects were r and omized 1:1 to receive 0.3 mg ( n = 1169 ) or 0.5 mg ( n = 1209 ) intravitreal ranibizumab for 3 monthly loading doses . Dose groups were stratified by AMD treatment history ( treatment-naïve vs. previously treated ) . Cohort 1 subjects were retreated on the basis of optical coherence tomography ( OCT ) or visual acuity ( VA ) criteria . Cohort 2 subjects ( n = 1922 ) received an initial intravitreal dose of 0.5 mg ranibizumab and were retreated at physician discretion . Safety was evaluated at all visits . MAIN OUTCOME MEASURES Safety outcomes included the incidence of ocular and nonocular adverse events ( AEs ) and serious adverse events ( SAEs ) . Efficacy outcomes included changes in best-corrected VA over time . RESULTS Some 81.7 % of cohort 1 subjects and 49.9 % of cohort 2 subjects completed the 12-month study . The average total number of ranibizumab injections was 4.9 for cohort 1 and 3.6 for cohort 2 . The incidence of vascular and nonvascular deaths during the 12-month study was 0.9 % and 0.7 % in the cohort 1 0.3 mg group , 0.8 % and 1.5 % in the cohort 1 0.5 mg group , and 0.7 % and 0.9 % in cohort 2 , respectively . The incidence of death due to unknown cause was 0.1 % in both cohort 1 dose groups and cohort 2 . The number of vascular deaths and deaths due to unknown cause did not differ across cohorts or dose groups . Stroke rates were 0.7 % , 1.2 % , and 0.6 % in the 0.3 mg and 0.5 mg groups and cohort 2 , respectively . At month 12 , cohort 1 treatment-naïve subjects had gained an average of 0.5 ( 0.3 mg ) and 2.3 ( 0.5 mg ) VA letters and previously treated subjects had gained 1.7 ( 0.3 mg ) and 2.3 ( 0.5 mg ) VA letters . CONCLUSIONS Intravitreal ranibizumab was safe and well tolerated in a large population of subjects with neovascular AMD . Ranibizumab had a beneficial effect on VA . Future investigations will seek to establish optimal dosing regimens for persons with neovascular AMD . FINANCIAL DISCLOSURE(S ) Proprietary or commercial disclosure may be found after the references PURPOSE To compare the results of intravitreal bevacizumab ( IVB ) injection alone or in combination with intravitreal triamcinolone acetonide ( IVT ) versus macular laser photocoagulation ( MPC ) as a primary treatment of diabetic macular edema ( DME ) . DESIGN R and omized 3-arm clinical trial . PARTICIPANTS A total of 150 eyes of 129 patients with clinical ly significant DME and no previous treatment . METHODS The eyes were r and omly assigned to 1 of the 3 study arms : the IVB group , patients who received 1.25 mg IVB ( 50 eyes ) ; the IVB/IVT group , patients who received 1.25 mg of IVB and 2 mg of IVT ( 50 eyes ) ; and the MPC group , patients who underwent focal or modified grid laser ( 50 eyes ) . Retreatment was performed at 12-week intervals whenever indicated . MAIN OUTCOME MEASURES Change in best-corrected visual acuity ( VA ) at week 24 . RESULTS VA changes among the groups were statistically significant at 6 ( P<0.001 ) and 24 ( P = 0.012 ) weeks . The significant treatment effect was demonstrated in the IVB group at all follow-up visits and in the IVB/IVT group at 6 and 12 weeks . VA changes + /- st and ard deviation at 36 weeks were -0.28+/-0.25 , -0.04+/-0.33 , and + 0.01+/-0.27 logarithm of minimum angle of resolution in the IVB , IVB/IVT , and MPC groups , respectively ( P = 0.053 ) . Significant central macular thickness ( CMT ) reduction was observed in all groups only up to 6 weeks ; however , CMT changes were not significant among the groups in all visits . Overall , retreatment was required for 27 eyes up to 36 weeks ( 14 in the IVB group , 10 in the IVB/IVT group , and 3 in the MPC group ) . In the IVB group , in which a greater VA improvement was observed , only 1 injection was required in 72 % of the cases . VA improvement > 2 Snellen lines at 36 weeks was detected in 37 % , 25 % , and 14.8 % of patients in the IVB , IVB/IVT , and MPC groups , respectively . CONCLUSIONS Intravitreal bevacizumab injection in patients with DME yielded a better visual outcome at 24 weeks compared with macular photocoagulation . A change in CMT beyond the 6-week time point that corresponded to the vision change was not detected . No adjunctive effect of IVT was demonstrated . FINANCIAL DISCLOSURE(S ) The author(s ) have no proprietary or commercial interest in any material s discussed in this article OBJECTIVE The research ers sought to assess whether the widely used 1994 Cochrane Highly Sensitive Search Strategy ( HSSS ) for r and omized controlled trials ( RCTs ) in MEDLINE could be improved in terms of sensitivity , precision , or parsimony . METHODS A gold st and ard of 1,347 RCT records and a comparison group of 2,400 non-trials were r and omly selected from MEDLINE .  Terms occurring in at least 1 % of RCT records were identified . Fifty percent of the RCT and comparison group records were r and omly selected , and the ability of the terms to discriminate RCTs from non-trial records was determined using logistic regression . The best performing combinations of terms were tested on the remaining records and in MEDLINE . RESULTS The best discriminating term was " Clinical Trial " ( Publication Type ) . In years where the Cochrane assessment of MEDLINE records had taken place , the strategies identified few additional unindexed records of trials . In years where Cochrane assessment has yet to take place , " R and omized Controlled Trial " ( Publication Type ) proved highly sensitive and precise . Adding six more search terms identified further , unindexed trials at reasonable levels of precision and with sensitivity almost equal to the Cochrane HSSS . CONCLUSIONS Most reports of RCTs in MEDLINE can now be identified easily using " R and omized Controlled Trial " ( Publication Type ) . More sensitive search es can be achieved by a brief strategy , the Centre for Review s and Dissemination/Cochrane Highly Sensitive Search Strategy ( 2005 revision ) BACKGROUND Laser treatment for diabetic retinopathy is often associated with visual field reduction and other ocular side-effects . Our aim was to assess whether long-term lipid-lowering therapy with fenofibrate could reduce the progression of retinopathy and the need for laser treatment  in patients with type 2 diabetes mellitus . METHODS The Fenofibrate Intervention and Event Lowering in Diabetes ( FIELD ) study was a multinational r and omised trial of 9795 patients aged 50 - 75 years with type 2 diabetes mellitus . Eligible patients were r and omly assigned to receive fenofibrate 200 mg/day ( n=4895 ) or matching placebo ( n=4900 ) . At each clinic visit , information concerning laser treatment for diabetic retinopathy-a prespecified tertiary endpoint of the main study -was gathered . Adjudication by ophthalmologists masked to treatment allocation defined instances of laser treatment for macular oedema , proliferative retinopathy , or other eye conditions . In a sub study of 1012 patients , st and ardised retinal photography was done and photographs grade d with Early Treatment Diabetic Retinopathy Study ( ETDRS ) criteria to determine the cumulative incidence of diabetic retinopathy and its component lesions . Analyses were by intention to treat . This study is registered as an International St and ard R and omised Controlled Trial , number IS RCT N64783481 . FINDINGS  Laser treatment  was needed more frequently in participants with poorer glycaemic or blood pressure control than in those with good control of these factors , and in those with a greater burden of clinical microvascular disease , but the need for such treatment was not affected by plasma lipid concentrations . The requirement for first laser treatment for all retinopathy was significantly lower in the fenofibrate group than in the placebo group ( 164 [ 3.4 % ] patients on fenofibrate vs 238 [ 4.9 % ] on placebo ; hazard ratio [ HR ] 0.69 , 95 % CI 0.56 - 0.84 ; p=0.0002 ; absolute risk reduction 1.5 % [ 0.7 - 2.3 ] ) . In the ophthalmology sub study , the primary endpoint of 2-step progression of retinopathy grade did not differ significantly between the two groups overall ( 46 [ 9.6 % ] patients on fenofibrate vs 57 [ 12.3 % ] on placebo ; p=0.19 ) or in the subset of patients without pre-existing retinopathy ( 43 [ 11.4 % ] vs 43 [ 11.7 % ] ; p=0.87 ) . By contrast , in patients with pre-existing retinopathy , significantly fewer patients on fenofibrate had a 2-step progression than did those on placebo ( three [ 3.1 % ] patients vs 14 [ 14.6 % ] ; p=0.004 ) . An exploratory composite endpoint of 2-step progression of retinopathy grade , macular oedema , or laser treatments was significantly lower in the fenofibrate group than in the placebo group ( HR 0. 
    Output:
    
There was an increased rate of cataract development and raised intraocular pressure in eyes treated with anti-VEGF plus steroid versus anti-VEGF alone .
Patients were exposed to potential side effects of both these agents without reported additional benefit .
The majority of the evidence comes from studies of bevacizumab and triamcinolone used as primary therapy for DMO .
It is not known whether treatment response is different in eyes that are phakic and pseudophakic at baseline