***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: Objective To compare the clinical effectiveness and safety of 5-monthly fixed dosing vs pro-re-nata ( PRN ) Ozurdex treatment in patients with refractory diabetic macular oedema ( DMO ) . Design Prospect i ve , multicentre , r and omized active-controlled non-inferiority clinical trial . Participants Participants were 100 patients who attended Medical Retina Clinics for management of centre-involving refractory DMO . Interventions Participants were r and omized 1 : 1 to either 5-monthly fixed dosing or optical coherence tomography (OCT)-guided PRN regimen of Ozurdex therapy for DMO . Data were collected on best-corrected visual acuity ( BCVA ) , patient-reported outcome measures ( PROM ) , macular thickness and morphology , diabetic retinopathy status , number of injections and adverse events from baseline for a period of 12 months . Main outcome measures The primary outcome was the difference between arms in change in BCVA from baseline to 12 months . The prespecified non-inferiority margin was five ETDRS letters . Key secondary outcomes included change in PROM scores , change in macular thickness , change in retinopathy and macular morphology , and safety profile . Results The mean change in BCVA was + 1.48 ( SD 14.8 ) in the fixed arm vs −0.17 ( SD 13.1 ) in the PRN arm , with adjusted effect estimate + 0.97 , 90 % confidence interval ( −4.01 , + 5.95 ) , P=0.02 ( per protocol analysis ) . The conclusions of the ITT analysis were primarily supportive , −0.34 ( −5.49 , 4.81 ) P=0.07 , but sensitive to an alternative assumption on missing data , + 0.28 ( −4.72 , 5.27 ) P=0.04 . Conclusions The mean change in BCVA with 5-monthly fixed dosing of Ozurdex was non-inferior to OCT-guided PRN Ozurdex therapy for refractory DMO based on a per protocol analysis OBJECTIVE To report exp and ed 2-year follow-up of a previously reported r and omized trial evaluating intravitreal 0.5 mg ranibizumab or 4 mg triamcinolone combined with focal/grid laser compared with focal/grid laser alone for treatment of diabetic macular edema ( DME ) . DESIGN Multicenter , r and omized clinical trial . PARTICIPANTS A total of 854 study eyes of 691 participants with visual acuity of 20/32 to 20/320 ( approximate Snellen equivalent ) and DME involving the fovea . METHODS Continuation of procedures previously reported for the r and omized trial . MAIN OUTCOME MEASURES Best-corrected visual acuity and safety at the 2-year visit . RESULTS At the 2-year visit , compared with the sham + prompt laser group , the mean change in the visual acuity letter score from baseline was 3.7 letters greater in the ranibizumab + prompt laser group ( 95 % confidence interval adjusted for multiple comparisons [ aCI ] , -0.4 to + 7.7 ) , 5.8 letters greater in the ranibizumab + deferred laser group ( 95 % aCI , + 1.9 to + 9.8 ) , and 1.5 letters worse in the triamcinolone + prompt laser group ( 95 % aCI , -5.5 to + 2.4 ) . After the 1- to 2-year visit in the ranibizumab + prompt or deferred laser groups , the median numbers of injections were 2 and 3 ( potential maximum of 13 ) , respectively . At the 2-year visit , the percentages of eyes with central subfield thickness ≥250 μm were 59 % in the sham + prompt laser group , 43 % in the ranibizumab + prompt laser group , 42 % in the ranibizumab + deferred laser group , and 52 % in the triamcinolone + prompt laser group . No systemic events attributable to study treatment were apparent . Three eyes in 3 ( 0.8 % ) of 375 participants had injection-related endophthalmitis in the ranibizumab groups , whereas elevated intraocular pressure and cataract surgery were more frequent in the triamcinolone + prompt laser group . CONCLUSIONS The exp and ed 2-year results reported are similar to results published previously and reinforce the conclusions originally reported : Ranibizumab should be considered for patients with DME and characteristics similar to those of the cohort in this clinical trial , including vision impairment with DME involving the center of the macula OBJECTIVE Anti-vascular endothelial growth factor therapies have revolutionized the treatment of clinical ly significant diabetic macular edema ( CSDME ) ; yet these agents are expensive , and whether they are cost-effective is unclear . The purpose of this study is to determine the most cost-effective treatment option for patients with newly diagnosed CSDME :  focal laser photocoagulation alone ( L ) , focal laser plus intravitreal ranibizumab ( L+R ) , focal laser plus intravitreal bevacizumab ( L+B ) , or focal laser plus intravitreal triamcinolone ( L+T ) injections . DESIGN Cost-effectiveness analysis . PARTICIPANTS Hypothetical cohort of 57-year-old patients with newly diagnosed CSDME . METHODS By using a Markov model with a 25-year time horizon , we compared the incremental cost-effectiveness of treating patients with newly diagnosed CSDME using L , L+R , L+B , or L+T. Data came from the DRCRnet r and omized controlled trial , the Medicare fee schedule , and the medical literature . MAIN OUTCOME MEASURES Costs , quality -adjusted life years ( QALYs ) , and incremental costs per QALY gained . RESULTS Compared with L , the incremental cost-effectiveness of L+R and L+B was $ 89903/QALY and $ 11138/QALY , respectively . L+T was dominated by L. A probabilistic sensitivity analysis demonstrated that , at a willingness to pay ( WTP ) of $ 50000/QALY , L was approximately 70 % likely to be the preferred therapy over L+R and L+T. However , at a WTP of $ 100000/QALY , more than 90 % of the time , L+R therapy was the preferred therapy compared with L and L+T. In the probabilistic sensitivity analysis , L+B was found to be the preferred therapy over L and L+T for any WTP value > $ 10000/QALY . Sensitivity analyses revealed that the annual risk of cerebrovascular accident would have to be at least 1.5 % higher with L+B than with L+R for L+R to be the preferred treatment . In another sensitivity analysis , if patients require < 8 injections per year over the remainder of the 25-year time horizon , L+B would cost < $ 100000/QALY , whereas L+R would be cost-effective at a WTP of $ 100000/QALY if patients require fewer than 0.45 injections per year after year 2 . CONCLUSIONS With bevacizumab and ranibizumab assumed to have equivalent effectiveness and similar safety profiles when used in the management of CSDME , bevacizumab therapy confers the greatest value among the different treatment options for CSDME . FINANCIAL DISCLOSURE(S ) The author(s ) have no proprietary or commercial interest in any material s discussed in this article PURPOSE To provide 2-year results comparing anti-vascular endothelial growth factor ( VEGF ) agents for center-involved diabetic macular edema ( DME ) using a st and ardized follow-up and retreatment regimen . DESIGN R and omized clinical trial . PARTICIPANTS Six hundred sixty participants with visual acuity ( VA ) impairment from DME . METHODS R and omization to 2.0-mg aflibercept , 1.25-mg repackaged ( compounded ) bevacizumab , or 0.3-mg ranibizumab intravitreous injections performed up to monthly using a protocol -specific follow-up and retreatment regimen . Focal/grid laser photocoagulation was added after 6 months if DME persisted . Visits occurred every 4 weeks during year 1 and were extended up to every 4 months thereafter when VA and macular thickness were stable . MAIN OUTCOME MEASURES Change in VA , adverse events , and retreatment frequency . RESULTS Median numbers of injections were 5 , 6 , and 6 in year 2 and 15 , 16 , and 15 over 2 years in the aflibercept , bevacizumab , and ranibizumab groups , respectively ( global P = 0.08 ) . Focal/grid laser photocoagulation was administered in 41 % , 64 % , and 52 % , respectively ( aflibercept vs. bevacizumab , P < 0.001 ; aflibercept vs. ranibizumab , P = 0.04 ; bevacizumab vs. ranibizumab , P = 0.01 ) . At 2 years , mean VA improved by 12.8 , 10.0 , and 12.3 letters , respectively . Treatment group differences varied by baseline VA ( P = 0.02 for interaction ) . With worse baseline VA ( 20/50 to 20/320 ) , mean improvement was 18.1 , 13.3 , and 16.1 letters , respectively ( aflibercept vs. bevacizumab , P = 0.02 ; aflibercept vs. ranibizumab , P = 0.18 ; ranibizumab vs. bevacizumab , P = 0.18 ) . With better baseline VA ( 20/32 to 20/40 ) , mean improvement was 7.8 , 6.8 , and 8.6 letters , respectively ( P > 0.10 , for pairwise comparisons ) . Anti-Platelet Trialists ' Collaboration ( APTC ) events occurred in 5 % with aflibercept , 8 % with bevacizumab , and 12 % with ranibizumab ( global P = 0.047 ; aflibercept vs. bevacizumab , P = 0.34 ; aflibercept vs. ranibizumab , P = 0.047 ; ranibizumab vs. bevacizumab , P = 0.20 ; global P = 0.09 adjusted for potential confounders ) . CONCLUSIONS All 3 anti-VEGF groups showed VA improvement from baseline to 2 years with a decreased number of injections in year 2 . Visual acuity outcomes were similar for eyes with better baseline VA . Among eyes with worse baseline VA , aflibercept had superior 2-year VA outcomes compared with bevacizumab , but superiority of aflibercept over ranibizumab , noted at 1 year , was no longer identified . Higher APTC event rates with ranibizumab over 2 years warrants continued evaluation in future trials Purpose : To determine safety and efficacy of intravitreal triamcinolone acetonide ( IVTA ) for refractory clinical ly significant diabetic macular edema ( DME ) . Design : Prospect i ve , r and omized , dose-escalation pilot study comparing single injection of 2 mg versus 4 mg doses of IVTA . Methods : Inclusion criteria included clinical ly significant DME persisting ≥3 months after maximal laser treatment and visual acuity ≤20/40 . Best-corrected ETDRS vision , intraocular pressure , presence of DME , and fluorescein angiography ( FA ) were evaluated at 3 months and 6 months after injection . Results : Mean change in visual acuity at 3 months compared to baseline was 7.1 letters ( P = 0.01 ) in the 2 mg group and 12.5 letters in the 4 mg group ( P < 0.0001 ) . However , there was not a significant difference in visual improvement between the 2 mg and 4 mg dose groups ( P = 0.11 ) . Vision improved > 15 letters at 3 months in 23 % ( 3/13 ) of 2 mg group and in 33 % ( 5/15 ) of 4 mg group ( P = 0.69 ) , and 0 % ( 0/11 ) and 21 % ( 3/14 ) at 6 months , respectively ( P = 0.23 ) . Visual improvement was more likely in cystoid-type DME than diffuse DME . Intraocular pressure rise of ≥10 mmHg occurred in 19 % ( 3/16 ) of 2 mg group and 41 % ( 7/17 ) of 4 mg group . Conclusions : Both doses of IVTA were well tolerated and had significant positive effects on refractory DME for short term . There were consistent trends throughout the study that suggest that a 4 mg IVTA may be more effective than a 2 mg dose . The benefit of IVTA was greater for cystoid-type DME OBJECTIVE To report the 3-year follow-up results within a previously reported r and omized trial evaluating prompt versus deferred ( for ≥24 weeks ) focal/grid laser treatment in eyes treated with intravitreal 0.5 mg ranibizumab for diabetic macular edema ( DME ) . DESIGN Multicenter , r and omized clin 
    Output:
    
Treatment with either intravitreal ranibizumab ( IVR ) or intravitreal bevacizumab ( IVB ) falls within acceptable cost-effectiveness thresholds in the diabetic macular oedema ( DMO ) population ; however , in the non-DMO population , the marginal benefit of IVR or IVB in relation to the marginal cost relative to laser does not justify their use .
Among the anti-vascular endothelial growth factor ( VEGF ) therapies , IVB appears more attractive from an economic point of view due to its lower cost .
Moreover , fluocinolone implants appear cost effective compared with sham implants , or when treating refractory DMO .