***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 report the interim 34-week safety and efficacy results of a 3-year study to evaluate an investigational intravitreal fluocinolone acetonide ( FA ) implant in patients with noninfectious posterior uveitis . DESIGN Prospect i ve , dose-masked , dose-r and omized , historically controlled , multicenter trial in patients with unilateral or bilateral disease . PARTICIPANTS A total of 278 patients with recurrent noninfectious posterior uveitis were r and omized to receive a 0.59-mg ( n = 110 ) or 2.1-mg ( n = 168 ) implant . In patients with bilateral disease , the more severely affected eye received the implant . METHODS The implant was inserted surgically into the vitreous cavity through a pars plana incision . Follow-up visits were scheduled on day 2 , week 1 , and then every 4 to 6 weeks through 34 weeks after implantation . Systemic , periocular , and topical therapies were reduced as allowed by the clinical response . MAIN OUTCOME MEASURES The primary efficacy outcome was a comparison of the recurrence rate in the implanted eye from the 34 weeks before implantation to the 34 weeks after implantation . Visual acuity ( VA ) , need for adjunctive therapy , and safety also were assessed . RESULTS Combining both doses , the FA implant reduced the rate of recurrences from 51.4 % in the 34 weeks preceding implantation to 6.1 % postimplantation ( P<0.0001 ) in the study eyes . Comparatively , there was a significant increase in the recurrence rate in the fellow nonimplanted eyes from 20.3 % preimplantation to 42.0 % postimplantation ( P<0.0001 ) . Visual acuity was stabilized or improved in 87 % of implanted eyes and generally was associated with reductions in the area of macular hyperfluorescence . The percentage of eyes that required systemic medications , periocular injections , and topical corticosteroids decreased from 52.9 % , 63.0 % , and 35.7 % , respectively , preimplantation to 12.1 % , 2.2 % , and 16.5 % postimplantation ( P < or = 0.0001 in all cases ) . At week 34 , 51.1 % of implanted eyes required ocular antihypertensive drops , and 5.8 % underwent glaucoma filtering surgery . Lens opacity scores increased by > or = 2 grade s in 19.8 % of phakic implanted eyes , and 9.9 % required cataract surgery . There were no statistically significant differences in any of the parameters studied for the 0.59-mg implant , compared with the 2.1-mg implant . CONCLUSIONS The FA implant significantly reduced uveitis recurrences , improved VA , and decreased the need for adjunctive therapy in the studied patient population . The most common side effects included increased intraocular pressure and cataract progression Background The purpose of this study is to evaluate the ocular tolerability and efficacy of sirolimus administered as subconjunctival or intravitreal injections in patients with non-infectious uveitis .  Sirolimus as a Therapeutic Approach for Uveitis ( SAVE ) is a prospect i ve , r and omized , open-label , interventional study . Thirty patients were enrolled and r and omized in 1:1 ratio to receive either intravitreal injections of 352 μg sirolimus or subconjunctival injections of 1,320 μg at days 0 , 60 , and 120 , with primary endpoint at month 6 . Results At month 6 , all subjects with active uveitis at baseline showed reduction in vitreous haze of one or more steps . Forty percent of subjects showed reduction of two steps or more of vitreous haze ( four in each group ) , and 60 % showed a reduction of one-step vitreous haze ( seven in group 1 and five in group 2 ) . Changes in the inflammatory indices were statistically significant ( p < 0.05 ) in both study groups . Thirty percent of patients gained one or more lines of visual acuity , 20 % lost one or more lines , and 50 % maintained the same visual acuity . There were no statistically significant differences between the two study groups at month 6 . No serious adverse events were found to be related to the study drug . Conclusion Local administration of sirolimus , either intravitreally or subconjunctivally , appears to be safe and tolerable . No drug-related systemic adverse events or serious adverse events were noted . Sirolimus delivered as either an intravitreal or subconjunctival injection has demonstrated bioactivity as an immunomodulatory and corticosteroid-sparing agent in reducing vitreous haze and cells , improving visual acuity , and in decreasing the need for systemic corticosteroids 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 PURPOSE To evaluate the safety and possible efficacy of subconjunctival sirolimus for the treatment of chronic active anterior uveitis . DESIGN Prospect i ve , nonr and omized , open-label clinical trial . METHODS This single-center pilot trial enrolled 5 patients with chronic active anterior uveitis . The study drug was administered as a single subconjunctival injection of 30 μL ( 1320 μg ) sirolimus in the study eye at the baseline visit . Study visits were performed at baseline , at 2 weeks , at 4 weeks , and monthly until 4 months , and included a complete ophthalmic examination , review of systems , adverse event assessment at each visit , physical examination , and ancillary ophthalmic testing at some visits . The primary outcome measure was a 2-step reduction in the anterior chamber inflammation within 4 weeks of injection of the study drug . RESULTS There were 3 female and 2 male patients ; 4 patients had idiopathic anterior uveitis and 1 had psoriatic arthritis-associated anterior uveitis . Three of the 5 patients met the primary outcome criteria by showing at least a 2-step decrease in inflammation within 4 weeks ; 2 patients showed a 1-step decrease in inflammation within the same time frame . No recurrence was encountered during a 4-month follow-up . There were no serious adverse events . CONCLUSIONS Subconjunctival sirolimus appears to be well tolerated in this pilot trial and shows promise as a treatment for active inflammation in patients with chronic anterior uveitis . Larger studies are needed to assess its usefulness in uveitis PURPOSE To determine the efficacy and safety of repeated intravitreal and subconjunctival administrations of sirolimus in patients with noninfectious uveitis at 1 year in the Sirolimus as a Therapeutic Approach UVEitis ( SAVE ) Study . METHODS Open-label , prospect i ve , and r and omized interventional clinical trial in which 30 patients with noninfectious intermediate , posterior , or panuveitis were r and omized 1:1 to receive sirolimus 352-μg intravitreal or 1320-μg subconjunctival . Sirolimus was administered at days 0 , 60 , and 120 . At month 6 , all subjects were allowed to receive sirolimus at intervals greater than or equal to 2 months and until month 12 . Changes in vitreous haze ( VH ) , visual acuity ( VA ) , and retinal thickness at month 12 were compared with baseline . RESULTS Of patients with active uveitis at baseline ( n = 20 ) , 70 % showed greater than or equal to 2 steps reduction of VH at month 12 ( P < 0.05 ) , 88 % ( n = 7 ) of patients with inactive uveitis at baseline showed either no change or reduction of VH to no haze , 36 % ( n = 10 ) of all patients ( n = 28 ) gained greater than or equal to one line of VA , 21 % ( n = 6 ) lost greater than or equal to 1 line , and 43 % ( n = 12 ) showed no change . At the end of 1 year , no statistical differences in efficacy were found between intravitreal and subconjunctival groups . No serious adverse events were determined to be secondary to sirolimus . CONCLUSIONS Repeated subconjunctival/intravitreal injections of sirolimus appear to be tolerated by patients with noninfectious uveitis over 12 months . Results from the index study suggest that sirolimus may provide benefits to patients with uveitis . Both intravitreal and subconjunctival routes demonstrate similar bioactivity/efficacy . The intravitreal route , however , was better tolerated . TRANSLATIONAL RELEVANCE The SAVE Study illustrates for the first time the application of local formulations of sirolimus in non-infectious intermediate , posterior , and pan-uveitis . Subconjunctival/Intravitreal sirolimus may help to control inflammation while offering better tolerability/safety profiles than systemic therapies , including immunosuppressants and corticosteroids Aims : To determine the efficacy of sirolimus in the treatment of patients with severe non-infectious uveitis . Methods : Eight patients with severe non-infectious uveitis were recruited to an open study . Inclusion criteria were limited to patients whose disease was not controlled with at least two or more separate steroid sparing immunosuppressants ( either because of unacceptable side effects or ineffectiveness of the drug ) or who required regular doses of corticosteroids either as high dose systemic or orbital floor injections in order to control their disease .  Intraocular inflammation , visual acuity , symptoms , corticosteroid burden , drug toxicity , and side effects were monitored . Results : Sirolimus therapy was effective in five of the eight patients , all of whom had their dose of corticosteroids reduced or discontinued . Treatment in three patients was considered a failure as it caused intolerable side effects and /or failed to control the uveitis . Side effects were common and were typically gastrointestinal or cutaneous in nature . The severity of symptoms was dose dependent in most cases and occurred at trough blood levels above 25 ng/ml . Conclusion : Sirolimus is an effective and potent immunosuppressive treatment in the majority of patients with non-infectious uveitis and can reduce the need for long term supplementary corticosteroid therapy . Further studies are required to establish the long term efficacy and safety of sirolimus alone or in combination with other steroid sparing immunosupressants PURPOSE Corticosteroids ( CS ) are the only approved drug class for treatment of noninfectious uveitis by the U.S. Food and Drug Administration . Serious side effects are associated with chronic use of systemic CS ; established guidelines recommend the use of steroid-sparing agents if control of uveitis can not be achieved with ≤ 10 mg/day of prednisone ( or equivalent ) within 3 months . This study evaluated the treatment patterns among physicians who routinely manage patients with noninfectious uveitis to determine how treatment guidelines are followed . DESIGN Cross-sectional , multicenter study conducted across the United States . PARTICIPANTS Sixty ophthalmologists and 3 rheumatologists were recruited using payer reimbursement International Classification of Diseases , Ninth Revision codes . METHODS Patient data were reported using a study -specific question naire . Physicians were also asked if they were aware of or used recommended treatment guidelines . MAIN OUTCOME MEASURES Uveitis treatment patterns were compared with guidelines . RESULTS Physicians managed a mean of 5555 patients ; patients with uveitis who required systemic CS treatment comprised approximately 5 % of each physician 's practice . A total of 580 patients with noninfectious uveitis were r and omly selected for analyses . Anterior uveitis requiring systemic therapy was diagnosed in 168 patients ( 29 % ) , intermediate uveitis was diagnosed in 140 patients ( 24 % ) , posterior uveitis was diagnosed in 150 patients ( 26 % ) , and panuveitis was diagnosed in 122 patients ( 21 % ) ; 199 patients ( 34 % ) had active disease . The mean time interval from the diagnosis of uveitis to the time of survey was 3.1 to 4.5 years . A systemic disorder was associated with uveitis in 16 % to 54 % of patients ; 57 % to 100 % of patients received systemic immunosuppressive therapy . In all , 360 of 580 patients ( 62 % ) received systemic CS , with a mean initial daily dose of 44 mg , tapered to 34 mg prednisone ( or equivalent ) as maintenance dose . Among physicians surveyed , 75 % did not use or were not aware of treatment guidelines for uveitis . CONCLUSIONS The study reveals that the majority of physicians surveyed are not familiar with or do not adhere to currently recommended guidelines for management of uveitis . High CS doses are used to maintain control of disease , and there is a low level of awareness of recommended guidelines to treat noninfectious uveitis . The finding underscores the need to place further emphasis on educating the medical community and reinforcing treatment guidelines to improve the care of patients with uveitis PURPOSE To determine if two different doses of intravitreal sirolimus , an mTOR inhibitor , can decrease inflammation and is safe in eyes with non-infectious posterior , intermediate , or panuveitis in the Sirolimus as a Therapeut 
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The CS-sparing effect of sirolimus was also well demonstrated .
Conclusion This review provided evidence that sirolimus is a promising treatment option for controlling inflammatory activity , improving visual acuity , and sparing CS use with minor adverse events for NIU