this retrospective study was approved by the institutional review board of yonsei university , seoul , south korea . all patient data were collected from the department of ophthalmology , severance hospital , and gangnam severance hospital . we reviewed the medical records of 38 eyes of 38 patients who were treated with the dex implant for intravitreal bevacizumab ( 1.25 mg/0.05 ml avastin ; genentech , south san francisco , ca , usa ) for refractory macular edema secondary to brvo that did not respond after at least two consecutive ibis between january 2012 and december 2014 . all subjects underwent a comprehensive ophthalmologic examination at the time of initial disease presentation and the beginning of the dex implant treatments , including initial fluorescein fundus angiography , best - corrected visual acuity ( bcva ) determinations , dilated fundus examinations , fundus photography , and spectral domain optical coherence tomography ( sd - oct ; spectralis oct ver . after the dex implant , bcva measurements , tonometry , slit - lamp biomicroscopy , a dilated fundus examination , and oct were repeated at the 2 month and 6 month follow - up visits . we designated patients who demonstrated an increase of 0.1 or more logarithm of the minimal angle of resolution ( logmar ) bcva as the responsive group , while the other patients were designated as the nonresponsive group at the 6-month follow - up visit . the inclusion criteria were as follows : ( 1 ) initially treated with two or more consecutive ibis , ( 2 ) refractory to ibi , no improvement or worsening visual acuity , < 150 m reduction in central subfield macular thickness ( csmt ) , and csmt > 300 m , and ( 3 ) followed - up for at least 6 months after dex implantation . the following were used as exclusion criteria : severe media opacity , previous vitreoretinal surgery , intraocular inflammation , and other disorders that may have inf luenced macular function ( e.g. , exudative age - related macular degeneration , proliferative diabetic retinopathy , and epiretinal membrane ) . patients with a visual acuity worse than 20 / 400 were also excluded . the csmt was defined as the mean retinal thickness of the 1 mm center , as described in the early treatment diabetic retinopathy study . choroidal thickness was measured by enhanced depth imaging oct , which was performed by positioning the objective lens of the spectralis oct scanner close enough in proximity to invert the image , as described in previous reports . central subfoveal choroidal thickness ( csct ) , defined as the vertical distance between the hyperreflective line of bruch 's membrane and the outermost hyperreflective line of the chorioscleral interface at the fovea , was measured manually using the built - in caliber . if it was difficult to identify the outer choroid in its entirety , we chose 10 points at which the chorioscleral interface could be identified easily and created a segmentation line . all image measurements were averaged and were performed by two independent observers ( khl and eck ) who were masked to the clinical information . serial comparisons of the mean bcva , csmt , and csct were performed using paired t - test . comparisons of the mean bcva , csmt , and , csct between the two subgroups ( responsive and nonresponsive ) were analyzed using the wilcoxon signed - rank test . all statistical analyses were performed using spss ver . 20.0 for windows ( ibm corp . , armonk serial comparisons of the mean bcva , csmt , and csct were performed using paired t - test . comparisons of the mean bcva , csmt , and , csct between the two subgroups ( responsive and nonresponsive ) were analyzed using the wilcoxon signed - rank test . all statistical analyses were performed using spss ver . 20.0 for windows ( ibm corp . , armonk , ny , usa ) . thirty - eight eyes from 38 patients were included in this study , which included 12 men and 26 women . twenty - five eyes ( 66% ) were phakic at the time of the dex implant . the duration of macular edema between initial presentation and dex implant was 22.45  19.53 months . the number of previous anti - vegf injections was 6.32  4.66 . the initial mean bcva at the time of disease presentation was 0.66  0.40 logmar , and the baseline mean bcva was 0.53  0.26 logmar at dex implantation . the baseline csmt and csct were 504.00  121.54 m and 237.46  92.21 m , respectively . previous grid and sector pan retinal photocoagulation were performed on 3 ( 8% ) and 7 ( 18% ) eyes , respectively ( table 1 ) . mean logmar bcva at 2 months after dex implantation significantly improved from 0.53  0.26 to 0.41  0.25 ( p < 0.01 ) . the amount of visual gain decreased at 6 months to 0.45  0.23 logmar , but it was still statistically significant compared to baseline ( p < 0.01 ) . both csmt and csct were decreased at 2 months after dex implantation from 504.00  121.54 m and 237.46  92.21 m to 293.21  74.17 m and 204.75  74.74 m , respectively ( both p < 0.001 ) . six months after dex implantation , csmt and csct were slightly increased to 427.28  119.57 m and 226.86  90.77 m , respectively . csmt was still significantly thinner than baseline values ( p = 0.002 ) , but csct was not ( p = 0.455 ) ( fig . low initial ( p = 0.025 ) and baseline logmar bcva values ( p = 0.028 ) were correlated with visual gain 2 months after dex implantation , but age , number of ibis , initial csmt , initial csct , and thickness change in csmt and csct were not significantly associated with visual change . twenty - two eyes ( 58% ) showed 0.1 or more logmar bcva improvement , while 16 eyes ( 42% ) showed no change in bcva or worsening bcva . we divided the patients into a responsive group and a nonresponsive group according to this criterion . in the responsive group , the mean initial and baseline logmar bcva were significantly higher than those in the nonresponsive group , 0.77  0.46 and 0.61  0.24 compared to 0.49  0.25 and 0.42  0.23 ( p = 0.049 and p = 0.019 ) , respectively . the duration of macular edema between symptom presentation and dex implantation for the responsive group was shorter than that of the nonresponsive group , 18.55  17.73 months for the responsive group and 27.81  16.90 months for the nonresponsive group ( p = 0.022 ) . the number of ibis before dex implantation was smaller in the responsive group ( 5.95  5.46 times ) than in the nonresponsive group ( 6.81  3.35 times ) , but the difference was not statistically significant ( p = 0.195 ) . age , sex , and previous laser treatment ( grid laser or sector pan retinal photocoagulation ) were not significantly different between the two groups ( table 2 ) . csmt and csct significantly improved 2 months after dex implantation in both the responsive and nonresponsive groups , but the amount of improvement decreased after 6 months . the mean csmt changes were 220.40  125.86 m and 199.69  153.70 m ( p = 0.012 and p = 0.101 ) , respectively , and the mean csct changes were 41.69  30.49 m and 24.93  24.41 m ( p = 0.005 and p = 0.552 ) . a notable increase in iop ( > 10 mmhg from baseline ) was noted in five eyes ( 13.1% ) , which were subsequently treated with topical antiglaucoma medication . two cases showed notable cataract progression and underwent cataract extraction 6 and 8 months after dex implantation . after a single dex implant , two eyes ( 5.26% ) needed no additional treatment due to complete resolution of macular edema , which was confirmed by oct , while the other eyes needed additional treatment such as ibi or the dex implant . mean logmar bcva at 2 months after dex implantation significantly improved from 0.53  0.26 to 0.41  0.25 ( p < 0.01 ) . the amount of visual gain decreased at 6 months to 0.45  0.23 logmar , but it was still statistically significant compared to baseline ( p < 0.01 ) . both csmt and csct were decreased at 2 months after dex implantation from 504.00  121.54 m and 237.46  92.21 m to 293.21  74.17 m and 204.75  74.74 m , respectively ( both p < 0.001 ) . six months after dex implantation , csmt and csct were slightly increased to 427.28  119.57 m and 226.86  90.77 m , respectively . csmt was still significantly thinner than baseline values ( p = 0.002 ) , but csct was not ( p = 0.455 ) ( fig . low initial ( p = 0.025 ) and baseline logmar bcva values ( p = 0.028 ) were correlated with visual gain 2 months after dex implantation , but age , number of ibis , initial csmt , initial csct , and thickness change in csmt and csct were not significantly associated with visual change . twenty - two eyes ( 58% ) showed 0.1 or more logmar bcva improvement , while 16 eyes ( 42% ) showed no change in bcva or worsening bcva . we divided the patients into a responsive group and a nonresponsive group according to this criterion . in the responsive group , the mean initial and baseline logmar bcva were significantly higher than those in the nonresponsive group , 0.77  0.46 and 0.61  0.24 compared to 0.49  0.25 and 0.42  0.23 ( p = 0.049 and p = 0.019 ) , respectively . the duration of macular edema between symptom presentation and dex implantation for the responsive group was shorter than that of the nonresponsive group , 18.55  17.73 months for the responsive group and 27.81  16.90 months for the nonresponsive group ( p = 0.022 ) . the number of ibis before dex implantation was smaller in the responsive group ( 5.95  5.46 times ) than in the nonresponsive group ( 6.81  3.35 times ) , but the difference was not statistically significant ( p = 0.195 ) . age , sex , and previous laser treatment ( grid laser or sector pan retinal photocoagulation ) were not significantly different between the two groups ( table 2 ) . csmt and csct significantly improved 2 months after dex implantation in both the responsive and nonresponsive groups , but the amount of improvement decreased after 6 months . the mean csmt changes were 220.40  125.86 m and 199.69  153.70 m ( p = 0.012 and p = 0.101 ) , respectively , and the mean csct changes were 41.69  30.49 m and 24.93  24.41 m ( p = 0.005 and p = 0.552 ) . a notable increase in iop ( > 10 mmhg from baseline ) was noted in five eyes ( 13.1% ) , which were subsequently treated with topical antiglaucoma medication . two cases showed notable cataract progression and underwent cataract extraction 6 and 8 months after dex implantation . after a single dex implant , two eyes ( 5.26% ) needed no additional treatment due to complete resolution of macular edema , which was confirmed by oct , while the other eyes needed additional treatment such as ibi or the dex implant . in the present study , a single dex implant was associated with significant improvement of visual acuity in ibi refractory macular edema attributable to brvo . the mean bcva improved to 0.12 logmar at 2 months and 0.08 logmar at 6 months after the dex implant , but the efficacy was lower than previous studies that used a dex implant as a first treatment . however , considering that our patients had long - standing disease with multiple ibis or laser and clinical ibi refractory macular edema , there was still significant efficacy . improvement in bcva and anatomical change in macular edema likely resulted from the specific effect of dexamethasone , which has somewhat different effects from anti - vegf agents . the strong efficacy of anti - vegf treatment indicates that vegf plays an important role in the development of macular edema due to rvo . however , various cytokines , including interleukin-6   and interleukin-8 , can also be an effective treatment for macular edema in rvo . it is possible that the cases of macular edema in our study population refractory to intravitreal anti - vegf injection involved pathological changes unrelated to vegf . furthermore , steroid injection can reduce interleukin-6   and interleukin-8 , levels , which can not be modulated by anti - vegf therapy . however , only about half of the patients ( 22 eyes , 58% ) experienced a bcva improvement greater than 0.1 logmar . we separated patients into the nonresponsive group and responsive group according to visual gain of 0.1 or more logmar bcva . in the subgroup analysis , low bcva at the time of dex implant , low bcva at initial disease presentation , and shorter duration of macular edema a small number of patients with previous ibis also showed an association with dex implants , but this correlation was not statistically significant ( p = 0.195 ) . recently , a study reported that csct in eyes with rvo was significantly greater than in normal contralateral eyes , and that csct decreased significantly after dex implants . that study also reported that improved visual acuity correlated with a decrease in csct after the dex implant . these findings are consistent with our data showing that the dex implant decreased csct , but we did not find any significant correlation between csct or csmt and visual improvement . in our study , the safety profile was consistent with the results of the phase iii geneva clinical trial , showing no serious ocular or systemic adverse events during the follow - up period . the most frequent adverse event was an increase in iop , which required a topical iop - lowering medication ; however , this was only necessary in a small number of patients . previous studies have reported intravitreal use of steroids for refractory macular edema secondary to rvo . to the best of our knowledge , this is the first study to investigate the prognostic factors of dex implant for bevacizumab refractory macular edema secondary to brvo . however , there were some limitations to this study , specifically in the retrospective design . the number of anti - vegf injections before dex implantation was also not well controlled . in conclusion , dex implants were found to be beneficial for patients with ibi refractory macular edema secondary to brvo . at 2 months after implantation , patients gained a mean 0.12 logmar bcva and demonstrated a marked reduction in macular edema that lasted for up to 6 months . moreover , about half of the patients showed a greater than 0.1 logmar bcva gain , with a mean of 0.20  0.13 logmar bcva improvement , especially in patients with low initial baseline bcva and a shorter duration of macular edema . in addition to a relatively convenient dosing schedule , longer drug action period , and low cost with minimal complications , our study suggests that dex implants can be a valid treatment for ibi refractory macular edema secondary to brvo . further studies that involve long - term results of dex implants for ibi refractory macular edema , together with comparisons of other treatment options with large populations , are therefore warranted to determine optimal treatment approaches .
purposeto evaluate the prognostic factors and outcomes of dexamethasone intravitreal implant ( dex implant ) for intravitreal bevacizumab refractory macular edema secondary to branch retinal vein occlusion ( brvo).methodsthis was a retrospective , interventional case series . 
 medical records were reviewed , and a total of 38 eyes that were treated with dex implant for macular edema secondary to brvo that did not respond to at least two consecutive intravitreal bevacizumab injections ( ibis ) were included . 
 best - corrected visual acuity ( bcva ) , central subfield macular thickness , and central subfoveal choroidal thickness were evaluated at baseline , 2 months , and 6 months after dex implantation.resultspatients had undergone an average of 6.32  4.66 prior ibi treatments . 
 the average bcva improved from 0.53  0.26 to 0.41  0.25 and 0.44  0.23 logarithm of the minimal angle of resolution ( logmar ) at 2 and 6 months , respectively ( p < 0.001 ) . the average central subfield macular thickness was 504.00  121.54 m at baseline and changed to 293.21  74.17 m and 427.28  119.57 m at 2 and 6 months , respectively ( p < 0.001 and p = 0.002 ) . 
 average central subfoveal choroidal thickness was 237.46  92.21 m at baseline and changed to 204.75  74.74 m and 226.86  90.77 m at 2 and 6 months , respectively ( p < 0.001 and p = 0.455 ) . 
 twenty - two eyes ( 58% ) gained 0.1 logmar at 2 months , while 16 eyes showed no improvement . 
 low bcva at symptom presentation , low baseline bcva , and shorter duration of macular edema were correlated with increased bcva after treatment.conclusionsthe dex implant improves functional and anatomical outcomes for up to 6 months in about half of the patients treated with ibi refractory macular edema secondary to brvo , particularly in patients with low initial and baseline bcva .