THE OMAR STUDY Comparison of Ozurdex and Triamcinolone Acetonide for Refractory Cystoid Macular Edema in Retinal Vein Occlusion AHMET OZKOK, MD,* OMAR A. SALEH, MD,*† DOUGLAS K. SIGFORD, MD,* JAMES W. HEROMAN, MD,* SHLOMIT SCHAAL, MD, PHD* Purpose: To compare the risks and benefits of adding either intravitreal dexamethasone implant (DEX) or preservative-free triamcinolone acetonide (TA) to bevacizumab monotherapy in refractory cystoid macular edema due to retinal vein occlusion. Methods: This is a multicenter, comparative, interventional, retrospective study that included 74 patients who were initially treated with intravitreal bevacizumab and later received either DEX or TA for the treatment of recalcitrant cystoid macular edema due to retinal vein occlusion. Main outcomes were best-corrected visual acuity, central macular thickness, cost of therapy, frequency of intravitreal injections, and side effects. Results: Thirty-nine patients received TA and 35 patients received DEX injections. Groups were similar in age and gender distribution. Although the mean central macular thickness improved significantly for all groups (P , 0.0001), logMAR best-corrected visual acuity did not change significantly after steroid introduction (P = 0.06). Frequency of any intravitreal injection decreased significantly from 0.66 ± 0.18 to 0.26 ± 0.08 injections per month after initiation of steroids (P , 0.0001). This effect was greater in the DEX groups (P , 0.0001). Monthly cost decreased with TA but increased with DEX. Conclusion: Adding steroids improved anatomical outcome but did not affect final vision. Injection frequency decreased significantly after adding steroids, more so with DEX. There was no difference between TA and DEX regarding anatomical or functional outcomes or the incidence of side effects. RETINA 35:1393–1400, 2015

T

role of vasoproliferative and inflammatory mediators in the pathophysiology of RVO resulted in major paradigm shifts in the management of its complications. Recently published data from prospective randomized clinical trials have revolutionized the standard of care for patients with CME secondary to RVO by popularizing the use of intravitreal injections of vascular endothelial growth factor (anti-VEGF) agents and corticosteroids, which are not only effective and safe but also yield superior visual outcomes compared with the previous management paradigm.1–10 Randomized clinical trials, such as SCORE,1,2 CRUISE,3,4 BRAVO,5,10 GENEVA,8,9 and COPERNICUS6,7 evaluated intravitreal injections of anti-VEGF agents or corticosteroids for the treatment of macular edema secondary to RVO. In the randomized clinical trials, mean changes in bestcorrected visual acuity (BCVA) in letters at Month 12 in patients with branch retinal vein occlusion (BRVO)

he goals in the clinical management of retinal vein occlusion (RVO) are to treat its two major complications, namely, cystoid macular edema (CME) and retinal/iris neovascularization, and to improve or maintain patient visual acuity. Over the past few years, our improved understanding of the essential

From the *Department of Ophthalmology and Visual Sciences, University of Louisville, Louisville, Kentucky; and †Department of Ophthalmology, Jordan University of Science and Technology, Irbid, Jordan. Supported in part by an institutional unrestricted grant from Research to Prevent Blindness. Presented at the American Society of Retina Specialists Annual Meeting in San Diego, 2014. None of the authors have any conflicting interests to disclose. A. Ozkok, and O. A. Saleh shared first authorship. Reprint requests: Shlomit Schaal, MD, PhD, Department of Ophthalmology and Visual Sciences, University of Louisville, 301 E Muhammad Ali Boulevard, Louisville, KY 40202; e-mail: [email protected]

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patients for bevacizumab, ranibizumab, dexamethasone implant (DEX), and triamcinolone acetonide (TCA) were +15.5, +18.3, +6, and +5.7, respectively. The mean changes in BCVA in letters at Month 12 in patients with central retinal vein occlusion (CRVO) for bevacizumab, ranibizumab, aflibercept, DEX, and TCA were +16.1, +13.9, +16.2, +2, and −1.2, respectively. Although intravitreal anti-VEGFs are mainstay of the treatment for CME due to RVO, there are a considerable number of cases who do not respond or become recalcitrant with time to anti-VEGF treatment.11,12 In these cases, intravitreal steroids are commonly used, as it has been shown that they have the ability to reduce tachyphylaxis to anti-VEGF agents.12 Two of the available injectable intravitreal steroids are DEX and TCA. This study was designed to compare the effects of adding DEX or triamcinolone to bevacizumab (Avastin) in the treatment of recalcitrant CME secondary to RVO with a primary focus on the frequency of intravitreal injections, changes in central macular thickness (CMT) and visual acuity, and the cost of therapy.

Materials and Methods This was a retrospective multicenter study performed by collaboration of investigators who belong to different institutions. The study was reviewed and approved by the Institutional Review Board at the University of Louisville. Exclusion criteria included macular ischemia on fluorescein angiography, history of focal/grid laser, and follow-up duration less than 12 weeks both before and after initiation of steroid injection. Medical records of 484 patients with RVO were reviewed and 74 patients, who were initially treated with intravitreal injections of bevacizumab (1.25 mg/0.1 mL) and later on received 0.7 mg DEX or 4 mg/0.1 mL intravitreal preservative-free triamcinolone acetonide (compounded from Westmoreland Pharmacy, Jeffersonville, IN) for CME between November 2009 and December 2013, were identified and included in the study. All patients were diagnosed with perfused RVO, confirmed by fluorescein angiography. Patients were initially treated with at least three injections of bevacizumab monotherapy and later received one of the intravitreal steroids because of refractory CME. Reinjection of either drug was based on persistence or recurrence of CME demonstrated by spectral domain optical coherence tomography (SD-OCT; Spectralis, Heidelberg, Germany). Patients were divided into two groups depending on whether they had BRVO or CRVO, and these two



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groups further were divided into four groups depending on whether they received DEX or TA injection (BRVOTA, BRVO-DEX, CRVO-TA, CRVO-DEX groups). Data collected at each visit included BCVA, CMT measured by SD-OCT, and the type of intravitreal drug injected, if any. Change in BCVA during the follow-up period was plotted over time to evaluate the functional effect of treatment. Anatomical effects of treatment were assessed based on the change in CMT demonstrated by SD-OCT. The frequency of any intravitreal injection and the cost of treatment were calculated and compared between the groups before and after initiating intravitreal steroids. Values of Snellen BCVA were converted to logarithm of minimum angle of resolution equivalent units (logMAR) for the purpose of statistical calculations.13 The cost calculations included the office visit, the SD-OCT scan, the intravitreal injection fee, and the cost of the drug injected. Statistical Analysis Statistical evaluations were performed using MedCalc (version 12.3.0.0; MedCalc software, Mariakerte, Belgium) and Microsoft Excel 2013 (Microsoft, Redmond, WA). The chi-square test or Fisher’s exact test was used to compare categorical data. Two-tailed Student’s t-test or analysis of variance was used for the analysis of the continuous variables. A P value less than 0.05 was considered statistically significant. Results Thirty-nine patients received TA (BRVO-TA 20; CRVO-TA 19) and 35 patients received DEX (BRVODEX 18; CRVO-DEX 17) injections. The mean ages and gender distribution were not statistically different between the groups (Table 1). The mean total follow-up durations in BRVO patients were 81.4 ± 30.4 weeks and 82.1 ± 40.3 weeks in TA and DEX groups, respectively (P = 0.951). The mean total follow-up durations in CRVO patients were 87.1 ± 23.7 weeks and 74.1 ± 29.8 weeks in TA and DEX groups, respectively (P = 0.172) (Table 1). Patients had a mean of 5.16 ± 1.85 bevacizumab injections before initiation of intravitreal steroids. Bevacizumab was discontinued after initiation of steroids in 7 (35%) patients in the BRVO-TA group, and 10 (55%) patients in the BRVO-DEX group (P = 0.327). The mean number of monthly injections decreased from 0.60 ± 0.20 to 0.29 ± 0.07 (P , 0.0001) after initiating steroids in the BRVO-TA group and from 0.65 ± 0.18 to 0.21 ± 0.07 (P , 0.0001) in the BRVO-DEX group (Table 2; Figure 1).

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Table 1. Epidemiologic Characteristics of Study Subjects BRVO

CRVO

Parameter

TA

DEX

P

TA

DEX

P

Number of patients Age Gender (F/M) HT+ DM+ Follow-up, weeks

20 66.2 ± 13.3 10/10 11 3 81.4 ± 30.4

18 69.9 ± 10.8 7/11 14 5 82.1 ± 40.3

0.357 0.531 0.181 0.438 0.951

19 73.3 ± 12.7 11/8 13 4 87.1 ± 23.7

17 75.7 ± 11 7/10 10 6 74.4 ± 29.8

0.535 0.505 0.488 0.462 0.172

DM, diabetes mellitus; HTN, hypertension; TA, intravitreal triamcinolone acetonide.

Bevacizumab was discontinued after initiation of steroids in 6 (31%) patients in the CRVO-TA group and 11 (65%) patients in the CRVO-DEX group (0.093). The mean number of monthly injections decreased from 0.69 ± 0.11 to 0.30 ± 0.06 (P , 0.0001) and from 0.70 ± 0.20 to 0.23 ± 0.06 (P , 0.0001) after steroid injections in CRVO-TA and CRVO-DEX groups, respectively (Table 3; Figure 1). In BRVO cases, the mean numbers of steroid injections were 2.1 ± 0.7 and 1.4 ± 0.5 in the BRVO-TA and BRVO-DEX groups, respectively (P = 0.0011). On average, patients received a steroid injection every 19.9 ± 4.3 weeks in the BRVO-TA group and every 27.8 ± 11.9 weeks in the BRVODEX group (P = 0.009). In CRVO cases, the mean numbers of steroid injections were 2.6 ± 0.6 and 1.6 ± 0.6 in the CRVO-TA and CRVO-DEX groups, respectively (P , 0.0001). On average, patients received a steroid injection every 18.2 ± 4.8 weeks in the CRVO-TA and every 25.0 ± 12.5 weeks in the CRVO-DEX groups (P = 0.034). Visual acuity measurement before and after initiation of steroid injections are shown in Figure 2. The BCVA increased slightly after starting steroid injections in all groups, but the increase was statistically significant only at the 6-week mark for the CRVO-TA

group and the 12-week mark for the remaining groups (P , 0.05). As the follow-up duration was not the same in all subjects, we used the final BCVA value in Tables 2 and 3; however, Figure 2 shows the available results of the subjects at the corresponding week. This is similar for CMT—final CMTs are indicated in the tables, whereas Figure 3 represents fluctuations in CMT throughout the follow-up period. The final visual acuity was not statistically different from the visual acuity at the time of steroid initiation. For the BRVO subgroups, the number of patients who gained 3 or more Snellen lines were 1 (5%) and 3 (16.7%) in the BRVO-TA and BRVO-DEX groups, respectively (P = 0.522); the number of patients who lost 3 or more lines were 1 (5%) and 1 (5.5%) in the BRVO-TA and BRVO-DEX groups, respectively (P = 0.939). For the CRVO subgroups, the number of patients who gained 3 or more Snellen lines were 3 (15.8%) and 1 (5.9%) in the CRVO-TA and the CRVO-DEX groups, respectively (P = 0.637); the number of patients who lost 3 or more lines were 2 (10.5%) and 2 (11.8%) in the CRVO-TA and the CRVO-DEX groups, respectively (P = 0.954; Table 3). Central macular thickness changes for the duration of the study are shown in Figure 3. The mean CMT decreased from the initiation of steroid

Table 2. Results for Patients With BRVO

Number of intravitreal injections/month Before steroid After steroid BCVA logMAR (Snellen) Before steroid Final CMT (mm) Before steroid Final Number of steroid injections Interval between steroid injections, weeks Number of patients $3 line gain Number of patients $3 line loss TA, intravitreal triamcinolone acetonide.

BRVO-TA

BRVO-DEX

P

0.60 ± 0.20 0.29 ± 0.07

0.65 ± 0.18 0.21 ± 0.07

0.210 0.002

0.40 (20/50) 0.36 (20/46)

0.44 (20/55) 0.36 (20/46)

0.405 0.920

499.5 ± 78 311.6 ± 82.3 2.1 ± 0.7 19.9 ± 4.3 1 (5%) 1 (5%)

467.8 ± 124.5 310.3 1.4 ± 0.5 27.8 ± 11.9 3 (16.7%) 1 (5.6%)

0.360 0.962 0.001 0.009 0.522 0.939

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Fig. 1. Trend line graph demonstrating the function of the change in the number of injections per month between the periods before and after initiation of steroid. Black, BRVO; gray, CRVO; solid line, TA; intravitreal triamcinolone acetonide; broken line, DEX.

therapy through all follow-up visits (P , 0.05 in all groups). Details of steroid-related cataract and intraocular pressure (IOP) increase are summarized in Table 4. Of the 12 phakic patients in the TA groups, 2 (16.6%) needed cataract surgery, whereas of the 8 phakic patients in DEX groups, 1 (12.5%) needed cataract surgery. This difference was not statistically significant (P = 0.701). Of the 39 patients in the TA groups, 10 (25.6%) had an IOP increase more than 6 mmHg, whereas of the 35 patients in DEX groups, 7 (20%) had an IOP increase of more

than 6 mmHg. This difference was not statistically significant (P = 0.764). Fifteen patients (38%) in TA groups and 11 patients (31%) in DEX groups had IOP . 21 mmHg after initiation of steroids (P = 0.462). In all except 1 of the cases of ocular hypertension, IOP was controlled with topical drops alone. One patient in the TA-CRVO group required trabeculectomy. The cost analysis data are summarized in Table 5. The mean monthly cost of therapy increased from $222 ± 87 to $313 ± 152 in BRVO (P = 0.03) and from $239 ± 83 to $351 ± 125 in CRVO (P = 0.01)

Table 3. Results for Patients With CRVO

Number of intravitreal injections/month Before steroid After steroid BCVA logMAR (Snellen) Before steroid Final CMT, mm Before steroid Final Number of steroid injections Interval between steroid injections (weeks) Number of patients $3 line gain Number of patients $3 line loss TA, intravitreal triamcinolone acetonide.

CRVO-TA

CRVO-DEX

P

0.69 ± 0.11 0.30 ± 0.06

0.70 ± 0.20 0.23 ± 0.06

0.476 0.002

0.71 (20/103) 0.64 (20/87)

0.75 (20/112) 0.72 (20/104)

0.678 0.496

549.9 ± 92.1 327.5 ± 86.2 2.6 ± 0.6 18.2 ± 4.8 3 (15.8%) 2 (10.5%)

518.2 ± 160.2 330.1 ± 93.1 1.6 ± 0.6 25.0 ± 12.5 1 (5.9%) 2 (11.8%)

0.480 0.933 ,0.0001 0.034 0.637 0.954

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Fig. 2. Graph demonstrating the change in CMT in mm during the follow-up period. Black, BRVO; gray, CRVO; solid line, intravitreal triamcinolone acetonide (TA); broken line, DEX.

after dexamethasone injections were added to bevacizumab therapy. The mean monthly cost of therapy decreased from $213 ± 63 to $80 ± 17 in BRVO (P , 0.0001) and from $219 ± 46 to $92 ± 14 in CRVO (P , 0.0001) after TA injections were added to bevacizumab therapy (Table 5).

Discussion We compared the effectiveness of addition of either TA or DEX in patients with RVO-related CME resistant

to bevacizumab. Frequency of injections decreased after initiation of steroids, and the decrease was more prominent in DEX groups. This finding emphasizes the longer duration of effect of DEX compared with TA. Although CMT improved in all steroid groups, there was no statistically significant difference between the DEX and TA groups in terms of BCVA and CMT changes. To the best of our knowledge, this is the first study to compare the two available intravitreal steroids in this particular patient group. We also compared the rates of steroid-related ocular side effects including cataract and IOP between the

Fig. 3. Graph demonstrating Snellen and logMAR visual acuity changes during the follow-up period in all groups. Black, BRVO; gray, CRVO; solid line, intravitreal triamcinolone acetonide (TA); broken line, DEX.

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Table 4. Comparison of Steroid Related Ocular Complications Between TA and DEX Groups

Number of phakic cases Number of cases that needed cataract surgery Number of cases with IOP increase .6 mmHg or needed IOP decreasing drops Number of cases with IOP .21 mmHg after steroids Number of cases that needed glaucoma surgery

TA

DEX

P

12 2 (16.6%) 10 (25.6%)

8 1 (12.5%) 7 (20%)

0.701 0.764

15 (38%) 1 (2.6%)

11 (31%) 0 (0%)

0.462 0.340

Both BRVO and CRVO cases included. TA, intravitreal triamcinolone acetonide.

preferring anti-VEGF agents, bevacizumab being the most popular.14 Intravitreal steroids constitute an important alternative in cases with RVO-related CME that is bevacizumab resistant. Sharareh et al15 reported improved BCVA and CMT with a short follow-up interval after initiation of DEX in RVO-related CME that is resistant to bevacizumab. This study showed statistically significant improvements in BCVA and CMT in the short term after initiation of DEX. The improvement in CMT was stable, but the improvement in BCVA was temporary, losing significance after the first 12 weeks. Although CMT improved in both steroid groups, there was no statistically significant difference between the steroid groups in terms of BCVA and CMT improvements. Data regarding the cost of RVO treatment is limited and is mostly outdated. In a retrospective analysis of secondary insurance payment data-based study, Fekrat et al16 reported 16% to 22% higher 1-year costs and 12% to 15% higher 3-year costs in RVO patients compared with patients with hypertension. The annual direct cost of RVO treatment for Medicare population is estimated to reach 5.8 billion dollars in 2006.17 Obviously, management of RVO has changed significantly since 2006. Taylor et al18 evaluated the costeffectiveness of ranibizumab versus observation and/or laser photocoagulation by using the data of BRAVO, CRUISE, and HORIZON trials, and they reported ranibizumab as a cost-effective option with an incremental cost-effectiveness ratio of £17.103. This study is the first to evaluate the cost of RVO treatment in the era of intravitreal injections. Monthly cost increased significantly after the initiation of

two steroids. There was no statistically significant difference between TA and DEX groups in terms of steroid related side effects in this study. To the best of our knowledge, this is the first study to directly compare the side effect profiles of these two injectable steroids. In this study, the percentages of cases that needed IOP lowering medications were in agreement with the SCORE study, which investigated the use of 4 mg TA,1,2 and with the GENEVA study, which studied 0.7 mg DEX implant.9 There was no statistically significant difference in the proportion of patients requiring cataract surgery between the TA group (16.6%) and the DEX group (12.5). However, both groups showed a higher proportion of cataract progression than previously reported: 4.3% in the SCORE study for 4 mg TA and 1.3% in the GENEVA study DEX groups.1,2,8,9 Further studies comparing the side effects of the two medicines are needed to figure out the side effect rates in different indications such as uveitis, diabetic CME, and RVO-related CME. Dexamethasone implant has received approval from the Food and Drug Administration for the treatment of macular edema secondary to RVO in June 2009. However, its use in clinical practice remains largely overshadowed by anti-VEGF agents, particularly the off-label drug bevacizumab. According to Preferences and Trends (PAT) 2013 survey released by the American Society of Retina Specialists, only 0.5% to 2% of member retina specialists recommended the use of DEX or TA as initial therapy for CME secondary to RVO compared with more than 90% of members

Table 5. Results of Cost Analysis in US Dollars BRVO TA Total $ cost Monthly $ cost overall Monthly $ cost before steroid Monthly $ cost after steroid

3.074 162 213 80

TA, intravitreal triamcinolone acetonide.

± ± ± ±

CRVO

DEX 570 34 63 17

4.976 278 222 313

± ± ± ±

1.300 87 79 152

P ,0.0001 ,0.0001 0.68 ,0.0001

TA 3.300 168 219 92

± ± ± ±

DEX 511 17 46 14

5.241 302 239 351

± ± ± ±

1.172 67 83 125

P ,0.0001 ,0.0001 0.38 ,0.0001

OZURDEX VERSUS TRIAMCINOLONE ACETONIDE IN RVO  OZKOK ET AL

steroid therapy in DEX groups. In contrary, the monthly cost decreased significantly after initiation of steroid therapy in TA groups. These differences were noted despite a larger decrease in the frequency of intravitreal injections in the DEX groups compared with the TA groups. This study has limitations as it does not have focal/ grid laser groups to compare the effects of laser in BRVO patients. As the number of cases with focal/grid laser in our cohort was too few to compare and most of them also had steroids, to eliminate the possible effect of laser treatment, we excluded these cases. Although BCVA was used as a functional measurement, other benefits of reduced macular edema such as reduction of central scotoma were not measured in this study. Although not typically measured in clinical studies, it can be of great functional benefit to patients. Patients receiving TA often have short-lived (hours to days) “cloudy vision” from dispersed drug particles, which are not experienced with long-acting DEX implant. Transient cloudy vision should be considered in the decision-making process because it may affect daily living activities especially in monocular patients. In addition, there are patients who are unresponsive to bevacizumab who do show clinical response to other anti-VEGF medications. Of note, here are patients who respond to combined anti-VEGF therapy with steroids who experience exceptional anatomical and functional improvement if instituted early before negative prognostic changes. In the era of SD-OCT and SS-OCT, the central retinal thickness outcome should be accompanied by future studies analyzing extensively the status of the inner segment/outer segment (IS/OS) line (ellipsoid layer), the cone outer segment tips (COST) line, and also the inner retina degeneration before and after treatment. Indeed, one of the major findings of this study was that although central retinal thickness improved after steroid initiation, BCVA did not. Nonimprovement of vision has been associated with disruption of photoreceptors and atrophy of the inner retina. This may explain why BCVA did not improve —probably because long-standing CME unresponsive to anti-VEGF therapy leads to photoreceptors atrophy. Qualitative structural changes in OCT at the time of the decision to add steroids or after addition of steroids were not analyzed in this study. Future studies to investigate this hypothesis are warranted. In conclusion, adding steroids to bevacizumab for refractory CME in RVO patients improved significantly the anatomical outcome, but did not affect visual acuity. Injection frequency decreased significantly after adding steroids, more significantly in DEX groups compared with TA groups. Cost of treatment increased in DEX

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groups but decreased in TA groups. There was no difference between TA and DEX regarding anatomical or functional outcomes or rates of side effects. Starting steroid addition to anti-VEGF therapy earlier in the course of the disease may yield better functional results and needs to be further investigated. Key words: refractory cystoid macular edema, retinal vein occlusion, cost of therapy, combination therapy, bevacizumab, dexamethasone implant, triamcinolone acetonide. References 1. Ip MS, Scott IU, VanVeldhuisen PC, et al. A randomized trial comparing the efficacy and safety of intravitreal triamcinolone with observation to treat vision loss associated with macular edema secondary to central retinal vein occlusion: the Standard Care vs Corticosteroid for Retinal Vein Occlusion (SCORE) study report 5. Arch Ophthalmol 2009;127:1101–1114. 2. Scott IU, Ip MS, VanVeldhuisen PC, et al. A randomized trial comparing the efficacy and safety of intravitreal triamcinolone with standard care to treat vision loss associated with macular Edema secondary to branch retinal vein occlusion: the Standard Care vs Corticosteroid for Retinal Vein Occlusion (SCORE) study report 6. Arch Ophthalmol 2009;127:1115–1128. 3. Brown DM, Campochiaro PA, Singh RP, et al. Ranibizumab for macular edema following central retinal vein occlusion: sixmonth primary end point results of a phase III study. Ophthalmology 2010;117:1124–1133; e1121. 4. Campochiaro PA, Brown DM, Awh CC, et al. Sustained benefits from ranibizumab for macular edema following central retinal vein occlusion: twelve-month outcomes of a phase III study. Ophthalmology 2011;118:2041–2049. 5. Brown DM, Campochiaro PA, Bhisitkul RB, et al. Sustained benefits from ranibizumab for macular edema following branch retinal vein occlusion: 12-month outcomes of a phase III study. Ophthalmology 2011;118:1594–1602. 6. Boyer D, Heier J, Brown DM, et al. Vascular endothelial growth factor Trap-Eye for macular edema secondary to central retinal vein occlusion: six-month results of the phase 3 COPERNICUS study. Ophthalmology 2012;119: 1024–1032. 7. Brown DM, Heier JS, Clark WL, et al. Intravitreal aflibercept injection for macular edema secondary to central retinal vein occlusion: 1-year results from the phase 3 COPERNICUS study. Am J Ophthalmol 2013;155:429–437. 8. Haller JA, Bandello F, Belfort R Jr, et al. Dexamethasone intravitreal implant in patients with macular edema related to branch or central retinal vein occlusion twelve-month study results. Ophthalmology 2011;118:2453–2460. 9. Haller JA, Bandello F, Belfort R Jr, et al. Randomized, shamcontrolled trial of dexamethasone intravitreal implant in patients with macular edema due to retinal vein occlusion. Ophthalmology 2010;117:1134–1146; e1133. 10. Campochiaro PA, Heier JS, Feiner L, et al. Ranibizumab for macular edema following branch retinal vein occlusion: sixmonth primary end point results of a phase III study. Ophthalmology 2010;117:1102–1112; e1101. 11. Pielen A, Feltgen N, Isserstedt C, et al. Efficacy and safety of intravitreal therapy in macular edema due to branch and central retinal vein occlusion: a systematic review. PLoS One 2013;8: e78538.

1400 RETINA, THE JOURNAL OF RETINAL AND VITREOUS DISEASES 12. Schaal S, Kaplan HJ, Tezel TH. Is there tachyphylaxis to intravitreal anti-vascular endothelial growth factor pharmacotherapy in age-related macular degeneration? Ophthalmology 2008;115:2199–2205. 13. Ferris FL 3rd, Kassoff A, Bresnick GH, Bailey I. New visual acuity charts for clinical research. Am J Ophthalmol 1982;94:91–96. 14. Preferences and Trends (PAT) Survey 2013. Available at: https:// www.asrs.org/content/documents/_2013asrspatsurveyresults.pdf. Accessed October 22, 2014. 15. Sharareh B, Gallemore R, Taban M, et al. Recalcitrant macular edema after intravitreal bevacizumab is responsive to an



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intravitreal dexamethasone implant in retinal vein occlusion. Retina 2013;33:1227–1231. 16. Fekrat S, Shea AM, Hammill BG, et al. Resource use and costs of branch and central retinal vein occlusion in the elderly. Curr Med Res Opin 2010;26:223–230. 17. Laouri M, Chen E, Looman M, Gallagher M. The burden of disease of retinal vein occlusion: review of the literature. Eye (Lond) 2011;25:981–988. 18. Taylor M, Serbetci E, Ferreira A, et al. A United Kingdombased economic evaluation of ranibizumab for patients with retinal vein occlusion (RVO). J Med Econ 2014;17:423–434.

THE OMAR STUDY: Comparison of Ozurdex and Triamcinolone Acetonide for Refractory Cystoid Macular Edema in Retinal Vein Occlusion.

To compare the risks and benefits of adding either intravitreal dexamethasone implant (DEX) or preservative-free triamcinolone acetonide (TA) to bevac...
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