Table 1.
Summary of Studies of DEX Implant in RVO with Macular Edema
| Study (Year) | Design | n | Intervention | Outcome Measure(s) | Time Point(s) | Results | Comments |
|---|---|---|---|---|---|---|---|
| Kuppermann et al. (2007)25 | Phase 2, six-month, sham-controlled RCT, persistent macular edema, various etiologies | 315 | Single injection of DEX implant (350 mcg or 700 mcg) versus sham | ≥10 letter BCVA gain | Day 90 | 35% (700 mcg), 24% (350 mcg) and 13% sham gained ≥ 10 letters | 11% IOP increase ≥10 mm Hg Similar result in DME, RVO, uveitis, and Irvine Gass syndrome |
| Haller et al. (2010) GENEVA Study Group26 | Phase 3, six-month, sham-controlled RCT, RVO with ME | 1267 | Single injection of DEX implant (350 mcg or 700 mcg) versus sham | ≥ 15 letter BCVA gain | Various time points. Peak benefit at day 60 | 29% gainers at day 60, same for both doses. No difference from sham at 180 | IOP ≥25 mm Hg in 16% at day 60 for both doses. Returned to baseline by day 180 |
| Haller et al. (2011)27 | Six-month open label extension of GENEVA trial | 1256 | Single DEX implant 0.7 mg at day 180 if indicated (n=997) | ≥ 15 letter BCVA gain | Day 60 | 32% gainers after second injection (30% after first) | ≥10 mm Hg IOP elevation in 12.6% after first, and 15.4 after the second. 30% showed cataract progression after two injections |
| Li et al. (2018)30 | Phase 3, six-month, sham-controlled RCT followed by two month open-label extension for eyes with ME from RVO | DEX 129, sham 130 | Single injection of 0.7 mg DEX implant versus sham. DEX implant at 6 months for pre-specified criteria | ≥ 15 letter BCVA gain | Various time points. Peak effect at day 60 | VA gainers. 35% DEX versus 12% sham. Mean change +10.6 letters (DEX) versus +1.7 letters (sham) | Duration of benefit 3–4 months. IOP normalized by 4 months |
| Gado and Macky (2014)31 | Six-month, RCT, eyes with perfused CRVO with ME | 60 (30 in each group) | 0.7 mg DEX implant versus PRN bevacizumab | BCVA change between the groups | Monthly for six months | No difference in BCVA between the two groups. Bevacizumab group had thinner CST at one month, no difference thereafter | Higher IOP in DEX group. All eyes in DEX group needed second implant around 4 months. Mean 4.3 injections in bevacizumab group |
| Hoerauf et al. (2016) COMRADE-C32 | Six-month RCT, RZB versus DEX implant for ME secondary to CRVO | 124 RZB, 119 DEX | Monthly RZB for three months followed by PRN versus single DEX implant | Change in BCVA | Monthly for six months | No difference in BCVA at month 1 and 2. RZB superior from month 3–6. +12.86 letters in RZB, +3 in DEX at 6 months | 4.52 injections in RZB versus single in DEX |
| Hattenbach et al. (2018) COMRADE-B33 | Six-month RCT, RZB versus DEX implant for ME secondary to BRVO | 126 RZB, 118 DEX | Monthly RZB for three months followed by PRN versus single DEX implant | Change in BCVA | Monthly for six months | No difference in BCVA at month 1 and 2. RZB superior from month 3–6. +17.3 letters in RZB, +9.2 in DEX at 6 months | 4.68 RZB injections versus single DEX |
| Bandello et al. (2018)34 | Twelve-month RCT, DEX v RZB in ME caused by BRVO | DEX 154, RZB 153 | DEX at baseline and 5 months, optional at month 10 or 11, RZB 5 monthly injections followed by PRN | Change in BCVA | 12 months | +7.4 letters in DEX, +17.4 in RZB at 12 months | 2.5 DEX v 8 RZB injections. RZB superior to DEX regarding visual outcomes |
| Chatziralli et al. (2017) RANIDEX35 | Retrospective Chart review, RZB v DEX for ME from CRVO | RZB 25, DEX 17 | RZB, or DEX monotherapy | Change in BCVA and CST | Various time points over one year | CST. RZB superior at month 5 and 6. No difference at month 12 BCVA. +8.4 letters in RZB and +6.9 in DEX (NS) |
5.1 injections in RZB, 2.1 in DEX. RZB group was likely undertreated |
| Gu et al. (2017)36 | Six-month retrospective comparative Study. RZB v DEX for ME from RVO | RZB 32, DEX 32 | RZB, or DEX monotherapy | BCVA and CST | Various time points up to six months | No difference between DEX and RZB | Only 3.4 and 3.5 injections of RZB in CRVO and BRVO respectively, likely undertreatment |
| Yuksel et al. (2018)37 | Retrospective study. RZB v DEX. ME from BRVO | 44 eyes. RZB 14, DEX 15, Laser 15 | RZB, DEX, or laser | BCVA change, percent gaining ≥10 letters, and CST | 6 months | No difference at six months in all three groups. +13.5 letters DEX, +7.1 RZB | Only 2.4 injections of RZB over 14 months, likely undertreatment |
| De Salles et al. (2021)38 | Retrospective study of eyes with ME from RVO | 492 | Anti-VEGF versus DEX | BCVA and CST change | Final follow-up (variable time) | Superior visual and anatomical gains in anti-VEGF group for both BRVO and CRVO | Patients received about 4.5 anti-VEGF injections, and 1.8 DEX injections annually |
| Gale et al. (2021)39 | Retrospective study of BRVO ME patients | 5661 | Laser, anti-VEGF or DEX implant | Change in BCVA | Up to 3 years | Anti-VEGF superior to DEX at 12 and 18 months. (+9.6 v +4.5 letters) | 5.1 anti-VEGF v 1.5 DEX injections at 12 months. |
| Gale et al. (2021)40 | Retrospective study of CRVO ME patients | 4626 | Anti-VEGF or DEX implant | Change in BCVA | 12, 18 and 36 months | Anti-VEGF superior to DEX at all time points (+10 v +8.4 letters at 12 months, +10.4 v +1.6 at 18 month, +11.5 v +5.7 at 36 months) | Injections at 12 months (anti-VEGF/DEX)=5.6/1.6 At 18 months. 6/1.7 At 36 months 7/1.8 Higher endophthalmitis in DEX (0.09%) v anti-VEGF (0.003%) |
| Manoursaridis et al. (2017)41 | Retrospective chart review of RZB resistant ME secondary to RVO switched to DEX implant | 11 | Single DEX implant for eyes resistant to ≥3 RZB injections | Change in BCVA and CST | Various time points up to 6 months | 0.2 logMAR gain at 2 and 3 months. Return to baseline by month 6. CST improvement mainly at 2 and 3 months | DEX implant was effective in RZB resistant eyes for about 3 months |
| Georgalas et al. (2019)42 | Prospective nonrandomized. Switch to DEX for persistent ME from RVO after ≥ 5 anti-VEGF injections | 23 (13 BRVO, 10 CRVO) | DEX implant baseline, repeated as needed at six month | Change in BCVA and CST | 2,4,6,8,10 and 12 month visits | BRVO. Best VA at 4 months after first and second injections. CRVO. Best VA and CST at 2 months after first and second injections |
Reinjections sooner than 6 months are needed especially in CRVO |
| Mayer et al. (2012)43 | Prospective, consecutive, nonrandomized | 64 | 38 DEX, 26 3 monthly BCB followed by DEX | BCVA and CST change. | 6 months | No benefit from BCB loading | Recurrence of ME 3–4 months after DEX injection in various groups |
| Singer et al. (2012)44 | Prospective, nonrandomized | 34 | BCB followed 2 weeks later by DEX, retreatment as needed with same regimen | Time to reinject, BCVA gain, CST change | Monthly visits up to six months | +16.8 letter BCVA gain at six months, 64% gained ≥15 letters at six months | Retreatment in 82% at a mean of 126 days. No comparison group |
| Maturi et al. (2014)45 | Prospective randomized | 30 | BCB monotherapy PRN versus PRN BCB+ single DEX one week later. Repeat DEX at 4 months PRN | Primary: Change in BCVA Secondary: CST, number of injections |
6 months | No difference in BCVA, Fewer BCB (2 versus 3) and greater CST reduction in combination group, | The primary endpoint was not met. One less BCB injection in combination group balanced by DEX injection |
| Giuffre et al. (2020)46 | Prospective, nonrandomized. ME secondary to RVO unresponsive to aflibercept and DEX monotherapies | 30 | Same day DEX+ aflibercept. Retreatment allowed after 4 months | BCVA and CST changes | 12 months | No change in BCVA but CST reduction by 226 microns at 12 months. | Good anatomical response but not visual. Mean duration of ME was 25 months prior to combination therapy. |
| Harb et al. (2021)47 | Prospective nonrandomized | 74 | DEX monotherapy versus Aflibercept followed by DEX two weeks later combination | BCVA and CST change, number of retreatments | 12 months | Better BCVA gain in combination group compared to DEX monotherapy | No difference in CST or number of retreatments between the groups. Superior BCVA gain in combination group is hard to explain. |
| Bezatis et al. (2013)48 | Retrospective, noncomparative | 102 | Single DEX implant for ME from RVO | BCVA and CST change | Up to 6 months | Peak effect at two months (about 0.3 logMAR gain) | Retreatment in 50% around 4 months |
| Korobelnik et al. (2016) LOUVRE49 | Prospective, multicenter, real-world study in France | 375 | DEX monotherapy at baseline, retreatment at physician’s discretion | Primary. Change in BCVA Secondary. Other therapies, side effects, IOP |
2 years | At 6 months: DEX +5.5, DEX + other therapies +4.2 letters. At 2 yrs: DEX: +20.7 single DEX, +4.9 multiple DEX, +2.3 DEX plus others |
2.6 DEX injections over two years. Mean interval 6.6 months between injections, 55% received other therapy (laser or anti-VEGF). Cataract progression in 40%, increased IOP in 34.4%. Switch to other therapies did not improve outcomes |
| Capone et al. (2014) SHASTA50 | Retrospective, multicenter chart review | 289 | DEX implant at baseline, other therapies per physician's discretion | Change in BCVA, CST, side effects | Variable (3–6 months after last DEX) | Peak change in BCVA from 4–20 weeks after DEX +1 line. 60% BRVO and 66% CRVO gained ≥2 lines | Mean reinjection interval 5.6 months, Increased IOP (≥10) in 32.6%. DEX monotherapy in 29.1%, adjunctive therapy in others |
| Eter et al. (2017)52 | Prospective, multi-center, real-world, Germany | 573 | Single DEX at baseline. Additional treatment per physician's discretion | Change in BCVA at 12 weeks | 12 weeks. Duration of study 6 months | At 12 weeks, +7.8 letters gain, 34% gained ≥3 lines. | ≤90 days duration of ME had the best visual outcomes. 19.9% received other adjunctive treatments |
| Horner et al. (2020)53 | Retrospective, real-world, single site, UK | 66 | Initial RZB, later DEX/laser | Change in BCVA and CST | Year 1 and 3 | 40% gained ≥3 lines at year 3 | Diminished need for injections in year 3 compared to year 1 (2.5 v 5.5) |
| Kim et al. (2021)54 | Prospective, multicenter, real-world, S Korea | 700 | DEX implant at baseline. Subsequent treatment per physician's discretion | Change in BCVA, responder rate, side effects | Month 1, 2, 4 and 6 | Peak benefit at 2 months (approx. 2 lines). | Better vision gains in younger patients, worse presenting vision and treatment naïve status |
| Garay-Aramburu et al. (2021)55 | Retrospective, short-term, real-world study | 111 | DEX implant at baseline | Visual and anatomical improvement | Unspecified | Worse presenting vision (<60 ETDRS letters), first injection, and non-chronic ME predictor of better visual outcomes. | Baseline CST ≥400 microns and central macular volume >12 mm3 predictors of ≥50% CST reduction |
Abbreviations: RVO, retinal vein occlusion; RCT, randomized controlled trial; BCVA, best-corrected visual acuity; IOP, intraocular pressure; ME, macular edema; CRVO, central retinal vein occlusion; CST, central subfield thickness; BCB, bevacizumab; RZB, ranibizumab; BRVO, branch retinal vein occlusion; NS, non-significant; VEGF, vascular endothelial growth factor.