Table 1.
Main clinical trials dedicated on the assessment of anti-VEGF molecules in diabetic retinopathy. The order of appearance follows the year of publication.
| N | Title | Acronym | Design | Number of Patients | Max duration | Drug | Year of publication | Main conclusions | Reference |
|---|---|---|---|---|---|---|---|---|---|
| 1 | Two-year outcomes of the ranibizumab for edoema of the mAcula in diabetes (READ-2) study | READ-2 | Prospective, randomized, interventional, multicenter clinical trial | 126 | 24 months | Ranibizumab | 2010 | Ranibizumab is effective in DME management with or without laser | 77 |
| 2 | Safety and efficacy of ranibizumab in diabetic macular edoema (RESOLVE Study): a 12-month, randomized, controlled, double-masked, multicenter phase II study | RESOLVE | Randomized, controlled, double-masked, multicenter phase II study | 151 | 12 months | Ranibizumab | 2010 | Ranibizumab is effective in DME management | 78 |
| 3 | The RESTORE study: ranibizumab monotherapy or combined with laser versus laser monotherapy for diabetic macular edoema | RESTORE | Randomized, double-masked, multicenter, laser-controlled phase III study | 345 | 12 months | Ranibizumab | 2011 | Ranibizumab with or without laser is superior to laser monotherapy for DME management | 79 |
| 4 | Ranibizumab for diabetic macular edoema: results from 2 phase III randomized trials: RISE and RIDE | RISE and RIDE | Two parallel, methodologically identical, phase III, multicenter, double-masked, sham injection-controlled, randomized studies | 377 (RISE) and 382 (RIDE) | 24 months | Ranibizumab | 2012 | Ranibizumab is effective in DME management | 80 |
| 5 | Randomized clinical trial evaluating intravitreal ranibizumab or saline for vitreous haemorrhage from proliferative diabetic retinopathy. | Protocol N | Phase 3, double-masked, randomized, multicenter clinical trial | 261 | 4 months | Ranibizumab | 2013 | Ranibizumab is useful in vitrectomy setting of PDR | 122 |
| 6 | A randomized trial to assess functional and structural effects of ranibizumab versus laser in diabetic macular edoema (the LUCIDATE study). | LUCIDATE | Prospective, randomized, single-masked clinical trial | 33 | 12 months | Ranibizumab | 2014 | Ranibizumab is effective in DME management | 81 |
| 7 | The REVEAL Study: Ranibizumab monotherapy or combined with laser versus laser monotherapy in Asian patients with diabetic macular edoema. | REVEAL | Randomized, double-masked, multicenter, laser-controlled, phase III study | 396 | 12 months | Ranibizumab | 2015 | Ranibizumab with or without laser is superior to laser monotherapy for DME management | 82 |
| 8 | Ranibizumab 0.5 mg for diabetic macular edoema with bimonthly monitoring after a phase of initial treatment: 18-month, multicenter, phase IIIB RELIGHT Study. | RELIGHT | Phase IIIb, prospective, open-label, multicenter, single-arm study | 109 | 18 months | Ranibizumab | 2015 | Ranibizumab is effective in DME management | 83 |
| 9 | Panretinal photocoagulation vs intravitreous Ranibizumab for proliferative diabetic retinopathy: a randomized clinical trial | Protocol S | Randomized, multicenter, clinical trial | 394 | Up to five years | Ranibizumab | 2015-2018 | Ranibizumab not inferior to PRP for PDR management | 86,87 |
| 10 | Intravitreal Aflibercept for diabetic macular edoema: 100-week results from the VISTA and VIVID studies. | VISTA and VIVID | Two similarly designed, double-masked, randomized, phase 3 trials, VISTA(DME) and VIVID(DME) | 872 | 24 months | Aflibercept | 2015 | Aflibercept is effective in DME management | 99,100 |
| 11 | A study of Abicipar Pegol in patients with diabetic macular edoema (NCT02186119). | N/A | Randomized, multicenter study | 151 | 12 months | Abicipar pegol | 2015 | Abicipar pegol non-inferior to ranibizumab for DME management | N/A |
| 12 | Ranibizumab 0.5 mg treat-and-extend regimen for diabetic macular oedema: the RETAIN study. | RETAIN | Single-masked, randomized study | 372 | 24 months | Ranibizumab | 2016 | Ranibizumab is effective in DME management | 84 |
| 13 | Twenty-four-month outcomes of the Ranibizumab for edoema of the macula in diabetes – protocol 3 with high dose (READ-3) Study | READ-3 | Randomized, controlled, double-masked (to the dose), interventional, multicenter clinical trial | 152 | 24 months | Ranibizumab | 2016 | Ranibizumab is effective in DME management | 85 |
| 14 | Aflibercept, bevacizumab, or ranibizumab for diabetic macular edoema | Protocol T | Randomized, multicenter, clinical trial | 660 | 24 months | Aflibercept, bevacizumab, and ranibizumab | 2016 | Aflibercept, bevacizumab, and ranibizumab non-inferiority study | 88 |
| 15 | Ranibizumab 0.3 mg for persistent diabetic macular edoema after recent, frequent, and chronic Bevacizumab: The ROTATE Trial. | ROTATE | Open-label, prospective study | 30 | 12 months | Ranibizumab and bevacizumab | 2016 | Ranibizumab demonstrated improved outcome in patients with persistent DME following bevacizumab | 93 |
| 16 | Outcomes with as-needed Aflibercept and macular laser following the Phase III VISTA DME Trial: ENDURANCE 12-month extension study. | ENDURANCE | Phase IV, multicenter, open-label extension study (12-month extension of VISTA and VIVID) | 60 | 36 months | Aflibercept | 2017 | Aflibercept with or without laser is superior to laser monotherapy for DME management | 101 |
| 17 | Clinical efficacy of intravitreal aflibercept versus panretinal photocoagulation for best corrected visual acuity in patients with proliferative diabetic retinopathy at 52 weeks (CLARITY): a multicentre, single-blinded, randomized, controlled, phase 2 b, non-inferiority trial. | CLARITY | Phase 2 b, single-blind, non-inferiority trial | 232 | 12 months | Aflibercept | 2017 | Aflibercept is more effective than PRP for PDR management | 123 |
| 18 | Visual acuity outcomes in diabetic macular edoema with Fluocinolone Acetonide 0.2 μg/day versus Ranibizumab plus deferred laser (DRCR Protocol I). | Protocol I | Randomized, multicenter study | 188 | 36 months | Ranibizumab and Fluocinolone Acetonide | 2018 | Fluocinolone Acetonide was comparable to ranibizumab plus deferred laser for DME management | 89 |
| 19 | The RELATION study: efficacy and safety of ranibizumab combined with laser photocoagulation treatment versus laser monotherapy in NPDR and PDR patients with diabetic macular oedema. | RELATION | Double-masked, multicentre phase IIIb study | 128 | 12 months | Ranibizumab | 2018 | Ranibizumab with or without laser is superior to laser monotherapy for DME management | 94 |
| 20 | Ranibizumab plus panretinal photocoagulation versus panretinal photocoagulation alone for high-risk proliferative diabetic retinopathy (PROTEUS Study). | PROTEUS | Prospective, randomized, multicenter, open-label, phase II/III study | 87 | 12 months | Ranibizumab | 2018 | Ranibizumab plus PRP superior to PRP monotherapy for DME management | 124 |
| 21 | Ranibizumab plus panretinal photocoagulation versus panretinal photocoagulation alone for high-risk proliferative diabetic retinopathy (PROTEUS Study). | PROTEUS | Prospective, randomized, multicenter, open-label, phase II/III study | 87 | 12 months | Ranibizumab | 2018 | Ranibizumab plus laser superior than laser alone for PDR management | 124 |
| 22 | Efficacy and safety of ranibizumab 0.5 mg in Chinese patients with visual impairment due to diabetic macular edoema: results from the 12-month REFINE study. | REFINE | Phase III, double-masked, multicenter, laser-controlled study | 384 | 12 months | Ranibizumab | 2019 | Ranibizumab with or without laser is superior to laser monotherapy for DME management | 95 |
| 23 | Effect of initial management with Aflibercept vs laser photocoagulation vs observation on vision loss among patients with diabetic macular edoema involving the centre of the macula and good visual acuity: a randomized clinical trial. | Protocol V | Randomized, multicenter study | 702 | 24 months | Aflibercept | 2019 | Aflibercept is more effective than laser for DME management | 102 |
| 24 | Simultaneous inhibition of angiopoietin-2 and vascular endothelial growth factor-A with Faricimab in diabetic macular edoema: BOULEVARD Phase 2 randomized trial. | BOULEVARD | Prospective, randomized, active comparator-controlled, double-masked, multicenter, phase 2 study | 229 | 6 months | Faricimab | 2019 | Faricimab was statistically superior than ranibizumab for DME management | 120 |
| 25 | Real-world outcomes following 12 months of intravitreal aflibercept monotherapy in patients with diabetic macular edoema in France: results from the APOLLON study. | APOLLON | Prospective, observational cohort study | 147 | 12 months | Aflibercept | 2020 | Aflibercept is effective in DME management | 125 |
| 26 | A randomized, double-masked, multicenter, Phase III Study assessing the efficacy and safety of Brolucizumab versus Aflibercept in patients with visual impairment due to diabetic macular edoema (KITE). | KITE and KESTREL | Ongoing prospective, randomized, phase III clinical studies | 361 (KITE) and 561 (KESTREL) | 24 months | Brolucizumab and aflibercept | 2020 | Brolucizumab non-inferior to aflibercept for DME management | 115 |
| 27 | Long-term outcomes of treat-and-extend ranibizumab with and without navigated laser for diabetic macular oedema: TREX-DME 3-year results | TREX-DME | Multicenter, prospective, randomized clinical trial | 116 | 36 months | Ranibizumab | 2021 | Ranibizumab is effective in DME management | 90–92 |
| 28 | Evaluation of intravitreal aflibercept for the treatment of severe nonproliferative diabetic retinopathy: results from the PANORAMA randomized clinical trial. | PANORAMA | Double-masked, multicenter, randomized clinical trial | 402 | 24 months | Aflibercept | 2021 | Aflibercept is effective in DME management | 126 |
| 29 | Effect of intravitreous anti-vascular endothelial growth factor vs sham treatment for prevention of vision-threatening complications of diabetic retinopathy: the protocol W randomized clinical trial. | Protocol W | Randomized, multicenter study | 328 | 24 months | Aflibercept | 2021 | Aflibercept is associated with lower progression to PDR than sham | 103 |
| 30 | Intravitreal conbercept for diabetic macular oedema: 2-year results from a randomized controlled trial and open-label extension study. | SAILING | Multicentre, randomized, double-masked, double-sham, parallel controlled, phase III trial (Sailing Study), followed by a 12-month open-label extension study | 251/157 | 12 + 12 months | Conbercept | 2021 | Conbercept is more effective than laser for DME management | 106 |
| 31 | Effect of Aflibercept on diabetic retinopathy severity and visual function in the RECOVERY Study for proliferative diabetic retinopathy. | RECOVERY | Prospective, longitudinal, multicenter clinical trial | 40 | 12 months | Aflibercept | 2021 | Aflibercept is associated with improvement of Diabetic Retinopathy Severity Scale for PDR eyes | 127 |
| 32 | A multi centre, randomized, double-masked, active-controlled, comparative clinical study to evaluate the efficacy and safety of MYL-1701P and Eylea® in subjects with diabetic macular edoema | N/A | Multi Centre, randomized, double-masked, active-controlled, comparative clinical study | 355 | 12 months | MYL-1701P and aflibercept | N/A | Ongoing | 121 |
| 33 | A Phase III, multicenter, randomized, double-masked, active comparator-controlled study to evaluate the efficacy and safety of Faricimab (RO6867461) in patients with diabetic macular edoema (RHINE) | RHINE | Phase III, multicenter, randomized, double-masked, active comparator-controlled study | 951 | 24 months | Faricimab and aflibercept | N/A | Ongoing | 121 |
| 34 | A Phase III, multicenter, randomized, double-masked, active comparator-controlled study to evaluate the efficacy and safety of Faricimab (RO6867461) in patients with diabetic macular edoema (YOSEMITE) | YOSEMITE | Phase III, multicenter, randomized, double-masked, active comparator-controlled study | 940 | 24 months | Faricimab and aflibercept | N/A | Ongoing | 121 |