Table 1.
Anti-angiogenic agents for the treatment of DR.
| Classification | Drugs | Status for DR Treatment | Clinical Benefits | Adverse Effects |
|---|---|---|---|---|
| Anti-VEGF | Ranibizumab (Lucentis) [42,43] | FDA approved | Greater BCVA improvement and greater reduction in CRT over laser in treating DME (DRCR.net Protocol T, RESOLVE and RESTORE trials); non-inferior to PRP in treating PDR at two years (DRCR.net Protocol S) | a. Elevation in intraocular pressure b. Vitreous hemorrhage c. Inflammation [47] |
| Pegaptanib (Macugen) [52] | FDA approved | Greater BCVA improvement over sham groups in treating DME (phase 2/3, multicenter, two-year trial) | a. Conjunctival hemorrhage b. Elevation in intraocular pressure |
|
| Aflibercept (EYLEA) [44] | FDA approved | Greater BCVA improvement over laser in treating DME (VISTA, VIVID, DRCR.net Protocol T trials) and PDR (CLARITY trial) | a. Elevation in intraocular pressure b. Vitreous hemorrhage c. Inflammation [47] |
|
| Bevacizumab (Avastin) [47] | Off-label use | Greater reduction in CRT and better median visual acuity over laser (DRCR.net Protocol T trial) | a. Elevation in intraocular pressure b. Vitreous hemorrhage c. Inflammation |
|
| Non-specific anti-angiogenic | Squalamine (inhibits VEGF and other growth factors) [50] | Phase 2 trial (clinicaltrials.gov ID: NCT02349516) in progress | - | - |
| AKB-9778 (Tie2 activator) [51] | Phase 2 trial (clinicaltrials.gov ID: NCT01702441) in progress | Greater reduction in CRT in the combination group over ranibizumab monotherapy group (phase 2a clinical trial) | a. Diabetic retinal edema worse b. Visual acuity reduced |
|
| Nesvacumab (Anti-Ang-2) (Section 3.1.2) | Clinical trial (RUBY trial) in progress | Results of phase 2 RUBY trial did not provide sufficient differentiation between the combined (nesvacumab + aflibercept) and aflibercept monotherapy treatments to warrant phase 3 development | No new safety signals observed when compared with other anti-angiogenic agents | |
| RO6867461 (bispecific antibody: anti-ang-2 + anti-VEGF) | Clinical trial (BOULEVARD trial) in progress (Section 3.1.2) | Greater adjusted BCVA improvement and greater reduction in CRT over ranibizumab in DME patients (phase 2 BOULEVARD trial) | Well tolerated with no new safety signals observed |