Eylea (aflibercept, Regeneron Pharmaceuticals), also known as “VEGF Trap-eye,” highly binds to its receptor while maintaining a slow degradation process, potentially yielding a longer duration of effect than other anti-VEGF agents. Researchers have already proven that Eylea is effective for the treatment of wet AMD and macular edema associated with retinal vein occlusion.1-6
Diabetic macular edema (DME) is the leading cause of blindness among our working adult patients. Anti-VEGF therapy provides visual improvement for many of our DME patients. However, the need for frequent follow-up and retreatment poses several potential disadvantages.
Fortunately, Eylea shows tremendous promise for vision restoration and decreased dosing intervals for DME patients. We await publication of the two-year results to further evaluate its efficacy and safety.
In July 2014, Eylea secured FDA approval for the treatment of DME following publication of two global clinical trials––VISTA and VIVID.7,8 In these one-year trials, researchers evaluated the efficacy and safety of Eylea at variable dosing schedules compared to conventional macular photocoagulation for the treatment of centrally involved DME.7-10
Approximately 460 patients in the US participated in the VISTA-DME study, and 400 patients from countries outside the US participated in the VIVID-DME study.7-10 Patients in both studies were randomized into one of three subgroups (two treatment groups and one control group). Patients in the first treatment group received monthly Eylea injections and patients in the second treatment group received Eylea injections every two months following five initial monthly doses. Those in the control group received photocoagulation therapy.
Diabetic macular edema detected upon dilated funds exam.
In both studies, the primary endpoint was improvement from initial best-corrected visual acuity using the ETDRS scale chart. Secondary endpoints included:
- The number of patients who gained ≥10 to 15 ETDRS letters from baseline.
- The number of patients with a ≥ two-line improvement from baseline.
- Change in central retinal thickness from baseline (assessed via SD-OCT).
- Change in visual function from baseline (as assessed by the National Eye Institute’s Visual Functioning Questionnaire-25 activities sub-scale).
VISTA and VIVID Results
After one year, visual acuity in the treatment groups in both studies showed robust, statistically significant improvement compared to the control groups.10 Patients in both treated groups consistently gained an average of two additional lines of visual acuity, compared to no negligible change in the control groups.
A Bird's-eye View of Anti-VEGF
Diabetic macular edema (DME) is a complex, multifactorial disease associated with a hypoxic environment, as well as vasculature alteration. Hypoxia leads to increased levels of vascular endothelial growth factor (VEGF), which increases inflammation and permeability. This complex cascade may lead to extracellular leakage near or within the macula that eventually manifests as macular edema.
Focal/grid laser photocoagulation remains a potential treatment option for patients with DME, but anti-VEGF therapy now is the gold standard. In some instances, conventional laser may be combined with anti-VEGF treatment. The choice between Eylea, another anti-VEGF drug or laser is up to the retina specialist.
VEGF plays a critical role in the development of macular edema, and high levels of VEGF have been found in the aqueous humor of patients with DME.11,12 Anti-VEGF blocks proteins that cause neovascularization and DME development.13
Researchers have shown that both Lucentis (ranibizumab, Genentech/Roche) and off-label use of Avastin (bevacizumab, Genentech/Roche) are safe and effective treatment options for patients with wet AMD.11,12,14 Recent clinical data also suggest comparable efficacy between Lucentis and Avastin in the treatment of DME.14
Yet, one of the main limitations of both drugs is the need for frequent retreatment to maintain optimal vision during the course of the disease. Thus, researchers have studied newer treatment options, such as Eylea, to help diminish this burden by increasing the therapeutic duration and efficacy.
Overall, patients tolerated Eylea well. Patients in the treated groups experienced a similar incidence of adverse events. The most common ocular side effects included conjunctival hemorrhage, vitreous floaters and eye pain. The safety and tolerance profiles were similar to those previously reported in the literature for the use of Eylea for the treatment of wet AMD and macular edema associated with central retinal vein occlusion.1,2,4,5
1. ClinicalTrials.gov. Double-masked study of efficacy and safety of IVT VEGF Trap-Eye in subjects with wet AMD (VIEW 1). ClinicalTrials.gov identifier: NCT00509795. Available at: www.clinicaltrials.gov/ct2/show/ NCT00509795. Accessed September 24, 2014.
2. ClinicalTrials.gov. VEGF Trap-Eye: Investigation of efficacy and safety in wet AMD (VIEW 2). ClinicalTrials.gov identifier: NCT00637377. Available at: www.clinicaltrials.gov/ct2/show/NCT00637377. Accessed September 24, 2014.
3. Heier JS, Brown DM, Chong V, et al. Intravitreal aflibercept (VEGF trap-eye) in wet age-related macular degeneration. Ophthalmology. 2012;119(12):2537-48.
4. Holz FG1, Roider J, Ogura Y, et al. VEGF Trap-Eye for macular edema secondary to central retinal vein occlusion: 6-month results of the phase III GALILEO study. Br J Ophthalmol. 2013 Mar;97(3):278-84.
5. 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. 2013Mar;155(3):429-37.
6. Heier JS, Clark WL, Boyer DS, et al. Intravitreal aflibercept injection for macular edema due to central retinal vein occlusion: two-year results from the COPERNICUS study. Ophthalmology. 2014 Jul;121(7):1414-20.e1.
7. Clinicalstrials.gov. Study of intravitreal administration of VEGF Trap-eye (BAY86-5321) in patients with diabetic macular edema (VISTA DME). Available at: www.clinicaltrials.gov/show/NCT01363440. Accessed April 16, 2013.
8. Clinicaltrials.gov. Japanese safety study of VEGF trap-eye in DME (diabetic macular edema) (VIVID-Japan). Available at: www.clinicaltrials.gov/ct2/show/NCT01512966. Accessed April 16, 2013.
9. Do DV, Nquyen QD, Boyer D, et al One-year outcomes of the da Vinci Study of VEGF Trap-Eye in eyes with diabetic macular edema. Ophthalmology. 2012 Aug;119(8):1658-65.
10. Brown DM. IAI for DME: Primary and additional endpoint results from the 12-month, phase III VISTA-DME & VIVID-DME Studies. Paper presented at ARVO, May 2014. Poster #5052.
11. Funatsu H, Yamashita H, Sakata K, et al. Vitreous levels of vascular endothelial growth factor and intercellular adhesion molecule 1 are related to diabetic macular edema. Ophthalmology. 2005 May;112(5):806-16.
12. Aiello LP, Avery RL, Arrigg PG, et al. Vascular endothelial growth factor in ocular fluid of patients with diabetic retinopathy and other retinal disorders. N Engl J Med. 1994 Dec 1;331(22):1480-7.
13. Ho A, Scott I, Kim S, et al. Anti-vascular endothelial growth factor pharmacotherapy for diabetic macular edema: a report by the American Academy of Ophthalmology. Ophthalmology. 2012 Oct;119(10):2179-88.
14. Nguyen QD, Brown DM, Marcus DM, et al. Ranibizumab for diabetic macular edema: Results from 2 phase III randomized trials: RISE and RIDE. Ophthalmology. 2012 Apr;119(4):789-801.