Ziv-aflibercept in Diabetic Macular Edema: Relation of Subfoveal Choroidal Thickness with Visual and Anatomical Outcomes


Purpose: To evaluate the effects of intravitreal ziv-aflibercept injections (IVZ) on subfoveal choroidal thickness (SCT) as well as on central macular thickness (CMT) and on best corrected visual acuity (BCVA) changes in eyes with center-involved diabetic macular edema (CI-DME).

Methods: Fifty-seven eyes of 36 patients with CI-DME were included in this prospective interventional case series. Structural optical coherence tomography (OCT) and enhanced depth imaging OCT were performed at baseline followed by three monthly 1.25 mg IVZ injections. Changes of SCT, CMT, and BCVA at each follow-up session were assessed. The association between baseline SCT and its monthly changes with final visual and anatomical outcomes were also assessed.

Results: CMT at baseline, and at the first, second, and third month follow-up sessions were 396 ± 119, 344 ± 115, 305 ± 89, and 296 ± 101 μm, respectively (P-value < 0.001). SCT at baseline, and at months one, two, and three were 236 ± 47, 245 ± 56, 254 ± 54, and 241 ± 54 μm, respectively (Pvalue > 0.99). Corresponding figures for BCVA were 0.58 ± 0.29, 0.47 ± 0.31, 0.4 ± 0.24, and 0.37 ± 0.23 LogMAR, respectively (P-value < 0.001). There was a statistically significant positive correlation between BCVA and CMT changes following IVZ injections (P-value < 0.001). However, there were no significant correlations between SCT changes and visual acuity (VA) and CMT changes following IVZ injections.

Conclusion: IVZ improved visual outcomes and macular thickness profiles in patients with CI-DME. However, IVZ had no significant effect on SCT. Baseline SCT and its monthly changes had no association with visual and anatomical outcomes.


Center-involved Diabetic Macular Edema, Central Macular Thickness, Intravitreal, Subfoveal Choroidal Thickness, Ziv-Aflibercept

1. Moss SE, Klein R, Klein BE. The 14-year incidence of visual loss in a diabetic population. Ophthalmology 1998;105:998–1003.

2. Klein R, Klein BE, Moss SE, Cruickshanks KJ. The wisconsin epidemiologic study of diabetic retinopathy. Xiv. Ten-year incidence and progression of diabetic retinopathy. Arch Ophthalmol 1994;112:1217–1228.

3. Yiu G, Manjunath V, Chiu SJ, Farsiu S, Mahmoud TH. Effect of anti-vascular endothelial growth factor therapy on choroidal thickness in diabetic macular edema. Am J Ophthalmol 2014;158:745–751.

4. Singh SR, Stewart MW, Chattannavar G, Ashraf M, Souka A, ElDardeery M, et al. Safety of 5914 intravitreal zivaflibercept injections. Br J Ophthalmol 2019;103:805–810.

5. Mansour AM, Stewart MW, Farah ME, Mansour HA, Chhablani J. Ziv-aflibercept: A cost-effective, off-label, highly potent antagonist of vascular endothelial growth factor. Acta Ophthalmol 2020;98:e540–e548.

6. HodjatJalali K, Mehravaran S, Faghihi H, Hashemi H, Kazemi P, Rastad H. Intravitreal injection of ziv-aflibercept in the treatment of choroidal and retinal vascular diseases. J Curr Ophthalmol 2017;29:228–231.

7. Jabbarpoor Bonyadi MH, Baghi A, Ramezani A, Yaseri M, Soheilian M. One-year results of a trial comparing 2 doses of intravitreal ziv-aflibercept versus Bevacizumab for treatment of diabetic macular edema. Ophthalmol Retina 2018;2:428–440.

8. Baghi A, Jabbarpoor Bonyadi MH, Ramezani A, Azarmina M, Moradian S, Dehghan MH, et al. Two doses of intravitreal ziv-aflibercept versus bevacizumab in treatment of diabetic macular edema: A three-armed, double-blind randomized trial. Ophthalmol Retina 2017;1:103–110.

9. Mansour AM, Dedhia C, Chhablani J. Three-month outcome of intravitreal ziv-aflibercept in eyes with diabetic macular oedema. Br J Ophthalmol 2017;101:166–169.

10. de Andrade GC, de Oliveira Dias JR, Maia A, Farah ME, Meyer CH, Rodrigues EB. Intravitreal ziv-aflibercept for diabetic macular edema: 48-week outcomes. Ophthalmic Surg Lasers Imaging Retina 2018;49:245–250.

11. Ashraf M, Kayal HE, Souka AAR. Safety and efficacy of ziv-aflibercept in the treatment of refractory diabetic macular edema. Ophthalmic Surg Lasers Imaging Retina 2017;48:399–405.

12. Rayess N, Rahimy E, Ying GS, Bagheri N, Ho AC, Regillo CD, et al. Baseline choroidal thickness as a predictor for response to anti-vascular endothelial growth factor therapy in diabetic macular edema. Am J Ophthalmol 2015;159:85-91.e1–e3.

13. Bagheri N, Rayess N, Rahimy E, Juhn A, Hsu J. Initial choroidal thickness and response to treatment in diabetic macular edema. Invest Ophthalmol Vis Sci 2014;55:1747.

14. Cao J, McLeod DS, Merges CA, Lutty GA. Choriocapillaris degeneration and related pathologic changes in human diabetic eyes. Arch Ophthalmol 1998;116:589–597.

15. Querques G, Lattanzio R, Querques L, Del Turco C, Forte R, Pierro L, et al. Enhanced depth imaging optical coherence tomography in type 2 diabetes. Invest Ophthalmol Vis Sci 2012;53:6017–6024.

16. Adamis AP, Miller JW, Bernal MT, D’Amico DJ, Folkman J, Yeo TK, et al. Increased vascular endothelial growth factor levels in the vitreous of eyes with proliferative diabetic retinopathy. Am J Ophthalmol 1994;118:445–450.

17. de Oliveira Dias JR, Xavier CO, Maia A, de Moraes NS, Meyer C, Farah ME, et al. Intravitreal injection of zivaflibercept in patient with refractory age-related macular degeneration. Ophthalmic Surg Lasers Imaging Retina 2015;46:91–94.

18. Grading diabetic retinopathy from stereoscopic color fundus photographs–An extension of the modified Airlie House classification. ETDRS report number 10. Early Treatment Diabetic Retinopathy Study Research Group. Ophthalmology 1991;98:786–806.

19. Malik D, Tarek M, Caceres del Carpio J, Ramirez C, Boyer D, Kenney MC, et al. Safety profiles of anti-VEGF drugs: Bevacizumab, ranibizumab, aflibercept and ziv-aflibercept on human retinal pigment epithelium cells in culture. Br J Ophthalmol 2014;98:i11–i16.

20. de Oliveira Dias JR, Badaró E, Novais EA, Colicchio D, Chiarantin GM, Matioli MM, et al. Preclinical investigations of intravitreal ziv-aflibercept. Ophthalmic Surg Lasers Imaging Retina 2014;45:577–584.

21. Chhablani J, Narayanan R, Mathai A, Yogi R, Stewart M. Short-term safety profile of intravitreal ziv-aflibercept. Retina 2016;36:1126–1131.

22. Eliwa TF, Hegazy OS, Mahmoud SS, Almaamon T. Choroidal thickness change in patients with diabetic macular edema. Ophthalmic Surg Lasers Imaging Retina 2017;48:970–977.

23. Lee SH, Kim J, Chung H, Kim HC. Changes of choroidal thickness after treatment for diabetic retinopathy. Curr Eye Res 2014;39:736–744.

24. Tatsumi T, Oshitari T, Baba T, Takatsuna Y, Yamamoto S. Effects of switching from anti-VEGF treatment to triamcinolone acetonide in eyes with refractory macular edema associated with diabetic retinopathy or retinal vein occlusion. Biomed Res Int 2020;2020:4529850.

25. Sarda V, Eymard P, Hrarat L, Fajnkuchen F, Giocanti- Aurégan A. Comparison of the effect of ranibizumab and aflibercept on changes in macular choroidal thickness in patients treated for diabetic macular edema. J Ophthalmol 2020;5708354.

26. Sohn HJ, Han DH, Kim IT, Oh IK, Kim KH, Lee DY, et al. Changes in aqueous concentrations of various cytokines after intravitreal triamcinolone versus bevacizumab for diabetic macular edema. Am J Ophthalmol 2011;152:686– 694.