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International Ophthalmology

, Volume 39, Issue 10, pp 2361–2371 | Cite as

Optical coherence tomography angiography analysis of macular vessel density before and after anti-VEGF therapy in eyes with diabetic retinopathy

  • Osama A. Sorour
  • Almyr S. Sabrosa
  • A. Yasin Alibhai
  • Malvika Arya
  • Akihiro Ishibazawa
  • Andre J. Witkin
  • Caroline R. Baumal
  • Jay S. Duker
  • Nadia K. WaheedEmail author
Original Paper

Abstract

Purpose

To evaluate changes in macular vessel density following intravitreal anti-VEGF injection in patients with diabetic macular edema (DME) and proliferative diabetic retinopathy (PDR).

Methods

In this retrospective case series, optical coherence tomography angiography (OCTA) images from 55 eyes of 35 patients with either DME (46 eyes) or PDR (9 eyes) were included. Macular capillary vessel density at the level of the superficial retinal capillary plexus (SCP), deep retinal capillary plexus (DCP) and total retinal capillary plexus (TCP) before and after anti-VEGF treatment was calculated. Longitudinal changes in vessel density following serial anti-VEGF treatment were analyzed in a subset of eyes.

Results

Vessel density in the SCP, DCP or TCP was not found to be significantly different after one, two or three intravitreal injections (p > 0.05 for all time points). Subgroup analysis revealed no significant change in the DME and PDR subgroups (all p > 0.05). Multivariate analysis revealed no effect of type of injected anti-VEGF agent or presence of previous treatment on VD measurements (all p > 0.05). There was no correlation between the anatomic response of DME to treatment and VD measurements.

Conclusions

In this study, macular vessel density remained statistically unchanged following up to three intravitreal injections of any anti-VEGF agent. This indicates that there may not be an early effect of anti-VEGF treatment on macular vessel density and its effect on macular perfusion may not be a direct change in microvascular flow.

Keywords

Aflibercept Anti-VEGF Bevacizumab, diabetic retinopathy Macular edema Optical coherence tomography angiography Proliferative diabetic retinopathy Ranibizumab Vessel density 

Notes

Acknowledgement

Authors acknowledge Nihaal Mehta, at New England Eye Center, Boston, for his effort in preparation of this manuscript.

Funding

Macula Vision Research Foundation (MVRF), Massachusetts Lions Clubs.

Compliance with ethical standards

Conflict of interest

The authors declare that they have no competing interests.

Financial disclosure

Sorour: None, Sabrosa: None, Alibbhai: None, Arya: None, Ishibazawa: Speaker, Topcon Medical Systems, Inc., Nidek Medical Products, Inc, Witkin: None; Baumal: Consultant, Genentech, Speaker, Carl Zeiss Meditec; Duker: Consultant and Financial Support, Carl Zeiss Meditec, Inc., Optovue, Inc., Topcon Medical Systems, Inc., Novartis Pharma AG., and Roche; Waheed: Financial Support, Macula Vision Research Foundation, Topcon Medical Systems, Inc., Nidek Medical Products, Inc., and Carl Zeiss Meditec, Inc., Consultant, Optovue, Inc., Regeneron, and Genentech.

References

  1. 1.
    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 (1991). Ophthalmology 98(5 Suppl):786–806Google Scholar
  2. 2.
    Adhi M, Brewer E, Waheed NK, Duker JS (2013) Analysis of morphological features and vascular layers of choroid in diabetic retinopathy using spectral-domain optical coherence tomography. JAMA Ophthalmol 131(10):1267–1274.  https://doi.org/10.1001/jamaophthalmol.2013.4321 CrossRefPubMedPubMedCentralGoogle Scholar
  3. 3.
    Simo R, Hernandez C (2008) Intravitreous anti-VEGF for diabetic retinopathy: hopes and fears for a new therapeutic strategy. Diabetologia 51(9):1574–1580.  https://doi.org/10.1007/s00125-008-0989-9 CrossRefPubMedGoogle Scholar
  4. 4.
    Or C, Sabrosa AS, Sorour O, Arya M, Waheed N (2018) Use of OCTA, FA, and Ultra-Widefield imaging in quantifying retinal ischemia: a review. Asia Pac J Ophthalmol 7(1):46–51.  https://doi.org/10.22608/APO.201812 CrossRefPubMedCentralGoogle Scholar
  5. 5.
    Sorour O, Arya M, Waheed N (2018) New findings and challenges in OCT angiography for diabetic retinopathy. Ann Eye Sci 3:44CrossRefGoogle Scholar
  6. 6.
    de Carlo TE, Chin AT, Bonini Filho MA, Adhi M, Branchini L, Salz DA, Baumal CR, Crawford C, Reichel E, Witkin AJ, Duker JS, Waheed NK (2015) Detection of microvascular changes in eyes of patients with diabetes but not clinical diabetic retinopathy using optical coherence tomography angiography. Retina 35(11):2364–2370.  https://doi.org/10.1097/IAE.0000000000000882 CrossRefPubMedPubMedCentralGoogle Scholar
  7. 7.
    Chandra S, Sheth J, Anantharaman G, Gopalakrishnan M (2018) Ranibizumab-induced retinal reperfusion and regression of neovascularization in diabetic retinopathy: an angiographic illustration. Am J Ophthalmol Case Rep 9:41–44.  https://doi.org/10.1016/j.ajoc.2018.01.006 CrossRefPubMedPubMedCentralGoogle Scholar
  8. 8.
    Reddy RK, Pieramici DJ, Gune S, Ghanekar A, Lu N, Quezada-Ruiz C, Baumal CR (2018) Efficacy of ranibizumab in eyes with diabetic macular edema and macular nonperfusion in RIDE and RISE. Ophthalmology.  https://doi.org/10.1016/j.ophtha.2018.04.002 CrossRefPubMedGoogle Scholar
  9. 9.
    Writing Committee for the Diabetic Retinopathy Clinical Research Network, Gross JG, Glassman AR, Jampol LM, Inusah S, Aiello LP, Antoszyk AN, Baker CW, Berger BB, Bressler NM, Browning D, Elman MJ, Ferris FL 3rd, Friedman SM, Marcus DM, Melia M, Stockdale CR, Sun JK, Beck RW (2015) Panretinal photocoagulation versus intravitreous ranibizumab for proliferative diabetic retinopathy: a randomized clinical trial. JAMA 314(20):2137–2146.  https://doi.org/10.1001/jama.2015.15217 CrossRefGoogle Scholar
  10. 10.
    Shimura M, Yasuda K (2010) Macular ischaemia after intravitreal bevacizumab injection in patients with central retinal vein occlusion and a history of diabetes and vascular disease. Br J Ophthalmol 94(3):381–383.  https://doi.org/10.1136/bjo.2009.160986 CrossRefPubMedGoogle Scholar
  11. 11.
    Leung LS, Silva RA, Blumenkranz MS, Flynn HW Jr, Sanislo SR (2012) Macular infarction following intravitreal bevacizumab for treatment of central retinal vein occlusion. Ophthalmic Surg Lasers Imaging 43 (Online):e73-79.  https://doi.org/10.3928/15428877-20120712-05
  12. 12.
    Optuvue (2017) User manual international software version 2017.1 with DualTrac. RTVue XR Avanti User Manual Fremont, CA, USAGoogle Scholar
  13. 13.
    Ghasemi Falavarjani K, Iafe NA, Hubschman JP, Tsui I, Sadda SR, Sarraf D (2017) Optical coherence tomography angiography analysis of the foveal avascular zone and macular vessel density after anti-VEGF therapy in eyes with diabetic macular edema and retinal vein occlusion. Invest Ophthalmol Vis Sci 58(1):30–34.  https://doi.org/10.1167/iovs.16-20579 CrossRefPubMedPubMedCentralGoogle Scholar
  14. 14.
    Hwang TS, Gao SS, Liu L, Lauer AK, Bailey ST, Flaxel CJ, Wilson DJ, Huang D, Jia Y (2016) Automated quantification of capillary nonperfusion using optical coherence tomography angiography in diabetic retinopathy. JAMA Ophthalmol 134(4):367–373.  https://doi.org/10.1001/jamaophthalmol.2015.5658 CrossRefPubMedPubMedCentralGoogle Scholar
  15. 15.
    Dimitrova G, Chihara E, Takahashi H, Amano H, Okazaki K (2017) Quantitative retinal optical coherence tomography angiography in patients with diabetes without diabetic retinopathy. Invest Ophthalmol Vis Sci 58(1):190–196.  https://doi.org/10.1167/iovs.16-20531 CrossRefPubMedPubMedCentralGoogle Scholar
  16. 16.
    Agemy SA, Scripsema NK, Shah CM, Chui T, Garcia PM, Lee JG, Gentile RC, Hsiao YS, Zhou Q, Ko T, Rosen RB (2015) Retinal vascular perfusion density mapping using optical coherence tomography angiography in normals and diabetic retinopathy patients. Retina 35(11):2353–2363.  https://doi.org/10.1097/IAE.0000000000000862 CrossRefPubMedPubMedCentralGoogle Scholar
  17. 17.
    Kim AY, Chu Z, Shahidzadeh A, Wang RK, Puliafito CA, Kashani AH (2016) Quantifying microvascular density and morphology in diabetic retinopathy using spectral-domain optical coherence tomography angiography. Invest Ophthalmol Vis Sci 57(9):OCT362-370.  https://doi.org/10.1167/iovs.15-18904 CrossRefGoogle Scholar
  18. 18.
    Al-Sheikh M, Akil H, Pfau M, Sadda SR (2016) Swept-source OCT angiography imaging of the foveal avascular zone and macular capillary network density in diabetic retinopathy. Invest Ophthalmol Vis Sci 57(8):3907–3913.  https://doi.org/10.1167/iovs.16-19570 CrossRefPubMedPubMedCentralGoogle Scholar
  19. 19.
    Mastropasqua R, Toto L, Mastropasqua A, Aloia R, De Nicola C, Mattei PA, Di Marzio G, Di Nicola M, Di Antonio L (2017) Foveal avascular zone area and parafoveal vessel density measurements in different stages of diabetic retinopathy by optical coherence tomography angiography. Int J Ophthalmol 10(10):1545–1551.  https://doi.org/10.18240/ijo.2017.10.11 CrossRefPubMedPubMedCentralGoogle Scholar
  20. 20.
    Yanik Odabas O, Demirel S, Ozmert E, Batioglu F (2018) Repeatability of automated vessel density and superficial and deep foveal avascular zone area measurements using optical coherence tomography angiography: diurnal findings. Retina 38(6):1238–1245.  https://doi.org/10.1097/IAE.0000000000001671 CrossRefPubMedGoogle Scholar
  21. 21.
    Spaide RF (2016) Volume-rendered optical coherence tomography of retinal vein occlusion pilot study. Am J Ophthalmol 165:133–144.  https://doi.org/10.1016/j.ajo.2016.02.037 CrossRefPubMedGoogle Scholar
  22. 22.
    Campochiaro PA, Bhisitkul RB, Shapiro H, Rubio RG (2013) Vascular endothelial growth factor promotes progressive retinal nonperfusion in patients with retinal vein occlusion. Ophthalmology 120(4):795–802.  https://doi.org/10.1016/j.ophtha.2012.09.032 CrossRefPubMedGoogle Scholar
  23. 23.
    Campochiaro PA, Wykoff CC, Shapiro H, Rubio RG, Ehrlich JS (2014) Neutralization of vascular endothelial growth factor slows progression of retinal nonperfusion in patients with diabetic macular edema. Ophthalmology 121(9):1783–1789.  https://doi.org/10.1016/j.ophtha.2014.03.021 CrossRefPubMedGoogle Scholar
  24. 24.
    Toto L, D’Aloisio R, Di Nicola M, Di Martino G, Di Staso S, Ciancaglini M, Tognetto D, Mastropasqua L (2017) Qualitative and quantitative assessment of vascular changes in diabetic macular edema after dexamethasone implant using optical coherence tomography angiography. Int J Mol Sci.  https://doi.org/10.3390/ijms18061181 CrossRefPubMedPubMedCentralGoogle Scholar
  25. 25.
    Michalska-Malecka K, Heinke Knudsen A (2017) Optical coherence tomography angiography in patients with diabetic retinopathy treated with anti-VEGF intravitreal injections: case report. Medicine 96(45):e8379.  https://doi.org/10.1097/MD.0000000000008379 CrossRefPubMedPubMedCentralGoogle Scholar
  26. 26.
    Lee J, Moon BG, Cho AR, Yoon YH (2016) Optical coherence tomography angiography of DME and its association with anti-VEGF treatment response. Ophthalmology 123(11):2368–2375.  https://doi.org/10.1016/j.ophtha.2016.07.010 CrossRefPubMedPubMedCentralGoogle Scholar
  27. 27.
    Bahrami B, Hong T, Zhu M, Schlub TE, Chang A (2017) Switching therapy from bevacizumab to aflibercept for the management of persistent diabetic macular edema. Graefe’s Arch Clin Exp Ophthalmol = Albrecht von Graefes Archiv fur klinische und experimentelle Ophthalmologie 255(6):1133–1140.  https://doi.org/10.1007/s00417-017-3624-y CrossRefGoogle Scholar
  28. 28.
    Ehlers JP, Wang K, Singh RP, Babiuch AS, Schachat AP, Yuan A, Reese JL, Stiegel L, Srivastava SK (2018) A prospective randomized comparative dosing trial of ranibizumab in bevacizumab-resistant diabetic macular edema: the REACT study. Ophthalmol Retina 2(3):217–224.  https://doi.org/10.1016/j.oret.2017.07.004 CrossRefPubMedPubMedCentralGoogle Scholar
  29. 29.
    Laiginhas R, Silva MI, Rosas V, Penas S, Fernandes VA, Rocha-Sousa A, Carneiro A, Falcao-Reis F, Falcao (2018) Aflibercept in diabetic macular edema refractory to previous bevacizumab: outcomes and predictors of success. Graefe’s Arch Clin Exp Ophthalmol = Albrecht von Graefes Archiv fur klinische und experimentelle Ophthalmologie 256(1):83–89.  https://doi.org/10.1007/s00417-017-3836-1 CrossRefGoogle Scholar

Copyright information

© Springer Nature B.V. 2019

Authors and Affiliations

  • Osama A. Sorour
    • 1
    • 2
  • Almyr S. Sabrosa
    • 1
    • 3
  • A. Yasin Alibhai
    • 1
  • Malvika Arya
    • 1
  • Akihiro Ishibazawa
    • 1
    • 4
  • Andre J. Witkin
    • 1
  • Caroline R. Baumal
    • 1
  • Jay S. Duker
    • 1
  • Nadia K. Waheed
    • 1
    Email author
  1. 1.New England Eye Center, Tufts Medical CenterBostonUSA
  2. 2.Ophthalmology DepartmentTanta UniversityTantaEgypt
  3. 3.Institute Ophthalmology Rio de Janeiro/Hospital da GamboaRio de JaneiroBrazil
  4. 4.Department of OphthalmologyAsahikawa Medical UniversityHokkaidoJapan

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