Preview

Russian Ophthalmological Journal

Advanced search

The role of optical coherence tomography angiography biomarkers in assessing the outcome of long-term anti-VEGF therapy of diabetic macular edema

https://doi.org/10.21516/2072-0076-2021-14-4-95-102

Abstract

The purpose of the study was to assess the changes of biomarkers of diabetic macular edema activity by optical coherence tomography angiography (OCTA) data and the relationship of these biomarkers with the response to anti-VEGF therapy during a two-year follow-up. 
Material and methods. The study included 59 patients (101) eyes, averagely aged 60.27 ± 9.50 years. The average number of intravitreal injections of aflibercept over the treatment period was 12.87 ± 3.50. The initial size of the foveolar avascular zone (FAZ) area — 0.37 ± 0.22 mm2 , and the acircularity index — 0.56 ± 0.14 remained unchanged after 5 months: 0.36 ± 0.24 mm2  and 0.56 ± 0.12, respectively, and being practically in the same level in 12 and 24 months. The large FAZ area, noted in the group where disorganization of retinal inner layers (DRIL) was observed (0.39 ± 0.21 mm2 ), correlated with a lower visual acuity (r = 0.67, p = 0.003). The acircularity index remained unchanged; no significant differences were found in the DRIL patient groups. After 5 loading injections, the average initial density of vessels in the macular region increased from 12.33 ± 3.86 mm to 12.75 ± 1.14 mm, after 1 year it was 13.48 ± 1.15 mm, after 2 years — 13.25 ± 3.39 mm. The average density of retinal perfusion increased at the 5th month from 29.81 ± 10.85 % to 31.55 ± 2.34 %, after 12 months to 32.91 ± 3.45, and by the end of the observation period to 31.41 ± 9.79 %. In the DRIL group, the baseline vascular density and mean perfusion volume were significantly lower: 11.17 ± 2.09 mm vs. 13.49 ± 1.14 mm and 28.40 ± 4.53 % vs. 31.20 ± 2.44 %). 
Conclusion. DRIL, a biomarker reflecting impaired capillary blood flow in the superficial capillary plexus and correlating with functional results, can be used as a predictor of antiangiogenic therapy effectiveness. After antiangiogenic therapy with DMO, the microcirculation indices (FAZ and acircularity) remained stable, and the vascular density and perfusion volume tended to increase, which testifies to the absence of ischemic damage.

About the Authors

A. Zh. Fursova
Novosibirsk State Region Hospital; Novosibirsk State Medical University
Russian Federation

Anzhella Zh. Fursova — Dr. of Med. Sci., head of ophthalmology department, head of chair of ophthalmology

130, Nemirovich-Danchenko str, Novosibirsk, 630087

52, Krasny Prospect, Novosibirsk, 630091



A. S. Derbeneva
Novosibirsk State Region Hospital; Novosibirsk State Medical University
Russian Federation

Anna S. Derbeneva — ophthalmologist, assistant professor of chair of ophthalmology

130, Nemirovich-Danchenko str, Novosibirsk, 630087

52, Krasny Prospect, Novosibirsk, 630091



M. S. Tarasov
Novosibirsk State Region Hospital; Novosibirsk State Medical University
Russian Federation

Mikhail S. Tarasov — ophthalmologist, assistant professor of chair of ophthalmology

130, Nemirovich-Danchenko str, Novosibirsk, 630087

52, Krasny Prospect, Novosibirsk, 630091



M. V. Vasil’eva
Novosibirsk State Region Hospital
Russian Federation

Maria V. Vasil’eva — ophthalmologist

130, Nemirovich-Danchenko str, Novosibirsk, 630087



J. A. Gamza
Novosibirsk State Region Hospital; Novosibirsk State Medical University
Russian Federation

Julia A. Gamza — ophthalmologist, assistant professor of chair of ophthalmology

130, Nemirovich-Danchenko str, Novosibirsk, 630087

52, Krasny Prospect, Novosibirsk, 630091



N. V. Chubar
Novosibirsk State Region Hospital
Russian Federation

Nadezhda V. Chubar — ophthalmologist

130, Nemirovich-Danchenko str, Novosibirsk, 630087



References

1. Douvali M., Chatziralli I.P., Theodossiadis P.G., et al. Effect of macular ischemia on intravitreal ranibizumab treatment for diabetic macular edema. Ophthalmologica. 2014; 232: 136–43. https://doi.org/10.1159/00036090

2. Neroev V.V., Okhotsimskaya T.D., Fadeeva V.A. An account of retinal microvascular changes in diabetes acquired by OCT angiography. Russian ophthalmological journal. 2017; 10 (2): 40–5 (In Russian). https://doi.org/10.21516/2072-0076-2017-10-2-40-45

3. Neroev V.V., Kiseleva T.N., Okhotsimskaya T.D., Fadeeva V.A.,Ramasanova K.A. Impact of antiangiogenic therapy on ocular blood flow and microcirculation in diabetic macular edema. Vestnik oftal’mologii. 2018; 134 (4): 3–10 (In Russian). https://doi.org/10.17116/oftalma20181340413

4. Fursova A.Zh., Derbeneva A.S., Tarasov M.S., et al. Clinical efficacy of antiangiogenic therapy for diabetic macular edema in real clinical practice (2-year results). Russian ophthalmological journal. 2021; 14 (2): 42–9 (In Russian). https://doi.org/10.21516/2072-0076-2021-14-2-42-49

5. Fursova A.Zh., Chubar N.V., Tarasov M.S., Saifullina I.F., Pustovaya G.G. Clinical associations between photoreceptor status and visual outcomes in diabetic macular edema. Vestnik oftal’mologii. 2017; 133 (1): 11–8 (In Russian). https://doi.org/10.17116/oftalma2017133111-18

6. Takase N., Nozaki M., Kato A., et al. Enlargement of foveal avascular zone in diabetic eyes evaluated by en face optical coherence tomography angiography. Retina. 2015; 35 (11): 2377–83. https://doi.org/10.1097/IAE.0000000000000849

7. Nicholson L., Ramu J., Triantafyllopoulou I., et al. Diagnostic accuracy of disorganization of the retinal inner layers in detect- ing macular capillary nonperfusion in diabetic retinopathy. Clin. Exp. Ophthalmol. 2015; 43 (8): 735–41. https://doi.org/10.1111/ceo.12557

8. Sakata K., Funatsu H., Harino S., et al. Relationship of macular microcirculation and retinal thickness with visual acuity in diabetic macular edema. Ophthalmology 2007; 114 (11): 2061–9. https://doi.org/10.1016/j.ophtha.2007.01.003

9. Moein H.R., Novais E.A., Rebhun C.B., et al. Optical coherence tomography angiography to detect macular capillary ischemia in patients with inner retinal changes after resolved diabetic macular edema. Retina. 2018; 38 (12 Dec.): 2277–84. https://doi.org/10.1097/IAE.0000000000001902

10. Heier J., Korobelnik J., Brown D., et al. Intravitreal Aflibercept for diabetic macular edema. Ophthalmology. 2016; 123 (11): 2376–85. https://doi.org/10.1016/j.ophtha.2016.07.032

11. Brown D., Schmidt-Erfurth U., Do D., et al. Intravitreal Aflibercept for diabetic macular edema. Ophthalmology. 2015; 122 (10): 2044–52. https://doi.org/10.1016/j.ophtha.2015.06.017

12. Gill A., Cole E. D., Novais E. A., et al. Visualization of changes in avascular zone in both observed and treated diabetic macular edema using optical coherence tomography angiography. Int. J. Retina Vitreous. 2017; 3. Available at: https://journalretinavitreous.biomedcentral.com/articles/10.1186/s40942-017-0074-y

13. Di G., Weihong Y., Xiao Z., et al. A morphological study of the foveal avascular zone in patients with diabetes mellitus using optical coherence tomography angiography. Graefes Arch. Clin. Exp. Ophthalmol. 2016; 254 (5 May): 873–9. https://doi.org/10.1007/s00417-015-3143-7

14. Freiberg F.J., Pfau M., Wons J., et al. Optical coherence tomography angiography of the foveal avascular zone in dia- betic retinopathy. Graefes Arch. Clin. Exp. Ophthalmol. 2016; 254 (6 Jun.): 1051–8. https://doi.org/10.1007/s00417-015-3148-2

15. Sun J.K., Lin M.M., Lammer J., et al. Disorganization of the retinal inner layers as a predictor of visual acuity in eyes with center-involved diabetic macular edema. JAMA Ophthalmol. 2014; 132: 1309–16. https://doi.org/10.1001/jamaophthalmol.2014.2350

16. Hsieh Y.T., Alam M.N., Le D., et al. OCT Angiography biomarkers for predicting visual outcomes after Ranibizumab treatment for diabetic macular edema. Ophthalmol. Retina. 2019; 3 (10 Oct.): 826–34. https://doi.org/10..1016/j.oret.2019.04.027

17. Vance S.K., Chang L.K., Imamura Y., Freund K.B. Effects of intravitreal antivascular endothelial growth factor treatment on retinal vaculature in retinal vein occlusion as determined by ultra-wide field fluorscein angiography. Retinal Cases Brief Reports. 2011; 5 (4): 343–7. https://doi.org/10.1097/ICB.0b013e3181ff0999

18. Dabir S., Rajan M., Parasseril L., et al. Early visual functional outcomes and morphological responses to anti-vascular growth factor therapy in diabetic macular oedema using Optical Coherence Tomography Angiography. Clin. Ophthalmol. 2021; 15: 331–9. https://doi.org/10.2147/OPTH.S285388

19. Manousaridis K., Talks J. Macular ischaemia: a contraindication for anti-VEGF treatment in retinal vascular disease? Br. J. Ophthalmol. 2012; 96: 179–84. https://doi.org/10.1136/bjophthalmol-2011-301087

20. Mendrinos E., Mangioris G., Papandopoulou D.N., Donati G., Pournaras C.J. Long-term results of the effect of intravitreal ranibizumab on the retinal arteriolar diameter in patients with neovascular age-related macular degeneration. Acta Ophthalmol. 2013; 91: e 184–90. https://doi.org/10.1111/aos.12008

21. Falavarjani K.G., Iafe N.A., Hubschman J., et al. 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. 2017; 58 (1): 30–4. https://doi.org/10.1167/iovs.16-20579

22. Spaide R.F. Volume-rendered optical coherence tomography of retinal vein occlusion pilot study. Am. J. Ophthalmol. 2016; 165: 133–44. https://doi.org/10.1016/j.ajo.2016.02.037

23. Wangsa-Wirawan N.D., Linsenmeier R.A. Retinal oxygen: fundamental and clinical aspects. Arch. Ophthalmol. 2003; 121: 547–57. https://doi.org/10.1001/archopht.121.4.547

24. Campochiaro P.A., Bhisitkul R.B., Shapiro H., Rubio R.G. Vascular endothelial growth factor promotes progressive retinal non- perfusion in patients with retinal vein occlusion. Ophthalmology. 2013; 120 (4): 795–802. https://doi.org/10.1016/j.ophtha.2012.09.032

25. Campochiaro P.A., Wykoff C.C., Shapiro H., Rubio R.G., Ehrlich J.S. Neutralization of vascular endothelial growth factor slows progression of retinal nonperfusion in patients with diabetic macular edema. Ophthalmology. 2014; 121: 1783–9. https://doi.org/10.1016/j.ophtha.2014.03.021

26. Sun J.K., Lin M.M., Lammer J., et al. Disorganization of the retinal inner layers as a predictor of visual acuity in eyes with center-involved diabetic macular edema. JAMA Ophthalmol. 2014; 132: 1309–16. https://doi.org/10.1001/jamaophthalmol.2014.2350

27. Bek T. Transretinal histopathological changes in capillary-free areas of diabetic retinopathy. Acta Ophthalmol. (Copenh). 1994; 72: 409–15. https://doi.org/10.1111/j.1755-3768.1994.tb02787.x

28. Grewal D. S., O’Sullivan M. L., Kron M., Jaffe G.J. Association of disorganization of retinal inner layers with visual acuity in eyes with uveitic cystoid macular edema. Am. J. Ophthalmol. 2017; 177: 116–25. https://doi.org/10.1016/j.ajo.2017.02.017

29. Nadri G., Saxena S., Stefanickova J., et al. Disorganization of retinal inner layers correlates with ellipsoid zone disruption and retinal nerve fiber layer thinning in diabetic retinopathy. J. Diabetes Complicat. 2019; 33: 550–3. https://doi.org/10.1016/j.jdiacomp.2019.05.006

30. Das R., Spence G., Hogg R.E., Stevenson M., Chakravarthy U. Disorganization of inner retina and outer retinal morphology in diabetic macular edema. JAMA Ophthalmol. 2018; 136: 202–8. https://doi.org/10.1001/jamaophthalmol.2017.6256

31. Yeung L., Lima V.C., Garcia P., et al. Correlation between spectral domain optical coherence tomography findings and fluorescein angiography patterns in diabetic macular edema. Ophthalmology. 2009; 116 (6 Jun.): 1158–67. https://doi.org/10.1016/j.ophtha.2008.12.063


Review

For citations:


Fursova A.Zh., Derbeneva A.S., Tarasov M.S., Vasil’eva M.V., Gamza J.A., Chubar N.V. The role of optical coherence tomography angiography biomarkers in assessing the outcome of long-term anti-VEGF therapy of diabetic macular edema. Russian Ophthalmological Journal. 2021;14(4):95-102. (In Russ.) https://doi.org/10.21516/2072-0076-2021-14-4-95-102

Views: 789


Creative Commons License
This work is licensed under a Creative Commons Attribution 4.0 License.


ISSN 2072-0076 (Print)
ISSN 2587-5760 (Online)