Advertisement

Effects of intravitreal injection of ranibizumab on choroidal structure and blood flow in eyes with diabetic macular edema

  • Masahiro Okamoto
  • Mariko Yamashita
  • Nahoko Ogata
Retinal Disorders

Abstract

Purpose

To determine the effects of an intravitreal injection of ranibizumab (IVR) on the choroidal structure and blood flow in eyes with diabetic macular edema (DME).

Methods

Twenty-eight consecutive patients with DME who received an IVR and 20 non-diabetic, age-matched controls were followed for 1 month. The eyes with DME were divided into those with prior panretinal photocoagulation (PRP, n = 16) and those without prior PRP (no-PRP, n = 12). The enhanced depth imaging optical coherence tomography (EDI-OCT) scans and Niblack’s image binarization were performed to determine the choroidal structure. The choroidal blood flow was determined by laser speckle flowgraphy.

Results

The subfoveal choroidal thickness at the baseline was significantly thicker in the no-PRP group than in the PRP-treated group. After IVR, the best-corrected visual acuity (BCVA) and central retinal thickness in eyes with DME were significantly improved compared to the baseline values. There were significant differences in the choroidal thickness, total choroidal area, and choroidal vascularity index between the groups after IVR. Choroidal vascular index and choroidal blood flow were significantly reduced only in the no-PRP group and not in the PRP-treated group. In addition, the correlation between the central retinal thickness and the choroidal blood flow was significant in the no-PRP group (r = 0.47, P < 0.05).

Conclusions

A single IVR will reduce the central retinal thickness and improve the BCVA in eyes with DME in both the no-PRP and PRP-treated group. IVR affected the choroidal vasculature and blood flow significantly, and a significant correlation was found between the central retinal thickness and the choroidal blood flow in eyes without PRP.

Keywords

Diabetic macular edema Intravitreal injection of ranibizumab Choroidal structure Choroidal thickness Choroidal blood flow 

Notes

Acknowledgments

The authors thank Professor Emeritus Duco Hamasaki of the Bascom Palmer Eye Institute for discussions and manuscript revision.

Compliance with ethical standards

Conflict of interest

The authors declare that they have no competing interests.

Ethical approval

All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki Declaration and its later amendments or comparable ethical standards.

Informed consent

For this type of study, formal consent is not required.

References

  1. 1.
    Romero-Aroca P (2011) Managing diabetic macular edema: the leading cause of diabetes blindness. World J Diabetes 2:98–104CrossRefPubMedPubMedCentralGoogle Scholar
  2. 2.
    Cao J, McLeod S, Merges CA, Lutty GA (1998) Choriocapillaris degeneration and related pathologic changes in human diabetic eyes. Arch Ophthalmol 116:589–597CrossRefPubMedGoogle Scholar
  3. 3.
    Querques G, Lattanzio R, Querques L et al (2012) Enhanced depth imaging optical coherence tomography in type 2 diabetes. Invest Ophthalmol Vis Sci 53:6017–6024CrossRefPubMedGoogle Scholar
  4. 4.
    Esmaeelpour M, Považay B, Hermann B et al (2011) Mapping choroidal and retinal thickness variation in type 2 diabetes using three-dimensional 1060-nm optical coherence tomography. Invest Ophthalmol Vis Sci 52:5311–5316CrossRefPubMedGoogle Scholar
  5. 5.
    Vujosevic S, Martini F, Cavarzeran F, Pilotto E, Midena E (2012) Macular and peripapillary choroidal thickness in diabetic patients. Retina 32:1781–1790CrossRefPubMedGoogle Scholar
  6. 6.
    Regatieri CV, Branchini L, Carmody J, Fujimoto JG, Duker JS (2012) Choroidal thickness in patients with diabetic retinopathy analyzed by spectral-domain optical coherence tomography. Retina 32:563–568CrossRefPubMedPubMedCentralGoogle Scholar
  7. 7.
    Brown DM, Nguyen QD, Marcus DM et al (2013) Long-term outcomes of ranibizumab therapy for diabetic macular edema: the 36-month results from two phase III trials: RISE and RIDE. Ophthalmology 120:2013–2022CrossRefPubMedGoogle Scholar
  8. 8.
    Totan Y, Akyüz TK, Güler E, Güragaç FB (2016) Evaluation of ocular pulse amplitude and choroidal thickness in diabetic macular edema. Eye 30:369–374CrossRefPubMedGoogle Scholar
  9. 9.
    Sonoda S, Sakamoto T, Yamashita T et al (2014) Effect of intravitreal triamcinolone acetonide or bevacizumab on choroidal thickness in eyes with diabetic macular edema. Invest Ophthalmol Vis Sci 55:3979–3985CrossRefPubMedGoogle Scholar
  10. 10.
    Gerendas BS, Waldstein SM, Simader C et al (2014) Three-dimensional automated choroidal volume assessment on standard spectral-domain optical coherence tomography and correlation with the level of diabetic macular edema. Am J Ophthalmol 158:1039–1048CrossRefPubMedPubMedCentralGoogle Scholar
  11. 11.
    Sonoda S, Sakamoto T, Yamashita T et al (2014) Choroidal structure in normal eyes and after photodynamic therapy determined by binarization of optical coherence tomographic images. Invest Ophthalmol Vis Sci 55:3893–3899CrossRefPubMedGoogle Scholar
  12. 12.
    Sonoda S, Sakamoto T, Yamashita T et al (2015) Luminal and stromal areas of choroid determined by binarization method of optical coherence tomographic images. Am J Ophthalmol 159:1123–1131CrossRefPubMedGoogle Scholar
  13. 13.
    Wilkinson CP, Ferris FL 3rd, Klein RE, Global diabetic retinopathy project group et al (2003) Proposed international clinical diabetic retinopathy and diabetic macular edema disease severity scales. Ophthalmogy 110:1677–1682CrossRefGoogle Scholar
  14. 14.
    Bressler NM, Beck RW, Ferris FL (2011) Panretinal photocoagulation for proliferative diabetic retinopathy. N Engl J Med 365:1520–1526CrossRefPubMedGoogle Scholar
  15. 15.
    Geyer O, Neudorfer M, Snir T et al (1999) Pulsatile ocular blood flow in diabetic retinopathy. Acta Ophthalmol Scand 77:522–525CrossRefPubMedGoogle Scholar
  16. 16.
    Okamoto M, Matsuura T, Ogata N (2016) Effects of panretinal photocoagulation on choroidal thickness and choroidal blood flow in patients with severe non-proliferative diabetic retinopathy. Retina 36:805–811CrossRefPubMedGoogle Scholar
  17. 17.
    Spaide RF, Koizumi H, Pozzoni MC (2008) Enhanced depth imaging spectral-domain optical coherence tomography. Am J Ophthalmol 146:496–500CrossRefPubMedGoogle Scholar
  18. 18.
    Brown JS, Flitcroft DI, Ying G et al (2009) In vivo human choroidal thickness measurements: evidence for diurnal fluctuations. Invest Ophthalmol Vis Sci 50:5–12CrossRefPubMedGoogle Scholar
  19. 19.
    Tan CS, Ouyang Y, Ruiz H, Sadda SR (2012) Diurnal variation of choroidal thickness in normal, healthy subjects measured by spectral domain optical coherence tomography. Invest Ophthalmol Vis Sci 53:261–266CrossRefPubMedGoogle Scholar
  20. 20.
    Sugiyama T, Araie M, Riva CE et al (2010) Use of laser speckle flowgraphy in ocular blood flow research. Acta Ophthalmol 88:723–729CrossRefPubMedGoogle Scholar
  21. 21.
    Saito M, Saito W, Hashimoto Y et al (2013) Macular choroidal blood flow velocity decreases with regression of acute central serous chorioretinopathy. Br J Ophthalmol 97:775–780CrossRefPubMedGoogle Scholar
  22. 22.
    Kim JT, Lee DH, Joe SG, Kim JG, Yoon YH (2013) Changes in choroidal thickness in relation to the severity of retinopathy and macular edema in type 2 diabetic patients. Invest Ophthalmol Vis Sci 54:3378–3384CrossRefPubMedGoogle Scholar
  23. 23.
    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 131:1267–1274CrossRefPubMedPubMedCentralGoogle Scholar
  24. 24.
    Laíns I, Figueira J, Santos AR et al (2014) Choroidal thickness in diabetic retinopathy: the influence of antiangiogenic therapy. Retina 34:1199–1207CrossRefPubMedGoogle Scholar
  25. 25.
    Yiu G, Manjunath V, Chiu SJ, Farsiu S, Mahmoud TH (2014) Effect of antivascular endothelial growth factor therapy on choroidal thickness in diabetic macular edema. Am J Ophthalmol 158:745–751CrossRefPubMedPubMedCentralGoogle Scholar
  26. 26.
    Rayess N, Rahimy E, Ying GS et al (2015) Baseline choroidal thickness as a predictor for response to anti-vascular endothelial growth factor therapy in diabetic macular edema. Am J Ophthalmol 59:85–91 e1-3CrossRefGoogle Scholar
  27. 27.
    Nitta F, Kunikata H, Aizawa N et al (2014) The effect of intravitreal bevacizumab on ocular blood flow in diabetic retinopathy and branch retinal vein occlusion as measured by laser speckle flowgraphy. Clin Ophthalmol 8:1119–1127PubMedPubMedCentralGoogle Scholar
  28. 28.
    Örnek N, Inal M, Erbahceci IE, Oğurel T, Örnek K (2015) Effect of intravitreal bevacizumab on retrobulbar blood flow of patients with diabetic macular edema. Eur J Ophthalmol 25:539–545CrossRefPubMedGoogle Scholar
  29. 29.
    Mendivil A (1997) Ocular blood flow velocities in patients with proliferative diabetic retinopathy after panretinal photocoagulation. Surv Ophthalmol 42:S89–S95CrossRefPubMedGoogle Scholar
  30. 30.
    Esmaeelpour M, Brunner S, Ansari-Shahrezaei S et al (2012) Choroidal thinning in diabetes type 1 detected by 3-dimensional 1060 nm optical coherence tomography. Invest Ophthalmol Vis Sci 53:6803–6809CrossRefPubMedGoogle Scholar
  31. 31.
    Ogata N, Ando A, Uyama M, Matsumura M (2001) Expression of cytokines and transcription factors in photocoagulated human retinal pigment epithelial cells. Graefes Arch Clin Exp Ophthalmol 239:87–95CrossRefPubMedGoogle Scholar
  32. 32.
    Ogata N, Nishikawa M, Nishimura T, Mitsuma Y, Matsumura M (2002) Unbalanced vitreous levels of pigment epithelium-derived factor and vascular endothelial growth factor in diabetic retinopathy. Am J Ophthalmol 134:348–353CrossRefPubMedGoogle Scholar
  33. 33.
    Gaudreault J, Fei D, Beyer JC et al (2007) Pharmacokinetics and retinal distribution of ranibizumab, a humanized antibody fragment directed against VEGF-A, following intravitreal administration in rabbits. Retina 27:1260–1266CrossRefPubMedGoogle Scholar

Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2018

Authors and Affiliations

  • Masahiro Okamoto
    • 1
  • Mariko Yamashita
    • 1
  • Nahoko Ogata
    • 1
  1. 1.Department of OphthalmologyNara Medical UniversityKashiharaJapan

Personalised recommendations