Serial optical coherence tomography angiography for corneal vascularization

  • Yijun Cai
  • Jorge L. Alio del Barrio
  • Mark R. Wilkins
  • Marcus AngEmail author



Recently, optical coherence tomography angiography (OCTA) has been used to successfully delineate vessels within the retina. This current study aims to assess corneal vascularization secondary to herpetic keratitis pre- and post-treatment using serial OCTA imaging adapted for the anterior segment.


All eyes were scanned using the split-spectrum amplitude decorrelation angiography (SSADA) algorithm on the AngioVue OCTA system (Optovue Inc. Fremont, CA, USA) with an anterior segment lens adapter. Multiple scans in the regions of interest (ROI) before and after treatment were analysed to assess change in corneal vascularization in response to each treatment modality.


We analyzed a total of 12 OCTA scans in three eyes with corneal vascularization, comparing images pre- and 3 months post-treatment. We found that the OCTA was able to detect a significant decrease in area of vascularization in all eyes: including fine-needle diathermy (48 ± 7 to 41 ± 5 %, P = 0.048), subconjunctival bevacizumab (45 ± 7 to 38 ± 5 %, P = 0.015) and systemic steroid treatment following graft rejection (38 ± 1 to 32 ± 2 %, P = 0.003).


Our preliminary study of serial OCTA scans suggests that this may be a useful tool for objective quantification of corneal vascularization. Future development of image processing software will be needed for clinical use or trials to evaluate anti-vascular therapies.


Corneal vascularization Optical coherence tomography angiography Anterior segment angiography 


Compliance with ethical standards


Singhealth Research Foundation (R1275/81/2015)

Conflict of interest

All authors certify that they have no affiliations with or involvement in any organization or entity with any financial interest (such as honoraria; educational grants; participation in speakers’ bureaus; membership, employment, consultancies, stock ownership, or other equity interest; and expert testimony or patent-licensing arrangements), or non-financial interest (such as personal or professional relationships, affiliations, knowledge or beliefs) in the subject matter or materials discussed in this manuscript.

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

Informed consent was obtained from all individual participants included in the study.


  1. 1.
    Spaide RF, Klancnik JM, Cooney MJ (2015) Retinal vascular layers imaged by fluorescein angiography and optical coherence tomography angiography. JAMA Ophthalmol 133:45–50. doi: 10.1001/jamaophthalmol.2014.3616 CrossRefPubMedGoogle Scholar
  2. 2.
    Qazi Y, Maddula S, Ambati BK (2009) Mediators of ocular angiogenesis. J Genet 88:495–515CrossRefPubMedPubMedCentralGoogle Scholar
  3. 3.
    Lee P, Wang CC, Adamis AP (1998) Ocular neovascularization: an epidemiologic review. Surv Ophthalmol 43:245–269CrossRefPubMedGoogle Scholar
  4. 4.
    Ang M, Mehta JS, Sng CC, Htoon HM, Tan DT (2012) Indications, outcomes, and risk factors for failure in tectonic keratoplasty. Ophthalmology 119:1311–1319. doi: 10.1016/j.ophtha.2012.01.021 CrossRefPubMedGoogle Scholar
  5. 5.
    Cursiefen C, Colin J, Dana R, Diaz-Llopis M, Faraj LA, Garcia-Delpech S, Geerling G, Price FW, Remeijer L, Rouse BT, Seitz B, Udaondo P, Meller D, Dua H (2012) Consensus statement on indications for anti-angiogenic therapy in the management of corneal diseases associated with neovascularisation: outcome of an expert roundtable. Br J Ophthalmol 96:3–9. doi: 10.1136/bjo.2011.204701 CrossRefPubMedGoogle Scholar
  6. 6.
    Ang M, Cai Y, MacPhee B, Sim DA, Keane PA, Sng CC, Egan CA, Tufail A, Larkin DF, Wilkins MR (2016) Optical coherence tomography angiography and indocyanine green angiography for corneal vascularisation. Br J Ophthalmol. doi: 10.1136/bjophthalmol-2015-307706 Google Scholar
  7. 7.
    Ang M, Sim DA, Keane PA, Sng CC, Egan CA, Tufail A, Wilkins MR (2015) Optical coherence tomography angiography for anterior segment vasculature imaging. Ophthalmology 122:1740–1747. doi: 10.1016/j.ophtha.2015.05.017 CrossRefPubMedGoogle Scholar
  8. 8.
    Hsu CC, Chang HM, Lin TC, Hung KH, Chien KH, Chen SY, Chen SN, Chen YT (2015) Corneal neovascularization and contemporary antiangiogenic therapeutics. J Chin Med Assoc 78:323–330. doi: 10.1016/j.jcma.2014.10.002 CrossRefPubMedGoogle Scholar
  9. 9.
    Gonzalez L, Loza RJ, Han KY, Sunoqrot S, Cunningham C, Purta P, Drake J, Jain S, Hong S, Chang JH (2013) Nanotechnology in corneal neovascularization therapy—a review. J Ocul Pharmacol Ther 29:124–134. doi: 10.1089/jop.2012.0158 CrossRefPubMedPubMedCentralGoogle Scholar
  10. 10.
    Ang M, Cai Y, Shahipasand S, Sim DA, Keane PA, Sng CC, Egan CA, Tufail A, Wilkins MR (2015) En face optical coherence tomography angiography for corneal neovascularisation. Br J Ophthalmol. doi: 10.1136/bjophthalmol-2015-307338 Google Scholar
  11. 11.
    Sharma A, Bettis DI, Cowden JW, Mohan RR (2010) Localization of angiotensin converting enzyme in rabbit cornea and its role in controlling corneal angiogenesis in vivo. Mol Vis 16:720–728PubMedPubMedCentralGoogle Scholar
  12. 12.
    Zheng Y, Kaye AE, Boker A, Stewart RK, Tey A, Ahmad S, Willoughby CE, Bron AJ, Kaye SB (2013) Marginal corneal vascular arcades. Invest Ophthalmol Vis Sci 54:7470–7477. doi: 10.1167/iovs.13-12614 CrossRefPubMedGoogle Scholar
  13. 13.
    Spiteri N, Romano V, Zheng Y, Yadav S, Dwivedi R, Chen J, Ahmad S, Willoughby CE, Kaye SB (2015) Corneal angiography for guiding and evaluating fine-needle diathermy treatment of corneal neovascularization. Ophthalmology 122:1079–1084. doi: 10.1016/j.ophtha.2015.02.012 CrossRefPubMedGoogle Scholar
  14. 14.
    Petsoglou C, Balaggan KS, Dart JK, Bunce C, Xing W, Ali RR, Tuft SJ (2013) Subconjunctival bevacizumab induces regression of corneal neovascularisation: a pilot randomised placebo-controlled double-masked trial. Br J Ophthalmol 97:28–32. doi: 10.1136/bjophthalmol-2012-302137 CrossRefPubMedGoogle Scholar
  15. 15.
    Papathanassiou M, Theodoropoulou S, Analitis A, Tzonou A, Theodossiadis PG (2013) Vascular endothelial growth factor inhibitors for treatment of corneal neovascularization: a meta-analysis. Cornea 32:435–444. doi: 10.1097/ICO.0b013e3182542613 CrossRefPubMedGoogle Scholar
  16. 16.
    Ang M, Mehta JS, Arundhati A, Tan DT (2009) Anterior lamellar keratoplasty over penetrating keratoplasty for optical, therapeutic, and tectonic indications: a case series. Am J Ophthalmol 147(697–702):e692. doi: 10.1016/j.ajo.2008.10.002 Google Scholar
  17. 17.
    Kirwan RP, Zheng Y, Tey A, Anijeet D, Sueke H, Kaye SB (2012) Quantifying changes in corneal neovascularization using fluorescein and indocyanine green angiography. Am J Ophthalmol 154:850–858.e852. doi: 10.1016/j.ajo.2012.04.021 CrossRefPubMedGoogle Scholar
  18. 18.
    Nieuwenhuizen J, Watson PG, Emmanouilidis-van der Spek K, Keunen JE, Jager MJ (2003) The value of combining anterior segment fluorescein angiography with indocyanine green angiography in scleral inflammation. Ophthalmology 110:1653–1666. doi: 10.1016/S0161-6420(03)00487-1 CrossRefPubMedGoogle Scholar
  19. 19.
    Watson PG, Bovey E (1985) Anterior segment fluorescein angiography in the diagnosis of scleral inflammation. Ophthalmology 92:1–11CrossRefPubMedGoogle Scholar
  20. 20.
    Chan CM, Chew PT, Alsagoff Z, Wong JS, Tan DT (2001) Vascular patterns in pterygium and conjunctival autografting: a pilot study using indocyanine green anterior segment angiography. Br J Ophthalmol 85:350–353CrossRefPubMedPubMedCentralGoogle Scholar
  21. 21.
    Kim YJ, Yoo SH, Chung JK (2014) Reconstruction of the limbal vasculature after limbal-conjunctival autograft transplantation in pterygium surgery: an angiography study. Invest Ophthalmol Vis Sci 55:7925–7933. doi: 10.1167/iovs.14-15288 CrossRefPubMedGoogle Scholar
  22. 22.
    Conrad TJ, Chandler DB, Corless JM, Klintworth GK (1994) In vivo measurement of corneal angiogenesis with video data acquisition and computerized image analysis. Lab Invest 70:426–434PubMedGoogle Scholar
  23. 23.
    Girard MJ, Ang M, Chung CW, Farook M, Strouthidis N, Mehta JS, Mari JM (2015) Enhancement of corneal visibility in optical coherence tomography images using corneal adaptive compensation. Transl Vis Sci Technol 4:3. doi: 10.1167/tvst.4.3.3 CrossRefPubMedPubMedCentralGoogle Scholar
  24. 24.
    Bock F, Onderka J, Hos D, Horn F, Martus P, Cursiefen C (2008) Improved semiautomatic method for morphometry of angiogenesis and lymphangiogenesis in corneal flatmounts. Exp Eye Res 87:462–470. doi: 10.1016/j.exer.2008.08.007 CrossRefPubMedGoogle Scholar
  25. 25.
    Bock F, Konig Y, Kruse F, Baier M, Cursiefen C (2008) Bevacizumab (Avastin) eye drops inhibit corneal neovascularization. Graefes Arch Clin Exp Ophthalmol 246:281–284. doi: 10.1007/s00417-007-0684-4 CrossRefPubMedGoogle Scholar
  26. 26.
    Cursiefen C, Bock F, Horn FK, Kruse FE, Seitz B, Borderie V, Früh B, Thiel MA, Wilhelm F, Geudelin B, Descohand I, Steuhl KP, Hahn A, Meller D (2009) GS-101 antisense oligonucleotide eye drops inhibit corneal neovascularization: interim results of a randomized phase II trial. Ophthalmology 116:1630–1637. doi: 10.1016/j.ophtha.2009.04.016 CrossRefPubMedGoogle Scholar
  27. 27.
    Ang M, Chong W, Huang H, Tay WT, Wong TY, He MG, Aung T, Mehta JS (2013) Comparison of anterior segment optical tomography parameters measured using a semi-automatic software to standard clinical instruments. PLoS One 8:e65559. doi: 10.1371/journal.pone.0065559 CrossRefPubMedPubMedCentralGoogle Scholar
  28. 28.
    Ang M, Sng C, Milea D (2016) Optical coherence tomography angiography in dural carotid-cavernous sinus fistula. BMC Ophthalmol 16:93. doi: 10.1186/s12886-016-0278-1 CrossRefPubMedPubMedCentralGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 2016

Authors and Affiliations

  • Yijun Cai
    • 1
  • Jorge L. Alio del Barrio
    • 2
  • Mark R. Wilkins
    • 1
  • Marcus Ang
    • 1
    • 3
    Email author
  1. 1.Moorfields Eye Hospital NHS Foundation TrustLondonUK
  2. 2.Cornea, Cataract and Refractive Surgery UnitVissum CorporaciónAlicanteSpain
  3. 3.Singapore Eye Research InstituteSingapore National Eye CenterSingaporeSingapore

Personalised recommendations