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Anterior Segment Optical Coherence Tomography Angiography Assessment of Corneal Vascularisation After Combined Fine-Needle Diathermy with Subconjunctival Ranibizumab: A Pilot Study

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Abstract

Introduction

To describe anterior segment optical coherence tomography angiography (AS-OCTA) imaging to monitor corneal vascularisation (CoNV) and scar reduction after combined fine-needle diathermy (FND) with subconjunctival ranibizumab.

Methods

Prospective clinical study of six eyes from six subjects with corneal scar and CoNV which underwent combined FND with subconjunctival ranibizumab. All eyes were imaged using slit-lamp photography (SLP) and AS-OCTA (Optovue, Inc., Fremont, CA, wavelength: 840 nm) before and after the operation, with two independent masked assessors analysing all images. Main outcome measures were changes in median corneal scar area and vessel density (AS-OCTA) comparing pre- and postoperative imaging up to month 3 and 6.

Results

The mean age of the subjects was 60 ± 23 years, with three males and three females. CoNV and corneal scarring involving the visual axis were present in all eyes, secondary to previous infective keratitis (n = 3), severe blepharokeratoconjunctivitis (n = 2), or chemical injury (n = 1). Follow-up time frame ranged from 2 to 6 months postoperation. There was a reduction in median corneal scar area from 30.2 mm2 (IQR 18.7–38.5) before surgery to 14.8 mm2 (IQR 7.1–19.6) after surgery, with a median reduction of 37.1% (IQR = − 3.1–86.9, p = 0.046). There was also a reduction in median cornea vessel density (AS-OCTA) from 20.8% (IQR 16.1–20.8) before surgery to 17.6% (IQR 14.0–17.6) after surgery, with a median reduction of 15.1% (IQR 13.2–15.1, p < 0.001).

Conclusions

Combined imaging of SLP and AS-OCTA is useful for monitoring treatment response of corneal scarring and CoNV after combined FND with subconjunctival Ranibizumab.

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References

  1. Azar DT. Corneal angiogenic privilege: angiogenic and antiangiogenic factors in corneal avascularity, vasculogenesis, and wound healing (an American Ophthalmological Society thesis). Trans Am Ophthalmol Soc. 2006;104:264–330.

    PubMed  PubMed Central  Google Scholar 

  2. Chang JH, Gabison EE, Kato T, Azar DT. Corneal neovascularization. Curr Opin Ophthalmol. 2001;12(4):242–9.

    Article  CAS  Google Scholar 

  3. Feizi S, Azari AA, Safapour S. Therapeutic approaches for corneal neovascularization. Eye Vis (Lond). 2017;4:28.

    Article  Google Scholar 

  4. Sharif Z, Sharif W. Corneal neovascularization: updates on pathophysiology, investigations & management. Rom J Ophthalmol. 2019;63(1):15–22.

    Article  Google Scholar 

  5. Armitage WJ, Goodchild C, Griffin MD, Gunn DJ, Hjortdal J, Lohan P, Murphy CC, Pleyer U, Ritter T, Tole DM, Vabres B. High-risk corneal transplantation: Recent developments and future possibilities. Transplantation. 2019;103(12):2468.

    Article  CAS  Google Scholar 

  6. Stevenson W, Cheng SF, Dastjerdi MH, Ferrari G, Dana R. Corneal neovascularization and the utility of topical VEGF inhibition: ranibizumab (Lucentis) vs bevacizumab (Avastin). Ocul Surf. 2012;10(2):67–83.

    Article  Google Scholar 

  7. Pillai CT, Dua HS, Hossain P. Fine needle diathermy occlusion of corneal vessels. Invest Ophthalmol Vis Sci. 2000;41(8):2148–53.

    CAS  PubMed  Google Scholar 

  8. Le VN, Hou Y, Bock F, Cursiefen C. Supplemental anti Vegf A-therapy prevents rebound neovascularisation after fine needle diathermy treatment to regress pathological corneal (LYMPH) angiogenesis. Sci Rep. 2020;10(1):1–8.

    Article  Google Scholar 

  9. Koenig Y, Bock F, Kruse FE, Stock K, Cursiefen C. Angioregressive pretreatment of mature corneal blood vessels before keratoplasty: fine-needle vessel coagulation combined with anti-VEGFs. Cornea. 2012;31:887–92.

    Article  Google Scholar 

  10. Elbaz U, Mireskandari K, Shen C, Ali A. Corneal fine needle diathermy with adjuvant bevacizumab to treat corneal neovascularization in children. Cornea. 2015;34(7):773–7.

    Article  Google Scholar 

  11. Hussain R, Savant V. Fine-needle diathermy with simultaneous subconjunctival bevacizumab. Semin Ophthalmol. 2017;32(5):550–2.

    Article  Google Scholar 

  12. Zou L, Lai H, Zhou Q, Xiao F. Lasting controversy on ranibizumab and bevacizumab. Theranostics. 2011;1:395.

    Article  CAS  Google Scholar 

  13. Koenig Y, Bock F, Horn F, Kruse F, Straub K, Cursiefen C. Short-and long-term safety profile and efficacy of topical bevacizumab (Avastin®) eye drops against corneal neovascularization. Graefes Arch Clin Exp Ophthalmol. 2009;247(10):1375–82.

    Article  CAS  Google Scholar 

  14. Gaudreault J, Fei D, Rusit J, Suboc P, Shiu V. Preclinical pharmacokinetics of Ranibizumab (rhuFabV2) after a single intravitreal administration. Invest Ophthalmol Vis Sci. 2005;46(2):726–33.

    Article  Google Scholar 

  15. Ferrari G, Dastjerdi MH, Okanobo A, Cheng SF, Amparo F, Nallasamy N, Dana R. Topical ranibizumab as a treatment of corneal neovascularization. Cornea. 2013;32(7):992.

    Article  Google Scholar 

  16. Chen Y, Wiesmann C, Fuh G, Li B, Christinger HW, McKay P, Vos AM, Lowman HB. Selection and analysis of an optimized anti-VEGF antibody: crystal structure of an affinity-matured Fab in complex with antigen. J Mol Biol. 1999;293:865–81.

    Article  CAS  Google Scholar 

  17. Kim JH, Seo HW, Han HC, Lee JH, Choi SK, Lee D. The effect of bevacizumab versus ranibizumab in the treatment of corneal neovascularization: a preliminary study. Korean J Ophthalmol. 2013;27(4):235–42.

    Article  Google Scholar 

  18. Cheng SF, Ferrari G, Okanobo A, et al. Sustained efficacy of topical bevacizumab in the treatment of corneal neovascularization (NV). Invest Ophthalmol Vis Sci. 2011;154(6):940–48.e1.

    Google Scholar 

  19. Anijeet DR, Zheng Y, Tey A, Hodson M, Sueke H, Kaye SB. Imaging and evaluation of corneal vascularization using fluorescein and indocyanine green angiography. Invest Ophthalmol Vis Sci. 2012;53:650–8.

    Article  Google Scholar 

  20. Kirwan RP, Zheng Y, Tey A, Anijeet D, Sueke H, Kaye SB. Quantifying changes in corneal neovascularization using fluorescein and indocyanine green angiography. Am J Ophthalmol. 2012;154:850–8.

    Article  Google Scholar 

  21. Di Lee W, Devarajan K, Chua J, Schmetterer L, Mehta JS, Ang M. Optical coherence tomography angiography for the anterior segment. Eye Vision. 2019;6(1):4.

    Article  Google Scholar 

  22. Ong HS, Tey KY, Ke M, et al. A pilot study investigating anterior segment optical coherence tomography angiography as a non-invasive tool in evaluating corneal vascularisation. Sci Rep. 2021;11:1212.

    Article  CAS  Google Scholar 

  23. Feizi S, Azari AA, Safapour S. Therapeutic approaches for corneal neovascularization. Eye Vision. 2017;4(1):28.

    Article  Google Scholar 

  24. Ahn YJ, Hwang HB, Chung SK. Ranibizumab injection for corneal neovascularization refractory to bevacizumab treatment. Korean J Ophthalmol. 2014;28(2):177–80.

    Article  Google Scholar 

  25. Sener E, Yuksel N, Yildiz DK, Yilmaz B, Ozdemir O, Caglar Y, Degirmenci E. The impact of subconjuctivally injected EGF and VEGF inhibitors on experimental corneal neovascularization in rat model. Curr Eye Res. 2011;36(11):1005–13.

    Article  CAS  Google Scholar 

  26. Alldredge OC, Krachmer JH. Clinical types of corneal transplant rejection. Their manifestations, frequency, preoperative correlates, and treatment. Arch Ophthalmol. 1981;99:599–604.

    Article  CAS  Google Scholar 

  27. Hos D, Le VN, Hellmich M, Siebelmann S, Roters S, Bachmann BO, Cursiefen C. Risk of corneal graft rejection after high-risk keratoplasty following fine-needle vessel coagulation of corneal neovascularization combined with bevacizumab: a pilot study. Transplant Direct. 2019;5(5):e452.

    Article  Google Scholar 

  28. Le VN, Schneider AC, Scholz R, Bock F, Cursiefen C. Fine needle-diathermy regresses pathological corneal (lymph) angiogenesis and promotes high-risk corneal transplant survival. Sci Rep. 2018;8(1):1–8.

    Google Scholar 

  29. Oie Y, Nishida K. Evaluation of corneal neovascularization using optical coherence tomography angiography in patients with limbal stem cell deficiency. Cornea. 2017;36(Suppl 1):S72–5.

    Article  Google Scholar 

  30. Cai Y, Del Barrio JL, Wilkins MR, Ang M. Serial optical coherence tomography angiography for corneal vascularization. Graefes Arch Clin Exp Ophthalmol. 2017;255(1):135–9.

    Article  Google Scholar 

  31. Ang M, Baskaran M, Werkmeister RM, et al. Anterior segment optical coherence tomography. Prog Retin Eye Res. 2018;66:132–56. https://doi.org/10.1016/j.preteyeres.2018.04.002.

    Article  PubMed  Google Scholar 

  32. Fung SS, Stewart RM, Dhallu SK, Sim DA, Keane PA, Wilkins MR, Tuft SJ. Anterior segment optical coherence tomographic angiography assessment of acute chemical injury. Am J Ophthalmol. 2019;1(205):165–74.

    Article  Google Scholar 

  33. Liu Z, Karp CL, Galor A, Bayyat GJ, Jiang H, Wang J. Role of optical coherence tomography angiography in the characterization of vascular network patterns of ocular surface squamous neoplasia. Ocular Surf. 2020. https://doi.org/10.1136/bjophthalmol-2015-307706.

    Article  Google Scholar 

  34. Ang M, Cai Y, MacPhee B, Sim DA, Keane PA, Sng CC, Egan CA, Tufail A, Larkin DF, Wilkins MR. Optical coherence tomography angiography and indocyanine green angiography for corneal vascularisation. Br J Ophthalmol. 2016;100(11):1557–63.

    Article  Google Scholar 

  35. Ang M, Cai Y, Shahipasand S, Sim DA, Keane PA, Sng CC, Egan CA, Tufail A, Wilkins MR. En face optical coherence tomography angiography for corneal neovascularisation. Br J Ophthalmol. 2016;100(5):616–21.

    Article  Google Scholar 

  36. Faraj LA, Elalfy MS, Said DG, Dua HS. Fine needle diathermy occlusion of corneal vessels. Br J Ophthalmol. 2014;98(9):1287–90.

    Article  Google Scholar 

Download references

Acknowledgements

We thank Ms. Teo Kai Ying from Singapore Eye Research Institute for her assistance in obtaining the AS-OCTA images for the study.

Funding

This work was funded by grants from the National Medical Research Council (CG/C010A/2017; OFIRG/0048/2017; OFLCG/004c/2018), Singapore. Funding support from the Singapore Eye Research Institute was used to fund the Journal’s rapid service fee.

Authorship

All named authors meet the International Committee of Medical Journal Editors (ICMJE) criteria for authorship for this article, take responsibility for the integrity of the work as a whole, and have given their approval for this version to be published.

Author Contributions

Conceptualisation, methodology, and funding acquisition: M.A. Formal analysis and writing of manuscript: V.F, C.T. Image analysis: K.M.Y. Review and editing of the manuscript: M.A, J.M, and L.S.

Disclosures

Foo Hui Xian Valencia, Ke Mengyuan, Chelsea Tan Qiu Lin, Leopold Schmetterer, Jodhbir S Mehta, and Marcus Ang have nothing to disclose.

Compliance with Ethics Guidelines

Our study followed the principles of the Declaration of Helsinki of 1964, with approval obtained from the SingHealth ethics committee (IRB number: 2018/1435). Informed written consent was obtained from all study participants.

Data Availability

The datasets generated during and analysed during the current study are available from the corresponding author on reasonable request.

Author information

Authors and Affiliations

  1. Singapore National Eye Centre, Singapore Eye Research Institute, Singapore, Singapore

    Valencia Hui Xian Foo, Mengyuan Ke, Leopold Schmetterer, Jodhbir S. Mehta & Marcus Ang

  2. Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore

    Chelsea Qiu Lin Tan

  3. Department of Ophthalmology and Visual Science, Duke-NUS Graduate Medical School, 8 College Road, Singapore, 169857, Singapore

    Leopold Schmetterer, Jodhbir S. Mehta & Marcus Ang

  4. SERI-NTU Advanced Ocular Engineering (STANCE), 50 Nanyang Drive, Singapore, 637553, Singapore

    Leopold Schmetterer

  5. Institute for Health Technologies, Nanyang Technological University, 50 Nanyang Drive, Singapore, 637553, Singapore

    Leopold Schmetterer

  6. Department of Clinical Pharmacology, Medical University of Vienna, Währinger Gürtel 18-20, 1090, Vienna, Austria

    Leopold Schmetterer

  7. Center for Medical Physics and Biomedical Engineering, Medical University of Vienna, Währinger Gürtel 18-20, 1090, Vienna, Austria

    Leopold Schmetterer

  8. Institute of Clinical and Experimental Ophthalmology, Klybeckstrasse 141, WKL 420, 4057, Basel, Switzerland

    Leopold Schmetterer

  9. Department of Ophthalmology and Visual Sciences, Duke-NUS Medical School, Cornea and Refractive Service, Singapore National Eye Center, 11 Third Hospital Avenue, Singapore, 168751, Singapore

    Marcus Ang

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  1. Valencia Hui Xian Foo
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Corresponding author

Correspondence to Marcus Ang.

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Foo, V.H.X., Ke, M., Tan, C.Q.L. et al. Anterior Segment Optical Coherence Tomography Angiography Assessment of Corneal Vascularisation After Combined Fine-Needle Diathermy with Subconjunctival Ranibizumab: A Pilot Study. Adv Ther 38, 4333–4343 (2021). https://doi.org/10.1007/s12325-021-01849-w

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  • DOI: https://doi.org/10.1007/s12325-021-01849-w

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