Optical Coherence Tomography for Diagnosis and Treatment of Corneal Diseases

Optical coherence tomography (OCT) is a modern non-contact real-time imaging of anterior and posterior eye’s segments. Based on the principle of low-coherence interferometry, it provides the analysis of tissue structures. In this review, we discuss technical aspects of two different OCT platforms: Time-Domain OCT (TD-OCT), and Spectral-Domain (SD-OCT) with the use of Fourier transformation — Fourier-Domain (FD-OCT). Over the last several years, the development of OCT has increased the resolution of images by different ways of optical filtering. The usage of tunable swept laser instead of superluminescent diode in modern Swept-Source OCT (SS-OCT) provides the sufficient quality of image. Anterior segment OCT can detect the pathological changes in different ocular structures and may be a key tool for monitoring of their progression. In pterygium OCT shows the true extent of fibrovascular granulation tissue in stromal layers, whereas in keratitis it provides imaging of corneal infiltration. Frequently, OCT-pachymetry can be advantageous in the detection of subclinical keratectasias. In patients with bullous keratopathy OCT can help to distinguish corneal edema and fibrosis. The new era of OCT is characterized by application of this method in keratorefractive surgery. Microscope-mounted (portable) and microscopeintegrated OCT systems have been developed. During LASIK surgery intraoperative OCT (iOCT) helps to assess flap interface, measure flap and residual bed thickness. It is a useful tool to reveal the structural changes during corneal collagen crosslinking. At the beginning of keratoplasty, iOCT helps to determine the corneal thickness, extent and depth of opacity, Descemet membrane perforation. iOCT guides decision-making regarding keratoplasty modification, depth and diameter of trephination. Furthermore, a real-time visualization of ocular structures during keratoplasty decreases the frequency of intra- and postsurgical complications. 

1. Fercher A.F., Roth E. Ophthalmic Laser Interferometry. Proc. SPIE: Optical Instrumentation for Biomedical Laser Applications. 1986; 0658. DOI: 10.1117/12.938523

2. Huang D., Swanson E.A., Lin C.P., Schuman J.S., Stinson W.G., Chang W., Hee M.R., Flotte T., Gregory K., Puliafito C.A. Optical coherence tomography. Science. 1991; 254(5035):1178–1181. DOI: 10.1126/science.1957169

3. Zaharova M.A., Kuroedov A.V. Optic coherent tomography — technology which became a reality. Russian Medical Journal. Clinical ophthalomology. = Rossiyskiy medicinskiy zhurnal. Klinicheskaya oftal’mologiya. 2015;4:204–211 (In Russ.).

4. Stoyukhina A.S., Budzinskaya M.V., Stoyukhin S.G., Aslamazova A.E. Optical coherence tomography angiography in ophthalmic oncology The Russian Annals of Ophthalmology = Vestnik oftal’mologii. 2019;135(1):104–111 (In Russ.). DOI: 10.17116/oftalma2019135011104

5. Popescu D.P., Choo-Smith L.P., Flueraru, C., Mao Y., Chang S., Disano J., Sherif S., Sowa M.G. Optical coherence tomography: fundamental principles, instrumental designs and biomedical applications. Biophysical reviews. 2011; 3(3):155. DOI: 10.1007/s12551-011-0054-7

6. Svirin A.V., Kiiko Yu.I., Obruch B.V., Bogomolov A.V. Spectral optic coherent tomography: principles and possibilities. Russian Medical Journal. Clinical ophthalomology = Rossiyskiy medicinskiy zhurnal. Klinicheskaya oftal’mologiya.. 2009;10(2):50–53 (In Russ.).

7. Ang M., Baskaran M., Werkmeister R.M., Chua J., Schmidl D., Aranha Dos Santos V., Garhöfer G., Mehta J.S., Schmetterer L. Anterior segment optical coherence tomography. Prog Retin Eye Res. 2018;66:132–156. DOI: 10.1016/j.preteyeres.2018.04.002

8. Fercher A.F., Mengedoht K., Werner W. Eye-length measurement by interferometry with partially coherent light. Opt Lett. 1988;13(3):186–188. DOI: 10.1364/ol.13.000186

9. Swanson E.A., Izatt J.A., Hee M.R., Huang D., Lin C.P., Schuman J.S., Puliafito C.A., Fujimoto J.G. In vivo retinal imaging by optical coherence tomography. Opt Lett. 1993;18(21):1864–1866. DOI: 10.1364/ol.18.001864

10. Izatt J.A., Hee M.R., Swanson E.A., Lin C.P., Huang D., Schuman J.S., Puliafito C.A., Fujimoto J.G. Micrometer-scale resolution imaging of the anterior eye in vivo with optical coherence tomography. Arch Ophthalmol. 1994;112(12):1584–1589. DOI: 10.1001/archopht.1994.01090240090031

11. Podoleanu A.G. Optical coherence tomography. J Microsc. 2012;247(3):209–219. DOI: 10.1111/j.1365-2818.2012.03619.x

12. Leitgeb R., Hitzenberger C., Fercher A. Performance of fourier domain vs. time domain optical coherence tomography. Opt Express. 2003;11(8):889–894. DOI: 10.1364/oe.11.000889

13. Radhakrishnan S., Rollins A.M., Roth J.E., Yazdanfar S., Westphal V., Bardenstein D.S., Izatt J.A. Real-time optical coherence tomography of the anterior segment at 1310 nm. Arch Ophthalmol. 2001;119(8):1179–1185. DOI: 10.1001/archopht.119.8.1179

14. Yaqoob Z., Wu J., Yang C. Spectral domain optical coherence tomography: a better OCT imaging strategy. Biotechniques. 2005;39(6 Suppl):S6–13. DOI: 10.2144/000112090

15. Kiernan D.F., Mieler W.F., Hariprasad S.M. Spectral-domain optical coherence tomography: a comparison of modern high-resolution retinal imaging systems. Am J Ophthalmol. 2010;149(1):18–31. DOI: 10.1016/j.ajo.2009.08.037

16. Ghaleb K.I.S., Proskurin S.G. Spekl-noise reduction in structural OCT image reconstruction. Basic research. = Fundamental’nye issledovanija. 2014;4:479–483 (In Russ.).

17. Semenova N.S., Larichev A.V., Akopyan V.S. Sweptsource optical coherence tomography: a technology review. The Russian Annals of Ophthalmology = Vestnik oftal’mologii. 2020;136(1):111–116 (In Russ.). DOI: 10.17116/oftalma2020136011111

18. Han S.B., Liu Y.C., Noriega K.M., Mehta J.S. Applications of Anterior Segment Optical Coherence Tomography in Cornea and Ocular Surface Diseases. J Ophthalmol. 2016;4971572. DOI: 10.1155/2016/4971572

19. Nanji A.A., Sayyad F.E., Galor A., Dubovy S., Karp C.L. High-Resolution optical coherence tomography as an adjunctive tool in the diagnosis of corneal and conjunctival pathology. Ocul Surf. 2015;13(3):226–235. DOI: 10.1016/j.jtos.2015.02.001

20. Wang S.B., Cornish E.E., Grigg J.R., McCluskey P.J. Anterior segment optical coherence tomography and its clinical applications. Clin Exp Optom. 2019;102(3):195– 207. DOI: 10.1111/cxo.12869

21. Werkmeister R.M., Sapeta S., Schmidl D., Garhöfer G., Schmidinger G., Aranha Dos Santos V., Aschinger G.C., Baumgartner I., Pircher N., Schwarzhans F., Pantalon A., Dua H., Schmetterer L. Ultrahigh-resolution OCT imaging of the human cornea. Biomed Opt Express. 2017;8(2):1221–1239. DOI: 10.1364/BOE.8.001221

22. Kieval J.Z., Karp C.L., Abou Shousha M., Galor A., Hoffman R.A., Dubovy S.R., Wang J. Ultra-high resolution optical coherence tomography for differentiation of ocular surface squamous neoplasia and pterygia. Ophthalmology. 2012;119(3):481– 486. DOI: 10.1016/j.ophtha.2011.08.028

23. Lim S.H. Clinical applications of anterior segment optical coherence tomography. J Ophthalmol. 2015:605729. DOI: 10.1016/10.1155/2015/605729

24. Soliman W., Mohamed T.A. Spectral domain anterior segment optical coherence tomography assessment of pterygium and pinguecula. Acta Ophthalmol. 2012;90(5):461–465. DOI: 10.1111/j.1755-3768.2010.01994.x

25. Konstantopoulos A., Kuo J., Anderson D., Hossain P. Assessment of the use of anterior segment optical coherence tomography in microbial keratitis. Am J Ophthalmol. 2008;146(4):534–542. DOI: 10.1016/j.ajo.2008.05.030

26. Park Y.M., Lee J.S., Yoo J.M., Park J.M., Seo S.W., Chung I.Y., Kim S.J. Comparison of anterior segment optical coherence tomography findings in acanthamoeba keratitis and herpetic epithelial keratitis. Int J Ophthalmol. 2018;11(8):1416–1420. DOI: 10.18240/ijo.2018.08.26

27. Petrovic A., Hashemi K., Blaser F., Wild W., Kymionis G. Characteristics of linear interstitial keratitis by in vivo confocal microscopy and anterior segment optical Coherence tomography. Cornea. 2018;37(6):785–788. DOI: 10.1097/ICO.0000000000001552

28. Igbre A.O., Rico M.C., Garg S.J. High-speed optical coherence tomography as a reliable adjuvant tool to grade ocular anterior chamber inflammation. Retina. 2014;34(3):504–508. DOI: 10.1097/IAE.0b013e31829f73bd

29. Osipyan G.A., Sheludchenko V.M., Khraystin Kh. Modern methods of surgical treatment of keratectasias. The Russian Annals of Ophthalmology = Vestnik oftal’mologii. 2019;135(2):138–143 (In Russ.). DOI: 10.17116/oftalma2019135021138

30. Li Y., Tan O., Brass R., Weiss J.L., Huang D. Corneal epithelial thickness mapping by Fourier-domain optical coherence tomography in normal and keratoconic eyes. Ophthalmology. 2012;119(12):2425–2433. DOI: 10.1016/j.ophtha.2012.06.023

31. Rocha K.M., Perez-Straziota C.E., Stulting R.D., Randleman J.B. SD-OCT analysis of regional epithelial thickness profiles in keratoconus, postoperative corneal ectasia, and normal eyes. J Refract Surg. 2013;29(3):173–179. DOI: 10.3928/1081597X20130129-08

32. Ramos J.L., Li Y., Huang D. Clinical and research applications of anterior segment optical coherence tomography — a review. Clin Exp Ophthalmol. 2009;37(1):81–89. DOI: 10.1111/j.1442-9071.2008.01823.x

33. Yip H., Chan E. Optical coherence tomography imaging in keratoconus. Clin Exp Optom. 2019;102(3):218–223. DOI: 10.1111/cxo.12874

34. Fuentes E., Sandali O., El Sanharawi M., Basli E., Hamiche T., Goemaere I., Borderie V., Bouheraoua N., Laroche L. Anatomic predictive factors of acute corneal hydrops in keratoconus: an optical coherence tomography study. Ophthalmology. 2015;122(8):1653–1659. DOI: 10.1016/j.ophtha.2015.04.031

35. Price M.O., Mehta J.S., Jurkunas U.V., Price F.W.Jr. Corneal endothelial dysfunction: evolving understanding and treatment options [published online ahead of print]. Prog Retin Eye Res. 2020;100904. DOI: 10.1016/j.preteyeres.2020.100904

36. Trufanov S.V., Fisenko N.V. Molecular genetic aspects of Fuchs’ endothelial corneal dystrophy pathogenesis. The Russian Annals of Ophthalmology = Vestnik oftal’mologii. 2020;136(5):260–267 (In Russ.). DOI: 10.17116/oftalma2020136052260

37. Wertheimer C.M., Elhardt C., Wartak A., Luft N., Kassumeh S., Dirisamer M., Siedlecki J., Vounotrypidis E., Priglinger S.G., Mayer W.J. Corneal optical density in Fuchs endothelial dystrophy determined by anterior segment optical coherence tomography [published online ahead of print]. Eur J Ophthalmol. 2020;1120672120944796. DOI: 10.1177/1120672120944796

38. Yasukura Y., Oie Y., Kawasaki R., Maeda N., Jhanji V., Nishida K. New severity grading system for Fuchs endothelial corneal dystrophy using anterior segment optical coherence tomography [published online ahead of print]. Acta Ophthalmol. 2020;10.1111/aos.14690. DOI: 10.1111/aos.14690

39. Salovarova E.P., Trufanov S.V., Novikov I.A. Analysis of light scatteing ability of the cornea before and after endothelial keratoplasty. The Russian Annals of Ophthalmology = Vestnik oftal’mologii. 2020;136(3):39–45 (In Russ.). DOI: 10.17116/oftalma202013603139

40. Trufanov S.V., Malozhen S.A., Pivin E.A. Restoring anatomical and functional integrity of human corneal endothelium after large Descemet’s membrane tear (clinical case). Ophthalmology in Russia = Oftal’mologiya. 2015;12(1):96–100 (In Russ.). DOI: 10.18008/1816-5095-2015-1-96-100

41. Eguchi H., Hotta F., Kusaka S., Shimomura Y. Intraoperative optical coherence tomography imaging in corneal surgery: a literature review and proposal of novel applications. J Ophthalmol. 2020; 2020:1497089. DOI: 10.1155/2020/1497089

42. Ehlers J.P. Intraoperative optical coherence tomography: past, present, and future. Eye (Lond). 2016;30(2):193–201. DOI: 10.1038/eye.2015.255

43. Ray R., Barañano D.E., Fortun J.A., Schwent B.J., Cribbs B.E., Bergstrom C.S., Hubbard G.B., Srivastava S.K. Intraoperative microscope-mounted spectral domain optical coherence tomography for evaluation of retinal anatomy during macular surgery. Ophthalmology. 2011;118(11):2212–2217. DOI: 10.1016/j.ophtha.2011.04.012

44. Ehlers J.P., Dupps W.J., Kaiser P.K., Goshe J., Singh R.P., Petkovsek D., Srivastava S.K. The Prospective Intraoperative and Perioperative Ophthalmic ImagiNg with Optical CoherEncE TomogRaphy (PIONEER) Study: 2-year results. Am J Ophthalmol. 2014;158(5):999-1007. DOI:10.1016/j.ajo.2014.07.034

45. Avetisov S.E., Petrov S.Yu., Volzhanin A.V. Optical coherence tomography for examination of glaucoma surgery site. The Russian Annals of Ophthalmology = Vestnik oftal’mologii. 2018;134(5):250–256 (In Russ.). DOI: 10.17116/oftalma2018134051250

46. Ehlers J.P., Tam T., Kaiser P.K., Martin D.F., Smith G.M., Srivastava S.K. Utility of intraoperative optical coherence tomography during vitrectomy surgery for vitreomacular traction syndrome. Retina. 2014;34(7):1341–1346. DOI: 10.1097/IAE.0000000000000123

47. Shetty R., Malhotra C., D’Souza S., Wadia K. WaveLight FS200 vs Hansatome LASIK: intraoperative determination of flap characteristics and predictability by hand-held bioptigen spectral domain ophthalmic imaging system. J Refract Surg. 2012;28(11 Suppl):S815–S820. DOI: 10.3928/1081597x-20121005-01

48. Han S.B., Woo S.J., Hyon J.Y. Delayed-onset interface fluid syndrome after laser in situ keratomileusis secondary to combined cataract and vitreoretinal surgery. J Cataract Refract Surg. 2012;38(3):548–550. DOI: 10.1016/j.jcrs.2011.12.014

49. Balestrazzi A., Balestrazzi A., Giannico M.I., Michieletto P., Balestrazzi E. Diagnosis, clinical trend, and treatment of diffuse lamellar keratitis after femtosecond laserassisted in situ keratomileusis: a case report. Case Rep Ophthalmol. 2018;9(3):457– 464. DOI: 10.1159/000493338

50. Beckman K.A., Gupta P.K., Farid M., Berdahl J.P., Yeu E., Ayres B., Chan C.C., Gomes J.A.P., Holland E.J., Kim T., Starr C.E., Mah F.S., ASCRS Cornea Clinical Committee. Corneal crosslinking: current protocols and clinical approach. J Cataract Refract Surg. 2019;45(11):1670–1679. DOI: 10.1016/j.jcrs.2019.06.027

51. Titiyal J.S., Kaur M., Nair S., Sharma N. Intraoperative optical coherence tomography in anterior segment surgery. Surv Ophthalmol. 2021;66(2):308–326. DOI: 10.1016/j.survophthal.2020.07.001

52. Kymionis G.D., Grentzelos M.A., Plaka A.D., Stojanovic N., Tsoulnaras K.I., Mikropoulos D.G., Rallis K.I., Kankariya V.P. Evaluation of the corneal collagen crosslinking demarcation line profile using anterior segment optical coherence tomography. Cornea. 2013;32(7):907–910. DOI: 10.1097/ICO.0b013e31828733ea

53. Barbara R., Barbara A., Naftali M. Depth evaluation of intended vs actual intacs intrastromal ring segments using optical coherence tomography. Eye (Lond). 2016;30(1):102–110. DOI: 10.1038/eye.2015.202

54. Singh R., Gupta N., Vanathi M., Tandon R. Corneal transplantation in the modern era. Indian J Med Res. 2019;150(1):7–22. DOI: 10.4103/ijmr.IJMR_141_19

55. Anwar M., Teichmann K.D. Big-bubble technique to bare Descemet’s membrane in anterior lamellar keratoplasty. J Cataract Refract Surg. 2002;28(3):398–403. DOI: 10.1016/s0886-3350(01)01181-6

56. Scorcia V., Busin M., Lucisano A., Beltz J., Carta A., Scorcia G. Anterior segment optical coherence tomography-guided big-bubble technique. Ophthalmology. 2013;120(3):471–476. DOI: 10.1016/j.ophtha.2012.08.041

57. De Benito-Llopis L., Mehta J.S., Angunawela R.I., Ang M., Tan D.T. Intraoperative anterior segment optical coherence tomography: a novel assessment tool during deep anterior lamellar keratoplasty. Am J Ophthalmol. 2014;157(2):334–341.e3. DOI: 10.1016/j.ajo.2013.10.001

58. Steven P., Le Blanc C., Velten K., Lankenau E., Krug M., Oelckers S., Heindl L.M., Gehlsen U., Hüttmann G., Cursiefen C. Optimizing descemet membrane endothelial keratoplasty using intraoperative optical coherence tomography. JAMA Ophthalmol. 2013;131(9):1135–1142. DOI: 10.1001/jamaophthalmol.2013.4672

59. Au J., Goshe J., Dupps W.J., Srivastava S.K., Ehlers J.P. Intraoperative optical coherence tomography for enhanced depth visualization in deep anterior lamellar keratoplasty from the PIONEER study. Cornea. 2015;34(9):1039–1043. DOI: 10.1097/ICO.0000000000000508

60. Ehlers J.P., Goshe J., Dupps W.J., Kaiser P.K., Singh R.P., Gans R., Eisengart J., Srivastava S.K. Determination of feasibility and utility of microscope-integrated optical coherence tomography during ophthalmic surgery: the DISCOVER Study RESCAN Results. JAMA Ophthalmol. 2015;133(10):1124–1132. DOI: 10.1001/jamaophthalmol.2015.2376