Skip to main content
Top

13-11-2024 | Keratoconus | Cornea

The role of corneal epithelial thickness map in detecting early keratoconus

Authors: Zizhen Wang, Ruilan Dong, Yifei Yuan, Yu Zhang, Yueguo Chen

Published in: Graefe's Archive for Clinical and Experimental Ophthalmology

Login to get access

Abstract

Purpose

To detect subtle changes in early keratoconus by evaluating corneal epithelial thickness differences among patients with binocular very asymmetric ectasia (VAE) and normal subjects.

Methods

Corneal epithelial thickness was measured using the Fourier-domain AS-OCT system RTVue® 100 (Optovue, Fremont, CA, USA). 152 eyes from 76 patients were divided into three groups: Very asymmetry ectasia-ectasia (VAE-E, n = 38), Very asymmetry ectasia-normal topography (VAE-NT, n = 38), and Normal control (NC, n = 76). Discrimination capacity was assessed using areas under the curve (AUC) of receiver operator characteristic (ROC) curves.

Results

In the keratoconus group, the epithelial Min (minimum), central, midperipheral I (inferior), midperipheral IT (inferior-temporal), peripheral IT, and midperipheral T (temporal) were thinner (all P < 0.05). The topography normal group had thinner midperipheral IN (inferior-nasal), peripheral IN, midperipheral T, and peripheral T, and larger Max-Min and Std. Dev (P < 0.05). For diagnosing typical keratoconus, Std. Dev (AUC = 0.982, sensitivity 97.4%, specificity 92.1%) had the highest diagnostic efficiency. Combining four variables (Minimum, Max-Min, Midperipheral IT, and Midperipheral I) performed well in distinguishing topography normal eyes (AUC = 0.896, sensitivity 76.3%, specificity 89.5%). Multivariable analysis using epithelial parameters combined with Pentacam random forest index (PRFI) yielded the best results (AUC = 0.951, sensitivity 90.6%, specificity 89.5%).

Conclusions

The corneal epithelial parameters play an important auxiliary role in the diagnosis of keratoconus and the screening of subclinical keratoconus. Combination of epithelial parameters and tomographic parameters can improve the sensitivity of early stage keratoconus detection.
Literature
1.
go back to reference Mas-Aixala E, Gispets J, Lupon N, Cardona G (2016) The variability of corneal and anterior segment parameters in keratoconus. Cont Lens Anterior Eye 39(6):466–470CrossRefPubMed Mas-Aixala E, Gispets J, Lupon N, Cardona G (2016) The variability of corneal and anterior segment parameters in keratoconus. Cont Lens Anterior Eye 39(6):466–470CrossRefPubMed
2.
go back to reference Pinero DP, Alio JL, Aleson A, Escaf Vergara M, Miranda M (2010) Corneal volume, pachymetry, and correlation of anterior and posterior corneal shape in subclinical and different stages of clinical keratoconus. J Cataract Refract Surg 36(5):814–825CrossRefPubMed Pinero DP, Alio JL, Aleson A, Escaf Vergara M, Miranda M (2010) Corneal volume, pachymetry, and correlation of anterior and posterior corneal shape in subclinical and different stages of clinical keratoconus. J Cataract Refract Surg 36(5):814–825CrossRefPubMed
4.
go back to reference Mas Tur V, MacGregor C, Jayaswal R, O’Brart D, Maycock N (2017) A review of keratoconus: diagnosis, pathophysiology, and genetics. Surv Ophthalmol 62(6):770–783CrossRefPubMed Mas Tur V, MacGregor C, Jayaswal R, O’Brart D, Maycock N (2017) A review of keratoconus: diagnosis, pathophysiology, and genetics. Surv Ophthalmol 62(6):770–783CrossRefPubMed
5.
go back to reference Dong Y, Li D, Guo Z, Liu Y, Lin P, Lv B, Lv C, Xie G, Xie L (2021) Dissecting the Profile of corneal thickness with Keratoconus Progression based on Anterior Segment Optical Coherence Tomography. Front Neurosci 15:804273CrossRefPubMed Dong Y, Li D, Guo Z, Liu Y, Lin P, Lv B, Lv C, Xie G, Xie L (2021) Dissecting the Profile of corneal thickness with Keratoconus Progression based on Anterior Segment Optical Coherence Tomography. Front Neurosci 15:804273CrossRefPubMed
6.
go back to reference Schallhorn JM, Tang M, Li Y, Louie DJ, Chamberlain W, Huang D (2017) Distinguishing between contact lens warpage and ectasia: usefulness of optical coherence tomography epithelial thickness mapping (43, pg 60, 2017). J Cataract Refr Surg 43(10):1367–1368 Schallhorn JM, Tang M, Li Y, Louie DJ, Chamberlain W, Huang D (2017) Distinguishing between contact lens warpage and ectasia: usefulness of optical coherence tomography epithelial thickness mapping (43, pg 60, 2017). J Cataract Refr Surg 43(10):1367–1368
7.
go back to reference Catalan S, Cadarso L, Esteves F, Salgado-Borges J, Lopez M, Cadarso C (2016) Assessment of corneal epithelial thickness in asymmetric keratoconic eyes and normal eyes using Fourier Domain Optical Coherence Tomography. J Ophthalmol 2016:5697343CrossRefPubMedPubMedCentral Catalan S, Cadarso L, Esteves F, Salgado-Borges J, Lopez M, Cadarso C (2016) Assessment of corneal epithelial thickness in asymmetric keratoconic eyes and normal eyes using Fourier Domain Optical Coherence Tomography. J Ophthalmol 2016:5697343CrossRefPubMedPubMedCentral
8.
go back to reference Temstet C, Sandali O, Bouheraoua N, Hamiche T, Galan A, El Sanharawi M, Basli E, Laroche L, Borderie V (2015) Corneal epithelial thickness mapping using Fourier-domain optical coherence tomography for detection of form fruste keratoconus. J Cataract Refract Surg 41(4):812–820CrossRefPubMed Temstet C, Sandali O, Bouheraoua N, Hamiche T, Galan A, El Sanharawi M, Basli E, Laroche L, Borderie V (2015) Corneal epithelial thickness mapping using Fourier-domain optical coherence tomography for detection of form fruste keratoconus. J Cataract Refract Surg 41(4):812–820CrossRefPubMed
9.
go back to reference Li Y, Meisler DM, Tang M, Lu AT, Thakrar V, Reiser BJ, Huang D (2008) Keratoconus diagnosis with optical coherence tomography pachymetry mapping. Ophthalmology 115(12):2159–2166CrossRefPubMed Li Y, Meisler DM, Tang M, Lu AT, Thakrar V, Reiser BJ, Huang D (2008) Keratoconus diagnosis with optical coherence tomography pachymetry mapping. Ophthalmology 115(12):2159–2166CrossRefPubMed
10.
go back to reference Sella R, Zangwill LM, Weinreb RN, Afshari NA (2019) Repeatability and reproducibility of corneal epithelial thickness mapping with spectral-domain optical coherence tomography in normal and diseased cornea eyes. Am J Ophthalmol 197:88–97CrossRefPubMed Sella R, Zangwill LM, Weinreb RN, Afshari NA (2019) Repeatability and reproducibility of corneal epithelial thickness mapping with spectral-domain optical coherence tomography in normal and diseased cornea eyes. Am J Ophthalmol 197:88–97CrossRefPubMed
11.
go back to reference Li Y, Chamberlain W, Tan O, Brass R, Weiss JL, Huang D (2016) Subclinical keratoconus detection by pattern analysis of corneal and epithelial thickness maps with optical coherence tomography. J Cataract Refract Surg 42(2):284–295CrossRefPubMedPubMedCentral Li Y, Chamberlain W, Tan O, Brass R, Weiss JL, Huang D (2016) Subclinical keratoconus detection by pattern analysis of corneal and epithelial thickness maps with optical coherence tomography. J Cataract Refract Surg 42(2):284–295CrossRefPubMedPubMedCentral
13.
go back to reference Amsler M (1961) [The forme fruste of keratoconus]. Wien Klin Wochenschr 73:842–843PubMed Amsler M (1961) [The forme fruste of keratoconus]. Wien Klin Wochenschr 73:842–843PubMed
14.
go back to reference Li X, Rabinowitz YS, Rasheed K, Yang H (2004) Longitudinal study of the normal eyes in unilateral keratoconus patients. Ophthalmology 111(3):440–446CrossRefPubMed Li X, Rabinowitz YS, Rasheed K, Yang H (2004) Longitudinal study of the normal eyes in unilateral keratoconus patients. Ophthalmology 111(3):440–446CrossRefPubMed
15.
go back to reference Steinberg J, Siebert M, Katz T, Frings A, Mehlan J, Druchkiv V, Bühren J, Linke SJ (2018) Tomographic and Biomechanical Scheimpflug Imaging for Keratoconus characterization: a validation of current indices. J Refract Surg 34(12):840–CrossRefPubMed Steinberg J, Siebert M, Katz T, Frings A, Mehlan J, Druchkiv V, Bühren J, Linke SJ (2018) Tomographic and Biomechanical Scheimpflug Imaging for Keratoconus characterization: a validation of current indices. J Refract Surg 34(12):840–CrossRefPubMed
16.
go back to reference Ambrósio R, Lopes BT, Faria-Correia F, Salomao MQ, Bühren J, Roberts CJ, Elsheikh A, Vinciguerra R, Vinciguerra P (2017) Integration of Scheimpflug-based corneal tomography and biomechanical assessments for enhancing Ectasia Detection. J Refract Surg 33(7):434–CrossRefPubMed Ambrósio R, Lopes BT, Faria-Correia F, Salomao MQ, Bühren J, Roberts CJ, Elsheikh A, Vinciguerra R, Vinciguerra P (2017) Integration of Scheimpflug-based corneal tomography and biomechanical assessments for enhancing Ectasia Detection. J Refract Surg 33(7):434–CrossRefPubMed
17.
go back to reference Lopes BT, Ramos IC, Salomao MQ, Guerra FP, Schallhorn SC, Schallhorn JM, Vinciguerra R, Vinciguerra P, Price FW, Price MO et al (2018) Enhanced Tomographic Assessment to detect corneal Ectasia based on Artificial Intelligence. Am J Ophthalmol 195:223–232CrossRefPubMed Lopes BT, Ramos IC, Salomao MQ, Guerra FP, Schallhorn SC, Schallhorn JM, Vinciguerra R, Vinciguerra P, Price FW, Price MO et al (2018) Enhanced Tomographic Assessment to detect corneal Ectasia based on Artificial Intelligence. Am J Ophthalmol 195:223–232CrossRefPubMed
18.
go back to reference Schmoll T, Unterhuber A, Kolbitsch C, Le T, Stingl A, Leitgeb R (2012) Precise thickness measurements of Bowman’s layer, epithelium, and tear film. Optom Vis Sci 89(5):E795–802CrossRefPubMed Schmoll T, Unterhuber A, Kolbitsch C, Le T, Stingl A, Leitgeb R (2012) Precise thickness measurements of Bowman’s layer, epithelium, and tear film. Optom Vis Sci 89(5):E795–802CrossRefPubMed
19.
go back to reference Lu NJ, Chen D, Cui LL, Wang L, Chen SH, Wang QM (2019) Repeatability of Cornea and SubLayer thickness measurements using Optical Coherence Tomography in corneas of anomalous refractive status. J Refract Surg 35(9):600–CrossRefPubMed Lu NJ, Chen D, Cui LL, Wang L, Chen SH, Wang QM (2019) Repeatability of Cornea and SubLayer thickness measurements using Optical Coherence Tomography in corneas of anomalous refractive status. J Refract Surg 35(9):600–CrossRefPubMed
20.
go back to reference Latifi G, Mohammadi SS (2020) Repeatability and agreement of total corneal and sublayer pachymetry with 2 different algorithms of Fourier-domain optical coherence tomography in myopic and postphotorefractive keratectomy eyes. J Cataract Refract Surg 46(12):1644–1651CrossRefPubMed Latifi G, Mohammadi SS (2020) Repeatability and agreement of total corneal and sublayer pachymetry with 2 different algorithms of Fourier-domain optical coherence tomography in myopic and postphotorefractive keratectomy eyes. J Cataract Refract Surg 46(12):1644–1651CrossRefPubMed
21.
go back to reference Reinstein DZ, Yap TE, Archer TJ, Gobbe M, Silverman RH (2015) Comparison of corneal epithelial thickness measurement between Fourier-Domain OCT and very high-frequency Digital Ultrasound. J Refract Surg 31(7):438–U481CrossRefPubMedPubMedCentral Reinstein DZ, Yap TE, Archer TJ, Gobbe M, Silverman RH (2015) Comparison of corneal epithelial thickness measurement between Fourier-Domain OCT and very high-frequency Digital Ultrasound. J Refract Surg 31(7):438–U481CrossRefPubMedPubMedCentral
22.
go back to reference Rocha KM, Perez-Straziota CE, Stulting RD, Randleman JB (2013) SD-OCT analysis of regional epithelial thickness profiles in keratoconus, postoperative corneal ectasia, and normal eyes. J Refract Surg 29(3):173–179CrossRefPubMedPubMedCentral Rocha KM, Perez-Straziota CE, Stulting RD, Randleman JB (2013) SD-OCT analysis of regional epithelial thickness profiles in keratoconus, postoperative corneal ectasia, and normal eyes. J Refract Surg 29(3):173–179CrossRefPubMedPubMedCentral
23.
go back to reference Reinstein DZ, Archer TJ, Urs R, Gobbe M, RoyChoudhury A, Silverman RH (2015) Detection of Keratoconus in clinically and algorithmically topographically normal fellow eyes using epithelial thickness analysis. J Refract Surg 31(11):736–744CrossRefPubMedPubMedCentral Reinstein DZ, Archer TJ, Urs R, Gobbe M, RoyChoudhury A, Silverman RH (2015) Detection of Keratoconus in clinically and algorithmically topographically normal fellow eyes using epithelial thickness analysis. J Refract Surg 31(11):736–744CrossRefPubMedPubMedCentral
24.
go back to reference Yang Y, Pavlatos E, Chamberlain W, Huang D, Li Y (2021) Keratoconus detection using OCT corneal and epithelial thickness map parameters and patterns. J Cataract Refract Surg 47(6):759–766CrossRefPubMedPubMedCentral Yang Y, Pavlatos E, Chamberlain W, Huang D, Li Y (2021) Keratoconus detection using OCT corneal and epithelial thickness map parameters and patterns. J Cataract Refract Surg 47(6):759–766CrossRefPubMedPubMedCentral
25.
go back to reference Reinstein DZ, Archer TJ, Gobbe M (2009) Corneal epithelial thickness profile in the diagnosis of keratoconus. J Refract Surg 25(7):604–610CrossRefPubMed Reinstein DZ, Archer TJ, Gobbe M (2009) Corneal epithelial thickness profile in the diagnosis of keratoconus. J Refract Surg 25(7):604–610CrossRefPubMed
26.
go back to reference Tang M, Li Y, Chamberlain W, Louie DJ, Schallhorn JM, Huang D (2016) Differentiating Keratoconus and corneal warpage by analyzing focal change patterns in corneal topography, Pachymetry, and epithelial thickness maps. Invest Ophthalmol Vis Sci 57(9):OCT544–549CrossRefPubMedPubMedCentral Tang M, Li Y, Chamberlain W, Louie DJ, Schallhorn JM, Huang D (2016) Differentiating Keratoconus and corneal warpage by analyzing focal change patterns in corneal topography, Pachymetry, and epithelial thickness maps. Invest Ophthalmol Vis Sci 57(9):OCT544–549CrossRefPubMedPubMedCentral
27.
go back to reference Ostadian F, Farrahi F, Mahdian Rad A (2019) Comparison of corneal epithelial thickness map measured by Spectral Domain Optical Coherence Tomography in Healthy, subclinical and early keratoconus subjects. Med Hypothesis Discov Innov Ophthalmol 8(2):85–91PubMedPubMedCentral Ostadian F, Farrahi F, Mahdian Rad A (2019) Comparison of corneal epithelial thickness map measured by Spectral Domain Optical Coherence Tomography in Healthy, subclinical and early keratoconus subjects. Med Hypothesis Discov Innov Ophthalmol 8(2):85–91PubMedPubMedCentral
28.
go back to reference Hwang ES, Schallhorn JM, Randleman JB (2020) Utility of regional epithelial thickness measurements in corneal evaluations. Surv Ophthalmol 65(2):187–204CrossRefPubMed Hwang ES, Schallhorn JM, Randleman JB (2020) Utility of regional epithelial thickness measurements in corneal evaluations. Surv Ophthalmol 65(2):187–204CrossRefPubMed
29.
go back to reference Li Y, Tan O, Brass R, Weiss JL, Huang D (2012) Corneal epithelial thickness mapping by Fourier-domain optical coherence tomography in normal and keratoconic eyes. Ophthalmology 119(12):2425–2433CrossRefPubMed Li Y, Tan O, Brass R, Weiss JL, Huang D (2012) Corneal epithelial thickness mapping by Fourier-domain optical coherence tomography in normal and keratoconic eyes. Ophthalmology 119(12):2425–2433CrossRefPubMed
30.
go back to reference Reinstein DZ, Gobbe M, Archer TJ, Silverman RH, Coleman DJ (2010) Epithelial, stromal, and total corneal thickness in keratoconus: three-dimensional display with Artemis very-high frequency digital ultrasound. J Refract Surg 26(4):259–271CrossRefPubMedPubMedCentral Reinstein DZ, Gobbe M, Archer TJ, Silverman RH, Coleman DJ (2010) Epithelial, stromal, and total corneal thickness in keratoconus: three-dimensional display with Artemis very-high frequency digital ultrasound. J Refract Surg 26(4):259–271CrossRefPubMedPubMedCentral
31.
go back to reference Qin B, Chen S, Brass R, Li Y, Tang M, Zhang X, Wang X, Wang Q, Huang D (2013) Keratoconus diagnosis with optical coherence tomography-based pachymetric scoring system. J Cataract Refract Surg 39(12):1864–1871CrossRefPubMedPubMedCentral Qin B, Chen S, Brass R, Li Y, Tang M, Zhang X, Wang X, Wang Q, Huang D (2013) Keratoconus diagnosis with optical coherence tomography-based pachymetric scoring system. J Cataract Refract Surg 39(12):1864–1871CrossRefPubMedPubMedCentral
32.
go back to reference Toprak I, Vega A, Del Alio JL, Espla E, Cavas F, Alio JL (2021) Diagnostic value of corneal epithelial and stromal thickness distribution profiles in Forme Fruste Keratoconus and Subclinical Keratoconus. Cornea 40(1):61–72CrossRefPubMed Toprak I, Vega A, Del Alio JL, Espla E, Cavas F, Alio JL (2021) Diagnostic value of corneal epithelial and stromal thickness distribution profiles in Forme Fruste Keratoconus and Subclinical Keratoconus. Cornea 40(1):61–72CrossRefPubMed
33.
go back to reference Hwang ES, Perez-Straziota CE, Kim SW, Santhiago MR, Randleman JB (2018) Distinguishing highly asymmetric Keratoconus eyes using combined Scheimpflug and spectral-domain OCT analysis. Ophthalmology 125(12):1862–1871CrossRefPubMed Hwang ES, Perez-Straziota CE, Kim SW, Santhiago MR, Randleman JB (2018) Distinguishing highly asymmetric Keratoconus eyes using combined Scheimpflug and spectral-domain OCT analysis. Ophthalmology 125(12):1862–1871CrossRefPubMed
34.
go back to reference Kaya S, Schmidl D, Schmetterer L, Garhofer G, Werkmeister R (2015) Effect of hyaluronic acid on tear film thickness as assessed with ultra-high resolution optical coherence tomography. Acta Ophthalmol 93(5):439–443 Kaya S, Schmidl D, Schmetterer L, Garhofer G, Werkmeister R (2015) Effect of hyaluronic acid on tear film thickness as assessed with ultra-high resolution optical coherence tomography. Acta Ophthalmol 93(5):439–443
35.
go back to reference Baghdasaryan E, Tepelus TC, Marion KM, Bagherinia H, Sadda SR, Hsu HY (2019) Evaluation of corneal epithelial thickness imaged by high definition Optical Coherence Tomography in healthy eyes. Cornea 38(1):62–66CrossRefPubMed Baghdasaryan E, Tepelus TC, Marion KM, Bagherinia H, Sadda SR, Hsu HY (2019) Evaluation of corneal epithelial thickness imaged by high definition Optical Coherence Tomography in healthy eyes. Cornea 38(1):62–66CrossRefPubMed
Metadata
Title
The role of corneal epithelial thickness map in detecting early keratoconus
Authors
Zizhen Wang
Ruilan Dong
Yifei Yuan
Yu Zhang
Yueguo Chen
Publication date
13-11-2024
Publisher
Springer Berlin Heidelberg
Keyword
Keratoconus
Published in
Graefe's Archive for Clinical and Experimental Ophthalmology
Print ISSN: 0721-832X
Electronic ISSN: 1435-702X
DOI
https://doi.org/10.1007/s00417-024-06682-9