Intraobserver reproducibility and interobserver agreement of demarcation line depth measurements following corneal cross linking

Abstract

Purpose:

The aim of this study was to evaluate the intraobserver reproducibility of demarcation line depth measurement in keratoconic patients after epithelium-off corneal collagen cross linking and assess the interobserver variability/agreement among examiners of various experience levels.

Methods:

56 eyes of 56 patients undergoing corneal collagen cross linking for progressive keratoconus were enrolled. After 4 weeks, all patients underwent an anterior segment optical coherence tomography (AS-OCT; CASIA SS-1000; Tomey, Nagoya, Japan) in the cross-linked eye by four masked examiners (two medical students (S1 and S2) and two corneal fellows (F1 and F2)) in order to identify and measure the demarcation line depth in experienced and non-experienced users. The intraclass correlation coefficient and the coefficient of variation were calculated. Agreement between raters was evaluated using Bland–Altman plots, intraclass correlation coefficient and weighted-kappa statistics comparing raters in pairs.

Results:

The average demarcation line depth of all measurements was 254.34 ± 72.3 μm, varying from 84 to 459 μm. The intraclass correlation coefficient evaluating the reproducibility of measurements for F1 was 0.9379 (95% confidence interval (CI) =0.9035–0.9619), for the second (F2), it was 0.9837 (95% confidence interval = 0.9743–0.9901), while intraclass correlation coefficient between medical students was calculated 0.844. The overall intraclass correlation coefficient among all four observers was 0.8706 (95% confidence interval = 0.8061–0.9185). The coefficient of variation for repeated measurements was 5.981 μm (95% confidence interval = 3.966–7.471) and 3.312 μm (95% confidence interval = 2.468–3.981) for F1 and F2 raters, respectively. The percentage of demarcation line detection was 90.32%.

Conclusion:

The reproducibility of demarcation line measures although very good (intraclass correlation coefficient > 0.9), yielded a difference between the two experienced raters. Furthermore, the novice raters did not reach an excellent level of agreement with the expert ones showing greater variability in their recordings.

Keywords

Keratoconus demarcation line depth optical coherence tomography corneal cross linking reproducibility

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References

Wollensak

Spoerl

Seiler

Riboflavin/ultraviolet-A-induced collagen crosslinking for the treatment of keratoconus. Am J Ophthalmol 2003; 135(5): 620–627.

Lin

Efficacy of corneal collagen cross-linking for treatment of keratoconus: a meta-analysis of randomized controlled trials. PLoS ONE 2015; 10(5): e0127079.

O’Brart

DPS

Chan

Samaras

, et al. A randomised, prospective study to investigate the efficacy of riboflavin/ultraviolet A (370 nm) corneal collagen crosslinkage to halt the progression of keratoconus. Br J Ophthalmol 2011; 95(11): 1519–1524.

Vinciguerra

Romano

Camesasca

, et al. Corneal cross-linking as a treatment for keratoconus: four-year morphologic and clinical outcomes with respect to patient age. Ophthalmology 2013; 120(5): 908–916.

Raiskup

Theuring

Pillunat

, et al. Corneal collagen crosslinking with riboflavin and ultraviolet-A light in progressive keratoconus: ten-year results. J Cataract Refract Surg 2015; 41(1): 41–46.

Caporossi

Mazzotta

Paradiso

, et al. Transepithelial corneal collagen crosslinking for progressive keratoconus: 24-month clinical results. J Cataract Refract Surg 2013; 39(8): 1157–1163.

Seiler

Hafezi

Corneal cross-linking-induced stromal demarcation line. Cornea 2006; 25(9): 1057–1059.

Doors

Tahzib

Eggink

, et al. Use of anterior segment optical coherence tomography to study corneal changes after collagen cross-linking. Am J Ophthalmol 2009; 148(6): 844–851.e2.

Yam

Chan

Cheng

AC.

Corneal collagen cross-linking demarcation line depth assessed by Visante OCT after CXL for keratoconus and corneal ectasia. J Refract Surg 2012; 28(7): 475–481.

10.

Kymionis

Tsoulnaras

Liakopoulos

, et al. Corneal stromal demarcation line depth following standard and a modified high intensity corneal cross-linking protocol. J Refract Surg 2016; 32(4): 218–222.

11.

Kymionis

Grentzelos

Plaka

, et al. Correlation of the corneal collagen cross-linking demarcation line using confocal microscopy and anterior segment optical coherence tomography in keratoconic patients. Am J Ophthalmol 2014; 157(1): 110–115.e1.

12.

Kymionis

Tsoulnaras

Grentzelos

, et al. Corneal stroma demarcation line after standard and high-intensity collagen crosslinking determined with anterior segment optical coherence tomography. J Cataract Refract Surg 2014; 40(5): 736–740.

13.

Moramarco

Iovieno

Sartori

, et al. Corneal stromal demarcation line after accelerated crosslinking using continuous and pulsed light. J Cataract Refract Surg 2015; 41(11): 2546–2551.

14.

Gatzioufas

Balidis

Kozeis

Is the corneal stromal demarcation line depth a true indicator of corneal collagen crosslinking efficacy?

J Cataract Refract Surg 2016; 42(5): 804.

15.

Kymionis

Tsoulnaras

Grentzelos

, et al. Evaluation of corneal stromal demarcation line depth following standard and a modified-accelerated collagen cross-linking protocol. Am J Ophthalmol 2014; 158(4): 671–675.

16.

Chan

Lai

, et al. Comparison of the central and peripheral corneal stromal demarcation line depth in conventional versus accelerated collagen cross-linking. Cornea 2015; 34(11): 1432–1436.

17.

Kymionis

Grentzelos

Plaka

, et al. Evaluation of the corneal collagen cross-linking demarcation line profile using anterior segment optical coherence tomography. Cornea 2013; 32(7): 907–910.

18.

Vinciguerra

Romano

Arbabi

, et al. In vivo early corneal biomechanical changes after corneal cross-linking in patients with progressive keratoconus. J Refract Surg 2017; 33: 840–846.

19.

Wollensak

Spoerl

Wilsch

, et al. Keratocyte apoptosis after corneal collagen cross-linking using riboflavin/UVA treatment. Cornea 2004; 23(1): 43–49.

20.

Brittingham

Tappeiner

Frueh

BE.

Corneal cross-linking in keratoconus using the standard and rapid treatment protocol: differences in demarcation line and 12-month outcomes. Invest Ophthalmol Vis Sci 2014; 55(12): 8371–8376.

21.

Peyman

Nouralishahi

Hafezi

, et al. Stromal demarcation line in pulsed versus continuous light accelerated corneal cross-linking for keratoconus. J Refract Surg 2016; 32(3): 206–208.

22.

Vinciguerra

Romano

Rosetta

, et al. Transepithelial iontophoresis versus standard corneal collagen cross-linking: 1-year results of a prospective clinical study. J Refract Surg 2016; 32(10): 672–678.

23.

Cantemir

Alexa

Galan

, et al. Iontophoretic collagen cross-linking versus epithelium-off collagen cross-linking for early stage of progressive keratoconus – 3 years follow-up study. Acta Ophthalmol 2017; 95(7): e649–e655.

24.

Pircher

Lammer

Holzer

, et al. Correlation between central stromal demarcation line depth and changes in K values after corneal cross-linking (CXL). Graefes Arch Clin Exp Ophthalmol 2018; 256: 759–764.

25.

Yam

Cheng

AC.

Reduced cross-linking demarcation line depth at the peripheral cornea after corneal collagen cross-linking. J Refract Surg 2013; 29(1): 49–53.

26.

Malta

Renesto

Moscovici

, et al. Stromal demarcation line induced by corneal cross-linking in eyes with keratoconus and non keratoconic asymmetric topography. Cornea 2015; 34(2): 199–203.

27.

Lhuillier

Ghetemme

Boiché

, et al. Visibility and depth of the stromal demarcation line after corneal collagen cross-linking using anterior segment optical coherence tomography: comparison between isoosmolar and hypoosmolar riboflavin. Cornea 2018; 37: 567–573.