Patients and methods: In total, 50 eyes of 25 keratoconic patients before and after cross linking treatment were analyzed in this study. Pachymetry measurements were performed at center, inferior and superior temporal and nasal locations using US pachymeter, OCT and Scirus. One way ANOVA, intra-class correlation coefficient (ICC), coefficient of variation (COV) and Bland and Altman plots were used for statistical analysis.
Results: The mean corneal thicknesses measured at center, ST, and IT before cross-linking and at center, ST, SN and IN after crosslinking was statistically different between pachymeters. The highest correlation coefficient was found to be between US and OCT at IT (0.868) before cross-linking and between US and OCT at center (0.826) and ST (0.801) after cross-linking. Poorest agreement prior to cross-linking was between Scirus and OCT at SN (0.211), and after cross-linking between US and Scirus at IT (0.003), between US and OCT (0.099) as well as and between US and Scirus (ICC = 0.098) at IT. Variation was negligible for OCT and maximal for US pachymetry before and after cross-linking.
Conclusion: OCT displayed high agreement with ultrasound pachymeter and least variations in readings before and after crosslinking of keratoconous eyes. Hence it is recommended to use only OCT for pre-surgical evaluation and follow-up. However, replication of the results in larger sample size is needed.
Keywords: Pachymetry; Keratoconous; OCT; Scirus US pachymeter; Corneal thickness; cross linking;
Numerous devices have been developed to measure the corneal thickness which includes ultrasound pachymetry, optical pachymetry, contact and noncontact specular microscope, scanning slit topography/pachymetry, corneal confocal microscopy, ultrasound biomicroscopy, partial coherence interferometry, and optical coherence tomography [7,8,9]. However, the ideal device should be able to measure the corneal thickness accurately and safely as the outcome and success rate of corneal cross-linking depends on the accuracy and precision of pachymetry measurements [10]. Ultrasound pachymetry is considered the gold standard for determining corneal thickness due to high degree of inter-observer and inter-instrument reproducibility [11]. Nonetheless, this device uses contact method for measuring corneal thickness which requires application of topical anesthesia and is unsafe due to many reasons such as direct contact of the probe with cornea increases the risk of tear film, incorrect and unrepeatable probe placement, and differences in pressure applied during measurement [9,12,13]. Additionally, with each contact of the probe, the machine can determine the corneal thickness at one single point only. Therefore, non-contact methods of measuring corneal thickness have gained popularity.
The Scirus uses a rotating Scheimpflug camera system and provides 3-dimensional scanning of the whole anterior segment of the eye, information regarding corneal pachymetry, anterior and posterior corneal topography, anterior chamber depth, volume, and angle and lens density [14]. The noncontact measuring process with the Scirus system takes 2s, performing 12– 50 single captures while rotating around the optical axis of the eye. As every slit image consists of 500 true elevation points, the Scirus system detect, in total, up to 2500 height values, which are processed to a 3-dimensional model of the entire anterior eye segment [15]. The slit-lamp OCT (SL-OCT) combines slit-lamp biomicroscopy and imag¬ing technology of OCT and it can also be used to measure the corneal thickness [8].
Pachymeters are highly expensive instruments. It incurs heavy expenses on the hospitals to keep more than one pachymeters for patient examination. Further, high variability in the outcome is expected when corneal thickness is measured with one pachymeter before cross-linking and with another after crosslinking. To address the issues related to variability in outcome most of the studies so far have assessed the agreement of noncontact pachymeters with ultrasound pachymeter (the gold standard) in pre- and post-treated keratoconic eyes [7,15,16]. However, along with above mentioned evaluation, assessing the agreement between pre- and post- cross-linking corneal thickness measurements by each non contact pachymeter is necessary as it gives the most accurate outcome of the treatment during follow-up, beside reducing the hospital expenses.
In this study, we evaluated the agreement between contact (ultrasound pachymeter) and non contact instruments (Sirius and OCT) in measuring corneal thickness at different locations in Keratoconous patients before and after corneal cross-linking and also evaluated the variability in readings by three devices before and after the treatment.
Inclusion criteria: All keratoconus patients with corneal thickness more than 400 micron.
Exclusion criteria: The patients with corneal thickness less than 400 micron were excluded. Moreover, the patients with Vogt’s striae, scaring, previous hydrops, refractive excimer cornea surgery, and corneal ring or previous cross linking treatment were also excluded.
Corneal thickness was noted at five different locations: center, superior temporal (ST), inferior temporal (IT), superior nasal (SN), and inferior nasal (IN) repeated three times and average of the three reading was recorded. The corneal thickness at the geometric center was used as the reference for defining the rest of the locations through the x-y Cartesian coordinate grid embedded in the software of each instrument. Subjects were asked to blink before every scanning for an optically smooth tear film over the cornea, head was positioned in rest, and they were asked to fixate on the target on the center of the camera without blinking during the scan.
All images and pachymetric maps were analyzed after recording the measurements with the respective software of the respective machines. All the above measurements were repeated after six month postoperatively.
Measurement localization |
Pre cross-linking |
P value |
Post cross-linking |
P value |
|
(Mean ± SD µm) |
(Mean ± SD µm) |
||
Central |
||||
US Pachymeter |
480.28 ± 17.25 |
0.003 |
424.42 ± 11.61 |
0.000 |
Scirus |
468.28 ± 18.85 |
406.32 ± 18.18 |
||
OCT |
471.04 ± 18.03 |
421.70 ± 13.60 |
||
ST |
||||
US Pachymeter |
511.38 ± 19.29 |
0.000 |
451.96 ± 14.77 |
0.000 |
Scirus |
515.32 ± 29.44 |
432.14 ± 19.89 |
||
OCT |
496.82 ± 20.70 |
448.26 ± 16.87 |
||
IT |
||||
US Pachymeter |
508.76 ± 17.38 |
0.002 |
444.42 ± 58.98 |
0.260 |
Scirus |
522.76 ± 27.89 |
433.80 ± 17.87 |
||
OCT |
509.96 ± 16.59 |
444.04 ± 14.42 |
||
SN |
||||
US Pachymeter |
503.50 ± 17.83 |
0.578 |
447.16 ± 13.71 |
0.000 |
Scirus |
508.48 ± 24.18 |
429.88 ± 20.01 |
||
OCT |
501.96 ± 47.53 |
442.26 ± 15.33 |
||
IN |
||||
US Pachymeter |
509.46 ± 17.63 |
0.273 |
454.64 ± 10.27 |
0.000 |
Scirus |
503.28 ± 20.75 |
434.02 ± 19.51 |
||
OCT |
505.52 ± 19.50 |
449.34 ± 13.97 |
Measurement localization |
Pre cross-linking |
P value |
Post cross-linking |
P value |
|
Mean diff. |
Mean diff. |
||
Central |
||||
US Pachymetervs. Scirus |
12.0 |
0.003 |
18.1 |
0.000 |
Pachymeter vs. OCT |
9.24 |
0.031 |
2.72 |
0.626 |
Scirusvs.OCT |
-2.76 |
0.726 |
-15.38 |
0.000 |
ST |
||||
US Pachymetervs. Scirus |
-3.94 |
0.682 |
19.82 |
0.000 |
Pachymeter vs. OCT |
14.56 |
0.007 |
3.7 |
0.535 |
Scirusvs.OCT |
18.50 |
0.000 |
-16.12 |
0.000 |
IT |
||||
US Pachymetervs. Scirus |
-14.0 |
0.004 |
10.62 |
0.317 |
Pachymeter vs. OCT |
-1.2 |
0.957 |
0.38 |
0.999 |
Scirusvs.OCT |
12.8 |
0.009 |
-10.24 |
0.343 |
SN |
||||
US Pachymetervs. Scirus |
-4.98 |
0.724 |
17.28 |
0.000 |
Pachymeter vs. OCT |
1.54 |
0.969 |
4.9 |
0.304 |
Scirusvs.OCT |
6.52 |
0.575 |
-12.38 |
0.001 |
IN |
||||
US Pachymetervs. Scirus |
6.18 |
0.250 |
20.62 |
0.000 |
Pachymeter vs. OCT |
3.94 |
0.566 |
5.3 |
0.187 |
Scirusvs.OCT |
-2.24 |
0.832 |
-15.32 |
0.000 |
Measurement localization |
Pre cross-linking |
Post cross-linking |
||
ICC (r) |
95% CI |
ICC (r) |
95% CI |
|
Central |
|
|
|
|
US Pachymetervs. Scirus |
0.683*** |
0.025 – 0.879 |
0.291*** |
-0.086 – 0.588 |
US Pachymeter vs. OCT |
0.786*** |
0.128 – 0.925 |
0.826*** |
0.694 – 0.901 |
Scirusvs.OCT |
0.771*** |
0.629 – 0.823 |
0.331*** |
-0.040 – 0.604 |
ST |
|
|
|
|
US Pachymetervs. Scirus |
0.447*** |
0.197 – 0.643 |
0.347*** |
-0.087 – 0.650 |
US Pachymeter vs. OCT |
0.513*** |
0.062 – 0.751 |
0.801*** |
0.653 – 0.886 |
Scirusvs.OCT |
0.555*** |
0.049 – 0.788 |
0.334*** |
-0.013 – 0.593 |
IT |
|
|
|
|
US Pachymetervs. Scirus |
0.490*** |
0.153 – 0.705 |
0.003 |
-0.270 – 0.277 |
US Pachymeter vs. OCT |
0.868*** |
0.779 – 0.923 |
0.099 |
-0.188 – 0.368 |
Scirus vs.OCT |
0.510*** |
0.190 – 0.714 |
0.355** |
0.069 – 0.582 |
SN |
|
|
|
|
US Pachymetervs. Scirus |
0.676*** |
0.489 – 0.803 |
0.226** |
-0.054 – 0.478 |
US Pachymeter vs. OCT |
0.326* |
0.051 – 0.554 |
0.644*** |
0.421 – 0.788 |
Scirus vs.OCT |
0.211 |
-0.068 – 0.460 |
0.276** |
0.008 – 0.510 |
IN |
|
|
|
|
US Pachymeter vs. Scirus |
0.795*** |
0.578 – 0.894 |
0.098 |
-0.077 – 0.303 |
Pachymeter vs. OCT |
0.573*** |
0.355 – 0.732 |
0.693*** |
0.390 – 0.839 |
Scirus vs.OCT |
0.612*** |
0.406 – 0.760 |
0.332*** |
-0.022 – 0.596 |
(Table 5) shows the homogeneity in variances within different modalities for corneal measurements. At central location before surgery, all the three instruments had good agreement in the measurements (p = 0.872) which was absent post surgery (p < 0.001). Similarly, at SN and IN also, the measurements between instruments are in accord before surgery which is not present after surgery. All the three instruments were in agreement for corneal measurement after surgery at IT position. At ST position, all the three instruments differed considerably in corneal measurements in both time points (pre-and post-surgery).
Measurement localizations |
Pre cross-linking |
Post cross-linking |
F- value |
p-value |
Central |
||||
US Pachymeter |
0.030 ± 0.018 |
0.021 ± 0.016 |
6.322 |
0.014 |
Scirus |
0.033 ± 0.022 |
0.036 ± 0.024 |
0.566 |
0.454 |
OCT |
0.031 ± 0.021 |
0.025 ± 0.019 |
2.094 |
0.151 |
ST |
||||
US Pachymeter |
0.032 ± 0.018 |
0.023 ± 0.022 |
4.464 |
0.037 |
Scirus |
0.044 ± 0.035 |
0.037 ± 0.025 |
1.216 |
0.273 |
OCT |
0.030 ± 0.028 |
0.029 ± 0.023 |
0.033 |
0.856 |
IT |
||||
US Pachymeter |
0.029 ± 0.017 |
0.044 ± 0.124 |
0.748 |
0.389 |
Scirus |
0.044 ± 0.029 |
0.033 ± 0.024 |
4.208 |
0.043 |
OCT |
0.026 ± 0.018 |
0.026 ± 0.018 |
0.000 |
0.987 |
SN |
||||
US Pachymeter |
0.030 ± 0.017 |
0.023 ± 0.019 |
3.134 |
0.080 |
Scirus |
0.039 ± 0.026 |
0.036 ± 0.028 |
0.215 |
0.644 |
OCT |
0.044 ± 0.083 |
0.027 ± 0.021 |
2.006 |
0.160 |
IN |
||||
US Pachymeter |
0.030 ± 0.018 |
0.021 ± 0.016 |
16.735 |
0.000 |
Scirus |
0.030 ± 0.018 |
0.021 ± 0.016 |
0.252 |
0.616 |
OCT |
0.030 ± 0.018 |
0.021 ± 0.016 |
1.396 |
0.240 |
Corneal locations |
Levene statistic |
P value |
Pre - Central |
0.137 |
0.872 |
Post - Central |
6.190 |
0.003 |
Pre - ST |
4.260 |
0.016 |
Post - ST |
3.623 |
0.029 |
Pre - IT |
9.883 |
0.000 |
Post - IT |
0.746 |
0.476 |
Pre - SN |
0.965 |
0.383 |
Post - SN |
3.392 |
0.036 |
Pre - IN |
0.519 |
0.596 |
Post - IN |
10.273 |
0.000 |
At five different locations where corneal thickness was measured, OCT showed maximum agreement with US pachymeter before and after cross-linking. Although corneal thickness measured centrally (mean difference, 9.24) and supratemporally (mean difference, 14.56) by OCT was lower in keratoconic eyes earlier to cross-linking when compared to US (p < 0.05), they were in complete agreement after the treatment. In accordance with our results, previous researches have also shown that OCT underestimated the central corneal thickness compared to US [15,16,17]. The maximum difference between US and OCT was 5.3 which are lower than what other studies have reported. With OCT, Ho et al [15] found the mean corneal thickness to be 11.64 ± 12.87 μm lower than with US pachymetry in post-LASIK eyes (P < 0.01). Ponce and colleagues found a decrease of 7.5 ± 1.4 μm in mean in pachymetry measurements with OCT which was comparable with keratoconus-suspect or post-LASIK eyes (P > 0.05). [16] Contrary to our other studies, Li et al [18], have noted higher mean value of corneal thickness for OCT than US. Higher US pachymetry values are attributed to corneal edema produced by anesthetic drops. [18] OCT pachymetry values tend to be accurate due to improved centration and perpendicularity. [18,19] On the other hand, tear-film displacement caused by US pachymetry may lead to lower pachymetry values than those obtained by OCT. [15,18,19] Research by other two groups, Li et al [20] and Beutelspacher et al [8], showed no significant dif¬ference between these two modalities. This high correlation of measurement values between the two modalities may be due to the similar mechanism of the two instruments – both use reflection of waves to determine the anterior and pos¬terior boundaries of the cornea. [21] Moreover, many studies consider OCT to be superior over other tomographic devices, such as Orbscan II (Bausch & Lomb), because it obtains corneal-thickness profiles in less time and is not influenced by stromal reflections or haze. [15,18,19] In addition to diagnosis, OCT systems can screen and monitor the progression of the keratoconus [22].
In this study, mean corneal thickness obtained by Scirus machine was variable at different locations in pre-surgical keratoconic eyes while they were remarkably less than both US and OCT in post surgical eyes. Our results were in agreement with the results of Ho et al [15], Ponce et al [16] and with the recent meta-analysis. All the three studies showed that Scirus considerably underestimated the corneal thickness at center in post-LASIK eyes compared to OCT and US [15,17,23]. Even in normal eyes, Lackner et al [24], showed Scirus readings to be slightly smaller (9.8 mm) than US. Contrarily, Ackay et al [22], reported that Scirus measurements were higher than OCT at different locations except at center in keratoconous eyes. In normal eyes, good correlation between US and Scirus readings were noted. [25] In our study although correlation between US and Scirus was good before cross-linking, it reduced greatly in post treated eyes and became non-significant at IT and IN locations.
Although few studies have analyzed the inter and intra operator variability of the pachymeters, none so far have focused on variations between measurements taken by same machine before and after surgery. [26,27] in the present study, variation in OCT measurements before and after cross-linking at different locations was comparable. Scirus significantly differed in pre and post readings at IT. Interestingly, US considerably varied in readings at three different locations before and after crosslinking. This poses a question on using of US pachymeter for follow-up after corneal cross-linking.
The two major limitations of the study include lack of the intra- and inter observer reproducibility of the measurements obtained with each instrument and small sample size.
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