Agreement between anterior segment Optical Coherence Tomography, Lenstar and Ultrasound Biomicroscopy measurements of anterior segment parameters

Purpose To compare anterior chamber depth (ACD) and central corneal thickness (CCT) measurements by anterior segment optical coherence tomography (AS-OCT), Lenstar and ultrasound biomicroscopy (UBM). A retrospective cross section study. A total of 83 eyes from 54 patients were included. Central corneal thickness (CCT) and anterior chamber depth (ACD) values obtained from three devices (AS-OCT, Lenstar and UBM) were recorded. All patients were collected from Oct. 2015 to Aug. 2016 in the Fourth Affiliated Hospital of China Medical University. Differences of these three devices (ACD and CCT) were statistically analyzed by randomized blocks analysis. Pearson correlative analysis and Bland-Altman analysis were used to compare the correlation and agreement. there were significant differences in other two groups (AS-OCT and AS-OCT and Lenstar) (P<0.05). significant by the three were high measuring ACD (all P<0.001, r1=0.928,r2=0.982,r3=0.932, respectively), and CCT(all P<0.001,r1=0.957,r2=0.949,r3=0.928, respectively).

imaging, high-resolution and has been widely applied in the ocular surface diseases, excimer surgery, glaucoma, lens diseases, anterior segment neoplasm etc. Through using AS-OCT, clear ocular surface images such as tear river and corneal structure, height of the tears, CCT, corneal curvature and refractive power can be obtained; and ACD, angle structure (including Schlemm tube), crystal thickness can be displayed.
In this study, the anterior segment parameters were measured by AS-OCT, Lenstar and UBM in normal eyes in order to reveal whether the measurements obtained with those three devices are comparable. The agreement, difference and correlation of ACD and CCT measured by AS-OCT, Lenstar and UBM were estimated.

Materials And Methods
The research adhered to the tenets of the Declaration of Helsinki and was approved by the Institutional Review Board of China Medical University. Trail registration: The name of the trail registry is Agreement between anterior segment Optical Coherence Tomography, 4 Lenstar and Ultrasound Biomicroscopy measurements of anterior segment parameters. The registry's URL is www.medresman.org and the registration number is ChiCTR1900021378.
This was a hospital-based, retrospective, and cross-sectional study that patients underwent routine ophthalmologic examinations (including visual acuity, IOP,  In this study, all descriptive analysis, difference analysis and correlation analysis were performed using SPSS19.0 (SPSS Inc, USA). and the agreement analysis was performed using MedCalc15.0 (MedCalc Software, Belgium). Descriptive statistics (means ± standard deviations [SDs]) of normally distributed variables (age) were calculated. The data were in accordance with the normal distribution and the variance was homogeneous. Differences of three devices were analyzed by the randomized block analysis of variance (LSD); the differences of any two devices were analyzed by paired t-test. Otherwise, the nonparametric tests were used. Correlations and agreement of three devices used Pearson correlation analysis and Bland-Altman analysis (Significance was set at P < 0.05). Differences of ACD and CCT measured by the three devices 6 The measurements of ACD and CCT of three groups are all with the normal distribution and the homogeneity of variance, and the differences of three were compared using the randomized block analysis of variance. There was a significant difference of the three groups in measuring ACD (P <0.05). The differences of ACD except measured by Lenstar and UBM were not statistically significant (P = 0.124). The other comparisons (AS-OCT and Lenstar, As-OCT and UBM), the differences were statistically significant (P<0.05). There were significant differences among three groups in measuring CCT (P <0.05). There were significant differences between any two groups (P <0.05) (Table2).

Agreement of ACD and CCT measured by the three devices
The agreement of the ACD measurements of the three devices were analyzed by Bland-Altman diagram. Lenstar and AS-OCT: 1 out of 166 points (1/166, 0.60% approximately) were outside the 95% confidence interval ( Figure 3A); Lenstar and UBM: 4 out of 166 points (4/166, 2.41% approximately) were outside the 95% confidence interval ( Figure   3B); AS-OCT and UBM: 2 out of 166 points (2/166, 1.20% approximately) were outside the 95% confidence interval ( Figure 3C). The results from Bland-Altman diagram showed that the data of any two groups of ACD measurements were within the 95% agreement interval and the confidence interval was relatively narrow, with no significant difference, and could be clinically acceptable. Bland-Altman diagram analysis showed good agreement of the 7 ACD measurements of three groups.
The agreements of the CCT measurements of three devices were analyzed by Bland-Altman diagram. Lenstar and AS-OCT: 4 out of 166 points (4/166, 2.41% approximately) were outside the 95% confidence interval ( Figure 4A); Lenstar and UBM: 3 out of 166 points (3/166, 1.81% approximately) were outside the 95% confidence interval ( Figure   4B); AS-OCT and UBM: 4 out of 166 points (4/166, 2.41% approximately) were outside the 95% confidence interval (Figure4C). The Bland-Altman diagram of any two of three devices CCT measurements showed that more than 95% of the data points were in the 95% agreement interval and the confidence interval was relatively narrow, with no significant difference, and could be clinically accepted. The results of Bland-Altman diagram analysis showed that the results of CCT measurements measuring by three devices were in good agreement. The Bland-Altman diagram showed that the data of any two groups of CCT measurements were within the 95% agreement interval and the confidence interval was relatively narrow, with no significant difference, and could be clinically acceptable. The results of Bland-Altman diagram analysis showed that the results of CCT measurements of the three groups were in good agreement.

Discussion
The anterior chamber is a structure which central is deep and peripheral shallow, mean ACD of normal people is about 3mm, which varies with age and refractive status (young people and myopia are deeper, the elderly and hyperope are shallower) {Fukuda, 2013 #630}. When the chamber angle structure cannot be directly measured, the ACD can reflect the opening and closing state of the anterior chamber angle to a certain extent. It is also one of the most simple and easy-to-obtain anatomical parameters, which has reference value for early screening of glaucoma{Baskaran, 2007 #687}. According to the too thin or unregular corneal thickness, the keratoconus may appear after the excimer 8 laser and corneal ulcer easily lead to corneal perforation; CCT will result in some errors of intraocular pressure and other tests{Abolbashari, 2013 #631;Elgin, 2016 #632}. Therefore, accurate measurements of ACD and CCT can be helpful in early screening and diagnosis.
They are some of factors that can influence the measurements of CCT and ACD such as Tear film thickness might have played a role in measuring CCT by Lenstar and AS-OCT{El-Fayoumi, 2018 #675}. Without adjusting the curve of the anterior corneal surface, the CCT measurements will be much longer, but adjusting the curve may cause the measured value shorter. The single measurement time of AS-OCT is about 3 to 4 seconds, which is shorter than Lenstar. So in the measuring time of AS-OCT, interference of blink and tear film rupture is small, but is still larger than the other two devices. The corneal curve of AS-OCT can be manually adjusted, and the tear film interference can be excluded to the maximum degree in high resolution, so the measured value is minimal. The single measurement time by Lenstar is about 6 seconds, measured after blinking, so it is more easily to be affected by the tear film{Luft, 2015 #676}. Lenstar is measured automatically by the computer, so the measurements are higher than of AS-OCT. Patients with symptoms and signs of DED (tear osmolarity, sodium fluorescein tear break-up time, ocular surface staining, Schirmer test) and significant tear hyperosmolarity symptoms showed reduced CCT using Fourier-domain optical coherence tomography{Deinema, 2017 #690}. UBM is measured in the medium, the tear film thickness may be thickened due to the influence of the medium{Wolfel, 2018 #677}. When the thickness of the CCT is manually drawn, due to the influence of the resolution, the interference of the tear film is high and the measured value is high. Therefore, The CCT measurement by UBM is the thickest among the three devices{Wolfel, 2018 #677}. The thickness of the tear film is about 7μm.
At present there is no definite gold standard for ACD measurement, and there is no uniform standard for the fluctuation range of ACD{Mosler, 2015 #678}. Therefore, noncontact examination is an effective alternative, with less damage to obtain more accurate results. In addition to measuring ACD and CCT, Lenstar is also be used for eye axial and corneal curvature measurement, IOL calculation, preoperative safety analysis of IOL, preoperative design and postoperative follow-up observation, and it also has an important reference significance for surgical method option in glaucoma patients. So in terms of the practicability, Lenstar in cataract surgery is greater, and its repeatability is better than UBM that can easy to follow up. However, UBM and AS-OCT can simultaneously measure anterior chamber angle during measuring ACD, and can examine the entire anterior segment structure, which can be used to diagnose glaucoma or suspected glaucoma. UBM is a contact examination in supine postiton, and doctor's skillful operation and patient's high coordination are very important too. The characteristics of early glaucoma screening should be simple, noninvasive, fast, accurate and can obtain comprehensive ocular parameters. Measuring by AS-OCT is more simple, fast, easy to operate, more practical and so on. In the early screening of glaucoma, AS-OCT has more advantages. And UBM is still be necessary for further confirmation.

Conclusion
In conclusion, although there were differences in the measurement values, a significant correlation and agreement was observed in CCT and ACD measurements. The three devices can be interchanged in some cases. AS-OCT can be used as the first choice for early glaucoma screening, evaluation before anterior segment surgery and also for the follow-up of ICL implantation.

Declarations
Trail registration Trail registration: The name of the trail registry is Agreement between anterior segment Optical Coherence Tomography, Lenstar and Ultrasound Biomicroscopy measurements of anterior segment parameters. The registry's URL is www.medresman.org and the registration number is ChiCTR1900021378.

Funding source
We have not financial interest and we have not received direct or indirect funding.

Availability of data and materials
The datasets for the analysis of this study are readily available from the corresponding author on reasonable request. And an administrative permission from the 4th affiliated hospital of China Medical University is required to access the raw data.   Figure 1 The correlation diagram of ACD measured by the three instruments a Lenstar and AS-OCT. b UBM and Lenstar. c, The X axis represents UBM.

Figure 2
The correlation diagram of CCT measured by the three instruments. a Lenstar and AS-OCT. b UBM and Lenstar. c UBM and AS-OCT.