We sincerely thank Dr. Wan and colleague for their interest in our recent article, entitled “Corneal Epithelial Thickness Measured Using AS-OCT as a Diagnostic Parameter for Limbal Stem Cell Deficiency”,1 and for giving us the opportunity to further elaborate on our study. We previously showed that central corneal epithelial thickness (CET) obtained using in vivo confocal microscopy (IVCM-CET) decreased substantially in eyes with limbal stem cell deficiency (LSCD).2, 3 In addition, the degree of epithelial thinning in the central cornea reflected the global function of limbal stem cells. The purpose of our recent study was to develop the methodology of CET measurement using anterior segment optical coherence tomography (OCT) as a diagnostic test for LSCD. Our decision to evaluate the 3-point measurement (OCT-CET3) stemmed from our clinical observation that CET could vary within the central 2 mm zone in eyes with sectoral LSCD and the 1-point measurement (OCT-CET1) might not be as accurate.
We showed that the inter-observer measurements of CET were highly consistent (< 5% variation) between the 2 masked observers. We calculated the repeatability coefficient of OCT-CET1 and OCT-CET3 measurements to be 11.15 μm and 3.58 μm, respectively. The intraclass correlation coefficient of OCT-CET1 and OCT-CET3 was 0.859 and 0.985, respectively. These results support a higher degree of reliability and smaller measurement error of OCT-CET3 than OCT-CET1.
Limit of Agreement (LOA) would be necessary if the purpose of the study was to establish OCT as a surrogate of a gold standard test. We did not consider IVCM as the gold standard for CET measurement but as a control. Nevertheless, we performed the analysis and found that LOA of OCT-CET1 was larger than that of OCT-CET3 (−11.96 ± 11.61 μm vs −9.78 ± 9.67 μm), which is consistent with the correlation analysis.
The area under the receiver operator characteristics curve (AUC) of OCT-CET3 was evaluated in our study, which was higher than that of the maximum limbal epithelial thickness in all four limbal regions. The AUC of OCT-CET1 (0.932) and IVCM-CET (0.911) were smaller than that of OCT-CET3 (0.973), which supports our conclusion that OCT-CET3 is a reliable value of CET as a diagnostic parameter to confirm LSCD.
We agree with Dr. Wan and colleague that appropriate statistical analyses is necessary to support the conclusion of all research. In depth knowledge of the subject of investigation and correct data acquisition are equally important in conducting a sound and meaningful study.
Acknowledgments
a. Funding/Support:
This work is supported in part by an unrestricted grant from Research to Prevent Blindness to the Department of Ophthalmology at the University of California, Los Angeles. SXD received grant support from the National Eye Institute (2R01 EY021797 and R01 EY028557), California Institute for Regenerative Medicine (TR2 TR2-01768, CLIN1-08686, CLIN2-11650).
b. Financial Disclosures:
SXD is a consultant for W. L. Gore & Associates, F-Prime Capital Partners, Dompe US and Kowa Research Institute, Inc.; QFL: none; CHT: None.
c. Other acknowledgement:
Statistical analysis was performed by Chi-hong Tseng, PhD.
References
- 1.Liang Q, Le Q, Cordova DW, Tseng CH, Deng SX. Corneal Epithelial Thickness Measured Using AS-OCT as a Diagnostic Parameter for Limbal Stem Cell Deficiency. Am J Ophthalmol 2020. [DOI] [PMC free article] [PubMed] [Google Scholar]
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