Identifying Borderline Trachoma Grades Using a Three-Latent Class Model

Vinayak Prathikanti F. I. Proctor Foundation, Department of Ophthalmology, University of California, San Francisco, California;

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Renee Casentini F. I. Proctor Foundation, Department of Ophthalmology, University of California, San Francisco, California;

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Jonathan Hwang F. I. Proctor Foundation, Department of Ophthalmology, University of California, San Francisco, California;

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Amza Abdou Programme National de Lutte Contre la Cecité, Niamey, Niger;

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Nassirou Beidou Programme National de Lutte Contre la Cecité, Niamey, Niger;

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Boubacar Kadri Programme National de Sante Oculaire, Niamey, Niger

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Ariktha Srivathsan F. I. Proctor Foundation, Department of Ophthalmology, University of California, San Francisco, California;

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Isabelle Prieto F. I. Proctor Foundation, Department of Ophthalmology, University of California, San Francisco, California;

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Winnie Huang F. I. Proctor Foundation, Department of Ophthalmology, University of California, San Francisco, California;

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Daniel G. Eyassu F. I. Proctor Foundation, Department of Ophthalmology, University of California, San Francisco, California;

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Elisabeth Gebreegziabher F. I. Proctor Foundation, Department of Ophthalmology, University of California, San Francisco, California;

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Corinne Pierce F. I. Proctor Foundation, Department of Ophthalmology, University of California, San Francisco, California;

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Hadley Burroughs F. I. Proctor Foundation, Department of Ophthalmology, University of California, San Francisco, California;

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Jeremy D. Keenan F. I. Proctor Foundation, Department of Ophthalmology, University of California, San Francisco, California;

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Thomas M. Lietman F. I. Proctor Foundation, Department of Ophthalmology, University of California, San Francisco, California;

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The WHO has a simplified grading system for assessing trachoma. However, even for experts, it can be difficult to classify certain cases as strictly positive or negative for a given grade. Given the absence of a true gold standard, we performed a Latent Class Analysis (LCA) on a set of 200 graded photos of the superior tarsal conjunctiva. Ten trained graders assessed the presence of two trachoma grades: trachomatous inflammation–follicular (TF) and trachomatous inflammation–intense (TI). The LCA was modeled in two different ways: first with two classes (presence/absence), and then with three classes, with the extra class presumed to represent a more discrepant “borderline” case. Cohen’s κ-statistics measuring agreement between graders were calculated for TF and TI grades (separately) before and after removing the third latent class. The κ-statistic increased by 0.10 (95% CI = 0.72–0.85; P <0.001) for TF and 0.13 (95% CI = 0.81–0.90; P <0.001) for TI, indicating that the third latent class represented a discrepant-case borderline class. The identification of borderline grading cases using a three-class LCA may be useful in creating balanced grader certification examinations that represent the full spectrum of disease. Additionally, a multiclass LCA could act as a probabilistic gold standard used to train and analyze future convolutional neural network models.

Author Notes

Financial support: The Trachoma Elimination Follow-up trial received financial support from the Bernard Osher Foundation, the International Trachoma Initiative, the Bodri Foundation, the South Asia Research Fund, the Harper Inglis Trust, Research to Prevent Blindness, All May See Foundation, and the NIH (Grants R01EY025350, UG1EY030833, and UG1EY028088). The Partnership for Rapid Elimination of Trachoma trial was funded by the Bill and Melinda Gates Foundation, and azithromycin was donated to the National Trachoma Control Programs of each country by Pfizer Inc. through the International Trachoma Initiative.

Disclosure: Upon review by the UCSF Committee on Human Research/Institutional Review Board, this study used deidentified photos and was classified as exempt research.

Current contact information: Vinayak Prathikanti, Renee Casentini, Jonathan Hwang, Ariktha Srivathsan, Isabelle Prieto, Winnie Huang, Daniel G. Eyassu, Elisabeth Gebreegziabher, Corinne Pierce, Hadley Burroughs, Jeremy D. Keenan, and Thomas M. Lietman, F. I. Proctor Foundation, Department of Ophthalmology, University of California, San Francisco, CA, E-mails: vinayak.prathikanti@gmail.com, casentini1@kenyon.edu, jonhwan@nuevaschool.org, ariktha.srivathsan@ucsf.edu, isabelleprieto1@gmail.com, winnieh531@gmail.com, deyassu@tulane.edu, elisabeth.gebreegziabher@ucsf.edu, coreypierce@berkeley.edu, hadley.burroughs@ucsf.edu, jeremy.keenan@ucsf.edu, and tom.lietman@ucsf.edu. Amza Abdou, Nassirou Beidou, and Boubacar Kadri, Programme National De Santé Oculaire, Ministère De La Santé Publique, Niamey, Niger, E-mails: dr.amzaabdou@gmail.com, nasbeido@yahoo.fr, and boubacarkadri@gmail.com.

Address correspondence to Thomas M. Lietman, F.I. Proctor Foundation, University of California, 490 Illinois St. #25, San Francisco, CA 94158. E-mail: tom.lietman@ucsf.edu
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