June 2017
Volume 58, Issue 8
Open Access
ARVO Annual Meeting Abstract  |   June 2017
Tear molecular biomarkers can predict the development of ocular chronic graft versus host disease before hematopoietic stem cell transplantation
Author Affiliations & Notes
  • Lidia Cocho
    IOBA (Institute of Applied OphthalmoBiology). University of Valladolid, Valladolid, Spain
  • Itziar Fernández
    CIBER-BBN (Biomedical Research Networking Center in Bioengineering, Biomaterials and Nanomedicine). Carlos III National Institute of Health , Madrid, Spain
    IOBA (Institute of Applied OphthalmoBiology). University of Valladolid, Valladolid, Spain
  • Margarita Calonge
    IOBA (Institute of Applied OphthalmoBiology). University of Valladolid, Valladolid, Spain
    CIBER-BBN (Biomedical Research Networking Center in Bioengineering, Biomaterials and Nanomedicine). Carlos III National Institute of Health , Madrid, Spain
  • Maite Sainz De La Maza
    Clinical Institute of Ophthalmology (ICOF), Barcelona, Spain
  • Montserrat Rovira
    Clinical Institute of Hematologic and Oncological Diseases (ICMHO), Barcelona, Spain
  • Carmen García-Vázquez
    IOBA (Institute of Applied OphthalmoBiology). University of Valladolid, Valladolid, Spain
  • Michael E Stern
    IOBA (Institute of Applied OphthalmoBiology). University of Valladolid, Valladolid, Spain
    ImmunEyez, Orange County, California, United States
  • Amalia Enriquez-De-Salamanca
    IOBA (Institute of Applied OphthalmoBiology). University of Valladolid, Valladolid, Spain
    CIBER-BBN (Biomedical Research Networking Center in Bioengineering, Biomaterials and Nanomedicine). Carlos III National Institute of Health , Madrid, Spain
  • Footnotes
    Commercial Relationships   Lidia Cocho, None; Itziar Fernández, None; Margarita Calonge, None; Maite Sainz De La Maza, None; Montserrat Rovira, None; Carmen García-Vázquez, None; Michael Stern, ImmunEyez (E); Amalia Enriquez-De-Salamanca, None
  • Footnotes
    Support  SAF2016-77080-P
Investigative Ophthalmology & Visual Science June 2017, Vol.58, 2648. doi:
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      Lidia Cocho, Itziar Fernández, Margarita Calonge, Maite Sainz De La Maza, Montserrat Rovira, Carmen García-Vázquez, Michael E Stern, Amalia Enriquez-De-Salamanca; Tear molecular biomarkers can predict the development of ocular chronic graft versus host disease before hematopoietic stem cell transplantation. Invest. Ophthalmol. Vis. Sci. 2017;58(8):2648.

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      © ARVO (1962-2015); The Authors (2016-present)

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Abstract

Purpose : To develop a model based on tear levels of a panel of inflammatory mediators to predict the occurrence of ocular chronic Graft Versus Host Disease (cGVHD) before Hematopoietic Stem Cell Transplantation (HSCT).

Methods : 25 patients undergoing HSCT were prospectively followed for up to 3 years. Ocular examination results were recorded, and tears were collected before HSCT and after several time-points. Levels of 19 molecules (EGF, eotaxin 1/CCL11, fractalkine/CX3CL1, IL-1Ra, IL-1β, IL-2, IL-4, IL-5, IL-6, IL-8/CXCL8, IL-10, IL-12p70, IL-13, IL-17A, IP-10/CXCL10, IFN-γ, VEGF, TNF-α, and RANTES/CCL5) were measured by multiplex bead assay. Multistate models (MSM) considering four states (HSCT, systemic cGVHD, ocular cGVHD, and decease) were used to identify cytokine tear levels that may be associated with the progress of transplanted patients and predict patients’ risk of developing ocular cGVHD. Molecules included in the final multivariable model were reduced by a supervised Principal Components Analysis (PCA). For internal validation of the final MSM, bootstrap re-sampling was used. Model discriminatory ability was determined according to the time-dependent ROC curves, and the corresponding AUC.

Results : A multistate model was constructed based on fractalkine/CX3CL1, IL-1Ra and IL-6 tear levels, which had a significant influence in the transition between the four different states. This model, based on a new variable built upon combination of these three molecules, displayed an AUC value between 67%-80% throughout follow up, which corresponds to a good discriminatory ability.

Conclusions : Tear levels of several molecules before HSCT were relatedto individual risk of developing ocular cGVHD. The model based on fractalkine/CX3CL1, IL-1Ra, and IL-6 tear levels before HSCT may allow patient’ stratification according to risk of developing ocular cGVHD prior to transplantation, thus allowing clinicians to adequately manage those high-risk patients.

This is an abstract that was submitted for the 2017 ARVO Annual Meeting, held in Baltimore, MD, May 7-11, 2017.

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