June 2015
Volume 56, Issue 7
Free
ARVO Annual Meeting Abstract  |   June 2015
Corneal Dendritic Cells as a Surrogate Biomarker of Therapeutic Efficacy in Dry Eye-Associated Corneal Inflammation
Author Affiliations & Notes
  • Yureeda Qazi
    Ophthalmology, Massachusetts Eye and Ear Infirmary, Boston, MA
  • Ahmad Kheirkhah
    Ophthalmology, Massachusetts Eye and Ear Infirmary, Boston, MA
  • Thomas H Dohlman
    Ophthalmology, Massachusetts Eye and Ear Infirmary, Boston, MA
  • Andrea Cruzat
    Ophthalmology, Massachusetts Eye and Ear Infirmary, Boston, MA
  • Bernardo Cavalcanti
    Ophthalmology, Massachusetts Eye and Ear Infirmary, Boston, MA
  • Clara Colon
    Ophthalmology, Massachusetts Eye and Ear Infirmary, Boston, MA
  • Reza Dana
    Ophthalmology, Massachusetts Eye and Ear Infirmary, Boston, MA
  • Pedram Hamrah
    Ophthalmology, Massachusetts Eye and Ear Infirmary, Boston, MA
  • Footnotes
    Commercial Relationships Yureeda Qazi, None; Ahmad Kheirkhah, None; Thomas Dohlman, None; Andrea Cruzat, None; Bernardo Cavalcanti, None; Clara Colon, None; Reza Dana, Bausch and Lomb (F), MEEI (P); Pedram Hamrah, MEEI (P)
  • Footnotes
    Support None
Investigative Ophthalmology & Visual Science June 2015, Vol.56, 291. doi:
  • Views
  • Share
  • Tools
    • Alerts
      ×
      This feature is available to Subscribers Only
      Sign In or Create an Account ×
    • Get Citation

      Yureeda Qazi, Ahmad Kheirkhah, Thomas H Dohlman, Andrea Cruzat, Bernardo Cavalcanti, Clara Colon, Reza Dana, Pedram Hamrah; Corneal Dendritic Cells as a Surrogate Biomarker of Therapeutic Efficacy in Dry Eye-Associated Corneal Inflammation. Invest. Ophthalmol. Vis. Sci. 2015;56(7 ):291.

      Download citation file:


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

      ×
  • Supplements
Abstract

Purpose: To quantify changes in corneal dendritic cell (DC) density using in vivo confocal microscopy (IVCM) before and after anti-inflammatory therapy in evaporative dry eye (EDE), and to compare these changes to symptoms and clinical signs.

Methods: A phase IV, randomized, vehicle-controlled, double-masked, single-center clinical trial was conducted with 54 subjects clinically diagnosed with EDE that received either steroid alone (Loteprednol Etabonate 0.5%, LE, n=17), steroid with antibiotic (Loteprednol Etabonate 0.5% + Tobramycin, LE/T, n=17), or artificial tears alone (AT, n=20) for 4 weeks with quantification of central corneal DC densities on IVCM pre- and post-treatment. Sixty-two healthy reference controls were also included for comparison. Symptom severity was measured using the Ocular Surface Disease Index (OSDI) questionnaire. Clinical improvement was assessed by corneal fluorescein staining (CFS) and tear break-up time (TBUT). Both eyes of each subject were analyzed. Based on normality of datasets, parametric or non-parametric tests were applied. Correlation was determined using Pearson’s correlation coefficient (R).

Results: Corneal DCs increased by over five-fold in EDE (P<0.0001) with no differences between the treatment groups at baseline (P=0.59). Following treatment, DC density reduced in both the steroid-containing treatment groups, LE/T and LE (P<0.01), but not AT (P=0.44) demonstrating specificity of response. The reduction in corneal DCs was comparable between the two steroid-containing drugs (LE: 58%, LE/T: 49%, P=0.19). DC density correlated with CFS (R=0.48, P<0.0001), OSDI scores (R= 0.37, P<0.0001), and TBUT (R=-0.25, P<0.01). CFS and OSDI scores improved by 24% (P=0.03) and 11% (P=0.06) in the LE-treated group, and by 21% (P=0.06) and 15% (P=0.09) in the AT-treated group, respectively. TBUT did not improve in any of the treatment groups (P=0.14).

Conclusions: Corneal DCs, an indicator of tissue immune response, are increased in EDE-associated ocular surface disease. Quantification of DC density in vivo allows detection of changes in the corneal immune response following anti-inflammatory therapy, providing a responsive endpoint. Given the modest but significant correlation of corneal DC density to symptoms and clinical signs, this in vivo imaging parameter may therefore serve as a surrogate biomarker of therapeutic efficacy in clinical trials.

×
×

This PDF is available to Subscribers Only

Sign in or purchase a subscription to access this content. ×

You must be signed into an individual account to use this feature.

×