July 2019
Volume 60, Issue 9
Free
ARVO Annual Meeting Abstract  |   July 2019
Change in Dendritiform Cell Density by In Vivo Confocal Microscopy may be used as a Surrogate Biomarker for Therapeutic Response in Dry Eye Disease Patients Enriched for Presence of Inflammation: Results from the Therapeutic Response to Anti-inflammatory agents in the Corneal Epithelium (TRACE) Study
Author Affiliations & Notes
  • Pedram Hamrah
    Center for Translational Ocular Immunology, Department of Ophthalmology, Tufts Medical Center, Boston, Massachusetts, United States
    Cornea Service, Department of Ophthalmology, New England Eye Center, Tufts Medical Center, Boston, Massachusetts, United States
  • Anam Akhlaq
    Center for Translational Ocular Immunology, Department of Ophthalmology, Tufts Medical Center, Boston, Massachusetts, United States
    Cornea Service, Department of Ophthalmology, New England Eye Center, Tufts Medical Center, Boston, Massachusetts, United States
  • Mehmet Cuneyt Ozmen
    Center for Translational Ocular Immunology, Department of Ophthalmology, Tufts Medical Center, Boston, Massachusetts, United States
    Cornea Service, Department of Ophthalmology, New England Eye Center, Tufts Medical Center, Boston, Massachusetts, United States
  • Ahmad Kheirkhah
    Ocular Surface Imaging Center, Department of Ophthalmology, Massachusetts Eye & Ear Infirmary, Harvard Medical School, Boston, Massachusetts, United States
    Cornea Service, Massachusetts Eye & Ear Infirmary, Department of Ophthalmology, Harvard Medical School, Boston, Massachusetts, United States
  • Shruti Aggarwal
    Ocular Surface Imaging Center, Department of Ophthalmology, Massachusetts Eye & Ear Infirmary, Harvard Medical School, Boston, Massachusetts, United States
  • Bernardo Cavalcanti
    Ocular Surface Imaging Center, Department of Ophthalmology, Massachusetts Eye & Ear Infirmary, Harvard Medical School, Boston, Massachusetts, United States
  • Rodrigo Mueller
    Ocular Surface Imaging Center, Department of Ophthalmology, Massachusetts Eye & Ear Infirmary, Harvard Medical School, Boston, Massachusetts, United States
  • Alessandro Abbouda
    Center for Translational Ocular Immunology, Department of Ophthalmology, Tufts Medical Center, Boston, Massachusetts, United States
    Cornea Service, Department of Ophthalmology, New England Eye Center, Tufts Medical Center, Boston, Massachusetts, United States
  • Zeina Salem
    Center for Translational Ocular Immunology, Department of Ophthalmology, Tufts Medical Center, Boston, Massachusetts, United States
    Cornea Service, Department of Ophthalmology, New England Eye Center, Tufts Medical Center, Boston, Massachusetts, United States
  • Gabriela Dieckmann
    Center for Translational Ocular Immunology, Department of Ophthalmology, Tufts Medical Center, Boston, Massachusetts, United States
    Cornea Service, Department of Ophthalmology, New England Eye Center, Tufts Medical Center, Boston, Massachusetts, United States
  • Reza Dana
    Cornea Service, Massachusetts Eye & Ear Infirmary, Department of Ophthalmology, Harvard Medical School, Boston, Massachusetts, United States
  • Footnotes
    Commercial Relationships   Pedram Hamrah, Aeri Pharmaceuticals (C), Allergan (F), Allergan (C), Axero (C), Bausch and Lomb (F), Clementia (C), Coopervision (F), Dompe (F), Dompe (C), Eyegate (C), GlaxoSmithKline (F), Heidelberg Engineering (C), Kala Pharmaceuticals (C), Novabay (C), Novaliq (C), Noveome (C), Ocunova (C), Revision Optics (C), Sanofi (C), Santen (C), Shire (F), Shire (C), Tissue Tech (F), Valeant (C); Anam Akhlaq, None; Mehmet Ozmen, None; Ahmad Kheirkhah, None; Shruti Aggarwal, None; Bernardo Cavalcanti, None; Rodrigo Mueller, None; Alessandro Abbouda, None; Zeina Salem, None; Gabriela Dieckmann, None; Reza Dana, Allergan (F), Claris Biotherapeutics (I), Kala (C), Santen (C), Shire (C)
  • Footnotes
    Support  GlaxoSmithKline, Tufts Institutional Support
Investigative Ophthalmology & Visual Science July 2019, Vol.60, 5207. doi:https://doi.org/
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      Pedram Hamrah, Anam Akhlaq, Mehmet Cuneyt Ozmen, Ahmad Kheirkhah, Shruti Aggarwal, Bernardo Cavalcanti, Rodrigo Mueller, Alessandro Abbouda, Zeina Salem, Gabriela Dieckmann, Reza Dana; Change in Dendritiform Cell Density by In Vivo Confocal Microscopy may be used as a Surrogate Biomarker for Therapeutic Response in Dry Eye Disease Patients Enriched for Presence of Inflammation: Results from the Therapeutic Response to Anti-inflammatory agents in the Corneal Epithelium (TRACE) Study. Invest. Ophthalmol. Vis. Sci. 2019;60(9):5207. doi: https://doi.org/.

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

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Abstract

Purpose : Corneal immune dendritiform cell (DC) density and morphology, as visualized by in vivo confocal microscopy (IVCM), is altered in dry eye disease (DED). DC density may thus be used as a surrogate biomarker of response to anti-inflammatory therapy. The purpose of this study was to test if after enrichment of DED patients by IVCM for increased inflammation, DC density and morphology can be used as optical biomarkers for therapeutic efficacy to topical steroids.

Methods : A prospective, multicenter, double-masked randomized placebo-control trial was conducted in 38 DED patients [n=67 eyes with central DC density >75cells/mm2, calculated as >2 SD from healthy cornea (32.0 ± 24.4cells/mm2)]. Patients were randomized into treatment arm (18 patients, n=31 eyes) receiving loteprednol etabonate (LE) 0.5% suspension, and control arm (20 patients, n=36 eyes) receiving Soothe Tired Eyes Lubricant Eye Drops artificial tears (AT) 4x/day for 2 weeks, 2x/day for 2 weeks, and once daily for 2 weeks. Clinical and DC parameters were assessed at baseline, 2 and 6 weeks (significance=p<0.05).

Results : Mean(±SD) age of LE and AT arm was 57.2±12.1 and 55.4±15.6 years, respectively (p>0.05). Clinical and imaging parameters were comparable at baseline (p>0.05 for all). DC density decreased from baseline (mean difference ±SEM) in the LE arm at 2 weeks (-104.3±17.2cells/mm2, p<0.0001) and 6 weeks (-107.6±18.1cells/mm2, p<0.0001) but not in the AT arm (2 weeks=-34.4±26.2cells/mm2, p=0.20 6 weeks=-17.3±27.8cells/mm2, p=0.20). Similarly, DC field decreased from baseline in the LE arm at 2 weeks (-1,378.0±199.3mm2, p<0.0001) and 6 weeks (-1,462.0±230.3mm2, p<0.0001), but not in the AT arm (2 weeks=-474.1±354.1mm2, p=0.19; 6 weeks=44.3±404.1mm2, p=0.91). DC size did not differ from baseline to 6 weeks (p>0.05 for both arms). Corneal fluorescein staining correlated with DC density (R=0.37, p<0.0001) and field (R=0.38, p<0.0001).

Conclusions : Enrichment of DED patients for inflammation using IVCM prior to treatment with topical steroids yields a pronounced decrease in DC density and field. Hence, these DC parameters may be used as surrogate biomarkers of inflammation to assess therapeutic efficacy to anti-inflammatory therapies.

This abstract was presented at the 2019 ARVO Annual Meeting, held in Vancouver, Canada, April 28 - May 2, 2019.

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