September 2016
Volume 57, Issue 12
Open Access
ARVO Annual Meeting Abstract  |   September 2016
Alterations to Bowman's layer and local molecular deregulation driving focal corneal weakening: new evidence towards Keratoconus etiopathogenesis
Author Affiliations & Notes
  • Natasha Pahuja
    Cornea-Refractive, Narayana Nethralaya, Pune, Maharashtra, India
  • Nimisha R Kumar
    Narayana Nethralaya, Bangalore, India
  • RUSHAD SHROFF
    Cornea-Refractive, Narayana Nethralaya, Pune, Maharashtra, India
  • rohit shetty
    Cornea-Refractive, Narayana Nethralaya, Pune, Maharashtra, India
  • Abhijit Sinha Roy
    Narayana Nethralaya, Bangalore, India
  • Arkasubhra Ghosh
    Narayana Nethralaya, Bangalore, India
  • Footnotes
    Commercial Relationships   Natasha Pahuja, None; Nimisha Kumar, None; RUSHAD SHROFF, None; rohit shetty, None; Abhijit Sinha Roy, Avedro (F), Bioptigen (F), Carl Zeiss (F), Cleveland Clinic Innovations (P), Narayana Nethralaya (P), Topcon (F); Arkasubhra Ghosh, None
  • Footnotes
    Support  None
Investigative Ophthalmology & Visual Science September 2016, Vol.57, 2912. doi:
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      Natasha Pahuja, Nimisha R Kumar, RUSHAD SHROFF, rohit shetty, Abhijit Sinha Roy, Arkasubhra Ghosh; Alterations to Bowman's layer and local molecular deregulation driving focal corneal weakening: new evidence towards Keratoconus etiopathogenesis. Invest. Ophthalmol. Vis. Sci. 2016;57(12):2912.

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

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Abstract

Purpose : To elucidate local factors in ectatic cones of Keratoconus(KC) patients which may reveal a functional cause for focal corneal weakening characteristic of the disease.

Methods : Samples were collected after informed written consent and with Institutional Ethics committee approval. The Bowman's layer in KC patients as imaged by high resolution anterior segment optical coherence tomography(ASOCT) was segmented using combination of Graph search and Djikstra’s algorithm. In patients (n=70) undergoing corneal crosslinking, corneal epithelium over 4.5mm cornea, centered on the cone (located by corneal topography) was trephine marked and debrided whereas the surrounding periphery was debrided separately. Non-ectatic refractive surgery patients (n=26) served as controls. Gene expression levels were estimated separately in cone and periphery samples of each eye and ratio of the values used to correlate differential expression for each molecular factor with clinical parameters and biomechanical data.

Results : ASOCT revealed local aberrations and focal loss of Bowman’s layer in some KC cones. Epithelium from the cone apex of these particular patients had highly elevated MMP9, TNFα and IL6 but reduced IL10, TIMP1, Collagen IV and Collagen I expression relative to peripheral epithelium indicating a cone-specific local effect. Data across the cohort revealed significant loss of LOX (p=0.002) Collagen IV (p=0.008) and Collagen I (p=0.01) expression in the cone of KC patients compared to controls. MMP9 levels (p=0.009) were significantly elevated in the cone while its inhibitor TIMP1 showed a reducing trend in KC patients. Inflammatory genes TNFα and IL6 were elevated in the cone in KC patients while IL10 showed slight reduction. The same results were validated in matched cone vs periphery samples of corneal stroma as well as epithelium from 4 KC patients undergoing keratoplasty.

Conclusions : Our study uncovers the first evidence in KC patients that local alterations to Bowman's layer due to injury, eye rubbing, structural defects, etc may trigger a focal, cone specific degenerative process. Consequently deregulated local epithelial molecular factors drive changes that could cause the focal thinning and protrusion. This data also suggests that functional correction using collagen crosslinking should be concentrated at the cone rather than entire KC cornea

This is an abstract that was submitted for the 2016 ARVO Annual Meeting, held in Seattle, Wash., May 1-5, 2016.

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