Cornea Image Analysis Reading Center

Established in 1989 at Case Western Reserve University and University Hospitals Cleveland Medical Center, the Cornea Image Analysis Reading Center (CIARC) - formerly the Specular Microscopy Reading Center (SMRC) - has participated in numerous corporate and federal clinical studies requiring standardized determination of corneal endothelial cell density and morphology from specular and confocal images, as well as qualitative and quantitative assessment of the corneal epithelium and stroma from confocal and OCT images.

The CIARC is a shared resource of the hospital and its academic partner, Case Western Reserve University School of Medicine. The Center is led by Medical Director Jonathan Lass, MD, Charles I Thomas Professor in the CWRU Department of Ophthalmology and Visual Sciences, and University Hospitals Eye Institute, and Technical Director Beth Ann Benetz, CRA, FOPS, Professor of Ophthalmology in the CWRU Department of Ophthalmology and Visual Sciences.


Clinical trial standards require accurate and reproducible endothelial cell counts to evaluate the safety of:

  • Topical/subconjunctival/intravitreal medications
  • Intraocular irrigating solutions
  • Corneal preservation media
  • Intraocular devices
  • New intraocular drug delivery systems
  • Assessing new surgical techniques: DSEK, DMEK, refractive

The capabilities of the CIARC include collection and analyses of pre-, during and post-cell changes of the endothelium. The CIARC has developed external calibration techniques that allow us to analyze images from a variety of specular microscopes and confocal instruments. A web-based image management system enables seamless transfer of images to the CIARC.

The CIARC has experience with multicenter, national and international corporate and federally (Cornea Donor Study and Cornea Preservation Time Study) sponsored clinical trials. The CIARC conducts focused web trainings detailing study-specific procedures for image capture, export and upload to the reading center.

The CIARC has pioneered the use of a dual-grading reading method, whereby all images are read and analyzed by two separate readers, and adjudicated by a third reader, as necessary, ensuring the validity of the image analysis (Current Eye Res 31:1-9, 2006). Parameters and methods of analysis of the CIARC for the endothelium include:

  • Mean cell density: variable frame, corners, center, center-flex methods
  • Mean cell area: corners, center methods
  • Coefficient of variation (CV)(polymegathism): corners , center methods
  • % hexagonal cells (pleomorphism): corners, center methods

Methods for Cell Density and Morphometric Analyses

Epithelium, Stroma and Corneal Thickness
With greater availability of confocal instrumentation for corneal studies, the CIARC has now expanded its capabilities to quantitate changes in the epithelium and stroma in a controlled manner from confocal images.

Parameters measured include:

  • Basal epithelium
  • Superficial epithelium
  • Qualitative changes over time
  • Density
  • Reflectivity (light scattering)
  • Stroma
  • Qualitative changes over time
  • Density
  • Reflectivity (light scattering)

Regional Differences

Using confocal microscopy with repeated measurements of qualitative and quantitative changes in the epithelium and stroma, CIARC can provide objective, non-biased data examining the dynamic changes in the cornea, for example, topical administration of a drug.

CIARC also has capability of determining thickness across the cornea with optical coherence tomography or confocal images and various thickness measurements related to refractive surgery procedures.


The CIARC has a more than 20-year history of publications. It was the reading center for the Specular Microscopy Ancillary Study (SMAS) of the Cornea Donor Study, a National Eye Institute-sponsored 10-year, 1,100-patient multicenter study examining the effect of donor age on graft survival and endothelial cell loss (Ophthalmology 115:620-26, 2008; 115:627-32, 2008; 120:2419-27, 2013; 120:2428-35, 2013). It is now the reading center for the NEI-sponsored Cornea Preservation Time Study (CPTS), a five-year, 1,330 eyes study involving 40 clinical sites and 22 eye banks examining the effect of preservation time on graft survival and endothelial cell loss (Cornea 34:601-08, 2015).

Contact Us for More Information

To learn more about the Cornea Image Analysis Reading Center, please contact:

Jonathan H. Lass, MD
CIARC Medical Director

Beth Ann Benetz, MA, CRA, FOPS
Director, CIARC

Tanisha Rankins-Coker, CCRP
CIARC Project Manager

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