Cornea Image Analysis Reading Center

Established in 1989 at Case Western Reserve University and University Hospitals Case 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 and more recently qualitative and quantitative assessment of the corneal epithelium and stroma from confocal 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 and Chairman of the CWRU Department of Ophthalmology and Visual Sciences, Director of UH Eye Institute, and Technical Director Beth Ann Benetz, CRA, FOPS, Associate Professor of Ophthalmology at CWRU School of Medicine.


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
  • Assessing new surgical techniques

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 multi-center, national and international federal and corporate 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

Corners Method for Cell Density and Morphometric Analyses

Corners Method

Variable Frame Method for Cell Density and Morphometric Analyses

Variable Frame Method

Center Method for Cell Density and Morphometric Analyses

Center Method

Center Flex Method for Cell Density and Morphometric Analyses

Center Flex Method

Epithelium and Stroma

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:

  • 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.


The CIARC has a more than 20-year history of publications. It is the reading center for the Specular Microscopy Ancillary Study (SMAS) of the Cornea Donor Study, a National Eye Institute-sponsored five-year, 1,100-patient multi-center study examining the effect of donor age on graft survival and endothelial cell loss.

Results of this study showed not only that donor age had no effect on graft success in patients undergoing penetrating keratoplasty for primary endothelial failure (Ophthalmology 115:620-26, 2008), but also endothelial cell loss is comparable (Ophthalmology 115:627-32, 2008). This study has been extended for another five years to continue examining the effect of age on graft and endothelial survival, as well as other donor and recipient factors.

Recently the SMAS study also reported that the baseline cell count does not predict graft failure; rather the six-month count is predictive. This study also found that 15% of grafts are clear even with counts below 500 cells/mm2. (Arch Ophthalmol 128:63-69, 2010).

Finally, the CIARC has shown that the cell loss with DSEK is significantly higher at six month as compared to a cohort of SMAS patients. However, the rate of cell loss flattens out thereafter, demonstrating that the type of endothelial loss with DSEK is quite different than PK (Ophthalmology 117:438-44, 2010).

Contact us for more information

Jonathan H. Lass, MD
CIARC Medical Director and Chairman

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

Nicola Goodall, MSW

Jonathan Volpe, MBA
Administrative Manager

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