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Clinical Sciences |

Endothelial Morphometric Measures to Predict Endothelial Graft Failure After Penetrating Keratoplasty

Beth Ann Benetz, MA; Jonathan H. Lass, MD; Robin L. Gal, MSPH; Alan Sugar, MD; Harry Menegay, PhD; Mariya Dontchev, MPH; Craig Kollman, PhD; Roy W. Beck, MD, PhD; Mark J. Mannis, MD; Edward J. Holland, MD; Mark Gorovoy, MD; Sadeer B. Hannush, MD; John E. Bokosky, MD; James W. Caudill, MD; for the Cornea Donor Study Investigator Group
JAMA Ophthalmol. 2013;131(5):601-608. doi:10.1001/jamaophthalmol.2013.1693.
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Importance Endothelial morphometric measures have potential value in predicting graft failure after penetrating keratoplasty.

Objective To determine whether preoperative and/or postoperative central morphometric measures (endothelial cell density [ECD], coefficient of variation [CV], and percentage of hexagonality [HEX]) and their postoperative changes are predictive of graft failure caused by endothelial decompensation after penetrating keratoplasty to treat a moderate-risk condition, principally Fuchs dystrophy or pseudophakic corneal edema.

Design In a subset of Cornea Donor Study participants with graft failure, a central reading center determined preoperative and postoperative ECD, CV, and HEX from available central endothelial specular images.

Setting Cornea Image Analysis Reading Center of the Specular Microscopy Ancillary Study.

Participants Eighteen patients with graft failure due to endothelial decompensation and 54 individuals matched for most donor and recipient measures at baseline whose grafts did not fail.

Main Outcome Measure Change in ECD, CV, and HEX values.

Results Preoperative ECD was not associated with graft failure (P = .43); however, a lower ECD at 6 months was predictive of subsequent failure (P = .004). Coefficient of variation at 6 months was not associated with graft failure in univariate (P = .91) or multivariate (P = .79) analyses. We found a suggestive trend of higher graft failure with lower HEX values at 6 months (P = .02) but not at the established statistical significance (P < .01). The most recent CV or HEX values, as time-dependent variables, were not associated with graft failure (P = .26 and P = .81, respectively). Endothelial cell density values decreased during follow-up, whereas CV and HEX appear to fluctuate without an apparent trend.

Conclusions and Relevance Endothelial cell density at 6 months after penetrating keratoplasty is predictive of graft failure, whereas CV and HEX appear to fluctuate postoperatively, possibly indicating an unstable endothelial population in clear and failing grafts.

Trial Registration clinicaltrials.gov Identifier:NCT00006411

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Figures

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Figure 1. Box plot of endothelial cell density (ECD) over time in study participants with graft failures due to endothelial decompensation (n = 18) and in those whose grafts did not fail (n = 54). Numbers above the whiskers indicate the number of failed grafts available for analysis; numbers below, grafts that did not fail that were available for analysis. Black dots indicate mean values; horizontal lines in the boxes, medians; the bottom and top of the boxes, the 25th and 75th percentiles, respectively; and whiskers, minimum and maximum values.

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Figure 2. Box plot of the coefficient of variation of cell area over time in study participants with graft failures due to endothelial decompensation (n = 18) and in those whose grafts did not fail (n = 54). Numbers above the whiskers indicate the number of failed grafts available for analysis; numbers below, grafts that did not fail that were available for analysis. Black dots indicate mean values; horizontal lines in the boxes, medians; the bottom and top of the boxes, the 25th and 75th percentiles, respectively; and whiskers, minimum and maximum values.

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Figure 3. Box plot of the percentage of hexagonal cells (HEX) over time in study participants with graft failures due to endothelial decompensation (n = 18) and in those whose grafts did not fail (n = 54). Numbers above the whiskers indicate the number of failed grafts available for analysis; numbers below, grafts that did not fail that were available for analysis. Black dots indicate mean values; horizontal lines in the boxes, medians; the bottom and top of the boxes, the 25th and 75th percentiles, respectively; and whiskers, minimum and maximum values.

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Figure 4. Plots of morphometric measures at baseline by donor age in 68 study participants with gradable images. A, Coefficient of variation (CV) (correlation = 0.16 [95% CI, −0.08 to 0.39]). B, Percentage of hexagonal cells [HEX]) (correlation = 0.12 [95% CI, −0.12 to 0.35]). Five-year plots for both variables exhibited a similar relationship.

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