Donor, Recipient, and Operative Factors Associated With Increased Endothelial Cell Loss in the Cornea Preservation Time Study

Abstract

; for the Cornea Preservation Time Study Group IMPORTANCE Determining factors associated with endothelial cell loss after Descemet stripping automated endothelial keratoplasty (DSAEK) could improve long-term graft survival. OBJECTIVE To evaluate the associations of donor, recipient, and operative factors with endothelial cell density (ECD) 3 years after DSAEK in the Cornea Preservation Time Study. DESIGN, SETTING, AND PARTICIPANTS This cohort study was a secondary analysis of data collected in a multicenter, double-masked, randomized clinical trial. Forty US clinical sites with 70 surgeons participated, with donor corneas provided by 23 US eye banks. Individuals undergoing DSAEK for Fuchs dystrophy or pseudophakic/aphakic corneal edema were included. INTERVENTIONS The DSAEK procedure, with random assignment of a donor cornea with a preservation time of 0 to 7 days or 8 to 14 days. MAIN OUTCOMES AND MEASURES Endothelial cell density at 3 years as determined by a reading center from eye bank and clinical specular or confocal central endothelial images. RESULTS The study included 1090 participants (median age, 70 years) with 1330 affected eyes (240 bilateral cases [22.0%]), who underwent DSAEK for Fuchs dystrophy (1255 eyes [94.4%]) or pseudophakic/aphakic corneal edema (PACE) (75 eyes [5.6%]). Of these, 801 eyes (60.2%) belonged to women and 1207 (90.8%) to white individuals. A total of 749 participants (913 eyes; 164 [21.9%] bilateral cases) had functioning grafts with acceptable endothelial images preoperatively and at 3 years postoperatively and were included in this analysis. Factors associated with a lower ECD at 3 years (estimated effect with 99% CI) in the final multivariable model included donors with diabetes (−103 [−196 to −9] cells/mm 2), lower screening ECD (−234 [−331 to −137] per 500 cells/mm 2), recipient diagnosis of PACE (−257 [−483 to −31] in cells/mm 2), and operative complications (−324 [−516 to −133] in cells/mm 2). Endothelial cell loss (ECL) from a preoperative measurement to a 3-year postoperative measurement was 47% (99% CI, 42%-52%) for participants receiving tissue from donors with diabetes vs 43% (99% CI, 39%-48%) without diabetes; it was 53% (99% CI, 44%-62%) for participants diagnosed with PACE vs 44% (99% CI, 39%-49%) for those diagnosed with Fuchs dystrophy, and 55% (99% CI, 48%-63%) in participants who experienced operative complications vs 44% (99% CI, 39%-48%) in those who did not. No other donor, recipient, or operative factors were significantly associated with 3-year ECD. CONCLUSIONS AND RELEVANCE Donor diabetes, lower screening ECD, a PACE diagnosis in the recipient, and operative complications were associated with lower ECD at 3 years after DSAEK surgery and may be associated with long-term graft success. While causation cannot be inferred, further studies on the association of donor diabetes and PACE in recipients with lower 3-year ECD warrant further study.

Descemet Stripping Automated Endothelial Keratoplasty

“…The complication rate and postoperative ECD for triple procedures compared to the DSAEK alone cases have not been shown to be different for short-term periods (6 months and 12 months) or longer-term follow-up of 3 to 5 years. [ 12 – 14 ] The 5 year ECL in our study (44.4%) was comparable to the 3 year ECL in the CPTS for the Fuchs dystrophy subgroup (44%). [ 12 ] The Price et al study reported a higher 5 year ECL at 53% compared to our study.…”

“…[ 12 – 14 ] The 5 year ECL in our study (44.4%) was comparable to the 3 year ECL in the CPTS for the Fuchs dystrophy subgroup (44%). [ 12 ] The Price et al study reported a higher 5 year ECL at 53% compared to our study. [ 22 ] In our study here with a longer follow-up time than the CPTS and over 200% more analyzed eyes than prior single center studies, [ 22 ] we have confirmed that the triple procedure is comparable to DSAEK alone surgery at 5 years postoperatively.…”

“…[ 9 , 10 ] However, there is a theoretical risk that the greater instability of the newly placed intraocular lens (IOL) in a triple procedure and the added postoperative inflammation from the concomitant cataract surgery may increase the endothelial cell loss rate in a triple procedure graft v a DSAEK without other simultaneous surgery. [ 11 ] While the Cornea Preservation Time Study [ 12 ] (CPTS) and other single center studies [ 13 , 14 ] did not show a significant difference in endothelial cell loss of Triples v DSAEK alone, the study presented here has a longer postoperative time frame than the CPTS and more patients to analyze for the 5 year postoperative visit than any prior single center study.…”

“…The CPTS found that a higher preoperative cell density was not correlated with a higher graft survival rate at 3 years, [ 15 ] but did find that there was a significant positive correlation with the postoperative endothelial cell density at 3 years. [ 12 ] In this single center study, we evaluated the correlation of preoperative cell densities to postoperative cell densities out to a longer time frame of 5 years.…”

Towards Clinical Trials in Fuchs Endothelial Corneal Dystrophy: Classification and Outcome Measures—The Bowman Club Lecture 2019

“…Peripheral endothelial cell density can be measured accurately preoperatively because these regions are usually devoid of guttae. Sustained health of the peripheral corneal endothelium in FECD is important, as poor peripheral endothelial cell reserve is associated with an increased risk of graft failure56–58 (it is unknown if this can be extrapolated to failure of non-graft interventions at this time). Changes in endothelial cell morphology, specifically a decrease in the percentage of hexagonal cells and an increase in the coefficient of variation of cell size, have provided limited information in long-term studies of corneal transplantation 53.…”