Effect of Cornea Preservation Time on Success of Descemet Stripping Automated Endothelial Keratoplasty: A Randomized Clinical Trial

Abstract

Importance: Demonstrating that success of Descemet stripping automated endothelial keratoplasty is similar across donor cornea preservation times (PTs) could increase the donor pool.

Objective: To determine whether the 3-year rate of graft success using corneal donor tissue preserved 8 to 14 days is noninferior to that of donor tissue preserved 7 days or less.

Design, setting, and participants: A multicenter, double-masked, randomized noninferiority clinical trial was conducted from April 16, 2012, to June 5, 2017, at 40 clinical sites (70 surgeons) in the United States, with donor corneas provided by 23 US eye banks. A total of 1090 individuals (1330 study eyes) underwent Descemet stripping automated endothelial keratoplasty (1255 eyes [94.4%] for Fuchs endothelial corneal dystrophy).

Interventions: Descemet stripping automated endothelial keratoplasty with random assignment of a donor cornea with a PT of 7 days or less (0-7d PT) or 8 to 14 days (8-14d PT).

Main outcomes and measures: Graft success at 3 years.

Results: Of the 1090 participants (1330 study eyes; 60.2% women and 39.8% men; median age at enrollment, 70 years [range, 42-90 years]), the 3-year cumulative probability of graft success was 95.3% (95% CI, 93.6%-96.9%) in the 0-7d PT group and 92.1% (95% CI, 89.9%-94.2%) in the 8-14d PT group (difference, 3.2%). The upper limit of the 1-sided 95% CI on the difference was 5.4%, exceeding the prespecified noninferiority limit of 4%. The difference was mostly owing to more primary donor failures in the 8-14d PT group, with the conditional probability of failure after the first month being 2.4% in the 0-7d PT group and 3.1% in the 8-14d PT group. In preplanned secondary analyses, longer PT was associated with a lower rate of graft success (unadjusted hazard ratio for graft failure per additional day of PT, 1.10; 95% CI, 1.03-1.18; P = .008 [PT analyzed as days]), with success rates of 96.5% (95% CI, 92.3%-98.4%) for PT of 4 days or less, 94.9% (95% CI, 92.5%-96.6%) for PT of 5 to 7 days, 93.8% (95% CI, 91.0%-95.8%) for PT of 8 to 11 days, and 89.3% (95% CI, 84.4%-92.7%) for PT of 12 to 14 days (P = .01 [PT analyzed as categorical variable]).

Conclusions and relevance: The 3-year success rate in eyes undergoing Descemet stripping automated endothelial keratoplasty was high irrespective of PT. However, the study was unable to conclude that the success rate with donor corneas preserved 8 to 14 days was similar to that of corneas preserved 7 days or less with respect to the prespecified noninferiority limit. Although longer PT was associated with a lower success rate, the difference in rates was small when PT was less than 12 days.

Trial registration: ClinicalTrials.gov NCT01537393.

Figure 1.. Enrollment and 3-Year Follow-up Flowchart

A total of 480 study eyes completed bilateral surgery (240 participants) and 850 eyes completed unilateral surgery. Deviations from preservation time (PT) group assignment: 2 eyes had their assigned donor corneas inadvertently switched and received the opposite of their intended PT group. This switch resulted in 1 of these participants receiving a donor cornea in both study eyes from the same PT group (the group that received a donor cornea with a PT of 8 to 14 days [8-14d PT group]). These cases are counted in the PT group as treated. One participant received a donor cornea that was stored for 15 days and was included in the 8-14d PT group. The lost-to-follow-up category includes 20 eyes with no data in the 3-year window but with data in the 4-year window; these eyes were censored prior to 3 years in the primary analyses. Overall graft failure was 31 in the group with PT of 0 to 7 days [0-7d PT group] and 50 in the 8-14d PT group; 1 graft failure in each PT group was censored owing to a severe event unrelated to the PT. The 3-year-visit-completed category includes only eyes without graft failure and includes 13 eyes that did not complete a 3-year visit, but medical records were available to capture data either within the 3-year window (35-42 months) or within the acceptable late out-of-window range (42-44 months).

Figure 2.. Graft Success During 3 Years

A, Graft success estimate by preservation time groups (0-7 days [n = 674], 95.3% [95% CI, 93.6%-96.9%] and 8-14 days [n = 655], 92.1% [95% CI, 89.9%-94.2%]). The 3-year graft success difference was 3.2%, and the upper limit of the 1-sided 95% CI on the difference was 5.4%. B, Graft success by preservation time subgroups (0-4 days [n = 173], 96.5% [95% CI, 92.3%-98.4%]; 5-7 days [n = 501], 94.9% [95% CI, 92.5%-96.6%]; 8-11 days [n = 409], 93.8% [95% CI, 91.0%-95.8%]; and 12-14 days [n = 246], 89.3% [95% CI, 84.4%-92.7%]). All failure or censoring events within the 3-year visit window were mapped to month 36. Available data beyond the designated 3-year visit (or the cutoff for the 3-year window when a 3-year visit was not completed) were not used in determination of failure status or censor date for the primary analyses. This protocol affected the following: 20 eyes with no data in the 3-year window but with data in the 4-year window were censored prior to 3 years in the primary analyses. One eye initiated failure before the end of the 3-year window but after the 3-year visit date that did not count as a 3-year failure in the primary analysis. Data beyond the 3-year protocol window (35-42 months) but prior to the 4-year window (42-44 months) were used to determine failure status or censor dates. This protocol affected the following: 28 eyes were permitted to complete their 3-year visit late out of window between 42 and 44 months. Four eyes did not complete a 3-year visit, but medical records were available to capture data between 42 and 44 months.