Random Survival Forests Analysis of Intraoperative Complications as Predictors of Descemet Stripping Automated Endothelial Keratoplasty Graft Failure in the Cornea Preservation Time Study

Abstract

Importance: A new analytic method can evaluate factors of interest associated with graft failure after Descemet stripping automated endothelial keratoplasty (DSAEK) or more generally in any ophthalmic surgical setting with a time-to-event outcome.

Objective: To reanalyze types of intraoperative complications associated with DSAEK graft failure in the Cornea Preservation Time Study using random survival forests.

Design, setting, and participants: This cohort study, initially conceived in April 2019, used a prediction model to conduct a post hoc 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. The study included 1090 participants, representing 1330 eyes, undergoing DSAEK for Fuchs dystrophy (1255 eyes [94.4%]) or pseudophakic or aphakic corneal edema (75 eyes [5.6%]). Enrollment occurred between April 16, 2012, and February 20, 2014, and follow-up ended June 5, 2017. Statistical analysis was performed from July 10, 2019, to May 29, 2020.

Intervention: Descemet stripping automated endothelial keratoplasty with random assignment of a donor cornea with preservation time of 7 days or less or 8 to 14 days.

Main outcomes and measures: Ranked variable importance for intraoperative complications among 50 donor, recipient, and eye bank variables and restricted mean survival time through 47 months (1434 days) after DSAEK were examined. Random survival forests, a nonparametric method (with less restrictive model assumptions) that is far more flexible in its ability to model nonlinear effects and interactions, was used to analyze the data.

Results: This study included 1090 participants (663 women [60.8%]; median age, 70 years [range, 42-90 years]), representing 1330 eyes. Random survival forests ranked a DSAEK intraoperative complication as the third most predictive factor of graft failure, after surgeon and eye bank, in the final model with 5 predictors. In the first 47 months after DSAEK, the estimated mean difference in restricted mean survival time for grafts that experienced a DSAEK intraoperative complication vs those that did not was -227 days (99% CI, -352 to -70 days) based on the final RSF model.

Conclusions and relevance: These findings, while post hoc, support the hypothesis that random survival forests allow for an improved analytic approach for identifying factors predictive of graft failure and for obtaining adjusted graft survival estimates. Random survival forests offer the opportunity to guide the development of future population-based cohort ophthalmic surgical studies, establishing definitive factors for procedural success.

Figure 1.. Variable Importance Plot for Predicting Graft Failure for the 4 Predictors Selected by Variable Hunting Using Variable Importance After Requiring Preservation Time

Any predictor with variable importance above the line at 0.00 contributes to the prediction accuracy of the final model. Any variable with variable importance less than 0.00 is a noisy variable in the final model, which is the case with preservation time, which we required to be included. This is consistent with the results of the primary study, which found that graft survival at 3 years was indistinguishable through 11 days of preservation time and the decrement in survival was modest for corneas preserved 12 to 14 days. DSAEK indicates Descemet stripping automated endothelial keratoplasty; and presvToSurgDays, preservation to surgery (in days).

Figure 2.. Unadjusted Survival Curves for Presence or Absence of a Descemet Stripping Automated Endothelial Keratoplasty (DSAEK) Intraoperative Complication

The survival curves were estimated nonparametrically via the Kaplan-Meier method (1330 eyes).

Figure 3.. Adjusted Survival Curves for Presence or Absence of a Descemet Stripping Automated Endothelial Keratoplasty (DSAEK) Intraoperative Complication

The survival curves were estimated nonparametrically via random survival forests (1330 eyes).