Predicting Edema Resolution After Descemet Membrane Endothelial Keratoplasty for Fuchs Dystrophy Using Scheimpflug Tomography

Abstract

Predicting the extent of corneal edema resolution after Descemet membrane endothelial keratoplasty (DMEK) may help in preoperative decision-making by identifying patients who may benefit from restoring endothelial function.OBJECTIVE To develop and validate a predictive model for edema resolution after DMEK using Scheimpflug tomographic imaging. DESIGN, SETTING, AND PARTICIPANTSTwo prospective studies recruited participants with advanced Fuchs dystrophy at a university-based tertiary referral center between July 1, 2017, and August 31, 2019. Analyses were designed in November 2019 and completed on June 30, 2020. Development of a predictive model using linear least absolute shrinkage and selection operator regression was conducted in a derivation cohort (100 eyes). Overall performance, discrimination, and calibration were tested in the separate validation cohort (32 eyes).EXPOSURES Preoperative Scheimpflug parameters and patient-reported visual disability were considered as potential predictors of edema resolution: (1) tomographic features (irregularity of lines of equal corneal thickness, displacement of the thinnest point of corneal thickness from the inferior-temporal quadrant, and absolute amount of focal posterior corneal depression), (2) standardized anterior and posterior corneal backscatter, (3) preoperative central corneal thickness, and (4) Fuchs dystrophy-specific visual disability. MAIN OUTCOMES AND MEASURES Decrease in central corneal thickness after DMEK indicative of edema resolution. RESULTSOf the 88 patients included in the analysis, 54 were women (61%); median age was 68 years (interquartile range [IQR], 59-76 years). A median of 13 months after DMEK (IQR, 9-16 months), median corneal thickness was 77 μm lower (IQR, 51-94 μm) in the derivation cohort and 75 μm lower in the validation cohort (IQR, 54-96 μm) than before surgery. Per 10-μm edema resolution, eyes gained 0.66 Early Treatment Diabetic Retinopathy Study letters (95% CI, 0.09-1.23) in best-corrected visual acuity. Three tomographic features were present in 68 of 100 eyes (68%) in the derivation cohort and in 18 of 32 eyes (56%) in the validation cohort before DMEK and in only 1 of 132 eyes (1%) after DMEK. To predict edema resolution after DMEK based on preoperative assessment, 5 variables were selected by the statistical learning algorithm: nonparallel isopachs, focal posterior depression, anterior and posterior corneal backscatter, and central corneal thickness. In the separate validation cohort, the model showed high overall performance, discrimination, and calibration.CONCLUSIONS AND RELEVANCE These post hoc analyses of prospective cohorts support a model for use in the prediction of edema resolution after DMEK using Scheimpflug measurement to identify patients benefitting most from DMEK.

Predicting Corneal Improvement after Descemet Membrane Endothelial Keratoplasty for Fuchs Endothelial Corneal Dystrophy

“…In contrast, our model assessed tomography map patterns independent of preoperative CCT (Figure 4), and had much higher predictive power than the model by Zander and colleagues. 7 Our study is not without limitations. The limits of agreement for the validation group (Figure 1D) were wider than those of the derivation group (Figure 1B) because the model significantly underestimated the predicted change in CCT in 1 eye.…”

“…17 The strongest factor in the model proposed by Zander and colleagues was preoperative CCT; this is not surprising because change in CCT is calculated in part from preoperative CCT (i.e., these variables are related) and their model had few other candidate parameters. Indeed, when we applied the Zander model coefficient estimates (using standardized backscatter) 7 to our derivation data, we found that 70% (from R 2 ) of the predicted change in CCT was attributed to preoperative CCT (Figure 4), whereas in reality, only 15% (from R 2 ) of the observed change in CCT was explained by preoperative CCT (Figure 4).…”

“…Predicting the presence of corneal edema in FECD from an isolated measurement of CCT is not possible and therefore models that are strongly dependent on preoperative CCT should be used with caution, if at all. As a result, the model by Zander and colleagues 7 will predict more improvement in thicker preoperative corneas whether edema is present or not, and this is similar to erroneously making clinical practice decisions based on cutoffs of preoperative CCT.…”

“…Recently, Zander and colleagues developed a model to predict corneal improvement in FECD after DMEK by using Scheimpflug imaging. 7 They assessed pre-determined parameters for predicting the change in CCT, including subjective categorical assessment of isopach irregularity, and continuous assessment of posterior surface depression, corneal backscatter, and CCT. Of note, they assessed posterior surface depression as displacement from the best-fit sphere rather than the volume of depressed tissue; we assessed several volumetric parameters in our study (see Table, available at https://www.ophthalmologyscience.org), but none were strong enough to be incorporated into our final model.…”

“…6 Importantly, this method is independent of CCT measurement, which was previously used as a guideline for when to consider keratoplasty in clinical practice; however, clinical decisions based on absolute values of CCT can result in inappropriate treatment (a change in CCT over time is more helpful than isolated values of CCT). Scheimpflug tomography has the potential to objectively quantify corneal edema and its improvement with therapy, and although such a model was recently proposed for this, 7 it was largely dependent on preoperative CCT and therefore subject to the same caveats of using CCT measurements in clinical practice. 4,6 However, Scheimpflug pachymetry patterns are potentially more important than pachymetry values, and their quantification could provide an objective assessment of corneal edema and its improvement after therapy, with potential application in clinical trials of novel therapeutic agents.…”