1. Postoperative Visual Acuity in Patients With Fuchs Dystrophy Undergoing Descemet Membrane–Stripping Automated Endothelial Keratoplasty: Correlation With the Severity of Histologic Changes Happ DM, Lewis DA, Eng KH, et al. Postoperative visual acuity in patients with Fuchs dystrophy undergoing Descemet membrane–stripping automated endothelial keratoplasty: correlation with the severity of histologic changes. Arch Ophthalmol. 2012;130(1):33-38. Copyright restrictions may apply

2. Introduction Fuchs endothelial dystrophy is a common cause of decreased visual acuity due to cornea-related pathologic changes. Progressive and possibly irreversible changes in the corneal stroma associated with increasing severity of Fuchs dystrophy may limit postoperative best-corrected visual acuity (BCVA) following Descemet membrane–stripping automated endothelial keratoplasty (DSAEK) in more severe cases of Fuchs dystrophy. Objective: To investigate a correlation between the severity of histologic changes of the Descemet membrane, which we believe would correlate to the severity of corneal stromal changes, in patients with Fuchs dystrophy and the postoperative BCVA following DSAEK. Copyright restrictions may apply

3. Methods Retrospective study design. A total of 92 DSAEK specimens of patients with a clinical diagnosis of Fuchs endothelial dystrophy were obtained from 3 corneal surgeons. Thirteen specimens were excluded owing to visually significant comorbid disease, graft failure, or surgical complications. Copyright restrictions may apply

4. Methods Data Analysis –The DSAEK specimens were evaluated under light microscopy, and a histologic grading system was created based on 4 characteristics: (1) guttae dispersion; (2) presence of a laminated Descemet membrane; (3) presence of embedded guttae; and (4) density of guttae. Based on the total score, the cases were categorized into mild, moderate, or severe disease. –Preoperative BCVA and postoperative BCVA at 6 months, 1 year, and 2 years were obtained. –Regression models were used to compare the histologic score (mild, moderate, severe), presence of the 4 individual histologic features used for grading, preoperative BCVA, and postoperative BCVA at 6 months, 1 year, and 2 years. Copyright restrictions may apply

5. Methods Grading System for Histologic Changes Observed in Descemet Membrane Copyright restrictions may apply

6. Methods Limitations –No clinical correlation. –No confocal microscopy for comparison. –Unknown accuracy of the weight of the factors used for histologic grading. –Unable to determine the stromal changes or the association with the severity of Fuchs dystrophy in relation to changes in the Descemet membrane based solely on DSAEK specimens. Copyright restrictions may apply

7. Results No significant relationship between preoperative BCVA, the individual histologic features, or the histologic score was found. There was a mild correlation between the preoperative and final BCVAs. There was no correlation between the 4 individual histologic features or the histologic score and the postoperative BCVA at 6 months, 1 year, and 2 years following DSAEK. Copyright restrictions may apply

8. Results Simple linear regression of preoperative and postoperative visual acuity (VA) (left column) and a piecewise linear regression (right column) show that patients’ VA improves regardless of preoperative VA. This trend is observed at 6 months (top row), 12 months (middle row), and 24 month (bottom row). Copyright restrictions may apply

9. Results Patients with laminated Descemet membrane but without embedded guttae are less responsive to DSAEK and do not obtain the same postoperative BCVA benefit. Copyright restrictions may apply

10. The subgroup of patients with lamination and no embedded guttae appear to be less responsive to DSAEK. Results Copyright restrictions may apply

11. Comment Implications for future clinical work: histologic findings of lamination of Descemet membrane without concordant embedded guttae may be used by the surgeon to explain why postoperative BCVA following DSAEK did not show the anticipated improvement. An explanation for why patients with a laminated Descemet membrane without embedded guttae may have poorer outcomes could be the separation of the layers of Descemet membrane during DSAEK and thus incomplete removal of the recipient’s Descemet membrane. Remnants of the recipient’s Descemet membrane would then be present at the host-donor interface. 1 Preoperative BCVA is mildly correlated with postoperative BCVA, and earlier surgical intervention (DSAEK) may have better visual outcomes for patients. Copyright restrictions may apply 1 Dapena I, Ham L, Moutsouris K, Melles GR. Incidence of recipient Descemet membrane remnants at the donor-to- stromal interface after descemetorhexis in endothelial keratoplasty. Br J Ophthalmol. 2010;94(12):1689-1690.

12. Comment Implications for future research in this area: there are no methods currently available to implicate the development of a laminated Descemet membrane or embedded guttae, and there are no known risk factors that suggest a higher risk for their development. Investigations may be warranted into what factors may cause the development of lamination of Descemet membrane without embedded guttae as this was a rare finding, because lamination of Descemet membrane with guttae was highly correlated. Copyright restrictions may apply

13. Contact Information If you have questions, please contact the corresponding author: –Daniel M. Albert, MD, MS, Department of Ophthalmology and Visual Sciences, University of Wisconsin–Madison, Room K6/412 Clinical Science Center, 600 Highland Ave, Madison, WI 53792 (dalbert@wisc.edu). Funding/Support This study was supported by core grant for vision research P30 EY016665 from the National Institutes of Health and by an unrestricted department award from Research to Prevent Blindness. Copyright restrictions may apply