INTRODUCTION

Descemet membrane endothelial keratoplasty (DMEK) is an attractive alternative to corneal transplantation for patients with endothelial dysfunction. The procedure involves transplantation of a graft consisting of donor endothelium and Descemet membrane (DM) that replaces the host endothelium and DM. This procedure offers certain advantages over Descemet stripping (automated) endothelial keratoplasty (DS(A)EK) in which the graft includes portions of stromal tissue that may distort the corneal architecture, produce more higher-order aberrations, and provide more immunogenic tissue that could possibly precipitate graft rejection^(1-5). Although DMEK has been shown to have quicker and more pronounced visual rehabilitation than DSEK⁽¹⁾, the different techniques and learning curve of DMEK have limited widespread adoption of this approach.

One of the most important challenges facing DMEK is preventing postoperative graft detachment, which is the most frequent complication of the procedure. Detachment rates reported in the literature vary, with one recent multicenter study reporting rates of 34.6%⁽⁶⁾. These detachments may necessitate postoperative intervention involving reinjection of intraocular air.

Although some surgeons use air for tamponade during the procedure, longer-acting inert gases, such as sulfur hexafluoride (SF₆), have been explored for this application recently. SF₆ has a higher buoyancy and a longer half-life than those of air⁽⁷⁾, which possibly provides advantages for maintaining graft attachment postoperatively. A recent study of 44 patients who underwent DSEK compared SF₆ with air for graft attachment and noted that, although patients who received air had five graft detachments, there were no detachments reported in the group that received SF₆ ⁽⁸⁾. Additionally, Guell et al., recently demonstrated reduced detachment rates with SF₆ from those with air in their series, and no effect on corneal endothelial cell counts was observed⁽⁹⁾. In the present study, we compared graft detachment rates between SF₆ and air for intraocular tamponade in DMEK.

METHODS

A retrospective chart review was performed to evaluate patients who underwent DMEK by a single surgeon (A.S.J.) at the Wilmer Eye Institute of Johns Hopkins Hospital between January 2012 and December 2014. Forty-two eyes were identified; 21 received air for intraocular tamponade and 21 received SF₆. Approval from the Institutional Review Board of Johns Hopkins University was obtained, and the study was conducted in concordance with the ethical principles established in the Declaration of Helsinki.

Data on patient demographics, preoperative and postoperative intraocular pressure (IOP), best spectacle corrected visual acuity (BSCVA), graft detachment, and donor tissue were collected from the patients' operative and follow-up notes and from tissue bank information. BSCVA was measured using the Snellen chart, and IOP was measured using Goldmann applanation tonometry. The indication for all operations was bullous keratopathy caused by Fuchs' endothelial dystrophy.

RESULTS

Forty-two eyes were included; 21 received air and the next 21 consecutive eyes received SF₆ for intraocular tamponade. Table 1 summarizes the baseline characteristics for each group. The preoperative BSCVA values were significantly different between the two groups (Group 1 (air): logMAR, 0.33 ± 0.15; Group 2 (SF₆): logMAR, 0.48 ± 0.21 (p=0.014), with no significant differences in the other preoperative measures.

For other ocular comorbidities, one patient in group 1 had diabetic macular edema, one patient in group 1 had epiretinal membranes in both eyes, one in group 1 had a history of optic neuritis, two patients in group 2 were glaucoma suspects, and one patient in group 2 had mild amblyopia OS.

DISCUSSION

In this study, we compared the outcomes of 42 eyes that underwent DMEK at our institution, 21 with 20% SF₆ and 21 with 100% air used for intraocular tamponade, and focused on detachment and intervention rates. We demonstrated a lower detachment rate when SF₆ was used, and no significant differences in other outcome measures were observed.

Complication rates with DMEK have improved over the years with refinements in surgical technique and increased surgical experience. Graft detachment rates have dramatically improved. An important criterion to consider, however, is the surgeon's determination of which detachments require intervention. A recent series by Terry using SF₆ for DMEK demonstrated a 6% graft rebubbling rate, although a 47% graft detachment rate as measured by optical coherence tomography (OCT) was reported ⁽¹¹⁾. Their rebubbling criteria were separation of donor Descemet membrane causing central corneal edema affecting vision and/or evidence of progressive separation of the graft over successive visits. Guell et al. noticed a similar rebubbling rate but stated that they also had detachments that did not fit their criteria for rebubbling⁽⁹⁾. In our study, all of the partial graft detachments were determined to fit our criteria for rebubbling, which included central corneal edema affecting vision. There are limited data on whether more aggressive intervention is necessary or beneficial to long-term vision recovery, and currently the decision to intervene is at the surgeon's discretion.

In our experience, the incorporation of SF₆ coincided with the transition to smaller trephine size (8.0 mm). Both smaller trephine size and use of SF₆ correlated with reduced risk of detachment in the univariate analysis (Table 3). Multivariate analysis with both variables included was, therefore, partially confounded. However, comparison of the detachment rates between eyes with the same graft size but that had received SF₆ or air suggests a benefit for the former. For example, 8.5-mm grafts showed detachments rates of 68% for group 1 (13/19) and 20% for group 2 (1/5). For graft sizes of ≤8.0 mm, the detachment rates were 50% for group 1 (1/2) and 19% for group 2 (3/16). However, the coinciding changes in smaller graft size from 8.5 to 8.0 mm with the introduction of SF₆ led to only two eyes in our series receiving both 8.0-mm graft size and air, which made a more robust analysis difficult. The high odds ratio for reduced detachment rate with SF₆ use and the significance from univariate and multivariate analyses with graft size removed strongly suggest that the gas used is a significant factor affecting detachment rate. Additionally, the gas used had a much more statistically significant effect than did graft size when both were included in the multivariate model. However, because our study design was retrospective, and changes in graft size coincided with the change from air to SF₆, our analysis could not determine the relative contribution of these two factors.

An additional concern with use of SF₆ is potential toxicity to the corneal endothelium⁽¹²⁾. Although the gas is thought to be inert, increased buoyancy and longevity of the gas may have mechanical effects on the endothelial surface⁽¹³⁾. A recent in vitro study, however, found no significant difference between SF₆ and air on endothelial cell counts or toxicity of corneal endothelial cells⁽¹⁴⁾. Additionally, Guell et al. found no difference in endothelial cell counts between use of SF₆ or air ≤3years after DMEK⁽⁹⁾.

One weakness of our study was that the SF₆ procedures followed the air procedures chronologically because detachment rates have been found to diminish with experience of the surgeon⁽¹⁵⁾. However, the reduction in detachment rates from the first 21 to the next 21 consecutive eyes was dramatic, and detachment rates were equivalent between those in the first half of air cases and those in the second half. Although technical improvement of the surgeon may account for some of this difference, SF₆ was found to have a substantial impact on maintaining graft adherence and preventing graft detachment post-surgery without any significant differences in other outcome measures in our study. Randomized prospective studies could further address this important question.