Laurence E. Frank

Prevention and Management of Graft Detachment in Descemet Membrane Endothelial Keratoplasty

OBJECTIVE To describe the prevention and management of various types of graft detachment after Descemet membrane endothelial keratoplasty. METHODS In 150 consecutive eyes that underwent Descemet membrane endothelial keratoplasty, the incidence and type of graft detachment were studied at 1, 3, 6, 9, 12, and 24 months after surgery in a nonrandomized, prospective clinical study at a tertiary referral center. Four groups of detachments were identified: a partial detachment of one-third or less of the graft surface area (n = 16; group 1); a partial detachment of more than one-third of the graft surface area (n = 8; group 2); a graft positioned upside down (n = 4; group 3); and a free-floating Descemet roll in the host anterior chamber (n = 8; group 4). RESULTS Partial or complete graft detachment was found in 36 cases (24%), of which 18 (12%) were clinically significant. All 24 eyes with a partial detachment (groups 1 and 2) showed spontaneous corneal clearance, and all but 6 of these eyes (75%) reached visual acuity of 20/40 or better (≥0.5). A reversed clearance pattern and interface spikes were observed in eyes with the graft positioned upside down (group 3). Eyes with a free-floating graft (group 4) showed persistent corneal edema. Detachments were associated with inward folds (12 eyes [33%]), insufficient air-bubble support (7 eyes [19%]), upside-down graft positioning (4 eyes [11%]), use of plastic materials (2 eyes [6%]), irido-graft synechiae (1 eye [3%]), poor endothelial morphology (1 eye [3%]), and stromal irregularity under the main incision (1 eye [3%]); 14 (58%) of the partial detachments were localized inferiorly. CONCLUSIONS Awaiting spontaneous clearance may be advocated in eyes with a partial detachment. Minor adjustments in surgical protocol as well as careful patient selection may further reduce the incidence of graft detachment after Descemet membrane endothelial keratoplasty to 4% or less. TRIAL REGISTRATION clinicaltrials.gov Identifier: NCT00521898.

Outcomes of Descemet membrane endothelial keratoplasty in phakic eyes

PURPOSE: To determine the clinical outcomes of isolated Descemet membrane transplantation (ie, Descemet membrane endothelial keratoplasty [DMEK]) in phakic eyes. SETTING: Tertiary referral center. DESIGN: Cohort study. METHODS: Phakic eyes from a larger group of consecutive eyes that had DMEK for Fuchs endothelial dystrophy were examined. The examination included corrected distance visual acuity (CDVA), subjective and objective refractions, endothelial cell density (ECD), and intraoperative and postoperative complications at 1, 3, and 6 months. RESULTS: The study enrolled 52 phakic eyes from a group of 260 DMEK eyes. Of the phakic eyes, 69% reached a CDVA equal to or better than 20/40 (≥0.5) within 1 week and 85% reached equal to or better than 20/25 (≥0.8) at 6 months. Compared with an age‐matched control group of pseudophakic eyes, phakic eyes had a similar visual rehabilitation rate, final visual outcome, mean ECD at 6 months (1660 cells/mm2 ± 470 [SD]), minor hyperopic shift (+0.74 diopter), and graft detachment rate (4%). Visual acuity equal to or better than 20/13 (≥1.5) was limited to phakic eyes, suggesting better optical quality with the crystalline lens in situ. Temporary mechanical angle‐closure glaucoma due to air‐bubble dislocation behind the iris was the main complication (11.5%). Two eyes (4%) required phacoemulsification after DMEK. CONCLUSIONS: In phakic eyes, DMEK may give excellent visual outcomes without an increased risk for complications. Visual acuities equal to or better than 20/13 (≥1.5) may indicate that the almost anatomic repair after DMEK is associated with near perfect optical quality of the transplanted cornea. Financial Disclosure: Dr. Melles is a consultant to D.O.R.C. International/Dutch Ophthalmic USA. No author has a financial or proprietary interest in any material or method mentioned.

Endothelial Survival After Descemet Membrane Endothelial Keratoplasty: Effect of Surgical Indication and Graft Adherence Status

IMPORTANCE This study evaluates the longevity of Descemet membrane endothelial keratoplasty (DMEK) grafts in terms of endothelial survival and endothelial failure. OBJECTIVE To determine endothelial survival and its association with the indication for surgery and/or partial graft detachment in DMEK. DESIGN, SETTING, AND PARTICIPANTS Retrospective cross-sectional study of data collected from August 8, 2006, until June 17, 2015, at a tertiary referral center. A total of 352 eyes were evaluated up to 8 years after DMEK for Fuchs endothelial corneal dystrophy (FECD; n = 314), bullous keratopathy (BK; n = 31), and failed previous endothelial graft (n = 7), of which 314 eyes had complete graft attachment and 38 eyes had partial graft detachment (one-third of the graft surface area or less). Endothelial cell density was measured with specular microscopy, and Kaplan-Meier survival estimates were based on eyes with endothelial failure. Endothelial survival was followed up to 8 years after DMEK. MAIN OUTCOMES AND MEASURES Endothelial cell density, endothelial failure, and endothelial survival. RESULTS Endothelial cell density decreased to a mean (SD) of 952 (366) and 771 (321) cells/mm2 at 7 and 8 years postoperatively, respectively. Higher endothelial cell densities were found in eyes with FECD compared with those with BK (estimated mean difference, 261 cells/mm2; 95% CI, 118-404; P = .003) and in eyes with attached grafts compared with those with partially detached grafts (estimated mean difference, 330 cells/mm2; 95% CI, 208-452; P < .001), until 8 years. In 11 eyes (3.1%) that had concomitant ocular pathology, endothelial failure occurred within 4 years after DMEK. The overall graft survival probability was 0.96 at 5 and 8 years (95% CI, 0.94-0.99). At 8 years, better survival rates were found in eyes with FECD than in those with BK (survival probability, 0.97 [95% CI, 0.95-0.99] vs 0.84 [95% CI, 0.70-0.99], respectively); until the same follow-up, survival probabilities in eyes with attached and partially detached grafts were 0.97 (95% CI, 0.95-0.99) and 0.91 (95% CI, 0.82-0.99), respectively. CONCLUSIONS AND RELEVANCE Endothelial decay was higher in eyes with a partial graft detachment than in those with attached grafts and lower in eyes with FECD than in those with BK. Endothelial failure only occurred in eyes with concomitant ocular pathology. These results suggest that eyes with DMEK that have undergone surgery for FECD with a completely attached graft may have an excellent prognosis.

Towards an evidence-based treatment model for cognitive behavioral interventions focusing on chronic fatigue syndrome

OBJECTIVE The purpose of the present study was to develop a treatment model for cognitive behavioral interventions focusing on chronic fatigue syndrome (CFS) based on the model of perpetuating factors introduced by Vercoulen et al. [Journal of Psychosomatic Research 1998;45:507-17]. METHODS For this purpose, we reanalyzed the data of a previously conducted randomized controlled trial in which a low intensity cognitive behavioral intervention was compared to a waiting list control group. Structural equation modeling was used to test a treatment model in which changes in focusing on symptoms, perceived problems with activity, and sense of control over fatigue were hypothesized to mediate the effect of our intervention on fatigue severity and disability. RESULTS In the final model, which had a good fit to the data, the effect of treatment was mediated by a decrease in perceived problems with activity and an increase in sense of control over fatigue. CONCLUSION Our findings suggest that cognitive behavioral interventions for CFS need to change the illness perception and beliefs of their patients in order to be effective.

Incidence of irregular astigmatism eligible for contact lens fitting after Descemet membrane endothelial keratoplasty

Purpose To evaluate the incidence and causes of anterior corneal surface irregularities after successful Descemet membrane endothelial keratoplasty (DMEK) and the efficacy of contact lens fitting in these cases. Setting Tertiary referral center. Design Retrospective study of prospectively collected data. Methods Eyes with a subnormal visual outcome or monocular diplopia after successful DMEK were fitted with a contact lens. These cases were evaluated with Pentacam rotating Scheimpflug camera imaging preoperatively and 6 months postoperatively, and outcomes were compared with those in a randomly selected DMEK control group. Results In a series of 262 surgeries, 23 eyes (21 patients) were fitted with contact lenses; the control group comprised 23 eyes. Indications for contact lens fitting included (1) obvious corneal surface irregularities due to preexisting corneal scarring, (2) surface irregularities associated with longstanding preoperative stromal edema, and (3) undetectable optical imperfections. The postoperative corrected distance visual acuity (CDVA) with spectacles improved after contact lens correction (P<.001). Preoperative and postoperative irregularity indices were significantly higher in the contact lens group than in the DMEK control group (P<.05). Positive correlations were found between the duration of preoperative stromal edema and postoperative Scheimpflug camera indices (P<.02). Conclusions After successful DMEK, 23 of 262 eyes (9%) showed subnormal spectacle CDVA and/or monocular diplopia due to corneal scarring, surface irregularities, or undetectable optical imperfections that could be managed by contact lens fitting. Prolonged preoperative corneal edema for more than 12 months may be a risk factor for diffuse irregular astigmatism after DMEK. Financial Disclosure Dr. Melles is a consultant to DORC International BV/Dutch Ophthalmic USA. No author has a financial or proprietary interest in any material or method mentioned.

Association Between Graft Storage Time and Donor Age With Endothelial Cell Density and Graft Adherence After Descemet Membrane Endothelial Keratoplasty

IMPORTANCE After retrospectively evaluating the clinical outcome of 500 consecutive cases after Descemet membrane endothelial keratoplasty (DMEK), we extended the analysis in this study by assessing the effect of donor-related parameters on endothelial cell density (ECD) decline and detachment rate in this group. OBSERVATIONS This retrospective case series included 500 cases who had undergone DMEK from October 2007 to September 2012 at the Netherlands Institute for Innovative Ocular Surgery (NIIOS), Rotterdam, the Netherlands. Logistic regression analysis (n = 332 eyes) showed that donor age might be associated with a 3% increase in the risk for a detachment (odds ratio, 0.97; 95% CI, 0.94-1.00; P = .049) (ie, higher donor age seems to be associated with lower chances of a detachment). In addition, linear regression analysis indicated that graft storage time in medium was associated with ECD decrease (ie, the longer the storage time, the larger the decrease at 6 months after DMEK) (P = .01). CONCLUSIONS AND RELEVANCE We showed an association between graft storage time and ECD decline after DMEK and possibly between donor age and graft detachment. Therefore, donor storage times should be kept as short as possible to improve short-term ECDs. More research is needed to draw definite conclusions on the possible effect of donor age on the chance of a detachment after DMEK.

Two-year Clinical Outcome of 500 Consecutive Cases Undergoing Descemet Membrane Endothelial Keratoplasty

Purpose: To evaluate the clinical outcome of 500 consecutive cases up to 2 years after Descemet membrane endothelial keratoplasty (DMEK) and to assess which parameters may have influenced the clinical outcome. Methods: From a group of 500 eyes (393 patients), which underwent DMEK for Fuchs endothelial corneal dystrophy (FECD), bullous keratopathy, failed corneal transplants and other indications, clinical outcomes [best-corrected visual acuity (BCVA), central endothelial cell density (ECD), and central corneal thickness] were evaluated before, and at 6, 12, and 24 months after DMEK and postoperative complications were documented. Results: At 12 months postoperatively, 81% of eyes reached a BCVA of ≥20/25 (≥0.8), 49% ≥20/20 (≥1.0), and 15% ≥20/18 (≥1.2) (n = 396) and remained stable up to 24 months (P = 0.828). Compared with preoperative ECD, mean postoperative ECD decreased by 37 (±18)%, 40 (±18)%, and 45 (±18)% at 6, 12, and 24 months, respectively (P < 0.05 for all time points). Surgery indication and graft attachment status were related to postoperative BCVA and ECD results. Eyes with FECD and attached grafts showed better BCVA outcomes and higher ECD (P < 0.05). Central corneal thickness decreased by 20 (±11)% to 525 (±46) &mgr;m from preoperative to 6 months postoperatively and remained stable thereafter (P > 0.05). Within the study period, retransplantation was required in 32 eyes (6.4%). Principal longer-term complications were secondary graft failure (1.4%) and allograft rejection (1.4%). Conclusions: Clinical outcomes remain excellent up to 2 years after DMEK, in particular for eyes operated on for FECD and with completely attached grafts.

Two-Year Refractive Outcomes After Descemet Membrane Endothelial Keratoplasty.

Purpose: To monitor refractive changes after Descemet membrane endothelial keratoplasty (DMEK) and to determine what may influence these changes and the time point of stabilization. Methods: From 67 pseudophakic DMEK eyes operated on for Fuchs endothelial dystrophy at a tertiary referral center, biomicroscopy, visual acuity, subjective refraction, and Scheimpflug-based corneal tomography data were obtained before and up to 2 years postoperatively. Visual acuity and changes in spherical equivalent (SE), mean anterior and posterior simulated keratometry (Km), and central pachymetry were analyzed. Results: At 3 months postoperatively, both hyperopic (28/67 eyes) and myopic (21/67 eyes) shifts were observed; 18/67 eyes showed no SE change. The mean change in SE at 3 months was +0.33 diopters (D) (95% confidence interval = [0.11, 0.54], P = 0.028), which stabilized thereafter (P > 0.466). Initial flattening of mean anterior Km by 0.66D (95% confidence interval = [−0.81, −0.51], P < 0.001) at 3 months was followed by a slow steepening, which became significant between 1 and 2 years postoperatively (P < 0.001). Posterior Km stabilized after 3 months (P > 0.252). Preoperative to 3 months postoperative absolute changes in anterior Km were positively related to preoperative backscattered light from the central anterior cornea (P = 0.035), and the presence of partial graft detachment postoperatively (P = 0.013). Conclusions: After DMEK, SE and posterior corneal curvature were on average stable at 3 months after surgery, whereas the mean anterior corneal curvature showed an ongoing gradual change. Changes in anterior corneal curvature may be related to preoperative anterior corneal densitometry or postoperative partial graft detachment.

Feature selection in feature network models: finding predictive subsets of features with the Positive Lasso.

A set of features is the basis for the network representation of proximity data achieved by feature network models (FNMs). Features are binary variables that characterize the objects in an experiment, with some measure of proximity as response variable. Sometimes features are provided by theory and play an important role in the construction of the experimental conditions. In some research settings, the features are not known a priori. This paper shows how to generate features in this situation and how to select an adequate subset of features that takes into account a good compromise between model fit and model complexity, using a new version of least angle regression that restricts coefficients to be non-negative, called the Positive Lasso. It will be shown that features can be generated efficiently with Gray codes that are naturally linked to the FNMs. The model selection strategy makes use of the fact that FNM can be considered as univariate multiple regression model. A simulation study shows that the proposed strategy leads to satisfactory results if the number of objects is less than or equal to 22. If the number of objects is larger than 22, the number of features selected by our method exceeds the true number of features in some conditions.

Multicenter Study of 6-Month Clinical Outcomes After Descemet Membrane Endothelial Keratoplasty

Purpose: To report the 6-month clinical outcomes of a large cohort of Descemet membrane endothelial keratoplasty (DMEK) eyes operated by 55 starting or experienced surgeons. Methods: This is a retrospective, multicenter, interventional, cohort study with a total of 2485 eyes. Best-corrected visual acuity (BCVA), endothelial cell density (ECD) decrease, and intra- and post-operative complications were evaluated. Three groups based on case order were compared: group I (cases 1–24), group II (cases 25–99), and group III (cases ≥100). Forty-nine percent of the surgeons were in their learning curve (<25 cases), representing 10.4% of the surgeries. Results: Six months after DMEK, BCVA improved in 90.5% of eyes, remained unchanged in 4.6%, and deteriorated in 4.9% (n = 1936); 75.4% of eyes reached a BCVA of ≥20/40 (≥0.5), 45.4% ≥20/25 (≥0.8), and 25.8% ≥20/20 (≥1.0) (n = 1959) and ECD decreased by 40% (±19) (n = 1272, P < 0.05). BCVA and ECD outcomes did not differ between groups I and III (P > 0.05). Intraoperative complications were reported for 9.4% of eyes, whereas graft detachment was the main postoperative complication (27.4%), with lower intra- and post-operative complication rates in group III than group I (P < 0.05). Rebubbling was performed in 20.1% of eyes; 13.8% required secondary keratoplasty within 6 months. Conclusions: DMEK is applicable for surgeons in various settings with good clinical outcomes. After an arbitrary learning curve (<25 cases), virtually all transplant-related complications declined with experience. Notably, surgeons with a higher annual caseload may pass faster through their learning curve than surgeons performing their first surgeries over an extended period.