Impact of DMEK on visual quality in patients with Fuchs' endothelial dystrophy.

PURPOSE: To investigate short-term (3 months follow-up) changes in visual quality following Descemet membrane endothelial keratoplasty (DMEK) for Fuchs endothelial dystrophy (FED). METHODS: In this prospective institutional case series, 51 patients that underwent DMEK for FED were included. Assessment included the Quality of Vision (QoV) questionnaire preoperatively, at 1 month, and 3 months after surgery. Secondary outcome measures were anterior segment parameters acquired by Scheimpflug imaging, corrected distance visual acuity (CDVA), and endothelial cell density (ECD). RESULTS: Glare, hazy vision, blurred vision, and daily fluctuation in vision were the symptoms mostly reported preoperatively. All symptoms demonstrated a significant reduction of item scores for severity, frequency, and bothersome in the course after DMEK (P < 0.01). Glare and fluctuation in vision remained to some extent during the follow-up period (median score = 1). Preoperatively, corneal densitometry correlated moderately to weakly with severity of hazy vision (rs = 0.39; P = 0.03) and frequency (rs = 0.26; P = 0.02) as well as severity (rs = 0.27; P = 0.03) of blurry vision. CDVA and central corneal thickness (CCT) did not correlate with visual complains. CONCLUSIONS: Following DMEK for FED, patient-reported visual symptoms assessed by the QoV questionnaire represent a useful tool providing valuable information on the impact of DMEK on visual quality that cannot be directly estimated by morphological parameters and visual acuity only.

Refractive outcome and tomographic changes after Descemet membrane endothelial keratoplasty in pseudophakic eyes with Fuchs' endothelial dystrophy.

PURPOSE: To analyze refractive and topographic changes secondary to Descemet membrane endothelial keratoplasty (DMEK) in pseudophakic eyes with Fuchs' endothelial dystrophy (FED). METHODS: Eighty-seven pseudophakic eyes of 74 patients who underwent subsequent DMEK surgery for corneal endothelial decompensation and associated visual impairment were included. Median post-operative follow-up time was 12 months (range: 3-26 months). Main outcome measures were pre- and post-operative manifest refraction, anterior and posterior corneal astigmatism, simulated keratometry (CASimK) and Q value obtained by Scheimpflug imaging. Secondary outcome measures included corrected distance visual acuity (CDVA), central corneal densitometry, central corneal thickness, corneal volume (CV), anterior chamber volume (ACV) and anterior chamber depth (ACD). RESULTS: After DMEK surgery, mean pre-operative spherical equivalent (± SD) changed from + 0.04 ± 1.73 D to + 0.37 ± 1.30 D post-operatively (p = 0.06). CDVA, proportion of emmetropic eyes, ACV and ACD increased significantly during follow-up. There was also a significant decrease in posterior corneal astigmatism, central corneal densitometry, central corneal thickness and corneal volume over time (p = 0.001). Only anterior corneal astigmatism and simulated keratometry (CASimK) remained fairly stable after DMEK. CONCLUSION: Despite tendencies toward a hyperopic shift, changes in SE were not significant and refraction remained overall stable in pseudophakic patients undergoing DMEK for FED. Analysis of corneal parameters by Scheimpflug imaging mainly revealed changes in posterior corneal astigmatism pointing out the relevance of posterior corneal profile changes during edema resolution after DMEK.

Influence of rebubbling on anterior segment parameters and refractive outcomes in eyes with DMEK for Fuchs endothelial dystrophy.

PURPOSE: To evaluate the potential impact of rebubbling on the anterior segment parameters and refractive outcomes in patients with graft detachment following uneventful DMEK for Fuchs endothelial dystrophy (FED). METHODS: Retrospective institutional cohort study of comparing 34 eyes of 31 patients with rebubbling for graft detachment following Descemet membrane endothelial keratoplasty (DMEK) to 33 eyes of 28 patients with uneventful DMEK. Main outcome parameters were various corneal parameters obtained by Scheimpflug imaging, refractive outcome, corrected distance visual acuity (CDVA), and endothelial cell density (ECD). RESULTS: Anterior and posterior corneal astigmatism, corneal densitometry, central corneal thickness, and anterior chamber depth and volume showed no significant differences. Preoperative distribution of astigmatism axis orientations showed a high proportion of anterior corneal with-the-rule astigmatism (71%) in eyes requiring rebubbling. Mean postoperative cylinder in the rebubbling group (1.21 ± 0.85 D) was significantly higher compared to the controls (p = 0.04), while differences in spherical equivalent (SE) were insignificant (p = 0.24). Postoperative CDVA was 0.11 ± 0.11 in the control group compared to 0.21 ± 0.17 in the rebubbling group (p = 0.03). Eyes with subsequent rebubbling demonstrated a significantly higher endothelial cell loss (56% versus 37%) (p < 0.001). CONCLUSION: Apart from higher cylinder values, refractive outcome and corneal parameters assessed by Scheimpflug imaging were comparable in eyes with rebubbling and controls. However, a reduced visual acuity and an increased endothelial cell loss should be taken into consideration prior to rebubbling especially in eyes with circumscribed graft detachment.

Characteristics of preoperative and postoperative astigmatism in patients having Descemet membrane endothelial keratoplasty.

PURPOSE: To evaluate the characteristics of preoperative and postoperative astigmatism in patients having Descemet membrane endothelial keratoplasty (DMEK). SETTING: Department of Ophthalmology, Goethe University, Frankfurt, Germany. DESIGN: Retrospective case series. METHODS: Measurements were obtained using a Scheimpflug camera (Pentacam AXL) preoperatively and 3 months and 12 months postoperatively. Values of front and back astigmatism and total astigmatism in the central 4.0 mm diameter zone (TCA4) were analyzed. RESULTS: Fifty-three eyes of 45 patients were included. The prevalence of TCA4 above 1.0 diopter (D) was considerably higher (79%) and with-the-rule astigmatism was less frequent in this cohort of European patients with Fuchs endothelial dystrophy (mean age 65 years) than that reported in a meta-analysis of healthy European eyes. The TCA4 values correlated with anterior astigmatism preoperatively and postoperatively (P < .001) and with posterior astigmatism at the 1-year follow-up (P < .01). Although, no correlation was found between the preoperative and 1-year results for anterior astigmatism (P = .12), posterior astigmatism (P = .35), or total corneal astigmatism (P = .47), the difference in vector analysis between the two measurements was only 0.01 at 109 degrees, 0.03 at 98 degrees, and 0.02 at 157 degrees, respectively. However, the greater the difference between the preoperative TCA3 and preoperative TCA5 values, the greater the decrease in corneal astigmatism (P < .001). CONCLUSIONS: The percentage of eyes with corneal astigmatism above 1.0 D was higher preoperatively and postoperatively in patients with Fuchs endothelial dystrophy than in a healthy population. Predicting postoperative astigmatism based on preoperative results is not possible; however, in eyes with a high difference between TCA3 and TCA5, a reduction in corneal astigmatism after DMEK is likely.

Corneal Densitometry After Secondary Descemet Membrane Endothelial Keratoplasty.

PURPOSE: To evaluate Scheimpflug corneal densitometry (CD) in patients undergoing secondary Descemet membrane endothelial keratoplasty (DMEK) after previous Descemet stripping automated endothelial keratoplasty or DMEK surgery. METHODS: This was a retrospective institutional case series of 37 eyes of 37 patients. Two secondary DMEK groups, group 1A (n = 12 DMEK after Descemet stripping automated endothelial keratoplasty), group 1B (n = 11 repeat DMEK), and group 2 (n = 14 primary DMEK for Fuchs endothelial dystrophy) were formed. CD was obtained preoperatively, 1, 6, and 12 months postoperatively. In addition, corrected distance visual acuity, central corneal thickness, and endothelial cell density were assessed. RESULTS: A significant decrease in grayscale units was observed in the 0- to 2-mm and 2- to 6-mm zones in all groups. For the 0- to 2-mm zone, values decreased from 49.11 ± 17.96 preoperatively to 22.87 ± 5.24 at 12 months (group 1A), from 45.16 ± 9.22 to 24.53 ± 14.21 (group 1B), and from 27.90 ± 8.30 to 16.64 ± 1.51 (group 2) (P < 0.01). Group 2 showed significantly lower grayscale units than groups 1A and 1B preoperatively and 12 months postoperatively in the 0- to 2-mm and 2- to 6-mm zones. Significant correlations of CD and corrected distance visual acuity were found in groups 1A and 1B in the 0- to 2-mm zone at 12 months. There were no significant correlations between CD and central corneal thickness postoperatively. CONCLUSIONS: A decrease in CD could be demonstrated in secondary DMEK. Nevertheless, CD values remained significantly higher than in controls. This might point out the relevance of secondary corneal structural changes.

Outcome of Descemet membrane endothelial keratoplasty for graft failure after Descemet stripping automated endothelial keratoplasty.

PURPOSE: To investigate the efficacy and safety of Descemet membrane endothelial keratoplasty (DMEK) for corneal decompensation following primary Descemet stripping automated endothelial keratoplasty (DSAEK). METHODS: This was a retrospective case series of 15 patients that underwent DMEK surgery for corneal decompensation after failed DSAEK. Main outcome parameter was corrected distance visual acuity (CDVA) after DMEK and DSAEK. Secondary outcome measures included central corneal thickness (CCT), endothelial cell density (ECD), rebubbling rate, and primary graft failure after DMEK. Explanted DSAEK grafts were evaluated by light microscopy. RESULTS: The mean (±SD) time period between DSAEK and DMEK surgery was 15±8 months (range, 6-31 months). Preoperative CDVA was 1.72±0.62 (logMAR). After DMEK, CDVA improved significantly to 0.78±0.48 at 1 month and to 0.23±0.24 after 12 months (P=0.022). Visual acuity data after DMEK were significantly better compared to preoperative values. The average CCT after DMEK decreased significantly from 869±210 µm (preoperative) to 505±45 µm (1 month postoperative) (P<0.001) and remained stable over 12 months. The ECD decreased from 2,589±209/mm2 (preoperative) to 1,691±589/mm2 (12 months postoperative). Rebubbling DMEK was required in three patients (=20%). CONCLUSION: DMEK represents a feasible and safe procedure in achieving better functional results compared to DSAEK. Visual acuity and optical quality can be effectively reestablished after unsuccessful primary DSAEK surgery even in patients with long-standing corneal decompensation. Further investigations are required to validate the preliminary clinical findings.

Functional outcome of repeat Descemet membrane endothelial keratoplasty (DMEK) for corneal decompensation following graft failure after primary DMEK.

PURPOSE: To evaluate if repeat Descemet membrane endothelial keratoplasty (DMEK) is appropriate to achieve functional improvements in patients with corneal decompensation from secondary graft failure after primary DMEK. METHODS: This is a retrospective monocentric cohort study including 13 eyes of 13 patients with repeat DMEK for corneal decompensation following primary DMEK. Eyes with primary DMEK only and comparable preoperative corrected distance visual acuity (CDVA) served as control. Main outcome parameter was CDVA. Secondary outcome measures were central corneal thickness (CCT), endothelial cell density, and rebubbling rate (RR). RESULTS: The average time interval (±SD) between primary and secondary DMEK was 12.5±6 months. Preoperative CDVA (logMAR) was 1.97±0.90 in the repeat DMEK group and 1.38±0.92 in the primary DMEK group. At 6 months, both groups showed significant improvement in visual acuity (repeat DMEK group, 0.49±0.35, P<0.01 and primary DMEK group, 0.40±0.36, P<0.01). CDVA did not differ significantly between both groups at all time points examined (1, 3, and 6 months postoperatively). Mean CCT values at 3 and 6 months postoperatively did not differ significantly between the two groups (P>0.05). The RR was 23% (n=3) in both groups. CONCLUSION: Repeat DMEK is a useful therapeutic approach in the setting of corneal decompensation following primary DMEK. Functional results of repeat DMEK, visual acuity in particular, are comparable to patients with single DMEK only.

Comparison of standard and accelerated corneal cross-linking for the treatment of keratoconus: a meta-analysis.

PURPOSE: To compare results between standard and accelerated corneal collagen cross-linking (CXL) for the treatment of progressive keratoconus. METHODS: We performed literature searches in PubMed, Cochrane Library, Web of Science, ISRCTN registry, ClinicalTrials.gov, and EMBASE for studies comparing conventional Dresden (C-CXL) and accelerated CXL (A-CXL). Outcomes were clinical results and changes in corneal properties. Weighted mean differences were used to evaluate the effects. RESULTS: Here, 22 studies with 1158 eyes (C-CXL: 577 eyes; A-CXL: 581 eyes) were included. At the last follow-up, C-CXL was superior regarding minimum keratometry (p < 0.00001) and demarcation line depth (p < 0.00001), whereas A-CXL should be favoured when considering minimum corneal thickness (p = 0.0005). No differences in uncorrected and corrected distance visual acuity (p = 0.09 and 0.98), spherical equivalent (p = 0.11), spherical and cylindrical error (p = 0.29 and 0.32), maximal and average keratometry (p = 0.05 and 0.65), central corneal thickness (p = 0.15), corneal biomechanical properties (p ≥ 0.21 respectively), time of reepithelialization (p = 0.76), subbasal nerve density (p = 0.69), endothelial cell density (p = 0.30) and morphology (p ≥ 0.40 respectively) were found among both groups. CONCLUSION: Consideration of less corneal thinning favours A-CXL, whereas the deeper demarcation line and greater changes in minimum keratometric values in C-CXL may indicate a higher treatment efficacy. Altogether, C-CXL, as well as A-CXL, provides successful results in the strengthening of corneal tissue.

Identification of flubendazole as potential anti-neuroblastoma compound in a large cell line screen.

Flubendazole was shown to exert anti-leukaemia and anti-myeloma activity through inhibition of microtubule function. Here, flubendazole was tested for its effects on the viability of in total 461 cancer cell lines. Neuroblastoma was identified as highly flubendazole-sensitive cancer entity in a screen of 321 cell lines from 26 cancer entities. Flubendazole also reduced the viability of five primary neuroblastoma samples in nanomolar concentrations thought to be achievable in humans and inhibited vessel formation and neuroblastoma tumour growth in the chick chorioallantoic membrane assay. Resistance acquisition is a major problem in high-risk neuroblastoma. 119 cell lines from a panel of 140 neuroblastoma cell lines with acquired resistance to various anti-cancer drugs were sensitive to flubendazole in nanomolar concentrations. Tubulin-binding agent-resistant cell lines displayed the highest flubendazole IC50 and IC90 values but differences between drug classes did not reach statistical significance. Flubendazole induced p53-mediated apoptosis. The siRNA-mediated depletion of the p53 targets p21, BAX, or PUMA reduced the neuroblastoma cell sensitivity to flubendazole with PUMA depletion resulting in the most pronounced effects. The MDM2 inhibitor and p53 activator nutlin-3 increased flubendazole efficacy while RNAi-mediated p53-depletion reduced its activity. In conclusion, flubendazole represents a potential treatment option for neuroblastoma including therapy-refractory cells.