Comparison of rebubbling rate between preloaded endothelium-in and preloaded no-touch endothelium-out Descemet membrane endothelial keratoplasty transplantation.

BACKGROUND: To compare the difference in rebubbling rates between patients undergoing Descemet membrane endothelial keratoplasty (DMEK) with endothelium-in using a standard IOL cartridge and those with endothelium-out DMEK utilizing a no-touch technique with borosilicate glass cartridge transplantation. METHODS: This retrospective study included all eyes that underwent preloaded endothelium-in or endothelium-out DMEK transplantation from June 2019 to December 2023 at the Hanusch Hospital, Vienna, Austria. All DMEKs were harvested, prepared and preloaded at the European Eye Bank of Venice, Italy. DMEK surgeries were done by one experienced surgeon and the procedure was completed by air tamponade of the anterior chamber. RESULTS: Overall, 32 eyes each of 31 endothelium-out patients and of 29 endothelium-in patients were included. 32 preloaded endothelium-in procedures were followed by 32 preloaded endothelium-out procedures. Rebubbling rate for endothelium-in was 15/32 (47%) and for endothelium-out was 7/25 (28%) (p = 0.035, Pearson's chi-squared test). Donor age was the most important variable for rebubbling in a random forest algorithm model (ROC: 0.69). CONCLUSIONS: Rebubbling rate in endothelium-out DMEK was less than two-thirds compared to endothelium-in DMEK favoring no-touch endothelium-out DMEK as the preferred technique of DMEK transplantation.

Clinical outcome analysis of two approaches to trypan blue dyeing for DMEK.

To evaluate the clinical implications of the different trypan blue dyeing techniques used during liquid bubble (LBT) and manual peel (MPT) DMEK lenticule preparation techniques. This study retrospectively compared the degree to which endothelial cells are preserved using selective Descemet Membrane (DM) staining (LBT) versus bath-staining (MPT) when performed by a single surgeon, sourced from a single eye bank. Endothelial cell density measured after the 3-month follow-up was 1805 and 1916 cells/mm2 respectively, differing significantly (p = 0.012). A double-scroll graft formation was found and maintained until implantation in 94% of preparations with bath staining and 50% of preparations using selective DM staining. Preoperative visual acuity was comparable between preparation techniques at 0.4 logMAR as well as postoperatively, at an average of 0.1 logMAR. Reducing chemical stress on the endothelium by avoiding any contact with trypan blue allows for a significantly higher degree of cell preservation. However, achieving the often-desired double-scroll graft formation was possible less frequently. It remains unclear which factors define the differences graft scrolling behavior observed between LBT and MPT.

Enhanced Migration of Fuchs Corneal Endothelial Cells by Rho Kinase Inhibition: A Novel Ex Vivo Descemet's Stripping Only Model.

Descemet's Stripping Only (DSO) is a surgical technique that utilizes the peripheral corneal endothelial cell (CEnC) migration for wound closure. Ripasudil, a Rho-associated protein kinase (ROCK) inhibitor, has shown potential in DSO treatment; however, its mechanism in promoting CEnC migration remains unclear. We observed that ripasudil-treated immortalized normal and Fuchs endothelial corneal dystrophy (FECD) cells exhibited significantly enhanced migration and wound healing, particularly effective in FECD cells. Ripasudil upregulated mRNA expression of Snail Family Transcriptional Repressor (SNAI1/2) and Vimentin (VIM) while decreasing Cadherin (CDH1), indicating endothelial-to-mesenchymal transition (EMT) activation. Ripasudil activated Rac1, driving the actin-related protein complex (ARPC2) to the leading edge, facilitating enhanced migration. Ex vivo studies on cadaveric and FECD Descemet's membrane (DM) showed increased migration and proliferation of CEnCs after ripasudil treatment. An ex vivo DSO model demonstrated enhanced migration from the DM to the stroma with ripasudil. Coating small incision lenticule extraction (SMILE) tissues with an FNC coating mix and treating the cells in conjunction with ripasudil further improved migration and resulted in a monolayer formation, as detected by the ZO-1 junctional marker, thereby leading to the reduction in EMT. In conclusion, ripasudil effectively enhanced cellular migration, particularly in a novel ex vivo DSO model, when the stromal microenvironment was modulated. This suggests ripasudil as a promising adjuvant for DSO treatment, highlighting its potential clinical significance.

Simultaneous Deep Anterior Lamellar Keratoplasty and Descemet Membrane Endothelial Keratoplasty for Corneal Endothelial Failure With Stromal Scarring.

ABSTRACT: We present an alternative surgical procedure including simultaneous deep anterior lamellar keratoplasty (DALK) and Descemet membrane endothelial keratoplasty (DMEK) in a case with endothelial failure and stromal scarring. A 62-year-old woman presented with vision loss caused by pseudophakic bullous keratopathy. While waiting for a corneal transplant, the patient developed infectious keratitis, which was treated with medication. Although the keratitis healed, it left a scar. To improve the patient's vision, a corneal transplant surgery that included simultaneous DALK and DMEK was performed. Postoperatively, the corneal graft was clear, and the Descemet membrane was well attached. However, there was an interface haze because of residual stromal tissue. The patient's best-corrected visual acuity improved from hand motion to 0.2 (decimal). This combined procedure allows for lamellar keratoplasty in cases with coexistence of corneal endothelial and stromal involvement.

Emerging alternatives to keratoplasty for corneal endothelial cell dysfunction.

PURPOSE OF REVIEW: While effective for treating endothelial dysfunction, keratoplasty has shortcomings including limited access to donor tissue for much of the world. Thus, alternative strategies are under development. This review explores the main advancements achieved in this field during 2022-2023. RECENT FINDINGS: Recent publications further support the validity of intracameral cultivated allogeneic endothelial cell injection and Descemet stripping only, while emphasizing the benefits of adjunctive Rho-associated kinase inhibitor (ROCKi) therapy. New donor-independent artificial implants, such as EndoArt, show favorable results. Multiple pharmacologic agents, especially ROCKi, show promise as monotherapies, yet none are currently approved for human treatment. Multiple regenerative and genetic therapies are being investigated but all are still in preclinical stages. SUMMARY: A plethora of innovative alternatives to keratoplasty for endothelial disease is in development. Among these, surgical methods are still the mainstay of treatment and closest to clinical application, though further studies to establish their benefits over keratoplasty are needed. Albeit promising, pharmacologic, regenerative, and genetic approaches require validation and are farther from clinical application.

Outcomes after reversed corneal graft rejection: a report from the European VISICORT project.

OBJECTIVE: This study aims to describe the outcome of corneal grafts, both low risk and high risk, after successfully reversed immunological rejection. METHODS: Datasets on reversed rejection episodes in penetrating and endothelial keratoplasties between 2014 and 2019 (n=876) were extracted from the Adverse Immune Signatures and their Prevention in Corneal Transplantation database, which contains the prospectively and consecutively collected corneal transplants from five European centres. Stratified by the preoperatively determined risk status for immunological rejection, the outcome parameters analysed included visual acuity, intraocular pressure, endothelial cell density and central corneal thickness before and after reversed rejection episodes. RESULTS: Fourty-seven (52%) out of a total of 91 identified rejection episodes were successfully reversed and were available for analysis (23 penetrating and 24 endothelial keratoplasties). No statistically significant change was found for any of the parameters studied between the values before and the values 3 months after the rejection episode, irrespective of the preoperative risk status. CONCLUSION: The outcome of corneal grafts that survive immunological rejection may be clinically indistinguishable from the state before immunological rejection, irrespective of graft type and risk status. These findings support clinicians by providing information on prognosis after reversed rejection episodes and by giving patients realistic expectations regarding the outcome.

[Modern techniques and features of selective keratoplasty]. / Sovremennye tekhnologii i vozmozhnosti selektivnoi keratoplastiki.

Selective keratoplasty involves replacing the affected layers of the cornea with similar donor tissue. In case of pathological changes in the middle and posterior stroma, deep anterior lamellar keratoplasty (DALK) is performed. Chronic corneal edema caused by endothelial dysfunction is an indication for endothelial keratoplasty - Descemet membrane endothelial keratoplasty (DMEK) or Descemet Stripping Endothelial Keratoplasty (DSAEK). Compared to penetrating keratoplasty (PK), these operations are characterized by a low risk of damage to intraocular structures and a relatively short rehabilitation period. Complications of selective keratoplasty include the formation of a false chamber between the lamellar graft and the recipient's cornea, ocular hypertension during anterior chamber air tamponade. Persistent epithelial defect can be a sign of primary graft failure in DALK, DSAEK and DMEK. Selective keratoplasty is characterized by a lower incidence of immune rejection than PK. In some cases, DALK can be complicated by corneal changes related to suture fixation of the graft. Long-term postoperative use of topical glucocorticoids can cause ocular hypertension and cataracts.

3D Mapping of the DMEK Detachment Area from OCT Scans of the Anterior Segment of the Eye - Clinical Applications. / 3D-Kartierung der DMEK-Abhebungsfläche aus OCT-Scans des vorderen Augensegmentes mit klinischen Anwendungen.

Graft detachment is the most common complication after Descemet membrane endothelial keratoplasty (DMEK). To assess the amount of graft detachment, precision is limited when using slit-lamp biomicroscopy. Detachment of DMEK grafts can be assessed automatically on anterior segment optical coherence tomography (AS OCT) images and allows visualization of the area and volume of detachment using 3D maps. This article provides an overview of its applications such as accurately assessing the course of natural graft attachment, identification of potential risk factors for detachment and evaluation of the long-term effect of graft detachment. The 3D map of DMEK detachment may support researchers and clinicians in precise quantification of the area and volume of graft detachment even in large data sets, and the intuitive, fast and reliable evaluation.

Double-Bubble Technique Assisted by Holding Forceps: A Modified Technique in Descemet Membrane Endothelial Keratoplasty for Vitrectomized Eyes With Scleral Fixated Intraocular Lens.

PURPOSE: Several techniques have been developed for graft unfolding approaches in Descemet membrane endothelial keratoplasty (DMEK). However, despite these techniques, graft deployment and configuration in eyes with deep anterior chambers remain challenging in some cases. Therefore, in this study, we described a modified technique for DMEK, known as the "double-bubble technique assisted by holding forceps." METHODS: This was a retrospective interventional case series. Patients who underwent DMEK between August 2022 and July 2023, including cases with a history of vitrectomy and scleral fixation of intraocular lens, were enrolled in this study. Two experienced surgeons performed DMEK. In brief, after graft insertion into the anterior chamber, the first bubble with a small volume of air was injected above the graft to open the tight roll, and the graft edge was held using a 25-gauge graft manipulator. The second bubble was injected underneath the graft for fixation, while the graft edge was grasped using forceps during gas injection. The graft was released from the forceps. Best spectacle corrected visual acuity, central corneal thickness, endothelial cell density, and incidence of postoperative complications were measured before and after DMEK. RESULTS: Eleven eyes of 11 patients were included in this study (mean follow-up period, 4.5 ± 4.4 months). Best spectacle corrected visual acuity and central corneal thickness significantly improved postoperatively ( P < 0.001). Rebubbling was required in 2 eyes; no other postoperative complications or primary graft failure were observed. CONCLUSIONS: The present technique enables safe and feasible DMEK surgery in vitrectomized eyes with scleral fixated IOLs and in those with a deep anterior chamber.

Epithelial ingrowth in descemet membrane endothelial keratoplasty associated with vitreous loss.

BACKGROUND: Epithelial ingrowth is a rare but potentially sight-threatening complication caused by the invasion of corneal or conjunctival epithelial cells into the eye during ocular surgeries. DMEK is emerging as a widely used surgery for endothelial keratoplasty with its improved safety profile. We describe a case of epithelial ingrowth in the graft-host interface after uneventful DMEK associated with vitreous prolapse in the anterior chamber. CASE PRESENTATION: An 81-year-old female with Fuchs endothelial dystrophy underwent DMEK for corneal decompensation following cataract surgery. During the DMEK procedure, vitreous prolapse was observed around the intraocular lens (IOL). Her early postoperative course was unremarkable, but a dense paracentral interface opacity was observed during the 3-month follow-up. The area of epithelial ingrowth was imaged with optical coherence tomography (OCT) as a uniform nodule with a discrete increase in interface hyperreflectivity. A low-energy YAG laser was applied to remove the opacity. She maintained good vision and clear cornea without reoccurrence after treatment. CONCLUSIONS: We propose that, in addition to the introduction of epithelial cells during surgery, vitreous retention in the anterior chamber may be a risk factor by providing a scaffold that potentially aggravates epithelial ingrowth in DMEK. Our case demonstrated that early YAG intervention may disrupt interface epithelial cell growth, and the transmitted laser energy may fragment the scaffold vitreous noninvasively.

Analysis of Graft Detachments and Re-Bubblings After 450 Descemet Membrane Endothelial Keratoplasty Procedures.

PURPOSE: To objectify the indication for re-bubbling by analyzing graft detachments (GDs) after Descemet membrane endothelial keratoplasty. METHODS: In this retrospective monocentric observational study, re-bubbling cases of 450 Descemet membrane endothelial keratoplasties and the percentage of the residual gas filling (RGF) in the anterior chamber on the first postoperative day were collected. The number/location/extent of GDs and the corneal thickness above GDs were analyzed using anterior segment optical coherence tomography. RESULTS: From a total of 450 grafts, 384 (85.3%) had at least a minimal degree GD. One hundred twenty-two of 450 grafts (27.1%) underwent at least 1 re-bubbling. The mean RGF was significantly lower in eyes with GD (67.7 ± 12.6%) than in eyes without GD (74.2 ± 11.3%). GDs occurred most frequently in the inferotemporal quadrant (46.0%). GDs were significantly more likely to require a re-bubbling when the central parts of the graft were affected (94.0% vs. 35.7%). The number of detachments per graft was directly proportional to the re-bubbling rate. The GDs which required a re-bubbling were on average 56 µm higher and 461 µm wider than the untreated ones. The cornea above the GDs that needed a re-bubbling was significantly thicker than above the untreated GDs (mean 988 ± 102 µm vs. 951 ± 99 µm). CONCLUSIONS: The RGF seems to be a major influencing factor for graft attachment. The most susceptible location of the GD is inferotemporal. The main factors that need to be investigated to decide if a re-bubbling is required are the number of detachments per graft, their dimensions, whether the central portions of the graft are involved, and the corneal thickness above GDs.

One-year Outcomes of Ultrathin Descemet Stripping Automated Endothelial Keratoplasty Combined with Cataract Surgery in the Korean Population.

PURPOSE: To evaluate the refractive outcomes after ultrathin Descemet stripping automated endothelial keratoplasty (UT-DSAEK) combined with phacoemulsification and intraocular lens implantation (triple procedure) in the South Korean population. METHODS: This retrospective observational study included 37 eyes of 36 patients who underwent the UT-DSAEK triple procedure between 2012 and 2021 in a single tertiary hospital. Preoperative and postoperative refractive outcomes and endothelial parameters at 1, 3, 6, and 12 months were observed. RESULTS: At the final postoperative 12-month period, the average best-corrected visual acuity was 0.4 ± 0.5 in logarithm of the minimum angle of resolution. The mean endothelial cell density at 12 months was 1,841.92 ± 731.24 cells/mm2, indicating no significant endothelial cell loss compared to the baseline (p = 0.128). The mean postoperative central corneal thickness at 12 months was 597.41 ± 86.26 µm. The postoperative mean absolute error at 12 months was 0.96 ± 0.89 diopters (D) and mean error was 0.89 ± 0.97 D. CONCLUSIONS: The results of our South Korean cohort study on UT-DSAEK triple surgery showed favorable and safe outcomes. Regardless of graft thickness, it should be noted that a hyperopic shift of 1.00 to 2.00 D needs to be considered in the case of UT-DSAEK triple surgery.

Predictive factors for re-bubbling after DMEK: focus on the posterior corneal surface.

PURPOSE: To understand whether the preoperative morphology of the posterior corneal surface influences the rate of re-bubbling after Descemet membrane endothelial keratoplasty (DMEK). METHODS: After retrospectively analyzing the medical records of patients undergoing DMEK, in this multicentric cross-sectional study, we performed a binomial logistic regression analysis to assess significant predictors of re-bubbling and re-transplantation after surgery. Analyzed parameters included the preoperative diagnosis, anterior and posterior surface K1/K2, central corneal thickness, posterior Q value, and other posterior corneal surface parameters evaluated on the elevation maps produced by anterior segment optical coherence tomography. Results were stratified based on the surgeons' experience. RESULTS: We included 202 eyes of 202 patients with a mean age of 69.5 ± 12.4 years; 154 eyes were operated by a high-volume surgeon and 48 by one with less experience; 48 eyes (23.8%) underwent ≥ 1 re-bubbling and 14(6.9%) ≥ 1 re-transplantation. The presence of positive/less-negative posterior corneal irregularities and irregularities with greater absolute height had a significantly higher risk of re-bubbling in both the expert and less expert group (OR = 2.85 and 1.42, OR = 3.22 and 3.01, respectively, p < 0.05), whereas more negative posterior K1 and K2 were significant risk factors only in the former group (OR = 0.67 and 0.55, respectively, p < 0.05). Endothelial decompensation other than Fuchs and pseudophakic bullous keratopathy, more negative posterior Q values and smaller distances between center, and the highest/lowest posterior corneal surface irregularity correlated with an increased risk of graft failure (OR 1.23, 1.21, and 1.29, respectively, p < 0.05). CONCLUSION: Posterior corneal surface morphology significantly influences the risk of re-bubbling after DMEK.

Chamber shallowing technique for challenging DMEK cases: Tucking cellulose spears under the speculum to augment posterior pressure.

Some anterior chambers do not readily shallow because of insufficient posterior pressure and/or very deep anterior chamber anatomy, which can make unscrolling descemet membrane endothelial keratoplasty (DMEK) tissue more challenging with an unmodified tap technique. We present a hands-free method for augmenting posterior pressure by temporarily tucking cellulose sponges under the blades of the eyelid speculum. The sponges transfer some of the eyelid speculum's weight onto the bulbar surface posterior to the iris, thereby indenting the sclera and causing the iris diaphragm to bulge further forward. This hands-free technique can transform a potentially challenging DMEK case into a more straightforward one by facilitating both a shallow anterior chamber and a bimanual unscrolling technique. However, it only works in bicameral eyes with a vitreous body (e.g., an eye with penetrating keratoplasty, vitreous syneresis, and axial myopia) and will not work in unicameral eyes after vitrectomy (e.g., an eye with an Anterior Chamber Intraocular Lens (ACIOL)).

Hitting the refractive target in corneal endothelial transplantation triple procedures: A systematic review.

In phakic patients Descemet stripping automated endothelial keratoplasty (DSAEK) or Descemet membrane endothelial keratoplasty (DMEK) are frequently combined with phacoemulsification and intraocular lens (IOL) implantation (triple procedure). This surgery might cause a refractive shift difficult to predict. Early DMEK and DSAEK results have shown a tendency toward a hyperopic shift. Myopic postoperative refraction is typically intended to correct this postoperative refractive defect and to bring all eyes as close to emmetropia as possible. We sought to understand the mechanism underlying the hyperopization and to identify predictive factors for poorer refractive outcomes, the most suitable target refraction and IOL calculation methods in patients undergoing combined cataract extraction and lamellar endothelial corneal transplantation (DSAEK or DMEK) for endothelial dysfunctions. Of the 407 articles analyzed, only 18 were included in the analysis. A myopic target between -0.50 D and -0.75 was the most common (up to -1.50 for DSAEK triple procedures), even though no optimum target was found. Hyperopic surprises appeared more frequently in corneas that were flatter in the center than in the periphery (oblate posterior profile). Among the numerous IOL calculation formulas, there was no apparent preference.

Intraocular pressure-related side-effects after endothelial keratoplasty.

PURPOSE: To investigate circumpapillary retinal nerve fibre layer (RNFL) thickness, pupillary function and diameter after phacoemulsification and lens implantation alone or combined with endothelial keratoplasty (EK). METHODS: This study was a secondary analysis of data from a randomized, single-masked trial, that included 72 patients with Fuchs' endothelial dystrophy and cataract, equally allocated (1:1) to ultrathin Descemet's stripping automated endothelial keratoplasty or Descemet's membrane endothelial keratoplasty. The cataract extraction (CE) group included 40 patients undergoing cataract surgery only. All patients were treated with phacoemulsification and lens implantation. RESULTS: RNFL thickness was significantly lower in the CE group than after EK for the global (p < 0.01), nasal (p = 0.04), and temporal sectors (p = 0.01) 12 months after surgery. RNFL thickness was comparable between patients treated with rebubbling and others (p ≥ 0.16 for all comparisons) after 12 months. The CE group and patients treated with EK demonstrated a comparable scotopic (p = 0.34) and photopic pupil diameter (p = 0.95) as well as a comparable maximum (p = 0.83) and average pupillary constriction velocity (p = 0.95) after 12 months. In contrast, patients treated with rebubbling had a significantly smaller scotopic pupil diameter (p = 0.04). CONCLUSION: In this study, no evidence was found indicating a negative impact on the RNFL thickness after EK when compared to CE 12 months after surgery. Iris function and pupil diameter were comparable between the CE group and patients treated with EK after 12 months.

Corneal Endothelium Viability Assay Using Trypan Blue Dye After Preloaded Descemet Membrane Endothelial Keratoplasty Graft Preparation.

PURPOSE: The purpose of this study was to establish a validated method, consistent with Eye Bank Association of America medical standards, for evaluating endothelial cell loss (ECL) from an entire Descemet membrane endothelial keratoplasty (DMEK) graft using trypan blue dye as an alternative to specular microscopy. METHOD: Twenty-nine corneas were prepared for preloaded DMEK by a single technician, and the endothelium was stained with trypan blue dye for 30 seconds. The technician estimated total cell loss as a percentage of the graft and captured an image. Images were evaluated by a blinded technician using ImageJ software to determine ECL and compared with endothelial cell density from specular microscopy. Tissue processing intervals were analyzed for 4 months before and after implementation of this method. RESULTS: For the 29 grafts, there was no statistically significant difference ( t test, P = 0.285) between ECL estimated by a processor (mean = 5.8%) and ECL calculated using an ImageJ software (mean = 5.1%). The processor tended to estimate greater ECL than the actual ECL determined by ImageJ (paired t test, P = 0.022). Comparatively, postprocessing endothelial cell density measured by specular microscopy were higher compared with the preprocessing endothelial cell density (mean = 4.5% P = 0.0006). After implementation of this evaluation method, DMEK graft processing time intervals were reduced by 47.9% compared with specular microscopy evaluation ( P < 0.001). CONCLUSIONS: Our results show that visual ECL estimation using trypan blue staining by a DMEK graft processor is a reliable and efficient method for endothelial assessment. Unlike specular microscopy, this method achieves comprehensive visualization of the entire endothelium, reduces total time out of cold storage, and decreases total time required to prepare and evaluate DMEK grafts.

[Chinese expert consensus on corneal endothelial transplantation (2024)].

Endothelial keratoplasty (EK) is an effective therapy for corneal endothelial diseases and mainly includes Descemet stripping endothelial keratoplasty and Descemet membrane endothelial keratoplasty. Compared with penetrating keratoplasty, EK has better vision rehabilitation and a lower rate of allograft rejection after surgery. However, EK poses a series of technical challenges, and varied complications may occur intraoperatively and postoperatively. A successful EK surgery depends on the standardized technical manipulations and the management of surgical complications. In order to standardize the surgical procedure of EK in China, the Cornea Group of Ophthalmology Branch of Chinese Medical Association has made a comprehensive discussion about indications of surgery, preoperative evaluation, surgical manipulations, and the management of complications based on the literature available thus far and clinical practice in China, and eventually established this consensus, which may guide corneal surgeons in performing the EK surgery.

Optimized Kalinnikov-Dinh technology for effective pre-Descemet's endothelial keratoplasty (PDEK) graft preparation and preservation.

We report an optimized Kalinnikov-Dinh technology for pre-Descemet's endothelial keratoplasty (PDEK) that involves the use of a ring fixator, base, 30G needle connected to a 5-ml syringe with a spring-loaded plunger, and storage media. Our method allows to minimize graft preparation failure and preserves the PDEK graft efficiently, by reducing complications associated with the formation of type 1 big bubbles, including bubble rupture, perforation of Descemet's membrane and endothelium, and formation of type 2 or mixed type of big bubbles, and may contribute to increasing the number of surgeons performing PDEK around the globe.