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Purpose: Endothelial keratoplasty (EK) is the conventional treatment to improve visual acuity of corneal endothelium decompensation (CED) patients, with other therapies mainly for symptomatic relief. However, the shortage of corneal grafts and other limitations to EK urge the development of novel alternative treatments. In the last decade, novel options have been proposed, yet only a limited number of reviews have systematically reported on outcomes. Therefore, this systematic review evaluates the existing clinical evidence of novel surgical approaches for CED., Method: We identified 24 studies that illustrated the clinical observations of the surgical approaches in interest. We included Descemet stripping only (DSO), Descemet membrane transplantation (DMT) where Descement membrane alone instead of corneal endothelium with cells is transplanted, and cell-based therapy., Results: In general, these therapies may provide visual outcomes comparable with EK under specific conditions. DSO and DMT target CED with relatively healthy peripheral corneal endothelium like Fuchs' corneal endothelial dystrophy, while cell-based therapy offers more versatile applications. Side effects of DSO would decrease with modifications to surgical techniques. Moreover, Rho-associated protein kinase inhibitor adjuvant therapy could enhance clinical results in DSO and cell-based therapy., Conclusion: Long-term controlled clinical trials with larger sample size on the therapies are needed. The simplicity of DSO and the high translational potential of cell-based therapy to treat CED of most etiologies made these two treatment strategies promising., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Purpose: To evaluate different corneal parameters in identifying patients at risk of a hyperopic shift after (DMEK)., Methods: This retrospective study included 92 eyes of patients with FECD after DMEK surgery. Pachymetry parameters, various tomographic parameters and densitometry values before and after DMEK were determined using a rotating Scheimpflug system (Pentacam HR, Oculus). For assessing the posterior to anterior corneal curvature relationship, we calculated the R PA (posterior to anterior corneal curvature radii ratio)., Results: The average keratometry reading of the posterior corneal surface (Km B) increased and the total corneal refractive power (TCRP) decreased significantly after surgery (P < .001). There was a significant difference between the preoperative and postoperative R PA (P < .001) and the posterior Q value (P < .001). The strongest correlation was found between the change in the Km B and the preoperative R PA (Spearman's correlation coefficient = 0.872, P < .001). In the receiver operating characteristic (ROC) analysis, the highest AUC values (for ∆Km B ) among the different preoperative parameters tested were obtained for R PA and posterior Q value (Asph. Q B ) with AUROC (area under the ROC) values of 0.95 and 0.89, respectively., Conclusions: The Q value and the R PA showed the highest correlation with the change in corneal refractive power and the greatest AUC. These parameters could be used as surrogate markers to identify eyes that might be at risk of a greater postoperative hyperopic shift, which would allow more accurate setting of refractive goals.

Purpose: To assess the morphological and functional outcomes of Descemet membrane endothelial keratoplasty (DMEK) performed with pre-stripped tissue preserved in organ culture medium containing dextran compared to tissue preserved in dextran-free medium., Methods: In this retrospective study, we reviewed the clinical records of 103 patients who underwent DMEK surgery with pre-stripped tissue in our department between June 2015 and September 2016. The endothelium-Descemet membrane layer was preserved in organ culture medium for a maximum of 48 h for all patients. For group 1, 49 endothelium-Descemet membrane (EDM) were stripped and preserved in medium 1 (dextran-free organ culture medium), while 54 EDM were stripped and preserved in medium 2 (organ culture medium supplemented with 6% dextran T-500) for group 2. Outcome measures included best-corrected visual acuity (BCVA), central corneal thickness (CCT), and endothelial cell density (ECD) of all eyes in both groups at three consecutive postoperative time points: 2 weeks, 6 weeks, and 6 months postoperatively. We also compared the repeat keratoplasty rates between the groups., Results: Group 1 showed a statistically significant better BCVA compared to group 2 at each time point (p < 0.05). The percentage of grafts achieving 0.5 or better after 6 months in group 1 was 96% and in group 2, it was 66% (P < 0.001). CCT was significantly lower in group 1 compared to group 2 at 2 weeks and 6 months after surgery (p < 0.05). ECD was comparable between donor grafts before surgery but was significantly greater in groups 1 after 2 and 6 weeks (p < 0.05), but not after 6 months. Necessity for repeat keratoplasty (repeat DMEK, subsequent penetrating keratoplasty (PKP)) was significantly lower in group 1 (p < 0.05)., Conclusions: Pre-stripped tissue for DMEK preserved in dextran-free medium led to better visual recovery, thinner postoperative corneas, a higher endothelial cell density, and a lower rate of repeat keratoplasty, indicating that dextran has an unfavorable impact on the preservation of pre-stripped DMEK tissue.

Purpose: Although the functional results following DMEK are better than after DSAEK, DSAEK still seems to be the standard procedure, as surgeons fear losing grafts during DMEK graft preparation. Therefore, eye banks offer precut DMEK grafts for direct use by the surgeon. Here, we analysed the functional results and complication rates for a precut technique compared to fresh preparations., Methods: We retrospectively compared 453 standard to 11 precut (1-2 days before surgery) DMEK cases. Precut preparations did not differ from the standard preparation, except that the preparation was stopped after trephination with the graft still attached in a small central area. The preparation had to be completed before surgery by peeling off the centrally attached part of the graft. This technique was first tested in an experimental series of 14 grafts, which were unsuitable for transplantation. All surgeries were performed in the same standardized way., Results: There was no significant endothelial cell loss during the storage period following precut preparation. We found a statistically significantly higher endothelial cell loss and graft failure rate for the precut grafts., Conclusion: Because of the statistically significant higher graft failure rate in the precut group, we stopped using this technique, so the numbers in this retrospective case series are small. The higher graft failure rate may be explained by (ultra)structural changes in the DMEK graft (e.g. accumulation of dextran) during the second storage period. Therefore, careful evaluation is recommended before using precut DMEK grafts stored in dextran containing media in order to avoid early primary graft failures.

Purpose: According to some pioneer surgeons, lamellar endothelial keratoplasty techniques (EK), including Descemet membrane endothelial keratoplasty (DMEK) and Descemet stripping automated endothelial keratoplasty (DSAEK), yield excellent clinical results. However, there is a lack of studies with high levels of evidence and results of large national keratoplasty registers are contradictory. Therefore, two large cohorts of DMEK and DSAEK procedures are compared to a cohort of penetrating keratoplasty (PK)., Methods: The study reports 868 keratoplasty procedures at a single centre (694 eyes with Fuchs endothelial dystrophy (FED) and 174 with bullous keratopathy (BK)). Patients underwent DMEK (450 eyes), DSAEK (89 eyes), or PK (329 eyes). Postoperative visual acuity, endothelial cell density (ECD), rate of regrafting, and rejections were recorded., Results: Visual acuity recovers faster and to a greater extent in EK compared to PK. DMEK performs better than DSAEK. ECD drops faster initially for EK compared to PK. In EK the rate of regrafting is higher than in PK (7 % in DMEK, 20 % in DSAEK and 2 % in PK in FED). The rejection rate is lowest following DMEK (7 % after DMEK, 21 % after DSAEK and 18 % after PK in FED)., Conclusions: In contrast to recent reports from national keratoplasty registers, the overall clinical outcome of EK in FED and BK is superior to PK. Including ocular comorbidities and learning curves, these data reflect a realistic setting for comparing the different keratoplasty techniques. Corneal surgeons may be encouraged to preferentially use DMEK in FED and BK.

Purpose: To evaluate the 1-year clinical outcome after semi-circular Descemet membrane endothelial keratoplasty (hemi-DMEK) in a first case series., Methods: In three eyes of three patients with Fuchs endothelial dystrophy, best corrected visual acuity (BCVA), endothelial cell density (ECD), pachymetry, and intra- and postoperative complications were evaluated after transplantation of a semi-circular ~12 mm diameter Descemet graft (hemi-DMEK graft)., Results: All corneas cleared within 6 months and showed a stable pachymetry thereafter (527, 535, and 490 μm, respectively). Compared to preoperative measurements, average central ECDs dropped by 51 % (56, 39, and 59 %, respectively) at 3 months, 53 % (57, 38, and 63 %, respectively) at 6 months, and 59 % (60, 47, and 71 %, respectively) at 12 months. Denuded stromal areas adjacent to the hemi-DMEK graft cleared and at 12 months peripheral ECD counts ranged from 724 to 1051 cells/mm(2). At 12 months, BCVA was 20/22 (0.9), 20/40 (0.5, amblyopic eye) and 20/17 (1.2). No postoperative complications occurred throughout the study period., Conclusions: Hemi-DMEK may provide visual outcomes similar to those in standard DMEK at the 1-year postoperative mark. If also graft survival and complication rates prove to be similar, hemi-DMEK could become the next step in endothelial keratoplasty, owing to its potential to double the yield of transplants from the same donor pool (two hemi-DMEK grafts can be prepared from one donor cornea).

Purpose: To evaluate the impact of venting incisions on the best corrected visual acuity (BCVA), astigmatism, aberrations, and risk of graft detachment in Descemet stripping automated keratoplasty (DSAEK)., Methods: This was a retrospective, comparative, consecutive case series of DSAEK procedures performed with (n = 266) and without (n = 110) venting incisions. Patients were treated with DSAEK for Fuchs' endothelial dystrophy at Aarhus University Hospital between 2011 and 2013. Data included preoperative keratometry and postoperative BCVA, subjective astigmatism, and Pentacam® HR tomography with corneal front surface (CFS) aberrations at 1 to 2 years of follow-up. Numbers of triple procedures (concurrent cataract surgery) and post-operative graft detachments were also noted. The venting and non-venting groups were compared by the data-means. Unpaired t-tests and Mann-Whitney tests were used for normally and non-normally distributed data, respectively. Differences in graft detachments were analyzed with Fisher's exact and Chi square test., Results: There was no significant difference in any parameter, except the numbers of triple procedures. BCVA (logMAR) was 0.25 ± 0.18 in the venting group and 0.25 ± 0.19 in the non-venting group (p = 0.92), subjective astigmatism was -1.53 ± 0.99 diopters and -1.33 ± 0.78 diopters (p = 0.15), respectively. CFS astigmatism and higher order aberrations were statistically uniform. The relative risk (RR) of graft detachment was also uniform between the venting versus non-venting group (RR 0.72, p = 0.40), and between triple versus non-triple procedures (RR 0.71, p = 0.43). The preoperative corneal curvature had no impact on the risk of graft detachment (p = 0.74)., Conclusion: Venting incisions in DSAEK do not significantly alter BCVA, astigmatism, CFS aberrations or reduce the risk of graft detachment in triple or non-triple procedures.

Purpose: To analyze potential alterations in corneal nerve morphology and function in different stages of Fuchs' endothelial corneal dystrophy (FECD)., Methods: Thirty eyes with FECD underwent in vivo confocal microscopy using the Heidelberg Retina Tomograph II (HRT II; Heidelberg Engineering, Heidelberg, Germany) and the Rostock Cornea Module (RCM) to quantify the morphology of the central subbasal corneal nerve plexus (total nerve length, total nerve number, number of main nerve trunks, number of nerve branches) as well as esthesiometry (using the Cochet-Bonnet esthesiometer) of the central cornea to determine central corneal sensation as a measure of nerve function. Findings were correlated with an age-matched control group of 30 healthy individuals. Comparisons to biomicroscopical stage of FECD, visual acuity and central corneal thickness were performed using Spearman correlation., Results: Depending on slit-lamp examination, all 30 eyes were classified into FECD stage 1-4 (stage 1: six eyes; stage 2: 15 eyes; stage 3: six eyes; stage 4: three eyes). Total nerve length (ρ = -0.8, p < 0.001), total nerve number (ρ = -0.7, p < 0.001), number of main nerve trunks (ρ = -0.6, p < 0.001), and number of nerve branches (ρ = -0.7, p < 0.001) decreased significantly with increasing FECD stages. Comparing to the visual acuity, significant positive correlations were found for total nerve length (ρ = 0.5, p = 0.012), total nerve number (ρ = 0.5, p = 0.005), number of main nerve trunks (ρ = 0.4, p = 0.017), and number of nerve branches (ρ = 0.5, p = 0.009). With central corneal thickness, there were significant inverse correlations for total nerve length (ρ = -0.6, p = 0.001), total nerve number (ρ = -0.5, p = 0.012), number of main nerve trunks (ρ = -0.4, p = 0.015), and number of nerve branches (ρ = -0.4, p = 0.017). Central corneal sensation was full in all FECD stage 1, stage 2 and stage 3 eyes, but mildly reduced in FECD stage 4 eyes., Conclusions: Increasing severity of Fuchs' endothelial corneal dystrophy (FECD) is concurrent with marked attenuation of the density, as well as mild diminishment of the function, of the subbasal corneal nerve plexus in late stage of the disease.

Background: Descemet membrane endothelial keratoplasty (DMEK) is being proposed as the procedure of choice in corneal endothelial disease as it achieves better visual and refractive outcomes than Descemet stripping automated endothelial keratoplasty (DSAEK). Nevertheless, primary graft failure is frequent, especially during the learning curve, and secondary back-up procedure consists on DSAEK. We aim to compare corneal haze and visual acuity of patients undergoing primary DSAEK vs. patients undergoing DSAEK as a back-up procedure after primary DMEK failure., Methods: This study is a comparative case series that included 19 eyes from 16 patients with early stages of corneal failure and limitation of daily activities after primary DSAEK or secondary DSAEK. A control group of non-operated corneas included 10 aged-matched normal eyes. The study was conducted at University Hospital Ramón y Cajal and Vissum Hospital, Madrid, Spain. Corneal densitometry readings and postoperative best-corrected visual acuity in subjects with primary and secondary DSAEK were recorded 6 months after the surgery using the Pentacam Scheimpflug system (Oculus, inc.,Wetzlar, Germany)., Results: In primary DSAEK median densitometry values (range) were statistically significantly higher (p < 0.05) than normal subjects for the full thickness, posterior and anterior part of the paracentral cornea; and the anterior part of the central cornea. In secondary DSAEK, median densitometry values were statistically significantly higher than normal subjects at all levels of the central and paracentral cornea. In secondary DSAEK, median densitometry values (range) were statistically significantly higher than in primary DSAEK in the full-thickness, anterior part and interface of the central cornea and in the full-thickness and posterior part of the paracentral cornea. Median visual acuity between groups (p = 0.47) was statistically better for the primary DSAEK group, which also had a higher percentage of patients achieving BCVA of ≥ 20/40 and ≥ 20/25 than the secondary DSAEK group (100% vs. 62% and 60% vs. 0% respectively)., Conclusions: There is an increase in central corneal light scattering after secondary DSAEK performed after a failed DMEK as compared to primary DSAEK. This has a negative impact on final visual acuity that needs to be considered in each patient when starting DMEK surgery.

Purpose: To evaluate the outcomes of Descemet's stripping endothelial keratoplasty (DSEK) in patients with congenital hereditary endothelial dystrophy (CHED)., Methods: Retrospective, interventional case series of five eyes of five patients with congenital hereditary endothelial dystrophy (CHED) undergoing Descemet's stripping endothelial keratoplasty (DSEK) from June 2009 to June 2010 by a single surgeon. Patients were evaluated during the postoperative period for visual acuity, refraction, corneal clarity, lenticule status, and intraocular pressure. Anterior segment ocular coherence tomography (OCT) and confocal microscopy were performed when possible., Results: Three male and two female children with an average age of 7.8 years (range 5-12 years) with CHED underwent DSEK. Surgery was uneventful in all patients and the lenticules stayed attached during the postoperative period. All the patients had 1-year follow-up. Corneal clarity improved in all the patients over the period of follow-up. Anterior segment OCT showed a gradual reduction in the thickness of the central corneal thickness and the graft over a period of time., Conclusions: DSEK is a viable alternative to penetrating keratoplasty in patients with CHED with distinct advantages of reduced postoperative astigmatism and potential reduction of postoperative complications.