Emerging treatments for corneal endothelium decompensation - a systematic review.

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.

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.

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.

CTG18.1 expansion in transcription factor 4 (TCF4) in corneal graft failure: preliminary study.

Fuchs endothelial corneal dystrophy (FECD) is caused by a corneal endothelial cell loss, leading to corneal edema and visual impairment. The most significant genetic risk factor for FECD is an expansion of the CTG18.1 locus in transcription factor 4 (TCF4). The current treatment for severe FECD is corneal transplantation, with Descemet stripping automated keratoplasty (DSAEK) as a common surgical method. Although successful in most cases, the risk for transplant failure due to diverse causes must be considered. In this study, we investigated if presence of TCF4 CTG18.1 expansion with more than 31 (n ≥ 31) repeats in donated corneal grafts could be a reason for corneal transplant failure after DSAEK. For this, nine consecutively failed DSAEK corneal grafts were genotyped for CTG18.1 repeat length. One-sided Mann-Whitney U test was performed to evaluate if failed DSAEK corneal grafts had longer CTG18.1 repeats than healthy controls from the same population. All failed corneal grafts had CTG18.1 n ≤ 27 with a median of 18 (IQR 8.0) repeats for the longest allele. There was no statistical difference in CTG18.1 repeat lengths between failed corneal grafts and the geographically matched healthy control group. In conclusion, none of the nine failed corneal grafts in our material had CTG18.1 repeat lengths ≥ 31, a cut-off known to have a biological relevance in FECD. Thus, our results suggest that the assessment of donors and inspection of the corneal tissue before the decision for procurement is sufficient, in terms of recognizing FECD in the donor.

Different Course of Immune Reactions and Endothelial Cell Loss after Penetrating Low-Risk Keratoplasty and Descemet Membrane Endothelial Keratoplasty for Fuchs Endothelial Dystrophy. / Unterschiedlicher Verlauf von Immunreaktionen und Endothelzellverlust nach perforierender Low-Risk-Keratoplastik und Descemet Membrane Endothelial Keratoplasty bei Fuchs-Endotheldystrophie.

BACKGROUND: The aim of this study was to compare the incidence of immune reactions and endothelial cell loss after penetrating keratoplasty (PKP) vs. Descemet membrane endothelial keratoplasty (DMEK) in patients with Fuchs endothelial dystrophy (FED). PATIENTS AND METHODS: In the present retrospective study, a total of 962 surgeries (225 excimer laser PKP and 727 DMEK) of 700 patients performed between 28.06.2007 and 27.08.2020 in the Department of Ophthalmology at Saarland University Medical Center UKS were statistically evaluated. On the one hand, the prevalence and the temporal course of the immune reactions that occurred were analysed using the Kaplan-Meier method, as well as the effect of the immune reactions on the endothelial cells and corneal thickness. Secondly, endothelial cell density, pleomorphism, and polymegethism of the endothelial cells were evaluated for the time points U1 = preoperative, U2 = 6 weeks postoperative, U3 = 6 to 9 months postoperative, U4 = 1 to 2 years postoperative, and U5 = 5 years postoperative. In addition, statistical tests were carried out for differences between the two types of surgery and in the longitudinal course. RESULTS: A total of 54 immune reactions occurred during the observed period, whereby the probability of such a reaction was significantly greater in the PKP group with 8.9% than in the DMEK group with 4.5% (p = 0.011). The comparison of the two Kaplan-Meier curves also showed a significant difference between the two surgical techniques in the log-rank test (p = 0.012). The endothelial cell loss due to the immune reaction was only significant in PKP (p = 0.003). For all surgical procedures, endothelial cell density decreased significantly with time in both surgical techniques (p < 0.0001 in each case), but more strongly with DMEK than with PKP (p < 0.0001). Furthermore, this cell density was significantly higher with PKP than with DMEK for the whole observation time (p < 0.0001). Polymegethism decreased significantly in the DMEK group (p < 0.0001). Pleomorphism was significantly higher, on average, in DMEK than in PKP (p < 0.0001). CONCLUSION: The prognosis of DMEK in patients with FED seems to be more favourable after immune reactions than that of PKP, as not only were immune reactions less frequent, but they were also milder. However, endothelial cell density was significantly higher in the PKP group during the entire follow-up.

[Outcomes of hemi-Descemet membrane endothelial keratoplasty and phacoemulsification for the treatment of primary Fuchs' endothelial corneal dystrophy combined with cataract]. / Rezul'taty transplantatsii destsemetovoi membrany s endoteliem i fakoemul'sifikatsii pri pervichnoi endotelial'noi distrofii rogovitsy Fuksa, sochetannoi s kataraktoi.

PURPOSE: This study evaluates the long-term results of surgical treatment of patients with Fuchs' endothelial corneal dystrophy and cataract. MATERIAL AND METHODS: The study included 24 patients (24 eyes) with primary Fuchs' endothelial corneal dystrophy and cataract, who underwent cataract phacoemulsification with IOL implantation and of Descemet's membrane endothelial keratoplasty with a semicircular graft (hemi-DMEK). The effect of treatment was assessed by best corrected visual acuity (BCVA), central corneal thickness (CCT) and endothelial cell density (ECD). RESULTS: In total, surgical treatment involved 14 donor corneas that were divided in half during the preparation and isolation of the Descemet's membrane (DM). By month 12 after the surgery an increase in visual functions and graft transparency were observed in 23 patients (23 eyes) out of 24. Repeated keratoplasty was required in one case due to fibrosis of the posterior layers of recipient's corneal stroma. At 12 months postoperatively, the study group showed an increase in BCVA from 0.16±0.1 to 0.75±20, a decrease in CCT from 650.9±4.5 µm to 519.6±43.9, and a decreased in ECD from 2850.5±84.7 cells/mm2 up to 1285.5±277.2 cells/mm2. Thus, the loss of endothelial cells at one year after surgery amounted to 54.9%. CONCLUSIONS: The developed method for transplantation of a semicircular DM fragment provides a tissue-saving approach to endothelial keratoplasty, and considering the high percentage of transparent engraftment of grafts and complete visual rehabilitation, it can be recommended in the treatment of patients with cataract and Fuchs' endothelial corneal dystrophy.

Descemet Stripping Automated Endothelial Keratoplasty versus Descemet Membrane Endothelial Keratoplasty for Fuchs Endothelial Corneal Dystrophy: A National Registry-Based Comparison.

PURPOSE: To compare the outcome between posterior lamellar corneal transplant procedures for Fuchs endothelial corneal dystrophy, taking preoperative patient characteristics in consideration. Surgical methods compared were Descemet membrane endothelial keratoplasty (DMEK), Descemet stripping automated endothelial keratoplasty (DSAEK), and DSAEK with concomitant cataract surgery (phacoemulsification plus DSAEK). DESIGN: Registry-based study with propensity score matching. PARTICIPANTS: One thousand six hundred seventy-seven patients from all Swedish corneal transplantation units treated from 2012 through 2019. METHODS: All patients undergoing endothelial keratoplasty performed from 2012 through 2019 with completed 2-year follow-up data reported to The Swedish Corneal Transplant Register were included, totaling 1677 patients. Three comparable groups (DMEK, DSAEK, and phacoemulsification plus DSAEK) with 216 patients in each group were generated with propensity score matching based on preoperative visual acuity, age, sex, year of surgery, and preoperative risk factors such as inflammation, vascularization, and glaucoma. MAIN OUTCOME MEASURES: Best-corrected visual acuity (BCVA) at the 2-year follow-up, frequency of graft dislocation, graft rejection episodes, and graft failure within 2 years including primary graft failure. RESULTS: The preoperative corneal status was affected more severely in the DSAEK group before matching. In the matched groups, the median BCVA 2 years after surgery was 0.1 logarithm of the minimum angle of resolution (logMAR) in both the DMEK and the phacoemulsification plus DSAEK groups and 0.15 logMAR in the DSAEK group (P = 0.001). The frequency of graft dislocation was higher among the patients undergoing phacoemulsification plus DSAEK, but the frequency of graft failure and primary graft failure was higher in the DMEK group. CONCLUSIONS: Visual acuity improved in most patients (90%) with all 3 surgical methods. However, DMEK and phacoemulsification plus DSAEK reached higher levels of visual acuity 2 years after surgery, and phacoemulsification plus DSAEK was superior considering graft survival rate. All 3 surgical procedures showed both strengths and weaknesses, suggesting that the choice of surgical method should be individualized, taking into consideration not only the cornea, but each patient's complete medical status as well as the entire course of postoperative medical care. FINANCIAL DISCLOSURE(S): The author(s) have no proprietary or commercial interest in any materials discussed in this article.

Predictors of Receiving Keratoplasty for Fuchs' Endothelial Corneal Dystrophy among Medicare Beneficiaries.

PURPOSE: To identify factors associated with receipt of endothelial keratoplasty (EK) and penetrating keratoplasty (PK) in patients with Fuchs' endothelial corneal dystrophy (FECD). DESIGN: Retrospective cohort study. PARTICIPANTS: Medicare beneficiaries 65 years of age or older with a FECD diagnosis between 2011 and 2019. METHODS: The 100% Medicare fee-for-service administrative claims database was queried for treatment-naïve FECD patients. A multivariate logistic regression model including age, race and ethnicity, sex, geography, ocular comorbidities and surgeries, Charlson comorbidity index (CCI), and socioeconomic status was used to identify factors associated with receipt of EK and PK. Kaplan-Meier survival analyses were used to determine the rate of EK after cataract or complex or other anterior segment surgery. MAIN OUTCOME MEASURES: Factors associated with receipt of an EK or PK, plus rate of EK after cataract or complex or other anterior segment surgery. RESULTS: Of 719 066 beneficiaries identified, 31 372 (4.4%) received an EK and 2426 (0.3%) received a PK. In a multivariate analysis, female sex decreased likelihood of both EK and PK (adjusted odds ratio 0.83 [95% confidence interval 0.81-0.85] and 0.84 [0.78-0.92], respectively), while Western residence (1.33 [1.29-1.38]; 1.25 [1.11-1.42]) compared to Southern and history of complex or other anterior segment surgery (1.62 [1.54-1.70]; 5.52 [4.97-6.12]) increased the likelihood of both. Compared to Whites, the likelihood of EK was decreased for Black (0.76 [0.72-0.80]), Asian or Pacific Islander (0.54 [0.48-0.61]), and Hispanic or Latino (0.62 [0.55-0.70]) race and ethnicity, while for the same groups likelihood of PK was increased (for Black 1.32 [1.14-1.53]; Asian/Pacific Islander 1.46 [1.13-1.89]; and Hispanic/Latino 1.62 [1.25-2.11]). Following cataract or complex/other anterior segment surgery, rates of EK were 1.3% and 3.3% at 1 year and 2.3% and 5.6% at 8 years, respectively. CONCLUSIONS: In a multivariate analysis, women beneficiaries are less likely to receive EK or PK for FECD compared with men, whereas non-White beneficiaries are less likely to receive EK and more likely to receive PK compared with White beneficiaries.

Cost Drivers of Endothelial Keratoplasty: A Time-Driven Activity-Based Costing Analysis.

PURPOSE: To determine cost drivers of endothelial keratoplasty (EK) through evaluation of surgical costs and procedure length based on type of EK, use of preloaded grafts, and performance of simultaneous cataract surgery. DESIGN: This study was an economic analysis of EKs at a single academic institution using time-driven activity-based costing (TDABC) methodology. PARTICIPANTS: Endothelial keratoplasty surgical cases, including Descemet membrane endothelial keratoplasty (DMEK) and Descemet stripping automated endothelial keratoplasty (DSAEK), at the University of Michigan Kellogg Eye Center from 2016 to 2018 were included in the analysis. METHODS: Data and inputs were obtained via the electronic health record (EHR) and from prior literature. Simultaneous cataract surgeries were included and separately categorized for analysis. Endothelial keratoplasty expenses were determined with TDABC, a method for cost calculation that incorporates the time that key resources are used and each resource's associated cost rate. MAIN OUTCOME MEASURES: Main outcome measures included surgery length (in minutes) and day-of-surgery costs. RESULTS: There were 559 EKs included: 355 DMEKs and 204 DSAEKs. Fewer DSAEKs had simultaneous cataract extraction (47; 23%) than DMEK (169; 48%). Of the DMEKs, 196 (55%) used preloaded corneal grafts. Descemet membrane endothelial keratoplasty cost $392.31 less (95% confidence interval, $251.05-$533.57; P < 0.0001) than DSAEK and required 16.94 fewer minutes (14.16-19.73; P < 0.0001). Descemet membrane endothelial keratoplasty cases that used preloaded corneal grafts cost $460.19 less ($316.23-$604.14; P < 0.0001) and were 14.16 minutes shorter (11.39-16.93; P < 0.0001). In multivariate regression, preloaded graft use saved $457.19, DMEK (compared with DSAEK) saved $349.97, and simultaneous cataract surgery added $855.17 in day-of-surgery costs. CONCLUSIONS: Cost analysis of TDABC identified a day-of-surgery cost and surgical time reduction associated with the use of preloaded grafts for DMEK, DMEK compared with DSAEK, and isolated EK compared with EK combined with cataract surgery. This study provides an improved understanding of surgical cost drivers and margin incentivization, which may explain trends and indirectly influence patient care decisions in cornea surgery practices. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

Inhibition of Rho-associated protein kinase activity enhances oxidative phosphorylation to support corneal endothelial cell migration.

Corneal endothelial cell (CEC) dysfunction causes corneal edema and severe visual impairment that require transplantation to restore vision. To address the unmet need of organ shortage, descemetorhexis without endothelial keratoplasty has been specifically employed to treat early stage Fuchs endothelial corneal dystrophy, which is pathophysiologically related to oxidative stress and exhibits centrally located corneal guttae. After stripping off central Descemet's membrane, rho-associated protein kinase (ROCK) inhibitor has been found to facilitate CEC migration, an energy-demanding task, thereby achieving wound closure. However, the correlation between ROCK inhibition and the change in bioenergetic status of CECs remained to be elucidated. Through transcriptomic profiling, we found that the inhibition of ROCK activity by the selective inhibitor, ripasudil or Y27632, promoted enrichment of oxidative phosphorylation (OXPHOS) gene set in bovine CECs (BCECs). Functional analysis revealed that ripasudil, a clinically approved anti-glaucoma agent, enhanced mitochondrial respiration, increased spare respiratory capacity, and induced overexpression of electron transport chain components through upregulation of AMP-activated protein kinase (AMPK) pathway. Accelerated BCEC migration and in vitro wound healing by ripasudil were diminished by OXPHOS and AMPK inhibition, but not by glycolysis inhibition. Correspondingly, lamellipodial protrusion and actin assembly that were augmented by ripasudil became reduced with additional OXPHOS or AMPK inhibition. These results indicate that ROCK inhibition induces metabolic reprogramming toward OXPHOS to support migration of CECs.

Role of descemet's stripping without keratoplasty in management of endothelial disease.

PURPOSE OF REVIEW: To summarize recent literature on Descemet's stripping only (DSO) in management of endothelial disease with particular focus on Fuchs endothelial corneal dystrophy (FECD). RECENT FINDINGS: DSO is currently indicated in patients with early FECD, central guttae, and preserved peripheral corneal endothelial cell (CEC) count. Time to corneal clearance may be accelerated and maintained with addition of topical rho-kinase inhibitor (ROCKi). There are reports describing successful use of DSO to treat endothelial disease due to iatrogenic trauma. In patients with transcription factor 4 gene mutation, increased cytosine, thymine, guanine (CTG) triplet repeat load may be associated with DSO failure risk. Emerging pharmacotherapies and cell-suspension treatments may improve procedure effectiveness and expand clinical indications. SUMMARY: DSO can be used as the initial surgical treatment in management of symptomatic endothelial disease due to FECD where peripheral CEC function appears preserved. Stand-alone DSO or DSO combined with cataract surgery is effective and postoperative topical ROCKi supplementation will improve time to corneal clearance and CEC count.

Graft failure rate and complications after Descemet membrane endothelial keratoplasty in eyes with pre-existing glaucoma.

PURPOSE: To evaluate the outcome of Descemet Membrane Endothelial Keratoplasty (DMEK) in eyes with pre-existing glaucoma. DESIGN: In this retrospective, observational case series we included data of 150 consecutive DMEKs in eyes with pre-existing glaucoma of 150 patients after excluding data of the second treated eye of each patient and of re-DMEKs during follow-up. Cumulative incidences of IOP elevation (IOP > 21 mmHg or ≥ 10 mmHg increase in IOP from preoperative value), post-DMEK glaucoma (need of an additional intervention due to worsening of the IOP), graft rejection, and graft failure rate were analyzed using Kaplan-Meier survival analysis. COX regression analysis was used to evaluate independent risk factors. RESULTS: The 36-month cumulative incidence of IOP elevation was 53.5% [95 CI 43.5-63.5%] and of post-DMEK glaucoma 36.3% [95 CI 26.3-46.3%]. Graft rejection occurred with a 36-month cumulative incidence of 9.2% [CI 95% 2.3-16.1]. None of the analyzed risk factors increased the risk for the development of graft rejection. The 36-month cumulative incidence of graft failure was 16.6% [CI 95% 8.4-24.8]. Independent risk factors for graft failure were the indication for DMEK "status after graft failure" (n = 16) compared to Fuchs' dystrophy (n = 74) (p = 0.045, HR 8.511 [CI 95% 1.054-68.756]) and pre-existing filtrating surgery via glaucoma drainage device (GDD) (n = 10) compared to no surgery/iridectomy (n = 109) (p = 0.014, HR 6.273 [CI 95% 1.456-27.031]). CONCLUSION: The risks of postoperative complications (IOP elevation, post-DMEK glaucoma, graft rejection, and graft failure) in patients with pre-existing glaucoma are high. In particular, pre-existing filtrating surgery via GDD implantation-but not trabeculectomy-and DMEK after graft failure increase the risk of graft failure.

12-year follow-up of the first endothelial keratoplasty without Descemet stripping in a 3-month newborn with Congenital Hereditary Endothelial Dystrophy (CHED).

BACKGROUND: Endothelial Keratoplasty (EK) is now considered as the standard treatment for Congenital Hereditary Endothelial Dystrophy (CHED) by many surgeons. We present the 12-year clinical outcome of the youngest operated patient with CHED in which we successfully performed a bilateral EK procedure without removing the recipient endothelium-Descemet complex. CASE PRESENTATION: In November 2010 we performed EK without Descemet Stripping in a 3-month female newborn, thinking that the lower manipulation obtained by leaving the recipient endothelium-Descemet complex could be the key factor for the success of our surgery. Such a particular technique was new in newborns. The surgery was a success, but the long-term visual result was not predictable at that time. We followed the patient at 4 months, and then yearly. At the latest visit in October 2022 the visual, cognitive, and motorial developments were normal, with Best-corrected Distance Visual Acuity of 0.4 LogMAR with - 0.75 D sf + 2.75 D cyl @ 105° in the right eye (RE) and 0.4 LogMAR with + 1.50 D sf + 2.50 D cyl @ 60° in the left eye (LE). The endothelial microscope showed an unexpected healthy endothelium, with a cell count of 2383 cells/mm2 in the RE and of 2547 cells/mm2 in the LE from a starting donor count of 2900 cells/mm2. No secondary procedures were performed during the 12-year follow-up. CONCLUSION: EK without Descemet stripping has proved to be a successful procedure over time in our newborn. The unexpected healthy endothelium suggests a role of the Descemet membrane in CHED.

Descemet membrane endothelial keratoplasty combined with presbyopia-correcting and toric intraocular lenses - a narrative review.

Fuchs endothelial corneal dystrophy (FECD) is the leading indication for EK and may coexist with cataract and presbyopia. Notably, the outcomes of phacoemulsification in FECD patients are not as favorable as those in eyes without this condition. Historically, only monofocal intraocular lenses (IOLs) were recommended for these patients. However, recent reports have described the implantation of Premium-IOLs (such as Multifocal IOLs, Enhanced Depth of Focus IOLs, and Toric IOLs) in FECD eyes undergoing cataract surgery and Descemet membrane endothelial keratoplasty (DMEK). While the results are encouraging, they are not as optimal as those from unoperated eyes, especially when comparing simultaneous procedures to sequential ones. It's advised to perform the DMEK first to improve the accuracy of IOL calculations. Still, even successfully operated eyes may experience secondary graft failure or graft rejection after DMEK. The success rate of a secondary DMEK is typically lower than that of the initial procedure. Furthermore, if the postoperative thickness after DMEK is less than anticipated, laser enhancements might not be an option. There's a pressing need for more controlled and randomized clinical trials to ascertain the safety and effectiveness of Premium-IOLs for FECD eyes. This narrative review aims to collate evidence on the use of Premium IOL technologies in eyes receiving EK and to underscore key points for surgeons performing EK combined with cataract surgery.

Comparison of penetrating and endothelial keratoplasty in patients with iridocorneal endothelial syndrome: A registry study.

BACKGROUND: To compare graft survival of endothelial keratoplasty (EK) versus penetrating keratoplasty (PK) in patients with iridocorneal endothelial (ICE) syndrome and identify ocular features associated with graft survival. METHODS: Observational, prospective, cohort study. A total of 30 806 first grafts performed between 1985 and 2020 were identified through the Australian Corneal Graft Registry and included in this observational, prospective cohort study. A total of 196 eyes underwent a primary corneal graft for ICE syndrome. Kaplan-Meier graft survival plots and Chi-squared tests were performed to identify graft survival rates for EK and PK. A history of raised intraocular pressure (IOP) was also recorded and analysed. Graft survival of eyes with ICE syndrome were compared to that of other indications. RESULTS: Grafts performed for ICE syndrome increased to 0.8% of all cases during the 2005 to 2020 period compared with 0.5% between 1985 to 2004 (χ2 =9.35, p = 0.002). From 2010, EK surpassed PK as the preferred graft type. Survival of primary grafts in eyes with ICE syndrome was lower than for other indications (log-rank = 56.62, p < 0.001). Graft survival was higher following PK than Descemet stripping (automated) endothelial keratoplasty (DS(A)EK) (log-rank = 10.56, p = 0.001). Graft survival was higher in eyes without a history of raised IOP compared to those with a reported history of raised IOP (log-rank = 13.06, p < 0.001). CONCLUSIONS: ICE syndrome carries a poor prognosis for graft survival. DS(A)EK had a poorer prognosis than PK. A history of raised IOP is associated with higher risk of graft failure.

Long-Term Outcomes of Excimer Laser-Assisted Penetrating Keratoplasty Using a Commercially Available Laser System - A Retrospective Case Series.

BACKGROUND: Favorable functional outcomes have been reported after excimer laser-assisted penetrating keratoplasty (EXL PKP). But this technique has not been widely adopted, and there are reports on EXL PKP from only a very limited number of institutions. Some of these results refer to operations carried out with laser systems that are not commercially available. In this retrospective case series, we report the long-term outcome of EXL PKP using the Schwind Amaris 500E laser system. MATERIAL AND METHODS: This retrospective consecutive case series included 30 eyes of 29 patients who had undergone EXL PKP between 2010 and 2013. Primary outcome measures were topographic astigmatism and visual acuity. Secondary outcome measures were the rates of graft rejection and graft failure, and the rate of grafts with an endothelial cell density below 500 cells/mm2. Survival analyses were carried out for the following endpoints: visual acuity, rate of graft rejection, and rate of grafts with endothelial cell densities higher than 500 cells/mm2. RESULTS: The median interquartile range (IQR) duration of follow-up was 45 (36) months. The indications for PKP were keratoconus (n = 21), corneal scarring (n = 6), Fuchs endothelial dystrophy (n = 1), and corneal dystrophy other than Fuchs endothelial dystrophy (n = 2). The median (IQR) topographic astigmatism at the end of the follow-up period was 5.3 (2.9) D. Forty-five months after surgery, 73% of all eyes had a visual acuity better than 0.3 LogMAR. The rate of graft rejection after 45 months of follow-up was 32%. All eyes maintained endothelial cell densities higher than 500 cells/mm2. There was no graft failure. CONCLUSIONS: EXL PKP is a safe and effective surgical procedure. No general conclusions can be drawn on the refractive outcome of EXL PKP. Potential advantages, such as a higher degree of graft-host congruity, that could possibly improve the refractive outcome should be weighed against the higher costs of EXL PKP.

Predictive factors of graft detachment and rebubbling after descemet membrane endothelial keratoplasty.

PURPOSE: To identify risk and predictive factors associated with the need of rebubbling in the eye of patients who underwent a descemet membrane endothelial keratoplasty (DMEK). METHODS: The records of patients who underwent DMEK were retrospectively analyzed. Data regarding comorbidities, intraoperative characteristics, and postoperative treatments or complications were collected. The central corneal thickness (CCT) was measured by optical coherence tomography before and the day after DMEK. Univariate and multivariate analyses were performed. RESULTS: Of the 333 DMEK, rebubbling was performed in 119 cases (36%). Preoperative subepithelial fibrosis and a history of penetrating keratoplasty (PK) were associated with significantly more graft detachment [OR of 3.55 (2.02-6.32; P < 0.001) and 5.89 (2.00-21.86; P = 0.003), respectively]. A decreased CCT the day after surgery reduced by 5.7-fold the risk of rebubbling (sensitivity/specificity of 0.42/0.93). Conversely, a 20% increase in the CCT the day after surgery increased by 4.5-fold the risk of rebubbling (sensitivity/specificity of 0.42/0.91). CONCLUSION: Variation of the CCT could be used as a predictive factor of rebubbling after DMEK. Patients with a 20% increase of CCT the day after surgery are at higher risk of graft detachment. Conversely, a reduced CCT the day after the surgery is associated with a reduced risk of rebubbling. Subepithelial fibrosis and history of PK were also identified as risk factors for rebubbling. Those predictive factors may help develop a customized approach for patients undergoing DMEK surgery.

The effect of anterior segment parameters on surgical success of Descemet membrane endothelial keratoplasty: a prospective study.

PURPOSE: To investigate how anterior segment parameters affect the success of Descemet membrane endothelial keratoplasty (DMEK) in patients with endothelial insufficiency without stromal opacities and to identify factors predisposing them to repeat keratoplasty. METHODS: Our prospective observational study included patients who underwent primary DMEK for Fuchs' endothelial dystrophy and pseudophakic bullous keratopathy between March 2019 and March 2020. After a detailed ophthalmologic examination, corneal topographic analysis, anterior segment optical coherence tomography (AS-OCT) scans, endothelial cell density (ECD) and axial length (AL) measurements were performed. Surgical success was defined as no endothelial dysfunction during follow-up. Changes in the parameters and how preoperative parameters affect surgical success were investigated. RESULTS: In 43 eyes of 43 patients (mean age: 68.58 ± 8.51 years), mean visual acuity was 1.73 ± 0.74 LogMAR before DMEK and 0.31 ± 0.29 LogMAR in the final visit. Central corneal thickness (CCT, p = 0.026) and mean anterior chamber depth (ACD, p = 0.001) affected surgical success. Preoperative CCT values greater than 770 µm increased the risk of repeat keratoplasty by 8.75-fold, whereas preoperative ACD values less than 2.5 mm increased the risk by 2.92-fold. CONCLUSION: Preoperative higher CCT and lower ACD values were associated with surgical failure after DMEK. Early surgery may be considered for more successful results. TRIAL REGISTRATION: This prospective study has been registered on the ClinicalTrials.gov system with the registration number NCT04420429 on 06/06/2020.

[Corneal changes in Fuchs endothelial corneal dystrophy and bullous keratopathy]. / Izmeneniya rogovitsy pri endotelial'noi distrofii Fuksa i vtorichnoi bulleznoi keratopatii.

OBJECTIVE: Evaluation of structural and immunohistochemical features of cornea in Fuchs endothelial corneal dystrophy (FECD) and bullous keratopathy (BK). MATERIAL AND METHODS: Group 1 - 44 patients (46 eyes) with FECD, group 2 - 42 patients (42 eyes) with BK. All patients underwent keratoplasty. Preoperative anterior segment optical coherence tomography (AS-OCT, RTVue-100, Optovue, USA) was performed. Endothelium-Descemet membrane (EDM) complexes, corneal buttons were obtained intraoperatively. Morphological (H&E staining) and immunohistochemical (primary antibodies to pancytokeratin, vimentin, fibronectin) studies were performed at the light microscope level (Leica DM-2500, Leica Application Suite V4.8, Leica Microsystems, Switzerland). RESULTS: A direct correlation is found between the results of DM analysis in vivo with OCT and ex vivo with light microscopy. DM thickness (AS-OCT) was significantly greater in FECD (23.0 [19.0; 27.0] µm), than in BK (13.0 [12.0; 14.0] µm). Morphological study of EDM and corneal buttons showed similar difference in DM thickness: 17.9 [16.1; 20.0] µm in FECD and 11.9 [11.3; 13.0] µm in BK. Irregular optical density of stroma is a feature of edema and local fibrosis. In FECD and BK pancytokeratin is expressed in epithelial and endothelial cells, vimentin - in keratocytes, macrophages and vascular endothelium, fibronectin - in DM. In FECD, vimentin is expressed in endothelial cells. CONCLUSION: FECD and BK are associated with different DM' and endothelium' abnormalities, which lead to similar changes of stroma and epithelium. AS-OCT is a useful method of FECD and BK in vivo diagnostics and the selection of treatment option.

Disparities in Visual Acuity Outcomes after Endothelial Keratoplasty: An Intelligent Research in Sight Registry Analysis.

PURPOSE: To assess risk factors for lack of vision improvement after endothelial keratoplasty (EK). DESIGN: Retrospective cohort study. PARTICIPANTS: Patients aged 18 years and older in the Intelligent Research in Sight (IRIS®) Registry who underwent EK surgery in the United States between 2013 and 2018. METHODS: Change in visual acuity (VA) relative to baseline were determined at 6 months and 1 year. A multivariable population-average marginal model estimated using generalized estimating equations adjusting for sociodemographic factors, baseline vision, surgical indication, ocular comorbidities, and postoperative complications was used to identify factors associated with worse VA outcomes. MAIN OUTCOME MEASURES: Visual acuity and lack of VA improvement at 1 year compared with preoperative status. RESULTS: A total of 30 600 EK procedures (N = 25 666 unique patients) were included in the analysis. Overall, VA improved from median logarithm of the minimum angle of resolution (logMAR) 0.54 (Snellen 20/69) (interquartile range [IQR] ± 0.70) preoperatively to median logMAR 0.40 (20/50) (IQR ± 0.36) at 6 months and median logMAR 0.30 (20/40) (IQR ± 0.36) at 1 year postoperatively. A total of 30.3% of the overall cohort, 29.8% of Fuchs' endothelial corneal dystrophy (FECD) subgroup, and 27.4% of the bullous keratopathy (BK) subgroup did not show visual improvement at 1 year postoperatively. In the FECD subgroup, older age (risk ratio [RR], 1.05 per 5-year increase, 95% confidence interval [CI], 1.03-1.07) and female sex (RR, 1.10, 95% CI, 1.04-1.16) were associated with VA worse than or equal to baseline at 1 year postoperatively. In both FECD and BK subgroups, eyes with higher baseline logMAR VA (per 0.1 unit increase in logMAR) were more likely to have visual improvement postoperatively (FECD: RR, 0.82, 95% CI, 0.81-0.84; BK: RR, 0.91, 95% CI, 0.91-0.92), whereas postoperative rebubbling (FECD: RR, 1.10, 95% CI, 1.02-1.19; BK: RR, 1.31, 95% CI, 1.17-1.48) and repeat keratoplasties (FECD: RR, 1.41, 95% CI, 1.32-1.52; BK: RR, 1.42, 95% CI, 1.28-1.57) were associated with higher risk of no VA improvement. CONCLUSIONS: In this large national cohort, postoperative rebubblings and repeat keratoplasties were identified as independent factors associated with worse VA outcomes after EK for both FECD and BK subgroups. Older age and female gender were associated with worse VA outcomes after EK in the FECD subgroup.