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Purpose: To determine predictive factors of higher levels of best-corrected visual acuity (BCVA) in the long-term after primary Descemet's membrane endothelial keratoplasty (DMEK)., Methods: Retrospective, single-surgeon case series of 129 successful primary DMEK eyes without graft failure and with a minimum postoperative follow-up of 12 months. Mixed effect model for repeated measurements (MMRM) analysis was performed to determine recipient, donor, surgical and postoperative factors associated with BCVA ≤ 0.10 logMAR (≥ 20/25 Snellen)., Results: After primary DMEK, there was a statistically significant improvement in BCVA with a global reduction in logMAR BCVA (p < 0.00001). There was also a global tendency towards increasing proportion of eyes with BCVA ≤ 0.10 logMAR at all time points (p < 0.00001), from 1.6% before DMEK to 64.4% in eyes with more than 5 years of F-U. Absence of retinal disease was associated with a decrease of 0.10 logMAR in postoperative BCVA after primary DMEK, maintaining constant the rest of variables (p < 0.001). The variables age (OR 0.960), postoperative time (OR 1.083), preoperative BCVA ≥ 0.375 logMAR (OR 0.162) and indication for DMEK (OR 5.412) were included in the predictive MMRM model of BCVA ≤ 0.10 logMAR., Conclusion: Primary DMEK is associated with statistically and clinically significant improvement in BCVA that occur early in the postoperative period and are continuous over time. Eyes with retinal comorbidities have increased risk of worse postoperative BCVA after DMEK. Younger recipient age, Fuchs' dystrophy eyes and eyes with better preoperative BCVA are more likely to achieve postoperative BCVA ≤ 0.10 logMAR., Competing Interests: Declarations Conflict of interest The authors declare no conflict of interests. Research involving human participants This retrospective chart review study involving human participants was in accordance with the ethical standards of the institutional and national research committee and with the 1964 Helsinki Declaration and its later amendments or comparable ethical standards. This study was approved by an institutional review board (IRB)—Comisión de Ética e Investigación Médica del Instituto de Microcirugía Ocular—CEIm, study COD IMO 210324-174., (© 2024. The Author(s), under exclusive licence to Springer Nature B.V.)

Purpose: The purpose of this study was to investigate the differences in guttae ultramorphology and their relation to visual function in eyes with Fuchs endothelial corneal dystrophy (FECD)., Methods: Thirty FECD eyes without ocular comorbidities were included. Visual functional parameters (best-corrected visual acuity with high-contrast and low-contrast letters and contrast sensitivity/LogCS) and corneal morphology measured with Scheimpflug tomography (Pentacam) were assessed. The surgically removed Descemet membranes were examined by light and transmission electron microscopy., Results: Preoperative mean best-corrected visual acuity (logarithm of the minimum angle of resolution) was 0.52 ± 0.18, LogCS 0.96 ± 0.21 and central corneal thickness 640 ± 55 μm. All eyes had signs of subclinical corneal edema in Scheimpflug tomography; clinically visible corneal edema was present in 40% of eyes. Histological findings included a posterior fibrillar zone (PFZ) in 10 specimens (33%) and abnormal collagen depositions in Descemet membranes in 14 specimens (47%). Guttae buried within the PFZ were present only in eyes with clinically visible edema (n = 4, 13%). There was no difference in visual function results and tomography parameters between eyes with and without PFZ or between protruding guttae and guttae embedded in a PFZ, respectively., Conclusions: Guttae morphology and density were not correlated with visual functional parameters. Guttae buried in a PFZ occurred only in eyes with clinically manifest edema, and thereby, they are an ultramorphological sign for advanced FECD. Subclinical edema was present in all eyes and might be more relevant for quality of vision than guttae ultramorphology., Competing Interests: The authors have no funding or conflicts of interest to disclose., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Fuchs endothelial corneal dystrophy (FECD) is a genetic and age-associated corneal disease characterized by an accelerated loss of corneal endothelial cells and an increased subendothelial deposition of extracellular matrix (ECM). Clinically, advanced disease leads to corneal edema with subsequent reduction in visual acuity. In the majority of patients with advanced FECD, a fibrillar layer (FL) appears on the posterior corneal surface. This FL is mostly localized in the inferotemporal corneal quadrant, marks areas with significantly reduced endothelial cell density and increased corneal thickness in the sense of edema and can be visualized and measured using Scheimpflug backscatter analysis due to increased backscatter. FECD is currently the most common indication for corneal transplantation worldwide, usually in the form of Descemet membrane endothelial keratoplasty (DMEK). New treatment approaches include variations of DMEK surgery such as hemi- or quarter DMEK with individualized and smaller grafts or Descemet membrane stripping only (DSO). In the future, clinical imaging of the FL as a particularly affected endothelial area could be important for FECD progression assessment and planning of surgical interventions. This article provides an overview of the current state of research on the clinical aspects, pathogenesis, fibrillar layer and individualized treatment of FECD., (© 2024. The Author(s), under exclusive licence to Springer Medizin Verlag GmbH, ein Teil von Springer Nature.)

Purpose: To determine whether the clinical and paraclinical course of Fuchs endothelial corneal dystrophy (FECD) over 1 year is related to the extent of triplet repetition in the transcription factor 4 (TCF4) gene., Methods: A prospective study with a 1-year follow-up was conducted. A total of 104 patients (160 eyes) with FECD and an equivalent number of age- and sex-matched control subjects without FECD were included. At inclusion, the corneas were graded using the modified Krachmer grade (KG) and patients were genotyped for the number of trinucleotide repeats (TNRs) in the TCF4 gene by the short tandem repeat assay. Visual acuity, Scheimpflug tomographic features, and the Visual Function and Corneal Health Status using a visual disability instrument were measured on 2 visits at 1-year intervals., Results: KGs ranged from 1 to 6, and 46% of eyes had grades 1 to 4. 71% of the patients harbored TNR expansion (>40) versus 13% in control subjects ( P < 0.001). Severity at inclusion was higher in the presence of TNR expansion when considering eyes independently (mean grade ±SD, 4.08 ± 1.42) without TNR expansion and 4.66 ± 1.27 with TNR expansion ( P = 0.024). In 1 year, the ETDRS score significantly decreased by -2.97 (95% confidence interval -4.69 to -1.26, P = 0.001) and the ETDRS score with glare by -4.25 (95% confidence interval -6.22 to -2.27, P < 10 -5 ). There was no relationship between the rate of decline and TNR expansion or KG. Central corneal thickness and Visual Function and Corneal Health Status scores did not significantly vary., Conclusions: It is possible to measure a subtle progression of FECD over a period as short as 1 year. We did not find a relationship between the presence of TNR expansion and the speed of deterioration over 1 year. This work should facilitate the design of future clinical trials on FECD., Competing Interests: Conflicts of interest statement: P. Gain, N. Koizumi, N. Okumura, and G. Thuret were shown using the ICMJE disclosures form. The remaining authors have no funding or conflicts of interest to disclose., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Competing Interests: Financial disclosures/conflicts of interest: None reported.

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., (© 2024 The Authors. Acta Ophthalmologica published by John Wiley & Sons Ltd on behalf of Acta Ophthalmologica Scandinavica Foundation.)

Purpose: The aim of this study was to compare visual function, with a focus on contrast sensitivity, between patients with Fuchs endothelial corneal dystrophy (FECD) with and without subclinical corneal edema., Methods: In this cross-sectional, observational, single-center study, 46 pseudophakic eyes of 31 patients with FECD were divided into 2 groups depending on the presence of subclinical corneal edema. All eyes presented with a Krachmer grade of 5 and no clinical corneal edema. The criteria for subclinical corneal edema were loss of regular isopachs, displacement of the thinnest point, and focal posterior surface depression in Scheimpflug tomography. If more than 1 criterion was present, subclinical corneal edema was diagnosed. The corrected distance visual acuity, contrast sensitivity (Pelli-Robson chart and CSV-1000 test with optional glare), and straylight were measured. The differences between both groups were analyzed using clustered Wilcoxon rank-sum tests., Results: The corrected distance visual acuity and the contrast sensitivity, measured with a Pelli-Robson chart, were significantly inferior in eyes with subclinical corneal edema compared with eyes without subclinical edema ( P < 0.05). At all spatial frequencies, eyes with subclinical edema demonstrated lower contrast sensitivity with a statistically significantly reduction in total contrast sensitivity when tested with ( P = 0.005) and without ( P = 0.002) glare. The straylight did not significantly differ between both groups ( P > 0.05)., Conclusions: The corrected distance visual acuity and contrast sensitivity were significantly reduced in FECD eyes with subclinical corneal edema compared with those with no subclinical edema. This decrease in visual quality may be considered when evaluating the need for surgical intervention at earlier stages of FECD., Competing Interests: R. Khoramnia reports grants, personal fees, and nonfinancial support from Johnson & Johnson Vision, Alcon Laboratories, Hoya Corp, Kowa Co, Ltd, Oculentis GmbH/Teleon, Physiol S.A., Sifi Medtech Srl, and Rayner Intraocular Lenses Ltd; grants and personal fees from Oculus Optikgeräte GmbH, Carl Zeiss Meditec AG, and Ophtec BV; and grants from Acu Focus Inc., outside the submitted work. G. U. Auffarth reports lecture fees and research grants from Johnson & Johnson Vision, Alcon Laboratories, Carl Zeiss Meditec AG, Hoya Corp, Kowa Co, Ltd, Oculentis GmbH/Teleon, Physiol S.A., Rayner Intraocular Lenses Ltd, Oculus Optikgeräte GmbH, Ophtec BV, Santen, Sifi Medtech Srl, Acu Focus Inc, Novartis, Ursapharm, and Biotech; nonfinancial support from Rheacell, Contamac, Cristalens, Croma, EyeYon, Hanita, and VSY, outside the submitted work. V. A. Augustin reports research grants from Kowa Co., outside the submitted work. The remaining authors have no funding or conflicts of interest to disclose., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Purpose: The purpose of this study was to describe a method to achieve a high success rate for nanothin (NT, ≤50 μm) Descemet stripping automated endothelial keratoplasty (DSAEK) graft preparation using anterior chamber pressurizer (ACP) with a modified setting and evaluate its postoperative efficacy., Methods: A prospective cohort (study group) of 24 patients with corneal endothelial dysfunction was consecutively enrolled and received DSAEK grafts using the modified ACP method from December 2021 to May 2022. The control group included 24 historical patients who received DSAEK grafts using conventional ACP procedure. Central graft thickness (CGT), graft regularity (3-mm and 5-mm diameter zones), best spectacle-corrected visual acuity, and endothelial cell density (ECD) were compared between 2 groups., Results: A 100% ultrathin (UT, ≤100 μm) DSAEK rate and 62.5% NT-DSAEK rate was achieved at 3 months postsurgery in the study group, with a 51.3 ± 14.8 μm CGT, while a 70.8% UT-DSAEK rate and 4.2% NT-DSAEK rate was achieved in the control group, with an 89.0 ± 15.4 μm CGT ( P <0.001). At 3-month postoperative follow-up, the regularity of graft thickness was significantly better in the study group (central-to-peripheral thickness difference: P = 0.044 and 0.014 for 3-mm and 5-mm diameter zones, respectively, graft thickness uniformity: P <0.001 and 0.012, respectively). There was no statistical difference in the best spectacle-corrected visual acuity ( P = 0.170) or ECD ( P = 0.833) between 2 groups at 3-month postoperative follow-up., Conclusions: DSAEK grafts harvested using modified ACP method were thinner and more regular compared with the conventional ACP method., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Purpose: Descemet stripping only (DSO) is a promising surgical option for select patients with Fuchs endothelial dystrophy (FED). There is growing support for the use of topical Rho-associated protein kinase inhibitors (ROCKi) to optimize DSO outcomes. However, in many settings, ROCKi are either unavailable or not approved to treat corneal diseases. This study sought to characterize patient outcomes after DSO in the absence of ROCKi and potentially broaden the settings where DSO can be offered to patients., Methods: Single-center retrospective case series of 15 eyes/11 patients (66 years; 52-74) that underwent DSO, alone or combined with cataract surgery, by one surgeon between August 2020 and January 2023. Patients included in analyses had FED with central guttae, no clinical evidence of corneal edema, and a clinically healthy peripheral corneal endothelium., Results: Mean follow-up time was 14 months (2-34). Fourteen of 15 eyes achieved corneal clearance (93.3%). Mean time to clearance was 8.5 weeks (3-23). Eleven eyes (73%) achieved corrected distance visual acuity of ≤0.2 with a significant postoperative improvement at 4 to 8 months ( P < 0.05) and sustained improvements at >12 months. No significant astigmatism was introduced by the procedure. Two eyes developed cystoid macular edema postoperatively. A trend toward earlier clearance was observed in the <65 years old group., Conclusions: Despite a longer time to corneal clearance in this cohort compared with the few studies using ROCKi, the overall success rate and visual outcomes for the patients in our cohort supports the use of DSO in settings where ROCKi are not readily available., Competing Interests: The authors have no funding or conflicts of interest to disclose., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Purpose: Descemet stripping only (DSO) is a relatively novel treatment for Fuchs endothelial corneal dystrophy (FECD). In this procedure, a central area of Descemet membrane and endothelium is removed without the insertion of donor tissue. Evaluation of long-term outcomes (≥5 years) after DSO is imperative to establish the validity of this procedure and to determine its role in the management of Fuchs endothelial dystrophy. Published outcomes are limited but promising. This study evaluates the 5- and 6-year outcomes of patients who had DSO at a single institution., Methods: This is a retrospective chart review of patients with FECD who underwent DSO in 2016 and 2017., Results: Eleven patients and 13 eyes met the criteria. Twelve of 13 eyes achieved corneal clearance. Two eyes had corneal decompensation requiring subsequent endothelial keratoplasty (EK). Of the 10 eyes that maintained clear corneas, 9 had a best-corrected visual acuity (BCVA) of at least 20/30 (mean logarithm of the minimim angle of resolution [logMAR] visual acuity [VA] 0.18 ± 0.16) at 5 years post-operatively (POY5). At 6 years, 7 of 8 eyes had a VA better than 20/40 (mean logMAR VA 0.17 ± 0.04). One patient had decreased VA due to progression of macular degeneration. Patients who required EK achieved good vision and corneal clearance., Conclusions: This is the largest series of patients with long-term follow-up after DSO. Ten of the 13 eyes (77%) responded and maintained clear central corneas for at least 5 years. Patients with failed DSO can achieve corneal clearance and good vision with subsequent EK. These patient outcomes support the role of DSO in the management of patients with FECD., Competing Interests: F. E. Hakim and A. K. Nagra have no conflicts of interest to disclose. D. K. Dhaliwal has received grant support from Kowa and is a consultant for Trefoil and Aurion Biotherapeutics. No other relevant financial interests to disclose., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

A 62-year-old woman with a history of moderate myopia, long-standing open-angle glaucoma (OAG), and Fuchs dystrophy in both eyes was referred for consultative care. She had prior trabeculectomy in 1984 and 1992 in the left and right eyes, respectively. She is 3 months post-Descemet-stripping endothelial keratoplasty (DSEK) in the left eye, now referred with uncontrolled intraocular pressure (IOP) despite maximum tolerated medical therapy. Current medical therapy for IOP consists of acetazolamide 250 mg by mouth 2 times a day, brimonidine 2 times a day in the left eye, dorzolamide 2 times a day in the left eye, and timolol 2 times a day in the left eye. The patient has a history of presumed steroid response; however, her corneal surgeon has requested that the steroid be continued for the next several months because of the recent DSEK. The IOP in the left eye has ranged from the mid-20s to mid-30s since DSEK. The right eye has consistently had pressure in the low teens and below for many years without topical antihypertensive medications. Examination revealed stable visual acuity at 20/30 and 20/40 in the right and left eyes, respectively, IOP was 12 mm Hg in the right eye and 25 mm Hg in the left eye by Goldman applanation, irregular but reactive pupils without afferent defect, and full confrontational visual fields. Slitlamp examination showed superior low avascular bleb, moderate-to-severe guttae, and posterior chamber IOL in the right eye. The left eye showed superior low diffuse bleb, clear DSEK graft, quiet chamber, superonasal iridectomy, and posterior chamber IOL with an open posterior capsule. The conjunctiva was moderately scarred but a repeat trabeculectomy or Xen Gel stent (Abbvie) appeared possible. The angles were wide open in each eye. Fundus examination was normal aside from myopic, anomalous-appearing nerves with an approximate cup-to-disc ratio of 0.90 in both eyes. Humphrey visual field showed nonspecific changes on the right and moderate nasal defect on the left eye, stable to previous examinations dating back to 2018 (Figure 1JOURNAL/jcrs/04.03/02158034-202407000-00018/figure1/v/2024-07-10T174240Z/r/image-tiff and Figure 2JOURNAL/jcrs/04.03/02158034-202407000-00018/figure2/v/2024-07-10T174240Z/r/image-tiff). Optical coherence tomography (OCT) of the retinal nerve fiber layer (RNFL) revealed moderated thinning in both eyes that was also stable to prior examinations (Figure 3JOURNAL/jcrs/04.03/02158034-202407000-00018/figure3/v/2024-07-10T174240Z/r/image-tiff). Her axial length measured 25.23 and 26.34 mm in the right and left eyes, respectively. Central corneal thickness was 553 μm in the right eye and 563 μm in the left eye before her DSEK procedure. What would be your approach to management of this patient's left eye, addressing the following: Rationale for your procedure of choice? Would you over-rule the corneal surgeon and stop the steroid in an attempt to obviate the need for glaucoma surgery? Does the age of onset of glaucoma affect your surgical decision making? Note that patient age at the time of trabeculectomy was 22 years. Are some procedures better suited for patients after DSEK surgery?, (Copyright © 2024 Published by Wolters Kluwer on behalf of ASCRS and ESCRS.)

Purpose: The aim of this study was to investigate mediators of visual acuity in ultrathin Descemet stripping automated endothelial keratoplasty (UT-DSAEK) compared with Descemet membrane endothelial keratoplasty (DMEK)., Methods: This was a prespecified secondary analysis of the Descemet Endothelial Thickness Comparison Trial, a prospective, randomized controlled trial comparing UT-DSAEK with DMEK. Subjects with Fuchs endothelial dystrophy or pseudophakic bullous keratopathy presenting to 2 academic centers were enrolled and randomized to either UT-DSAEK (n = 25 eyes) or DMEK (n = 25 eyes). Higher order aberrations (HOAs) and corneal densitometry were measured with Pentacam Scheimpflug imaging at 3, 6, 12, and 24 months., Results: The posterior corneal surface at the 6.0-mm optical zone had significantly less total HOAs ( P <0.001) in the DMEK group compared with UT-DSAEK at 24 months. Anterior and posterior corneal densitometry improved from baseline to 24 months for both UT-DSAEK and DMEK, but there was no significant difference between the 2 groups. Corneal densitometry and posterior HOAs were both associated with best-corrected visual acuity ( P <0.05). DMEK had 1.3 logarithm of the minimum angle of resolution better visual acuity compared with UT-DSAEK at 24 months. Approximately 64% of this effect was mediated through posterior HOAs, whereas none was mediated through anterior HOAs or densitometry., Conclusions: Decreased posterior HOAs mediate better visual acuity and account for improved vision after DMEK compared with UT-DSAEK. Corneal light scatter as measured by densitometry is similar between UT-DSAEK and DMEK, indicating that the increased thickness and stromal-stromal interface in UT-DSAEK do not significantly affect visual acuity., Competing Interests: The authors have no funding or conflicts of interest to disclose., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Purpose: The Supine Positioning for Descemet Membrane Endothelial Keratoplasty Attachment (SUPER-DMEK) trial assessed the efficacy of prolonged supine head positioning on graft attachment., Design: Randomized controlled trial., Methods: Participants with Fuchs' dystrophy were randomized to 5 days of supine head positioning (intervention) or to 1 day (control). Participants, surgeons, and investigators were masked until the day after surgery. Adherence to the allocated intervention was monitored using a head sensor. Main outcome measures were area and volume of graft detachment (coprimary end points) 2 weeks after surgery quantified using a validated neural network for image segmentation on anterior segment optical coherence tomography images, and repeat air injection (rebubbling), subjective visual function, and adverse events (secondary end points)., Results: A total of 86 participants received the allocated intervention (35 eyes intervention and 51 eyes control). In the intention-to-treat analysis, the mean area of graft detachment was 28.6% in the intervention arm and 27.5% in the control arm (adjusted between-arm difference, 1.3; 95% CI, -8.7 to 11.4; P = .80). Results for volume of detachment and as-treated analyses based on head position sensor data indicated no potentially clinically relevant effect of prolonged supine positioning on graft attachment. Results were not compatible with a relevant treatment effect on rebubbling or subjective visual function. Adverse events, most commonly back pain, were more common and more severe with the intervention., Conclusions: In this randomized controlled trial, graft attachment was not improved with prolonged supine head positioning. Prolonged supine positioning frequently caused back pain. Prolonged supine positioning after Descemet membrane endothelial keratoplasty for Fuchs' dystrophy may not be needed in routine practice., (Copyright © 2023 The Author(s). Published by Elsevier Inc. All rights reserved.)

Purpose: The purpose of this study was to investigate the associations between visual function and severity grading, corneal scatter, or higher-order aberrations (HOAs) in patients with Fuchs endothelial corneal dystrophy (FECD)., Methods: This observational case series study included 49 eyes of 27 patients with FECD and 10 eyes of 10 healthy individuals. We evaluated corrected distance visual acuity (CDVA) using Landolt-C and Early Treatment Diabetic Retinopathy Study charts and contrast sensitivity using the CSV-1000E chart and CSV-1000RN letter chart. We analyzed the associations between visual function and explanatory variables, including age, modified Krachmer grade, central corneal thickness (CCT), anterior segment optical coherence tomography (AS-OCT)-based grade, HOAs, intraocular straylight, and corneal densitometry. We additionally conducted receiver operating characteristic (ROC) analysis to identify the corneal densitometry thresholds for decreased visual function., Results: There were significant associations between visual function and the modified Krachmer grade, CCT, AS-OCT-based grade, HOAs, intraocular straylight, and corneal densitometry. A modified Krachmer grade ≥ 3 was identified as a threshold for decreased visual function. Multivariate analysis showed that corneal densitometry was significantly associated with all visual function parameters, and HOAs were significantly associated with CDVA but not with contrast sensitivity. ROC analysis revealed that corneal densitometry of the posterior layer at 0 to 2 mm ≥ 10 grayscale units (GSU), was identified as a threshold for decreased visual function., Conclusions: HOAs, forward and backward light scatter affected visual function, with backward light scatter being the most influential. In patients with FECD, modified Krachmer grade ≥ 3 and corneal densitometry ≥ 10 GSU were thresholds for visual disturbance.

Purpose: The aim of this study was to assess the long-term clinical outcome, complications, and graft survival of bilateral Descemet membrane endothelial keratoplasty (DMEK) in patients with Fuchs endothelial corneal dystrophy., Methods: This was a retrospective cohort study of 181 patients (362 eyes) with sequential bilateral DMEK for Fuchs endothelial corneal dystrophy. Clinical outcomes were assessed up to 5 years postoperatively. Outcome measures were best-corrected visual acuity, pachymetry, endothelial cell density, graft survival, and complication rates., Results: Contralateral DMEK was performed on average 15 ± 11 months (range: 2-60 months) after the first eye. From 1 until 5 years after DMEK, best-corrected visual acuity, pachymetry, endothelial cell density, and graft survival did not differ between the first and second eyes (all P > 0.05). Graft detachment occurred in 67 eyes (19% [18% first eyes, 19% second eyes], 6% bilateral), graft rejection in 9 eyes (3% [3% first eyes, 2% second eyes], 1% bilateral), glaucoma in 25 eyes (7% [8% first eyes, 6% second eyes], 2% bilateral), and graft failure in 22 eyes (6% [4% first eye, 8% second eye], 2% bilateral). All differences were not significant (all P > 0.05). Five-year graft survival rates were comparable for first and second eyes (0.95 and 0.92, respectively; P = 0.15)., Conclusions: Clinical outcomes after bilateral DMEK are similar in both eyes and sustainable in the longer term. Within the first 5 years, the same complication may rarely occur in the contralateral eye., Competing Interests: Lamis Baydoun is a consultant for DORC International and a speaker for Heidelberg Engineering. The other authors have no potential conflict of interest to disclose., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Objective: This study aimed to evaluate the long-term graft survivability of locally prestripped versus imported prestripped Descemet membrane endothelial keratoplasty (DMEK) grafts in Edmonton., Design: Prospective cohort study of patients who underwent DMEK surgery between January 1, 2020, and December 31, 2020., Participants: All patients receiving a DMEK transplant during the study period in Edmonton., Methods: Two local technicians were trained to prestrip DMEK grafts in Edmonton. When available, local tissue was prestripped for DMEK surgery; otherwise, prestripped DMEK grafts were imported from an accredited American eye bank. Patient characteristics and DMEK graft characteristics and DMEK survivability were evaluated and compared between the 2 groups., Results: Thirty-two locally prestripped DMEK grafts and 35 imported prestripped DMEK grafts were used during the study period. Donor cornea characteristics and patient characteristics were similar between the 2 groups. Best-corrected visual acuity improved up to 6 months postoperatively and was 0.2 logMAR in the locally prestripped DMEK group and 0.2 logMAR in the imported DMEK group (p = 0.56). Rebubble rates were 25% in the locally prestripped DMEK group and 19% in the imported DMEK group (p = 0.43). There was 1 primary graft failure in each group (p = 0.93). Endothelial cell density decreased by 37% in the locally prestripped DMEK group and by 33% in the imported DMEK group 2 years after transplantation., Conclusions: The long-term survivability of locally prepared DMEK grafts is comparable with that of DMEK grafts imported from American eye banks., (Copyright © 2023 Canadian Ophthalmological Society. Published by Elsevier Inc. All rights reserved.)

Aims: To compare best-corrected visual acuity (BCVA), contrast sensitivity and endothelial cell density (ECD) after ultrathin Descemet's stripping automated endothelial keratoplasty (UT-DSAEK) and Descemet's membrane endothelial keratoplasty (DMEK)., Methods: A randomised, single-blinded, single-centre design was used. 72 patients with Fuchs' endothelial dystrophy and cataract were randomised to UT-DSAEK or DMEK combined with phacoemulsification and lens implantation. 27 patients with cataract were included in a control group and treated with phacoemulsification and lens implantation. The primary outcome was BCVA at 12 months., Results: Compared with UT-DSAEK, DMEK resulted in better BCVA with mean differences of 6.1 early treatment diabetic retinopathy study (ETDRS) (p=0.001) after 3 months, 7.4 ETDRS (p<0.001) after 6 months and 5.7 ETDRS (p<0.001) after 12 months. The control group obtained significantly better BCVA with a mean difference of 5.2 ETDRS (p<0.001) compared with DMEK 12 months postoperatively. Compared with UT-DSAEK, contrast sensitivity was significantly better 3 months after DMEK with a mean difference of 0.10 LogCS (p=0.03). However, our study found no effect after 12 months (p=0.08). ECD was significantly lower after UT-DSAEK compared with DMEK with mean differences of 332 cells/mm 2 (p<0.01) after 3 months, 296 cells/mm 2 (p<0.01) after 6 months and 227 cells/mm 2 (p=0.03) after 12 months., Conclusions: Compared with UT-DSAEK, DMEK resulted in better BCVA 3, 6 and 12 months postoperatively. Twelve months postoperatively, DMEK had a higher ECD than UT-DSAEK; however, no difference in contrast sensitivity was found., Trial Registration Number: NCT04417959., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. No commercial re-use. See rights and permissions. Published by BMJ.)

Purpose: To report a challenging Descemet Membrane Endothelial Keratoplasty (DMEK) case, complicated by intraoperative aqueous misdirection and spontaneous anterior chamber fibrin reaction., Methods: A 70-year-old female affected by corneal edema due to Fuchs endothelial dystrophy underwent a triple procedure (cataract extraction - IOL implantation - DMEK surgery) in her left eye. This report illustrates the management of the intraoperative complications of aqueous misdirection syndrome and anterior chamber fibrin reaction., Results: Despite the optimal management of the posterior pressure and the thorough removal of the fibrinous reaction during the case, the DMEK graft was not completely unfolded and centred at the end of the surgical procedure. Nonetheless, the patient showed good long-term anatomical and functional recovery: at the last follow-up (2 years after surgery), central corneal thickness was 526 µm with a best corrected visual acuity of 20/25 and an endothelial cell density of 1112 cell/mm 2 ., Conclusion: Early recognition and prompt management of intraoperative aqueous misdirection syndrome and anterior chamber fibrin reaction during DMEK surgery is essential to ensure good functional and anatomical outcomes., Competing Interests: Declaration of conflicting interestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

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: Although the popularity of Descemet membrane endothelial keratoplasty (DMEK) is increased, there is still few clinical studies in Korea. In this study, we aimed to report the initial clinical outcomes of DMEK in patients followed up for more than 6 months., Methods: A total of 96 eyes that underwent DMEK by a single surgeon for Fuchs endothelial corneal dystrophy, pseudophakic bullous keratopathy, or other indications were evaluated for best-corrected visual acuity (BCVA), endothelial cell density (ECD), central corneal thickness (CCT), postoperative complications, and graft survival., Results: The postoperative BCVA significantly increased compared to the preoperative BCVA by 59.4% (1.00 ± 0.77 logarithm of the minimum angle of resolution vs. 0.67 ± 0.76 logarithm of the minimum angle of resolution, p &lt; 0.001). The average preoperative ECD was 754 ± 382 cells/mm2, increasing to 1,333 ± 562 cells/mm2 at 3 months (76.8%, p &lt; 0.001), 1,334 ± 632 cells/mm2 at 6 months (76.9%, p &lt; 0.001), 1,121 ± 474 cells/mm2 at 12 months (48.7%, p = 0.024), and 972 ± 458 cells/mm2 at 24 months postoperatively (28.9%, p = 0.445). Compared to 3 months, the ECD declined by 15.9% at 12 months (p = 0.009) and 27.1% at 24 months postoperatively (p = 0.158). The average CCT was 675 ± 113 μm preoperatively, decreasing to 581 ± 102, 574 ± 101, and 594 ± 94 μm at 6, 12, and 24 months after DMEK, respectively (p &lt; 0.001 between all follow-up time points). Allograft rejection was detected in three (3.1%) and 14 eyes (14.6%) underwent retransplantation at an average of 10.1 ± 8.4 months after DMEK., Conclusions: DMEK is promising for maintaining corneal clarity, low postoperative complication rates, and stable graft longevity.

Purpose: The aim of this study was to compare the long-term outcome of Descemet membrane endothelial keratoplasty (DMEK) in patients with Fuchs endothelial corneal dystrophy (FECD) and pseudophakic bullous keratopathy (PBK)., Methods: Records of consecutive DMEK surgeries performed between 2015 and 2016 at the Department of Ophthalmology, Cologne, Germany, were retrospectively reviewed from the prospective Cologne DMEK Database. Eyes with either PBK or FECD with a complete 3-year follow-up were enrolled. Main outcome parameters included central corneal thickness (CCT), peripheral corneal thickness (PCT), best spectacle-corrected visual acuity (BSCVA, logarithm of the Minimum Angle of Resolution), and endothelial cell count (ECC) before and after DMEK., Results: Four hundred two eyes from 402 patients were included (FECD n = 371, PBK n = 31). Preoperatively, CCT (FECD: 681.91 ± 146.78 μm; PBK: 932.25 ± 319.84 μm) and PCT (FECD: 732.26 ± 98.22 μm; PBK: 867.54 ± 88.72 μm) were significantly higher in the PBK group (P < 0.01). Three years after DMEK, CCT (FECD: 526.56 ± 27.94 μm; PBK 663.71 ± 132.36 μm) was significantly lower in both groups compared with the preoperative values (P < 0.01), whereas PCT showed no significant difference. PCT increased during the course in the PBK group from month 12 after DMEK (12 mo: 783.73 ± 127.73 μm; 24 mo: 837.50 ± 110.19 μm; 36 mo: 857.79 ± 140.76 μm). The increase in PCT correlated with an accelerated ECC loss starting 12 months after DMEK (P = 0.036). Before DMEK, BSCVA in FECD was significantly higher (P < 0.001) compared with that in PBK. After 3 years, BSCVA improved in FECD and PBK eyes without significant difference (P = 0.239)., Conclusions: Visual acuity after DMEK in PBK and FECD seems to be comparable during the long-term follow-up. Peripheral and central corneal edema seems to recur faster in eyes with PBK than in those with FECD. Therefore, using a donor graft with higher ECC or possibly a larger graft could be a promising approach for PBK patients., Competing Interests: The authors have no funding or conflicts of interest to disclose., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Kynurenine aminotransferases (KAT) are enzymes catalyzing formation of kynurenic acid (KYNA) from kynurenine. KYNA is a Janus-faced molecule of high biological activity. On the one hand KYNA was identified as a UV filter and neuroprotectant with free radical scavenging properties, but on the other hand it may contribute to photodamage of lens proteins resulting in cataract formation. Fuchs endothelial corneal dystrophy (FECD) and keratoconus (KC) are common, vision threatening corneal dystrophies whose etiology is not fully understood. In our previous works, we confirmed the presence of KATs in the human cornea together with GPR35, a receptor for KYNA. This prompted us to investigate the potential changes in the expression of three isoforms: KAT I, KAT II, and KAT III in normal and FECD- and KC-affected corneas. Immunohistochemistry accompanied by gene expression data mining revealed that the levels of neither KAT I, KAT II, nor KAT III are affected in FECD and KC. This constitutes evidence against the involvement of KATs in the pathophysiology of FECD and KC., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Purpose: The purpose of this article was to study the clinical, optical, and morphological correlates of visual function in patients with Fuchs endothelial corneal dystrophy (FECD)., Methods: The case records were analyzed for patients diagnosed with FECD between September 2019 and March 2020. The best-corrected visual acuity (BCVA) was recorded as decimal visual acuity and converted to the logarithm of the minimum angle of resolution units. Contrast sensitivity was measured with the Pelli-Robson contrast sensitivity test. Corneal alterations, including central corneal thickness, depression of the posterior cornea, and corneal densitometry values, were evaluated using Scheimpflug images. Corneal epithelial thickness was measured by spectral-domain optical coherence tomography., Results: A total of 107 eyes of 61 patients (18 male and 43 female) with FECD were retrospectively investigated. The Spearman rank correlation coefficient showed moderate correlation between BCVA and contrast sensitivity (ρ = -0.66, P < 0.001), with some patients maintaining relatively good BCVA but having reduced contrast sensitivity. Logistic regression analysis demonstrated that age, central corneal thickness, depression of the posterior cornea, and epithelial thickening were negatively associated with contrast sensitivity but not with BCVA., Conclusions: Contrast sensitivity is a useful tool for assessing visual dysfunction and should be incorporated into the assessment protocol of patients with FECD. Alterations in the cornea, including central corneal thickness, depression of the posterior cornea, and epithelial thickening, might be objective parameters that can help the clinician in grading the severity of the disease and tracking its progression., Competing Interests: The authors have no funding or conflicts of interest to disclose., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Purpose: To analyze if 6-month endothelial cell density (ECD) affects long-term ECD outcome and graft survival 5 years after Descemet membrane endothelial keratoplasty (DMEK) in eyes with Fuchs endothelial corneal dystrophy (FECD)., Design: Retrospective cohort study., Participants: A total of 585 DMEK eyes were included. The study group was divided into 4 groups based on 6-month ECD quartiles: group 1 (n = 146) with 313 to 1245 cells/mm 2 , group 2 (n = 148) with 1246 to 1610 cells/mm 2 , group 3 (n = 145) with 1611 to 1938 cells/mm 2 , and group 4 (n = 146) with 1939 to 2760 cells/mm 2 . Group 1 was further split into subgroups 1a (n = 36) with 6-month ECD of ≤828 cells/mm 2 , 1b (n = 37) with 829 to 1023 cells/mm 2 , 1c (n = 37) with 1024 to 1140 cells/mm 2 , and 1d (n = 36) 1141 to 1245 cells/mm 2 ., Methods: Descemet membrane endothelial keratoplasty., Main Outcome Measures: Long-term ECD, graft survival, and postoperative complication rates., Results: For group 1, 6-month ECD decreased from 951 (±233) cells/mm 2 (n = 146) to 735 (±216) cells/mm 2 (n = 99) at 5 years postoperatively. Group 1 graft survival probability was 0.95 (95% confidence interval [CI], 0.91-0.99] at 5 years postoperatively, which was lower than for groups 2 to 4 (P = 0.001). Five-year graft survival in subgroup 1a was 0.79 (95% CI, 0.67-0.94), which was lower than in subgroups 1b to 1d (P = 0.001). Preoperative ECD did not influence graft survival (P = 0.400), and higher 6-month ECD values were associated with lower graft failure rates (hazard ratio, 0.994; 95% CI, 0.99-1.00; P = 0.001)., Conclusions: Six-month ECD is associated with DMEK graft survival. High early cell loss after DMEK negatively affects long-term ECD outcome and graft survival. Grafts in the lowest 6-month ECD subgroup (≤828 cells/mm 2 ) are at higher risk of failure within 5 years after DMEK. To ensure sufficiently high 6-month ECD, preoperative graft quality assessment should be optimized, and cellular stress induced to the graft should be minimized. Additionally, developing therapeutic options for the treatment of low postoperative ECD could further improve DMEK graft longevity., (Copyright © 2021 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.)

Purpose: To report evidences that the abnormal endothelium of some Fuchs endothelial corneal dystrophy (FECD) present centripetal radial lines over 360 degrees., Methods: A case report of retroilluminated pictures of 2 patients with FECD and flat mounts of isolated Descemet membranes of 1 patient with FECD and of 1 healthy donor. Interpretation and development of a new pathophysiological theory., Results: The 3 FECD images unequivocally demonstrate the existence of very numerous radial centripetal lines over 360 degrees, in the central 8 to 9 mm of the cornea and ending in the area of maximum guttae concentration. These lines resemble, in a much longer length, the physiological striae that we described in 2012 at the periphery of the endothelium of normal corneas., Conclusions: We suppose that these lines reflect an accelerated migration of a population of pathological endothelial cells that deposit collagen on their path before being slowed down and then blocked in the center, explaining the progressive accumulation of guttae in this area. This new migration theory assumes that FECD behaves as a corneal endothelial stem-cell disease., Competing Interests: The authors have no funding or conflicts of interest to disclose., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Purpose: To compare quality of vision and vision-related quality of life (QOL) in patients undergoing Descemet membrane endothelial keratoplasty (DMEK) or ultrathin Descemet stripping automated endothelial keratoplasty (DSAEK)., Methods: Fifty-four eyes of 54 patients with Fuchs' dystrophy from six corneal clinics in the Netherlands were randomized to DMEK or ultrathin DSAEK and examined preoperatively, and 3, 6 and 12 months postoperatively. Main outcome measures were corneal higher-order aberrations (HOAs), contrast sensitivity, straylight and vision-related QOL., Results: Posterior corneal HOAs decreased after DMEK and increased after ultrathin DSAEK (p ≤ 0.001) 3 months after surgery and correlated positively with best spectacle-corrected visual acuity (12 months: r = 0.29, p = 0.04). Anterior and total corneal HOAs did not differ significantly between both techniques at any time point. Contrast sensitivity was better (p = 0.01), and straylight was lower (p = 0.01) 3 months after DMEK compared with ultrathin DSAEK; 95% confidence interval [CI] of log(cs) 1.10-1.35 versus 95% CI: 0.84 to 1.12, and 95% CI: log(s) 1.18 to 1.43 versus 95% CI: 1.41 to 1.66, respectively. Both were comparable at later time points. Vision-related QOL (scale 0-100) did not differ significantly between both groups at any time point and improved significantly at 3 months (β = 12 [95% CI: 7 to 16]; p < 0.001), and subsequently between 3 and 12 months (β = 5 [95% CI: 0 to 9]; p = 0.06)., Conclusions: Descemet membrane endothelial keratoplasty (DMEK) results in lower posterior corneal HOAs compared with ultrathin DSAEK. Contrast sensitivity and straylight recover faster after DMEK but reach similar levels with both techniques at 1 year. Vision-related QOL improved significantly after surgery, but did not differ between both techniques., (© 2021 The Authors. Acta Ophthalmologica published by John Wiley & Sons Ltd on behalf of Acta Ophthalmologica Scandinavica Foundation.)

Fuchs' endothelial corneal dystrophy (FECD) is a progressive vision impairing disease caused by thickening of Descemet's membrane and gradual degeneration and loss of corneal endothelial cells. The aim of this study was to identify differentially expressed genes between FECD-affected and unaffected corneal endothelium to gain insight into the pathophysiological mechanisms underlying this disease. Microarray gene expression analysis was performed on total RNA from FECD-affected and unaffected corneal endothelium-Descemet's membrane (CE-DM) specimens using the Illumina HumanHT-12 v4.0 expression array. RNA from pools of FECD-affected (n = 3 per pool) and individual unaffected (n = 3) specimens was used for comparison. Altered expression of a sub-set of differentially expressed genes was validated by quantitative reverse transcription-polymerase chain reaction (qRT-PCR) in independent specimens. Bioinformatics analysis was performed using InnateDB to reveal functional relationships among the differentially expressed genes and molecular pathways involved in the disease. A total of 16,513 genes were found expressed in the corneal endothelium of which 142 genes were differentially expressed between FECD-affected and unaffected endothelium (log 2 fold-change ≥1.5, corrected p-value ≤0.05). Most of the genes were up-regulated (126) and a small proportion down-regulated (16) in affected corneal endothelium. Of the twelve genes prioritised for validation, differential expression of 10 genes, including those ranked 57th and 81st by significance validated by qRT-PCR (8 up-regulated and 2 downregulated, corrected p ≤ 0.05), one gene showed a trend for up-regulation in affected endothelium, consistent with the microarray analysis and another was up-regulated in an independent study indicating robustness of the differential expression dataset. Bioinformatic analysis revealed significant over-representation of differentially expressed genes in extracellular matrix reorganisation, cellular remodelling, immune response, and inflammation. Network analysis showed functional inter-relatedness of the majority of the dysregulated genes and revealed known direct functional relationships between 20 of the genes; many of these genes have roles in macrophage differentiation, phagocytosis and inflammation. This is the second report of microarray gene expression analysis in FECD. This study revealed a set of highly dysregulated genes in the corneal endothelium in FECD. More than a third of the dysregulated genes in the disease have been discovered for the first time and thus are novel. The dysregulated genes strongly suggest the presence of phagocytic cells, most likely immune cells, and inflammation in corneal endothelium in the disease. This study provides a molecular framework for delineating the mechanisms underlying these cellular processes in FECD., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Purpose: To study the change in contrast sensitivities in eyes with Fuchs endothelial dystrophy and bullous keratopathy after Descemet membrane endothelial keratoplasty (DMEK)., Methods: In this prospective study, 50 pseudophakic eyes of 50 patients who received DMEK surgery at the Charité-Universitätsmedizin Berlin were included. Visual acuity; contrast sensitivity using OPTEC 6500 at spatial frequencies of 1.5, 3, 6, 12, and 18 cycles/degree in photopic and mesopic light with and without glare; central corneal thickness (CCT); and anterior and posterior corneal aberrations were measured preoperatively and at 3 and 12 months postoperatively., Results: Best-corrected visual acuity (preoperative 0.67 ± 0.46 and after 12 months 0.19 ± 0.16 LogMAR, P < 0.001) and photopic and mesopic contrast sensitivities with and without glare improved significantly, whereas CCT decreased significantly (preoperative 677 ± 114 μm, after 12 months 527 ± 29 μm, P < 0.001). Preoperative CCT correlates significantly with preoperative photopic contrast sensitivity (correlation coefficient -0.462, P = 0.002), and postoperative total anterior aberrations correlates with postoperative photopic contrast sensitivity (correlation coefficient -0.361, P = 0.006)., Conclusions: Photopic and mesopic contrast sensitivities, especially with glare, are impaired in patients with Fuchs endothelial dystrophy and bullous keratopathy. The extent of the corneal thickening seems to mainly influence the contrast sensitivity preoperatively. DMEK surgery improves the contrast sensitivity significantly. However, higher postoperative anterior corneal aberrations limit the postoperative contrast sensitivities., Competing Interests: The authors have no funding or conflicts of interest to disclose., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Purpose: To analyze the effect of anticoagulant therapy (ACT) for systemic diseases on the outcome of Descemet membrane endothelial keratoplasty (DMEK)., Methods: Consecutive eyes with Fuchs endothelial dystrophy that underwent DMEK between August 4, 2011, and July 15, 2016, were retrospectively analyzed. Data were obtained from the Cologne DMEK database at the University of Cologne, Germany. Best spectacle-corrected visual acuity (logMAR), endothelial cell density (at baseline and postoperatively up to 12 months), and rebubbling rates were compared between patients receiving ACT (ACT group) and those with no anticoagulant treatment (NCT group)., Results: In this study, 329 eyes of 329 patients were included (ACT group n = 97, NCT group n = 232; mean age 69.9 ± 9.1 years). Bleeding was more common in the ACT group (P < 0.001). Preoperative best spectacle-corrected visual acuity was 0.59 ± 0.44 and 0.48 ± 0.35 logMAR for the ACT and NCT groups, respectively, which improved to 0.13 ± 0.08 and 0.08 ± 0.16 logMAR, respectively, at 12 months postoperatively. No significant difference in endothelial cell density loss at 12 months was found between the groups (ACT group 36.2% ± 14.7%, NCT group 38.5% ± 15.1%; P = 0.467). Rebubbling rate was 19.6% in the ACT group and 28.9% in the NCT group (P = 0.08)., Conclusions: Although ACT increases the risk for preoperative and intraoperative bleeding in DMEK, there seems to be no negative effect on DMEK outcome. Thus, it is not advisable to stop ACT for DMEK surgery., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2020 Wolters Kluwer Health, Inc. All rights reserved.)

Purpose: To compare visual outcomes, complications, and vision-related quality of life (QoL) after microthin Descemet stripping automated endothelial keratoplasty (MT-DSAEK) versus Descemet membrane endothelial keratoplasty (DMEK) for the management of corneal endothelial dysfunction in Fuchs dystrophy., Methods: This is a prospective, double-blinded randomized controlled clinical trial. Patients with visually significant endothelial decompensation from Fuchs dystrophy were prospectively randomized to receive MT-DSAEK or DMEK surgery. The primary outcome was best spectacle-corrected visual acuity (BSCVA) at 12 months. Secondary outcomes included refraction, keratometry, endothelial cell count, complications, and vision-related QoL at 6 and 12 months postoperatively., Results: A total of 56 eyes of 56 patients were enrolled, 28 in each group. Postoperatively, LogMAR mean BSCVA in the MT-DSAEK group was 0.17 ± 0.08 and 0.11 ± 0.09 at 6 and 12 months compared with 0.09 ± 0.13 and 0.04 ± 0.13 after DMEK (P = 0.03, P = 0.002 respectively) with the DMEK cohort achieving 3.5 logarithm of the minimum angle of resolution letters better BSCVA at 1 year compared with MT-DSAEK. Complication rates were similar with 3.5% rebubbling rate in both groups, 1 primary graft failure in DMEK and a single endothelial rejection in the MT-DSAEK arm. Vision-related QoL was comparable at 6 and 12 months postoperatively, and no eyes demonstrated loss of vision from preoperative BSCVA., Conclusions: DMEK surgery resulted in significantly better BSCVA at 1, 3, 6, and 12 months postoperatively compared with MT-DSAEK. Patient satisfaction was similar with no differences reported in vision-related QoL scores, as was the complications profile between groups. Thus, our results favor DMEK as the better choice procedure for eyes with Fuchs-related corneal decompensation without ocular comorbidities., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2020 Wolters Kluwer Health, Inc. All rights reserved.)

Purpose: To evaluate off-label use of netarsudil 0.02% for treatment of corneal edema associated with Fuchs dystrophy., Design: Prospective, randomized clinical trial., Methods: Twenty-nine subjects with symptomatic Fuchs dystrophy were enrolled and randomized to use netarsudil or placebo eye drops once daily for 3 months. The primary outcomes were the change in central corneal thickness between baseline and 1 month and between baseline and 3 months. Secondary outcomes included change in scotopic corrected distance visual acuity (CDVA) at 3 months and change in scores on a visual disability questionnaire validated for use with Fuchs dystrophy., Results: Compared with use of placebo, use of netarsudil produced significant reduction in central corneal thickness at 1 month (mean difference, -20 µm; 95% confidence interval, -32 to -9 µm) and 3 months (mean difference, -26 µm; 95% confidence interval, -39 to -12 µm) and significant improvement in scotopic CDVA at 3 months (mean difference +1.6 lines; 95% confidence interval, 0.2-3.0 lines). Scores on the visual disability questionnaire did not change significantly in either arm or differ significantly between arms. One subject assigned to netarsudil had baseline epithelial bullae and withdrew from the study because of disabling glare., Conclusions: Use of netarsudil was associated with reduction of corneal edema and improvement in scotopic CDVA in Fuchs dystrophy patients. Further study is needed to more fully assess patient satisfaction and visual acuity under various lighting conditions and to compare use of netarsudil with other treatment options such as endothelial keratoplasty., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Purpose: Descemet membrane endothelial keratoplasty is often combined with phacoemulsification and intraocular lens implantation (DMEK + cataract/IOL triple procedure) in phakic patients. This procedure results in a refractive shift that is difficult to predict. The aim of this study was to evaluate the hypothesis that the refractive shift in the second eye follows the shift in the first eye., Methods: In this retrospective, single-center, consecutive case series, the refractive outcomes of 254 eyes of 127 patients who underwent DMEK + cataract/IOL triple procedure in both eyes for Fuchs endothelial corneal dystrophy have been analyzed. Main outcome measures were spherical equivalent outcome (shift calculations), best spectacle-corrected visual acuity, central corneal thickness, and posterior simulated keratometry., Results: The mean best spectacle-corrected visual acuity before surgery was 0.51 ± 0.24 and increased to 0.19 ± 0.15 (logMAR) after surgery (P < 0.001). After surgery, a mean hyperopic shift of 0.98 ± 0.89 D was observed. The refractive shift was 1.03 ± 0.93 D and 0.92 ± 1.02 D, in the first and second eyes, respectively (P = 0.435). In a paired analysis, the mean difference of the refractive shift between the first and second eyes was 0.49 ± 0.43 D., Conclusions: In our fellow eye comparison, the refractive shift after DMEK + cataract/IOL triple procedure in the second eye was comparable with the shift in the first eye. As a consequence, the refractive outcome of the first eye might serve as a reference for optimizing the refractive target in the second eye. Further studies investigating the influence of corneal parameters on refractive shift are needed for a more predictable lens power selection., Competing Interests: The authors have no funding or conflicts of interest to disclose., (Copyright © 2020 Wolters Kluwer Health, Inc. All rights reserved.)

Purpose: To evaluate changes in the anterior chamber of eyes that have undergone Descemet membrane endothelial keratoplasty (DMEK) and to identify factors that affect these changes., Methods: This retrospective study included 25 pseudophakic eyes of 25 patients who underwent DMEK. We determined the preoperative and postoperative values of the best spectacle-corrected visual acuity, spherical equivalent (SE), anterior chamber volume (ACV), anterior chamber depth (ACD), central corneal thickness (CCT), and scleral spur angle (SSA) evaluated using anterior segment optical coherence tomography and iris damage score and iris posterior synechiae score. We defined ∆ as the average change rate from the preoperative to postoperative value for each factor at 1 month (SE at 6-12 months) postoperatively. We also analyzed correlations between ∆ACV, ∆SE, and other preexisting factors., Results: Compared with the preoperative ACV value (128 ± 28 mm3), the postoperative value significantly increased to 155 ± 21 mm3 (P < 0.001); ∆SE was +1.01 ± 1.09 diopters. ∆ACV was negatively correlated with preoperative ACD (R = 0.643, P < 0.001) and SSA (R = 0.555, P = 0.001) and positively correlated with ∆ACD (R = 0.799, P < 0.001) and ∆SSA (R = 0.608, P < 0.001). ∆CCT, iris damage score, and iris posterior synechiae score were not significantly correlated with ∆ACV. ∆SE was positively correlated with ∆ACV, ∆ACD, and ∆SSA (R = 0.680, 0.455, and 0.478; P < 0.001, <0.05, and <0.05, respectively)., Conclusions: An increase in the ACV and hyperopic change was noted after successful DMEK, especially in eyes with narrow-angled shallow anterior chambers., Competing Interests: The authors have no funding or conflicts of interest to disclose., (Copyright © 2020 The Author(s). Published by Wolters Kluwer Health, Inc.)

Purpose: To evaluate the clinical outcomes of Descemet membrane endothelial keratoplasty (DMEK) for treating eyes with iridocorneal endothelial (ICE) syndrome and comparing the outcomes with those achieved after treating Fuchs endothelial dystrophy (FED)., Design: Prospective interventional comparative case series., Methods: Sixty-three patients (68 eyes) with ICE syndrome or FED were enrolled at the Zhongshan Ophthalmic Center between March 10, 2014 and May 11, 2018. Eligible patients were divided into 2 groups: ICE group (eyes, 24; patients, 24) and FED group (eyes, 44; patients, 39). DMEK was performed in all cases. Corrected distance visual acuity (CDVA), endothelial cell loss (ECL), intraocular pressure (IOP), graft survival, and surgical complications were documented., Results: In the ICE and FED groups, the mean follow-up duration was 24.9 ± 5 months and 25.2 ± 7.7 months, respectively. At 1 year postoperatively, Kaplan-Meier survival analysis demonstrated 85.7% and 100% cumulative graft success rates (P = .017) in patients with ICE and FED, respectively. Postoperative CDVA level was comparable between the 2 groups through 12-month follow-up; thereafter CDVA was better in the FED group than in the ICE group (P < .001). Moreover, postoperative ECL was significantly higher in the ICE group than in the FED group throughout the follow-up period (P < .001). A discernable increase in structural abnormalities of the anterior chamber angle was observed in 2 eyes (8.3%) in the ICE group; however, no significant differences were observed in the incidence of principal complications between the 2 groups., Conclusions: DMEK provides comparable short-term visual outcomes in the treatment of ICE to those observed in the treatment of FED, with higher postoperative ECL over FED., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Purpose: To describe 2 insertion techniques, outcomes, and complications of preloaded, trifolded Descemet membrane endothelial keratoplasty (DMEK) cases using the DMEK EndoGlide inserter., Methods: This retrospective, consecutive case series analyzed the first 35 cases using the DMEK EndoGlide performed between October 2018 and October 2019 at a single center. Preloaded, trifolded DMEK tissues were delivered through a fluid-injected or pull-through technique. To inject the tissue, a burst of fluid was delivered into the lumen of the injector with a second instrument. Postoperatively, best-spectacle corrected visual acuity (BSCVA), pachymetry, graft survival, and complications were assessed., Results: Thirty-five eyes of 29 patients underwent DMEK alone (n = 11), with cataract surgery (n = 21), or with additional surgeries (n = 3). Of these, 19 (54.3%) grafts were injected. Video analysis revealed a median time of 3.5 minutes from graft insertion to opening for gas insertion. Median preoperative BSCVA of 0.398 logMAR improved to 0.097 logMAR (P = 0.02) at 9 months. Median pachymetry decreased from 619 μm to 551 μm (P = 0.03) at 9 months. Median donor endothelial cell count of 2890.5 cells/mm2 reduced to 2123 cells/mm2 (26.6% endothelial cell loss; P = 0.008) 6 months postoperatively. One (2.9%) graft failed due to inverted marking at the eye bank and subsequent reverse implantation., Conclusions: Pre-loaded, tri-folded tissues can be implanted with acceptable levels of endothelial cell loss. We describe a no-touch method of injecting pre-loaded, tri-folded tissue and highlight incorrect marking as a potential complication. This may not be identifiable intraoperatively due to lack of scroll formation., Competing Interests: A. O. Eghrari has ownership interest in Treyetech and LuckyVision, LLC. The remaining authors have conflicts of interest to disclose., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Abstract: Endothelial keratoplasty has revolutionized the treatment of corneal endothelial dysfunction and lowered the threshold for treatment by providing rapid visual rehabilitation and setting a high standard for safety and efficacy. Over time, endothelial keratoplasty techniques have evolved toward the use of thinner tissue to optimize visual outcomes; refinements have facilitated donor tissue preparation, handling, and attachment; and adaptations have expanded utilization in eyes with challenging ocular anatomy. Despite early concerns about graft longevity, emerging 10-year endothelial cell loss and graft survival data have been encouraging. A shortage of human donor corneas restricts utilization in many areas of the world and is driving a search for keratoplasty alternatives. Further work is needed to expand the donor supply, minimize impediments to adoption, optimize graft survival, and improve refractive predictability., Competing Interests: The authors have no funding or conflicts of interest to disclose., (Copyright © 2020 The Author(s). Published by Wolters Kluwer Health, Inc.)

The role of femtosecond laser -assisted cataract surgery in patients with Fuchs endothelial corneal dystrophy remains poorly defined. This invited commentary examines the current evidence surrounding this often-debated topic.

Fuchs endothelial corneal dystrophy (FECD) is characterized by a progressive loss of corneal endothelial cells (CECs) and an abnormal accumulation of extracellular matrix in Descemet's membrane leading to increased thickness and formation of excrescences called guttae. Extracellular matrix homeostasis is modulated by an equilibrium between matrix metalloproteinases (MMPs) and their endogenous tissue inhibitors (TIMPs). This study aimed to investigate MMPs and TIMPs profile in FECD, taking into account cell morphology. Populations of FECD and healthy CECs were cultured and their conditioned media collected for analysis. The presence of proteases in the conditioned media was studied using a semi-quantitative proteome profiler array, and MMPs levels were assessed using quantitative assays (ELISA and quantitative antibody array). MMP activity was determined by zymography and fluorometry. The expression pattern of the membrane type 1-MMP (MT1-MMP, also known as MMP-14) was examined by immunofluorescence on ex vivo FECD and healthy explants of CECs attached to Descemet's membrane. Finally, MMPs and TIMPs protein expression was compared to gene expression obtained from previously collected data. FECD and healthy CEC populations generated cultures of endothelial, intermediate, and fibroblastic-like morphology. Various MMPs (MMP-1, -2, -3, -7, -8, -9, -10, and -12) and TIMPs (TIMP-1 to -4) were detected in both FECD and healthy CECs culture supernatants. Quantitative assays revealed a decrease in MMP-2 and MMP-10 among FECD samples. Both these MMPs can degrade the main extracellular matrix components forming guttae (fibronectin, laminin, collagen IV). Moreover, MMPs/TIMPs ratio was also decreased among FECD cell populations. Activity assays showed greater MMPs/Pro-MMPs proportions for MMP-2 and MMP-10 in FECD cell populations, although overall activities were similar. Moreover, the analysis according to cell morphology revealed among healthy CECs, both increased (MMP-3 and -13) and decreased (MMP-1, -9, -10, and -12) MMPs proteins along with increased MMPs activity (MMP-2, -3, -9, and -10) in the fibroblastic-like subgroup when compared to the endothelial subgroup. However, FECD CECs did not show similar behaviors between the different morphology subgroups. Immunostaining of MT1-MMP on ex vivo FECD and healthy explants revealed a redistribution of MT1-MMP around guttae in FECD explants. At the transcriptional level, no statistically significant differences were detected, but cultured FECD cells had a 12.2-fold increase in MMP1 and a 4.7-fold increase in TIMP3. These results collectively indicate different, and perhaps pathological, MMPs and TIMPs profile in FECD CECs compared to healthy CECs. This is an important finding suggesting the implication of MMPs and TIMPs in FECD pathophysiology., (Copyright © 2021. Published by Elsevier Ltd.)

Purpose: To assess the feasibility of Descemet membrane endothelial keratoplasty (DMEK) surgery using the glasses-assisted 3-dimensional (3D) display system NGENUITY (Alcon Laboratories, Fort Worth, TX) and to compare with standard DMEK surgery by using a conventional operating microscope., Methods: Twelve consecutive cases of DMEK surgery were performed using the glasses-assisted 3D display system NGENUITY (Alcon) and matched with similar cases performed by using the OPMI-Lumera 700 surgical microscope (Carl Zeiss Meditec, Jena, Germany) in this prospective cross-sectional study realized at the Rothschild Foundation, Paris, France. DMEK graft preparation time, graft unfolding time, time to perform the descemetorhexis (DM), and overall surgical time were recorded. Best corrected visual acuity, endothelial cell density of the donor tissue measured by specular microscopy, and the recipient's central corneal thickness were recorded preoperatively and again at 1 and 3 months postoperatively., Results: In the 3D group, time to perform the graft preparation, DM, and global surgical time were significantly higher in the 3D group than in the conventional groups (17 minutes 36 seconds ± 3 minutes 13 seconds and 14 minutes 50 seconds ± 1 minutes 28 seconds, P = 0.04; 6 minutes 18 seconds ± 2 minutes 30 seconds vs. 3 minutes 50 seconds ± 2 minutes 8 seconds, P = 0.03; and 31 minutes 30 seconds ± 6 minutes 10 seconds vs. 24 minutes 10 seconds ± 3 minutes 26 seconds, respectively, P = 0.05). The time to unfold the graft was higher, although not significantly so, in the 3D group compared with the conventional group (5 minutes 15 seconds ± 2 minutes 40 seconds vs. 4 minutes 40 seconds ± 2 minutes 25 seconds, P = 0.89). Mean central corneal thickness decreased about 168 ± 82 μm at 3 months after surgery in the 3D group and about 228 ± 123 μm in the conventional group without significant difference (P = 0.60). Best corrected visual acuity in the 3D group was 0.33 ± 0.32 LogMAR at 3 months after surgery with no significant differences found when compared with conventional surgery. The percent endothelial cell loss from preoperative at 3 months was 35% in the 3D group and 26% in the conventional group, respectively, with no significant difference (P > 0.05)., Conclusions: Performing DMEK surgery using a 3D display system is feasible; however, it is more challenging and the total surgical time is longer. This method would certainly be useful for instructional courses.

Purpose: To report the safety and efficacy of a novel cell injection therapy using cultured human corneal endothelial cells (hCECs) for endothelial failure conditions via the report of the long-term 5-year postoperative clinical data from a first-in-humans clinical trial group., Design: Prospective observational study., Participants: This study involved 11 eyes of 11 patients with pseudophakic endothelial failure conditions who underwent hCEC injection therapy between December 2013 and December 2014., Methods: All patients underwent follow-up examinations at 1 week, 4 weeks, 12 weeks, and 24 weeks and 1 year, 2 years, 3 years, 4 years, and 5 years after surgery. Specific corneal endothelial cell parameters (i.e., corneal endothelial cell density [ECD], coefficient of variation of area, and percentage of hexagonal cells) and central corneal thickness, best-corrected visual acuity (BCVA) on a Landolt C eye chart, and intraocular pressure (IOP) were recorded., Main Outcome Measures: The primary outcome was the change in central ECD after cell injection therapy, and the secondary outcome was corneal thickness, BCVA, and IOP during the 5-year-postoperative follow-up period., Results: At 5 years after surgery, normal corneal endothelial function was restored in 10 of the 11 eyes, the mean ± standard deviation central corneal ECD was 1257 ± 467 cells/mm 2 (range, 601-2067 cells/mm 2 ), BCVA improved significantly in 10 treated eyes, the mean visual acuity changed from 0.876 logarithm of the minimum angle of resolution before surgery to 0.046 logarithm of the minimum angle of resolution after surgery, and no major adverse reactions directly related to the hCEC injection therapy were observed., Conclusions: The findings in this study confirmed the safety and efficacy of cultured hCEC injection therapy for up to 5 years after surgery., (Copyright © 2020 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.)

Purpose: To compare the survival rate 1 year after Descemet membrane endothelial keratoplasty (DMEK) in pseudophakic eyes versus combined phacoemulsification and DMEK (triple-DMEK)., Methods: Retrospective, interventional, consecutive case series. From all DMEKs performed from January 1, 2017, to June 30, 2018, we selected those performed in pseudophakic eyes (pseudophakic DMEK) and those that underwent triple-DMEK. We compared the survival rate 1 year after surgery between both groups and between the Fuchs endothelial dystrophy (FED) cases in both groups, plus the FED cases versus the pseudophakic bullous keratopathy (PBK) cases in the pseudophakic DMEK group. Second, we compared rebubbling rates and the influence of the use of gas or corneal sutures on rebubbling and dislocation rates., Results: A total of 329 eyes were included (218 eyes pseudophakic DMEK and 111 eyes triple-DMEK). The survival rate at 1 year was 79.8% and 90%, respectively (P = 0.03). When only FED cases were included (133 pseudophakic DMEK and 108 triple-DMEK), no significant difference was found (87.9% vs. 90.7%, P = 0.59). Within the pseudophakic DMEK group, the survival rate was higher in FED cases (87.8%) compared with PBK cases (66.6%) (P = 0.0001). Rebubbling rates were 21.1% (pseudophakic DMEK) and 17.1% (triple-DMEK) (P = 0.39). The use of gas versus air or placing corneal sutures did not seem to influence the rebubbling (P = 0.64 and P = 0.13, respectively) or dislocation rates (P = 0.71 and P = 0.53, respectively)., Conclusions: In the FED cases, performing phacoemulsification before DMEK or doing a combined procedure did not seem to affect the rebubbling or survival rate up to 1 year postoperatively. PBK was associated with a higher failure rate compared with that of FED.

Purpose: To evaluate the speed of visual recovery in 16 consecutive patients with corneal endothelial dysfunction who received Descemetstripping automated endothelial keratoplasty (DSAEK)., Methods: This is a retrospective study of a novel method for smallincision endothelial transplantation (DSAEK). Endothelial replacement was accomplished with Descemet stripping of the recipient and insertion of a posterior donor tissue that had been prepared with a microkeratome. Best spectacle-corrected visual acuity (BSCVA) by manifest refraction, endothelial counts, and dislocation rates were measured up to 12 months after DSAEK., Results: Sixteen consecutive patients underwent uncomplicated DSAEK. Three patients had known optic nerve or macular disease precluding vision better than 20/200. Of the remaining 14 patients, 11 had BSCVA of 20/40 by postoperative week 12 (7 by week 6). The remaining 2 were 20/50 by weeks 6 and 12. All 14 patients were 20/40 or better at 1 year. One patient had a primary graft failure, and surgery was repeated with 20/40 BSCVA at 1 year. The dislocation rate was 25%. The average cell count between 7 and 10 months was 1714. The average pachymetry was 682., Conclusion: DSAEK surgery allows rapid, excellent BSCVAvisual recovery. The rate of visual recovery is more rapid than usually found with penetrating keratoplasty., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Purpose: To describe a surgical technique of Descemet membrane endothelial keratoplasty (DMEK) using an endothelium-in pull-through technique with novel infusion forceps and report 6-month clinical outcomes., Methods: This is a retrospective case series of 33 cases with Fuchs endothelial corneal dystrophy who underwent either DMEK alone (n = 5), DMEK combined with phacoemulsification (n = 27), or DMEK combined with intraocular lens exchange (n = 1) performed by surgeons at the beginning of the DMEK learning curve. Best-corrected visual acuity (BCVA), manifest refraction, central corneal thickness, endothelial cell density, intraoperative and postoperative complications, and need for additional surgeries including rebubbling were evaluated through 6 months postoperatively., Results: Preoperative BCVA was 0.37 ± 0.34 logarithm of the minimum angle of resolution and improved to 0.09 ± 0.10 logarithm of the minimum angle of resolution at 6 months (P < 0.001). Eighty-two percent of eyes obtained a BCVA of 20/25 or better. Central corneal thickness decreased significantly at 6 months (P < 0.001). Endothelial cell loss was 29.1% at 6 months (available for 20 of 33 eyes). All surgeries were uneventful. Six eyes required rebubbling for graft detachments. There were no primary or secondary graft failures at 6 months., Conclusions: DMEK with infusion microforceps is efficacious and safe in eyes with Fuchs endothelial corneal dystrophy and could offer a more controlled surgery, making it suitable for both novice and experienced DMEK surgeons., Competing Interests: A. S. Jun: co-inventor of DMEK spoon and infusion microforceps. The remaining authors have no funding or conflicts of interest to disclose., (Copyright © 2020 Wolters Kluwer Health, Inc. All rights reserved.)

Purpose: To conduct Fourier analysis on regular and irregular astigmatism of the anterior and posterior corneal surfaces using anterior segment optical coherence tomography in patients with Fuchs endothelial corneal dystrophy (FECD) DESIGN: Observational case series., Methods: This study included 75 eyes of 43 FECD patients and 34 eyes of 34 healthy subjects in Osaka University Hospital. Corneal dioptric data from the central 6-mm zone of the anterior and posterior corneal surface were expanded into spherical, regular astigmatism, asymmetry, and higher-order irregularity components using Fourier analysis. We analyzed the association between each component and modified Krachmer grade., Results: There were significant differences in regular astigmatism, asymmetry, and higher-order irregularity components of the anterior corneal surface, and spherical, regular astigmatism, asymmetry, and higher-order irregularity components of the posterior corneal surface among modified Krachmer grades (P = .036, <.001, <.001, <.001, <.001, <.001, and <.001, respectively). Asymmetry component of the anterior and posterior corneal surfaces gradually increased with FECD progression. Higher-order irregularity components of the anterior and posterior corneal surfaces drastically increased in Grade 6. Many eyes had an axis of 0°-180° for the asymmetry component of the anterior surface and 180°-360° for that of the posterior surface., Conclusion: Patients with severe FECD had a larger amount of asymmetry and higher-order irregularity components of the anterior and posterior corneal surfaces. Patients with FECD up to Grade 5 were characterized by anterior and posterior flattening in the inferior cornea, and those with Grade 6 showed irregularity in the anterior and posterior corneal surfaces., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Purpose: To compare the one-year outcomes of preloaded Descemet membrane endothelial keratoplasty (pDMEK) and non-preloaded DMEK (n-pDMEK) in patients with Fuchs endothelial corneal dystrophy (FECD)., Methods: This retrospective comparative cohort study consecutively included 68 eyes with Fuchs endothelial corneal dystrophy who underwent either pDMEK (n = 38) or n-pDMEK (n = 30) performed by cornea fellows with an experienced surgeon between 2016 and 2018 at the Massachusetts Eye and Ear Infirmary. Exclusion criteria were previous surgery (other than uncomplicated cataract surgery) and any documented evidence of macular or other corneal diseases. Corrected distance visual acuity (CDVA), central corneal thickness, intraocular pressure, patient characteristics, postprocessing endothelial cell count, donor graft data, and complications were compared., Results: CDVA showed similar results for pDMEK (0.12 ± 0.11 logarithm of the minimal angle of resolution [LogMAR]) and n-pDMEK (0.13 ± 0.13 LogMAR) (P = 0.827). Sixty-six percent of the pDMEK eyes and 57% of the n-pDMEK eyes achieved a VA of ≥0.1 LogMAR, and 95% and 97%, respectively, achieved a CDVA ≥0.3 LogMAR. The preoperative central corneal thickness of pDMEK and n-pDMEK (644 ± 62.2 μm, 660.5 ± 56.2 μm) decreased significantly after surgery (525.1 ± 43.6 μm, 526.5 ± 45.2 μm, P < 0.001), with no difference between groups (P = 0.840). The postprocessing endothelial cell count did not differ between pDMEK (2959.2 ± 182.9 cells/mm2) and n-pDMEK (2939.3 ± 278.7 cells/mm2) (P = 0.484). Complication rates were comparable with just the rebubbling performed in a minor procedure room showing a lower rate for pDMEK (13.16%) compared with n-pDMEK (33.33%) (P < 0.045)., Conclusions: One-year clinical outcomes were similar between pDMEK and n-pDMEK procedures, rendering eye bank-prepared pDMEK tissues a useful tool in the treatment of endothelial dysfunction., Competing Interests: The authors have no funding or conflicts of interest to disclose., (Copyright © 2020 Wolters Kluwer Health, Inc. All rights reserved.)

Mitochondrial function is essential for the viability of aerobic eukaryotic cells, as mitochondria provide energy through the generation of adenosine triphosphate (ATP), regulate cellular metabolism, provide redox balancing, participate in immune signaling, and can initiate apoptosis. Mitochondria are dynamic organelles that participate in a cyclical and ongoing process of regeneration and autophagy (clearance), termed mitophagy specifically for mitochondrial (macro)autophagy. An imbalance in mitochondrial function toward mitochondrial dysfunction can be catastrophic for cells and has been characterized in several common ophthalmic diseases. In this article, we review mitochondrial homeostasis in detail, focusing on the balance of mitochondrial dynamics including the processes of fission and fusion, and provide a description of the mechanisms involved in mitophagy. Furthermore, this article reviews investigations of ocular diseases with impaired mitophagy, including Fuchs endothelial corneal dystrophy, primary open-angle glaucoma, diabetic retinopathy, and age-related macular degeneration, as well as several primary mitochondrial diseases with ocular phenotypes that display impaired mitophagy, including mitochondrial encephalopathy lactic acidosis stroke, Leber hereditary optic neuropathy, and chronic progressive external ophthalmoplegia. The results of various studies using cell culture, animal, and human tissue models are presented and reflect a growing awareness of mitophagy impairment as an important feature of ophthalmic disease pathology. As this review indicates, it is imperative that mitophagy be investigated as a targetable mechanism in developing therapies for ocular diseases characterized by oxidative stress and mitochondrial dysfunction.

Fuchs endothelial corneal dystrophy (FECD) is the most common primary corneal endothelial dystrophy and the leading indication for corneal transplantation worldwide. FECD is characterized by the progressive decline of corneal endothelial cells (CECs) and the formation of extracellular matrix (ECM) excrescences in Descemet's membrane (DM), called guttae, that lead to corneal edema and loss of vision. FECD typically manifests in the fifth decades of life and has a greater incidence in women. FECD is a complex and heterogeneous genetic disease where interaction between genetic and environmental factors results in cellular apoptosis and aberrant ECM deposition. In this review, we will discuss a complex interplay of genetic, epigenetic, and exogenous factors in inciting oxidative stress, auto(mito)phagy, unfolded protein response, and mitochondrial dysfunction during CEC degeneration. Specifically, we explore the factors that influence cellular fate to undergo apoptosis, senescence, and endothelial-to-mesenchymal transition. These findings will highlight the importance of abnormal CEC-DM interactions in triggering the vicious cycle of FECD pathogenesis. We will also review clinical characteristics, diagnostic tools, and current medical and surgical management options for FECD patients. These new paradigms in FECD pathogenesis present an opportunity to develop novel therapeutics for the treatment of FECD., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Purpose: To assess the 3-year outcomes of tri-folded endothelium-in Descemet membrane endothelial keratoplasty (DMEK) using bimanual pull-through delivery technique., Design: Interventional case series., Methods: In this single-center study, we included 153 consecutive eyes that underwent DMEK for various indications (Fuchs endothelial corneal dystrophy [FECD]: n = 111; bullous keratopathy [BK]: n = 24; and failed graft: n = 18). DMEK grafts were loaded into a disposable cartridge in a tri-folded, endothelium-in configuration and delivered using bimanual pull-through technique. Main outcome measures were graft preparation and unfolding times, best spectacle-corrected visual acuity (BSCVA), endothelial cell density (ECD), and graft survival., Results: Mean graft preparation time was 5.9 ± 1.1 minutes; and mean graft unfolding time was 2.9 ± 0.9 minutes. Excluding eyes with comorbidities, logarithm of minimum angle of resolution BSCVA improved significantly from baseline preoperative values of 0.92 ± 0.58 to 0.02 ± 0.07 at 1 year (P < .001) and remained stable up to 3 years. Mean postoperative ECD decreased significantly (P < .001) from eye bank values to 1,818 ± 362, 1,675 ± 372, and 1,580 ± 423 cells/mm 2 at 1, 2, and 3 years, respectively. No significant differences in ECD were observed between eyes with FECD and BK, but ECD was significantly lower in eyes with previous failed graft (P < .05). Three-year cumulative graft survival rate was significantly (P < .001) lower for eyes with previous failed graft (71%) than for FECD (97%) and BK (92%)., Conclusions: Tri-folded endothelium-in DMEK requires minimal time for graft unfolding, which is the surgical step considered most challenging by corneal surgeons. Visual outcomes and complication rates are not adversely affected by the modification of the surgical technique., (Copyright © 2020 Elsevier Inc. All rights reserved.)