Evidence against involvement of kynurenate branch of kynurenine pathway in pathophysiology of Fuchs' dystrophy and keratoconus.

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.

Clinical, Morphological, and Optical Correlates of Visual Function in Patients With Fuchs Endothelial Corneal Dystrophy.

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.

Long-Term Outcome of Descemet Membrane Endothelial Keratoplasty in Eyes With Fuchs Endothelial Corneal Dystrophy Versus Pseudophakic Bullous Keratopathy.

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.

Differential gene expression analysis of corneal endothelium indicates involvement of phagocytic activity in Fuchs' endothelial corneal dystrophy.

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 (log2 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.

Effect of Six-Month Postoperative Endothelial Cell Density on Graft Survival after Descemet Membrane Endothelial Keratoplasty.

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/mm2, group 2 (n = 148) with 1246 to 1610 cells/mm2, group 3 (n = 145) with 1611 to 1938 cells/mm2, and group 4 (n = 146) with 1939 to 2760 cells/mm2. Group 1 was further split into subgroups 1a (n = 36) with 6-month ECD of ≤828 cells/mm2, 1b (n = 37) with 829 to 1023 cells/mm2, 1c (n = 37) with 1024 to 1140 cells/mm2, and 1d (n = 36) 1141 to 1245 cells/mm2. 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/mm2 (n = 146) to 735 (±216) cells/mm2 (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/mm2) 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.

Randomized, Double-Masked, Pilot Study of Netarsudil 0.02% Ophthalmic Solution for Treatment of Corneal Edema in Fuchs Dystrophy.

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.

Mitophagy: An Emerging Target in Ocular Pathology.

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.

Matrix metalloproteinases and their inhibitors in Fuchs endothelial corneal dystrophy.

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.

Radial Endothelial Striae Over 360 Degrees in Fuchs Corneal Endothelial Dystrophy: New Pathophysiological Findings.

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.

Recovery of Contrast Sensitivity After Descemet Membrane Endothelial Keratoplasty.

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.

Descemet-Stripping Automated Endothelial Keratoplasty.

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.

Comparison of Descemet Membrane Endothelial Keratoplasty for Iridocorneal Endothelial Syndrome and Fuchs Endothelial Dystrophy.

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.

Quality of vision and vision-related quality of life after Descemet membrane endothelial keratoplasty: a randomized clinical trial.

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 (ß = 12 [95% CI: 7 to 16]; p < 0.001), and subsequently between 3 and 12 months (ß = 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.

Techniques, Outcomes, and Complications of Preloaded, Trifolded Descemet Membrane Endothelial Keratoplasty Using the DMEK EndoGlide.

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.

Anatomical Changes in the Anterior Chamber Volume After Descemet Membrane Endothelial Keratoplasty.

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.

Effect of Anticoagulant Therapy on the Outcome of Descemet Membrane Endothelial Keratoplasty.

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.

Endothelial Keratoplasty Update 2020.

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.

Femtosecond Laser-Assisted Cataract Surgery: Does It Improve Outcomes in Fuchs Endothelial Corneal Dystrophy?

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.

Microthin Descemet Stripping Automated Endothelial Keratoplasty Versus Descemet Membrane Endothelial Keratoplasty: A Randomized Clinical Trial.

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.

Clinical Outcomes of Descemet Membrane Endothelial Keratoplasty in Pseudophakic Eyes Compared With Triple-DMEK at 1-Year Follow-up.

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.