Nanopore sequencing method for CTG18.1 expansion in TCF4 in late-onset Fuchs endothelial corneal dystrophy and a comparison of the structural features of cornea with first-degree relatives.

BACKGROUND: To evaluate the relationship between the number of trinucleotide repeats (TNR) in late-onset Fuchs corneal endothelial dystrophy (FCED) and to compare the endothelial properties of FCED, first-degree relatives, and controls. METHODS: Blood samples were collected from FCEDs to determine TNR number. The FCED patients, first-degree relatives, and controls were examined with specular microscopy for central corneal thickness (CCT), endothelial cell density (ECD), pleomorphism and polymegatism, and with corneal topography for specific indicators such as (i) displacement of thinnest point of cornea, (ii) loss of isopachs, (iii) focal posterior surface depression towards anterior chamber. RESULTS: This study included 92 patients with FCED, 92 first-degree relatives, and 96 controls. CCT was thickest in FCEDs (558.0 µm) (p < 0.05) while there was no difference between relatives (533.0 µm) and controls (530.4 µm) (p = 0.845). ECD was decreased in both FCED (2069.2 mm2) and relatives (2171.4 mm2) than controls (2822.9 mm2) (p < 0.05 in both). The presence of pleomorphism and polymegatism was significant in patients with FCED (93.4% and 93.4%, respectively), relatives (86.9% and 86.04%, respectively), and controls (8.33% and 1.04%, respectively) (p < 0.05). Specific topographic indicators differed among the groups (p < 0.05). The mean repeat number of the FCED patients was 17.48 ± 4.54 (12-25) times. The TNR number of FCED cases correlated with the relative CCT (p < 0.05, R = 0.615) and cell density (p = 0.009, R = -0.499). CONCLUSIONS: A strong association between the corneal endothelium in relatives and TNR number of FCEDs was defined. Relatives tended to have fewer corneal endothelial cells, even though they did not have clinical findings.

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

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

Clinical characteristics of viral-associated Fuchs uveitis syndrome and Posner-Schlossman syndrome in a Chinese population.

PURPOSE: To identify the types of viral infection in aqueous humor (AqH) among patients diagnosed as Fuchs uveitis syndrome (FUS) or Posner-Schlossman syndrome (PSS) and investigate their relevance to clinical manifestations and visual outcome. METHODS: A total of 375 patients and 171 patients were diagnosed as FUS or PSS in our department. AqH and serum samples from 68 FUS patients and 16 PSS patients were obtained during eye surgery. The viral etiologies, clinical features, auxiliary tests and visual prognosis of patients with FUS or PSS who underwent AqH analysis were analysed and compared. RESULTS: Among 68 FUS patients, rubella virus (RV), cytomegalovirus (CMV), herpes simplex virus (HSV) and varicella-zoster virus were identified in 17, 11, 1 and 1 patients, respectively. Seven patients with CMV and 1 with HSV were identified in 16 PSS patients. In both FUS and PSS groups, virus-associated eyes had higher proportion of secondary glaucoma and worse visual prognosis as compared with non-virus-associated eyes (all P < 0.05). In FUS group, specifically, CMV infection manifested as more obvious anterior segment inflammation and lower corneal endothelial cell density (CECD). RV infection showed a higher percentage of vitritis. In PSS group, CMV-associated PSS had a lower retinal nerve fiber layer thickness and CECD, worse visual prognosis as compared with non-virus-associated PSS (all P < 0.05). CONCLUSION: Our study identified 4 types of viral infection in FUS and 2 types of viral infection in PSS. Virus-associated patients are usually associated with more obvious clinical signs and poor visual prognosis.

Effects of graft detachment on the central corneal thickness after uncomplicated Descemet membrane endothelial keratoplasty.

PURPOSE: To determine if early central corneal thickness (CCT) and best-corrected visual acuity (BCVA) changes indicate graft detachment after uncomplicated Descemet membrane endothelial keratoplasty (DMEK). METHODS: In this analysis of our prospectively collected ADDA registry data ( https://drks.de/search/de/trial/DRKS00027180 ), 45 pseudophakic eyes underwent DMEK surgery at the Department of Ophthalmology, RWTH Aachen University. Anterior segment optical coherence tomography (AS-OCT), the presence of stromal ripples on the posterior corneal surface, and BCVA measurements were assessed prior to, 1 day, 1 week, 1 month, and 6 months after surgery. RESULTS: Eyes were categorized into three groups: no graft detachment (group 1) (20/45; 44.4%), < 1/3 graft detachment (group 2) (14/45; 31.1%), ≥ 1/3 graft detachment followed by rebubbling (group 3) (11/45; 24.4%). Eyes in group 3 had a greater CCT prior to (746.8 ± 95.8 µm vs. 665.0 ± 74.4 µm, P = 0.041), and 1 week (666.8 ± 119.5 µm vs. 556.5 ± 56.8 µm, P = 0.001) after DMEK compared to group 1. By 1 month, CCT in all groups aligned. Comparing prior to and 1 week after DMEK, none of the eyes in group 1 had an increase in CCT, while the CCT increased in 25.0% of eyes in group 2 and 22.2% in group 3. In group 1, 90.0% had a CCT of < 600 µm 1 week after DMEK, compared to only 50.0% in group 2 and 36.4% in group 3. In group 1, 90.0% (18/20) had an improved BCVA 1 week after DMEK, while in groups 2 and 3, 86.7% (12/14) and 18.2% (2/11) improved, respectively. One patient in group 3 showed posterior stromal ripples 1 day and 1 week after DMEK. CONCLUSION: If 1 week after uncomplicated DMEK CCT is < 600 µm and has decreased from before surgery, BCVA has improved, and there are no posterior stromal ripples, a graft detachment ≥ 1/3 and the need for rebubbling are very unlikely. In all other cases, meticulous slit-lamp and OCT inspection of the peripheral graft for detachments should be advised.

Fuchs endothelial corneal dystrophy: an updated review.

PURPOSE: The present review will summarize FECD-associated genes and pathophysiology, diagnosis, current  therapeutic approaches, and future treatment perspectives. METHODS: Literature review. RESULTS: Fuchs' endothelial corneal dystrophy (FECD) is the most common bilateral corneal dystrophy and accounts for one-third of all corneal transplants performed in the US. FECD is caused by a combination of genetic and non-heritable factors, and there are two types: early-onset FECD, which affects individuals from an early age and is usually more severe, and late-onset FECD, which is more common and typically manifests around the age of 40. The hallmark findings of FECD include progressive loss of corneal endothelial cells and the formation of focal excrescences (guttae) on the Descemet membrane. These pathophysiological changes result in progressive endothelial dysfunction, leading to a decrease in visual acuity and blindness in later stages. The present review will summarize FECD-associated genes and pathophysiology, diagnosis, current therapeutic approaches, and future treatment perspectives. CONCLUSION: With the characterization and understanding of FECD-related genes and ongoing research into regenerative therapies for corneal endothelium, we can hope to see more significant improvements in the future in the management and care of the disease.

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

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

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

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

Ultraviolet A light induces DNA damage and estrogen-DNA adducts in Fuchs endothelial corneal dystrophy causing females to be more affected.

Fuchs endothelial corneal dystrophy (FECD) is a leading cause of corneal endothelial (CE) degeneration resulting in impaired visual acuity. It is a genetically complex and age-related disorder, with higher incidence in females. In this study, we established a nongenetic FECD animal model based on the physiologic outcome of CE susceptibility to oxidative stress by demonstrating that corneal exposure to ultraviolet A (UVA) recapitulates the morphological and molecular changes of FECD. Targeted irradiation of mouse corneas with UVA induced reactive oxygen species (ROS) production in the aqueous humor, and caused greater CE cell loss, including loss of ZO-1 junctional contacts and corneal edema, in female than male mice, characteristic of late-onset FECD. UVA irradiation caused greater mitochondrial DNA (mtDNA) and nuclear DNA (nDNA) damage in female mice, indicative of the sex-driven differential response of the CE to UVA, thus accounting for more severe phenotype in females. The sex-dependent effect of UVA was driven by the activation of estrogen-metabolizing enzyme CYP1B1 and formation of reactive estrogen metabolites and estrogen-DNA adducts in female but not male mice. Supplementation of N-acetylcysteine (NAC), a scavenger of reactive oxygen species (ROS), diminished the morphological and molecular changes induced by UVA in vivo. This study investigates the molecular mechanisms of environmental factors in FECD pathogenesis and demonstrates a strong link between UVA-induced estrogen metabolism and increased susceptibility of females for FECD development.

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

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

Five-year follow-up of corneal morphology and corneal refractive power changes after uneventful DMEK.

PURPOSE: To investigate changes of corneal thickness spatial profile (CTSP), corneal volume (CV) distribution, and total corneal refractive power (TCRP) over a course of 60 months after uneventful Descemet membrane endothelial keratoplasty (DMEK). METHODS: In our prospective, comparative study, sixty DMEK cases without intraoperative and postoperative complications and with complete 60-month follow-up were included (group 1). CTSP at corneal apex (CCT) and at 2 mm, 4 mm, 6 mm, and 8 mm rings, CV in 3 mm, 5 mm, 7 mm, and 10 mm zones, and TCRF in 2 mm, 4 mm 6 mm, and 8 mm zones were evaluated preoperatively and at 3, 6, 12, 24, and 60 months postoperatively. The 60-month results were compared to an age-matched group of uncomplicated pseudophakic eyes (group 2; n = 20). RESULTS: The CCT and CTSP at 2, 4, and 6 mm increased significantly at 60 months compared to 3-month outcomes (P < 0.001). Similarly, CV increased significantly in 3 mm, 5 mm, and 7 mm zones at 60 months compared to 3 months outcomes (P < 0.001). The TCRP showed in all zones a significant decrease at 3 months (P < 0.001) followed by a continuous and significant increase at 60 months (P < 0.001). The 60-month CCT and CTSP at 2 mm were similar to group 2 (P ≥ 0.094). CONCLUSION: Sixty months after uneventful DMEK, CT within the central 2 mm zone and CV at 3 mm zone were similar to uncomplicated pseudophakic eyes. A continuous and statistically significant increase of TCRP was observed in all measured zones after the 3-month examination.

Ability of routinely collected clinical factors to predict good visual results after primary Descemet membrane endothelial keratoplasty: a cohort study.

BACKGROUND: A comprehensive analysis of routinely collected pre/perioperative demographic/clinical factors that could predict final visual acuity after primary Descemet membrane endothelial keratoplasty (DMEK) has not been conducted previously. METHODS: A retrospective monocenter cohort study was performed with consecutive patients with Fuchs endothelial corneal dystrophy (FECD) who underwent DMEK or triple-DMEK (DMEK combined with cataract surgery) in 2016-2020 in a French tertiary-care hospital. DMEK-only patients were pseudophakic. Patients were followed for 12 months. Surgery was considered successful when 12-month best-corrected visual acuity (BCVA) was ≤0.1 logMAR (≥0.8). Exploratory multivariate analysis was conducted with the following routinely collected variables to determine their ability to predict 12-month BCVA: patient age and sex; graft donor age; triple DMEK; preoperative values of BCVA, endothelial cell density (ECD), central corneal thickness (CCT), and mean anterior keratometry; and rebubbling. RESULTS: Of 100 eyes (100 patients; mean age, 72 years; 61% female), 81 achieved a 12-month BCVA of ≤0.1 logMAR. Logistic regression analysis showed that older age was a significant prognosticator for 12-month BCVA > 0.1 logMAR (Odds Ratio = 0.914, 95% confidence intervals = 0.846-0.987; p = 0.02). CONCLUSIONS: An older age associated with worse visual acuity outcomes after DMEK. This was confirmed by our analysis of the literature and supports the notion that DMEK should be conducted without delay once symptoms appear. Patient sex, donor age, triple-DMEK, and anterior keratometry also did not predict final BCVA in the literature. Preoperative CCT, ECD, and BCVA, and rebubbling occasionally appear in the literature as BCVA predictors, possibly reflecting an underlying ECD-BCVA axis.

Cataract Surgeries in Patients with Fuchs Endothelial Dystrophy. / Kataraktoperation beim Vorliegen einer Fuchs-Endotheldystrophie.

Patients with Fuchs endothelial dystrophy often develop visual symptoms between 50 - 60 years of age, which is the same time that the first symptoms of a developing cataract start to appear. On the other hand, in patients with a clinically significant cataract, corneal guttata may be detected by chance during a routine clinical workup. In both situations, the surgeon has to decide whether DMEK or cataract surgery should be performed alone or in combination. In the case of advanced Fuchs dystrophy with or without a clinically significant cataract, a combined surgery known as the triple procedure seems favorable as the clinical course after this procedure is the same as following sequential surgery. Furthermore, the affected patients will only have to undergo one surgery and will reach the final visual acuity much faster. Posterior lamellar keratoplasty alone can only be an option in the case of young patients with advanced Fuchs dystrophy, intact accommodation, and no signs of cataract. In the case of a clinically significant cataract combined with corneal guttata, clinical features including central corneal thickness and endothelial cell density, among others, can help to decide which surgical procedure seems to be the best. In case of cataract surgery alone, the surgeon needs to protect the corneal endothelium as well as possible. The softshell technique can help to reduce the loss of endothelial cells during cataract surgery, whereas femtosecond laser assisted cataract surgery is still controversial. The following review will discuss the most important preoperative, perioperative, and postoperative factors that need be considered in order to achieve the best result for our patients.

Demographic profile and clinical course of Fuchs endothelial corneal dystrophy in Mexican patients.

PURPOSE: To describe the demographic characteristics and clinical course of Fuchs endothelial corneal dystrophy (FECD) in a Mexican-mestizo population. METHODS: A retrospective observational and longitudinal study was performed in consecutive patients with the clinical diagnosis of Fuchs endothelial corneal dystrophy seen at our institution. Initial and last follow-up best-corrected visual acuity, slit-lamp findings, and specular microscopy endothelial morphometric parameters were analyzed. RESULTS: One hundred and two eyes belonging to 51 patients were included in the analysis. Median age at the time of diagnosis was 69 years (range, 25-87 years) with a female-to-male ratio of 3.3:1. Visual loss (40%) followed by glare (13.3%) and fluctuating matutine vision loss (13.3%) was the most common complaints at presentation. Regarding FECD staging, 65 (63.7%) were classified as stage-I FECD, 21 (20.6%) stage-II, and 15 (14.7%) as stage-III. A high percentage of eyes (44.1%) presented visual impairment ( ≤ 20/50) at presentation, and the presence of isolated corneal guttata was the most common stage of presentation (64%) at slit-lamp examination. While fifty-nine (57.8%) eyes did not require any medical or surgical management, 17 (16.7%) eyes were managed with hypertonic saline eyedrops alone or in combination with bandage contact lens, and 18 (17.6%) required corneal transplantation. Penetrating keratoplasty alone (8 eyes, 44.4%), or in combination with cataract extraction and intraocular lens implantation (3 eyes, 16.7%), was the most frequent surgical technique performed. CONCLUSION: Demographical characteristics of Fuchs dystrophy regarding age at presentation, gender distribution, and clinical stage at the time of diagnosis did not differ significantly from other international reports. Almost 20% of these patients will require keratoplasty during the disease, emphasizing the need for safer and more reproducible keratoplasty techniques.

[Fuchs corneal endothelial dystrophy treated with Descemet's stripping without endothelial keratoplasty (DWEK): a case report].

A patient with chief complaint of bilateral progressive visual impairment was diagnosed with Fuchs corneal dystrophy (FECD) in both eyes, macular hole in the left eye, and intraocular lens eye in the right eye. After communication with the patient and his family, they agreed to receive Descemet's stripping without endothelial keratoplasty (DWEK) in the left eye. One year after the operation, the cornea of the left eye was transparent, and the central posterior elastic layer was missing about 4.0 mm diameter. The naked vision of left eye was 0.1, and the correction was not improved. It can be seen that DWEK surgery has a good therapeutic effect on patients with mild FECD.

[Morphological features of the cornea in eyes with pseudophakic bullous keratopathy and Fuchs endothelial corneal dystrophy]. / Morfologicheskie osobennosti rogovitsy pri psevdofakichnoi bulleznoi keratopatii i endotelial'noi distrofii Fuksa.

PURPOSE: To evaluate the morphological features of posterior corneal layers in pseudophakic bullous keratopathy (PBK) and Fuchs endothelial corneal dystrophy (FECD). MATERIAL AND METHOD: The study included 20 patients (20 eyes) aged 73.8±7.8 with PBK and 24 patients (25 eyes) aged 72.5±10.6 with FECD. Central corneal thickness was measured in all eyes before the surgery by anterior segment optical coherence tomography (AS-OCT, RTVue-100, Optovue, USA). All patients underwent corneal transplantation (DSAEK or DMEK). Postoperative donor graft status was assessed as attached or detached by AS-OCT (RTVue-100, Optovue, USA). Specimens of Descemet's membranes (DMs) were obtained intraoperatively and investigated histologically (hematoxylin and eosin staining). Morphometric analysis was performed using optical microscope Leica DM-2500 (Digital Color Camera Leica DFC295) and ImageScope M software. RESULTS: There was no difference in thickness of DMs' prenatal anterior banded layer (2.58±0.49 µm) and postnatal posterior non-banded layer (11.30±2.64 µm) between PBK and normal cornea. In FECD eyes, DM was significantly thickened by additional collagen layer and guttate excrescences (postnatal layer thickness - 16.62±4.34 µm). Morphological study of the DMs of patients with graft detachment in the early postoperative period revealed residual stromal collagen fibrils that were fixed to the area with dense extracellular matrix. CONCLUSION: The study shows that chronic corneal edema is associated with pathological morphological changes in the posterior corneal layers in PBK and FECD. Individual features of the dense extracellular matrix in the DMs may play a key role in the attachment of donor graft to the corneal stroma and affect the postoperative outcome.

Five-Year Follow-up of First 11 Patients Undergoing Injection of Cultured Corneal Endothelial Cells for Corneal Endothelial Failure.

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/mm2 (range, 601-2067 cells/mm2), 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.

Influence of rebubbling on anterior segment parameters and refractive outcomes in eyes with DMEK for Fuchs endothelial dystrophy.

PURPOSE: To evaluate the potential impact of rebubbling on the anterior segment parameters and refractive outcomes in patients with graft detachment following uneventful DMEK for Fuchs endothelial dystrophy (FED). METHODS: Retrospective institutional cohort study of comparing 34 eyes of 31 patients with rebubbling for graft detachment following Descemet membrane endothelial keratoplasty (DMEK) to 33 eyes of 28 patients with uneventful DMEK. Main outcome parameters were various corneal parameters obtained by Scheimpflug imaging, refractive outcome, corrected distance visual acuity (CDVA), and endothelial cell density (ECD). RESULTS: Anterior and posterior corneal astigmatism, corneal densitometry, central corneal thickness, and anterior chamber depth and volume showed no significant differences. Preoperative distribution of astigmatism axis orientations showed a high proportion of anterior corneal with-the-rule astigmatism (71%) in eyes requiring rebubbling. Mean postoperative cylinder in the rebubbling group (1.21 ± 0.85 D) was significantly higher compared to the controls (p = 0.04), while differences in spherical equivalent (SE) were insignificant (p = 0.24). Postoperative CDVA was 0.11 ± 0.11 in the control group compared to 0.21 ± 0.17 in the rebubbling group (p = 0.03). Eyes with subsequent rebubbling demonstrated a significantly higher endothelial cell loss (56% versus 37%) (p < 0.001). CONCLUSION: Apart from higher cylinder values, refractive outcome and corneal parameters assessed by Scheimpflug imaging were comparable in eyes with rebubbling and controls. However, a reduced visual acuity and an increased endothelial cell loss should be taken into consideration prior to rebubbling especially in eyes with circumscribed graft detachment.

Refractive outcome and tomographic changes after Descemet membrane endothelial keratoplasty in pseudophakic eyes with Fuchs' endothelial dystrophy.

PURPOSE: To analyze refractive and topographic changes secondary to Descemet membrane endothelial keratoplasty (DMEK) in pseudophakic eyes with Fuchs' endothelial dystrophy (FED). METHODS: Eighty-seven pseudophakic eyes of 74 patients who underwent subsequent DMEK surgery for corneal endothelial decompensation and associated visual impairment were included. Median post-operative follow-up time was 12 months (range: 3-26 months). Main outcome measures were pre- and post-operative manifest refraction, anterior and posterior corneal astigmatism, simulated keratometry (CASimK) and Q value obtained by Scheimpflug imaging. Secondary outcome measures included corrected distance visual acuity (CDVA), central corneal densitometry, central corneal thickness, corneal volume (CV), anterior chamber volume (ACV) and anterior chamber depth (ACD). RESULTS: After DMEK surgery, mean pre-operative spherical equivalent (± SD) changed from + 0.04 ± 1.73 D to + 0.37 ± 1.30 D post-operatively (p = 0.06). CDVA, proportion of emmetropic eyes, ACV and ACD increased significantly during follow-up. There was also a significant decrease in posterior corneal astigmatism, central corneal densitometry, central corneal thickness and corneal volume over time (p = 0.001). Only anterior corneal astigmatism and simulated keratometry (CASimK) remained fairly stable after DMEK. CONCLUSION: Despite tendencies toward a hyperopic shift, changes in SE were not significant and refraction remained overall stable in pseudophakic patients undergoing DMEK for FED. Analysis of corneal parameters by Scheimpflug imaging mainly revealed changes in posterior corneal astigmatism pointing out the relevance of posterior corneal profile changes during edema resolution after DMEK.

[Comparative assessment of functional outcomes of different endothelial keratoplasty techniques]. / Sravnitel'naya otsenka funktsional'nykh rezul'tatov razlichnykh tekhnologii endotelial'noi keratoplastiki.

PURPOSE: Comparative analysis of the higher-order aberrations (HOA) of the cornea after endothelial keratoplasty (EK) using DSAEK and DMEK techniques; evaluation of the correlation between higher-order corneal aberrations and functional outcomes of the treatment. MATERIAL AND METHODS: The study included 47 patients (59 eyes). The main group consisted of 35 patients (35 eyes) with bullous keratopathy and Fuchs' endothelial dystrophy; among them, 19 patients underwent endothelial keratoplasty using the DSAEK technique and 16 - DMEK technique. The control group included 12 patients (24 eyes) of corresponding age without corneal pathology. Standard and special examination tests were performed before, as well as 6 and 12 months after the operation, including computed tomography and aberrometry of the cornea using the Pentacam HR system. Same tests were performed in the control group. RESULTS: The values of the main HOA of the anterior corneal surface: RMS coma (Z3±1, Z5±1), RMS spherical aberration (SA; Z40, Z60) and RMS HOA (Z3-6) 6 months after different EK techniques were statistically significantly higher than in the control group. A statistically significantly lower induction of aberrations of the posterior corneal surface after DMEK technique was revealed. Analysis of the final aberration pattern 6 months after surgery did not reveal any statistically significant differences in the values of the main (RMS coma, RMS SA, RMS HOA) total corneal aberrations after DSAEK and DMEK. A negative correlation was revealed between the best corrected visual acuity (BCVA) and HOA; however, it was statistically significant only for individual aberration values: RMS HOA (Z3-6) of the posterior corneal aberrations after DMEK (r= -0.634, p=0.049), and RMS coma (Z3±1, Z5±1) of the cornea after DSAEK (r= -0.57, p=0.042). CONCLUSION: Comparative analysis of total corneal HOA did not reveal a statistically significant difference in the main parameters: RMS coma, RMS SA, RMS HOA in patients after DSAEK and DMEK surgeries. Correlation analysis did not reveal any statistically significant effects of most aberrations on the functional outcomes of the treatment.

Diagnostic Performance of 3-Dimensional Thickness of the Endothelium-Descemet Complex in Fuchs' Endothelial Cell Corneal Dystrophy.

PURPOSE: To describe the diagnostic accuracy of 3-dimensional (3D) endothelium-Descemet's membrane complex thickness (En-DMT) in Fuchs' endothelial corneal dystrophy (FECD) and determine its potential role as an objective index of disease severity. DESIGN: Observational case-control study. PARTICIPANTS: One hundred four eyes of 79 participants (64 eyes of 41 FECD patients and 40 eyes of 38 healthy controls). METHODS: All participants received high-definition OCT imaging (Envisu R2210; Bioptigen, Buffalo Grove, IL). Fuchs' endothelial corneal dystrophy was classified clinically into early-stage (without edema) and late-stage (with edema) disease. Automatic and manual segmentation of corneal layers was performed using a custom-built segmental tomography algorithm to generate 3D maps of total corneal thickness (TCT) and En-DMT of the central 6-mm cornea. Regional En-DMT, regional TCT, and central-to-peripheral total corneal thickness ratio (CPTR) were evaluated and correlated to the clinical severity of FECD. Intraclass correlation coefficients (ICCs) and Bland-Altman plots were used to assess the reliability of the repeated measurements in all eyes. MAIN OUTCOME MEASURES: Central-to-peripheral total corneal thickness ratio and average En-DMT and TCT of central, paracentral, and peripheral regions. RESULTS: In FECD, a significant increase in En-DMT, CPTR, and TCT was found compared to controls (P < 0.001). For identifying FECD, average En-DMT of paracentral and peripheral regions achieved 94% sensitivity and 100% specificity (cutoffs, 19 µm and 20 µm, respectively), whereas CPTR showed 94% sensitivity with a 73% specificity (cutoff, 0.97). Regarding early-stage FECD, average En-DMT of central zones achieved 92% sensitivity and 97% specificity (cutoff, 18 µm), whereas CPTR showed 90% sensitivity and 88% specificity (cutoff, 0.97). The average En-DMT of central, paracentral, and peripheral regions was correlated highly with FECD clinical stage (Spearman's ρ = 0.813, 0.793, and 0.721, respectively; all P < 0.001), compared with CPTR and mean TCT of paracentral zones (0.672 and 0.481, respectively; P < 0.001). The ICC values ranged from 0.98 (En-DMT) to 0.99 (TCT) with a good agreement between the automatic and manual measurements. CONCLUSIONS: Regional 3D En-DMT is a novel diagnostic tool of FECD that can be used to quantify the disease severity with excellent reliability.