The influence of obesity, diabetes mellitus and smoking on fuchs endothelial corneal dystrophy (FECD).

To detect environmental factors, which may be possible risk factors in the disease course of Fuchs' endothelial corneal dystrophy (FECD). Evaluation of patients with FECD registered in the FECD genetics database of the Center for Ophthalmology, University Hospital Cologne. For the evaluation, disease onset, central corneal thickness, best spectacle corrected visual acuity (BSCVA, logMAR), and modified Krachmer grading (grades 1-6) were correlated with the presence of diabetes mellitus (DM), body mass index (BMI), and smoking behavior. To put the age-related increase in Krachmer grading into perspective, a correction of grading were formed. Depending on the variables studied, differences between groups were examined by Mann-Whitney U test and chi-square test. The significance level was 5%. 403 patients with FECD were included in the analysis. The mean age of the patients was 70.0 ± 10.32 (range 28-96) years. The mean age at diagnosis of those patients was 63.1 ± 13.2 years. The female-to-male ratio was 1.46:1. Patients with a BMI > 30.0 kg/m2 developed FECD significantly earlier than patients with a BMI < 30 kg/m2, p = 0.001. Patients with DM showed significantly more often an Krachmer grade of 5, p = 0.015. Smoking had a negative effect on Krachmer grading (p = 0.024). Using the mediation analysis, the presence of DM correlated Krachmer Grade 5 (p = 0.015), and the presence of DM correlated with BMI > 30.0 kg/m2 (p = 0.012). In addition to smoking and DM our study shows for the first time that obesity may have a negative impact on the development of FECD. Whether dietary interventions and hormones can influence the development or progression of the disease needs to be investigated in future studies.

Association Between Fuchs Endothelial Corneal Dystrophy, Diabetes Mellitus, and Multimorbidity.

PURPOSE: The aim of this study was to assess risk for demographic variables and other health conditions that are associated with Fuchs endothelial corneal dystrophy (FECD). METHODS: We developed a FECD case-control algorithm based on structured electronic health record data and confirmed accuracy by individual review of charts at 3 Veterans Affairs (VA) Medical Centers. This algorithm was applied to the Department of VA Million Veteran Program cohort from whom sex, genetic ancestry, comorbidities, diagnostic phecodes, and laboratory values were extracted. Single-variable and multiple variable logistic regression models were used to determine the association of these risk factors with FECD diagnosis. RESULTS: Being a FECD case was associated with female sex, European genetic ancestry, and a greater number of comorbidities. Of 1417 diagnostic phecodes evaluated, 213 had a significant association with FECD, falling in both ocular and nonocular conditions, including diabetes mellitus (DM). Five of 69 laboratory values were associated with FECD, with the direction of change for 4 being consistent with DM. Insulin dependency and type 1 DM raised risk to a greater degree than type 2 DM, like other microvascular diabetic complications. CONCLUSIONS: Female sex, European ancestry, and multimorbidity increased FECD risk. Endocrine/metabolic clinic encounter codes and altered patterns of laboratory values support DM increasing FECD risk. Our results evoke a threshold model in which the FECD phenotype is intensified by DM and potentially other health conditions that alter corneal physiology. Further studies to better understand the relationship between FECD and DM are indicated and may help identify opportunities for slowing FECD progression.

Demographic profile and clinical characteristics of Fuchs' endothelial corneal dystrophy in a tertiary eye care center.

Purpose: This study was performed to determine the demographic profile and clinical characteristics in patients with Fuchs' endothelial corneal dystrophy (FECD) reporting to a tertiary eye care center in India. It is a retrospective, single-center, observational study. Methods: The study included 280 patients (559 eyes) diagnosed with FECD presenting between January 2013 and December 2020. The data was collected from the electronic medical record system of the institute. Patient data included demographic features, clinical characteristics, investigations, and surgical interventions. Results: The mean age of the patients was 62 years. Late-onset FECD (95.7%) was more common than early-onset FECD (4.3%). Male: female ratio for late-onset FECD and early-onset FECD was 1:1.65 and 3:1, respectively. More than one-third of the patients had associated systemic history. Preexisting ocular diseases were seen in 5.9% of eyes. Blurring of vision was seen in 383 eyes (68.5%), 13 eyes (2.1%) had glare, and 163 eyes (29.2%) were asymptomatic. A total of 113 surgical interventions were done in 108 eyes (including repeat transplants). Only cataract surgery was done in 40 (7.2%) eyes, whereas penetrating keratoplasty, Descemet stripping endothelial keratoplasty, and Descemet membrane endothelial keratoplasty without or with cataract surgery (sequential or triple procedure) were done in 12 (2.1%), 47 (8.4%), and 14 (2.5%) eyes, respectively. Conclusion: Patients with FECD present mostly during the sixth decade. Posterior lamellar keratoplasty is the most common transplant procedure being performed on FECD patients.

Clinical profile and demographic distribution of Fuchs' endothelial dystrophy: An electronic medical record-driven big data analytics from an eye care network in India.

Purpose: To describe the demographics and clinical profile of Fuchs' endothelial corneal dystrophy (FECD) in patients presenting to a multi-tiered ophthalmology hospital network in India. Methods: This cross-sectional hospital-based study included 3,082,727 new patients presenting between August 2010 and December 2021. Patients with a clinical diagnosis of FECD in at least one eye were included as cases. The data were collected using an electronic medical record system. Results: Overall, 2570 (0.08%) patients were diagnosed with FECD. The majority of the patients were female (65.53%) and were predominantly adults (99.92%). The most common age group at presentation was during the seventh decade of life with 867 patients (33.74%). The overall prevalence was higher in patients from a higher socioeconomic status (0.1%) presenting from the urban geography (0.09%) and in retired individuals (0.4%). About half of the 5,140 eyes had mild or no visual impairment (< 20/70) in 2643 eyes (51.42%) followed by moderate visual impairment (>20/70 to 20/200) in 708 eyes (13.77%). The average logMAR was 0.61 ± 0.81 at presentation. The most documented corneal signs were guttae (76.63%), corneal scar (23%) and stromal edema (21.73%). The most associated ocular comorbidity was cataract (47.32%) followed by glaucoma (5.39%). More than a tenth of the affected eyes required a surgical intervention of endothelial keratoplasty (15.58%). Conclusion: FECD more commonly affects females presenting during the seventh decade of life. Majority of the eyes had mild or no visual impairment and endothelial keratoplasty is warranted in a tenth of the affected eyes.

TCF4 trinucleotide repeat expansion in Swedish cases with Fuchs' endothelial corneal dystrophy.

PURPOSE: Fuchs' endothelial corneal dystrophy (FECD) has been considered a genetically heterogeneous disease but is increasingly associated with the transcription factor 4 (TCF4) gene. This study investigates the prevalence of the cytosine-thymine-guanine (CTG)n repeat expansion in TCF4 among FECD patients in northern Sweden coupled to the phenotype. METHODS: Blood samples were collected from 85 FECD cases at different stages. Short tandem repeat PCR and triplet repeat-primed PCR were applied in order to determine TCF4 (CTG)n genotype. RESULTS: A (CTG)n repeat expansion (n > 50) in TCF4 was identified in 76 of 85 FECD cases (89.4%) and in four of 102 controls (3.9%). The median (CTG)n repeat length was 81 (IQR 39.3) in mild FECD and 87 (IQR 13.0) in severe FECD (p = 0.01). A higher number of (CTG)n repeats in an expanded TCF4 allele increased the probability of severe FECD. Other ocular surgery was overrepresented in FECD cases without a (CTG)n repeat expansion (44.4%, n = 4) compared with 3.9% (n = 3) in FECD cases with an (CTG)n repeat expansion (p < 0.001). CONCLUSION: In northern Sweden, the FECD phenotype is associated with (CTG)n expansion in the TCF4 gene, with nearly 90% of patients being hetero- or homozygous for (CTG)n expansion over 50 repeats. Furthermore, the severity of FECD was associated with the repeat length in the TCF4 gene. Ocular surgery might act as an environmental factor explaining the clinical disease in FECD without a repeat expansion in TCF4.

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.

Comparison of TCF4 repeat expansion length in corneal endothelium and leukocytes of patients with Fuchs endothelial corneal dystrophy.

Expansion of CTG trinucleotide repeats (TNR) in the transcription factor 4 (TCF4) gene is highly associated with Fuchs Endothelial Corneal Dystrophy (FECD). Due to limitations in the availability of DNA from diseased corneal endothelium, sizing of CTG repeats in FECD patients has typically been determined using DNA samples isolated from peripheral blood leukocytes. However, it is non-feasible to extract enough DNA from surgically isolated FECD corneal endothelial tissue to determine repeat length based on current technology. To circumvent this issue, total RNA was isolated from FECD corneal endothelium and sequenced using long-read sequencing. Southern blotting of DNA samples isolated from primary cultures of corneal endothelium from these same affected individuals was also assessed. Both long read sequencing and Southern blot analysis showed significantly longer CTG TNR expansion (>1000 repeats) in the corneal endothelium from FECD patients than those characterized in leukocytes from the same individuals (<90 repeats). Our findings suggest that the TCF4 CTG repeat expansions in the FECD corneal endothelium are much longer than those found in leukocytes.

Corneal transplantation activity in Catalonia, Spain, from 2011 to 2018: Evolution of indications and surgical techniques.

PURPOSE: To report corneal transplant activity carried out in Catalonia (Spain) and the evolving indications for keratoplasty over an 8-year period. METHODS: Annual reports from the Catalan Transplant Organization, Spain, on corneal graft indications and techniques from 2011 to 2018 were reviewed. RESULTS: A total of 9457 keratoplasties were performed in Catalonia, from January 2011 to December 2018. The most frequent indications were bullous keratopathy (BK; 20.5%), Fuchs endothelial dystrophy (FED; 17.9%), re-graft (13.7%), and keratoconus (11.3%). Penetrating keratoplasty (PKP) accounted for 63.4% of all performed keratoplasties. Since the introduction of eye bank precut tissue for Descemet stripping automated endothelial keratoplasty (DSAEK) in 2013 and for Descemet membrane endothelial keratoplasty (DMEK) in 2017 the number of endothelial keratoplasties has drastically increased. An increasing trend of posterior lamellar techniques over the total of keratoplasties was found (p<0.001). Endothelial keratoplasties for different endothelial diseases indications (BK, FED, and re-graft), also showed and increasing trend (p<0.001). DMEK is the technique with the highest increase (statistically significantly different from linearity) over other endothelial keratoplasties in FED (p<0.001) but not in BK (p = 0.67) or re-grafts (p = 0.067). CONCLUSION: Endothelial diseases represented the top indication for keratoplasty over the 8-year period. PKP is still the most used technique in Catalonia, but endothelial keratoplasties and especially DMEK showed a significant increasing trend over the last years. This is congruent with the main rationale nowadays for keratoplasties: to customize and transplant as less tissue as possible. Therefore, the availability of precut tissue could have definitely enforced such approach.

Fuchs endothelial corneal dystrophy: The vicious cycle of Fuchs pathogenesis.

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.

Real-World Outcomes of DMEK: A Prospective Dutch registry study.

PURPOSE: This study analyzed real-world practice patterns, graft survival, and outcomes of Descemet membrane endothelial keratoplasty (DMEK) in the Netherlands. DESIGN: Population-based interventional clinical study. METHODS: In this prospective registry study, all consecutive primary DMEK procedures registered in the Netherlands Organ Transplant Registry were identified. Short-term graft survival and outcomes of primary transplants for Fuchs' endothelial dystrophy (FED) were analyzed using Kaplan-Meier survival curves with log-rank test and Cox regression. Linear mixed model analyses were used for best spectacle-corrected visual acuity (BSCVA), spherical equivalent, hyperopic shift, and endothelial cell density. RESULTS: 752 DMEKs were identified between 2011 and 2018. In 90% of cases, the indication for DMEK was FED. Graft survival measured 87% at 3 months, 85% at 6 months, 85% at 1 year, and 78% at 2 years. DMEK procedures after 2015 showed better survival compared to previous years (Hazard ratio = 0.4; P < .001). Baseline BSCVA in primary transplants with FED measured on average 0.45 logarithm of the minimum angle of resolution (logMAR) (95% confidence interval [CI], 0.41-0.49), and significantly improved (overall P < .001) to 0.17 logMAR (95% CI, 0.14-0.21) at 3 months, 0.15 logMAR (95% CI, 0.11-0.18) at 6 months, 0.12 logMAR (95% CI, 0.08-0.16) at 1 year, and 0.08 (95% CI, 0.05-0.12) at 2 years. At 3 months, a hyperopic shift of +0.36 diopters (P < .001) was observed and endothelial cell loss measured 33%. CONCLUSION: Our findings provide real-world support that DMEK is an effective treatment for FED with respect to vision restoration, inducing a small hyperopic shift with an acceptable endothelial cell loss. Graft survival improved over time, suggesting a learning curve on a national level.

Trends in corneal transplantation in a single center in Barcelona, Spain. Transitioning to DMEK.

PURPOSE: To observe trends in surgical techniques for corneal transplantation and main indications in our hospital over the past five years. METHODS: Retrospective descriptive study, including all keratoplasties performed at the Hospital Clinic of Barcelona, Spain, between January 2014 and December 2018. RESULTS: In total, 332 keratoplasties were performed. In total, 127 (38.25%) were penetrating keratoplasties (PK), and 205 (61.75%) were lamellar keratoplasties (LK). In 2014, a total of 48 keratoplasties were carried-out, whereas in 2018, the total was 93, which represents a 93.75% increase in corneal transplantation surgeries. Eye bank-delivered precut tissue for DMEK was introduced in 2016, and 3 cases (6.25%), were carried out that year. In 2018, DMEK became the leading technique with 56 cases (60.22%). Fuchs' dystrophy was the leading indication for corneal transplant (37.63%) in 2018. CONCLUSION: Introduction of DMEK in a single center can be implemented in a relatively short period of time, becoming the most popular surgical procedure in corneal transplantation. A possible factor encouraging this change is the availability of eye bank-delivered precut tissue, and standardization of donor preparation and host surgical steps, optimizing surgical time in the operating room. This trend should lead to better visual outcomes, faster recovery times, and eventually to a higher surgical volume per year.

Comorbidity of Keratoconus and Fuchs' Corneal Endothelial Dystrophy: A Review of the Literature.

INTRODUCTION: Comorbidity of keratoconus (KC) and Fuchs' corneal endothelial dystrophy (FD) has been sporadically reported in the literature since the early nineties. This review summarizes findings from the related literature while examining the possibilities related to the concurrent development of these disorders and the clinical significance for the clinician. METHODS: NLM/PubMed, Ovid, Google Scholar, Cornea, and Cochrane database were reviewed for research papers presenting cases of comorbid KC and FD published between January 1990 and July 2019. RESULTS: Fifteen papers which presented 69 cases were included in the study. Most cases were women (56.5%), involvement was bilateral (59.4%), and the age range was wide (15-82 years) with a normal distribution. Incidence is expected to be approximately 1 per 100,000. FD is the most frequent comorbid corneal dystrophy diagnosed in KC patients. There are 4 distinct possibilities for the cooccurrence of KC and FD, the most likely being that of chance. CONCLUSION: The overall incidence of these disorders found in combination is very low and, in absence of other conclusively proven hypotheses, most likely attributable to chance. The treatment plan should be tailored to the needs of the individual patient, since the diagnosis can be made in any stage of life and could be part of a more complex presentation that includes another pathology of the cornea or senile cataract. The inclusion of preoperative topography and specular microscopy as routine in cataract preoperative assessment would protect against any postoperative complications in these patients.

Coexistence of Congenital Hereditary Endothelial Dystrophy and Fuchs Endothelial Corneal Dystrophy Associated With SLC4A11 Mutations in Affected Families.

PURPOSE: To evaluate parents of probands affected with autosomal recessive congenital hereditary endothelial dystrophy (CHED) for clinical signs of Fuchs endothelial corneal dystrophy (FECD) and to determine the genotypes of the SLC4A11 gene in the probands and their parents. METHODS: This study involved 9 patients affected with CHED from 8 families. The parents of such probands were examined to investigate for possible signs of FECD although they did not present with any visual complaints. Blood samples were collected after obtaining consent, from all 9 cases and the parents of each proband, for genetic analysis. Genomic DNA isolated from blood leukocytes was used for genetic analysis. Screening of the coding regions of the SLC4A11 gene for mutations was carried out by standard procedures using polymerase chain reaction (PCR) amplification and sequencing. Sequences were checked against the human SLC4A11 reference sequence to detect alterations and in normal control samples available in the laboratory. RESULTS: The probands had characteristic signs of CHED, whereas one of the parents of each of the probands showed early signs of FECD, characterized by the presence of guttae in the central cornea corroborative with the diagnosis of FECD, and were otherwise asymptomatic at that time. The CHED-affected probands were homozygous for various SLC4A11 mutations, and their parents were heterozygous for the same. The mutations included missense mutations in 6 probands and nonsense mutations in 2 cases. CONCLUSIONS: Heterozygosity for SLC4A11 mutations in the parents of children with autosomal recessive CHED appears to be a risk factor for the development of FECD in these cases.

REVIEW: Current understanding of the pathogenesis of Fuchs' endothelial corneal dystrophy.

Fuchs' endothelial corneal dystrophy (FECD) is the most prominent reason for corneal-endothelial transplantations across the globe. The disease pathophysiology manifests through a combination of various genetic and non-heritable factors. This review provides a comprehensive list of known genetic players that cause FECD, and discusses the prominent pathological features that participate in disease progression, such as channel dysfunction, abnormal extracellular matrix deposition, RNA toxicity, oxidative stress, and apoptosis. Although current practices to correct visual acuity involve surgical intervention, this review also discusses the scope of various non-surgical therapeutics to remedy FECD.

TCF4 and COL8A2 Gene Polymorphism Screening in a Greek Population of Late-onset Fuchs Endothelial Corneal Dystrophy.

BACKGROUND/AIM: Fuchs' endothelial corneal dystrophy (FECD) is a hereditary, progressive, bilateral, and irreversible disorder of the corneal endothelium. The purpose of this study was to develop a novel, accurate and high-throughput real-time polymerase chain reaction (PCR) method and melting-curve analysis in order to genotype the rs613872 polymorphism in the transcription factor 4 (TCF4) gene and to implement it on a well-ascertained sample of 22 Greek FECD patients and 58 healthy individuals, age- and sex-matched. PATIENTS AND METHODS: DNA was extracted from blood samples, which were screened with the DNA sequencing method in order to detect the g.31753T>G/p.L450W (rs8035192) and g.31767C>A/p.Q455K (rs8035191) mutations in a COL8A2 genomic region. RESULTS: TCF4 risk G allele frequency increased to 48% in FECD patients compared to 17% in healthy-subjects [OR=4.82 (95% CI=1.98-11.73)]. No p.L450W and p.Q455K COL8A2 gene mutations were detected. CONCLUSION: We confirmed that rs613872 in the TCF4 gene is strongly and statistically associated with late-onset FECD in a Greek population.

Fuchs Endothelial Corneal Dystrophy: Update on Pathogenesis and Future Directions.

Fuchs endothelial corneal dystrophy (FECD) is the most common indication for corneal transplantation in the United States, accounting 36% of the almost 47,000 transplants performed in 2016. Although the surgical management of FECD has undergone a revolution over the past 20 years, its pathogenesis remains elusive, with multiple putative disease pathways and an ever increasing number of candidate genes thought to play a role. This review will summarize the recent advancements in our understanding of the biology of FECD, including potential parallels with neurodegenerative disease like amyotrophic lateral sclerosis and will highlight prospects for future treatment advances.

["The Big Five" - Cataract Surgery Under Multiple Ocular Comorbidity: Customised Approach to Prevent Complications]. / "The Big Five" ­ Kataraktchirurgie bei multiplen okulären Komorbiditäten: individuelle Vorgehensweise zur Komplikationsvermeidung.

The co-occurence of 5 diseases (cataract, Fuchs dystrophy, pseudoexfoliation syndrome, age-related macular degeneration and dry eye syndrome) can lead to massive impairment of visual acuity. Our case series show that cataract surgery can lead to an enormous profit in visual rehabilitation and therefore in daily routine.

Association of polymorphisms in the intron of TCF4 gene to late-onset Fuchs endothelial corneal dystrophy: An Indian cohort study.

PURPOSE: Fuchs endothelial corneal dystrophy (FECD) is a progressive degenerative disease of the corneal endothelium. It is genetically heterogeneous and follows either an autosomal dominant or sporadic pattern of inheritance. Here, we have explored the association of four previously reported intronic single nucleotide polymorphisms and intronic CTG repeat expansions in TCF4 gene to FECD in an Indian cohort. METHODS: The cohort consisting of 52 sporadic late-onset cases, 5 early-onset cases, and 148 controls was taken for the study. rs2286812 and rs613872 were genotyped by allele specific polymerase chain reaction (ASPCR) and PCR-based restriction digestion, respectively; rs17595731 and rs9954153 were genotyped by Taqman assay using real-time PCR. The quantitative assessment of the CTG repeat region was performed by PCR/Sanger DNA sequencing. The repeats were assessed qualitatively by short tandem repeat and triplet repeat primed PCR assays. The statistical analysis was performed using two-tailed Fisher's exact probability test. RESULTS: SNPsrs613872 (G/T) for the 'G' allele (P value: 4.57 × 10-5) and rs17595731 (C/T) for the 'C' allele (P value: 1.87 × 10-5), respectively, showed a significant association to sporadic late-onset FECD. CTG repeat expansions were found to be associated with FECD with a P value = 2.4 × 10-3. CONCLUSION: rs613872, rs17595731, and CTG repeat expansions in intronic region of TCF4 are associated with increased risk of sporadic late-onset FECD in the Indian cohort studied.

CTG18.1 repeat expansion may reduce TCF4 gene expression in corneal endothelial cells of German patients with Fuchs' dystrophy.

PURPOSE: It was the aim of this investigation to elucidate the functional effects of CTG18.1 trinucleotide repeat expansion and the polymorphism rs613872 in the transcription factor 4 (TCF4) in corneas of patients affected by Fuchs' endothelial corneal dystrophy (FECD). METHODS: Sixty-one unrelated German patients with FECD and 113 unaffected controls were investigated and genotyped for the CTG18.1 locus by triplet primed PCR (TP-PCR) and the rs613872 polymorphism via Sanger sequencing and by employing genomic DNA from peripheral blood leucocytes. DNA and RNA retrieved from human corneal endothelial explants were examined for alterations in the gene expression of TCF4, ZEB1, E-cadherin, N-cadherin, as well as the CTG18.1 locus. RESULTS: The CTG18.1 trinucleotide repeat expansion (>50 repeats) was detected in the peripheral blood in 77% of affected FECD patients and 11.5% of the healthy volunteers. Applying the TP-PCR method, the length of CTG18.1 repeat expansions correlates in the blood and corneal cells. We noted that the CTG18.1 trinucleotide repeat expansion was associated with reduced TCF4 and ZEB1 gene expression, especially in the explanted corneal endothelial cells. While E-cadherin gene expression was not detected in any corneal endothelial cells, expression of CDH2 (N-cadherin) was detected in FECD-affected endothelium and in our controls. CONCLUSIONS: The CTG18.1 repeat expansion may reduce gene expression of TCF4 and ZEB1, suggesting that a mechanism triggering a loss of function may contribute to FECD. The correlation of CTG18.1 repeat expansion from blood and the cornea may represent the first step toward investigating the potential relevance of testing the blood of cornea donors to minimize the risk of transplanting grafts potentially affected with FECD.

[Development of Endothelial Cell Density after Penetrating Keratoplasty in Patients with Fuchs Dystrophy or Keratoconus - Comparison of Excimer Laser and Mechanical Trephination]. / Entwicklung der Endothelzelldichte nach perforierender Keratoplastik bei Patienten mit Fuchs-Dystrophie oder Keratokonus ­ Vergleich von Excimer-Laser- und mechanischer Trepanation.

Purpose The aim of this retrospective study was to compare the development of endothelial cell density (ECD) after penetrating keratoplasty (PKP) in patients with Fuchs dystrophy (FD), keratoconus (KC) or "other diagnoses" (OD), depending on the type of trephination. Patients and Methods In 104 eyes with Fuchs dystrophy, keratoconus or "other diagnoses", the ECD after PKP using either excimer laser (EXC) or mechanical trephination (MECH) was registered after 1.5, 6, 12, 18 and 24 months. With linear and exponential regression models, the endothelial cell loss (ECL) was determined as absolute and percentage cell loss per year. Results For the entire group of patients, ECD was significantly higher after EXC-PKP during the full range of follow-up (except 6 months). With a linear regression model, there was no significant difference in the absolute ECL per year (p = 0.084), but with an exponential regression model, there was a significant difference in the percentage ECL per year (p = 0.021) in favour of EXC trephination. For keratoconus (n = 33), except for the 24-month-follow-up (p = 0.035), ECD was not significantly different on the basis of EXC vs. MECH. With a linear regression model, there was a significant difference in the absolute ECL per year (p = 0.015) in favour of EXC-trephination, but with an exponential regression model there was no significant difference in the percentage ECL per year (p = 0.088) between the two types of threphination. In patients with FUCHS (n = 35) - except for the 6-week-follow-up (p = 0.024) - ECD was not significantly different for EXC vs. MECH. With linear/exponential regression model, the ECL per year was not significantly different in favour of any type of trephination (p = 0.287/p = 0.121). In patients with OD (n = 36), ECD was not significantly different for EXC vs. MECH. With a linear/exponential regression model, the ECL per year was not significantly different in favour of any type of trephination (p = 0.494/p = 0.787). Conclusion During the first 24 months after PKP, a significantly higher ECD and a significantly lower percentage of ECL per year was observed after EXC trephination for the entire group of patients. For the different diagnostic groups KC, FD and OD, no significant difference in ECD or ECL loss was noticed over a range of follow-up intervals. This may most likely be attributed to the small number of patients in the three subgroups.