Fuchs Corneal Dystrophy Research Articles

Clinical Outcomes in Patients With Traumatic Dehiscence of Penetrating Keratoplasty Grafts.

The purpose of this study was to report clinical characteristics and outcomes of surgical repair for patients with traumatic dehiscence of penetrating keratoplasty (PKP) grafts. Retrospective, consecutive chart review of patients evaluated at Bascom Palmer Eye Institute between 2015 and 2020 with traumatic dehiscence of penetrating keratoplasty grafts. The study cohort consisted of 65 eyes of 65 patients. The mean age at presentation was 72 years (SD 18), with a male predominance (65%). The most common indications for PKP included keratoconus (42%), corneal scar (31%), and Fuchs corneal dystrophy (8%). Dehiscence occurred as a result of blunt trauma in 94% of cases, and the mean wound length was 6.4 clock hours (SD 2.4), with a predominance of inferior dehiscence. The mean presenting visual acuity (VA) was 2.45 logMAR (SD 0.41), and the mean final VA was 2.17 logMAR (SD 0.99). Graft failure occurred in 64% of patients, and 22% underwent repeat PKP. When stratified by indication for corneal transplantation (keratoconus vs. other), there was no significant difference in graft age at the time of rupture, final VA, rate of graft failure, or rate of repeat PKP. Traumatic dehiscence of corneal grafts remains a rare but serious subtype of ocular trauma with generally poor visual prognoses. Presenting VA along with severity of trauma and posterior segment involvement tend to be the worst prognostic factors in final visual outcome.

Clinical experience in rehabilitation of patients with Fuchs corneal dystrophy and cataract by ultrasonic phacoemulsification and descemetorhexis

BACKGROUND: The potential for peripheral corneal endothelial capabilities is a novel, poorly understood direction. The comprehensive development of various modifications of endothelial keratoplasty goes hand in hand with a lack of donor material. This explains the continuous search for safe tissue-preserving techniques.
 AIM: The aim of this study is to evaluate the clinical and functional results of treatment of patients with Fuchs corneal dystrophy and cataract using a combination of cataract ultrasound phacoemulsification and descemetorhexis.
 MATERIALS AND METHODS: The study included 3 patients (3 eyes), 3 women aged 65 to 78 (on average 73.6 7.5 years). The follow-up period in the postoperative period was 36 months. The inclusion criteria were: patient complaints about glare, blurred vision and cloudy vision in the morning; the location of the guttae in the central 5 mm zone, central corneal stromal edema less than 610 microns, the inability to count endothelial cells in the center, endothelial cells density on the periphery in the upper quadrant more than 1400 cells/mm2. All patients underwent phacoemulsification of cataract with IOL implantation and subsequent descemetorhexis in the 4 mm zone.
 RESULTS: At 1 month an increase in the central corneal thickness and a slight increase in uncorrected visual acuity (UCVA) and in best corrected visual acuity (BCVA). By the 3rd month, positive dynamics was present: an increase in UCVA and BCVA in all cases, a decrease in the central corneal thickness (559 20 m), resorption of stromal edema, increase in corneal transparency, possibility to calculate the endothelial cells density in the center (866 46 cells/mm2). At 36 months, the BCVA was 0.6, 0.4 and 0.5, respectively.
 CONCLUSIONS: Restoration of corneal transparency was achieved in 100% of cases (3 out of 3). An analysis of the clinical results of the descemetorhexis + phacoemulsification + IOL operation demonstrated an increase in visual acuity, an increase in corneal transparency and a decrease in stromal edema in patients with initial Fuchs corneal dystrophy and cataract. The possibility of not using donor material for the treatment of Fuchs corneal dystrophy is a promising trend. Further accumulation of material is required.

The Ins and Outs of Clusterin: Its Role in Cancer, Eye Diseases and Wound Healing.

Clusterin (CLU) is a glycoprotein originally discovered in 1983 in ram testis fluid. Rapidly observed in other tissues, it was initially given various names based on its function in different tissues. In 1992, it was finally named CLU by consensus. Nearly omnipresent in human tissues, CLU is strongly expressed at fluid-tissue interfaces, including in the eye and in particular the cornea. Recent research has identified different forms of CLU, with the most prominent being a 75-80 kDa heterodimeric protein that is secreted. Another truncated version of CLU (55 kDa) is localized to the nucleus and exerts pro-apoptotic activities. CLU has been reported to be involved in various physiological processes such as sperm maturation, lipid transportation, complement inhibition and chaperone activity. CLU was also reported to exert important functions in tissue remodeling, cell-cell adhesion, cell-substratum interaction, cytoprotection, apoptotic cell death, cell proliferation and migration. Hence, this protein is sparking interest in tissue wound healing. Moreover, CLU gene expression is finely regulated by cytokines, growth factors and stress-inducing agents, leading to abnormally elevated levels of CLU in many states of cellular disturbance, including cancer and neurodegenerative conditions. In the eye, CLU expression has been reported as being severely increased in several pathologies, such as age-related macular degeneration and Fuch's corneal dystrophy, while it is depleted in others, such as pathologic keratinization. Nevertheless, the precise role of CLU in the development of ocular pathologies has yet to be deciphered. The question of whether CLU expression is influenced by these disorders or contributes to them remains open. In this article, we review the actual knowledge about CLU at both the protein and gene expression level in wound healing, and explore the possibility that CLU is a key factor in cancer and eye diseases. Understanding the expression and regulation of CLU could lead to the development of novel therapeutics for promoting wound healing.

Rho Kinase Inhibitors - Role in Glaucoma and Cornea Practice

The rho-kinase pathway has been implicated in the pathogenesis of various ocular disorders like glaucoma, Fuchs cornealdystrophy, diabetic retinopathy, diabetic macular edema, age-related macular degeneration (AMD), ROP. ROCK molecules andthe ROCK pathway regulate multiple physiological functions, such as cell contraction, migration, proliferation, angiogenesis,chemotaxis, neural protection and vasodilatation, mainly via reorganization of the cytoskeleton. Corneal endothelium increasesendothelial cell proliferation and adhesion and decreases endothelium to mesenchyme transformation. Various studies havedemonstrated their safety and efficacy for ophthalmic use. This review highlights the use of ROCK inhibitors in glaucoma andcorneal diseases.

Применение сверточных нейронных сетей для определения эндотелиальной дистрофии Фукса

Purpose. To evaluate the application of convolutional neural networks for the automatic detection of Fuchs' dystrophy. Material and methods. The study included 700 biomicroscopic images of the corneal endothelium (Tomey EM-3000) randomly selected from the database of the Saint-Petersburg brunch of the S. Fyodorov Eye Microsurgery Federal State Institution. At the first stage, the images were divided into 2 groups. The first group included images with the presence of Fuchs' dystrophy, the second – another pathology or a healthy cornea. The corneal endothelial cell density images were divided into three categories: training, validation, and test datasets. In our study we tested various architectures of convolutional neural networks: ResNet18, ResNet50, VGG16, VGG19 and GoogleNet. Results. The approbation of the neural network on the test sample has given the following values of the F-measure: ResNet18: 0.985; ResNet50: 1,000; VGG16: 0.940; VGG19: 0.990; GoogleNet: 0.987. Pre-trained network ResNet50 performed best with frozen layers, Adam optimizer, cross-entropy as a loss function, and a training step of 0.000005. Conclusion. The use of convolutional neural networks for the automatic detection of Fuchs' dystrophy can be successfully implemented as part of a doctor's decision support system. ResNet50 showed the best results among all types of models and did not give a single error on the test sample, which indicates the high efficiency of using this network in the classification algorithm for corneal endothelial images. Keywords: artificial intelligence, Fuchs corneal dystrophy, convolutional neural networks

Rho Kinase Inhibitors for Glaucoma and Optic Neuropathy Treatment: Enzyme Activity, Cell Effects, IOP-Lowering and Neuroprotection Perspectives

Rho kinases, (Rho-Associated Coiled-Coil Kinases; ROCKs) are ubiquitous enzymes found inside all cells of the body. Consequently, ROCKs are involved in numerous cellular functions such as cell contraction, cell migration and proliferation. As such, their over-expression / activation has been implicated in diseases ranging from diabetes, erectile dysfunction, hypertension, asthma, cancer, cardiovascular hypertrophy, inflammatory diseases, pulmonary hypertension and so on. In the eye, ROCKs are involved in the development of glaucoma, Fuchs corneal dystrophy, diabetic retinopathy and age-related macular degeneration. Inhibitors of ROCKs have proven useful drugs to treat the afore-mentioned disorders, and in particular they are effective intraocular pressure lowering agents with added neuroprotective activities. This review addresses the latter aspect of ROCK physiology, pharmacology and pathology, and the clinical utility of ROCK inhibitors towards preservation of eyesight from the ravages of glaucomatous optic neuropathy

Сравнительный анализ ультразвуковой и фемтолазер-ассистированной факоэмульсификации у пациентов с первичной эндотелиальной дистрофией роговицы Фукса

Comparative analysis of ultrasound and femtolaser-assisted phacoemulsification in patients with primary endothelial Fuchs corneal dystrophy

Cataract surgery and intraocular lens placement in patients with Fuchs corneal dystrophy: a review of the current literature.

Late-onset Fuchs endothelial corneal dystrophy (FECD) is seen in approximately 4% of individuals over the age of 40. With the growing population of adults over the age of 65, ophthalmologists need to be aware of the preoperative, perioperative, and postoperative considerations involved in cataract surgery in Fuchs patients. Management of cataract patients with FECD requires preoperative assessment of endothelial cell size, density, and morphology. Considerations for perioperative endothelial cell loss include patients with hyperopia and shallow anterior chambers, phacoemulsification technique, transfer of ultrasonic energy to the cornea, corneal-protective perioperative agents, as well as thermal and mechanical damage. Ophthalmologists performing cataract surgery on patients with FECD must carefully consider the risks of endothelial cell loss during surgery and minimize the risk of corneal decompensation after surgery. Preoperative management should evaluate the severity of the FECD as well as individual factors such as cataract density, the health and thickness of the cornea, and the anterior chamber depth. Perioperative techniques, adjustments to biometry calculations, and intraocular lens (IOL) selection may help optimize visual outcomes and recovery time.

Long-term Outcomes in Fellow Eyes Comparing DSAEK and DMEK for Treatment of Fuchs Corneal Dystrophy

To compare the long-term results of Descemet's stripping automated endothelial keratoplasty (DSAEK) and Descemet's membrane endothelial keratoplasty (DMEK) in fellow eyes for treatment of Fuchs endothelial corneal dystrophy. This study is a 2-centered, retrospective case series of 64 patients (128 eyes) with DSAEK followed by DMEK. The main outcomes measured were best spectacle-corrected visual acuity (BSCVA) and duration of time to achieve BSCVA as well as eye preference. Preoperative median logarithm of the minimum angle of resolution (logMAR) BSCVA was similar in eyes receiving DMEK 0.36 ± 0.26 and DSAEK 0.42 ± 0.34 (P=.266). The average follow-up time needed for the DMEK eyes to achieve BSCVA was faster than that of DSAEK (277 days vs 490 days, P=.0014). With long-term follow-up, the BSCVA of the DMEK eyes [0.09 ± 0.10 logMAR] and DSAEK eyes [0.11 ± 0.16 logMAR] did not show a statistically significant difference (P=.069). Twenty-two of the 64 preferred the DMEK eye, 17 patients preferred the DSAEK eye (P=.423), and 25 patients did not have a preference. In the DMEK group, the average spherical equivalent was -0.08 compared with the DSAEK group at 0.06 (P=.2854). In our fellow eye study with long-term follow-up, DMEK and DSAEK had comparable levels of BSCVA and patient satisfaction. The DMEK eyes reached their BSCVA sooner, whereas the DSAEK eyes improved over a longer time frame. A greater number of patients had 20/25 and 20/20 vision in the DMEK group; however, the difference was not statistically significant. NOTE: Publication of this article is sponsored by the American Ophthalmological Society.

Polymorphic amyloid degeneration of the cornea: A Clinical and In vivo confocal microscopy study

We report a rare case of polymorphic amyloid degeneration (PAD) with in vivo confocal microscopy and anterior segment optical coherence tomography (AS-OCT). A 74-year-old female presented to our service for suspected Fuchs corneal dystrophy. Her best-corrected visual acuity was 20/25 right eye (OD) and 20/20 left eye (OS). Slit-lamp biomicroscopy revealed bilateral punctate, refractile deposits in the deep stroma in an annular distribution with relative sparing of the central cornea. The remainder of the ocular examination was within expected limits. Central pachymetry was 546 μ OD and 535 μ OS. AS-OCT demonstrated focal hyper-reflective lesions in the deep stroma. Specular microscopy showed normal endothelial cell count and morphology. Confocal microscopy highlighted bright, enhancing punctate lesions in both the anterior stroma and deep stroma with normal intervening spaces. The patient was managed conservatively. Altogether, PAD is a rare, sporadically inherited condition that presents in the elderly. Confocal microscopy can aid in the diagnosis.

Early Complications With Preloaded Descemet Membrane Endothelial Keratoplasty Are Not Dependent on Optisol-GS Washout or Trypan Blue Restaining.

To describe the intraoperative and early postoperative complications using preloaded Descemet membrane endothelial keratoplasty (DMEK) grafts with intraocular injection of the graft in Optisol-GS and omission of trypan blue restaining. This is a retrospective case series of 132 consecutive eyes with Fuchs endothelial dystrophy or endothelial failure who underwent DMEK using preloaded donor tissue prepared as previously described. The graft was not restained with trypan blue by the surgeon, and Optisol-GS was injected with the graft into the eye instead of being rinsed from the injector. Early postoperative complications (0-8 wk) including intraoperative fibrin formation, intraocular inflammation, elevated intraocular pressure, partial graft detachment requiring rebubble, and early graft failure were recorded. No eyes developed intraoperative fibrin formation or postoperative inflammation (such as toxic anterior segment syndrome) or elevated intraocular pressure. For eyes with Fuchs corneal dystrophy, our rebubble rate was 21% (22/106 eyes). Early graft failure was noted in 2% (3/132 eyes), which is similar to previous reports. Our results suggest that injection of Optisol-GS into the anterior chamber during DMEK graft injection does not lead to increases in intraoperative or early postoperative complications. Trypan blue restaining is not necessary for intraoperative visualization. This simplification can reduce graft manipulation and save time and resources for this procedure.

Clinical Profile and Demographic Distribution of Corneal Dystrophies in India: A Study of 4198 Patients.

To describe the clinical profile and demographic distribution of corneal dystrophy in patients presenting to a multitier ophthalmology hospital network in India. This cross-sectional hospital-based study included 2,151,584 new patients presenting between March 2012 and December 2019 (∼8 year period). Patients with a clinical diagnosis of corneal dystrophy in at least 1 eye were included as cases. The data were collected by using an electronic medical record system. Overall, 4198 new patients (0.20%) were diagnosed with corneal dystrophy. The prevalence rates were 0.19% in children (age < 16 years) and 0.20% in adults. Most patients were women (51.86%). The mean age of the patients was 43.61 ± 21.39 years. Most patients (18.79%) were between 61 and 70 years of age. The most common anatomical location of the dystrophy was endothelium (51.71%), followed by stroma (43.55%) and Bowman membrane/epithelium (4.73%). The most common corneal dystrophy was Fuch endothelial corneal dystrophy (41.89%). Most eyes had mild or no visual impairment (43.43%). Of the 8193 eyes, 998 eyes (12.18%) underwent a corneal surgery. Among those who underwent surgical intervention, endothelial keratoplasty was the most commonly performed surgical procedure (52%), followed by penetrating keratoplasty (22%). Corneal dystrophy is a rare disease, affecting patients seeking eye care in India. Endothelial dystrophies were the most common, followed by stromal dystrophies. Among the stromal dystrophies, macular dystrophy was the most common. At initial presentation, visual impairment was mild to moderate in most patients, and surgical intervention was needed in 12.18% of the eyes during the study period.

Autophagy modulation in animal models of corneal diseases: a systematic review.

Autophagy is an intracellular catabolic process implicated in the recycling and degradation of intracellular components. Few studies have defined its role in corneal pathologies. Animal models are essential for understanding autophagy regulation and identifying new treatments to modulate its effects. A systematic review (SR) was conducted of studies employing animal models for investigations of autophagy in corneal diseases. Studies were identified using a structured search strategy (TS = autophagy AND cornea*) in Web of Science, Scopus, and PubMed from inception to September 2019. In this study, 230 articles were collected, of which 28 were analyzed. Mouse models were used in 82% of the studies, while rat, rabbit, and newt models were used in the other 18%. The most studied corneal layer was the epithelium, followed by the endothelium and stroma. In 13 articles, genetically modified animal models were used to study Fuch endothelial corneal dystrophy (FECD), granular corneal dystrophy type 2 (GCD2), dry eye disease (DED), and corneal infection. In other 13 articles, animal models were experimentally induced to mimic DED, keratitis, inflammation, and surgical scenarios. Furthermore, in 50% of studies, modulators that activated or inhibited autophagy were also investigated. Protective effects of autophagy activators were demonstrated, including rapamycin for DED and keratitis, lithium for FECD, LYN-1604 for DED, cysteamine and miR-34c antagomir for damaged corneal epithelium. Three autophagy suppressors were also found to have therapeutic effects, such as aminoimidazole-4-carboxamide-riboside (AICAR) for corneal allogeneic transplantation, celecoxib and chloroquine for DED.

Long-term Results of Intraocular Pressure Elevation and Post-DMEK Glaucoma After Descemet Membrane Endothelial Keratoplasty.

Intraocular pressure (IOP) elevation occurs regularly after Descemet membrane endothelial keratoplasty (DMEK). This study evaluated the long-term incidence of IOP elevation and post-DMEK glaucoma after DMEK. A total of 463 consecutive DMEKs in 352 patients performed between September 2011 and September 2014 at the Universitätsmedizin-Charité Berlin were reviewed. Data of the second treated eye of each patient and of re-DMEKs during the follow-up were excluded. The 12- and 36-month incidence of IOP elevation and post-DMEK glaucoma was analyzed using the Kaplan-Meier survival analysis. IOP elevation was defined as IOP ≥22 mm Hg or ≥10 mm Hg from preoperative baseline. COX regression analysis was used to evaluate the risk factors for IOP elevation and the development of a post-DMEK glaucoma. The 12-month incidence of IOP elevation was 15.9% [95 confidence interval (CI), 12.0%-19.8%] and that of post-DMEK glaucoma was 3.9% (95 CI, 1.7%-6.1%); the 36-month incidence was 18.8% (95 CI, 14.5%-23.1%) and that of post-DMEK glaucoma was 6.6% (95 CI, 3.7%-9.5%). The most frequent cause was steroid-induced IOP elevation with a 12-month incidence of 11.7% (95 CI, 8.2%-15.2%) and a 36-month incidence of 12.9% (95 CI, 9.2%-16.6%), respectively. The incidence of postoperative pupillary block IOP elevation was 7.5% (95 CI, 4.8%-10.2%). A preexisting glaucoma increased the risk of IOP elevation [P < 0.001, hazard ratio (HR) 3.331; 95% CI, 1.919-5.782] and the development of a post-DMEK glaucoma (P < 0.001, HR 6.633; 95% CI, 2.556-17.215). The preoperative diagnosis also influenced the risk of IOP elevation [Fuchs corneal dystrophy (FED) vs. bullous keratopathy; P = 0.012, HR 2.354; 95% CI, 1.203-4.608] and post-DMEK glaucoma (FED vs. graft failure; P = 0.01, HR 4.412; 95% CI, 1.419-13.723, FED vs. bullous keratopathy; P = 0.09, HR 2.679; 95% CI, 0.858-8.358). Incidence of IOP elevation is high in the first 12 months after DMEK, especially steroid-induced IOP elevation. Steroid-induced IOP elevation could be treated effectively by tapering down the steroid medication or changing the steroid drug. A preexisting glaucoma and the preoperative diagnosis increase the risk for an IOP elevation and a post-DMEK glaucoma.

Five Novel Mutations in LOXHD1 Gene Were Identified to Cause Autosomal Recessive Nonsyndromic Hearing Loss in Four Chinese Families.

Hearing loss is one of the most common sensory disorders in newborns and is mostly caused by genetic factors. Autosomal recessive nonsyndromic hearing loss (ARNSHL) is usually characterized as a severe-to-profound congenital sensorineural hearing loss and later can cause various degrees of defect in the language and intelligent development of newborns. The mutations in LOXHD1 gene have been shown to cause DFNB77, a type of ARNSHL. To date, there are limited reports about the association between LOXHD1 gene and ARNSHL. In this study, we reported six patients from four Chinese families suffering from severe-to-profound nonsyndromic hearing loss. We performed targeted next generation sequencing in the six affected members and identified five novel pathogenic mutations in LOXHD1 including c.277G>A (p.D93N), c.611-2A>T, c.1255+3A>G, c.2329C>T (p.Q777∗), and c.5888delG (p.G1963Afs∗136). These mutations were confirmed to be cosegregated with the hearing impairment in the families by Sanger sequencing and were inherited in an autosomal recessive pattern. All of the five mutations were absent in 200 control subjects. There were no symptoms of Fuchs corneal dystrophy in the probands and their blood-related relatives. We concluded that these five novel mutations could be involved in the underlying mechanism resulting in the hearing loss, and this discovery expands the genotypic spectrum of LOXHD1 mutations.

Molecular genetic aspects of Fuchs' endothelial corneal dystrophy pathogenesis

Fuchs' corneal dystrophy (FCD) is a common bilateral non-inflammatory endothelial pathology. It is a multigenic disorder with various expressivity, penetrance and population prevalence. This review discusses corneal endothelium pump function, FCD pathogenesis and its known genetic factors.

Pilot Study of Audiometric Patterns in Fuchs Corneal Dystrophy.

Although Fuchs corneal dystrophy (FCD) is considered an eye disease, a small number of studies have identified genes related to both FCD and hearing loss. Whether FCD is related to hearing loss is unknown. This is a case-control study comparing pure-tone audiometry hearing thresholds in 180 patients with FCD from a hospital-based ophthalmology clinic with 2,575 population-based controls from a nationally representative survey, the National Health and Nutrition Examination Survey (from cycles 2005-06 and 2009-10). Generalized estimating equations were used to compare mean better-hearing ear thresholds in the 2 groups adjusted for age, sex, race, and noise exposure. Patients with FCD had higher hearing thresholds (worse hearing) in lower frequencies (mean difference at 0.5 kHz = 3.49 dB HL) and lower hearing thresholds (better hearing) in higher frequencies (difference at 4 kHz = -4.25 dB HL) compared with population-based controls. In the first study to use objectively measured hearing, FCD was associated with poorer low-frequency and better high-frequency audiometric thresholds than population controls. Further studies are needed to characterize this relationship.

Further audiovestibular characterization of DFNB77, caused by deleterious variants in LOXHD1, and investigation into the involvement of Fuchs corneal dystrophy.

This study focuses on further characterization of the audiovestibular phenotype and on genotype-phenotype correlations of DFNB77, an autosomal recessive type of hearing impairment (HI). DFNB77 is associated with disease-causing variants in LOXHD1, and is genetically and phenotypically highly heterogeneous. Heterozygous deleterious missense variants in LOXHD1 have been associated with late-onset Fuchs corneal dystrophy (FCD). However, up to now screening for FCD of heterozygous carriers in DFNB77 families has not been reported. This study describes the genotype and audiovestibular phenotype of 9 families with DFNB77. In addition, carriers within the families were screened for FCD. Fifteen pathogenic missense and truncating variants were identified, of which 12 were novel. The hearing phenotype showed high inter- and intrafamilial variation in severity and progression. There was no evidence for involvement of the vestibular system. None of the carriers showed (pre-clinical) symptoms of FCD. Our findings expand the genotypic and phenotypic spectrum of DFNB77, but a clear correlation between the type or location of the variant and the severity or progression of HI could not be established. We hypothesize that environmental factors or genetic modifiers are responsible for phenotypic differences. No association was found between heterozygous LOXHD1 variants and the occurrence of FCD in carriers.

Identification of a Novel TCF4 Isoform in the Human Corneal Endothelium

Alternative splice isoforms of TCF4, a gene implicated in Fuchs corneal dystrophy, have been identified in multiple human tissues outside of the eye. The aim of this study was to identify the transcriptional profile of TCF4 in the corneal endothelium. We extracted RNA from the donor corneal endothelium and performed rapid amplification of cDNA ends. We tested the expression pattern of 1 newly identified isoform (7b) in a panel of cDNA derived from multiple human tissues and included cDNA from corneal endothelial (CE) and retinal pigment epithelial cell lines. To further delineate differential expression of TCF4 splice variants that span CTG18.1, we analyzed expression of 6 alternative splice isoforms that are transcribed from either exon 2 or 3 in RNA extracted from the corneal endothelium of 3 normal donors and a CE cell line. We identified 11 different isoforms in control CE tissue, including 1 isoform (7b) not reported previously. This isoform is enriched specifically in the corneal endothelium and placenta compared with other tissues in a panel of human cDNA. We demonstrate the complex expression profile of TCF4 in the human corneal endothelium and reveal expression of alternative splice variants of TCF4.

Omics Biomarkers in Ophthalmology.

"Omics" refers to high-throughput analyses of genes, proteins, or metabolites in a biological system, and is increasingly used for ophthalmic research. These system-based approaches can unravel disease-related processes and are valuable for biomarker discovery. Furthermore, potential therapeutic targets can be identified based on omics results, and targeted follow-up experiments can be designed to gain molecular understanding of the disease and to test new therapies. Here, we review the application of omics techniques in eye diseases, focusing on age-related macular degeneration (AMD), diabetic retinopathy (DR), retinal detachment (RD), myopia, glaucoma, Fuchs' corneal dystrophy (FCD), cataract, keratoconus, and dry eyes. We observe that genomic analyses were mainly successful in AMD research (almost half of the genomic heritability has been explained), whereas large parts of disease variability or risk remain unsolved in most of the other diseases. Other omics studies like transcriptomics, proteomics, and metabolomics provided additional candidate proteins and pathways for several eye diseases, although sample sizes in these studies were often very small and replication is lacking. In order to translate omics results into clinical biomarkers, larger sample sizes and validation across different cohorts would be essential. In conclusion, omics-based studies are increasing in ophthalmology, and further application to the clinic might develop in the years to come. Integration of genomics with other type of omics data has the potential to improve the accuracy of predictive tests. Moreover, in the future, omics may lead to stratification of patients into subgroups based on molecular profiles, enabling the development of personalized treatments.