Tissue-specific TCF4 triplet repeat instability revealed by optical genome mapping.

Background: Fuchs endothelial corneal dystrophy (FECD) is the most common repeat-mediated disease in humans. It exclusively affects corneal endothelial cells (CECs), with ≤81% of cases associated with an intronic TCF4 triplet repeat (CTG18.1).

Autosomal dominant stromal corneal dystrophy associated with a SPARCL1 missense variant.

Corneal dystrophies are phenotypically and genetically heterogeneous, often resulting in visual impairment caused by corneal opacification. We investigated the genetic cause of an autosomal dominant corneal stromal dystrophy in a pedigree with eight affected individuals in three generations. Affected individuals had diffuse central stromal opacity, with reduced visual acuity in older family members.

Deciphering novel TCF4-driven mechanisms underlying a common triplet repeat expansion-mediated disease.

Fuchs endothelial corneal dystrophy (FECD) is an age-related cause of vision loss, and the most common repeat expansion-mediated disease in humans characterised to date. Up to 80% of European FECD cases have been attributed to expansion of a non-coding CTG repeat element (termed CTG18.1) located within the ubiquitously expressed transcription factor encoding gene, TCF4.

A comparison of keratoconus progression following collagen cross-linkage using standard or personalised keratometry thresholds.

Objective: To define how estimates of keratoconus progression following collagen cross-linking (CXL) vary according to the parameter selected to measure corneal shape.

Materials And Methods: We estimated progression following CXL in 1677 eyes. We compared standard definitions of keratoconus progression based on published thresholds for Kmax, front K2, or back K2, or progression of any two of these three parameters, with the option of an increased threshold for Kmax values ≥ 55D.

Antifungal susceptibility profiles for fungal isolates from corneas and contact lenses in the United Kingdom.

Objective: To report the identification and results of susceptibility testing for fungal isolates from the cornea or contact lens care systems.

Materials And Methods: In this retrospective epidemiological study, we searched the results of fungal cultures from cornea or contact lens systems referred for identification and susceptibility testing to the United Kingdom National Mycology Reference Laboratory between October 2016 and March 2022. For each fungal isolate, we recorded the genus and species of the fungus and the minimum inhibitory concentration (MIC) to six antifungal agents available to treat corneal infection (amphotericin, econazole, itraconazole, natamycin, posaconazole, and voriconazole).

Phenotype and genotype of concurrent keratoconus and Fuchs endothelial corneal dystrophy.

Purpose: To characterise the phenotype and genotype of concurrent keratoconus and Fuchs endothelial corneal dystrophy (KC + FECD).

Methods: We recruited 20 patients with concurrent KC + FECD for a retrospective observational case series from the United Kingdom and the Czech Republic. We compared eight parameters of corneal shape (Pentacam, Oculus) with two groups of age-matched controls who had either isolated keratoconus (KC) or isolated FECD.

Antimicrobial resistance in topical treatments for microbial keratitis: protocol for a systematic review and meta-analysis.

Introduction: There is evidence for increased resistance against the antimicrobials used to treat keratitis. This review aims to provide global and regional prevalence estimates of antimicrobial resistance in corneal isolates and the range of minimum inhibitory concentrations (MIC) with their associated resistance breakpoints.

Methods And Analysis: We report this protocol following Preferred Reporting Items for Systematic Review and Meta-Analyses Protocols guidelines.

Potential new fluoroquinolone treatments for suspected bacterial keratitis.

Topical fluoroquinolones (FQs) are an established treatment for suspected microbial keratitis. An increased FQ resistance in some classes of bacterial pathogens is a concern. Some recently developed FQs have an extended spectrum of activity, making them a suitable alternative for topical ophthalmic use.

Snail Track Lesion with Flat Keratometry in Anterior Segment Dysgenesis Caused by a Novel Variant.

We report the phenotype of a 15-year-old female patient with anterior segment dysgenesis (ASD) caused by a novel heterozygous loss-of-function variant. The proband underwent an ophthalmic examination as well as a molecular genetic investigation comprising exome sequencing, a single nucleotide polymorphism array to access copy number and Sanger sequencing to exclude non-coding causal variants. There was bilateral mild iris hypoplasia with pupil deformation and iridocorneal adhesions.

Amniotic membrane transplantation for acute ocular burns.

Background: Ocular surface burns can be caused by chemicals (alkalis and acids) or direct heat. One effect of the burn is damage to the limbal epithelial stem cells of the ocular surface with delayed re-epithelialisation, stem cell failure, and conjunctivalisation of the cornea. Amniotic membrane transplantation (AMT) performed in the acute phase (day 0 to day 7) following an ocular surface burn is claimed to reduce pain and accelerate healing.

Graphical comparison of surgeon outcomes for the audit of a national corneal transplant registry (OTAG study 32).

Purpose: To compare Kaplan-Meier survival curves and funnel plots for the audit of surgeon-specific corneal transplantation outcomes.

Methods: We obtained data on all patients with Fuchs endothelial dystrophy (FED) receiving a first corneal transplant in one eye between January 2012 and December 2017. We produced 2-year Kaplan-Meier graft survival curves to compare a simulated individual surgeon's graft survival rate to national pooled data.

Personalized Model to Predict Keratoconus Progression From Demographic, Topographic, and Genetic Data.

Purpose: To generate a prognostic model to predict keratoconus progression to corneal crosslinking (CXL).

Design: Retrospective cohort study.

Methods: We recruited 5025 patients (9341 eyes) with early keratoconus between January 2011 and November 2020.

Posterior corneal vesicles are not associated with the genetic variants that cause posterior polymorphous corneal dystrophy.

Purpose: Posterior corneal vesicles (PCVs) have clinical features that are similar to posterior polymorphous corneal dystrophy (PPCD). To help determine whether there is a shared genetic basis, we screened 38 individuals with PCVs for changes in the three genes identified as causative for PPCD.

Methods: We prospectively recruited patients for this study.

Utility of investigation for suspected microbial keratitis: a diagnostic accuracy study.

Purpose: The true disease status of a population with suspected microbial keratitis (MK) cannot be verified. There is not an accurate (gold) reference standard to confirm infection and inter-test comparisons of sensitivity and specificity therefore lead to bias with questionable estimates of test utility. We present an alternative method to report results.

Bacterial keratitis: identifying the areas of clinical uncertainty.

Bacterial keratitis is a common corneal infection that is treated with topical antimicrobials. By the time of presentation there may already be severe visual loss from corneal ulceration and opacity, which may persist despite treatment. There are significant differences in the associated risk factors and the bacterial isolates between high income and low- or middle-income countries, so that general management guidelines may not be appropriate.

Machine Learning Algorithms to Detect Subclinical Keratoconus: Systematic Review.

Background: Keratoconus is a disorder characterized by progressive thinning and distortion of the cornea. If detected at an early stage, corneal collagen cross-linking can prevent disease progression and further visual loss. Although advanced forms are easily detected, reliable identification of subclinical disease can be problematic.

Novel disease-causing variants and phenotypic features of X-linked megalocornea.

Purpose: The aim of the study was to describe the phenotype and molecular genetic causes of X-linked megalocornea (MGC1). We recruited four British, one New Zealand, one Vietnamese and four Czech families.

Methods: All probands and three female carriers underwent ocular examination and Sanger sequencing of the CHRDL1 gene.

Effect of Corneal Cross-linking versus Standard Care on Keratoconus Progression in Young Patients: The KERALINK Randomized Controlled Trial.

Purpose: To examine the efficacy and safety of corneal cross-linking (CXL) for stabilization of progressive keratoconus.

Design: Observer-masked, randomized, controlled, parallel-group superiority trial.

Participants: Sixty participants 10 to 16 years of age with progressive keratoconus, one eye of each deemed the study eye.

Systemic interventions for severe atopic and vernal keratoconjunctivitis in children and young people up to the age of 16 years.

Background: Atopic keratoconjunctivitis (AKC) and vernal keratoconjunctivitis (VKC) are severe and potentially sight-threatening allergic eye diseases characterised by chronic inflammation of the ocular surface. Both topical and systemic treatments are used. This Cochrane Review focuses on systemic treatments.