Mutational spectrum of Korean patients with corneal dystrophy.

Corneal dystrophy typically refers to a group of rare hereditary disorders with a heterogeneous genetic background. A comprehensive molecular genetic analysis was performed to characterize the genetic spectrum of corneal dystrophies in Korean patients. Patients with various corneal dystrophies underwent thorough ophthalmic examination, histopathologic examination, and Sanger sequencing.

Pathogenesis and treatments of TGFBI corneal dystrophies.

Transforming growth factor beta-induced (TGFBI) corneal dystrophies are a group of inherited progressive corneal diseases. Accumulation of transforming growth factor beta-induced protein (TGFBIp) is involved in the pathogenesis of TGFBI corneal dystrophies; however, the exact molecular mechanisms are not fully elucidated. In this review article, we summarize the current knowledge of TGFBI corneal dystrophies including clinical manifestations, epidemiology, most common and recently reported associated mutations for each disease, and treatment modalities.

Femtosecond Laser-Assisted Lamellar Keratectomy for Corneal Opacities Secondary to Anterior Corneal Dystrophies: An Interventional Case Series.

Purpose: To report results of femtosecond laser-assisted lamellar keratectomy (FLK) for corneal opacities secondary to anterior corneal dystrophies.

Methods: Patients with a clinical diagnosis of Reis-Bücklers corneal dystrophy, granular corneal dystrophy, lattice corneal dystrophy, and macular corneal dystrophy were treated. FLK was performed to remove a central corneal free cap of 9.

Comparative Study of Anterior Eye Segment Measurements with Spectral Swept-Source and Time-Domain Optical Coherence Tomography in Eyes with Corneal Dystrophies.

Purpose: To compare anterior eye segment measurements and morphology obtained with two optical coherence tomography systems (TD OCT, SS OCT) in eyes with corneal dystrophies (CDs).

Methods: Fifty healthy volunteers (50 eyes) and 54 patients (96 eyes) diagnosed with CD (epithelial basement membrane dystrophy, EBMD = 12 eyes; Thiel-Behnke CD = 6 eyes; lattice CD TGFBI type = 15 eyes; granular CD type 1 = 7 eyes, granular CD type 2 = 2 eyes; macular CD = 23 eyes; and Fuchs endothelial CD = 31 eyes) were recruited for the study. Automated and manual central corneal thickness (aCCT, mCCT), anterior chamber depth (ACD), and nasal and temporal trabecular iris angle (nTIA, tTIA) were measured and compared with Bland-Altman plots.

Progressive cranial nerve involvement and grading of facial paralysis in gelsolin amyloidosis.

Introduction: Hereditary gelsolin amyloidosis (GA) is a rare condition caused by the gelsolin gene mutation. The diagnostic triad includes corneal lattice dystrophy (type 2), progressive bilateral facial paralysis, and cutis laxa. Detailed information on facial paralysis in GA and the extent of cranial nerve injury is lacking.

Natural course of Finnish gelsolin amyloidosis.

Background: Finnish type of hereditary gelsolin amyloidosis (FGA) is one of the most common diseases of Finnish disease heritage. Existing FGA knowledge is based only on smaller patient series, so our aim was to elucidate the natural course of the disease in a comprehensive sample of patients and to build up a national FGA patient registry.

Methods: An inquiry about the known and suspected signs of FGA, sent to the members of Finnish Amyloidosis Association, telephone contacts, and hospital records were utilized to create the registry.

Early Events in the Amyloid Formation of the A546T Mutant of Transforming Growth Factor β-Induced Protein in Corneal Dystrophies Compared to the Nonfibrillating R555W and R555Q Mutants.

The human transforming growth factor β-induced protein (TGFBIp) is involved in several types of corneal dystrophies where protein aggregation and amyloid fibril formation severely impair vision. Most disease-causing mutations are located in the last of four homologous fasciclin-1 (FAS1) domains of the protein, and it has been shown that when isolated, the fourth FAS1 domain (FAS1-4) mimics the behavior of full-length TGFBIp. In this study, we use molecular dynamics simulations and principal component analysis to study the wild-type FAS1-4 domain along with three disease-causing mutations (R555W, R555Q, and A546T) to decipher any internal difference in dynamical properties of the domains that may explain their varied stabilities and aggregation properties.

Near-complete 1H, 13C, 15N resonance assignments of dimethylsulfoxide-denatured TGFBIp FAS1-4 A546T.

The transforming growth factor beta induced protein (TGFBIp) is a major protein component of the human cornea. Mutations occurring in TGFBIp may cause corneal dystrophies, which ultimately lead to loss of vision. The majority of the disease-causing mutations are located in the C-terminal domain of TGFBIp, referred as the fourth fascilin-1 (FAS1-4) domain.

Protein Composition of TGFBI-R124C- and TGFBI-R555W-Associated Aggregates Suggests Multiple Mechanisms Leading to Lattice and Granular Corneal Dystrophy.

Purpose: Transforming growth factor beta-induced (TGFBI)-related dystrophies constitute the most common heritable forms of corneal dystrophy worldwide. However, other than the underlying genotypes of these conditions, a limited knowledge exists of the exact pathomechanisms of these disorders. This study expands on our previous research investigating dystrophic stromal aggregates, with the aim of better elucidating the pathomechanism of two conditions arising from the most common TGFBI mutations: granular corneal dystrophy type 1 (GCD1; R555W) and lattice corneal dystrophy type 1 (LCD1; R124C).

Development of a Transgenic Mouse with R124H Human TGFBI Mutation Associated with Granular Corneal Dystrophy Type 2.

Purpose: To investigate the phenotype and predisposing factors of a granular corneal dystrophy type 2 transgenic mouse model.

Methods: Human TGFBI cDNA with R124H mutation was used to make a transgenic mouse expressing human protein (TGFBIR124H mouse). Reverse transcription PCR (RT-PCR) was performed to analyze TGFBIR124H expression.

Prevalence and histopathological characteristics of corneal stromal dystrophies in Saudi Arabia.

Purpose: The aim was to determine the frequency and describe the main histopathologic features of corneal stromal dystrophy in Saudi Arabia.

Methods: A single-center, retrospective analysis of 193 corneal specimens diagnosed with stromal dystrophy. All samples were retrieved from the Histopathology Department at King Khaled Eye Specialist Hospital over a 10-year period (2002 to December 31, 2011).

Mutation Analysis of the TGFBI Gene in Consecutive Korean Patients With Corneal Dystrophies.

Background: Mutations in the transforming growth factor β-induced gene (TGFBI) are major causes of genetic corneal dystrophies (CDs), which can be grouped into TGFBI CDs. Although a few studies have reported the clinical and genetic features of Korean patients with TGFBI CD, no data are available regarding the frequency and spectrum of TGFBI mutations in a consecutive series of Korean patients with clinically diagnosed CDs.

Methods: Patients with any type of CD, who underwent both ophthalmologic examination and TGFBI gene analysis by Sanger sequencing at a tertiary care hospital in Seoul, Korea from 2006 to 2013, were enrolled in this study.

Fibril Core of Transforming Growth Factor Beta-Induced Protein (TGFBIp) Facilitates Aggregation of Corneal TGFBIp.

Mutations in the transforming growth factor beta-induced (TGFBI) gene result in a group of hereditary diseases of the cornea that are collectively known as TGFBI corneal dystrophies. These mutations translate into amino acid substitutions mainly within the fourth fasciclin 1 domain (FAS1-4) of the transforming growth factor beta-induced protein (TGFBIp) and cause either amyloid or nonamyloid protein aggregates in the anterior and central parts of the cornea, depending on the mutation. The A546T substitution in TGFBIp causes lattice corneal dystrophy (LCD), which manifests as amyloid-type aggregates in the corneal stroma.

Corneal topography analysis of stromal corneal dystrophies.

Objective: The aim was to compare the corneal topography and tomography parameters of macular corneal dystrophy (MCD), granular corneal dystrophy (GCD) and lattice corneal dystrophy (LCD) patients obtained by Scheimpflug imaging system.

Methods: The charts, photographs and topography images of patients were reviewed retrospectively. This study included 73 eyes of 73 patients (28 MCD, 20 GCG and 25 LCD patients).

[Analyses of TGFBI gene mutation spectrum in four Chinese families with corneal dystrophy].

Objective: To identify the genetic mutation of TGFBI gene in four Chinese families with corneal dystrophy. The pedigrees were Reis-Bücklers corneal dystrophy (RBCD), Avellino corneal dystrophy (ACD), lattice corneal dystrophy type I(LCDI) and lattice corneal dystrophy type I/IIIA (LCDI/IIIA) (n = 1 each).

Methods: Genomic DNA was extracted from leukocytes from 22 patients, 22 phenotypic normal family members and 100 normal controls from February 2010 to October 2012.

Genes in dizygote twins with Bowman layer corneal dystrophy.

Purpose: To report a de novo R124C mutation of transforming growth factor β-induced (TGFBI) gene in one of dizygotic twins with corneal dystrophy of the Bowman layer.

Case Report: An 11-year-old boy was one of dizygotic twins and had a history of bilateral blurred vision and recurrent corneal erosion. Examination of the visual acuity demonstrated 20/40 in his each eye.

Biochemical properties and aggregation propensity of transforming growth factor-induced protein (TGFBIp) and the amyloid forming mutants.

TGFBI-associated corneal dystrophies are characterized by accumulation of insoluble deposits of the mutant protein transforming growth factor β-induced protein (TGFBIp) in the cornea. Depending on the nature of mutation, the lesions appear as granular (non-amyloid) or lattice lines (amyloid) in the Bowman's layer or in the stroma. This review article emphasizes the structural biology aspects of TGFBIp.

Clinical characteristics and SAP scintigraphic findings in 10 patients with AGel amyloidosis.

The clinical features of hereditary gelsolin (AGel) amyloidosis include corneal lattice dystrophy, distal sensorimotor, cranial neuropathy and cutis laxa. To date, four mutations of the gelsolin (GSN) gene encoding the following variants have been identified as the cause of this malady; p.D214N, p.

Lattice corneal dystrophy type IIIA with hyaline component from a novel A620P mutation and distinct surgical treatments.

Purpose: The aim of this study was to report a lattice corneal dystrophy (LCD) family with a novel mutation of A620P in the TGFBI gene, its long-term treatment, follow-up data, and related pathologic findings.

Methods: A total of 28 family members were clinically examined, and blood samples or buccal epithelial cells were taken for DNA analysis. All exons from the entire TGFBI gene coding region were analyzed for mutations in 3 affected members.

LASIK and surface ablation in corneal dystrophies.

Corneal dystrophies are a rare group of hereditary disorders, that are bilateral, non-inflammatory, and progressive. Clinically, they can be classified based on the anatomic layer of the cornea affected. Refractive surgery and phototherapeutic keratectomy (PTK) can be performed with caution in patients with certain corneal dystrophies, but should be avoided in others.

Clinical and genetic aspects of the TGFBI-associated corneal dystrophies.

Corneal dystrophies are a group of inherited disorders localized to various layers of the cornea that affect corneal transparency and visual acuity. The deposition of insoluble protein materials in the form of extracellular deposits or intracellular cysts is pathognomic. Mutations in TGFBI are responsible for superficial and stromal corneal dystrophies.

Persistent staining of lattice lines after intraoperative trypan blue use in patients with lattice corneal dystrophy.

Purpose: The aim of this study was to report the persistent staining of corneal lattice lines resulting from the intraoperative use of trypan blue.

Methods: This is a case series.

Results: Four patients with lattice corneal dystrophy (LCD) who underwent either deep anterior lamellar keratoplasty or cataract extraction with intraoperative trypan blue use demonstrated persistent, postoperative trypan staining of lattice lines on slit-lamp examination out to final follow-up (range, 176 to 541 days postoperatively).

Full-field optical coherence tomography of human donor and pathological corneas.

Purpose: To evaluate the performance of a full-field optical coherence tomography (FF-OCT) system in the study of human donor and pathological corneas and assess its suitability for use in eye banks.

Methods: Our study was carried out using an FF-OCT system developed for non-invasive imaging of tissue structures in depth with ultrahigh resolution (1 µm in all directions). Images were acquired from eight stored human donor corneas (either edematous or after deswelling) and five surgical specimens of corneas with various diseases (bullous keratopathy, lattice corneal dystrophy, stromal scar after keratitis, keratoconus and Fuchs dystrophy).