OBJECTIVE: We wanted to investigate the radial peripapillary capillary (RPC) network in patients with Bietti crystalline dystrophy (BCD). METHODS: We compared RPC densities in the disk and different peripapillary regions, obtained using optical coherence tomography angiography in 22 patients with BCD (37 eyes) and 22 healthy subjects (37 eyes). The BCD group was then divided into Stage 2 and Stage 3 subgroups based on Yuzawa staging, comparing the RPC densities of the two. RESULTS: The disk area RPC density was 38.8% ± 6.3% in the BCD group and 49.2% ± 6.1% in the control group ( P < 0.001), and peripapillary region RPC density was significantly lower in the BCD group than in the control group (49.1% ± 4.7% and 54.1% ± 3.0%, respectively, P < 0.001). There were no significant RPC density differences between the tempo quadrant and inside disk of Stages 2 and 3 subgroups; the other areas showed a significantly lower RPC density in Stage 3 than in Stage 2 BCD. CONCLUSION The BCD group RPC density was significantly lower than the control group. The reduction of RPC density in the tempo quadrant occurred mainly in the Stage 1 BCD. In contrast, the reduction of RPC density in superior, inferior, and nasal quadrants occurred mainly in Stage 2.
Adult ; Aged ; Angiography ; Corneal Dystrophies, Hereditary/physiopathology* ; Female ; Humans ; Male ; Microvascular Density ; Microvessels/physiopathology* ; Middle Aged ; Retinal Diseases/physiopathology* ; Retinal Vessels/physiopathology* ; Tomography, Optical Coherence

OBJECTIVE: The CYP4V2 gene of two pedigrees affected with Bietti crystalline corneoretinal dystrophy was analyzed to indentify the cause of the disease and provide a basis for clinical diagnosis. METHODS: The probands were subjected to next generation sequencing (NGS). Suspected variants were verified by Sanger sequencing. Pathogenicity of the variants were searched through relevant databases and PubMed by following the ACMG guidelines. RESULTS: A homozygous variant in the CYP4V2 gene c. (802-8) _810delTCATACAGGTCATCGCTinsGC was detected in proband from pedigree 1, parents did not detect; CYP4V2 genes c. (802-8)_810delTCATACAGGTCATCGCTinsGC and c. 958 C>T (p.Arg320X) compound heterozygous variants existed in the proband of pedigree 2,both parents were variant carriers. The results of Sanger sequencing showed that the variant of CYP4V2 gene in the two families was consistent with the NGS sequencing. The c. (802-8)_810delTCATACAGGTCATCGCTinsGC of CYP4V2 gene was splicing variant, and both splicing variant and nonsense variant could produce truncated nonfunctional protein products. Based on standards and guidelines by American College of Medical Genetics and Genomics, the CYP4V2 genes c. (802-8)_810del TCATACAGGTCATCGCTinsGC and c. 958 C>T (p.Arg320X) were predicted to be pathogenic variants (PVS1+PS1+PM2+PM3). CONCLUSION The homozygous variant c. (802-8) _810delTCATACAGGTCATCGCTinsGC and the complex heterozygous variants c. (802-8) _810delTCATACAGGTCATCGCTinsGC and c.958C>T (p.Arg320X) in CYP4V2 gene are the cause of the disease in the probands of two pedigrees , respectively.
Corneal Dystrophies, Hereditary/pathology* ; Cytochrome P450 Family 4/genetics* ; Genetic Variation ; Humans ; Mutation ; Pedigree ; Phenotype ; Retinal Diseases/pathology*

OBJECTIVETo analyze the clinical features and TGFBI gene mutation in a Chinese family affected with Reis-Bucklers corneal dystrophy.

METHODSGenomic DNA was extracted from 53 members including 9 patients from the family. The 17 exons and splice region of introns of the TGFBI gene were amplified by PCR and directly sequenced. All family members were subjected to ophthalmologic examination.

RESULTSA heterozygous mutation (R124L) was found in exon 4 of the TGFBI gene among all patients from the family. The same mutation was not found among unaffected family members. The inheritance pattern of the family was identified as autosomal dominant, and the Reis-Bucklers corneal dystrophy in the family was diagnosed as the geographic type.

CONCLUSIONThe R124L mutation of the TGFBI gene probably underlies the pathogenesis of Reis-Bucklers corneal dystrophy in this Chinese family. Molecular genetic approach is useful for the proper diagnosis of this type of corneal dystrophy.

Corneal Dystrophies, Hereditary ; etiology ; genetics ; Female ; Humans ; Male ; Mutation ; Sequence Analysis, DNA ; Transforming Growth Factor beta1 ; genetics

PURPOSE: To compare the clinical characteristics and prognosis of Fuchs dystrophy patients according to COL8A2 gene mutation status. METHODS: Eighty-one patients (162 eyes) initially diagnosed with Fuchs dystrophy from 1996 to 2015 were divided into two groups according to COL8A2 gene mutation status. Retrospective analysis was performed comparing gender, age at diagnosis, presence of family history, diabetes mellitus, symptoms of blurred vision in the morning, changes in central corneal thickness and endothelial cell density with time, need for corneal transplantation, and pre-operative corneal status in the two groups. RESULTS: Of the 81 patients, 12 were shown to harbor a COL8A2 gene mutation. Individuals with mutation were significantly associated with presence of family history, diabetes mellitus, and blurred vision in the morning (p = 0.021, p = 0.024, p = 0.044, respectively). They also had significantly thicker central cornea and lower endothelial cell density at the time of diagnosis (p = 0.020, p = 0.005, respectively). The differences in central corneal thickness and endothelial cell density between the two eyes in one patient were significantly smaller in patients with gene mutation (p = 0.043, p = 0.022, respectively). Over a 5-year follow-up period, 60.0% of eyes in patients with gene mutation and 19.2% of eyes in patients without gene mutation underwent corneal transplantation, a significant difference between the two groups (p = 0.014). CONCLUSIONS: By testing for COL8A2 gene mutation, early binocular disease progression and the possible need for corneal transplantation in the future can be predicted among patients diagnosed with Fuchs dystrophy.
Cornea ; Corneal Transplantation ; Diabetes Mellitus ; Diagnosis ; Disease Progression ; Endothelial Cells ; Follow-Up Studies ; Fuchs' Endothelial Dystrophy* ; Humans ; Prognosis* ; Retrospective Studies ; Telescopes

No abstract available.
Asian Continental Ancestry Group ; Corneal Dystrophies, Hereditary/diagnosis/*genetics ; Cytochrome P450 Family 4/*genetics ; DNA Mutational Analysis ; Fluorescein Angiography ; Humans ; Male ; Middle Aged ; *Mutation ; Polymerase Chain Reaction ; Republic of Korea ; Retinal Diseases/diagnosis/*genetics ; Retinal Pigment Epithelium/pathology ; Tomography, Optical Coherence ; Visual Acuity

No abstract available.
Adult ; Corneal Dystrophies, Hereditary/physiopathology/*surgery ; Female ; Humans ; Keratoplasty, Penetrating/*methods ; Male ; Middle Aged ; Visual Acuity/*physiology

BACKGROUND: Mutations in the transforming growth factor beta-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. RESULTS: Among a total of 89 patients, 77 (86.5%) were diagnosed as having clinical TGFBI CD. Seventy-three out of 74 patients (98.6%) with granular CD type 2 (GCD2), had the p.R124H mutation. Of particular note, one patient with rapidly progressive CD had the p.R124H mutation as well as a novel nonsense variant with unknown clinical significance (p.A179*). In three patients with lattice CD type 1 (LCD1), one known mutation (p.R124C) and two novel variants (p.L569Q and p.T621P) in the TGFBI gene were identified. CONCLUSIONS: This study provides epidemiological insight into CDs in a Korean population and reaffirms that GCD2 is the most common TGFBI CD phenotype and that p.R124H is the only mutation identified in patients with GCD2. In addition, we broaden the spectrum of TGFBI mutations by identifying two novel missense variants in patients with LCD1.
Adolescent ; Adult ; Aged ; Asian Continental Ancestry Group/*genetics ; Corneal Dystrophies, Hereditary/diagnosis/*genetics ; DNA Mutational Analysis ; Female ; Humans ; Male ; Middle Aged ; Phenotype ; Polymorphism, Single Nucleotide ; Republic of Korea ; Retrospective Studies ; Transforming Growth Factor beta1/*genetics ; Young Adult

An 87-year-old woman visited our clinic for a scheduled cataract surgery. At the time of preoperative evaluation, slit lamp examination showed lattice-shaped and granular deposits with asymmetrical patterns in the stroma of both corneas. Genomic DNA samples of the patient, amplified by polymerase chain reaction, showed a single nucleotide substitution, c. 1580T>G (p.L527R), in the transforming growth factor-beta-induced TGFBI gene. We also found two additional SNP mutations, c.1620T>C (p.F540F) and c.1678+23G>A, along with the well-known L527R mutation. This is the first report of lattice corneal dystrophy type IV with an L527R mutation outside of Japan, and could challenge the idea that L527R is caused by a mutation from a single Japanese ancestor.
Aged, 80 and over ; Corneal Dystrophies, Hereditary/diagnosis/*genetics/metabolism ; DNA/*genetics ; DNA Mutational Analysis ; Extracellular Matrix Proteins/*genetics/metabolism ; Female ; Humans ; *Mutation ; Pedigree ; Polymerase Chain Reaction ; Transforming Growth Factor beta/*genetics/metabolism

An 87-year-old woman visited our clinic for a scheduled cataract surgery. At the time of preoperative evaluation, slit lamp examination showed lattice-shaped and granular deposits with asymmetrical patterns in the stroma of both corneas. Genomic DNA samples of the patient, amplified by polymerase chain reaction, showed a single nucleotide substitution, c. 1580T>G (p.L527R), in the transforming growth factor-beta-induced TGFBI gene. We also found two additional SNP mutations, c.1620T>C (p.F540F) and c.1678+23G>A, along with the well-known L527R mutation. This is the first report of lattice corneal dystrophy type IV with an L527R mutation outside of Japan, and could challenge the idea that L527R is caused by a mutation from a single Japanese ancestor.
Aged, 80 and over ; Corneal Dystrophies, Hereditary/diagnosis/*genetics/metabolism ; DNA/*genetics ; DNA Mutational Analysis ; Extracellular Matrix Proteins/*genetics/metabolism ; Female ; Humans ; *Mutation ; Pedigree ; Polymerase Chain Reaction ; Transforming Growth Factor beta/*genetics/metabolism

Bietti crystalline retinal dystrophy is a rare, inherited disorder whose hallmark is the presence of retinal crystal deposits associated with later chorioretinal degeneration. This condition may rarely be complicated by the development of cystoid macular oedema leading to rapid visual decline. Currently, treatment options for this complication of Bietti dystrophy are limited and the visual prognosis is poor. Here, we present a case of cystoid macular oedema associated with Bietti dystrophy that was successfully diagnosed using multimodal imaging techniques including optical coherence tomography and fluorescein angiography. These modalities confirmed the diagnosis of macular oedema and excluded other possible causes of oedema such as choroidal neovascularisation. In this patient, cystoid macular oedema was resolved with oral acetazolamide therapy, a treatment that has not been previously reported in this context. Acetazolamide treatment resulted in oedema resolution and improvement in visual function, and can be considered a therapeutic option for other patients with Bietti dystrophy who develop cystoid macular oedema.
Acetazolamide/*administration & dosage ; Administration, Oral ; Adult ; Corneal Dystrophies, Hereditary/*drug therapy/pathology ; Diuretics/*administration & dosage ; Humans ; Macular Edema/*drug therapy/pathology ; Male ; Retinal Diseases/*drug therapy/pathology ; Tomography, Optical Coherence ; Treatment Outcome