First Identification of a Triple Corneal Dystrophy Association: Keratoconus,Epithelial Basement Membrane Corneal Dystrophy and Fuchs’ Endothelial Corneal Dystrophy

Purpose

To report the observation of a triple corneal dystrophy association consisting of keratoconus (KC), epithelial basement membrane corneal dystrophy (EBMCD) and Fuchs’ endothelial corneal dystrophy (FECD).

Methods

A 55-year-old male patient was referred to our cornea service for blurred vision and recurrent foreign body sensation. He reported bilateral recurrent corneal erosions with diurnal visual fluctuations. He underwent corneal biomicroscopy, Scheimpflug tomography, in vivo HRT confocal laser scanning microscopy and genetic testing for TGFBI and ZEB1 mutations using direct DNA sequencing.

Results

Biomicroscopic examination revealed the presence of subepithelial central and paracentral corneal opacities. The endothelium showed a bilateral flecked appearance, and the posterior corneal curvature suggested a possible concomitant ectatic disorder. Corneal tomography confirmed the presence of a stage II KC in both eyes. In vivo confocal laser scanning microscopy revealed a concomitant bilateral EBMCD with hyperreflective deposits in basal epithelial cells, subbasal Bowman''s layer microfolds and ridges with truncated subbasal nerves as pseudodendritic elements. Stromal analysis revealed honeycomb edematous areas, and the endothelium showed a strawberry surface configuration typical of FECD. The genetic analysis resulted negative for TGFBI mutations and positive for a heterozygous mutation in exon 7 of the gene ZEB1.

Conclusion

This is the first case reported in the literature in which KC, EBMCD and FECD are present in the same patient and associated with ZEB1 gene mutation. The triple association was previously established by means of morphological analysis of the cornea using corneal Scheimpflug tomography and in vivo HRT II confocal laser scanning microscopy.Key words: Keratoconus, Fuchs’ endothelial corneal dystrophy, Epithelial basement membrane dystrophy, Cogan dystrophy, Confocal microscopy, ZEB1     

Fuchs’ Uveitis in Iranian Patients: A Review of 89 Eyes

Purpose: To describe clinical and imaging features of Fuchs’ Uveitis (FU) and investigate the rate of misdiagnosis in Iranian patients.

Methods: Records of 82 FU patients (89 eyes) were reviewed retrospectively.

Results: Remarkable findings included iris heterochromia in 14 (17.1%) patients and Fuchs’ keratic precipitates in 97.8%, vitritis in 89.7% and cataract in 69.7% eyes. FU discovered as an incidental finding in 7 patients (10.0%). Imaging revealed disc hyperfluorescence, mild vascular leakage and epiretinal membrane in 72.7%, 32.5% and 19.4% of eyes, respectively. The rate of misdiagnosis was 19.5% (16 patients) with intermediate uveitis being as the most common erroneous diagnosis (10 patients). Patients with the wrong diagnosis were significantly younger (p = 0.045) and more likely to have bilateral involvement (p = 0.004) or no anterior chamber cells (p = 0.039).

Conclusions: Heterochromia is an infrequent clinical feature in Iranian FU patients, however, vitreous involvement is common. Intermediate uveitis is a usual misdiagnosis.     

Arg124Cys Mutation of the βig-h3 Gene in a Japanese Family With Lattice Corneal Dystrophy Type I

To characterize severe lattice corneal dystrophy, we analyzed the βig-h3 gene, clinical features, histological findings, and genotype-phenotype correlation in an affected Japanese family. Deoxyribonucleic acid was extracted from leukocytes in 16 members (12 affected and 4 unaffected) of a Japanese family with lattice corneal dystrophy type I. Exon 4 of the βig-h3 gene was amplified and analyzed using molecular biological methods. Clinical and pathological data were also collected. We found a heterozygous point mutation that causes the disease phenotype. It was a single base-pair transition leading to an amino acid substitution (CGC→TGC, Arg124Cys). The phenotypic variation within families was not recognized. The affected members in the pedigree demonstrated severe visual disturbance in the third decade and required keratoplasty. Histopathological examination revealed amyloid deposits consisting of short and thin amyloid fibers and lattice corneal dystrophy type I. The heterozygous Arg124Cys mutation reported in Caucasian lattice corneal dystrophy caused severe lattice corneal dystrophy consisting of short and thin amyloid fibers in a Japanese family. Based on our study of many members of the family, we are able to construct the natural course of this disorder from its earliest clinical findings through its late manifestations.     

Analysis of iris structure and iridocorneal angle parameters with anterior segment optical coherence tomography in Fuchs’ uveitis syndrome

To evaluate the differences in the biometric parameters of iridocorneal angle and iris structure measured by anterior segment optical coherence tomography (AS-OCT) in Fuchs’ uveitis syndrome (FUS). Seventy-six eyes of 38 consecutive patients with the diagnosis of unilateral FUS were recruited into this prospective, cross-sectional and comparative study. After a complete ocular examination, anterior segment biometric parameters were measured by Visante^® AS-OCT. All parameters were compared between the two eyes of each patient statistically. The mean age of the 38 subjects was 32.5 ± 7.5 years (18 female and 20 male). The mean visual acuity was lower in eyes with FUS (0.55 ± 0.31) than in healthy eyes (0.93 ± 0.17). The central corneal thickness did not differ significantly between eyes. All iridocorneal angle parameters (angle-opening distance 500 and 750, scleral spur angle, trabecular–iris space (TISA) 500 and 750) except TISA 500 in temporal quadrant were significantly larger in eyes with FUS than in healthy eyes. Anterior chamber depth was deeper in the eyes with FUS than in the unaffected eyes. With regard to iris measurements, iris thickness in the thickest part, iris bowing and iris shape were all statistically different between the affected eye and the healthy eye in individual patients with FUS. However, no statistically significant differences were evident in iris thickness 500 μm, thickness in the middle and iris length. There were significant difference in iris shape between the two eyes of patients with glaucoma. AS-OCT as an imaging method provides us with many informative resultsin the analysis of anterior segment parameters in FUS.     

A Novel H572R Mutation in the Transforming Growth Factor-β-Induced Gene in a Thai Family with Lattice Corneal Dystrophy Type I

Purpose

To describe a large Thai family with lattice corneal dystrophy (LCD) type I and to determine whether this LCD is associated with mutations within the transforming growth factor-β-induced (TGFBI) gene.

Methods

A six-generation family with LCD type I was identified and diagnosed on the basis of clinical and/or histopathologic evaluation. Visual acuity testing and slit-lamp biomicroscopic evaluation were carried out and corneal photography was documented. All 17 exons and flanking intron sequences of the TGFBI gene were sequenced.

Results

Thirty-three participants demonstrated LCD in both eyes, most of which was symmetrical. Age at onset of decreased vision was the mid- to late twenties. Visual acuity varied from 6/6 to no light perception. Two patients, 74 and 42 years of age, demonstrated a thick yellowish plaque covering the corneal surfaces. DNA sequencing revealed a heterozygous mutation in exon 13 (A1762G), changing histidine to arginine at codon 572 (H572R). Ten of 42 clinically unaffected family members, all under 25 years of age, exhibited the same mutation.

Conclusions

This is the first report of a molecular analysis of LCD type I in Thai patients. The novel mutation identified is associated with distinct phenotypes and later onset of the disease compared with the more common R124C mutation.?Jpn J Ophthalmol 2006;50:403–408 © Japanese Ophthalmological Society 2006     

Long-term Change of Subfoveal Choroidal Thickness in Behçet’s Disease Patients with Posterior Uveitis

Purpose: To evaluate long-term changes of subfoveal choroidal thickness (SCT) in Behçet’s disease (BD) patients with posterior uveitis.

Methods: Changes in SCT measured with enhanced depth imaging optical coherence tomography during quiescent phase were assessed during >24 months in 63 BD patients and control group.

Results: Baseline characteristics showed no difference, but the BD group showed poorer visual acuity (p = 0.013) and smaller SCT (p = 0.006) at final examination. Mean SCT in the BD group decreased from 291.0 to 268.1 μm (p<0.001) during the mean period of 38.5 months. Mean change rate of SCT in the BD group was greater than controls (–7.2 vs 2.0 μm/year; p<0.001) and was associated with longer active inflammation (p<0.001). Patients with longer disease duration showed smaller baseline SCT (p = 0.03).

Conclusions: In BD patients, choroidal thickness decreased over time, which was associated with length of active inflammation. It suggests intraocular inflammation in BD affects the choroid as well as the retina.     

The Medial Canthal Tendon Is Composed of Anterior and Posterior Lobes in Japanese Eyes and Fixes the Eyelid Complementarily with Horner’s Muscle

Purpose To report that the medial canthal tendon (MCT) is not simply the aggregate of the orbicularis oculi muscle (OOM) and its tendon.Methods Twenty eyelids of 10 cadavers were used. The cadavers, seven male and three female, were all Japanese, with an average age of death of 76.2 years. The relationship between the MCT and the OOM, and between the tarsus and Horners muscle were investigated. Histological findings were obtained with hematoxylin and eosin staining.Results The MCT was structured with an anterior lobe, the tendon from the tarsal area of the OOM, and a posterior lobe, the muscle–tendon transition area in the orbital area of the OOM. The nasal aspect of the tarsus was fixed by Horners muscle.Conclusions The MCT and Horners muscle are located in an important area of the eyelid; therefore, it is essential to understand their precise anatomy. Jpn J Ophthalmol 2004;48:493–496 © Japanese Ophthalmological Society 2004     

Comparisons of Clinical Features in Japanese Patients with Behçet’s Uveitis Treated in the 1990s and the 2000s

ABSTRACT

Purpose: We investigated clinical characteristics of ocular Behçet’s disease (BD) patients treated in the 1990s and the 2000s.

Methods: We retrospectively examined records of 68 newly arrived patients with ocular BD followed for more than 4 months during the 2000s and compared to those of 107 patients during the 1990s. Patient profiles, ocular and systemic symptoms, frequency of ocular attacks, BD ocular attack score 24–6 months (BOS24-6M), best-corrected visual acuity (BCVA), and immunomodulatory treatment were noted.

Results: Clinical characteristics in the 2000s showed increases in iridocyclitis type, intestinal-, vasculo-, and neuro-BD cases, oral corticosteroid, methotrexate, and infliximab therapy usage, cataract and glaucoma surgery, and pseudophakia, and decreases in BOS24-6M and cyclophosphamide usage. BCVA of 20/30 or better at the final visit was slightly increased in the 2000s.

Conclusions: Milder ocular BD tendency was seen in cases in the 2000s, whereas the incidence of special type of BD might be increasing.     

Analysis of candidate genes ZEB1 and LOXHD1 in late-onset Fuchs’ endothelial corneal dystrophy in an Indian cohort

Background: Fuchs’ endothelial corneal dystrophy (FECD) is a complex degenerative disease of the corneal endothelium with genetic predisposition. Pathogenic rare variants have been identified in SLC4A11, LOXHD1, ZEB1, and AGBL1. Association of single nucleotide polymorphisms (SNPs) and CTG trinucleotide repeat expansions in the intron of TCF4 gene to FECD has been studied across multiple ethnicities. Recently, genome-wide association studies have also identified KANK4, LAMC1, and ATP1B1 as novel loci for FECD. Here, we report the contribution of ZEB1 and LOXHD1 genes in our sporadic late-onset FECD cohort.

Materials and methods: In the experimental study, coding regions of ZEB1 and LOXHD1 were screened by Sanger DNA sequencing in 52 late-onset and 5 early-onset FECD cases of Indian origin, recruited at a tertiary eye care center. Further, bioinformatics analysis was done.

Results: One reported missense mutation, c.2522A>C; p.(Q841P), and one variant of uncertain significance (VUS), c.619A>G; p.(S207G), were identified in the ZEB1 gene. One VUS, c.6413G>Ap.(R2138Q), was observed in LOXHD1. A 3D structural bioinformatic analysis of the missense variant in LOXHD1 predicted the variant to affect the structure–function relationship of the protein.

Discussion: While mutations in ZEB1 contributed to 2% of the late-onset FECD cases, the exact role of the two VUS identified in ZEB1 and LOXHD1 in FECD pathogenesis needs to be studied.     

Impact of DMEK on visual quality in patients with Fuchs’ endothelial dystrophy

Graefe's Archive for Clinical and Experimental Ophthalmology - To investigate short-term (3&nbsp;months follow-up) changes in visual quality following Descemet membrane endothelial...     

Utilization of Gene Mapping and Candidate Gene Mutation Screening for Diagnosing Clinically Equivocal Conditions： A Norrie Disease Case Study

Prenatal diagnosis was requested for an undiagnosed eye disease showing X-linked inheritance in a family. No medical records existed for the affected family members. Mapping of the X chromosome and candidate gene mutation screening identified a c.C267A[p.F89L] mutation in NPD previously described as possibly causing Norrie disease. The detection of the c.C267A[p.F89L] variant in another unrelated family confirms the pathogenic nature of the mutation for the Norrie disease phenotype. Gene mapping, haplotype analysis, and candidate gene screening have been previously utilized in research applications but were applied here in a diagnostic setting due to the scarcity of available clinical information. The clinical diagnosis and mutation identification were critical for providing proper genetic counseling and prenatal diagnosis for this family.     

The Preliminary Study of Glucocorticoid Receptor Gene in Chinese Patients with Glucocorticoid—induced Glaucoma^#

Background: To study the glucocorticoid receptor (GR) and the associated gene regulation in the pathogenesis of glucocorticoid- induced glaucoma (GIG) in Chinese patients.Methods: The trabecular cells of normal individuals and patients with GIG were cultured in vitro. By using polymerase chain reaction (PCR),gene fragments on GR DNA binding sites of trabecular cells were amplified. The product was detected by gel electrophoresis.Results: The trabecular cells were cultured successfully in normal individuals and patients with GIG in vitro. A single PCR product was obtained in both two groups with the same size of 545 base pairs.Conclusion: There is not any difference in gene on the GR DNA binding sites between normal individuals and patients with GIG. The results suggest the difference in mRNA or other functional genes. Eye Science 1999 ; 15 ; 46 - 50.     

An Analysis of 1 001 Blinding Patients with Corneal Disease in 1960—1989

Purpose:To investigate the condition and change of corneal blindness (CB) in the past 30 years.Methods: 1 001 blinding patients of corneal disease were clinically analysed from 1960 to 1989,including etiology, sex, age, occupation, difference between the urban and rural areas etc.Results: The male predominated. Infection stood the first cause of blinding corneal diseases, followed by trauma,malnutrition and the others.HSV-1 keratitis was the most frequent infection in 1980s. The highest incidence of CB was 20-40 year -old. The number of CB caused by occupational truauma was more than that by ordinary trauma in 1960s,but from 1970s, the latter was more than the former. The number of CB in rural area was more than that in the urban in 1960s,but from 1970s,there was no significant difference between the two areas. The percentage of bilateral CB was gradually decreased.Conclusion: We should try to find more effective strategies to prevent and treat CB caused by HSV-1 keratitis, pay special attention to pres