Genetic and Phenotypic Investigation of a Chinese Pedigree with Lattice Corneal Dystrophy ⅢB Subtype

Purpose：To investigate phenotypes and disease-causing mutation in the transforming growth factor b-induced gene （TGFBI） in a Southern Chinese pedigree with lattice corneal dystrophy （LCD） ⅢB with complicated cataract.Methods：A Southern Chinese pedigree with lattice corneal dystrophy ⅢB with complicated cataract was recruited.Comprehensive ophthalmic investigations were performed before and after cataract surgery of phacoemulsification and intraocular lens implantation in the proband＇s both eyes.Peripheral blood was collected from the proband,and genomic DNA was extracted.All exons of the TGFBI gene were sequenced to screen possible mutations.Results：A bilateral LCD ⅢB subtype was observed in the proband.Optical coherence tomography further revealed superreflective changes in the subepithelial and stroma layers of the cornea,with reduced central corneal thickness.Notably,bilateral cataract was found in the proband.Direct sequencing detected a recurrent heterozygous missense c.1877A＞G mutation in exon 14 of the TGFBI gene,resulting in substitution of histidine with arginine （p.H626R）.Conclusion：The current study was the first report of the TGFBI p.H626R mutation in Southern Chinese,suggesting that it could be a mutation hotspot across populations.Moreover,the mutation was associated with LCD ⅢB subtype with complicated cataract,which had not been reported before,pointing to clinical heterogeneity of the mutation.     

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.     

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     

The dilemma of the late-onset “Dystrophy”

A case of late-onset (age 51) visual loss and night-blindness is presented to illustrate the challenges of diagnosis. This patient had anti-enolase antibodies, and demonstrates the importance of auto-immune retinopathy as a potential cause of late-onset retinal “dystrophy.”     

Corneal Topographical Changes Following Strabismus Surgery

Purpose: To study corneal topographical changes after strabismus surgery. Methods: Computer-aided corneal topography was used in 43 strabismus patients (45 eyes) one or two days prior to and six or seven days after strabismus surgery. The spherical and cylindrical equivalents were calculated based on the simulated keratome-try.Results: After the surgery, only the changes at 3mm in the inferior quadrant were statistically significant. The changes at 3mm in the rest quadrants and the changes at 7mm were not significant. Significant changes in spherical equivalent were found post-operatively. Neither the horizontal nor the vertical meridional equivalent showed significant changes after surgery.Conclusions: The results of corneal topographical changes following strabismus surgery in our preliminary study indicated the little effect of strabismus surgery on corneal curvature and corneal astigmatism. Eye Science 1999; 15: 174 - 178.     

Are There Any Changes in Corneal Biomechanics and Central Corneal Thickness in Fuchs’ Uveitis?

Purpose: To compare corneal biomechanics, intraocular pressure (IOP) and central corneal thickness (CCT) of 38 patients with unilateral Fuchs’ uveitis (FU) with 42 healthy controls.

Methods: Corneal hysteresis (CH), corneal resistance factor (CRF), Goldmann-correlated and corneal-compensated IOP (IOPg and IOPcc, respectively) and CCT were measured.

Results: The mean CH, CRF, and IOPg of the involved FU eyes were significantly lower (9.5?±?1.6, 9.0?±?1.9 and 13.1?±?4.3?mmHg) than contralateral eyes (10.1?±?1.7, 9.9?±?1.7 and 14.6?±?3.4?mmHg), and controls (10.5?±?1.5, 10.3?±?1.5 and 14.8?±?2.5?mmHg), respectively. There was no significant difference for mean IOPcc between involved FU or contralateral eyes and controls (14.8?±?4.1, 15.5?±?3.4 and 15.0?±?2.7?mmHg). The CCT values correlated with CH and CRF in the involved and contralateral eyes.

Conclusions: Involved FU eyes had lower CH, CRF, and IOPg than contralateral eyes and controls, with no difference regarding IOPcc.     

Corneal Topography Research of Myopia in Chinese

Purpose: To determine corneal topography parameters of myopia in Chinese and help for studies of causes of myopia, distingiush other corneal diseases (such as early keratoconus), further explore the accurateness and safeness of the clinical effects of radii keratotomy(RK) or photorefractive keratectomy (PRK). Methods: Fifty-eight eyes with mild or moderate myopia were examined by computer-assisted photokeratography. (TMS-1 Computed Anatomy Inc. New York. NY)Results: The corneal topography of most (68%) of the examined eyes showed symmetric bowtie pattern; the corneal surface of most (75%) of the examined eyes showed positive aspheric shape (steeper centrally, flatter peripherally); the refractive power of central cornea is at mean 44. 165 ± 1. 429D; the refractive difference between 1 to 25 ring in keratoscpe was at mean 1. 655 ± 0. 785D; the mean SRI was 0. 558 ± 0. 768, the mean SAI was 0. 296 ± 0. 149; the mean Smik was 44. 209±1. 515D. The apex and visual axis were dislocation in all the cornea     

Corneal Topographic Analysis in Patients with Cataract

We studied the corneal curvature of 161 eyes in 101 patients, aged from 50 to 80 years (mean: 63 years), with senile cataract using the Topographic Modeling System (IMS) preoperatively. The results revealed that mean surface asymmetry index (SAD was 0. 36 and mean surface regularity index (SRI) 0. 79. Simulated keratometry reading (Sim K) was 44. 46 D, and 43. 56 D. Minimun K reading was 42. 60 D. The same patterns of corneal topography in both eyes were 50% in 60 patients who had binocular examination. Astigmatism less than 1 D was 23% in 161 corneas. Corneal patterns included round (21. 2%), oval 16. 1%), symmetric and asymmetric bow-tie (22. 2%), and irregular (40. 4%). SRI and SAI of the irregular pattern were statistically higher than those of the round, oval and bow-tie patterns in our patients (P<0. 01 and P<0. 05). The results of our study determined that the cornea of eye with senile cataract preoperatively is not a perfect spherocylin-der. It is asymmetrically aspheric, with less curvature per     

The Influence of Central Corneal Thickness and Corneal Curvature and Axial Length on the Measurement of Intraocular Pressure

Purpose: To examine the influence of central corneal thickness (CCT), cornealcurvature (CC), and axial length (AL) on intraocular pressure (IOP).Methods: Eighty-one clinically normal eyes were included in our study. The IOP, CCT,CC, AL were measured using a Goldmann applanation tonometer, optical pachymeter,keratometer and A-scan ultrasound biometer respectively in all subjects.Results: A highly significant positive correlation was identified between IOP and CCT.Linear regression analysis suggests that an increase in CCT of 0. 010 mm is associatedwith a 4. 946 mmHg increment in IOP. No significant positive correlation was identifiedbetween IOP and CC. P values are 0. 724 and 0. 414 respectively for vertical andhorizontal readings. A paradoxically reversed correlation was present between IOP andaxial length.Conclusion: Corneal thickness is a very important confounding factor in the measurementof intraocular pressure, which warrants further attention in our clinical practice. EyeScience 2002; 18: 176 - 18     

Intrastromal Corneal Ring Segments (ICRS®)

In the period from May 1997 to November 1998 twenty-one eyes of fifteen patients with sighted eyes received Intrastromal Corneal Ring Segments (ICRS®) for the surgical treatment of low myopia. The mean pre-operative refraction was –3.0 diopters (D) ranging from –1.5 D to –4.1 D. Three months results showed that 44% of the treated eyes had an uncorrected visual acuity (UCVA) of 1.0 or better while 94% had an UCVA of 0.5 or better. In 94% the postoperative refraction was within one diopter (D) of emmetropia and in 61% within 0.5 D of emmetropia. Mean induced astigmatism was 1.03 (std 0.75). The best spectacle corrected visual acuity (BSC VA) after 3 months was 1.0 or better in all patients. After six months the UCVA was 1.0 or better in 43% of the treated eyes while in 100% the UCVA was 0.5 or better. The post-operative refraction was within 1 D of emmetropia in 100% and within 0.5 D of emmetropia in 81%. Mean induced astigmatism was 1.00 (std 0.50). BSCVA was in 88% 1.0 or better and in 100% 0.9 or better. In one patient vascular ingrowth occurred due to a ring segment located under the incision. Three patients experienced a lower UCVA due to postoperative astigmatism. In only one patient in this series the ICRS® were removed because of induced astigmatism. These preliminary results show that the ICRS® seem to offer a safe, stable and reproducible method to correct low myopia. The operation carries a low risk but care must been taken to insert the ICRS® as central as possible to prevent postoperative astigmatism.     

Analysis of COL8A2 Gene Mutation in Japanese Patients with Fuchs’ Endothelial Dystrophy and Posterior Polymorphous Dystrophy

Purpose To determine whether Japanese patients with Fuchs endothelial corneal dystrophy (FECD) and posterior polymorphous dystrophy (PPMD) carry mutations in the COL8A2 gene, and to investigate the possible pathogenicity of the COL8A2 gene in these corneal dystrophies.Methods DNA analysis of the COL8A2 gene was performed in 15 unrelated Japanese patients with FECD, and 5 patients with PPMD using polymerase chain reaction and direct sequencing. Mutation screenings were also performed in 36 unrelated normal volunteers as controls, as well as slit-lamp and specular microscopy.Results Two types of heterozygous missense mutations of the COL8A2 gene (R155Q and T502M) in 5 of 15 FECD probands (R155Q, 3/30 chromosomes, 10.0%; T502M, 3/30 chromosomes, 10.0%) were found. No mutation was detected in the coding region of the COL8A2 gene in the remaining 10 patients with FECD nor in any of the 5 patients with PPMD. These two mutations were also found in normal Japanese volunteers (R155Q, 5/72 chromosomes, 6.9%; T502M, 11/70 chromosomes, 15.7%). The chromosomal frequency of the two mutations was not significant between the patients and normal controls.Conclusions The R155Q and T502M mutations of COL8A2 may not be the causative defect in the Japanese FECD and PPMD patients examined in this study. Jpn J Ophthalmol 2004;48:195–198 © Japanese Ophthalmological Society 2004     

Corneal Nerve and Epithelial Cell Alterations in Corneal Allodynia: An In Vivo Confocal Microscopy Case Series

Purpose

To investigate morphological changes of the corneal epithelium and subbasal nerves in patients with corneal allodynia using in vivo confocal microscopy (IVCM).

Production of Hypoxia-induced Corneal Edema in Aged Eyes

IntroductionThecorneahasanextremelywellorganizedstromalarchitecturewhichcontributestowardsauniformrefractiveindex[1].Thecorneahasaten鄄dencytoswellunderapassiveimbibitionpres鄄sure[2].Excessivewatermoleculesaredrivenoutbynumerousenergy鄄consumingionicpumpsontheposteriorcornealendothelium[3]soastomai鄄ntainatransparentcornea.Incaseofanydisrup鄄tiontothisfunction,thehydrationlevelwouldincrease鄄cornealedema.Anydisruptiontoanor鄄malswelling鄄deswellingphysiology[2],mightaf鄄fectthecornealtranspa…