An alphaA-crystallin gene mutation, Arg12Cys, causing inherited cataract-microcornea exhibits an altered heat-shock response.

PURPOSE: To investigate the clinical features and molecular basis of inherited cataract-microcornea caused by an alphaA-crystallin gene (CRYAA) mutation in a Chinese family. METHODS: A three-generation Chinese family with members having autosomal dominant cataract and microcornea was recruited. Genomic DNA from peripheral blood or buccal swab samples of five affected and five unaffected members were obtained. Based on 15 genes known to cause autosomal dominant cataract, single nucleotide polymorphisms (SNPs) or microsatellite markers were selected and genotyped for two-point linkage analysis. Direct sequencing was performed to identify the disease-causing mutation. The expression construct coding for recombinant COOH-terminal myc-His-tagged wild type or R12C alphaA-crystallin protein (CRYAA) was expressed in COS-7 cells. Detergent solubility and subcellular distribution of wild type and R12C CRYAA were examined by western blotting and immunofluorescence, respectively. Heat-shock response was monitored by quantitative polymerase chain reaction (qPCR) of heat-shock proteins 70 and 90alpha (HSP70 and HSP90alpha). RESULTS: The five affected family members showed variable lens opacities and microcornea. Clinical features of cataract were asymmetric in two eyes of some affected subjects. A heterozygous missense substitution, c.34C>T, in CRYAA, which is responsible for the R12C amino acid change, segregated with autosomal dominant cataract (ADCC) in this family. This substitution was absent in 103 unrelated controls. When expressed in COS-7 cells, the R12C mutant CRYAA resembled the wild type protein in its solubility when extracted with 0.5% Triton X-100 and with its cytoplasmic localization. However, mutant cells exhibited an altered heat-shock response, evidenced by the delayed expression of HSP70, when compared to cells expressing wild type CRYAA. CONCLUSIONS: The R12C mutation in CRYAA was responsible for a variable type of inherited cataract associated with microcornea in this Chinese family. The altered heat-shock response of mutant cells suggested a change of chaperoning capacity and networking, which could be associated with the pathogenesis of hereditary cataract-microcornea syndrome.

Anterior chamber angle measurement with anterior segment optical coherence tomography: a comparison between slit lamp OCT and Visante OCT.

PURPOSE: To compare anterior chamber angle measurements obtained from two anterior segment optical coherence tomography (OCT) instruments and to evaluate their agreements and interobserver reproducibility. METHODS: Forty-nine eyes from 49 healthy normal subjects were studied. The anterior chamber angle was imaged with the Visante anterior segment OCT (Carl Zeiss Meditec, Dublin, CA) and the slit lamp OCT (SLOCT, Heidelberg Engineering, GmbH, Dossenheim, Germany) on one randomly selected eye in each subject and measured by two independent observers. The angle-opening distance (AOD 500), the trabecular-iris angle (TIA 500), and the trabecular-iris space area (TISA 500) at the nasal and temporal angles were measured. The agreements between SLOCT and Visante OCT measurements and the interobserver reproducibility were evaluated. RESULTS: The mean nasal/temporal anterior chamber angles measured by Visante OCT and SLOCT were 527 +/- 249/572 +/- 275 microm (AOD), 0.180 +/- 0.091/0.193 +/- 0.102 mm(2) (TISA), and 38.1 +/- 12.3/39.6 +/- 13.2 degrees (TIA); and 534 +/- 234/628 +/- 254 microm (AOD), 0.191 +/- 0.089/0.217 +/- 0.093 mm(2)(TISA), and 37.8 +/- 10.1/40.6 +/- 10.7 degrees (TIA), respectively. No significant difference was found between Visante OCT and SLOCT measurements except the temporal TISA (P = 0.034). The interobserver coefficient of variation ranged between 4.4% and 7.8% for Visante OCT and 4.9% and 7.0% for SLOCT. The spans of 95% limits of agreement of the nasal/temporal angle measurements between Visante OCT and SLOCT were 437/531 mm(2), 0.174/0.186 mm(2), and 25.3/28.0 degrees for AOD, TISA, and TIA, respectively. CONCLUSIONS: Although Visante OCT and SLOCT demonstrate high interobserver reproducibility for anterior chamber angle measurements, their agreement was poor.

Optic disc measurements in myopia with optical coherence tomography and confocal scanning laser ophthalmoscopy.

PURPOSE: To evaluate the relationships between optic disc measurements, obtained by an optical coherence tomograph and a confocal scanning laser ophthalmoscope, and myopia. METHODS: One hundred thirty-three eyes from 133 healthy subjects with mean spherical equivalent -6.0 +/- 4.2 D (range, -13.13 to +3.25 D) were analyzed. Optic disc measurements including disc area, rim area, cup area, cup-to-disc area, and vertical and horizontal ratios were obtained with an optical coherence tomograph (StratusOCT; Carl Zeiss Meditec Inc., Dublin, CA) and a confocal scanning laser ophthalmoscope (Heidelberg Retina Tomograph, HRT 3; Heidelberg Engineering, GmbH, Dossenheim, Germany). The modified axial length method derived from prior published work was used to correct the OCT measurements for ocular magnification. Bland-Altman plots were used to evaluate the agreement for each optic disc parameter. Associations between optic disc area and axial length/spherical equivalent were evaluated by linear regression analysis. RESULTS: Disc area increased with the axial length/negative spherical equivalent in the HRT and the corrected OCT measurements although opposite directions of associations were found when the OCT measurements were not corrected for magnification. The difference of the corrected OCT and HRT disc area (corrected OCT disc area minus HRT disc area) was correlated with the axial length (r = 0.195, P = 0.025). When the ametropia was limited to -8.0 to +4.0 D, the correlations became insignificant in the HRT. Using the corrected OCT measurements, disc area, rim area, and cup area, cup-to-disc area, and cup-to-disc horizontal and vertical ratios were significantly larger than those measured by the HRT, with a span of 95% limits of agreement at 1.99, 1.33, and 1.86 mm(2) for the areas, 0.34, 0.53, and 0.58 for the ratios, respectively. CONCLUSIONS: While optic disc area generally increased with the axial length and myopic refraction, the HRT measurements demonstrated that optic disc size was largely independent of axial length and refractive error between -8 and +4 D. OCT may overestimate optic disc size in myopic eyes and results in poor agreement between the two instruments.

Regional variations in the relationship between macular thickness measurements and myopia.

PURPOSE: To investigate the relationship between myopia and macular thickness, as measured by optical coherence tomography. METHODS: A total of 143 normal subjects comprising 80 eyes with high myopia (spherical equivalent [SE] < -6.0 D), 37 eyes with low to moderate myopia (SE between -6.0 and -0.5 D), and 26 nonmyopic eyes (SE > -0.5 D) were analyzed in this cross-sectional study. Total average, foveal, and inner and outer average macular thicknesses measured by the StratusOCT (Carl Zeiss Meditec Inc., Dublin, CA) were compared among the three diagnostic groups. Associations between macular thickness and refractive error/axial length were evaluated by linear regression analysis. RESULTS: The minimum foveal and average foveal (1-mm ring on the OCT retinal thickness map) thicknesses were significantly greater, and the outer ring macular (3-6-mm) thicknesses significantly lower in the high myopic eyes than in the low to moderate myopic and nonmyopic eyes. No significant difference was found in the inner ring (1-3-mm) macular thickness measurements among the groups. There was a positive correlation between the axial length and the average foveal thickness (r = 0.374, P < 0.001). Negative correlations were found between axial length and the average outer ring macular thickness (r= -0.471, P < 0.001) and total average macular thickness (r= -0.311, P < 0.001). CONCLUSIONS: Retinal thickness is related to refractive error/axial length in normal subjects with regional variations in correlation within the 6-mm macular region. Analysis of macular thickness in the evaluation of macular diseases and glaucoma should be interpreted only in the context of refractive errors and the location of measurement.