A Modified Technique in Applying Sponge Soaked with Mitomycin C in Trabeculectomy.

ABSTRACT: Trabeculectomy with adjunctive use of Mitomycin C (MMC) has been a benchmark for glaucoma filtration surgery for decades. However, there are many variations in the ways that the sponges soaked with MMC are applied during the trabeculectomy surgery. We herein describe our way of placing the MMC-soaked sponges to improve the safety and efficacy of the trabeculectomy. The sponges are placed vertically and posteriorly with the long side of the sponge perpendicular to the limbus, not parallel. This will reduce the size of the conjunctival wound at the limbus to preserve more virgin conjunctiva that can be used for repeated trabeculectomy when needed. This will also facilitate a more posteriorly directed flow of aqueous drainage that, in turn, may increase the success rate of the trabeculectomy. We have obtained encouraging results in our practice, and further large-scale randomized studies seem warranted.

Quantitative Trait Locus Analysis of SIX1-SIX6 With Retinal Nerve Fiber Layer Thickness in Individuals of European Descent.

PURPOSE: To perform a quantitative trait locus (QTL) analysis and evaluate whether a locus between SIX1 and SIX6 is associated with retinal nerve fiber layer (RNFL) thickness in individuals of European descent. DESIGN: Observational, multicenter, cross-sectional study. METHODS: A total of 231 participants were recruited from the Diagnostic Innovations in Glaucoma Study and the African Descent and Glaucoma Evaluation Study. Association of rs10483727 in SIX1-SIX6 with global and sectoral RNFL thickness was performed. Quantitative trait analysis with the additive model of inheritance was analyzed using linear regression. Trend analysis was performed to evaluate the mean global and sectoral RNFL thickness with 3 genotypes of interest (T/T, C/T, C/C). All models were adjusted for age and sex. RESULTS: Direction of association between T allele and RNFL thickness was consistent in the global and different sectoral RNFL regions. Each copy of the T risk allele in rs10483727 was associated with -0.16 µm thinner global RNFL thickness (ß = -0.16, 95% confidence interval: -0.28 to -0.03; P = .01). Similar patterns were found for the sectoral regions, including inferior (P = .03), inferior-nasal (P = .017), superior-nasal (P = .0025), superior (P = .002) and superior-temporal (P = .008). The greatest differences were observed in the superior and inferior quadrants, supporting clinical observations for RNFL thinning in glaucoma. Thinner global RNFL was found in subjects with T/T genotypes compared to subjects with C/T and C/C genotypes (P = .044). CONCLUSIONS: Each copy of the T risk allele has an additive effect and was associated with thinner global and sectoral RNFL. Findings from this QTL analysis further support a genetic contribution to glaucoma pathophysiology.

Variation in optic nerve and macular structure with age and race with spectral-domain optical coherence tomography.

PURPOSE: To evaluate the effects of age and race on optic disc, retinal nerve fiber layer (RNFL), and macular measurements with spectral-domain optical coherence tomography (SD OCT). DESIGN: Cross-sectional observational study. PARTICIPANTS: Three hundred fifty adult subjects without ocular disease. METHODS: Data from SD OCT imaging of the optic nerve head, peripapillary RNFL, and macula of 632 eyes from 350 subjects without ocular disease were imaged with SD OCT. Multivariate models were used to determine the effect of age and race on quantitative measurements of optic disc, RNFL, and macula. MAIN OUTCOME MEASURES: Optic nerve, RNFL, and macular measurements with SD OCT across racial strata and age. RESULTS: For optic nerve parameters, participants of European descent had significantly smaller optic disc area than other groups (P<0.0001), and Indian participants had significantly smaller rim area than other groups (P<0.0001). Indian and Hispanic participants had thicker global RNFL measurements than other groups (P<0.0001). Participants of African descent were associated with thinner inner retinal thickness in the macula (P<0.0001). Age was associated with several parameters, with rim area reducing by 0.005 mm(2)/year, RNFL thickness reducing by 0.18 µm/year, and inner retinal thickness reducing by 0.1 µm/year (P<0.0001 for all age associations). CONCLUSIONS: Optic nerve, RNFL, and macular measurements with SD OCT all varied across racial groups and with age. These differences are important in defining the range of normal variation in differing populations and should be considered in the use of these instruments in the detection of optic nerve and macular disease across these population groups. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found after the references.

The effects of race, optic disc area, age, and disease severity on the diagnostic performance of spectral-domain optical coherence tomography.

PURPOSE: To evaluate the effect of race (African or European descent), age, disc area, and severity of disease on the diagnostic ability of spectral-domain optical coherence tomography (SDOCT) imaging of the optic nerve, macula, and retinal nerve fiber layer (RNFL) in the detection of glaucomatous injury. METHODS: In this cross-sectional observational study, data from SDOCT images of 312 eyes of 167 subjects without ocular disease and 233 eyes of 163 patients with open-angle glaucoma. A receiver operating characteristic (ROC) regression modeling technique was used to evaluate the influence of race on the diagnostic accuracy of the ONH, RNFL, and macular parameters in SDOCT in glaucoma, while adjusting and evaluating the possible confounding effects of age, disease severity, and size of the optic disc. RESULTS: The optimal performing measurements of the RNFL and macula were more effective than optic nerve (aROC(RNFL) = 0.87, aROC(inner macula) = 0.88, and aROC(rim area) = 0.81) for the overall group. No variation was noted in the diagnostic performance of SDOCT between racial groups nor was there any association of race with differences in disc area for structural parameters of the optic nerve, RNFL, and macula. Advanced disease severity was associated with increased diagnostic accuracy, with improved performance in eyes with more severe visual field loss. CONCLUSIONS: The diagnostic ability of ONH, RNFL, and macular measurements in the detection of glaucoma was similar across racial groups, and disc area had a minimal effect on the overall diagnostic efficacy of SDOCT. No significant differences were seen in the diagnostic performance of the SDOCT between these groups when generalized or race-specific normative data were used.

Assessment of scleral spur visibility with anterior segment optical coherence tomography.

PURPOSE: To develop a grading system to evaluate the scleral spur visibility and to investigate the association between this and the angle width. METHODS: Sixty healthy normal subjects (33 with open angles and 27 with narrow angles on dark room gonioscopy) underwent anterior segment imaging with the Visante OCT (Carl Zeiss Meditec, Dublin, CA). The anterior chamber angles at 12-o' clock hour positions were imaged and analyzed. The scleral spur at each clock hour position was independently graded by 2 observers. A scleral spur visibility score (SSVS) of 2 denotes clear visibility of the scleral spur. SSVS of 0 and 1 represent undetectable and moderately by visibile scleral spur, respectively. The interobserver agreement of the SSVS was evaluated with kappa statistics. The associations between age, sex, axial length, refraction, angle width [mean anterior chamber angle detection with edge measurement and identification algorithm (ACADEMIA) angle], and the mean SSVS were examined with univariate and multivariate analyses. RESULTS: The mean gonioscopy grades were 3.6 and 0.8 for the open and narrow angle groups, respectively. The interobserver agreement in grading the scleral spur visibility was 0.71. The inferior angle (6:00) had the worst visibility of the scleral spur (SSVS=1.05+/-0.49) whereas the scleral spur of the nasal angle (3:00) showed the best visibility (SSVS=1.66+/-0.46). There were significant differences between SSVS at 6:00 and the other clock hours except for 5:00 and 7:00. The mean SSVS correlated positively with gonioscopy grade, anterior chamber depth, and ACADEMIA angle, and negatively with age. The only significant factor associated with scleral spur visibility was the ACADEMIA angle (P=0.013) after adjustment for other covariates. CONCLUSIONS: The visibility of the scleral spur is an important determinant of the dimension of anterior chamber angle.

Identification and analysis of a novel mutation in the FOXC1 forkhead domain.

PURPOSE: To determine the genetic and biochemical defects that underlie Axenfeld-Rieger malformations, identify the pathogenic mutation causing these malformations, and understand how these mutations alter protein function. METHODS: FOXC1 was amplified from a proband with Axenfeld-Rieger malformations and the proband's mother. PCR products were sequenced to identify the pathogenic mutation. Site-directed mutagenesis was used to introduce this mutation into the FOXC1 cDNA. A synthetic mutation at the same position was also introduced, and both natural and synthetic proteins were tested for their ability to localize to the nucleus, bind DNA, and transactivate gene expression. RESULTS: A novel missense mutation (L86F) was identified in FOXC1 in this family. The mutation is located in alpha-helix 1 of the forkhead domain. Biochemical assays showed that the L86F mutation does not affect nuclear localization of FOXC1, but reduces DNA binding and significantly reduces transactivation. The severity of the disruption to FOXC1 protein activity does not appear to correspond well with the severity of the phenotype in the patient. Analogous studies using a L86P, a known alpha-helix breaker, severely disrupts FOXC1 function, revealing the importance of helix 1 in FOXC1 structure and function. CONCLUSIONS: A novel mutation in helix 1 of the FOXC1 forkhead domain has been identified and the importance of position 86 in FOXC1 activity demonstrated. These studies also identified the role of helix 1 in FOXC1 function and provide further evidence for the lack of strong genotype-phenotype correlation in FOXC1 pathogenesis. Normal development appears to be dependent on tight upper and lower thresholds of FOXC1 activity.