Evaluation of the beta2-adrenergic receptor gene as a candidate glaucoma gene in 2 ancestral populations.

OBJECTIVE: To determine whether the beta(2)-adrenergic receptor (ADRB2) gene is a glaucoma susceptibility locus. DESIGN AND METHODS: The design was an association study stratified by ancestry (white vs black African) and disease (primary open-angle glaucoma vs control subjects). The ADRB2 single nucleotide polymorphisms were determined by sequencing, and the haplotypes of the common single nucleotide polymorphisms affecting codons 16 and 27 were phased by allele-specific polymerase chain reaction and restriction enzyme digestion. We analyzed the association of single nucleotide polymorphisms and haplotypes by ancestry and disease with the Fisher exact test, chi(2) test, and standardized Pearson residual. RESULTS: A total of 583 subjects underwent genotyping (156 white subjects with primary open-angle glaucoma; 143 subjects of black African ancestry with primary open-angle glaucoma; 148 white controls; and 136 controls of black African ancestry). There were no differences in ADRB2 alleles and haplotypes between the primary open-angle glaucoma and control groups, whether analyzed together or by ancestry. Previously described ancestry-based differences in allele frequencies were found. We also found ancestry-based differences in ADRB2 haplotypes. CONCLUSION: The ADRB2 gene was not a glaucoma susceptibility locus in our study population. CLINICAL RELEVANCE: Because this gene is not a disease locus, we can now study the role of ADRB2 haplotypes in the glaucoma risk factor of intraocular pressure fluctuation and variation in intraocular pressure response to beta-blockers.

Concordance of aqueous humor flow in the morning and at night in normal humans.

PURPOSE: To test the hypothesis that an individual shows concordance of aqueous humor flow in the morning and at night in a prospective inpatient fluorophotometry study in healthy subjects. METHODS: Flow was measured in each eye every hour between 8 AM and noon and every 2 hours between midnight and 6 AM. Morning and nighttime flows were analyzed for differences between eyes and for differences between these two time points. Concordance of individual morning and nighttime flows were studied by categorization into low, medium, or high tertiles, dot plot, and ordinary least-squares regression (OLS) scatter plot. RESULTS: In 28 subjects, the flow was similar between eyes within a subject with healthy eyes. In the one eye examined in each subject, the average flow was 3.12 +/- 1.09 muL/min in the morning, which decreased significantly to 1.59 +/- 0.58 muL/min at night. During each time period, the individual flow data were normally distributed. Concordance of an individual's morning and nighttime flows was 68%. A scatter plot of morning versus nighttime flows also supported concordance with an OLS regression fit of r(2) = 0.45. CONCLUSIONS: The results provide evidence that aqueous humor flow is similar between eyes, that flow variation shows a normal distribution, and that individuals show a concordance of flow in the morning and at night. These observations support the posit that aqueous humor flow, which is a factor that contributes to the important clinical risk factor of IOP variation, is amenable to study as a quantitative trait.

Subconjunctival placement of human amniotic membrane during high risk glaucoma filtration surgery.

BACKGROUND AND OBJECTIVE: To determine whether subconjunctival placement of amniotic membrane improves filtration results in patients with glaucoma at high risk for surgical failure. PATIENTS AND METHODS: Retrospective review of 17 eyes of 15 patients who had amniotic membrane applied during glaucoma surgery with or without mitomycin C or 5-fluorouracil. RESULTS: Mean intraocular pressure decreased from 27.0 +/- 9.1 mm Hg preoperatively to 18.1 +/- 11.0 mm Hg postoperatively with a mean follow-up of 179 days. Complications included self-limited conjunctival wound dehiscence (n = 5), uveitis recurrence (n = 2), and cataract progression (n = 1). CONCLUSIONS: The results suggest that subconjunctival placement of amniotic membrane may improve filtration outcome in high risk eyes. It will be of interest to determine whether the anti-inflammatory, anti-angiogenic, and antifibrotic properties of amniotic membrane placed subconjunctivally and under the scleral flap will improve filtration surgery outcome by a prospective, randomized study.