A Genetic Variant in TGFBR3-CDC7 Is Associated with Visual Field Progression in Primary Open-Angle Glaucoma Patients from Singapore.

PURPOSE: To investigate whether known genetic loci for primary open-angle glaucoma (POAG) are associated with visual field (VF) progression in patients from a Singaporean Chinese population. DESIGN: Retrospective study. PARTICIPANTS: Patients with 5 or more reliable VF measurements who were being followed up at a Singapore hospital. METHODS: Visual field progression was identified using Progressor software version 3.7 (Medisoft, Leeds, United Kingdom) and defined by pointwise linear regression (PLR) criteria as follows: any 2 contiguous points in the same hemifield progressing (≤-1.00 dB/year for inner points and ≤-2.00 dB/year for edge points; P < 0.01). Single nucleotide polymorphisms (SNPs) and their proxies from 10 POAG-associated loci (CAV1-CAV2, CDKN2B-AS1, SIX1-SIX6, an intergenic region on chromosome 8q22, ABCA1, GAS7, AFAP1, GMDS, PMM2, and TGFBR3-CDC7) identified from genome-wide association studies were tested for association with VF progression using logistic regression with an additive genetic model adjusting for age, gender, average intraocular pressure (IOP), central corneal thickness (CCT), and baseline vertical cup-to-disc ratio (VCDR). MAIN OUTCOME MEASURE: Visual field progression. RESULTS: Of the 1334 patients included in the study, 469 subjects (35.1%) completed 5 or more reliable VF measurements (mean follow-up, 9.01 years; standard deviation, 5.00 years). The mean age of patients was 59.6 years (standard deviation, 9.0 years); 305 patients were men and all were Chinese. The average IOP in eyes fulfilling PLR progression was 16.5 mmHg versus 17.7 mmHg in those who did not (P = 0.52). Univariate analysis revealed that increased VCDR (P = 0.003), reduced CCT (P = 0.045), and reduced superior and inferior retinal nerve fiber layer thickness (P = 0.01, respectively) were associated with VF progression. No clinical or structural features were associated significantly with VF progression on multivariate analysis. The rs1192415 index SNP in TGFBR3-CDC7 (P = 0.002; odds ratio, 6.71 per risk allele) was the only SNP associated with VF progression. CONCLUSIONS: The presence of the index SNP rs1192415 (TGFBR3-CDC7) was associated with VF progression in POAG patients. These findings warrant further investigation in independent cohorts.

New corneal findings in chromosome 10 deletion syndrome: report of two cases of corneal ectasia of varying severity.

PURPOSE: To describe corneal changes associated with chromosome 10 terminal deletion (chromosome 10, monosomy 10qter) syndrome. METHODS: Report of two cases of bilateral corneal ectasia with literature review. RESULTS: Corneal pathology has not previously been reported in the limited number of case reports on 10qter syndrome. However, Rodrigues et al.(1) have reported sclerocornea in 10q translocation. CONCLUSIONS: Ophthalmic manifestations of 10qter syndrome include strabismus, lid, and facial anomalies. We present two cases of corneal ectasia of varying severity. Possible etiologies include the following: secondary to genetic factors, acquired corneal exposure during sleep, or possible intrinsic immunocompromise exacerbating ocular surface infections. Corneal ectasia with specific histological changes is a feature of various genetic disorders (e.g., Down's, Ehler's Danlos, and Marfan's syndromes). It is unknown whether genetics plays a role in the development of corneal changes in 10qter syndrome. Management of inflammation and visual rehabilitation in these patients poses a therapeutic challenge.