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Nazlee Zebardast, Srinivasan Kavitha, Palaniswamy Krishnamurthy, Sabyasachi Sengupta, Mohideen Abdul Kader, Ganesh Raman, Sharmila Reddy, Rengaraj Venkatesh, Pradeep Y Ramulu; Family history is a risk factor for severe stages of angles closure in a South Indian population. Invest. Ophthalmol. Vis. Sci. 2015;56(7 ):5819.
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To determine if more severe stages of angle closure, defined as primary angle closure or primary angle closure glaucoma (PAC/PACG), are more prevalent amongst siblings of PAC/PACG patients as compared to siblings of primary angle closure suspects (PACS).
Design: Cross-sectional clinical study<br /> Participants: A total of 596 South Indian proband-sibling pairs, including 422 probands with diagnosis of PACS and 174 with a diagnosis of PAC/PACG.<br /> Methods: A masked grader evaluated probands and siblings by gonioscopy, applanation tonometry, slit lamp biomicroscopy and optic nerve evaluation in order to define the angle closure phenotype. Probands were recruited from one of 2 groups based on the phenotype of the more severely affected eye: (1) PACS, or (2) PAC/PACG. One sibling of each proband was then examined and classified into one of 3 groups: open angles (OA), PACS, or PAC/PACG. Multivariable logistic regression models were used to estimate the odds of PAC/PACG in siblings of PAC/PACG probands as compared to siblings of PACS probands.
Across both sibling groups, 387 individuals (64.9%) had OA, 172 (28.9%) had PACS and 37 (6.2%) had PAC/PACG. There was no significant difference in the prevalence of any angle closure (PACS, PAC or PACG) among PACS siblings (35.3%) and PAC/PACG siblings (34.1%) (p=0.8). However, PAC/PACG was more prevalent among siblings of PAC/PACG probands as compared to siblings of PACS probands (9.7% vs 4.7% respectively; p=0.02). In multivariable models adjusting for proband and sibling age and gender, the odds of PAC/PACG was 2.1 times greater in PAC/PACG siblings as compared to PACS siblings (95% CI=1.1 to 4.3; p=0.03). PAC/PACG siblings were noted to have a significantly higher intraocular pressure as compared to PACS siblings, (β=+0.85 mmHg, 95% CI 0.22-1.48; p=0.008) but did not demonstrate higher cup/disc ratios (p=0.74) or more frequent peripheral anterior synechiae (PAS) (p=0.96).
Siblings of South Indian PAC/PACG probands have a greater than two times greater odds of a more severe stage of angle closure than siblings of probands with PACS, suggesting there may be different sets of genetic risk factors that determine whether iridotrabecular contact is tolerated, or whether it progresses towards PAS formation, elevated intraocular pressure and/or glaucomatous damage.
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