Determinants and Heritability of Intraocular Pressure and Cup-to-Disc Ratio in a Defined Older Population

Abstract

Purpose-To investigate the heritability of intraocular pressure (IOP) and cup-to-disc ratio (CDR) in an older well-defined population. Design-Family-based cohort study.Participants-Through the population-based Salisbury Eye Evaluation study, we recruited 726 siblings (mean age, 74.7 years) in 284 sibships.Methods-Intraocular pressure and CDR were measured bilaterally for all participants. The presence or absence of glaucoma was determined by a glacuoma specialist for all probands on the basis of visual field, optic nerve appearance, and history. The heritability of IOP was calculated as twice the residual between-sibling correlation of IOP using linear regression and generalized estimating equations after adjusting for age, gender, mean arterial pressure, race, self-reported diabetes status, and history of systemic steroid use. The heritability of CDR was calculated using the same model and adjustments as above, while also adjusting for IOP.Main Outcome Measures-Heritability and determinants of IOP and CDR, and impact of siblings' glaucoma status on IOP and CDR.Results-We estimated the heritability to be 0.29 (95% confidence interval [CI], 0.12-0.46) for IOP and 0.56 (95% CI, for CDR in this population. Mean IOP in siblings of glaucomatous probands was statistically significantly higher than in siblings of normal probands (mean difference, 1.02 mmHg; P = 0.017). The mean CDR in siblings of glaucomatous probands was 0.07 (or 19%) larger than in siblings of glaucoma suspect referrals (P = 0.045) and siblings of normal probands (P = 0.004).Conclusions-In this elderly population, we found CDR to be highly heritable and IOP to be moderately heritable. On average, siblings of glaucoma patients had higher IOPs and larger CDRs than siblings of nonglaucomatous probands.Primary open-angle glaucoma (POAG) is the second most common cause of blindness in the world 1 and affects approximately 2.2 million Americans. 2 Although the diagnosis of POAG centers on the characteristic excavation and atrophy of the optic nerve head and functional deficit measured by visual field (VF) change, 3 the heritability of intraocular pressure (IOP) and cup-to-disc ratio (CDR) have not been studied extensively thus far, despite the wellestablished role of heredity in POAG. In this study, we estimate the heritability of IOP and CDR from a cohort of sibships recruited through the Salisbury Eye Evaluation study. In addition, we also report the distribution of IOP and CDR among siblings of glaucomatous probands versus siblings of normal probands. Materials and Methods Subjects and General DesignBetween 1993 and 1995, a random sample of potential participants (ages 65 to 84 years) was chosen from the Health Care Financing Administration Medicare database and recruited from Salisbury, located on the Eastern Shore of Maryland, to engage in the population-based Salisbury Eye Evaluation study. 28 The cohort was invited for a follow-up examination including VF testing, optic nerve head imaging, and IOP measurement. All subjects with abnormal scr...

Primary open-angle glaucoma genes

“…Large studies of twins, siblings, and small pedigrees have shown that CCT, 76,77 cup-to-disc ratio, [78][79][80][81] and IOP [80][81][82][83][84] are all highly heritable traits and are likely determined in part by the actions of genes. Investigations to identify these genes will likely provide important insights into the pathophysiology of glaucoma.…”

Comparison of three methods of intraocular pressure measurement and their relation to central corneal thickness

“…1 Although it no longer forms part of the definition of the disease, elevated intraocular pressure (IOP) is the principal modifiable risk factor for the development and progression of open-angle glaucoma. [2][3][4] Although the Goldmann applanation tonometer (GAT) has been the 'gold standard' for measuring IOP in the clinical setting for several decades, recently there has been a growing interest in developing new technology to measure a more accurate IOP. 5 It is well known that GAT is affected by the central corneal thickness (CCT).…”

Morfometria comparativa entre discos ópticos de familiares de glaucomatosos e normais pelo HRTII

“…Um estudo genético da relação E/D entre parentes de primeiro grau relatou correlação altamente sugestiva de herança poligênica multifatorial (10) . Mais recentemente, Chang et al consideraram que a relação E/D em parentes de glaucomatosos era 0,07 (19%) maior que em parentes de probandos normais (p= 0,004) (11) . Existe controvérsia se discos ópticos maiores correlacionam-se com maior risco de dano glaucomatoso.…”

“…As diferenças observadas entre o grupo 1 e o grupo 3 reafirmam a noção de que um aumento na relação E/D em parentes próximos de portadores de glaucoma, possa ser realmente um traço herdado mais que puramente adquirido. Entretanto, sabe-se que a pressão intraocular permanece como importante fator de risco para a doença, também com hereditariedade estimada em 0,29 com diferença média de 1,02 mmHg (p=0,017) para mais em parentes de probandos com a doença (11) . Porém, não encontramos diferenças estatisticamente significantes para a pressão intraocular e espessura corneana central entre os grupos, fato esse justificado talvez pelo tamanho reduzido da amostra.…”