Elevated IOP is an important risk factor for glaucoma but is not required for a POAG diagnosis. Large population-based studies suggest a mean IOP of 15.5 mm Hg (standard deviation ± 2.6) in European-derived populations, but the normal distribution of IOP varies across racial and ethnic groups. This finding led to the definition of “normal” IOP as 2 standard deviations above and below the mean IOP or a range between 10 and 21 mm Hg. IOP greater than 21 mm Hg was thus traditionally defined as “abnormal,” but this definition has shortcomings.
*Note: This term is based on the historical use of argon laser technology; most green lasers currently used in ophthalmology are diode-pumped solid state (eg, frequency-doubled Nd:YAG or Nd:YLF) lasers.
It is known that IOP in the general population is not represented by a Gaussian distribution but rather is skewed toward higher pressures (see Chapter 2, Fig 4-2). Thus, IOPs of 22 mm Hg and above may not necessarily be abnormal from a statistical standpoint. More importantly, IOP distribution curves for glaucomatous and nonglaucomatous eyes show a great deal of overlap. Several studies indicate that as many as 30%–50% of individuals in the general population with glaucomatous optic neuropathy and/or visual field loss have initial IOP measurements below 22 mm Hg. Higher IOP, across its entire range observed in a population, is a continuous risk factor for POAG.
IOP may vary considerably over a 24-hour period, and elevations of IOP may occur only intermittently in some glaucomatous eyes (see Chapter 2). Thus, a single IOP measurement taken during office hours does not provide an accurate assessment of IOP variability over time. Table 7-1 lists some of the reasons that elevated IOP may be undetected in patients. Large diurnal fluctuation in IOP has been identified as an independent risk factor for progression of glaucoma in some studies, but not in others. Regardless, elevation of IOP is a strong risk factor for glaucoma progression.
As discussed in Chapter 2, central corneal thickness (CCT) affects the measurement of IOP. Thicker corneas resist the deformation inherent in most methods of tonometry, resulting in an overestimation of IOP. In contrast, tonometry in eyes with thin corneas underestimates the IOP. The average CCT in adult eyes, determined by ultrasonic pachymetry, ranges between about 525 and 550 μm and varies with race and ethnicity. For example, in persons of African ancestry, mean CCT is lower than in those of European ancestry.
Bengtsson B, Leske MC, Hyman L, Heijl A; Early Manifest Glaucoma Trial Group. Fluctuation of intraocular pressure and glaucoma progression in the early manifest glaucoma trial. Ophthalmology. 2007;114(2):205–209.
Bhan A, Browning AC, Shah S, Hamilton R, Dave D, Dua HS. Effect of corneal thickness on intraocular pressure measurements with the pneumotonometer, Goldmann applanation tonometer, and Tono-Pen. Invest Ophthalmol Vis Sci. 2002;43(5):1389–1392.
Brandt JD, Beiser JA, Kass MA, Gordon MO. Central corneal thickness in the Ocular Hypertension Treatment Study (OHTS). Ophthalmology. 2001;108(10):1779–1788.
Liu JH, Kripke DF, Twa MD, et al. Twenty-four-hour pattern of intraocular pressure in the aging population. Invest Ophthalmol Vis Sci. 1999;40(12):2912–2917.
Table 7-1 Potential Reasons for Undetected High-Tension Glaucoma
The Baltimore Eye Survey found that the prevalence of glaucoma increases dramatically with age, particularly among individuals of African descent, in whom prevalence exceeded 11% among those older than 80 years. In the Collaborative Initial Glaucoma Treatment Study (CIGTS; see Clinical Trial 7-1 at the end of this chapter), visual field defects were 7 times more likely to progress in patients 60 years or older than in those younger than 40 years. The Ocular Hypertension Treatment Study (OHTS; see Clinical Trial 7-2 at the end of this chapter) found an increased risk of progression to OAG with age (per decade): 43% in the univariate analysis and 22% in the multivariate analysis. Older age is an independent risk factor for both the development and the progression of glaucoma.
The prevalence of POAG in the United States is 3–4 times greater in individuals of African descent or Hispanic ethnicity than in primarily European-derived populations. Blindness from glaucoma is at least 4 times more common in black individuals than in white individuals. In addition, glaucoma is more likely to be diagnosed in black patients at a younger age and at a more advanced stage than it is in white patients. In a univariable analysis, the OHTS found that glaucoma was 59% more likely to develop in black patients with ocular hypertension (defined in this study as IOP ≥24 mm Hg in the absence of optic nerve or visual field abnormalities) than in white patients with ocular hypertension. However, this relationship was not present after controlling for corneal thickness and baseline vertical cup–disc ratio in a multivariable analysis (on average, black patients had thinner CCT and larger baseline vertical cup–disc ratios).
Thin central cornea and low corneal hysteresis
A thinner cornea is an important risk factor for disease progression in individuals with POAG (who have higher baseline IOPs) and for the development of glaucoma in individuals with ocular hypertension. This risk may not be entirely due to the underestimation of IOP measured by Goldmann tonometry in patients with thin corneas; therefore, attempting to correct IOP according to CCT is not supported by evidence. Thin corneas may be a biomarker for disease susceptibility. As mentioned previously, black patients have thinner corneas on average than white patients. Studies of corneal biomechanics, particularly hysteresis, have shown a relationship between these measurements and glaucoma progression (see Chapter 2).
Brandt JD, Gordon MO, Gao F, Besider JA, Miller JP, Kass MA; Ocular Hypertension Treatment Study. Adjusting intraocular pressure for central corneal thickness does not improve prediction models for primary open-angle glaucoma. Ophthalmology. 2012;119(3):437–442.
In the Baltimore Eye Survey, the relative risk of POAG increased approximately 3.7-fold for individuals who had a sibling with POAG. Increased risk of glaucoma within families is likely based on genetics, although simple mendelian inheritance of glaucoma is not common (see Chapter 1).
Population-based data support an association between POAG and myopia. In the Beaver Dam Eye Study (United States), myopia of greater than 1 diopter (D) spherical equivalent was significantly associated with a diagnosis of glaucoma. In the Rotterdam (Netherlands) follow-up study, high myopia of greater than 4 D was associated with a hazard ratio of 2.3 for developing glaucoma over 10 years. Myopia was also shown to be a risk factor in the Beijing Eye Study, in which high myopia (greater than 6 D spherical equivalent) conferred an odds ratio of 8 for having glaucoma compared to emmetropic eyes. The Blue Mountains Eye Study (Australia) found an odds ratio of 3.3 for participants with myopia of greater than 3 D. However, in the OHTS, no association between myopia and progression to glaucoma was observed.
The concurrence of POAG and myopia may complicate diagnosis and management in several ways. Evaluation of the optic nerve head is particularly challenging in highly myopic eyes that have tilted discs or posterior staphylomas. Also, the myopic refractive error may cause optical minification of the optic nerve, further complicating accurate optic nerve assessment. Myopia-related retinal degeneration or anomalies can cause visual field abnormalities that are difficult to distinguish from those caused by glaucoma (see Chapter 10, Myopia and Pathologic Myopia, in BCSC Section 12, Retina and Vitreous). In addition, patients who are highly myopic may have difficulty performing visual field tests, making interpretation of visual field abnormalities more challenging.
Mitchell P, Hourihan F, Sandbach J, Wang JJ. The relationship between glaucoma and myopia: the Blue Mountains Eye Study. Ophthalmology. 1999;106(10):2010–2015.
Varma R, Ying-Lai M, Francis BA, et al; Los Angeles Latino Eye Study Group. Prevalence of open-angle glaucoma and ocular hypertension in Latinos: the Los Angeles Latino Eye Study. Ophthalmology. 2004;111(8):1439–1448.
Wong TY, Klein BE, Klein R, Knudtson M, Lee KE. Refractive errors, intraocular pressure, and glaucoma in a white population. Ophthalmology. 2003;110(1):211–217.
Xu L, Wang Y, Wang S, Wang Y, Jonas JB. High myopia and glaucoma susceptibility: the Beijing Eye Study. Ophthalmology. 2007;114(2):216–220.
Excerpted from BCSC 2020-2021 series: Section 10 - Glaucoma. For more information and to purchase the entire series, please visit https://www.aao.org/bcsc.