Condition Definition

Open-angle glaucoma (OAG) is a chronic, progressive neurodegenerative disease of the optic nerve characterized by structural optic disc and/or retinal nerve fiber layer thinning, with associated visual field defects (some authorities consider typical optic nerve changes or visual field defects to be sufficient to diagnosis glaucoma).⁵ “Open” refers to an open anterior chamber angle on gonioscopy; this is in contrast to “closed” or narrow-angle glaucoma, which has a different presentation and treatment, and is outside the scope of this review. POAG, the focus of this review, is characterized by the absence of other known secondary causes, such as neovascularization, trauma, uveitis, or steroid use. OAG is generally bilateral, but can be asymmetric. The onset of POAG is often in mid to late adulthood. Although there is an association between elevated IOP (typically defined as ≥21 mm Hg) and OAG, up to 40 percent of patients with OAG do not have elevated IOP.^6–8

“Glaucoma suspect” is a nonspecific term describing individuals who do not meet criteria for glaucoma, but have findings or risk factors associated with developing OAG.⁵ Criteria for glaucoma suspect include a consistently elevated IOP, a suspicious appearance of the optic nerve, a strong family history of OAG, or visual field abnormalities consistent with glaucoma. “Ocular hypertension” refers to the presence of elevated IOP without glaucomatous changes of the optic nerve or visual fields.⁹ It can be difficult to distinguish a glaucoma suspect from a patient with early OAG, and prospective followup and repeat diagnostic testing are often necessary to make the distinction.

Prevalence and Burden of Disease/Illness

Glaucoma is the second leading cause of irreversible blindness in the United States (U.S.), and the leading cause in Black and Latino persons.^8,10 Earlier stages of glaucoma can also impact quality of life and function, including ability to drive and risk of motor vehicle crashes.¹¹ Age-stratified data indicate a decrease in glaucoma related blindness (incidence within 10 years of diagnosis 8.7 per 100,000 for persons diagnosed in 1965 to 1980 and 5.5 per 100,000 for persons diagnosed in 1981 to 2000).¹² The degree to which the observed trend is related to improved treatment/management, earlier diagnosis, or other factors is unclear. The prevalence of POAG in the U.S. is estimated at about 2 percent, based on optic nerve fundus photography assessment of participants in the 2005 to 2008 National Health and Nutrition Examination Survey.¹³ In 2011, an estimated 2.71 million persons had OAG; this number was projected to reach 3.7 million in 2020 and 4.3 million in 2025.^14,15 The number of persons with glaucoma increases with age, from an estimated 0.25 million persons 40 to 49 years of age to 1.28 million persons 70 to 79 years of age. In the U.S., Black and Latino persons a threefold or higher prevalence of OAG relative to non-Latino White persons.^8,13,16,17 In the U.S., the proportion of persons 40 years and older with ocular hypertension is estimated at 4.5 percent in non-Latino White and 3.5 percent in Latino persons.^14,16 Data on glaucoma suspect prevalence (not limited to ocular hypertension) are lacking.

Etiology and Natural History

The etiology of OAG is likely multifactorial, and includes genetic factors¹⁸ and age-related neurodegeneration of the optic nerve.¹⁹ The degree of IOP elevation correlates with the rapidity of OAG progression, though the susceptibility of individuals to IOP-related optic nerve damage varies.⁵ As noted above, a substantial proportion of patients with OAG have an IOP within the normal range, and some patients with elevated IOP do not develop glaucoma.^20,21 In the Ocular Hypertension Treatment Study (OHTS), 9.5 percent of untreated glaucoma suspects with elevated IOP progressed to glaucoma after 5 years²¹ and 29.5 percent after 20 years.²²

Other factors hypothesized to contribute to the optic nerve damage seen in OAG include a deficient blood supply to the optic nerve, inadequate structural support for the neurons that comprise the optic nerve, and insufficient supplies of neurotrophins. The typical natural history of OAG is of gradual, often insidious, loss of retinal ganglion cells and corresponding loss of peripheral and/or central vision, potentially progressing to blindness. The vision loss is generally irreversible. A study of newly diagnosed OAG glaucoma patients in Olmsted County, Minnesota found that after 20 years, 27 percent were blind in one eye and 9 percent in both eyes.²³ However, the rate of progression varies. Visual field loss is often detectable before visual acuity loss, which usually occurs late in patients with glaucoma. While treatment strategies (currently all based on IOP lowering) can slow the progression of glaucomatous vision loss, some patients continue to lose vision despite apparently adequate IOP lowering.²⁴

Risk Factors

A number of risk factors have been identified for OAG, including older age,^25–27 Black or Latino race/ethnicity,^8,16,25,28 family history,^26,29 higher IOP,^8,25 thinner central cornea,²⁵ optic disc hemorrhage,³⁰ large optic disc cup-to-disc ratio,²⁵ and lower ocular perfusion pressure (as determined by systemic blood pressure and IOP).³¹

Rationale for Screening/Screening Strategies

Untreated glaucoma can lead to irreversible vision loss or blindness. Early or mild glaucoma damage to the optic nerve may be asymptomatic and mild visual loss may not be perceived as warranting medical evaluation. Visual field loss from OAG is often not perceived by patients³² and 50 percent or more of patients with OAG are unaware that they have glaucoma.^8,17,27,33 Therefore, screening could identify patients with asymptomatic or mild OAG who could benefit from early treatment to prevent further visual loss. Screening could also identify patients who are glaucoma suspects and might benefit from treatments or monitoring to prevent progression to OAG and/or vision loss.²¹

Screening for glaucoma is based on a number of tests, including tonometry (for IOP), ophthalmoscopy on dilated eye examination (for evaluation of the optic nerve), perimetry (visual field test), gonioscopy (to measure the angle in the eye where the iris meets the cornea), pachymetry (to measure the thickness of the cornea), and visual acuity testing.³⁴ Imaging tests, such as optical coherence testing (OCT, which uses low-coherence light to image the retina) and optic disc photography (to view the optic nerve head and/or retina) can supplement the clinical examination. A challenge in screening for glaucoma in primary care settings is that with the exception of visual acuity and certain tonometry tests, primary care clinicians lack training or equipment to perform much of the glaucoma clinical examination, which is typically performed in an eye specialty setting. As previously described, tonometry and visual acuity testing lack sensitivity for glaucoma because a significant proportion of patients have normal IOP and visual acuity changes are a late finding. In addition, diagnostic criteria for glaucoma lack consensus and are difficult to standardize.

Interventions/Treatment

The only known modifiable risk factor for glaucoma is IOP. Therefore, all current glaucoma treatments aim to lower IOP, even in persons with non-elevated IOP. An optimal target IOP has not been identified, and the IOP target is typically individualized, though the American Academy of Ophthalmology (AAO) suggests a reduction in IOP of 25 percent from baseline as a reasonable initial goal in most patients. Current IOP lowering strategies include topical medicated drops (prostaglandin analogs, beta-blockers, alpha-adrenergic agonists, carbonic anhydrase inhibitors, Rho kinase inhibitors, nitric oxide donators, and less frequently cholinergic agents),^21,35 oral agents (carbonic anhydrase inhibitors, hyperosmotic agents), laser trabeculoplasty,^36,37 laser cyclophotocoagulation,^38,39 and incisional surgery (i.e., trabeculectomy, glaucoma drainage device implantation, and angle-based surgeries).^40,41 The AAO recommends medications or laser trabeculoplasty as initial therapy in most patients.⁵ Topical prostaglandins are currently the most commonly used initial medication for OAG. Selective laser trabeculoplasty (SLT) using a frequency-doubled neodynmium:yttrium-aluminum-garnet laser produces less thermal damage to the trabecular network compared with argon laser trabeculoplasty and is the most commonly used laser trabeculoplasty technique. Surgery is usually reserved for patients with severe visual field loss at baseline or patients with advanced OAG who do not respond to medications or laser trabeculoplasty, due to complications associated with surgery. In patients who are glaucoma suspects, the AAO recommends a shared decision making approach, based on the risk of developing glaucoma, to determine whether to initiate treatment.⁵ For persons with ocular hypertension, a risk calculator is available to estimate the risk of developing glaucoma in persons with ocular hypertension.⁴²

New developments in treatment for glaucoma since the prior USPSTF recommendation include the approval by the U.S. Food and Drug Administration (FDA) of two new medications for OAG and ocular hypertension: latanoprostene bunod⁴³ (a nitric oxide-donating medication) and netarsudil⁴⁴ (a Rho kinase inhibitor). These are the first new medications approved for glaucoma since 1996. Unlike the majority of medications for OAG that decrease IOP by reducing aqueous production, these medications increase aqueous outflow. The development of newer minimally-invasive surgical procedures for treatment of OAG is ongoing.⁴⁵

Current Clinical Practice/Recommendations of Other Groups

The AAO recommends a baseline comprehensive eye evaluation at age 40. In persons without risk factors for ocular disease, the AAO recommends examinations every 2 to 4 years for persons 40 to 54 years of age, every 1 to 3 years for persons 55 to 64 years of age, and every 1 to 2 years in persons 65 years of age or older.⁵ In persons at higher risk for ocular disease, the AAO recommends that decisions regarding when to initiate eye evaluations and the frequency of periodic examinations be based on the risks, but does not provide specific guidance. For glaucoma evaluation, the AAO describes a number of components of the comprehensive eye examination, including visual acuity measurement, pupil examination, anterior segment examination, IOP measurement, gonioscopy, optic nerve head and retinal nerve fiber layer examination, and fundus examination.⁵ Diagnostic tests include central corneal thickness measurement, visual field evaluation, and optic nerve hypoplasia and retinal nerve fiber layer imaging.

The American Academy of Family Physicians supports the USPSTF recommendation on glaucoma screening.⁴⁶

Data on the frequency of glaucoma screening in primary care settings are not available, though it is unlikely to be high due to a lack of training and specialized equipment. Data are also not available on the proportion of patients in primary care settings referred for glaucoma screening. An area of ongoing interest is use of telemedicine to facilitate glaucoma screening in primary care settings,⁴⁷ and use of artificial intelligence for screening, diagnosis, and classification of glaucoma.⁴⁸