Glaucoma is a group of diseases associated with elevated intraocular pressures (IOP). Over time, characteristic damage to the optic nerve can cause permanent visual loss.[1]

Glaucoma is the second-leading cause of blindness worldwide after cataracts, but, unlike with cataracts, blindness caused by glaucoma is irreversible, and therefore patients should be initiated on treatment as early as possible.

Two main subsets exist: open-angle and angle-closure. Primary and secondary causes of glaucoma further categorize the disease. Open-angle remains the most common form in the United States. Globally, it is the most common cause of irreversible blindness.[2]

Primary open-angle glaucoma (POAG), is the focus of this chapter.

Though the disease is initially asymptomatic, as it progresses, central vision is adversely affected. Fortunately, a routine ophthalmologic exam can diagnose glaucoma if elevated intraocular pressure or optic disc “cupping” is present. However, identifying unaffected or at-risk eyes is not as simple. High-risk findings on ophthalmologic examination include, but are not limited to, increased cup-disc ratio (CDR), CDR asymmetry, and/or disc hemorrhage.[3] Tonometry, when glaucoma is suspected, can quantify the increasing IOP and is a very helpful tool in these cases.

Generally, angle-closure glaucoma occurs in an anatomically predisposed eye. As intraocular pressure mounts, the eye often becomes red and painful, with nausea as the principal symptom. Emergent relief of the elevated pressure will help avoid severe visual loss or blindness. Causes of secondary glaucoma, such as cataract, inflammation, and derangement of the eye anatomy due to blunt trauma, neovascularization in diabetic retinopathy, pigment dispersion syndrome, pseudoexfoliation, and central retinal vein occlusion, are encountered less commonly in the clinic setting.

Risk Factors

Age. Glaucoma is rare before age 65. Its prevalence is approximately 1% at 70 years and 3% at 75 years.[2]

Elevated intraocular pressure. Elevated intraocular pressure is not an absolute requirement for diagnosis.

Race. In the US, Blacks and Hispanics have an increased prevalence of POAG, more severe glaucoma on presentation, and a higher risk of blindness, compared with Whites. POAG is also proportionately more prevalent in persons with Inuit, Chinese, Asian Indian, or Southeast Asian background.[4][5][6]

Family history. The relative risk in siblings is 3.7 of the affected person and 2.2 in those with affected parents.[7]

Additional risk factors include the use of systemic, inhaled, or intravitreal corticosteroids, high blood pressure (an independent risk factor for elevated IOP), cardiovascular disease, type 2 diabetes, low ocular perfusion pressure, and myopia.[8][9][10][11][12] Vascular dysregulation, oxidative stress, autoimmunity, and excitotoxicity are identified mechanisms putting individuals at risk, even in the presence of normal IOP.[13]

Diagnosis

Major visual field loss in POAG can occur prior to other symptoms because this condition is often an incidental finding during normal ophthalmologic examinations.

Fundus examination is required for diagnosis, along with visual field testing (confrontational visual field testing is not sufficiently accurate to diagnose) and measurement of IOP. Most persons with POAG will have an untreated IOP above 21 mm Hg at some point in the disease, compared with a normal IOP of about 15.3 for women and 15.5 for men.[14][15] Not all patients with elevated IOP will go on to develop glaucoma.

The American Academy of Ophthalmology describes POAG as chronic, asymmetrical, or bilateral, with the following:[16]

• Optic disc or retinal nerve fiber layer damage (thinning or notching in the optic disc rim, defects in the nerve fiber, progressive changes).
• Characteristic visual field abnormalities without any other explanation.
• Adult onset.
• Patent anterior chamber angles.
• No factors known to cause secondary open-angle glaucoma.

Treatment

Lowering IOP is the only known effective treatment for glaucoma. Elevated IOP can be relieved by decreasing the aqueous humor production or increasing drainage of aqueous humor from the posterior chamber(s). The goal of treatment is to preserve vision and prevent further vision loss.[17][18]

Target IOP can be individualized. Pressure must be lowered until no further damage occurs.[16] Because the disease may be asymptomatic until severe damage has occurred, many patients do not use their medicines or follow up as often as is recommended. Compliance should be monitored closely. Vision loss can worsen with poor adherence to a treatment plan.

Methods to lowering IOP: eye drops, systemic medications, laser treatment, and surgery.

Topical Medication

Prostaglandins, non-selective alpha-adrenergic agonists, and parasympathomimetic agents increase aqueous outflow. Prostaglandin analogues are typically first-line agents. They are largely effective, are well tolerated, and can be dosed daily.

Beta-blockers, carbonic anhydrase inhibitors, and selective alpha-adrenergic agonists decrease aqueous production. Beta-blockers had previously been first-line drugs but carry contraindications for patients with pulmonary or cardiovascular comorbidities.[19] Topical carbonic anhydrase inhibitors are preferred over systemic preparations because of multiple adverse side effects with systemic use. Adrenergic agonists (i.e., brimonidine) have potential adverse ocular and systemic side effects.

Systemic Therapy

Ginkgo biloba has been shown to improve visual field test results in patients with normal-tension glaucoma but requires cautious use because of its anticoagulant properties.[20]

Other systemic medications, such as carbonic anhydrase inhibitors, are second-line agents.

Laser Therapy

Trabeculoplasty (laser application to tissues for aqueous absorption in the angle between the cornea and iris) is acceptable as first-line therapy in select patients.[21] Laser therapy lowers IOP by increasing the drainage of aqueous humor.

Laser therapy or cryotherapy can also be used to destroy the ciliary body, which is the site of aqueous humor production.

Surgery

Surgery can create an alternative pathway for aqueous flow, but there is no clear advantage to early surgery over medical therapy.[22][23] Surgery is generally reserved for patients with severe disease or for those who are refractory to other treatments. Complications include vision loss, infection, and cataract formation.[24]

Nutritional Considerations

Metabolic syndrome, obesity, blood pressure abnormalities, and diabetes are risk factors for POAG.[25] As a result, a diet that helps maintain normal blood pressure and blood glucose concentrations helps reduce substantial risk for glaucoma. Controlled trials must be conducted to investigate this further (see chapters on Hypertension and Diabetes).

Nitrate-rich leafy greens. A large prospective study showed that a greater intake of nitrates via green leafy vegetables was associated with 20-30% lower risk of POAG. Dietary nitrates increase nitric oxide (NO) production via the nitrate‐nitrite‐NO pathway.[26] NO has emerged as a POAG therapeutic focus, as it may help to regulate IOP. The endogenous NO pathway may be compromised in POAG, and dietary nitrates from leafy greens offer an alternative pathway to increase NO production.[27]

Antioxidant-rich fruits and vegetables. A study with 584 Black women found that those who consumed 3 or more servings of fruit or fruit juice per day were 79% less likely to have glaucoma than those who consumed less than 1 serving. Fruits and vegetables high in vitamins A and C and carotenoids were especially protective.[28]

The Rotterdam Study, including 3,500 participants aged 55 years and older, showed that those with a higher retinol intake had half the risk of POAG compared with those with the lowest intakes.[29] The benefits come from food sources, whereas supplemental antioxidant vitamins do not appear to be beneficial.[30] More evidence is needed before specific recommendations can be distributed.

Studies have noted an association may exist between obesity and elevated IOP, as well as ocular hypertension.[31][32] The links between obesity and IOP have been thought to be the result of excessive infraorbital adipose tissue, increased blood viscosity, and episcleral venous pressure, causing impairment of aqueous outflow.[30] Evidence does not yet indicate that losing excess weight reduces the risk for glaucoma, although significant decreases in intraocular pressure have been reported in humans throughout weight loss (0.4-1.5 kg) and during periods of fasting, which leads to reduced waist circumference.[33][34]

Alcohol consumption. Alcohol consumption has been found to reduce intraocular pressure in both healthy individuals and those with glaucoma. However, a positive association between drinking and risk of POAG has been reported.[12] In a 2023 study, alcohol consumption was associated with increased risk for developing glaucoma.[35]

Coffee and tea consumption. Acute increases in IOP with caffeine intake have been reported in healthy and POAG patients. Some studies have reported a connection between caffeine intake and risk of POAG. These results have not been consistent, however, and mechanisms are not clear.[12] In a report of the 2005-2006 NHANES cohort of 1,678 individuals, no associations were found between the consumption of caffeinated or decaffeinated coffee, iced tea, and soft drinks and the risk of glaucoma. Those who drank at least 1 cup of hot tea per day had a 74% reduced risk of glaucoma compared with those who drank none.[34]

Ginkgo biloba. Ginkgo biloba has been found to increase ocular blood flow, improve retinal ganglion cell survival, and protect against oxidative stress. There have been studies demonstrating that Ginkgo biloba improves visual function while slowing the progression of visual field damage in patients with glaucoma.[12] Conversely, a study done in China found Ginkgo biloba had no effects on improvements in patients with glaucoma.[36]

Saffron. Daily intake of an aqueous saffron extract for 3 weeks statistically reduced IOP in patients with glaucoma in a pilot study. The antioxidative effects of the saffron were the proposed mechanism of this outcome.[37]

Orders

See Basic Diet Orders Chapter.

What to Tell the Family

It is essential for the patient to have regular ophthalmologic examinations, since affected individuals cannot assess treatment efficacy on their own. Significant optic nerve damage can occur prior to any presenting symptom. Failure to use glaucoma medications as prescribed can also result in severe damage. Family members should also be screened for glaucoma by an ophthalmologist or optometrist when appropriate.

References