Glaucoma: The Silent Killer of Eyesight

Glaucoma is a leading cause of blindness in the United States. The 2 main types of glaucoma are open-angle and narrow-angle. Glaucoma damages the optic nerve, typically resulting in loss of peripheral vision, which eventually progresses to involve the central visual field. Because patients with glaucoma are usually asymptomatic, primary care physicians can play a vital role in recognizing this silent cause of blindness. The goal of treatment, which consists of eye drops, laser trabeculoplasty, or surgery, is to lower intraocular pressure. Eye drops are effective but can have local as well as systemic side effects. Early recognition in the primary care setting and timely referral to ophthalmologists can prevent permanent vision loss.

Julia Song, MDAssistant Professor

Loma Linda University Health Care

PRACTICE POINTS

• Open-angle glaucoma is asymptomatic and painless, but some patients will complain of eye pain and/or blurry vision.
• Eye drops are the first-line therapy, and prostaglandin analogs are preferred.

Glaucoma is one of the leading causes of blindness in the world, second only to cataracts. In the United States, glaucoma, along with cataracts, is the most frequent cause of blindness in blacks¹ and is a leading cause of blindness in Latinos.² It is the third most frequent cause in whites, after age-related macular degeneration¹ and diabetic retinopathy. Currently, more than 2 million Americans have open-angle glaucoma. In addition, 1 million people are unaware that they are affected. With the rapid aging of the US population, the number of Americans with glaucoma is expected to increase to more than 3 million by 2020.³

Studies have shown that glaucoma affects about 1.86% of the general population.³ The incidence increases with advancing age, with a prevalence of 1.6 per 100,000 persons in the fourth decade of life and 94.3 per 100,000 persons in the eighth decade.⁴ The prevalence in whites aged 40 or older is 2%.⁵ That number is 4-to 5-fold higher (up to 10%) in blacks, 4.74% in Hispanics,⁶ and 3.9% in Japanese.⁷

Pathophysiology

The ciliary processes of the iris produce a fluid called aqueous humor at a constant rate of 2 to 3 ?L/min, which is equivalent to a turnover rate of 1% per minute (Figure 1). The influx and outflow of aqueous fluid creates intraocular pressure (IOP).

In glaucoma, resistance through the trabecular meshwork is increased. It is analogous to a clogged kitchen sink, in which there is a constant flow of fluid but the drain is blocked. The increased IOP damages the optic nerve, affecting the peripheral visual field and eventually resulting in blindness.

Open-angle and Narrow-angle Glaucoma

The 2 main types of glaucoma are open-angle and narrow-angle forms of the disease (Figure 2). Open-angle glaucoma is the most common type in the United States.³ It usually is bilateral but can present asymmetrically. Open-angle glaucoma is associated with central retinal vein occlusions. Minor risk factors include myopia, diabetes mellitus, hypertension, and cardiovascular disease.

Open-angle glaucoma can be subdivided into low-tension (ie, normal pressure), pseudoexfoliation, pigmentary dispersion, traumatic, and less common subtypes, such as uveitis. A rare subset of open-angle glaucoma is congenital glaucoma. Patients typically present with epiphora (tearing), photophobia, and blepharospasm. Because the scleral wall of the eye is flexible in children, buphthalmos (enlargement of the eye) is common, but it can be reversed by lowering the IOP. Congenital glaucoma is an ocular emergency, requiring an immediate referral to an ophthalmologist.

Narrow-angle or occludable-angle glaucoma occurs when the iris apposes the trabecular meshwork, blocking the drainage of aqueous humor. It can be acute, subacute, or chronic. The prevalence of angle-closure increases with age; this condition is more common in females and in patients with far-sightedness.

Causes of angle-closure glaucoma include tumors, scarring, inflammation, and hemorrhage. Medications, particularly anticholinergic and sympathomimetic drugs, can predispose to an attack of glaucoma. Other sympathetic responses, such as pain, fright, or stress, can also precipitate an angle-closure attack.

The Clinical Evaluation

Typically, open-angle glaucoma is an asymptomatic, painless disease, much like hypertension. Thus, primary care clinicians should be familiar with known risk factors (Table). Occasionally, patients may complain of eye ache and/or blurry vision. Patients with acute angle-closure glaucoma will typically report pain, blurry vision, rainbow-colored halos, nausea, and vomiting.

Glaucoma should be suspected either when IOP is elevated, indicating ocular hypertension, or when the optic nerves show structural glaucomatous damage, manifested as an increased cup-to-disc ratio of more than 0.4. Typically, patients will have elevated IOP. Average IOP is 16 mm Hg, with a range of 10 to 21 mm Hg. Ocular hypertension is much more prevalent than glaucoma, although by how much is controversial.

When examining the eyes, the pupils should be checked for an afferent pupillary defect (Marcus-Gunn pupil), in which the pupils do not remain constricted to light. This is indicative of optic-nerve damage. Slit-lamp microscopy performed by an ophthalmologist can assess for other signs of glaucoma, including defects of the iris, lens, and anterior chamber angle, which may not be visible with a direct ophthalmoscope.

The most crucial part of the examination is assessment of the size and shape of the optic-nerve head, which can be accomplished by any physician using direct ophthalmoscopy. The optic disc is typically round or oval, with a cup in the center. Between the cup and disc margin is the neural rim. Notation of the cup-to-disc ratio is critical, as is the contour of the neural rim. It is also important to examine the integrity of the blood vessels that emerge from the optic nerve and the nerve fiber layers.

Glaucomatous damage to the optic nerve, also called "cupping," occurs when the IOP is too high. This results in enlargement and excavation of the cup and an increased cup-to-disc ratio (Figure 3). Any enlargement of or asymmetry in the cup-to-disc ratio between a patient's eyes is suggestive of glaucoma. Other signs of damage from glaucoma include hemorrhages near the optic nerve and notching of the neural rim.

Ancillary Testing

Visual field testing, also known as perimetry, is critical to the diagnosis of glaucoma (Figure 4). This is an objective way of assessing a patient's visual field and determining progression. Typically, patients first lose peripheral vision; toward the later stages of the disease, central vision is affected. However, in some subtypes, central vision is affected first. Evidence suggests that black Americans have more severe visual field defects than white Americans.⁸

One study showed that central corneal thickness is the most significant risk factor for glaucoma, with a thinner cornea imparting a higher risk.⁹ In another study of more than 1000 individuals, blacks had thinner corneas than whites.¹⁰ Corneal thickness is also helpful in determining true IOP; if the cornea is thin, the IOP reading may be falsely low, resulting in an underestimation of actual pressure.

Laser scanning tomography is now being used for the evaluation of patients suspected of glaucoma. This combination of scanning laser ophthalmoscopy and confocal microscopy can assess for changes in the nerve-fiber layer. Patients with optic nerve damage have thinner nerve-fiber layers. Such thinning can be detected by the use of laser scanning tomography even before visual field loss is identified by perimetry.

Management

Prompt treatment of risk factors in high-risk patients has been shown to reduce the development of glaucoma by 50%.¹¹ The only risk factor that can currently be successfully treated is IOP, using either eye drops, lasers, or surgery.

Eye drops

Eye drops are considered the first-line of therapy, because they are the least invasive. There are several classes of eye drops, including beta-blockers, adrenergic agonists, alpha-agonists, carbonic anhydrase inhibitors, cholinergic agonists, and prostaglandin analogs. They work by different mechanisms; some reduce the production of aqueous fluid, others promote drainage of aqueous humor, and yet others do both. The prostaglandin analogs are typically the first choice because of their once-daily use and significant IOP-lowering effects.

Eye drops are associated with various adverse events that some patients find intolerable. The most common side effects of the prostaglandin analogs are increased pigmentation and thickening of eyelashes, darkening of the iris, reddening of the eye, and, rarely, intraocular inflammation. Topical beta-blocker eye drops are contraindicated in patients with diabetes or cardiovascular or respiratory disease. These agents can also alter the lipid profile and result in depression or sexual dysfunction. To reduce systemic absorption and side effects, patients should be instructed to apply pressure to the nasolacrimal sac for about 5 minutes after application.

Cholinergic agents are normally no longer used. In addition to constricting the pupil, causing brow ache, and changing refractive error (eyeglasses prescription), they can also accelerate cataract formation. Oral acetazolamide has largely been replaced by topical carbonic anhydrase inhibitor eye drops. The oral form has been associated with paresthesias, fatigue, metabolic acidosis, urolithiasis, idiosyncratic aplastic anemia, and Stevens-Johnson syndrome.

Laser therapy

Laser trabeculoplasty is an option for lowering the eye pressure when eye drops do not work. Applying the laser directly over the trabecular meshwork promotes increased outflow, thus lowering IOP. Laser treatment is sometimes considered before eye drops, if a patient cannot afford eye drops or has difficulty administering drops.

Narrow-angle glaucoma is treated with a laser that creates a hole in the iris, allowing aqueous fluid to pass anteriorly instead of through the pupil. Since the iris is no longer pushed against the trabecular meshwork, IOP is immediately reduced.

Surgery

When IOP cannot be lowered to an acceptable level with medications or with laser treatment, surgical intervention is necessary. Two types of surgery can be performed, both involve bypassing the eye's own drain and essentially creating another one. The gold standard is trabeculectomy, in which a hole is made in the sclera, creating a microscopic filter that allows fluid to exit the eye. In the second type, a tube is implanted to lower the eye pressure.

Conclusion

Once total vision loss occurs, it is irreversible. Glaucoma is both underdiagnosed and undertreated. Primary care physicians can play a vital role in preventing vision loss by recognizing this silent disease in its early stages. Screening patients by determining the presence of risk factors and examining the optic nerve with a direct ophthalmoscope can lead to a timely referral to an ophthalmologist.

SELF-ASSESSMENT TEST

1. Which of these statements about glaucoma is NOT true?

• Glaucoma can exist in an eye with normal IOP
• A thin central corneal is associated with a higher risk of glaucoma

2. Which of these groups has the lowest prevalence of glaucoma?

• Hispanics
• Blacks

3. All these are known risk factors for glaucoma, except:

• Thyroid disease
• Raynaud's phenomenon

4. All the following conditions are signs of glaucoma, except:

• Hemorrhage near the optic nerve
• Neural rim notching

5. Which of the following treatments should NOT be used in a patient with diabetes?

• Beta-blocker eye drops
• Trabeculectomy

(Answers at end of reference list)

Arch Ophthalmol.

1. Congdon N, O'Colmain B, Klaver CC, et al, for the Eye Diseases Prevalence Research Group. Causes and prevalence of visual impairment among adults in the United States. 2004;122:477-485.

Ophthalmology

2. Rodriguez J, Sanchez R, Munoz B, et al. Causes of blindness and visual impairment in a population-based sample of US Hispanics. . 2002;109:737-743.

Arch Ophthalmol

3. Friedman DS, Wolfs RC, O'Colmain BJ, et al, for the Eye Diseases Prevalence Research Group. Prevalence of open-angle glaucoma among adults in the United States. . 2004;122:532-538.

Ophthalmology.

4. Schoff EO, Hattenhauer MG, Ing HH, et al. Estimated incidence of open-angle glaucoma in Olmsted County, Minnesota. 2001;108:882-886.

Ophthalmology

5. Klein BE, Klein R, Sponsel WE, et al. Prevalence of glaucoma. The Beaver Dam Eye Study. . 1992;99:1499-1504.

Ophthalmology

6. Varma R, Ying-Lai M, Francis BA, et al, for the Los Angeles Latino Eye Study Group. Prevalence of open-angle glaucoma and ocular hypertension in Latinos: the Los Angeles Latino Eye Study. . 2004;111:1439-1448.

Ophthalmology

7. Iwase A, Suzuki Y, Araie M, et al, for the Tajimi Study Group and Japan Glaucoma Society. The prevalence of primary open-angle glaucoma in Japanese: the Tajimi Study. . 2004;111:1641-1648.

Ophthalmology

8. Advanced Glaucoma Intervention Study Group. The Advanced Glaucoma Intervention Study (AGIS): 3. Baseline characteristics of black and white patients. . 1998;105:1137-1145.

Arch Ophthalmol

9. Gordon MO, Beiser JA, Brandt JD, et al. The Ocular Hypertension Treatment Study: baseline factors that predict the onset of primary open-angle glaucoma. . 2002;120:714-720;829-830.

Ophthalmology

10. Brandt JD, Beiser JA, Kass MA, et al. Central corneal thickness in the Ocular Hypertension Treatment Study (OHTS). . 2001;108:1779-1788.

Arch Ophthalmol.

11. Higginbotham EJ, Gordon MO, Beiser JA, et al, for the Ocular Hypertension Treatment Study Group. Topical medication delays or prevents primary open-angle glaucoma in African American individuals. 2004;122:813-820.

Answers:

1. C; 2. A; 3. C; 4. A; 5. B