Overview and Risk Factors

Glaucoma is a group of eye diseases characterized by optic nerve damage that is usually associated with elevated intraocular pressure. It can cause permanent visual field loss and possible blindness.¹ Glaucoma is the second-leading cause of blindness worldwide after cataract, but, unlike cataract, blindness caused by glaucoma is irreversible.

The four principal types of glaucoma are primary open-angle, angle closure, secondary, and congenital.

The most common form of this disease, primary open-angle glaucoma (POAG), is the focus of this chapter. This condition is an asymptomatic progressive process that can irreversibly affect peripheral visual fields and ultimately central vision. An ophthalmologic exam can diagnose glaucoma if elevated intraocular pressure or optic disc "cupping" is present, but cannot otherwise identify unaffected or at-shadrisk eyes.

Angle-closure glaucoma generally occurs in an anatomically predisposed eye. As intraocular pressure mounts, the eye often becomes red and painful, but sometimes nausea is the principal symptom. Relief of the elevated pressure must occur emergently in most cases to avoid severe visual loss or blindness. Secondary glaucoma often results from cataract, inflammation, derangement of the eye anatomy due to blunt trauma, neovascularization in diabetic retinopathy, or central retinal vein occlusion.

Risk Factors

There are 4 major risk factors for POAG.²

• Age. There is <1% prevalence in persons under age 65, approximately 1% at 70 years, and 3% at 75 years.²
• Elevated intraocular pressure. However, high intraocular pressure is not necessary or sufficient for glaucoma pathogenesis.
• Race. Prevalence is 4 to 5 times greater in African Americans, compared with whites, and reaches 11% in African Americans aged 80 and over. The age-adjusted rate of blindness due to glaucoma is 6.6 times higher in African Americans, with blindness onset averaging 10 years earlier, compared with whites.^3,4
• Family history. There is a relative risk of 3.7 in siblings of the affected person and 2.2 in those with affected parents.⁵

Additional risk factors include:

• Use of corticosteroids.
• High blood pressure (a risk factor for elevated intraocular pressure).^6,7
• Diabetes.^6,8
• Homocysteine elevation .^9,10
• Low diastolic perfusion pressure.
• Cardiovascular disease.
• Hypothyroidism.
• Myopia.^11,12

Diagnosis and Treatment

Diagnosis

POAG is generally asymptomatic, and major visual field loss can occur prior to any visual symptoms.

Fundus examination is required for diagnosis, along with visual field testing (confrontational visual field testing is not sufficiently accurate to diagnose glaucoma) and measurement of intraocular pressure. Most persons with POAG will have an untreated intraocular pressure above 21 mmHg at some point in the disease,¹¹ compared with a normal intraocular pressure of about 15.3 for women and 15.5 for men.¹³

The American Academy of Ophthalmology describes POAG as chronic, generally bilateral, often asymmetrical, and with all of the following in one or both eyes:¹¹

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

Treatment

Lowering intraocular pressure is effective for reducing visual field loss in many patients.^14,15 More evidence is needed to confirm that these results translate to other patient populations, such as individuals with severe POAG.

The target for intraocular pressure is individualized. Pressure must be lowered until no further damage occurs. Because the disease is generally asymptomatic until severe damage has occurred, many patients do not use their medicines or follow up as recommended. Compliance should be monitored closely.

Methods of lowering intraocular pressure include eye drops, systemic medications, laser treatment, and surgery.

Topical Medication

Beta-blockers and carbonic anhydrase inhibitors decrease aqueous production.

• Beta-blockers are first-line drugs, unless contraindicated for pulmonary or cardiovascular reasons.
• Topical carbonic anhydrase inhibitors are preferred because of multiple adverse side effects with systemic use.

Prostaglandins, alpha-adrenergic agonists, and cholinergic agonists increase aqueous outflow.

• Prostaglandins are also first-line agents or are used in conjunction with beta-blockers.
• Adrenergic agonists (ie brimonidine) have potential (although uncommon) adverse ocular/systemic side effects.
• Cholinergic agonists have adverse ocular side effects.

Systemic Therapy

Gingko biloba has improved visual field test results in patients with normal-tension glaucoma,¹⁶ but requires cautious use because of its anticoagulant effect.

Other systemic medications, such as carbonic anhydrase inhibitors, are associated with many adverse side effects and are second-line agents.

Laser Therapy

Trabeculoplasty (laser application to tissues for aqueous absorption in the angle between the cornea and iris) is effective in the short term, but repeat therapy is usually needed, and the laser may cause new damage.  

Laser therapy or cryotherapy can also be used to destroy the ciliary body.

Surgery

Surgery creates an alternative pathway for aqueous flow, but there is no clear advantage of early surgery over medical therapy.^17,18 Surgery is generally reserved for patients with severe disease and can be associated with blinding complications, particularly infection.

Nutritional Considerations

High blood pressure and diabetes are risk factors for elevated intraocular pressure. A diet that helps maintain normal blood pressure and blood glucose concentrations may help reduce the risk for this disease, although no controlled trials have demonstrated the ability of diet to prevent or treat glaucoma (see Hypertension and Diabetes).

Orders

See Basic Diet Orders.

Ophthalmology consultation.

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 symptoms. Failure to use glaucoma medications as prescribed can result in severe visual damage. Family members should also be screened for glaucoma by an ophthalmologist.

 References

1. Weinreb RN, Khaw PT. Primary open-angle glaucoma. Lancet. 2004;363:1711-1720.
 
2. Leske MC. The epidemiology of open-angle glaucoma: a review. Am J Epidemiol. 1983;118:166-191.

3. Sommer A, Tielsch JM, Katz J, et al. Racial differences in the cause-specific prevalence of blindness in East Baltimore. N Engl J Med. 1991;325:1412-1417.

4. Tielsch JM, Sommer A, Katz J, et al. Racial variations in the prevalence of primary open-angle glaucoma. The Baltimore Eye Survey. JAMA. 1991;266:369-374.

5. Tielsch JM, Katz J, Sommer A, et al. Family history and risk of primary open- angle glaucoma. The Baltimore Eye Survey. Arch Ophthalmol. 1994;112:69-73.

6. Hennis A, Wu SY, Nemesure B, Leske MC; Barbados Eye Studies Group. Hypertension, diabetes, and longitudinal changes in intraocular pressure. Ophthalmology. 2003;110:908-914.

7. Nemesure B, Wu SY, Hennis A, Leske MC; Leske MC; Barbados Eye Studies Group. Factors related to the 4-year risk of high intraocular pressure: the Barbados Eye Studies. Arch Ophthalmol. 2003;121:856-862.

8. Distelhorst JS, Hughes GM. Open-angle glaucoma. Am Fam Physician. 2003;67:1937-1944.

9. Puustjarvi T, Blomster H, Kontkanen M, Punnonen K, Terasvirta M. Plasma and aqueous humour levels of homocysteine in exfoliation syndrome. Graefes Arch Clin Exp Ophthalmol. 2004;242:749-754.

10. Leibovitch I, Kurtz S, Shemesh G, et al.  Hyperhomocystinemia in pseudoexfoliation glaucoma. J Glaucoma. 2003;12:36-39.

11. American Academy of Ophthalmology. Preferred Practice Pattern, Primary Open-Angle Glaucoma. American Academy of Ophthalmology, 1996.

12. Girkin CA, McGwin G Jr, McNeal SF, et al. Hypothyroidism and the development of open-angle glaucoma in a male population. Ophthalmology. 2004;111:1649-1652.

13. Klein BE, Klein R, Linton KL. Intraocular pressure in an American community. The Beaver Dam Eye Study. Invest Ophthalmol Vis Sci. 1992;33:2224-2228.

14. Heijl A, Leske MC, Bengtsson B, et al. Reduction of intraocular pressure and glaucoma progression: results from the Early Manifest Glaucoma Trial. Arch Ophthalmol. 2002;120:1268-1279.

15. Higginbotham EJ, Gordon MO, Beiser JA, et al. The Ocular Hypertension Treatment Study: topical medication delays or prevents primary open-angle glaucoma in African American individuals. Arch Ophthalmol. 2004;122:813-820.

16. Quaranta L, Bettelli S, Uva MG, et al. Effect of Ginkgo biloba extract on preexisting visual field damage in normal tension glaucoma. Ophthalmology. 2003;110:359-362.

17. Lichter PR, Musch DC, Gillespie BW, et al. Interim clinical outcomes in the Collaborative Initial Glaucoma Treatment Study comparing initial treatment randomized to medications or surgery. Ophthalmology. 2001;108:1943-1953.

18. Janz NK, Wren PA, Lichter PR, et al. The Collaborative Initial Glaucoma Treatment Study: interim quality of life findings after initial medical or surgical treatment of glaucoma. Ophthalmology. 2001;108:1954-1965.