GLAUCOMA

1.What is glaucoma?

Glaucoma is a highly heterogeneous group of conditions in which tissues of the eye are damaged. Usually the optic nerve is damaged, resulting in a characteristic optic neuropathy with associated visual-field loss. In conditions such as acute angle-closure glaucoma, the lens, cornea, and other structures may be affected as well. The etiology of glaucoma is multifactorial. Elevated intraocular pressure (IOP) is one of the factors responsible for the damage. The role of IOP in glaucoma damage is variable. Increased IOP is the sole cause for the damage in acute angle-closure glaucoma, whereas, in low-tension glaucoma (LTG), IOP may play less of a role in the disease process.

2.How is glaucoma classified?

The broad classifications of glaucoma are somewhat artificial; they tend to blur as we learn more about the disease and its pathogenesis. Traditionally, glaucoma has been classified as open-angle or closed-angle based on the gonioscopic angle appearance. This differentiation plays an important role in treatment. Openand closed-angle glaucoma have been further classified as primary or secondary. Open-angle glaucoma is classified as primary when no identifiable contributing factor for the increased IOP can be identified. Secondary glaucoma identifies an abnormality to which the pathogenesis of

glaucoma can be ascribed. Examples include pseudoexfoliative, uveitic, angle recession, and pigmentary glaucoma.

3.How prevalent is glaucoma?

Glaucoma is the second leading cause of irreversible blindness in the United States and the third leading cause of blindness worldwide. Primary open-angle glaucoma affects approximately 2.5 million Americans. Half are unaware that they have the disease. Population-based studies have shown prevalence among Caucasians 40 years of age and older ranging from 1.1% to 2.1%. The prevalence among African Americans is three to four times higher. Prevalence also increases with age. People over 70 have a prevalence three to eight times higher than people in their forties.1

4.Name risk factors for the development of primary open-angle glaucoma.

Known risk factors include elevated intraocular pressure, age, race, and a positive family history of glaucoma. Decreased central corneal thickness also has been shown to contribute to the risk of developing glaucoma. Presumed risk factors for which evidence exists but sometimes appears conflicting include myopia and diabetes mellitus. Potential risk factors for which some association has been found include hypertension, cardiovascular abnormalities, sleep apnea, and vasospastic conditions such as Raynaud’s phenomenon or migraine. Disc hemorrhage, increased cup-to-disc ratio, and asymmetric cupping of the optic nerve may represent either risk factors or evidence of early disease.2

5.Discuss the genetics of primary open-angle glaucoma.

Primary open-angle glaucoma (POAG) is most likely inherited as a multifactorial or complex trait. A combination of multiple genetic factors or of genetic and environmental factors is required to develop the disease. One specific gene, the TIGR/myocilin gene, has been found to confer susceptibility to POAG. Family history is an important risk factor for the development of glaucoma. The Baltimore Eye Survey found the relative risk of having POAG is increased approximately 3.7 times for individuals having siblings with POAG.3,4

6.What is the pathogenesis of glaucoma?

The pathogenesis of glaucoma has been only partially elucidated. In some cases elevated intraocular pressure may cause optic nerve damage by mechanically deforming the optic nerve with poste-

rior bowing of the lamina cribrosa. In other cases a decrease in perfusion of the optic nerve may

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cause damage. This may happen from a sudden drop in blood pressure in response to blood loss or medications. Anemia can also result in ischemia of the optic nerve. Focal vasospasm may contribute to decreased perfusion and ischemia in patients with the low-tension forms of glaucoma. In most patients, several different pathogenetic mechanisms probably operate simultaneously.5

7.What is the clinical presentation of primary open-angle glaucoma?

Primary open-angle glaucoma is slowly progressive and painless. It is usually bilateral but often asymmetric. Central visual acuity is relatively unaffected until late in the disease; therefore, patients are often asymptomatic. Advanced disease may be present before symptoms are noticed.

8.What is normal intraocular pressure?

The line between normal and abnormal intraocular pressure is not clear. Mean intraocular pressure is around 16 mm Hg, with a standard deviation of 3 mm Hg. It is a non-Gaussian distribution skewed

toward higher pressures. Elevated intraocular pressure has been shown to be a risk factor for glaucoma; however, only 5% of people with pressures above 21 mm Hg eventually develop glaucoma. Conversely, patients with glaucoma damage may have intraocular pressures consistently in the normal range.6,7

9.True or false: Loss of peripheral vision is a warning sign of early glaucoma.

False. Loss of temporal vision (side vision) is the last to be affected in most types of glaucoma. The first area to be damaged in most people with glaucoma is vision to the nasal side of central vision. This helps explain why patients do not notice loss of vision until the damage is marked. Both eyes provide vision to the nasal side so a blind spot is not noted with both eyes open until vision is lost in both eyes.1

KEY POINTS: COMMON VISUAL-FIELD DEFECTS FOUND IN GLAUCOMA

1.Superior/inferior nasal step.

2.Superior/inferior arcuate defect.

3.Generalized depression.

4.Paracentral loss.

5. Temporal or central island with advanced disease.

10.What is a glaucoma suspect?

A glaucoma suspect is an adult who has an open angle on gonioscopy and one of the following findings in at least one eye:

•Optic nerve suspicious for glaucoma

•Visual-field defect consistent with glaucoma

•Elevated intraocular pressure consistently greater than 22 mm Hg

If a patient has two or more of the above findings, then a diagnosis of glaucoma is more likely. The

decision to treat a glaucoma suspect takes into account the above findings as well as additional risk factors and the general health of the patient.5

11.In examination of the optic nerve, what findings could be consistent with a diagnosis of glaucoma or suspicion of glaucoma?

Diffuse narrowing of the optic nerve rim, focal narrowing or notching of the optic nerve rim, vertical elongation of the optic cup, nerve fiber layer defects, nerve fiber layer hemorrhages, and asymmetric cupping of the optic nerves are all signs of glaucoma or suspicion of glaucoma. An acquired pit of the optic nerve is a pathognomonic sign of glaucoma.8

KEY POINTS: COMMON OPTIC NERVE FINDINGS IN GLAUCOMA

1. Diffuse narrowing of the neuroretinal rim.

2. Focal narrowing or notching of the neuroretinal rim. 3. Nerve fiber layer defects.

4. Disc hemorrhages.

5. Asymmetry of optic nerve cupping.

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12.A patient presents with optic nerve damage in one eye as pictured in Figure 15-1. The other eye has lower pressures and a healthier optic nerve with a normal visual field. What is the prognosis for the healthier optic nerve?

The optic nerve in Figure 15-1 shows complete loss of the inferotemporal rim. Optic nerve damage in one eye has been associated with a significantly increased risk of future damage in the other eye. Twenty-nine percent of untreated fellow undamaged eyes will show visual-field loss in an average of 5 years.9

13.A 74-year-old African American female presents for a routine eye examination. She has not been to an ophthalmologist in 10 years. Her intraocular pressures are 26 mm Hg in the right eye (OD) and 24 mm Hg in the left eye (OS). Her optic nerves are as pictured in Figure 15-2. What information is important to obtain from the patient?

The optic nerves in Figure 15-2 show significant asymmetry with a narrower rim supertemporally in the right eye in comparison to the left eye. She has not been seen by an ophthalmologist for years. The history is a crucial part of the evaluation; it identifies possible secondary causes for glaucoma (e.g., trauma, steroid use) as well as risk factors such as family history, helps determine the visual demands and support system of the patient, and can give an idea of the patient’s general health and

Figure 15-1.  Complete loss of the neuroretinal rim is a sign of advanced glaucoma.

Figure 15-2.  Asymmetry of the cup-to-disc ratio can be an early sign of glaucoma.

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life expectancy. All of these components help formulate a treatment plan most likely to be agreeable to the patient, least likely to be damaging, and of an appropriate level of aggressiveness for each individual patient.

14.If the patient in question 13 had been to another ophthalmologist several times a year and was presenting for the first time in your office, what information would be important to obtain?

Old records are valuable. Knowing about previous surgeries, lasers, and medicines (both those that worked and those that did not) helps formulate a current treatment plan. Previous intraocular pressure readings, former visual-field tests, and optic nerve evaluations can establish the rate of progres-

sion of the disease, a key piece of information in determining the level of aggressiveness needed in treatment.

15.True or false: If the patient in question 13 had a normal visual field, she would be unlikely to have glaucoma.

False. Visual-field defects may not be apparent until as much as 50% of the optic nerve fiber layer has been lost.

16.True or false: If the patient in question 13 had intraocular pressures of 19 mm Hg OD and 18 mm Hg OS, then she would be unlikely to have glaucoma.

False. A single intraocular pressure measurement in the normal range is not enough to eliminate the possibility of glaucoma. Several studies suggest that as many as 30 to 50% of individuals in the general population having glaucomatous optic nerve damage and visual-field defects have an initial IOP measurement of less than 22 mm Hg. Diurnal IOP fluctuation and artificially low measurements

due to decreased central corneal thickness or other factors may contribute to the normal IOP. In addition, patients with average-pressure glaucoma have glaucomatous optic neuropathies without ever demonstrating elevated intraocular pressures.10,11

17.How does intraocular pressure fluctuate in glaucoma patients?

Individuals without glaucoma may have an IOP fluctuation of 2 to 6 mm Hg over a 24-hour period. IOP in glaucoma patients may vary widely. Untreated glaucoma patients may vary by 15 mm Hg or more. The majority of patients demonstrate the highest pressures in the morning with decrease throughout the day. Other patterns with peak pressures at night or midday as well as flat patterns without variation have been reported.12

18.What role does central corneal thickness play in the evaluation of glaucoma?

Corneal thickness is important to consider for two reasons. First, corneal thickness affects the mea-

surement of IOP so that the measured IOP may be inaccurate if the corneal thickness is not average. The actual average central corneal thickness is approximately 544 μm. IOP is about 5 mm Hg lower than measured for each 100 μm that the cornea is thicker than normal. The true IOP is actually higher than measured when the cornea is thinner than average. Second, a thin central cornea, in itself, is associated with more severe glaucoma. The Ocular Hypertension Treatment Study identified reduced central corneal thickness as a risk factor for glaucoma in patients with IOP between 24 and 32 mm Hg.13,14

19.Name factors that affect the measurement of intraocular pressure.

Intraocular pressure measurements can be overestimated and underestimated based on several factors (see Table 15-1).

20.What role does imaging play in the evaluation and management of glaucoma?

Significant structural retinal nerve fiber layer (RNFL) loss occurs prior to functional visual-field loss. Periodic stereoscopic optic disc photography remains the gold standard for documentation of the optic nerve appearance and assessment of glaucoma progression over time. However, newer technologies such

as optical coherence tomography (OCT) are now available to assess the RNFL, optic nerve head, and ganglion cell complex. This technology may assist in the detection of RNFL loss in situations in which the subtle signs of disease could be overlooked on clinical exam. It can also help confirm the diagnosis or progression of glaucoma in the setting of corresponding RNFL defects and visual-field defects.15

21.What parameters on optical coherence tomography are useful in the diagnosis and management of glaucoma?

As pictured in Figure 15-3, OCT measures the RNFL thickness and then compares those data with a normative age-matched database. Green, yellow, and red colors signify the percentage chance that

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Table 15-1.  Factors Influencing the Measurement of Intraocular Pressure

Overestimation of IOP

Pressing on the globe

Thick tear meniscus (too much fluorescein) Thick central cornea

Valsalva (breath-holding or straining) Thick neck/obese patients

Anxiety Astigmatism

Orbital disease/restrictive ocular myopathy, as with Graves’ disease Corneal scarring and high corneal rigidity

Flat anterior chamber

Underestimation of IOP

Thin tear meniscus (too little fluorescein) Thin central cornea

Corneal edema

Repeated IOP measurements/prolonged contact with cornea Low corneal rigidity

the thickness is within the normal range for an age-matched population. OCT also documents optic nerve head parameters including optic rim area, optic disc area, average cup/disc ratio, vertical cup/ disc ratio, and optic cup volume.16

22.True or false: If the OCT showed no evidence of RNFL thinning, then the patient does not have glaucoma.

False. OCT technology may be limited by signal quality, image artifact, and confounding ocular disease. Serial imaging can be used as an adjunct to standard perimetry and optic disc photography. Clinical decisions should not be made on the basis of a single test or technology.

23.What is the primary goal of treatment of patients with glaucoma?

The primary goal in the treatment of glaucoma is enhancing the patient’s health by improving or preserving his or her vision. One way of preserving vision is by lowering the intraocular pressure. It is important not to lose sight of the primary goal in treatment. All treatment options carry side effects and risks. The patient’s general health and visual demands always need to be considered.

24.Name the initial treatment options for primary open-angle glaucoma.

Options include observation or lowering the intraocular pressure by using eyedrops, laser trabeculoplasty, or surgery.

25.What factors help determine which option to try?

When deciding on an initial treatment for a patient with glaucoma, several factors need to be considered. First, determine how aggressive the treatment needs to be. The level of aggressiveness takes into consideration the severity of the disease, the rapidity of progression, and the general health of the patient. Second, the toxicity and cost of the various treatment options need to be assessed. This will help predict compliance. For example, a 70-year-old healthy patient with advanced disease and an inability to tolerate medicines would most likely benefit from surgery. A healthy 45-year-old with mild-to-moderate disease may begin with medication or, if unable to be compliant or tolerate medicines, a laser trabeculoplasty. An elderly sick patient with mild-to-moderate disease may benefit from observation alone.

26.Are eyedrops safer than oral medications?

No. Eyedrops are directly absorbed into the blood through the nasal mucosa. This route bypasses the firstpass metabolism of drugs by the liver and can allow increased effects for a given amount of absorption.

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Figure 15-3.  OCT shows thinning of the RNFL in the patient from Figure 15-2.

27.Are some optic nerves more resistant to intraocular pressure damage than others?

Yes. Small nerves with no peripapillary atrophy but small central cups in which it is not possible to see laminar dots are less likely to become damaged than eyes with large optic nerves, large cups, peripapillary atrophy, and prominent laminar dots. A large cup does not necessarily correlate with glaucoma if the optic nerve itself is large. It is important to determine the optic nerve size when evaluating neuroretinal rim.

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Figure 15-4.  Elongation of the optic nerve cup can be an early finding in glaucoma. Splinter disc hemorrhages can be a prognostic indicator for progressive disease.

28.A patient being treated for glaucoma presents for a follow-up examination with an optic nerve appearance as shown in Figure 15-4. Discuss the findings.

Figure 15-4 demonstrates an optic nerve with vertical elongation of the cup. Narrowing at the superior and inferior rim often occurs in glaucoma. A nerve fiber layer hemorrhage is present at the inferotemporal rim of the optic nerve. Disc hemorrhages are commonly found in glaucoma patients. They are important prognostic signs for the development or progression of visual-field loss.17

29.Name five potential causes of disc hemorrhages.

•Glaucoma

•Posterior vitreous detachments

•Diabetes mellitus

•Branch retinal vein occlusions

•Anticoagulation

30.What is low-tension glaucoma?

Low-tension glaucoma is one of the traditional labels for a glaucomatous optic neuropathy that occurs without evidence of elevated intraocular pressure. Because “low” is a relative word, and because many people with “low tension” have IOP above the mean, but in the average range, a better term

is “average-pressure glaucoma” (APG). There is much controversy over whether APG is part of a spectrum of primary open-angle glaucoma with IOP that is not elevated above the average range or its own disease entity. The optic nerve in patients with APG is susceptible to damage at normal IOP. Ischemia may contribute significantly to the progression of the disease. Studies suggest a higher prevalence of vasospastic disorders such as migraine or Raynaud’s phenomenon, coagulopathies, cardiovascular disease, and autoimmune disease in patients with low-tension glaucoma. Nocturnal hypotension and anemia may also result in decreased optic nerve perfusion in patients with lowtension glaucoma.

31.What disease entities can mimic low-tension glaucoma?

Undetected “high-tension glaucoma” can mimic LTG. This could be the result of a missed elevation of IOP that occurs at times when the IOP was not measured, a thin central cornea, or an error in applanation. The patient could have suffered a previous episode of severe intraocular pressure elevation from a secondary glaucoma such as uveitic or steroid-induced glaucoma that had subsequently normalized. He or she could have suffered intermittent spikes from angle closure. The patient may have suffered an episode of optic nerve hypoperfusion due to blood loss from surgery or trauma. Compressive optic nerve lesions, ischemic optic neuropathy, congenital anomalies, and certain retinal disorders can also mimic APG (Table 15-2).18

32.What tests should be considered in the workup of a patient with glaucomatousappearing optic nerves and visual fields without elevated intraocular pressure?

Usually the diagnosis is clear on the basis of the appearance of the optic nerve, the visual field, and the asymmetry of IOP with the higher pressure in the eye with more damage. When not clear, a diurnal curve and central corneal thickness should be checked to be certain the condition is not a “hightension” glaucoma with low intraocular pressure readings. A computed tomography or magnetic