Glaucoma

What is glaucoma?

The newly diagnosed glaucoma patient leaves the doctor’s office with numerous important questions that we will address in this presentation. Typically, such patients have been told that the fluid pressure inside the eye (intraocular pressure, IOP) is elevated, and that the eye either has already suffered some damage or is threatened with undergoing “optic nerve damage.” These seem like complex and confusing terms when the patient wants to hear a straightforward answer to the question: What is glaucoma?

Today, glaucoma is defined as a group of eye diseases that have in common progressive damage to the optic nerve that if left untreated can result in substantial vision loss. The definition is broad, because it turns out the condition is more complex than once believed. In the past, the presence of elevated IOP in the majority of glaucoma patients was emphasized, but today we recognize that some glaucoma patients have a normal IOP, and this segment of the population is classified as having normal tension glaucoma (NTG). Others have an abnormally elevated IOP but do not go on to develop glaucoma. In addition, there are both many different causes of the pressure elevation in glaucoma, and for the optic nerve damage, so that a unifying description is not readily apparent. This is why the current definition focuses on the common feature of glaucoma, which is damage to the optic nerve, whether the damage results from an elevated IOP or is due to some other undetermined factor. (Primary open-angle glaucoma, preferred practice pattern. American Academy of Ophthalmology, San Francisco, 2005. Available at: http://one.aao.org/CE/PracticeGuidelines/PPP_Content.aspx?cid=a5a59e02-450b-4d50-8091-b2dd21ef1ff2.).

In its early stages, glaucoma is most often asymptomatic and requires a specialized examination by an eye doctor (ophthalmologist) for its detection. The optic nerve damage that occurs in glaucoma is associated with development of a characteristic visual field loss, affecting peripheral vision in its early stages, and progressing to involve the central field much later in the disease process. Thus, the eye specialist employs specific diagnostic tests to uncover physical signs (such as cupping of the optic nerve) and symptoms (loss of peripheral vision). Treatment is directed at lowering of the IOP regardless of the pressure level present, as this intervention is beneficial for both patients with an elevated pressure as well as those affected by NTG. Although there is currently no cure for glaucoma, in most cases early diagnosis and correct treatment can prevent blindness.

Eye tissue relationships and the development of glaucoma. 

Figure 1 is a diagram of the eye illustrating the important tissue relationships in the normal eye and in the development of glaucoma (select from HAW pp. 326 PLEASE SUPPLY). The eye has an external wall made up mostly by a white tissue called the sclera, which is covered by the conjunctiva, a thin and transparent membrane. The front part of the eye wall consists of the cornea, which is perfectly transparent (Fig. 1A). Light enters through the cornea and passes through the pupil, which is the opening formed by the iris, or colored part of the eye. The iris contracts and expands, controlling the size of the pupil, and the amount of light that enters the eye. The lens is located behind the pupil and iris (Fig. 1C) and the lens functions to focus light entering the eye onto the retina. The retina lines the inside of the eye and contains the photoreceptor cells known as rods and cones that are stimulated by light focused on the retina. The retina transmits light signals to the optic nerve, which then conveys the information gathered to the brain where a visual image is perceived.

Other structures that play an important role in the development and treatment of glaucoma are also shown in Figure 1. These include the ciliary body and its many finger-like processes, which lies behind the iris, and is responsible for producing aqueous humor, a fluid that has many important functions. This fluid fills up the eye generating a normal intraocular pressure as required for maintaining the optical system of the eye (including the cornea, lens and retina) in a stable physical relationship. The eye fluid also circulates around structures that do not contain blood vessels, such as the lens and vitreous, bringing nourishment to these tissues. Aqueous reaches the tissues in the front of the eye by passing between the iris and lens through the pupil to gain access to the front, or anterior chamber of the eye. The eye fluid finally exits from the eye by passing through a drainage system to return to the systemic venous circulation.

The location of the drainage system is shown in Figures 1 and 2. It is located around the periphery of the front of the eye, where the cornea and iris come together to form the so-called “angle” (Figure 1). This drainage system, or “outflow pathway” consists of a system of channels and supporting tissue known as the trabecular meshwork, which lead to Schlemm’s canal. Once aqueous reaches Schlemm’s canal, it exits the inside of the eye to return to the systemic venous circulation.

The state of the outflow pathway largely determines the IOP level because the pressure inside the eye must rise enough to overcome the resistance presented by the drainage system in order for aqueous to exit the eye. In the normal eye, relatively little resistance is presented and the resultant IOPs are within a range of 10-21 millimeters of mercury (mm Hg). In some types of glaucoma, the trabecular meshwork in the outflow pathway offers increased resistance to the exit of aqueous resulting in an elevated IOP [1]. Such high pressures can damage the delicate optic nerve and result in vision loss, although in NTG even normal pressure levels can result in damage to the optic nerve.

Types of glaucoma.

The various glaucomas are classified broadly based on the width of the angle formed by the iris and cornea at the periphery of the anterior chamber of the eye (Figure 1).

Open angle glaucoma:
In open angle glaucoma the iris and corneal tissues are separated from each other by a space measuring about 30-40 degrees (Figure 2). In these patients, the aqueous fluid has clear access to the drainage pathway, but the pathway itself does not function normally. There is increased resistance to the exit of aqueous as it drains out of the eye by passing through the trabecular meshwork and into Schlemm’s canal. This type of glaucoma, also known as primary open angle glaucoma (POAG), is the most common type of glaucoma in the United States, affecting about 3 million Americans. POAG is usually insidious in onset, slowly progressive, painless, and does not affect central vision (alerting the patient of the presence of vision loss) until late in the disease. For this reason, diagnosis based on symptoms alone may not occur until significant vision loss has already occurred. Thus, regular eye examinations are crucial to early diagnosis and treatment.

Risk factors for POAG, besides elevated IOP, include age, race, central corneal thickness, and family history. Increased IOP with age has been observed in many populations, and in part may explain why glaucoma is more common in the aged. In addition, some studies have shown a relationship between glaucoma and age, even without an increase in IOP, indicating that age is an independent risk factor for development of glaucoma. African Americans are at four to five times greater risk of developing POAG compared to other races. African Americans tend to have a thinner central cornea, which is also a risk factor for POAG, but race and thin central corneal thickness are also independent risk factors for development of POAG. Lastly, studies have shown that individuals with siblings who are affected by POAG are also at increased risk.

Most patients with POAG will retain useful vision in their lifetime. Treatment using medications, lasers, and surgeries are aimed at lowering the IOP, and can significantly slow down, or stop progression of the disease. Individual types of treatments are described in detail below.

Closed angle glaucoma:
In this type of glaucoma, also called angle closure glaucoma, or narrow angle glaucoma, the angle is narrow or closed (measuring 20 or fewer degrees), with the iris apposed to the cornea, blocking access of the aqueous fluid to the drainage area of the eye. This type of glaucoma tends to be less common in the United States, and more common in various Asian populations. Acute angle closure glaucoma usually results in an abrupt and dramatic rise in eye pressure, and one may experience symptoms of severe eye pain, redness, headaches, nausea and vomiting, blurred vision, and haloes around lights. Acute angle glaucoma is an ophthalmologic emergency and must be treated immediately to prevent serious and permanent damage to the eye.

Risk factors for primary angle closure glaucoma (PACG) include race, certain characteristics of the eye shape, age, gender, and family history. PACG tends to be less common in whites and Africans, and more common in East Asians and most common in Inuits. Eyes that are shorter in length tend to have crowding of the angle structures and are at higher risk of developing angle closure. This is seen more commonly in people who are farsighted (hyperopic). In addition, a thickened lens, as occurs with cataract formation with age, tends to push the iris forward and make angle closure more likely. Women are two to four times more frequently affected by angle closure, which is in part, but not completely explained by differences in the size and length of the eye. Lastly, genetics plays a part, as risk is increased in first-degree relatives.

There are two main mechanisms that may contribute to PACG, pupillary block and plateau iris configuration. In pupillary block, with increasing age the lens increases in size changing its position and coming into closer contact with the iris at the pupillary border, blocking aqueous fluid from moving around the pupil and into the anterior chamber (Figure 2). Thus, as aqueous is produced by the ciliary body behind the iris, it pushes the peripheral iris forward closing off the already narrow angle. As a result, no aqueous can leave the eye, and the IOP rises very quickly. This situation is more likely to occur in an eye that is shorter in length and has crowding of the structures in the front part of the eye, or in the eye that has a severely thickened lens due to cataract formation in the aged.

Plateau iris describes eyes having a narrow angle as well as a ciliary body that is positioned forward against the peripheral iris. Upon dilation when in a darkened environment, the dilating iris tissues are crowded into the limited space available at the anterior chamber angle. Thus, the iris tissues bunch up against the cornea thus closing off the angle. Unlike pupillary block, in plateau iris, the aqueous can get around the pupillary border, but once it is in the anterior chamber, the dilated iris tissues block the angle and fluid cannot leave the eye. Both pupillary block and plateau iris can lead to an angle closure attack, and it is very important to be able to distinguish between the two mechanisms, as the treatment for each is different. 

Treatment of an acute angle closure attack typically involves initial treatment with eye pressure-lowering medications: drops, oral medications, and/or intravenous medications. Once the pressure has improved, a laser procedure called a peripheral iridectomy is performed, whereby a small hole is made in the peripheral iris. This allows fluid to pass from the ciliary body, which is behind the iris, and where the aqueous fluid is produced, directly to the angle, facilitating drainage and lowering of the elevated IOP. Laser iridectomy is extremely effective at treating the pupillary block-type of angle closure glaucoma. Patients with plateau iris may also receive a laser iridectomy, but will subsequently need to be treated in an entirely different manner. The treatment is directed at preventing the dilating iris tissues from crowding out the narrow angles present in these patients by one of three different methods. The traditional treatment requires the application of eye drops (i.e. known a miotics, such as Pilocarpine) to maintain the pupil constricted even when the patient is in a darkened environment. Another treatment requires using a laser to make the iris periphery “stiff” in a procedure called iridoplasty, so that upon dilation the iris does not bunch up to block the drainage system. Patients who have angle closure in one eye are usually at risk for an attack in the other eye, and the doctor may treat the other eye with a laser iridectomy as a safety precaution. An acute attack of angle closure can be successfully treated by these means, but it is important to have regular check-ups, because a more chronic form of glaucoma can occur in particular when the nature of the particular mechanism involved, pupillary block vs. plateau iris, was not properly identified.

Secondary glaucoma:
Secondary glaucoma can occur when the drainage area of the eye is blocked due to processes going on in other parts of the eye, and this can be with an open angle or closed angle. Eye injury, most commonly unilateral, can lead to damage to the angle and decreased outflow of aqueous. Inflammatory diseases of the eye, or conditions that lead to pigment release in the eye, can cause clogging of the drainage channels in the angle (secondary open angle glaucoma). Inflammation can also lead to scarring within the eye, and the angle can become scarred shut (secondary angle closure glaucoma). Furthermore, tumors of the eye, advanced cases of diabetes and cataract, as well as certain drugs such as steroids, can also lead to secondary glaucoma. The treatment is aimed at the primary cause, as well as at lowering the eye pressure with any of the modalities described below. 

Infantile and childhood glaucoma:
This is a rare condition that occurs in infants, children and younger adults. The latter may have an early onset form of POAG. In younger patients, it is the result of incorrect or incomplete development of the drainage area of the eye. Unlike most adult forms of glaucoma, which are treated with medications and laser first, this type of glaucoma usually requires surgical intervention. Often, medications are required afterwards.

Diagnosis of glaucoma: what to expect during evaluation.

To make an accurate diagnosis of glaucoma, a complete eye examination and certain ancillary tests should be performed. Diagnosis of glaucoma is not always easy, and the doctor must look at several factors before a treatment plan is decided upon.

Tonometry measures the IOP using a device called an applanation tonometer. Eye drops are applied first to numb the eye, and then the tonometer is gently placed over the cornea, which gives a pressure reading. Eye pressure in the average population usually ranges between 10-21 mm Hg, though it is unique to each person and may be higher or lower as well. Most cases of glaucoma are diagnosed with the eye pressure higher than 20 mm Hg, but not always. It is important to use the eye pressure in context with results from the rest of the examination.

Pachymetry is used to measure the thickness of the cornea in a similar manner to the measurement of the IOP. The eye is numbed with eye drops, and an ultrasound instrument, the pachymeter, is gently brought in touch with the corneal surface. A measurement of the corneal thickness is then provided digitally. Since we now know that thin corneas confer a higher risk of primary open angle glaucoma, this measurement has become a standard part of the evaluation for glaucoma. In addition, the thickness of the cornea can influence the accuracy of the IOP readings, so it is important to know if the cornea is thin, average, or thick. Thin corneas can give a falsely low IOP reading, whereas thick corneas can give falsely high readings.

Gonioscopy involves using a special hand-held contact lens called a gonioscopy lens, which is placed over the cornea, to visualize the structures of the anterior chamber angle. This evaluation is extremely valuable in trying to determine the type of glaucoma present, should the diagnosis of glaucoma be made. Whether the angle is wide open or closed can help in the distinction between open angle and closed angle glaucoma. Gonioscopy can also reveal if there has been damage to the angle from prior surgery, trauma, deposition of pigment, or formation of abnormal blood vessels. (I had planned to show UBM of various angles, included an open angle in the light and then closed when in the dark, WILL BE SUPPLIED)

Ophthalmoscopy is used to examine the structures inside the eye, paying particular attention to the inner surface of the optic nerve or disc assessing for the presence of cupping, due to damage to this important structure. The pupils may need to be dilated to properly complete this part of the examination. However, it is also possible to visualize the optic disc through an undilated pupil. Special lenses are used to focus light through the cornea, pupil and lens to the back of the eye so that the optic disc can be seen. There are several components to the evaluation of the optic disc. First, your doctor will look at the overall appearance and size of the disc. A healthy disc is orange or pink in color, which indicates most often that the nerve tissues are well nourished or perfused by an intact circulation. An abnormal disc may be yellow and pale suggesting that the tissues have undergone atrophy or that blood supply to the disc is decreased. (FIGURES OF DISCS WILL BE SUPPLIED) 

Secondly, the thickness of the optic rim is evaluated. The inner border of the rim determines the level of “cupping” of the optic disc. People with glaucoma have thinner rims and bigger cups than people who do not have glaucoma (A COMPARATIVE VISUAL WILL BE SUPPLIED). You may hear your doctor refer to the “cup-to-disc” ratio, which is an estimation of what proportion of the disc that is made up of the cup, and is a number that may range from 0.1 (almost no cup), to 1.0 (entire disc is cupped). It is important that both eyes be examined, as an asymmetry between the two optic discs is also reason to suspect glaucoma. Serial examination of the optic disc to look for changes over time is essential in the diagnosis and management of glaucoma.

Visual field testing or perimetry is a method to formally test your complete field of vision, particularly your peripheral vision, which may be affected first in glaucoma. During the test, you are asked to look straight ahead, and press a signal button whenever you see a light flash in different parts of your vision. It is important to be well rested so that you can concentrate during the exam, since poor concentration can lead to the eye wandering around, and give an unreliable test result. Your doctor will look for characteristic visual field defects that may suggest an initial diagnosis of glaucoma, or a worsening of known glaucoma (FIGURES OF VFs WILL BE SUPPLIED). This test should be repeated at regular intervals to look for changes in your peripheral vision.

Imaging modalities are techniques that supplement ophthalmoscopy in the evaluation of the optic disc. The simplest type of imaging is the disc photo, which is usually obtained during baseline examination, and is used for comparison during subsequent examinations. There are now several other types of imaging tests available, including the Heidelberg Retinal Tomograph (HRT), Optical Coherence Tomography (OCT), and the Nerve Fiber Analyzer (GDx). These tests can provide more quantitative measurements of the optic disc and the nerve fiber layer, which is thinned in glaucoma.

Treatment.

Current treatments for glaucoma are aimed at lowering the IOP to slow damage to the optic nerve. Controlling the IOP can slow or halt the progression of glaucoma, but does not cure it. Medications are typically tried first, followed by laser, then surgery.

Medications have two main mechanisms of action to lower the IOP: they may increase drainage of aqueous out of the eye, or decrease aqueous production. There are several classes of medications, each of which have their advantages and disadvantages. Finding the best medication for each person is an individualized process, since what works well for one person may not work for another. If one medication lowers the IOP, but the IOP is still not as low as your doctor would like, additional medications may be added to your regimen. Dosing schedules can range from one to four times a day, depending on the medication. Currently, the main classes of medications are beta-blockers (e.g. Timolol), alpha-agonists (e.g. Brimonidine), carbonic anhydrase inhibitors (e.g. Dorzolamide), and prostaglandin analogs (e.g. Latanoprost). Many doctors start with the prostaglandin analogs because they are dosed at once daily, which is most convenient for patients. Patient factors, such as presence of other medical problems, will also guide the doctor’s choice of medication. For example, beta-blockers are avoided in patients with a history of asthma. Most medications have some side effects, which usually lessen after the first few weeks, but if you experience any unusual changes, you should notify your doctor immediately so that appropriate changes can be made.

Laser surgery is used as initial treatment in certain types of glaucoma (such as acute angle closure glaucoma), and in people who are unable to tolerate medications due to side effects. It is also used when one is on the maximum amount of medications, and the IOP is still too high. There are several types of glaucoma laser procedures, and the particular type used will depend on the type of glaucoma. The laser procedures can be performed in the doctor’s office. The eye is numbed with eye drops, and the laser is set up to focus the light beam precisely on the area of the eye to be treated. The most common types of laser surgery are laser peripheral iridotomy (LPI), argon laser trabeculoplasty (ALT), and selective laser trabeculoplasty (SLT). LPI is performed for angle closure glaucoma, and involves creating a small hole in the outer edge of the iris, allowing fluid to drain through this hole to access the angle and the trabecular meshwork. ALT and SLT are directed at the trabecular meshwork, and serve to open the drainage channels and lower the resistance to aqueous flow out of the eye. ALT is largely being replaced by SLT, since SLT causes less damage to surrounding tissues and can be repeated over time (FIGURE? WILL BE SUPPLIED). Less commonly used are laser procedures to decrease secretion of aqueous by the ciliary body (cyclophotocoagulation). In this procedure, a laser beam is aimed at the ciliary processes to purposely injure the tissues involved in secretion of aqueous. This decreases the amount of aqueous produced, which in turn lowers the IOP.

Incisional surgery is used in cases that are inadequately controlled by medications and laser, or as initial treatment in most cases of congenital glaucoma. Glaucoma surgery is usually directed at creating a new outflow pathway for aqueous fluid so that IOP can be lowered. There are two main types of glaucoma surgery. The first type is a trabeculectomy, in which a small opening is made in the sclera, creating a new channel for drainage of fluid. The scleral opening is covered by conjunctiva so that fluid does not drain directly to the outside of the eye and cause the IOP to go too low. The second type of surgery involves placing a drainage device on the outside of the eye, which is also covered by conjunctiva. Attached to this device, or plate, is a small tube that is inserted into the anterior chamber. Aqueous fluid drains through this tube, to the plate, and is absorbed under the conjunctiva, to lower the IOP. These surgeries are usually performed on an outpatient basis and require only local anesthesia. All surgeries do carry some risk, but glaucoma surgeries are usually successful at achieving the desired lowering of IOP.

Other sources of information.

Glaucoma Research Foundation: www.glaucoma.org
New York Glaucoma Research Institute: www.glaucoma.net

Figures
Figure 1: Diagram of the eye
Figure 2: Open Angle/Narrow Angle
Figure 3: tonometer
Figure 4: gonioscopy and the angle
Figure 5: photos of optic discs
Figure 6: visual fields
Figure 7: SLT
Consider other Figures as well.

REFERENCES

1.    Grant W and Trotter R. Factors responsible for the resistance to outflow of intraocular fluid. ACTA XVII Conc. Ophthal. 1955; 3:1536-1545.