Module 41 Glaucoma, Part 1

	Module 41
Home	Catalog	Contact us
	Get Post-Test

Module 41:	Glaucoma, Part 1

Introduction The Anterior Chamber and the Aqueous Humor Intra-ocular pressure (IOP) Optic Nerve Head Cupping Retinal Nerve Fiber Layer (RNFL) Thickness Visual Field Loss


Introduction Glaucoma is the second leading cause of blindness in the United States, following diabetic retinopathy. It is estimated that 3 to 5 million Americans have glaucoma, but that only about half of them know that they have it. Glaucoma is the leading cause of blindness in African-Americans, and the disease is about 7 times more common in African-Americans than it is in Caucasian-Americans. Everyone is at risk for glaucoma. Although uncommon, young people and even babies can have glaucoma. Glaucoma is most common in the senior age group. About 8% of those over age 70 have elevated intra-ocular pressure. Glaucoma is called the "sneak thief of sight" because it is usually symptom-less until significant vision loss has occurred. The eye gradually loses peripheral vision, which is not easily noticed, and eventually central vision is also lost. The only way to detect glaucoma is with a comprehensive eye examination, yet it is estimated that less than 50% of adult Americans have a dilated eye exam at least every 2 years. Glaucoma is not yet curable, but it is treatable. Once vision has been lost to glaucoma, it cannot be re-gained. Medical and surgical treatments for glaucoma slow (stop?) the rate of vision loss.
What causes glaucoma? In a nutshell, glaucoma is a plumbing problem. A fluid inside the eye called the aqueous is continuously being produced by the eye, circulated through the anterior chamber of the eye, and then drained from the eye. This process produces a pressure gradient inside the eye called the intra-ocular pressure (IOP). At the back of the eye, in the retina, are nerve fibers that carry visual nerve impulses through the optic nerve to the brain. These nerve fibers are damaged if the IOP increases above a "normal" range. Damaged nerve fibers result in blind areas in the field of vision. The IOP can rise above the normal level if there is disruption in the normal dynamics of the aqueous circulation, most likely caused by a restriction in the drainage of aqueous from the eye.

The Anterior Chamber and the Aqueous Humor

The anterior chamber is a space formed by the conjunction of the cornea and the iris.

The space in the chamber is filled with a watery fluid called the aqueous humor. This fluid is produced by the ciliary processes which lie behind the iris. The aqueous circulates through the pupil, within the anterior chamber, and then exits through the angle formed by the cornea and the iris.

The aqueous serves three primary functions: It provides a clear refractive media through which light passes to be focused on the retina. It carries nutrients which serve the metabolism of the cornea and the lens. It creates an intraocular pressure which serves to maintain the shape of the globe. Inside the angle structure of the anterior chamber, the aqueous exits through the trabecular meshwork and into a tub like structure called Schlemm's canal. Both of these structures make a continuous ring around the cornea in the area that is seen externally as the limbus. From Schlemm's canal, the aqueous travels through channels to the sclera and eventually to the bloodstream.


Intra-ocular pressure (IOP) Intra-ocular pressure is created by the natural resistance to the outflow of the aqueous humor from the eye. Think of your kitchen sink. When the faucet is running wide open, there is very little water collecting in the sink if the drain is clear. If you put a strainer in the drain, the water will back up a little in the sink as the water tries to drain through the small holes of the stainer. The trabecular meshwork is the strainer of the eye. The slight backup of fluid inside eye is what creates the normal IOP. If some spaghetti gets into the strainer of your sink, the water will become backed up more. A greater backup of fluid inside the eye causes the IOP to rise above normal. In the majority of glaucoma cases, it is not something that gets caught in the "strainer" that causes resistance to outflow, but it is some other mechanism. The IOP is not just a function of the outflow, but of the inflow as well. In the plumbing analogy, if the water coming out of the faucet is increased, the backup will increase, and vice versa. Some of the drugs used to treat glaucoma work on this side of the equation, they act to decrease the amount of aqueous being produced. The IOP is also affected by the time of day (usually higher in the morning) and the patient's pulse and respirations. An increase in blood pressure to the head and holding ones breath can temporarily raise the IOP. Steroid medications may cause the IOP to go higher while the patient is on the steroid medication, particularly if the steroid is an eye medication. Intra-ocular pressure is expressed in units of "millimeters of mercury" (mmHg). If you were to insert a needle into the anterior chamber, the needle could be connected to a closed reservoir of mercury with a tube extending upward from the reservoir. An eye with a pressure of "20" would exert a force through the tube that would push the mercury upward 20mm inside the tube. There is a similar technique called manometry that does not use mercury but it can be used to directly measure the IOP. For obvious reasons, this technique is only used for research purposes. All clinical techniques for measuring the IOP use an indirect method of measurement that is then converted to mmHg. All indirect techniques are subject to errors that are particular to the technique. The normal range of IOP is generally thought to be between 10 and 21 mmHg. The IOP is not an absolute indicator of glaucoma. Some patients with relatively low IOP readings can have glaucoma. Other patients can have relatively high IOP readings and not have any signs of glaucomatous damage. A pressure at or above 22 serves as a red flag that further investigation is needed. The eye doctor also uses pressure readings to gauge the effectiveness of the glaucoma treatment.

Clinical methods of measuring IOP

	Goldmann Applanation Tonometry is currently considered to be the most accurate clinical method for measuring the IOP. This method indirectly measures the IOP by gauging how much force it takes to flatten the cornea over a fixed surface area. This would be like pressing the palm of your hand against the surface of a balloon. If the balloon does not have much air in it and it is soft, then it does not take much force to cover the palm of your hand with the surface of the balloon. If the balloon has a lot of air in it and it is hard, it will take more force to cover the palm of your hand with the balloon. The word applanate means "to flatten".

The fixed surface area is the flat tip of the tonometer head. Pressure is applied to the cornea through the tip by turning the dial on the tonometer, which releases pressure from a spring inside the tonometer as the dial is moved toward the higher numbers. The fixed surface area of the tip is covered by the corneal surface when the inside circle of the mires just touch as observed through the ocular of the slit lamp.

An advantage of this method is that it is mounted on the slit lamp microscope, providing a stable base from which to handle the instrument. However, the slit lamp mount is a disadvantage in that the instrument is not portable. Another disadvantage is that fluorescein dye and a topical anesthetic must be instilled into the eye. The fluorescein dye aids in viewing the mires and the anesthetic is needed because the tip touches the cornea.

As an indirect method of measuring the IOP, applanation tonometry is subject to several sources of error: A tight collar on the the patient may cause the blood pressure in the head to be elevated, which may elevate the IOP. If the patient holds her breath, it may elevate the IOP.
The tip is designed to applanate the cornea on the corneal apex. If the patient is not looking straight ahead, and the tip is not perpendicular to the apex, then the pressure reading may be in error. The appearance of the mires is used to guide the operator to a proper alignment. The mires should be of equal size and centered in the field of view. If this is not the case, adjustments must be made in alignment.
Too much fluorescein on the tip of the applanator can cause a reading error due to the mires being too thick. Excess fluorescein should be removed from the lower canthus with a tissue prior to applanating.
Too little fluorescein on the cornea may result in a reading error due to the mires being too thin. This is usually not a problem unless the is a long time period between fluorescein instillation and measurement.
Lid contact with the applanator tip can cause a reading error because the contact will make the mires too thick. The lids can be held open with the operators fingers. Pressure on the globe by the operator's fingers or by patient lid squeezing can artificially raise the IOP. The operator should take care to only press the lids against the bony orbit and not against the globe.
Corneal astigmatism above 4 diopters may cause a reading error due to distortion of the mires from the normal circular shape. This error can be compensated for by aligning the red line on the applanator tip with the number on the mount that corresponds to the minus cylinder axis of the astigmatism.
Central corneal thickness (CCT) that is above or below normal can cause an error in the applanation tonometer reading. Corneal thickness that is significantly less than the normal 555 micron thickness will cause an underestimation of the IOP by the applanation tonometer. Thickness significantly greater than normal will cause an overestimation of the IOP. It has been estimated that a 20 micron change in the corneal thickness will affect the IOP by about 1 mmHg. Because of the CCT factor, pachymetry (measurement of corneal thickness) is an important measurement that your doctor may order for glaucoma patients. An erroneous reading can result from an applanation tonometer that is out of calibration. The calibration should be checked periodically. The tonometer must be serviced by a qualified service person if found to be out of calibration.

The Perkins tonometer is an applanation tonometer that is very similar in operation to the Goldmann applanation tonometer. It's advantage is that it is small and portable. This is also the disadvantage of the unit, in that it has no stable base from which to work. The headrest of the unit is placed on the patient's forehead and then the applanator tip is guided to the proper position on the cornea.


The Perkins tonometer The Schiotz tonometer

The Schiotz indentation tonometer was once widely used, but is now becoming scarce. This tonometer works by pressing a small metal shaft, through a base plate, onto the corneal apex. The softer the eye is, the farther the shaft will depress the corneal tissue. As the shaft moves downward, a small needle moves a corresponding amount along a scale that is converted to mmHg. The patient must be lying down looking straight upward with the anesthetized eye. Different weights are used to keep the needle in the middle range of the scale where it is most accurate. To operate properly, the unit must be disassembled and cleaned between patients. An eye with an abnormally hard or soft sclera can cause an erroneous measurement. This unit is still useful in the operating room because it can be sterilized. Although the Schiotz tonometer is portable and can be used for the bedridden patient, the Tono-Pen is more often used in this situation.

The Tono-Pen is handheld, can be used at almost any angle, and is easy to operate. It could be a standard IOP measuring device except that it is not always accurate, especially with pressure readings out of the normal range. A protective, disposable cover is placed over the tip, which is then touched against the anesthetized corneal apex. The instrument measures how much pressure is required to move a small plunger back into the instrument. The reading is then converted to mmHg.


The Tonopen A Non-contact tonometer

The Non-contact Tonometer is an instrument that works by puffing a jet of air toward the corneal apex. The unit measures how much time it takes to flatten a standard area of the cornea. Although the measurement takes a very short amount of time, the air puff tends to startle people. This unit is also most accurate in the normal pressure range, with decreasing accuracy in the higher range. Because it does not require eye drops to measure the pressure, this is a good screening device.

The physician can also estimate IOP by tactile pressure when no other measuring device is available. The finger is used to put pressure on the globe, usually through the closed lid. An eye that is relatively soft will have a relatively lower pressure, and vice versa. Obviously, the more experience the physician has with this technique, the more accurate the technique will be.

Serial IOP measurements Changes in IOP measurements over time can be an important factor in the doctor's decision making process regarding glaucoma. Consider the patient who has had IOP readings in the high teens for many years and then has successive readings in the low to mid twenties. This person may be at greater risk for glaucoma than the person who has had pressure readings in the low to mid twenties all along.

Optic Nerve Head Cupping

The nerve fibers travel from the brain through the optic nerve to the optic nerve head, from which they fan out over the expanse of the retina.



The retinal nerve fibers make up the top, innermost layer of the retina. Prolonged periods of above normal IOP damage the nerve fiber layer of the retina, specifically the retinal ganglion cells and their axons. The damage manifests itself as an atrophy or a degeneration of the nerve fiber tissue. The nerve fibers lose mass, and the nerve fiber layer loses thickness. Since the retinal nerve fibers collect in a bundle at the optic nerve head, this is a good place to observe these changes. In the normal topography of the optic nerve head, there is a dip in the tissue called the "cup" of the optic nerve nerve head. As glaucomatous damage progresses, the cup becomes observably deeper and wider. This is called "cupping" of the optic nerve head. Related to optic nerve head cupping is the appearance of the rim of the optic nerve head. Glaucoma causes the rim to become thinner and it may develop a notch. A standard way of recording and tracking the extent of cupping is with the "cup-to-disk ratio" or the "C/D ratio". If the width of the optic nerve head is divided into 10 units, then a cup that is 7 units wide would give a ration of 7/10, or .7. The greater this ratio is, the greater the apparent damage. In the optic nerve photos above, the cup on the left would be about a .5, and the cup on the right would be about a .9. However, some people have what is called a "physiological cup", meaning the nerve has a high C/D ratio, but the eye does not have glaucoma (as demonstrated by normal pressure readings and normal visual field tests). Because of this phenomenon, optic nerve head cupping is not an absolute indicator of glaucoma. What then becomes important is changes in the cupping over time. If the high C/D ratio is indeed physiological, then the C/D ratio will not change over time. If the high C/D ratio has been caused by glaucoma, then the eye doctor would see a worsening over time. Asymmetry in the optic nerve head cups is another indicator of glaucomatous changes. In most normal eyes, the appearance of the optic nerve heads is very similar. If the one eye or both have glaucoma, it is common to see more cupping in one eye than the other.

The eye doctor documents optic nerve head cupping by recording the C/D ratio, by drawing the profile of the optic nerve head, by taking a fundus photograph of the optic nerve head, or by using an instrument designed to map the optic nerve head topography. On subsequent visits, the information is compared in a search for any changes over time. Stereo optic nerve head photography has added another dimension to documentation of the optic nerve head. By adjusting the angle of view of consecutive photographs, the fundus camera can produce a "stereo pair" of photos that will give a 3-D view of the cupping when viewed with a special viewer. Although the additional information is useful, the technique is not entirely reproducible in that patient movement and camera technique can change the stereo effect. This means that an apparent increase in cup depth as compared to photos from the last visit may be due to a change in camera technique rather than being due to worsening glaucoma.

The Heidelberg HRT is an instrument that uses a scanning laser ophthalmoscope to map the optic nerve head topography.

		The software analyzes the topography of the cup, the rim, and the nerve fiber layer. It then compares the data to a normative ethnic database and it gives a "glaucoma probability score".


Retinal Nerve Fiber Layer (RNFL) Thickness Research has shown that there is significant loss of nerve fiber layer thickness before visual field loss is detectable with standard automated perimetry. For this reason, there have been efforts to produce instruments that will accurately and reproducibly measure the RNFL. As discussed earlier, the Heidelberg HRT uses a scanning laser ophthalmoscope to measure the RNFL. The GDx uses a scanning laser polarimeter to measure the the RNFL. The Zeiss Stratus OCT uses time domain optical coherence tomography. All three methods use software analysis to give the doctor information regarding the statistical significance of the scan, and all three compare the RNFL thickness of the scan to a normative database. The GDx printout is pictured below. The comparison is mapped on the so called "tee-snit" (TSNIT) graph (pictured directly above). The abbreviation stands for "temporal-superior-nasal-inferior-temporal", which are the quadrants of the circular measurement around the optic nerve head. A normal TSNIT graph will have the familiar "double humped camel" appearance, because the RNFL is normally thickest in the superior and inferior quadrants. Sources of error include poor image quality and eye movement during the scanning process. The HRT and the GDx have studies that indicate that the information they provide is statistically significant. The Zeiss Stratus OCT optic nerve scan suffers from a lack of registration, meaning successive scans may not be scanning the same area of the retina. Recent advances in high definition OCT instruments that register the scan to a retinal image may improve the OCT as a RNFL measuring device.

Visual Field Loss In the glaucomatous process, high IOP causes retinal nerve fiber loss, which eventually translates into loss of vision in the patient's visual field. The central part of the visual field is most commonly tested with the visual acuity chart, but this is the last area of vision that is lost in glaucoma. Early field loss occurs in the nerve fiber bundle area that fans out from the optic nerve head and surrounds the macula. The vision in this area is tested with standard automated perimetry.

There are several instruments that perform this testing, with the Humphrey Field Analyzer being the most widely used. One eye is tested at a time. The patient looks into a bowl and fixes his gaze on a central point. The instrument randomly projects points of light onto the bowl in a predetermined pattern. The patient responds with a button click when the point of light is seen. The instrument varies the intensity of the light stimuli in an attempt to find the level of the dimmest light that the patient can see on that particular point of the retina. In other words, the instrument is testing how sensitive the retina is to light in the areas that are most likely to lose sensitivity to glaucoma. See Modules 11 through 15 for more information.

The animation to the right demonstrates the correlation between the nerve fiber layer pattern and the glaucomatous visual field defect.

The red lines represent the pattern of the nerve fibers coming out of the optic nerve head and fanning over the expanse of the retina. The dot in the center is the fovea. The superior and inferior branches of the nerve fiber bundle meet at a horizontal line called the "horizontal raphe". The blue area represents a common glaucomatous nerve fiber layer defect called a "nerve fiber bundle defect". The corresponding visual field defect is called an "arcuate scotoma", or a "Bjerrrum scotoma". The black graph is a map of the visual field defect as the patient sees it. Notice that the nerve damage is below the horizontal raphe, but the patient experiences the defect in the superior field of vision. This has to do with the optical properties of the eye (see the Modules on optics). Below is an image of how this type of defect is displayed on a Humphrey Field Analyzer printout.
The problem with standard automated perimetry (SAP) is that there are many sources of error that call into question the results of the tests. An accurate visual field test requires the patient to maintain fixation on the target and to respond with accuracy to the stimulus presentations. It is not uncommon for the the patient to respond when a stimulus has not been presented, or to not respond to a stimulus that could be seen. Some patients even fall asleep during testing. As discussed in the Modules on visual field testing, there are various strategies designed to increase the reliability of automated perimetry. There have been studies that show that visual field defects can show up on SAP that are not caused by pathology, but are caused by the above mentioned sources of error. The defects disappear on subsequent testing. One study found that 86% of VF defects are not confirmed on retesting. So how is the ophthalmologist to know that a field defect is caused by glaucoma, or by some source of error in the testing? The visual field test printout will give the doctor several indicators of the reliability of the test. The doctor will give more weight to a test with good reliability scores. The doctor will also compare the results of serial field testing over time. Do today's results look worse than results from 6 months ago? Do last year's results look worse than the previous year?

As has been discussed, there is no absolute measure of glaucoma. The doctor must look at the IOP measurements, the appearance of the optic nerve head, the thickness measurements of the nerve fiber layer, and the results of automated perimetry in the glaucoma assessment. What carries the most weight is not the data on any one visit, but changes in the data over time. Is the patient getting worse in one or more of these areas of evaluation? This is why it is important for these patients to keep regularly scheduled appointments.

Back to top Get Post-Test