Why isn’t glaucoma either there or not there? - What makes you an open angle suspect?

“So, Dr. Quigley, if you’ve been studying and treating glaucoma for 40 years, how come you can’t tell me if I really have it or not?” While not every suspect for glaucoma who we meet asks this question straight out, we’re sure it must occur to a lot of them, and it has been asked quite a few times. The truth is that very few diseases are 100% clearly there or not there. For instance, an example of something that ought to be pretty straightforward is whether someone is alive or dead. I learned as an Intern that it’s not so easy to tell. In the middle of the night, on a cancer ward, I was awakened from sleep by the floor nurse who said I should go into Mrs. M’s room and “pronounce her” deceased. This nice lady had widespread cancer and I’d helped her through her last days. In the room, sitting at the bedside, I realized I hadn’t been taught the “rules” of how to be sure someone was gone. I watched for breathing for a minute. I used the blood pressure cuff and stethoscope but heard no sounds of blood moving. So, I was pretty sure. But, when I listened for her heart sounds, I could still hear her tummy grumbling. It was nearly a half hour before I felt confident enough to sign the paperwork. Likewise, you’re either pregnant or you aren’t, right ladies? Nope, since you could have a false positive test due to technical errors, or, the test could be positive if you have a disorder that makes the hormones the test thinks are only seen in pregnancy.

Diseases benefit from having very formal definitions. You may be aware that for life and death they sometimes use a test of brain electrical activity. But, until recently, both open angle and angle closure glaucoma had no agreed upon definitions of when they were present. This led to some doctors telling patients that they have glaucoma and others saying that they didn’t, even though both doctors agreed on exactly what the structure and function of the patient’s eyes were at the time. While there is room for judgment, a formal system was needed, and one was suggested by a panel that considered the issues and published their decisions in 2002.

The most important part of this glaucoma definition was to call it glaucoma only when there is measurable damage to ganglion cells, both structural and functional. This made formal a trend that most glaucoma specialists agree with now—namely, that we use the term glaucoma for damaged eyes, and call those in whom damage is either not present or might be present as “suspects.” For open angle glaucoma, this means that the level of eye pressure is not part of the definition. Not that it isn’t an important contributing feature, but we just don’t call it open angle glaucoma because the pressure is “elevated” or “abnormal.” There is now an international effort to update the formal definition of the optic nerve damage that qualifies someone as having glaucoma.

Open angle glaucoma suspects are suspicious for a variety of reasons. You may have a close blood relative with glaucoma. Your optic nerve head may naturally look similar to one affected by the early stages of glaucoma. In fact, there are a lot of people whose optic nerve head is big in diameter and these look to the eye doctor as if glaucoma has started, though it has not. Or, you may be one of the several million persons in the United States whose eye pressure is higher than the upper end of the average range (statisticians call this the 97.5 percentile, meaning only 100 minus 97.5 or 2.5% of people would have pressure that high). This is somewhere above 22 or 23 millimeters of mercury by tonometry and puts someone in the category of suspects for open angle glaucoma that are called ocular hypertensives. For 10 years, our Wilmer Glaucoma Center of Excellence followed the health of nearly 1,000 ocular hypertensives. Some were treated with eye drops, and some were not treated. We found that the rate at which they developed definite structural and functional damage (i.e. they got glaucoma by the formal definition), was about 2 out of 100 persons for each year that we watched them. That surprised some people who thought that the risk would be much higher. In fact, when a formal study was done nationally (the Ocular Hypertensive Treatment Study), our finding was found to be accurate. Furthermore, in this clinical study, half of the ocular hypertensive suspects were randomly assigned to take drops to lower pressure and half were assigned not to take drops. The rates of getting initial glaucoma per year were 2 in 100 in the untreated group and 1 in 100 in the treated group. We can conclude two main things: 1) treatment lowered the risk significantly, and 2) the risk is pretty low for the average ocular hypertensive suspect, treated or not.

Let’s stretch out the timeline for the ocular hypertensive suspect from when they first learn they have the problem (but not yet the disease) until when they are likely to die. Now I don’t know when any one person is going to die, but insurance companies make a lot of money by knowing how likely you are to die. They use this date to price your premiums. The average person at age 65 who is generally healthy will live on average for 20 more years. So, at the untreated suspect rate of 2% per year, they have about a 20 times 2%, or 40%, chance of getting early glaucoma damage in one eye. The other eye will probably still be normal at that point. An 80 year old person will live less than 10 more years, so for them the risk of being untreated is a 20% chance of one-eye damage (10 times 2%). In general, when the doctor finds that initial damage has begun, the patient won’t have been able to tell that anything is wrong with their vision. None of us wants to lose any function at all, so some persons who are suspects tell me that they want treatment in order to cut down this risk, even though the risk is very small. Others (in fact the majority) say that the risk sounds pretty small, and we can just carefully monitor the eyes’ status by ophthalmoscopy and imaging and visual field testing without treatment. This is particularly true for older patients.

Neither the suspect who chooses treatment nor the one who stays off treatment is making a bad choice. It depends on their actual risk (we’ll get more detailed in a moment), and their individual risk tolerance. Patients often ask me: “Would you start treatment for ocular hypertension if it was you, Dr. Quigley?” Before I answer them, I ask them if they want to know what kind of risk taker I am. For example, would you jump off a 40 foot cliff into a river without knowing for sure how deep it is? I once (foolishly) did that as a young person. Perhaps that shows some part of my own risk tolerance. The point is that the best way I can give treatment advice is to provide the best information we have on your actual risk and then ask how you feel about those chances. It isn’t the doctor’s choice to make, though some doctors act as if they have the answer etched on a stone tablet. It’s a shared decision.

We like to point out that people fall into different categories. Some people who are presented with the decision about treatment of their suspect status would go to bed every night convinced that they had lost another nerve fiber. They wouldn’t enjoy life as much from the worry. For that personality type, trying treatment is a good option. Another group of persons seems less worried by the disease than by the side effects of treatment. They’re convinced that drug companies are out to poison them (or at least to rob them) and they find the low level of worsening in untreated eyes to be not that scary. For them, careful follow up exams without treatment is the right choice. Yet, these two persons could have exactly the same statistical risk based on all the available information.

Asking which level of risk you can tolerate often helps to make the initial decision for a suspect patient. But, many others say: “I came to this big medical center to get your advice, so tell me what your opinion is”. If the decision is to be made mostly on risk calculation, then recent research based on the Ocular Hypertension study and extended by our group at Wilmer is important to consider. As we ticked of the contributing risk factors in the section How did you get glaucoma?, several factors had a measurable impact on risk of glaucoma damage. While the average untreated rate of conversion is 2%, there are those with less than 1% and some as high as 20% per year. The factors that increase risk that we can use mathematically to calculate the risk are: older age, higher eye pressure, larger cup to disc ratio, worse visual field test outcome, and thinner central cornea. If we take the actual number values for these factors and plug them into a formula for risk calculation, we can put each suspect on a scale of likely worsening. Many doctors are now doing this routinely as they help patients with their decision.

There are other risk factors that aren’t so easily incorporated into formal risk calculation. This is because they weren’t yet included in the data collected in studies that measure their impact or because they’re hard to quantify. These include degree of near-sightedness (myopia), presence of the exfoliation syndrome, having affected family members, low blood pressure, and being of African-derived ethnicity. Most eye doctors would increase risk for each of these and increase it a lot when someone has more than one.

Finally, we said that the risk is 2% per year, so if you are expected to have 50 more years of life, your chance of having some damage is expected to be 100%. This leads to the paradox that older age increases the risk of developing glaucoma, but a 40 year old person is more likely to develop damage than a 70 year old over the course of their remaining lives—if both start at those respective ages with the same level of other risk factors. So, we are much more likely to recommend treatment as a good option for the young ocular hypertensive than the elderly one. It isn’t that we don’t love and care for our senior citizens, especially now that one of us has signed up for Medicare. You may be a 75 year old suspect who has thought through all the issues and wants to take eye drop treatment despite hearing that it’s not “cost-effective.” On the other hand, if you’re an 80 year old who’s been taking drops for years and have very low risk, you may wish to discuss a temporary stopping of treatment with your doctor to see how it goes. Whether you choose treatment or no treatment, you’re going to continue careful monitoring by ophthalmoscopy/imaging and visual field testing, regardless.