Don’t be blind-sighted by glaucoma; the best defense against glaucoma is through early detection and treatment
Patrick Perry
An interview with Dr. Darrell WuDunn
The number one cause of preventable blindness, glaucoma was once inextricably linked to increased intraocular pressure (IOP). Pioneers in glaucoma research, however, disproved the assumption, after discovering significant damage to the optic nerve in patients with IOP in the normal range. Ophthalmologists then redefined the disease, affecting an estimated three million people in the United States, as a characteristic optic neuropathy that damages the cellular fibers in the optic nerve, which processes vision into signals sent to the brain.
Certainly, elevated pressure is a primary factor in glaucoma, but not the only one. Many individuals can harbor significant optic nerve damage, yet maintain eye pressures within the accepted guidelines, a condition called normal tension glaucoma (NTG).
How can one best defend against the disease? To learn more about advances in early detection, prevention, and treatment of glaucoma, the Post concludes its interview with ophthalmologist and researcher Dr. Darrell WuDunn from Indiana University School of Medicine.
Post: How is normal tension glaucoma treated?
WuDunn: Basically, normal tension glaucoma is treated not very differently than regular glaucoma in that we try to lower the intraocular pressure. A national trial–the Collaborative Normal Tension Glaucoma Study–found that compared to people with untreated normal tension glaucoma, people who were treated for normal tension glaucoma showed decreased rates of progression. The trial clearly showed that if you lowered pressure–and they used a 30 percent drop in pressure as their goal–the rate of progression dropped by two-thirds. Clearly, lowering intraocular pressure in normal tension glaucoma is helpful.
Another key finding was that the disease in some people progressed, even though pressure was lowered, and many people without treatment showed no progression. Once you are diagnosed with normal tension glaucoma, it does not necessarily mean that you are going to get worse.
Lowering pressure does involve eye drops, which we try first. If eye drop treatment is inadequate at lowering the pressure or presents with too many side effects, we can try laser treatments or surgery. The goal of all therapies is to lower intraocular pressure.
Post: How low do you go with IOP?
WuDunn: We usually shoot for a 30 percent drop, but I typically want to shoot for an IOP around 8 to 10.
Post: You wouldn’t go below 8?
WuDunn: Eight is about the limit. If pressure goes lower than six, for example, one can develop what we call hypotany, where the eye becomes basically too soft and starts to wrinkle.
If you think of the eye as a basketball, you need enough pressure inside the eye to maintain its normal shape. If the basketball is not inflated enough, the ball doesn’t bounce right. Similarly, the eye needs to have a minimum amount of pressure to keep everything in the right place; otherwise, it starts to fold and dent.
The only way that we can lower pressure too much is with surgery. Eye drops or laser surgery will never get the pressure down low enough to cause a problem. But in surgery, we are actually bypassing the eyes’ drainage system and can get the pressure down to zero very easily, which we try to avoid.
Post: Would a strong family history suggest the need to monitor a person more closely?
WuDunn: If you have a congenital history of glaucoma of any sort, it raises my index of suspicion that you are at higher risk for glaucoma, be it normal tension or high tension or any other type of glaucoma.
Post: What is the next step if ocular tension isn’t as low as you would like it in someone you consider to have normal tension glaucoma?
WuDunn: We treat persons with normal tension glaucoma in much the same way we treat persons with other types of glaucoma. If the ocular tension is not as low as we want with our treatment, then we advance treatment to the next step. We can switch to or add another medication, or we can recommend laser trabeculoplasty or glaucoma surgery.
Post: Would that step include, for example, taking another medication such as Lumigan twice a day to lower pressure?
WuDunn: Lumigan is best taken just once a day. In fact, studies have shown that once-a-day Lumigan lowers ocular tension better than twice-a-day Lumigan. If Lumigan by itself is not lowering pressure enough, then adding another drop such as brimonidine or a beta-blocker is usually the next step. In many instances, laser trabeculoplasty is a good option.
Post: What is pseudoexfoliation syndrome?
WuDunn: It is a type of glaucoma more typically found in people of Northern European or Scandinavian ancestry. In pseudoexfoliation syndrome, material on the lens and throughout the anterior chamber of the eye can clog up the drainage channels and cause pressure to elevate. If and when it progresses to glaucoma, it is called pseudoexfoliation glaucoma, a secondary type of glaucoma.
Post: What is the difference between primary and secondary glaucoma?
WuDunn: Most glaucoma in the United States is primary open-angle glaucoma, which basically means that there is pressure elevation or optic nerve damage, but there is no reason–that we can ascertain–for the elevated pressure.
In secondary glaucoma, either open- or closed-angle glaucoma, there are other reasons–for example, pseudoexfoliation material, pigment material dislodging from the iris and obstructing the eye’s drainage structures, inflammation in the eye, trauma, or chronic steroid use, all of which can cause pressure to go up. If we find a reason for the elevated pressure, we call it secondary glaucoma. If we can’t find a reason, we call it primary glaucoma.
Post: If someone has myasthenia gravis or a similar disorder and takes prednisone or another steroid, could that cause glaucoma?
WuDunn: Absolutely. Many conditions–such as asthma, where you take inhaled steroids–can cause IOP to elevate. Chronic topical steroid use for various disorders can cause pressure elevations, as can inflammation in the eye–all of which can lead to glaucoma.
If people using topical steroid creams don’t wash their hands after application and rub their eyes, they get a lot of steroid load into their eyes, which can cause eye pressure to elevate.
Post: Are boxers at higher risk for developing glaucoma?
WuDunn: That is certainly a potential cause of glaucoma. Basically with trauma to the eye, you can damage many structures in the eye, including the drains. Decades later, boxers could show glaucoma. If you can find a history of trauma to an eye, glaucoma usually develops in that eye.
Post: When airbags activate, can they potentially cause the damage to eyes that could lead to glaucoma?
WuDunn: We haven’t seen enough injuries as yet, but certainly that could cause trauma to the eye. Down the road, we will likely see more glaucoma secondary to airbag injury.
Post: Is there a connection between chronic low blood pressure and normal tension glaucoma?
WuDunn: It is an area of research, but a direct link has not yet been established. We know that traumatic loss of blood, heart attack, or massive hemorrhage with acute blood pressure drop can cause an optic neuropathy. Years later, even though everything has been corrected, it can appear like glaucoma. The injury caused damage to the optic nerve, looking like what is called cupping.
Post: What is cupping?
WuDunn: One of the signs of glaucoma is optic nerve cupping. Basically, cupping is loss of nerve tissue at the optic nerve disc. Pressure is normal, but patients may have optic neuropathy and visual field loss, so it is sometimes hard to differentiate between normal tension glaucoma and this other condition. But as I said, the hallmark of glaucoma is progression, so if the condition doesn’t progress, it is probably not glaucoma.
Post: If a patient continues the drops for years, can drops, such as the beta blocker Timolol, lower systemic blood pressure?
WuDunn: Timolol can lower systemic blood pressure. Studies show that drops can lower pressure a couple of points, depending upon how much is absorbed by the body.
I advise my patients when putting a drop in their eyes to close the eye for several minutes. By doing that, they reduce the amount of drop that enters the tear duct and sinuses, which is where it gets absorbed into the body. Every time you blink, you pump tears down the tear duct into the sinuses. When you cry or tear from irritation, nasal passages can get stopped up. If you don’t blink and keep your eye closed for a few minutes, the drop actually gets absorbed into the eye and not into the body.
All glaucoma drops can cause side effects. But the drops are safe, so it is unlikely that someone would have a heart attack or serious event while on drops, but it should be monitored.
Post: Could you discuss research on the role of neuroprotective drugs in eye disease, such as Copaxone used to treat multiple sclerosis?
WuDunn: An emerging area of research, neuroprotection is not just confined to the eye. Glaucoma is an optic neuropathy or disorder of nerves. A common theme among all neurodegenerative disorders is that you can have the primary insult to the nerve itself–say, from elevated eye pressure–but there is always secondary damage. First, nerve fibers injured by elevated pressure die off. When they die, they release toxins that cause collateral damage in surrounding nerve tissue not directly damaged by the primary insult from elevated pressure, for example. In short, the primary insult causes damage to individual nerve fibers, which release toxic substances that cause damage to surrounding tissue or secondary neurons.
Most neuroprotective therapies involve protecting secondary neurons. You can’t really help the primary nerve when it is damaged or killed off by insult, but you can prevent the collateral damage. Some of these therapies, like Copaxone, involve modulating the immune response to reduce the collateral damage often due to an inflammatory reaction. Neuroprotective agents serve as immune modulators, or cells that help clean up debris before the debris causes damage to other cells or nerve fibers. It boosts the immune response, which is protective. We are optimistic and hopeful about the potential of the therapy, If neuroprotective therapies work, they would be great new tools in treating glaucoma, because other than lowering eye pressure, we presently have no good treatments for the disease.
A neuroprotective medicine called memantine was recently approved to help treat Alzheimer’s disease. Research is under way to see if memantine may be able to protect the optic nerve in glaucoma.
Post: Could you discuss the potential of stem cells in future therapy?
WuDunn: Stem cell therapy is probably a long way off, but it certainly has potential. Any way that you can regenerate optic nerve or any type of nerve tissue has some promise, because now we have no way of restoring any damaged nerve tissue.
Stem cells have the potential not just for the optic nerve, but also for the pressure control as well. We think that pressure gets elevated because the ceils in the drains of the eye are not functioning well. They show senescence or aging and appear much older than they should be. By using stem cells, we could perhaps regenerate these cells, which may help control eye pressure better because drains will function better.
Post: Can family members calculate their risk if they know they have three or four relatives, for example, with glaucoma?
WuDunn: For glaucoma in general, if you have a sibling with glaucoma, your risk is two- or three-fold higher than the normal population, If you have a parent, it is, like, 1 1/2 times the risk. There are no statistics specific for normal tension glaucoma.
We think people most at risk for normal tension glaucoma are those with what we call vaso-spastic phenomena, such as migraine headaches or Raynaud’s phenomenon.
Females may be more affected than males, but that may be because there are more older females than males.
Post: How can we raise awareness of glaucoma?
WuDunn: The key issue with glaucoma is getting an ophthalmic examination, which is the only way to make an early diagnosis.
My advice is get a good optic nerve examination and possibly a visual field examination. We can also take pictures of the optic nerve and scan the optic nerve, using tests such as optical coherence tomography (OCT) or scanning laser ophthalmoscopy (SLO). In glaucoma, there are no symptoms. You can’t feel normal tension glaucoma, and you don’t know there is vision loss until very late in the disease. Sadly, we estimate that about half of the people in the United States with glaucoma are never diagnosed.
Post: Are people with glaucoma at higher risk for macular degeneration?
WuDunn: There is no association between the two conditions. You can certainly have both just by chance, or you can have one or the other. If you do have both, unfortunately MD affects the central vision and glaucoma affects your peripheral vision. Obviously, that is not good.
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