Monthly Archives: January 2007

The Genographic Project

Last night I went to hear Dr Spencer Wells speak at Benaroya Hall. He is the leading geneticist and director of The National Geographic Genographic Project. If you have not yet heard of his project, it is quite fascinating. By collecting DNA samples from every corner of the Earth, he is creating a very detailed family tree that reveals how every one of us is related. His data has shown that we were all related to each other through a common ancestor only 2000 generations ago. Last night, he gave an update on the data that he and his colleagues have collected so far over the past 2 years. One important theme he stressed was how the migration pattern of DNA responded to climatic change. He showed several slides of how the earth appeared over the past 50,000 years, showing how the African deserts as well as Asian coast lines were significantly affected by the 20,000 yr cycle of the Earth’s axial shift. He also showed how this time line corresponded to the time when our human ancestral “Adam” and “Eve” first migrated out of Africa. Another interesting story was how a Hungarian woman who participated by supplying her DNA, complained that her lineage analysis must have been incorrect because it showed that she was from Asia. That led him to further analyze all the Hungarians in the data pool which confirmed the early Asian origins of at least 5% of the Hungarian population.

Although analysis is currently limited to only the Y and mitochondrial DNA, perhaps migration patters will be sufficient to help explain some of the interesting patterns of disease incidence found in some populations but not others.  For example, the Inuit Eskimos and ethnic Chinese share a high incidence of angle closure glaucoma, where as the Japanese population does not.  An early separation of the Japanese population from the ethnic Chinese might explain this.  This information might help clinicians to better asses risk for diseases that might be more common in certain populations but that we do not have a specific genetic test for yet.  Especially for patients who are Hapa or of mixed ancestry, this type of individualized ethnic background data could help patients at least receive more optimized preventative medicine.

Angle Closure Glaucoma

When you last saw your ophthalmologist (EyeMD) or optometrist (OD), did he or she examine your eyes to rule out angle closure glaucoma?

Asians, particularly South Asians, ethnic Chinese and the Inuit Eskimos have been found to have a significantly higher incidence of a certain form of rapidly progressive and blinding glaucoma. In Caucasian and the African American population, the incidence is approximately 0.5%. In some Asian populations however, angle closure glaucoma is found as high as 3%, with 14% of the population having anatomically narrow angles. (Bourne RR 2003). Interestingly there is a significant amount of diversity among the Asian populations. A study of a Japanese population found incidence rates more comparable to those of non-Asian populations. (Iwase A et al) For those high risk Asian populations, this condition is their leading cause of blindness (Foster PJ 2000). More importantly, if detected early, this blindness is essentially preventable with a laser procedure.

Why are some Asians so much more likely to develop this type of eye problem?

The primary reason is because for these populations, the eye anatomy is significantly different. Although these differences can seem extremely small, measured in microns, comparative data over the past few years is beginning to reveal how clinically significant these differences can be. As with any difference, there is always a plus and a minus side.

Iris differences are an extremely interesting topic and probably deserve a separate discussion elsewhere. Beyond the most visible and obvious, iris color, the iris thickness, surface area and texture are also significantly different in Asians. Iris recognition technologies will soon (if not already) be able to categorize us all by racial ethnic background. As would be expected, for any differences in anatomy, there will be medically significant differences that result in varying disease incidence. As it turns out, some of the differences in the iris shape and positioning also greatly influence the likelihood of developing a certain type of glaucoma.

First I must explain which eye structures are involved in glaucoma. Where the iris meets the inside surface of the eyeball or globe, an angle is formed between the cornea and the shelf of the iris. In the corner of this angle is a drain that lies just anterior to the edge of the iris, called the trabecular meshwork. This is the primary outlet for the liquid aqueous humor, which is produced behind the iris, to slowly drain out of the eye and back into the blood stream. If this trabecular meshwork becomes clogged or malfunctions and the aqueous humor builds up, the eye pressure increases like much like pumping up a basketball. The higher the eye pressure, the smaller the pressure gradient for blood flow into the eye. Over time, high eye pressures essentially choke the retinal cells to death, resulting in an irreversible blindness called glaucoma.

Different types of glaucoma are typically classified by how the trabecular meshwork is inhibited. In open angle glaucoma, which causes nearly all the glaucoma in Caucasians and African Americans, the iris tissues are not occluding the trabecular meshwork. For them, the cause is usually with the trabecular meshwork itself. In angle closure, however, the trabecular meshwork is covered by the base of the iris. If the angle closes suddenly, the eye pressure can rise rapidly characteristically causing severe pain, nausea and “smoky” vision. More often however, the angle closes slowly in a creeping fashion or following recurrent milder episodes.

Asians are predisposed to this more severe form of glaucoma partly because their irises attach to the inside surface of the sclera (white fibrous framework tissue that shapes the globe) slightly more anteriorly, closer towards the cornea. This results in an anatomically narrower angle with a less exposured trabecular meshwork to begin with. This is particularly true of hyperopes, people who are far-sighted and wear magnifying type glasses. These hyperopic eyes are shorter than normal or near sighted eyes, and therefore have some extra crowding of their iris/cornea angles.

How do you know if your angles are narrow?

Gonioscopy is the close examination of the iris angle under a microscope using a contact lens. The angle structures are not visible without this contact lens. Although this procedure is still the gold standard to detect narrow or occludable angles, new machines are being developed for screening purposes. Using high frequency ultrasound, or UBM (Ultrasound Bio Microscopy), a cross sectional image can be taken through the eye to reveal narrow or suspicious angles. The advantage to this machine is that it will allow visualization through the iris to see what might be causing the iris to be pushed forward. A newer machine called the Visante-OCT (Carl Zeiss Meditec), can image the anterior structures without requiring any contact with the eye surface and performs as well as UBM. The comfort and simplicity of use will likely make this the easiest screening tool for patients. As it can be performed in the dark, when angle structures are likely to be most crowded, OCT may prove to be a better method of screening than gonioscopic examination.

If you do have narrow angles, what can be done to prevent angle closure glaucoma?

A laser treatment, called Laser Peripheral Iridotomy (LPI) has been used to prevent angle closure from occurring in at risk patients by preventing pupillary block. Pupillary block is usually only a transient event when the pupil opening forms a valve like seal against the lens. This typically occurs during transition into a darker room where the pupil achieves mid-dilation. When this happens, the aqueous fluid which is produced behind the iris builds up volume and pushes the lens-iris complex forward, shallowing the entire anterior chamber. In narrow angled patients, this can suddenly block off the trabecular meshwork inducing acute angle closure.

By lasering a hole through the iris, a safety passage is created that allows the aqueous to flow through the iris during these normally harmless transient episodes of pupillary block. This prevents pressure built up that moves the entire iris forward pushing an anatomically narrow patient into closure.

Unfortunately, persistently narrow angles after a LPI appears to be significantly more common than we once believed, occurring in perhaps 20% (updated 4/07) to 50% of Chinese. Sometimes this is due to scar tissue keeping the angles held closed, but in many the angle remains narrow be caused by what has been called plateau iris configuration.

In plateau iris, there is an anatomical tendency for the iris base to be pushed forward by the ciliary body, but leaving the rest of the iris flat. Narrowing of the angle in plateau iris is not the result of pupillary block, so LPI will have little or no effect. For these patients, another laser procedure called Iridoplasty can be performed to create a ring of scars on the peripheral iris surface that “pulls” the iris base away from the trabecular meshwork. This procedure is not without complications, and unfortunately it does not relieve the anterior positioning of the iris processes that have been pushed forward by a thick lens. Following earlier reports that standard cataract surgery with implantation of an artificial lens deepened the angle by about 10 degrees and deepened the anterior chamber by as much as 850um, some have proposed that cataract surgery be performed prophylacticly rather than LPI and iridoplasty, as removal of the lens relieves both pupillary block and the anterior positioning of the ciliary body. I believe narrow angles will become a new indication for cataract surgery, especially for the aging Asian population.