Glaucoma
Glaucoma, which is the second leading cause of blindness, is a chronic neuropathy of the optic nerve in which there is progressive degeneration at the optic disc (see lab). On visual examination, the rim of the optic disc becomes thinner and the optic disc cups inward. Histologically, retinal ganglion cell axons (see handout figure) degenerate, followed by their cell bodies.
The degeneration is linked to increased stress placed on the region of the optic disc by increased intraocular pressure. While increased intraocular pressure is not detected in every case, the reduction of degeneration is closely linked to reducing the pressure, and all the treatments are focused on this.
The increased intraocular pressure is due to excessive accumulation of aqueous humor. As we are studying in lab, aqueous humor is formed in the ciliary body, flows through the pupil, and exits through the trabecular network, which is found in the angle between the cornea and iris. An unusually good figure is found at this link. (May require login to UW system.)
While the trabecular meshwork is the primary, normal means of outflow of the aqueous humor, a second pathway does exist. Refer to the figure at this link showing the two means of outflow. While the second pathway, the uveoscleral outflow path through the interstices of the ciliary muscle, is much less important normally, apparently current drugs that increase drainage (prostaglandin analogs and alpha2 agonists) act through this pathway. Hopefully better drugs will be developed that target the trabecular meshwork since it is normally a much more open pathway.
Types of Glaucoma
There are two main types of glaucoma.
- Open-Angle Glaucoma. Open-angle glaucoma is the most common in the United States and typically does not cause overt symptoms until permanent damage has occurred. (In this respect, this disorder is like hypertension in the circulatory system in which it is unusually easy for patients not know they have the disorder or, if they do, to discontinue taking their medication.) The "angle" in the term refers to the angle between the cornea and iris where the trabecular network drains the aqueous humor. In open-angle glaucoma, this space is open so that there is no anatomical obstruction preventing the fluid reaching the trabecular network.
Closed-Angle Glaucoma. In closed-angle glaucoma, the angle between the edge of the cornea and pupil is narrowed to the extent that the aqueous humor has difficulty reaching the trabecular network, especially if the pupil is dilated. The patient usually seeks medical attention because acute episodes are painful and include symptoms such as halos around lights, and very high pressure within the eye causing dilated conjunctival blood vessels around the edge of the cornea. In the United States only 10% of glaucoma is of this type, although it is more common in certain populations. To the right is a picture of an eye in a closed-angle glaucoma crisis. Note the dilated blood vessels around the edge of the cornea. Photo is taken from Wikipedia.
An 80 year old woman is examined due to a complaint of slowly declining vision. She had a procedure called laser trabeculoplasty five years earlier. Which of the two types of glaucoma would is most likely?
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How do you suppose the physician might assess the actual damage that has occurred due to the glaucoma?
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Would the woman be slowly developing a blind spot over the part of the visual field detected at the optic disc?
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One hypothesis suggests that the transport of a type of substance back to the cell body is blocked as the elevated intraocular pressure pinches the axons at the optic disc. Apoptosis ensues. Based on earlier lecture material, can you speculate what type of substance this might be?
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Drugs Used in Glaucoma
Drugs used in glaucoma increase the drainage of the aqueous humor and/or reduce its rate of formation at the ciliary body. They are used mainly as eye drops. But enough of the drugs enter the circulation so some of side effects are systemic.
- Alpha2 adrenergic agonists both decrease the rate of formation at the ciliary body and increase the the drainage.
- Beta adrenergic antagonists decrease the rate of formation at the ciliary body. (Note, importantly, the alpha and beta receptors produce quite different actions in this case. While often true, don't draw any firm rules. Each system has its own characteristics.)
- Prostaglandin analogs increase the drainage of the aqueous humor.
- Cholinergic agonists decrease the production of aqueous humor and constrict the pupil, the latter effect being useful in closed-angle glaucoma.
- Carbonic anhydrase inhibitors act to reduce the formation of HCO3-, which in turn reduces solute and thus fluid secretion at the ciliary body. (In the kidney these are diuretics.)
- Cannabis apparently also reduces intraocular pressure significantly. The effect lasts 3 or 4 hours, so I suppose the drug needs to be smoked or eaten several times a day. Several marijuana shops have opened recently in my neighborhood, and I have been thinking about stopping in one of them to ask how they counsel people who need to pay attention at some point during the day. I don't believe the effect is supposed to be more effective than the conventional drugs.
The specific patient described above is being given timolol, which is a beta antagonist, and iatanoprost, which is a prostaglandin analog, as eye drops. Why would these two drugs be complementary?
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Surgical Treatments for Glaucoma
- Laser surgery is used to open up the trabecular network. The effect is not permanent.
- Conventional surgery can be used to create a opening through which the aqueous humor can drain out of the eye. There are a variety of techniques.
Risk Factors in Open-Angle Glaucoma
Risk factors in open-angle glaucoma include older age, black race, family history of glaucoma, myopia and especially elevated intraocular pressure. People with significant risk are usually urged to have a dilated pupil eye examination each year.
