Glaucoma is the second leading cause of irreversible blindness worldwide. The disease affects about 5 million Americans, mostly over age forty. Distressingly, many of these individuals are unaware of their affliction until long after the optic nerve has already been permanently damaged.
The term “glaucoma” refers to a group of similar conditions that damage the retina and optic nerve, leading to visual impairment. Glaucoma is sometimes called a “silent thief” because it slowly robs its victims of peripheral vision, which can go unnoticed until the loss becomes significant enough to interfere with everyday life.
Although glaucoma-related vision loss is not reversible, the progression of the disease can nearly always be slowed or halted. When diagnosed and treated early, it seldom leads to blindness.
Prescription medications and surgery can control the clinical manifestations, but the most commonly prescribed drugs carry unpleasant side effects, while there are risks associated with surgery.
Fortunately, recent scientific studies have illuminated natural strategies to help attenuate the progression of glaucoma. Investigations have shown that a combination of plant-based interventions derived from French maritime pine bark and bilberry target one of the most common underlying problems with glaucoma: increased pressure in the front of the eye, a condition known as elevated intraocular pressure (IOP).
Human studies reveal that these natural compounds complement conventional glaucoma medications as well, acting synergistically to optimize intraocular pressure (Steigerwalt 2010).
Moreover, conventional therapies do little to address a major contributor to visual impairment in glaucoma - mitochondrial dysfunction (Lascaratos 2011; Lee 2011). Coenzyme Q10 and pyrrloquinoline quinone (PQQ) are two powerful mitochondrial protectants that may play a considerable, yet unappreciated role in maintaining visual acuity for glaucoma patients.
After reading this Life Extension protocol, you will understand how glaucoma emerges and discover that making lifestyle changes to control risk factors can lessen the risk of glaucoma development and progression. You also will learn about exciting findings related to a number of natural compounds with the ability to target multiple mechanisms underlying the progression of glaucoma.
Structures of the Eye
Back of the Eye
The eye is a spherical structure. It is connected at its rear pole to the brain via the optic nerve. The optic nerve is a fibrous tube containing over one million horizontally running nerve fibers (axons), each one originating from a type of retinal cell called a ganglion cell. The retina and optic nerve are pictured in Figure 1.
The retina is composed of a thin sheet of cells (and related structures) that form the back wall of the eye. Its primary role is to capture light and transform it into electrical signals. The signals are transmitted to the brain by the optic nerve, where they are interpreted as the objects we “see.”
Ganglion cell axons are responsible for transmitting these electrical signals. The axons spread out across the retina to converge at the optic disc, the point of origin of the optic nerve. The optic disc is where damage from glaucoma is typically detected by an eye exam.
Front of the Eye
When we look at our eyes in the mirror, we see four main features of the front of the eyeball: the white sclera, the black pupil, the colored iris, and the dome-shaped cornea overlaying the iris and pupil. In most cases of glaucoma, the trouble lies immediately behind the cornea in the outflow of a fluid called aqueous humor (or aqueous fluid). Normally, aqueous humor flows from behind the iris (posterior chamber), where it is formed, to the front of the iris (anterior chamber) where it drains through the trabecular meshwork into Schlemm's canal and ultimately into the blood circulation (Figure 2). Aqueous humor should not be confused with tears, which are formed outside the eye.
Types of Glaucoma
There are two major forms of glaucoma: open angle glaucoma and angle-closure glaucoma. About 90% of cases of glaucoma are primary open angle glaucoma (POAG). The majority of others are angle-closure glaucoma.
Less common forms of glaucoma include congenital glaucoma, which tends to run in families and is present at birth; normal tension glaucoma; pigmentary glaucoma; pseudoexfoliative glaucoma; traumatic glaucoma; neovascular glaucoma; and irido corneal endothelial syndrome.
In the last several years, glaucoma has come to be described as a “neurodegenerative disease”, because it shares features with several brain disorders including Alzheimer's disease, amyotrophic lateral sclerosis (Lou Gehrig's disease), and Parkinson's disease (Gupta 2007).
Signs and Symptoms of Glaucoma
Signs and symptoms of glaucoma differ depending upon the type of glaucoma. Most patients do not have any symptoms in the disease's early stages. Others may experience severe pain and rapidly compromised vision. Even without symptoms, people with glaucoma are vulnerable to a loss of peripheral vision, followed by reductions in central vision and blindness. (Symptoms should always be reported to the examining ophthalmologist or optometrist.)
Risk Factors for Glaucoma
There are many risk factors for glaucoma, ranging from factors you can not control (genetic abnormalities and age) to lifestyle factors. Some of the known risk factors for glaucoma include:
Having a family history of glaucoma is a well-established risk factor, and the role of genetics in glaucoma continues to receive scientific scrutiny. In the late 1990s, researchers began identifying glaucoma gene mutations, including several in a gene that encodes for the protein TIGR found in the trabecular meshwork. They discovered the mutations by studying families with POAG. The mutation occurred in 4.4% of these patients, compared to 0.3% of the general population (Stone 1997).
Since then, several other genes (e.g., MYOC, OPTN) have been associated with POAG. Among the most recently noted is ADAMTS10, which was discovered in a unique population of beagles with glaucoma (Kuchtey 2011).
Another gene linked to glaucoma is CYP1B1. In some populations, CYP1B1 mutations are found in over half of all cases of congenital glaucoma (Patel 2011).
Researchers expect to find many more genes and other events involved in the initiation and progression of glaucoma. An important aspect will be to identify people with genetic and other risk factors and to counsel them about ways to reduce the likelihood of developing glaucoma.
Lastly, other drugs besides steroids can raise the risk of glaucoma, especially of angle-closure glaucoma. Categories of drugs known as anticholinergics, and adrenergics are the most common. Sulfa drugs, antihistamines, and decongestants can also cause problems. And several anti-cancer drugs can increase the risk of open angle glaucoma. Because the cause of the glaucoma is linked to the particular drug usage, the first line of treatment is to discontinue the drug. Note: If you have glaucoma, make sure to inform your healthcare provider and pharmacist. They should know what drugs to avoid.
Pathophysiology of Glaucoma
In the past, doctors thought of glaucoma as a disease with only one major feature: increased intraocular pressure (IOP), or essentially raised pressure in the eye. Although we now know that glaucoma can occur even in people with normal IOP, this is still the most common underlying symptom of the disease. In the most common form of glaucoma - open angle glaucoma - IOP can be subtly raised long before symptoms become discernible to the patient. This provides a critical window of time during which aggressive measures can be taken to reduce IOP and head off symptoms before they develop; hence the importance of regular eye check-ups, even if you do not have any symptoms. Once symptoms manifest and glaucoma is detected, it is important to take immediate and aggressive action to protect your eyesight.
Elevated IOP is caused by abnormal drainage of aqueous humor from the front chamber of the eye. In a healthy eye, fluid from the front chamber drains into a region known as the trabecular meshwork through an acute angle formed by the intersection of the cornea and iris. If the fluid cannot drain through this angle, it backs up into the eye itself, causing elevated IOP. There are two main reasons for a blockage at this angle: either the angle remains open and the fluid has complete access to the trabecular meshwork but for some reason its outflow is impeded (open angle glaucoma), or there is a physical barrier in the angle, sometimes caused by deformity in the iris, that causes reduced flow (closed angle glaucoma).
Open angle glaucoma
Open angle glaucoma occurs even though there is no obstruction to the flow of aqueous humor. It may be caused by a mutation in the GLC1A gene, which is responsible for the production of a protein called myocilin that is normally present in the trabecular network. This condition is known as primary open angle glaucoma (POAG). Secondary open angle glaucoma can be caused when particulate matter, such as clumps of protein and shedded portions of surrounding cells and fibers, clog the outflow channels.
Importantly, the events leading to impaired trabecular meshwork drainage in non-genetic open-angle glaucoma share several pathological characteristics with atherosclerosis, such as endothelial dysfunction (Bulboaca 2003; Resch 2009; Venkataraman 2010). Therefore, individuals who wish to preserve the integrity of their trabecular meshwork should consider the suggestions in Life Extension's Atherosclerosis and Cardiovascular Disease protocol as well.
Closed angle glaucoma
Primary angle-closure glaucoma is most common in eyes with a shallow (flatter) front chamber. Secondary angle closure glaucoma is usually related to abnormal biological events in the eye, such as displacement of the iris against the cornea, which inhibits the aqueous humor from reaching the trabecular meshwork. Surgery or trauma to the eye can also lead to scar tissue that interferes with drainage. Tumors, too, can grow in the aqueous production and outflow system and interfere with the trabecular meshwork.
Congenital glaucoma is present at birth. It is related to improper formation of the aqueous fluid outflow system during fetal development. Several gene mutations have been associated with congenital glaucoma. Congenital glaucoma is usually diagnosed at birth or within the first year of life (Mandal 2011).
Normal tension glaucoma
Not all people with glaucoma have elevated IOP. When IOP is normal but the person still has typical symptoms of glaucoma, the condition is called normal tension glaucoma.
Pseudoexfoliative glaucoma (PEX) is distinguished by clumps of amyloid protein that accumulate in the eye and ultimately end up blocking the outflow of aqueous humor by clogging the trabecular network. The cause is unknown, although a mutation in the LOXL1 gene may play a role. PEX is more common in women and in people of Northern European dissent.
Anatomic Changes in Glaucoma
In glaucoma, the retina and optic nerve at the back of the eye grow thinner as ganglion cells and axons die. This thinning can be seen by a doctor during an ophthalmic exam. Eye doctors refer to the visible changes as “cupping.”
A relatively new technology called optical coherence tomography (OCT) allows physicians to measure the progressive thinning of the retina and the cupping of the optic nerve and correlate the changes with visual field loss. Researchers have proposed that OCT be used for studying the effect of new drugs and devices being developed for treating glaucoma (Weinreb 2011). Other common tests, which provide similar diagnostic information, include Heidelberg Retina Tomography (HRT) and the GDxTM Nerve Fiber Analyzer (GDx).
Beyond the visual symptoms of cupping, glaucoma's damage extends deep into the cells of the eye. Like all human cells, the cells of your eyes are full of structures called mitochondria that produce energy for the cell to function. In glaucoma, researchers are learning that the mitochondria in the retinal ganglion cell become damaged. Without healthy mitochondria, cells are unable to engage in a natural repair processes following normal wear and tear, oxidative stress, and injury. As a result, the retinal ganglion cells become susceptible to a process called apoptosis, or cell death (Kong 2009).
In the eye, it appears that oxidative stress is a major feature of mitochondrial damage. Free radical attack in the sensitive retinal ganglion cells causes mitochondrial damage, which in turn causes cell death. Excessive calcium within the cells is also implicated in retinal ganglion cell death (McElnea 2011). Life Extension has long been at the forefront of identifying novel, natural ways to boost mitochondrial health.
Researchers have also uncovered another possible contributor to retinal ganglion cell death: excessive glutamate. Glutamate is the body's main excitatory neurotransmitter. Although it is vitally important to a healthy brain and nervous system, too much glutamate is toxic because it causes overstimulation of nerve cells. Normally, glutamate is cleared quickly. In glaucoma, however, it appears that high levels of glutamate in the retinal ganglion over-stimulate cells, resulting in cell death. Researchers are looking at ways to reduce glutamate signaling in the eye, thus protecting the retinal ganglion cells from its toxic effects. This could be especially important for patients whose glaucoma does not respond to IOP-lowering treatment (Fang 2010).