SECONDARY TYPES OF GLAUCOMA
- Exfoliation syndrome
- Pigment dispersion syndrome (pigmentary glaucoma) occurs when pigment from the iris flakes off and blocks the meshwork. This slows fluid drainage and increases IOP.
- Lens-induced glaucoma
- Uveitis and other ocular inflammatory diseases
- Intraocular tumors
- Raised episcleral venous pressure
- Prolonged or excessive use of topical or systemic corticosteroids
- Axenfeld-Rieger and other syndromes
- Complications of eye surgery or advanced cataracts and traumatic eye injuries
TYPES OF GLAUCOMA
Glaucomatous disorders are classified into different types. The most frequently diagnosed types are primary open-angle, angle-closure and normal-tension, or low-tension, glaucoma.
People who maintain elevated pressures in the absence of nerve damage or visual field loss exist as well. They are considered at risk for glaucoma and have been termed glaucoma suspects or ocular hypertensives.
Early diagnosis is the key to successful management of all types of glaucoma. Treatment strategies generally entail IOP-lowering drops, but may include trabeculectomy or other surgery as well as newer, neuroprotective approaches.
PRIMARY OPEN-ANGLE GLAUCOMA
Primary open-angle glaucoma (POAG) is a major worldwide health problem. It is usually non-symptomatic and progressive in nature, and is one of the leading preventable causes of blindness in the world. With early screening and treatment, POAG can usually be diagnosed and its progress stopped before significant vision loss occurs.
POAG is distinctly a multifactorial optic neuropathy that is chronic and progressive with a characteristic loss of optic nerve fibers and cupping and atrophy of the optic disc. The loss of optic nerve fibers is associated with open anterior chamber angles, visual field abnormalities, and IOP that is too high for the continued health of the eye.
Elevated IOP is a risk factor associated with the development of POAG but it is not the disease itself. As with other forms of glaucomatous neuropathies, the exact cause of POAG is not known. Many risk factors have been identified, including elevated IOP, family history, race, age older than 40 years, and myopia. Elevated IOP is the most studied because it is the most clinically treatable risk factor for glaucoma.
Theories explaining how IOP may initiate glaucomatous damage fall into two major camps divided between the possible causative factors of vascular compromise and mechanical dysfunction. One possible explanation is the onset of vascular dysfunction causing ischemia to the optic nerve. Another theory is that mechanical dysfunction via the cribriform plate compresses the axons and impairs flow. Other contemporary hypotheses of possible pathogenic mechanisms include:
- Excitotoxic damage from excessive retinal glutamate
- Deprivation of neuronal growth factors
- Peroxynitrite toxicity from increased nitric oxide synthase activity
- Immune-mediated nerve damage
- Oxidative stress
The exact role of IOP in combination with these other factors and their significance to the initiation and progression of subsequent glaucomatous neuronal damage and cell death over time is still hotly debated in the clinical literature.
IOP is the only clinical risk factor that has been successfully managed to date. Several studies have shown the incidence of new onset of glaucomatous damage in previously unaffected patients to be about:
- 2.6-3% for IOPs in the range of 21-25 mm Hg
- 12-26% incidence for IOPs 26-30 mm Hg
- 42% for those higher than 30 mm Hg
The Ocular Hypertension Treatment Study (OHTS) found that patients with IOPs ranging from 24-31 mm Hg, but with no clinical signs of glaucoma, have an average risk of 10% of developing glaucoma over 5 years. The study found that IOP-lowering therapy reduced the incidence of POAG in trial participants by more than 50% after 5 years, from 9.5% incidence in the observation group to 4.4% in the treatment group
Patients with elevated IOP should not, however, be thought of as homogeneous. Several studies have shown that as IOP rises above 21 mm Hg, the number of patients developing visual field loss increases rapidly, most notably at pressures higher than 26-30 mm Hg. A patient with an IOP of 28 mm Hg is about 15 times more likely to develop field loss than a patient with a pressure of 22 mm Hg, for example. Before initiating treatment based on a specific IOP measurement, the following factors may be considered:
- Disc cupping and nerve fiber layer losses of up to 40% have been shown to occur before actual visual field loss has been detected. Visual field examinations, therefore, cannot be the sole tool used to determine when a patient has begun to sustain glaucomatous damage.
- Effect of corneal thickness has on accuracy of IOP measurements
- Variability of tonometry measurements between different examiners (found to be about 10% in studies)
- Diurnal variation of IOP (often highest in the early morning hours)
In cases where POAG is associated with increased IOP, the cause for the elevated IOP is generally accepted to be decreased outflow of aqueous humor through the trabecular meshwork. Increased resistance to flow may be caused by:
- Obstruction of the trabecular meshwork by foreign material
- Loss of trabecular endothelial cells
- Reduction in trabecular pore density and size in the inner wall endothelium of the Schlemm canal
- Loss of giant vacuoles in the inner wall endothelium of the Schlemm canal
- Loss of normal phagocytic activity
- Disturbance of neurologic feedback mechanisms
Other processes thought to play a role in resistance to outflow include:
- Altered corticosteroid metabolism
- Dysfunctional adrenergic control
- Abnormal immunologic processes
- Oxidative damage to the meshwork
ANGLE-CLOSURE GLAUCOMA
Angle-closure glaucoma (ACG) is a condition in which the iris is apposed to the trabecular meshwork at the angle of the anterior chamber of the eye. Angle-closure relates to anatomic factors in the anterior segment (shallow anterior chamber, crowded drainage angle, pupil block) compounded by pathophysiologic events. The iris may be pushed forward into contact with the trabecular meshwork, as in pupillary block or plateau iris, or it may be pulled anteriorly, as occurs with other inflammatory conditions. The position of the iris in either case causes the normally open chamber angle to close. Aqueous humor that should drain out of the anterior chamber is trapped inside the eye. Pain, blurred vision, and nausea may occur if the ensuing rise in pressure is sudden.
Damage occurs potentially both to outflow pathways and to the optic nerve head. This causes a dramatic and painful rise in IOP. If closure of the angle occurs suddenly, symptoms are severe and dramatic. Acute ACG is an emergency and immediate treatment is essential to prevent damage to the optic nerve and loss of vision. If closure occurs intermittently or gradually, ACG may be confused with chronic open-angle glaucoma. Intermittent episodes of ACG over a long period of time will cause glaucomatous damage to the optic nerve.
The most common cause of ACG is pupillary block. Normally, aqueous humor is made by the ciliary epithelial cells in the posterior chamber and flows through the pupil to the anterior segment. Here it drains out of the eye through the trabecular meshwork and Schlemm canal. If contact happens between the lens and the iris, aqueous accumulates behind the pupil, increasing posterior chamber pressure and forcing the peripheral iris to shift forward and block the anterior chamber angle. The anterior surface of the iris may be apposed to the posterior surface of the cornea or to the trabecular meshwork. This blockage causes accumulation of aqueous in the anterior chamber and an acute rise in IOP.
Plateau iris is a condition in which anterior insertion of the iris to the ciliary body causes the anterior chamber angle to become occluded on dilation of the pupil. The iris may insert on the anterior edge of the ciliary body, close to the trabecular meshwork. This may cause the patient to have genetically narrow angles despite a normal anterior chamber depth. The iris also may appear unusually flat, not bowed as might be expected in ACG. A diagnosis of plateau iris can be confirmed with ultrasound biomicroscopy.
Patients with hyperopic eyes showing shallow anterior chambers and narrow angles are predisposed to develop ACG. Dilation of the eye may precipitate an attack of acute ACG because the peripheral iris relaxes when dilated to mid-position. When the iris is relaxed, it may bow anteriorly and maximize iris-lens apposition, possibly causing pupillary block.
Some medicines have been implicated in causing acute ACG. These include sulfa-derivative medications such as acetazolamide, sulfamethoxazole, and hydrochlorothiazide. A newer sulfa-derivative medication, topiramate, which blocks glutamate receptors and is labeled for use in treating seizures, has also been associated with ACG. The presumed mechanism of angle closure involves swelling of the ciliary body with anterior displacement of the lens-iris diaphragm. Stopping the medication is effective in treating this condition and requires a high index of suspicion by the treating physician.
Other mechanisms that can cause the iris-lens diaphragm to be pushed forward may cause ACG. A space-occupying lesion such as a tumor or swelling associated with ciliary body inflammation may cause the iris to block the trabecular meshwork, is one example. Other causative factors include central retinal vein occlusion, placement of a scleral buckle, history of panretinal photocoagulation, and nanophthalmos.
Normal-Tension & Low-Tension Glaucoma
People can develop optic neuropathy of glaucoma in the absence of documented elevated IOP. Patients who do not have elevated IOP but glaucomatous optic discs or visual fields may have normal-tension glaucoma (NTG), or low-tension glaucoma (LTG). This is a diagnosis of exclusion (after other causes for optic neuropathy, such as temporal arteritis, have been investigated and ruled out).
NTG is a chronic optic neuropathy that affects adults. Its clinical characteristics are similar to POAG, including optic disc cupping and visual field loss, with the exception of a consistently normal IOP of less than 22 mm Hg. Patients with NTG experience a chronic loss of retinal ganglion cells (RGC) due to a genetic hypersensitivity to IOP.
Research studies show that NTG is associated with a variety of vasospasm and ischemic disorders and conditions including migraine, peripheral vasospasm and Raynaud syndrome, systemic vascular disease including atherosclerotic disease, systemic nocturnal hypotension, autoimmune disorders, and sleep apnea.
WHY YOU NEED TO BE CHECKED FOR GLAUCOMA!
Glaucoma afflicts between 5 and 6 million Americans, or 4 to 10% of the total population older than 40 years in the United States and Canada. It is a leading cause of irreversible blindness, second only to macular degeneration. Approximately 120,000 people in the U.S. and Canada are blind from glaucoma, accounting for 9% to 12% of all cases of blindness in the U.S. and Canada. Glaucoma accounts for over 7 million visits to physicians each year.
Glaucoma is the second leading cause of blindness worldwide. Glaucoma accounts for 10 million, or about 12%, of the estimated 83 million bilaterally blind people worldwide. Blindness is 10 times higher in the developing than in the developed world. POAG is responsible for almost half (46%) of the irreversible blindness from glaucoma worldwide.
Many types of Glaucoma have no symptoms. You should have your eyes examined regularly to rule out eye disease.
PRIMARY OPEN-ANGLE GLAUCOMA
Intraocular Pressure (IOP). Although IOP is no longer considered a diagnostic criterion, POAG is more likely to occur at a higher IOP. Multiple randomized, controlled trials have shown that a reduction in IOP slows the progression of visual-field defects and prevents the onset of POAG. IOP is now thought to be one of many factors that cause optic neuropathy leading to glaucoma. Many people with glaucoma have normal IOP and, conversely, some with elevated IOP show no signs of optic neuropathy. IOP undergoes diurnal variations, and elevation in IOP is suspected to be worse after falling asleep. Since pharmacologic treatment of POAG focuses on lowering IOP, an understanding of the process would be beneficial to pharmacists.
Aqueous humor (AH) is produced by the epithelium of the ciliary body and is used to supply nourishment to the cornea and lens. AH is secreted into the posterior chamber, flows into the anterior chamber, and then drains from there. A decrease in the outflow of AH from the anterior chamber increases IOP. There are two mechanisms by which AH is drained from the anterior chamber, the conventional and unconventional pathways. The conventional pathway involves the outflow of AH through Schlemm’s canal. The trabecular meshwork controls the flow of AH into Schlemm’s canal and ultimately the bloodstream. The unconventional pathway is a collection of pathways and involves the seepage of AH through optic tissues. The most common of these pathways is the uveoscleral route (Figure 1).