Glaucoma is a group of conditions characterised by a progressive loss of vision. Glaucoma is classified as primary or secondary. The most common type of glaucoma, called “primary” open angle glaucoma, is a chronic disturbance of the normal fluid pressure inside the eye and is generally age-related. “Acute” or secondary closed angle glaucoma is more rare and is identified by a sudden, painful shutting down of the mechanisms controlling intraocular fluid pressure. In “secondary” glaucoma, factors such as trauma, certain drugs, infections, tumours or advanced cataracts cause an increase in the intraocular fluid pressure.

Glaucoma is the second leading cause of blindness worldwide. It is a heterogeneous group of disorders marked by damage to the structural or functional integrity of the optic nerve that causes characteristic atrophic changes. Over time, this may also lead to specific visual field defects. Damage can be arrested or diminished by adequate lowering of intraocular pressure (IOP). Yet, some debate still exists as to whether IOP should be included in the definition of glaucoma, as some subsets of patients can exhibit the characteristic optic nerve damage and visual field defects while having an IOP within the normal range.  PRESSURES DO NOT DETERMINE IF YOU HAVE GLAUCOMA.  You can have normal or low pressure and have glaucoma.  It is thought up to 50% of people with glaucoma have normal tension glaucoma. Your eye doctor must examine your optic nerve head to diagnose glaucoma.

The generic term “glaucoma” refers to the entire group of glaucomatous disorders as a whole, because multiple subsets of glaucomatous disease exist. Glaucoma is not just a disease of IOP but rather a multifactorial optic neuropathy. A more precise term should be used to describe the glaucomatous disorder, if the specific diagnosis is known.

glaucoma toronto eye clinic


Although anyone can get glaucoma, sundefinedome people are more at risk than others for “primary” openangle glaucoma. They include: people with a family history of glaucoma, anyone over the age of 60, and African-Americans.


Often glaucoma has no symptoms! Since the conditions are progressive, the earliest symptoms are often mild, such as a slight change in colour vision. Acute glaucoma may initially cause mild bouts of blurred vision, haloes around lights or eye discomfort. However, as the conditions progress, there is eventually a permanent vision loss.


Regular eye examinations are the best hope for early detection, especially for those in the high risk groups. Several tests performed during the eye examination are designed to look for signs of glaucoma. Your eye doctor will review both your general health and your ocular health during your visit as they also provide important clues.


Once detected, glaucoma may respond to drug therapy. If this treatment proves unsuccessful, surgery may be necessary. In the case of secondary glaucoma, the progression of the disease may be stopped by removing the source. Unfortunately, nerve cells do not regenerate once destroyed, therefore any vision loss which has occurred is permanent. Early detection is critical.


The drugs used to treat glaucoma may diminish night vision and peripheral vision. Caution is urged when driving. Also, glaucoma medications may aggravate certain medical conditions, such as emphysema. Certain medications can be potentially harmful when taken along with glaucoma medications. If you are a diabetic or have high blood pressure, your condition or its treatment may affect glaucoma.


Besides the basic evaluations done during an eye examination, you may need more specialized tests, depending on your age, medical history and risk of developing eye disease.  When evaluating glaucoma patients the doctors at the Toronto Eye Clinic recommend the following:

  • Pachymetry
    This test measures the thickness of your cornea — an important factor in evaluating your intraocular pressure measurement. After applying numbing eye drops, your eye doctor uses an instrument that emits ultrasound waves to measure your corneal thickness.  If you have thick corneas, your eye pressure reading may read artificially high even though you may not have glaucoma. Similarly, people with thin corneas can have normal pressure readings and still have glaucoma.  The OHTS study concluded that people with thin corneas that were diagnosed with glaucoma had a greater risk of optic nerve damage.
  • Visual field test (Perimetry 24-2)
    Your visual field is the area in front of you that you can see without moving your eyes. The visual field test determines whether you have difficulty seeing in any areas of your peripheral vision — the areas on the side of your visual field. There are a few different types of visual field tests:
  • Confrontation visual field exam. Your eye doctor sits directly in front of you and asks you to cover one eye. You look directly at your eye doctor while he or she moves his or her hand in and out of your visual field. You tell your doctor when you can see his or her hand or fingers.
  • Tangent screen exam. You sit a short distance from a screen and stare at a target at its center. You tell your doctor when you can see an object move into your peripheral vision.
  • Automated perimetry. Your eye doctor uses a computer program that flashes small lights as you look into a special instrument. You press a button when you see the lights.

Using your responses to one or more of these tests, your eye doctor determines the fullness of your peripheral vision. If you aren’t able to see in certain areas, noting the pattern of your visual field loss may help your eye doctor diagnose your eye condition. :

  • Optical Coherence Tomography (OCT)- Optical Coherence Tomography is a diagnostic test that provides high-resoulution, cross-sectional imaging of ocular tissues.  It is predominantly used for imaging of the back of the eye to measure retinal nerve thickness entering the optic nerve and macular area.  OCT is used to study and monitor diseases such as glaucoma and age-related macular degeneration.
  • Heidelberg Retinal Tomograph (HRT3)
    This technology is one of the best ways to follow further loss of optic nerve fibers.  Glaucoma management is largely about following progression or change in the optic nerve head.  See below for further discussion on HRT3.



The latest technology used in the early detection and follow-up of glaucoma is the Heidelberg Retinal Tomograph(HRT 3)

This instrument is a laser ophthalmoscope; which precisely measure and analyze the shape of your optic nerve. It is a scanning laser, not a treatment laser, and is no way harmful to the eye. Repeated measurements of the optic nerve with the HRT 3 unit can pick up glaucoma damage earlier than visual field testing. The Heidelberg Retinal Tomograph 3 has been shown to be superior to all other optic nerve imaging techniques available.

This test takes only moments to complete and usually does not require pupil dilation. You must be able to look steadily at a small light for approximately 10-15 second while the photograph of your optic nerve is being taken. Each eye is measured separately. A computer compares the shape of your optic nerve to norman data and analyses changes in your optic nerve over time.

At present, the cost of this examination is not covered by OHIP. The examination fee of $110. for both eyes will be billed directly to you. Please discuss this fee with your doctor if you have financial concerns. You will need an examination every 6 months for 3 visits to establish an accurate baseline, and then yearly if your condition remains stable. More frequent exams may be recommended if your glaucoma is aggressive or progressing.

The Heidelberg Retinal Tomograph 3 is an excellent addition to our diagnostic tools in glaucoma management. It will be used in combination with intraocular pressure measurement; visual field testing, pachymetry (the testing of the thickness of the cornea to determine if the intraocular pressures are being measured too high or too low due to the corneal thickness) and regular eye examination to better manage your glaucoma.


Mechanisms of Glaucoma

  • The primary causes of glaucomatous optic neuropathy are unknown. The disorder affects the individual axons of the optic nerve, which may die by apoptosis. Various theories to explain the possible role of elevated IOP in glaucomatous optic neuropathy include:
  • Mechanical compression theory suggesting that elevated IOP causes a rearward curving or bowing of the lamina cribrosa, kinking the axons as they exit through the lamina pores. This may lead to focal ischemia, deprive the axons of neurotrophins, or interfere with axoplasmic flow, triggering cell death.
  • Various vascular theories proposing that cell death is triggered by ischemia – whether induced by elevated IOP or other primary cause.
  • Genetic theories suggest that cell death is triggered by genetic predisposition. Substances may be released into the eye, after the death of individual axons, that cause a secondary reaction of apoptosis in neighboring cells, including glutamate (a neurotransmitter that may cause excitotoxicity), calcium, nitric oxide, and free radicals.
  • Factors that may play a role in the development of primary open-angle glaucoma, the most common form of glaucoma, include a history of vasospasm and vascular disorders ranging from migraine headaches, cardiovascular disease, diabetes, systemic hypertension and arteriosclerosis, to systemic hypotension associated with decreased perfusion.
Heidelberg Retinal Tomograph


  • 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


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 (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 (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.


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.


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).

Optic Nerve Damage. Retinal ganglion cell axons converge in the optic nerve head and exit through the lamina cribrosa. The degeneration of retinal ganglion cells in the optic nerve head is the end result of multiple processes and ultimately leads to vision loss. Increased IOP can lead to stress on the retinal ganglion cell axons by reducing the flow of important neurotrophic factors for the axon’s function. This stress also leads to the release of degenerative substances such as tumor necrosis factor alpha (TNF-α). This causes damage to retinal ganglion cell axons. As retinal ganglion cells begin to die, the nerve fiber layer begins to thin and the cup at the top of the nerve head begins to increase in size. The lamina cribrosa begins to bow as well, and this increases the amount of cupping. The cup-to-disc ratio is used to assess optic neuropathy.

Angle-closure Glaucoma

ACG is characterized by blockage of AH outflow due to the closure of the angle between the iris and cornea. This closure results in the pinching-off of access to the trabecular meshwork. The decrease in outflow can cause a gradual increase in IOP or, more commonly, a rapid increase in IOP, leading to pain and permanent vision loss.

Conventional and Unconventional Aqueous Humor Pathways

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

Glaucoma is described as optic nerve damage that leads to visual dysfunction. Generally, POAG is bilateral, asymmetric, and asymptomatic until significant peripheral vision loss occurs. ACG could include prodromal symptoms. It could also be an acute situation with distinct symptoms.

A thorough patient history should be conducted at the start of every comprehensive adult eye evaluation. Visual acuity is measured at both near and far distances. Both pupils are assessed for restricted constriction of the affected pupil(s). An anterior segment examination is conducted to assess the integrity of the cornea and anterior and posterior chambers. Tonometry measures IOP to determine the level of pressure elevation, if present. The time of day and instrument used are recorded due to diurnal variations. A goniolens (gonioscope) measures the angle between the iris and cornea in order to differentiate between POAG and ACG. The optic nerve head and retinal nerve fiber layer are examined for characteristic changes with glaucoma. The cup-to-disc ratio is used to assess the amount of glaucomatous atrophy, and anything >0.5 is suggestive of atrophy. Perimetry measures the visual field and is used to judge the extent of peripheral vision loss. Although glaucoma is a bilateral process, the level of severity is not necessarily congruent between both eyes

Glaucoma Treatment

Pharmacologic Treatment( 1st Option)

Medications for the treatment of glaucoma are aimed at lowering IOP through two mechanisms, decreasing AH production and increasing AH outflow. It is recommended that IOP be lowered to a target level. That level is generally 20% below the baseline as measured several times.[17] Prostaglandin analogues and beta-blockers are currently the most frequently used agents. Due to their once-daily dosing and effectiveness, prostaglandin analogues are generally selected as first-line options in treatment.

Beta-blockers. Topical beta-blockers are one of the most commonly used classes of medications in the treatment of POAG. They produce an IOP-lowering effect by reducing the production of AH by the ciliary body. Local side effects that occur with the beta-blockers consist of stinging, burning, irritation, inflammation, and blurred vision. The local side effects are normally minor. Side effects are generally short-lived and will go away in time.

Systemic side effects with beta-blockers are rare, but it is important to be aware of them. These include bradycardia, hypotension, bronchospasm, serum lipid changes, and masking of hypoglycemia. The nonselective beta-blockers are contraindicated in patients with asthma or chronic obstructive pulmonary disease (COPD) due to their ability to induce bronchospasm. All topical beta-blockers are contraindicated in patients with sinus bradycardia, secondor third-degree heart block, congestive heart failure, atherosclerosis, and diabetes. Topical beta-blockers should also be avoided in patients taking oral beta-blockers.

Prostaglandin Analogues. Topical prostaglandin analogues are usually the first choice by prescribers for POAG. In a large meta-analysis, it was concluded that prostaglandin analogues showed a greater 24-hour IOP reduction than timolol and other POAG medications.[19] In a separate systematic review that included tafluprost, all of the prostaglandin analogues except tafluprost were shown to have significantly greater IOP reduction than timolol. It was also shown that bimatoprost was most effective at achieving a 30% reduction in IOP, which was the goal of the study. Prostaglandin analogues lower IOP by increasing the uveoscleral outflow of AH. It is suspected that bimatoprost also increases AH outflow through the trabecular meshwork. The prostaglandins are dosed once daily at night, where they have shown to be most effective.

Systemic side effects are rare with these medications. Local adverse reactions are more common and include conjunctival hyperemia, lengthening and darkening of eyelashes, irreversible altered iris pigmentation, cornea inflammation, and macular edema.

Adrenergic Agonists. Dipivefrin is a nonspecific adrenergic agonist. It is a prodrug of epinephrine and decreases IOP by increasing AH outflow through the uveoscleral route and trabecular meshwork. Dipivefrin is less effective at lowering IOP than other treatment options and is poorly tolerated. Therefore, it is rarely used. There are currently no commercial dipivefrin products available in the U.S.

Brimonidine and apraclonidine are alpha2 adrenergic agonists that lower IOP by decreasing AH production. Brimonidine also increases uveoscleral outflow. Brimonidine lowers IOP at a similar level to timolol and can be considered as an initial therapy. Brimonidine can be used as a monotherapy or as adjunctive to beta-blockers or prostaglandin analogues, while apraclonidine is considered to be a second-line agent. Both are indicated for the treatment of glaucoma.

An ocular allergic-like reaction is the most common side effect with these agents. It occurs at a lower rate with brimonidine, but it is still significant and generally causes these medications to be discontinued. Other local events include burning, stinging, and irritation upon administration. Systemic side effects are rare, but dizziness, drowsiness, and dry mouth may occur. Caution should be used with coadministration of central nervous system (CNS) depressants, as these glaucoma agents could exacerbate CNS depression.

Cholinergics. Cholinergic agents lower IOP by increasing AH outflow through the trabecular meshwork. These agents are rarely used because of multiple daily dosing and adverse effects. The local adverse events include retinal detachment, myopia, miosis, and pupillary block. Systemic side effects would be typical cholinergic effects such as sweating, salivation, nausea, vomiting, diarrhea, and bradycardia.

Carbonic Anhydrase Inhibitors. These agents lower IOP by blocking the secretion of sodium and bicarbonate ions into the AH, thereby inhibiting the production of AH. Topical formulations (brinzolamide and dorzolamide) are considered for monotherapy or adjunctive therapy in those who do not achieve effective control with other medications. These are well tolerated, with adverse events including transient burning and stinging, blurred vision, tearing, and corneal edema. Dorzolamide is reported to produce more stinging than brinzolamide, while brinzolamide can cause more blurred vision than dorzolamide. Systemic effects are rare and are generally caused by oral formulations, although topical formulations can cause altered taste.

Oral formulations (acetazolamide and methazolamide) are used for those who do not effectively respond to maximum topical therapy. Systemic side effects are common and include malaise, depression, metallic taste, anorexia, diarrhea, kidney stones, metabolic acidosis, and decreased libido.

Cholinesterase Inhibitor. The cholinesterase inhibitor echothiophate widens the trabecular meshwork by inhibiting the destruction of acetylcholine and lowers IOP by increasing AH outflow. Side effects are a major reason for limited use. These include fibrinous iritis, iris cysts, conjunctival thickening, and nasolacrimal occlusion. In addition, this drug has limited commercial availability and should only be used in nonresponsive patients.

Combination Products. Products that combine timolol with brimonidine or dorzolamide are available. A product that combines brimonidine and brinzolamide is also available. Combination therapy should be considered when initial therapy produces only a partial response. Advantages of using one product instead of two include less total preservative exposure, no washout effect, a single copay, and a possible improvement in adherence to treatment.

Preservative-free Products. Recent research has shown that preservatives like benzalkonium chloride (BAK) in eyedrops could be causing a significant increase in local adverse events, such as dry eyes. These studies also showed that preservative-free eyedrops lead to a significant decrease in local adverse events. Studies have also found equal therapeutic efficacy between preservative-free and preserved products. Products with multiple daily dosing are more likely to cause side effects because of an increase in the amount of BAK These studies looked at products available primarily in Canada and Europe. The only currently available preservative-free product in the U.S. is Cosopt PF, a combination of timolol and dorzolamide.

Absorption of certain medications, especially beta-blockers and drugs that can produce anticholinergic effects, may produce serious systemic side effects. Therefore, pharmacists should counsel patients on the proper instillation of eyedrops, including the use of punctal occlusion (pressing on the bridge of the nose to prevent the drops from entering the nasolacrimal duct). Simply closing the eye (but not blinking) is an equally effective alternative. Either of these procedures should be done for about 2 minutes.

Adherence is a problem with glaucoma patients. In one study, 45% of patients were shown to take <75% of their doses.

Nonpharmacologic Treatment(2nd Option)

Laser Trabeculoplasty. This procedure is considered in patients who fail to be adherent to medication regimens, are unable to administer eyedrops, or cannot tolerate topical medications. Trabeculoplasty uses a very focused beam of light to cause increased drainage through the trabecular meshwork. The effects of this may wear off over time and, therefore, long-term benefit is uncertain.

Trabeculectomy. This is the most common surgical procedure used to lower IOP. It involves creating a new pathway for the drainage of AH via bypassing the trabecular meshwork. Trabeculectomy is generally considered after topical agents and trabeculoplasty have been deemed insufficient at controlling IOP. It may also be considered as an initial therapy when IOP is extremely elevated.

Cyclodestructive Procedures. These are used when medicaland surgical treatments have failed and glaucoma is highly advanced. During cyclodestructive procedures, the ciliary body is intentionally damaged so that AH production is permanently reduced.