GLAUCOMA

Glaucoma Information for Health Care Professionals

This word originates from the Greek language and refers to a greenish-blue color of the pupil resembling sea-water. It probably described advanced nuclear sclerosis of the lens (immature cataract). Although somewhat inaccurate, this term remains useful today to name a collection of disorders that share common features.

Glaucoma is characterized by three factors:

1. Elevated intraocular pressure (IOP)
   
2. Characteristic optic nerve damage (cupping)
   
3. Visual field loss (peripheral vision lost first, reading vision lost very late)

Glaucoma is the second leading cause of blindness in the world. In most forms of glaucoma, the IOP is elevated above normal limits, causing damage to the optic nerve and resulting in loss of visual field. Without treatment this can progress to total blindness. Most forms of glaucoma are chronic like diabetes. It cannot be cured, only managed to prevent further damage. The IOP is measured in millimeters of mercury (mmHg). The normal range is 10 to 21 mmHg and the average IOP is 15 mmHg.

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Aqueous Flow Dynamics

The aqueous humor is a transparent, cell-free fluid secreted by the epithelial cells of 70-75 ciliary processes. The amount of aqueous produced (aqueous inflow) should always be equal to the amount of aqueous that is filtered by the trabecular meshwork (aqueous outflow). This process maintains a normal IOP. The aqueous flows from the ciliary processes through the posterior chamber, bathes the lens, passes through the pupil and fills the anterior chamber: it is then filtered through the trabecular meshwork into the canal of Schlemm and leaves the eye through the episcleral venous system.

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Mechanism of Damage

Physiologic or mechanical obstruction at the level of the trabecular meshwork and Schlemm's canal will result in elevation of IOP and subsequent glaucoma. As mentioned, the main effect of elevated IOP is damage to the optic nerve. The optic nerve is like the cable that connects a video camera (the retina) to a TV monitor (the brain). The nerve fibers that connect the retina to the brain are damaged where they exit the eye at the optic nerve head. The absence of these fibers leads to enlargement of the optic cup. Since these fibers are part of the brain, they do not grow again and cannot be replaced. Elevated IOP can also damage other parts of the eye. A sudden increase or a chronic high elevation may lead to corneal edema and even permanent corneal damage. The blood supply of the iris may be obstructed leading to infarction (stroke) of the iris with an irregular pupil. Likewise, the retinal veins may be obstructed causing a central retinal vein occlusion.

Cup to Disc Ratio (C/D ratio): is the ratio of the size of the cup over the total size of the optic disc. The cup is a small depression in the center of the disc. A normal sized cup is less than or equal to one third or 30% of the optic disc. Any cup larger than 30% (C/D 0.3) is abnormal and may indicates glaucoma. Initially cupping tends to occur superiorly and inferiorly (vertical elongation, notching). When the cup takes up the entire nerve (C/D 1.0 or %100), it is called "total" cupping and the visual loss is often severe.

Visual Field Loss: Glaucomatous visual field defects stop at the horizontal midline creating a "nasal step" in contrast to neurological disorders which stop at the vertical midline. Early defects tend to occur in the arcuate area (corresponding to loss of arcuate nerve fibers from the superior and inferior disc). This progresses to loss of the nasal field (not noticed because of the patient's nose) and then most of the periphery. In endstage glaucoma, tunnel vision (small central area of reading vision) may occur or the central reading vision may be lost and only a small temporal island of vision remain (usually only hand motions or count fingers vision). Finally the eye loses the perception of light.

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Risk Factors in Glaucoma

• Intraocular pressure
  
• Age
  
• Heredity: The predisposition for glaucoma runs strongly in families
  
• Race: Open angle glaucoma is more common and more difficult to treat in blacks
  Angle closure glaucoma is more common in Eskimos, Asians and Arabs
  
• Myopia: The higher the myopia, the greater the risk of open angle glaucoma
  
• Hyperopia: Short hyperopic eyes have an anatomical predisposition for angle closure
  
• Trauma: Can cause changes to chamber angle structure that may lead to glaucoma
  
• Steroid use: Chronic ocular, intranasal or systemic steroids may raise IOP
  
• Systemic diseases: Vascular and inflammatory diseases

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Classification of Glaucoma

1. Primary Open Angle Glaucoma
   
2. Primary Angle Closure Glaucoma
   
3. Mixed or Combined Mechanism Glaucoma
   
4. Secondary Glaucoma
   
5. Congenital Glaucoma
   
6. Low or Normal Tension Glaucoma
   
7. Other types of glaucoma
   
8. Ocular Hypertension

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Primary Open Angle Glaucoma (POAG)

World-wide, this is the most common form of glaucoma. POAG (sometimes called COAG = Chronic OAG) results from microscopic blockage in the trabecular meshwork leading to decreased drainage of aqueous into Schlemm's canal (decreased aqueous outflow) and thus raising the IOP. POAG usually affects both eyes and is strongly associated with age and a positive family history. Because POAG is asymptomatic (no pain or sudden change in vision) and the early visual loss is in the periphery, the disease may not be detected until irreversible visual loss has occurred. Roughly half of the 2 million persons with POAG in the USA. do not know that they have glaucoma.

Symptoms: There are no symptoms of early disease. Late in the disease the patient will notice a constricted (tunnel) field of vision and eventual loss of central vision.

Signs: The only signs are elevated IOP, visual field defects and optic disc cupping. The pressure is usually above 21 mmHg, although half of POAG patients will have a normal reading on their first examination. Normal IOP fluctuates from day to day and this fluctuation is much greater in POAG.

Treatment: Medical treatment is the treatment of choice.

Medications

• Topical (not inclusive of all brand names)
  
  • Beta-blockers: timolol (Timoptic), betaxolol (Betoptic S), levobunolol (Betagan)
    
  • Miotics: pilocarpine, carbachol, Phospholine Iodide (no longer available)
    
  • Adrenergic agonists: brimonidine (Alphagan), Iopidine, Propine, epinephrine
    
  • Carbonic anhydrase inhibitors: TruSopt, Azopt
    
  • Prostaglandin analogs: latanoprost (Xalatan), bitmatoprost (Lumigan), travoprost (Travatan), unoprostone (Rescula)
    
  • Combinations: Timoptic + Trusopt (Cosopt)
• Oral medications
  
• Carbonic anhydrase inhibitors: Diamox, Neptazane - very rarely used today

Laser

Argon Laser Trabeculoplasty (ALT or LTP) may be performed when medical treatment is not tolerated or is unsuccessful at lowering IOP. Laser burns are applied along the trabecular meshwork to create scarring that pulls the channels of the meshwork open, thereby increasing outflow.

Surgery

Performed when medical treatment and laser procedures fail to lower the IOP adequately.

• Trabeculectomy: A trapdoor (scleral flap) is created in the sclera at the limbus. Underneath this flap, a segment of cornea/trabecular meshwork is removed to create a hole into the anterior chamber. The aqueous can now flow or "'filter" out of the eye from the anterior chamber to the space underneath the conjunctiva (a trabeculectomy is sometimes called a "filter"). This fluid lifts the conjunctiva away from the sclera forming the "filtering bleb". The trapdoor is sutured back in place to prevent excessive filtration which can cause too low a pressure ("hypotony"). If the pressure is still too high after surgery, the area near the bleb can be "massaged" to increase flow or the laser can be used to cut a flap suture, thus opening the trapdoor and lowering the pressure. Trabeculectomy can fail when scarring occurs over the scleral flap, decreasing flow and raising the pressure. 5-FU injections or mitomycin C are often used to slow down this scarring process.

• Drainage implant: If the conjunctiva is too scarred from previous surgery to do a trabeculectomy, a drainage tube may be implanted to drain aqueous from the anterior chamber to the subconjunctival space. Examples include the Baerveldt implant, the Ahmed valve, the Krupin valve and the Molteno implant.

• Cyclocryotherapy or Cyclophotocoagulation: These procedures are performed when all other procedures have failed to bring the IOP under control. A freezing or laser probe is applied to the outside of the eye to destroy part of the underlying ciliary body, thus decreasing aqueous production.

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Acute Angle Closure Glaucoma (AACG)

Acute Angle Closure Glaucoma (AACG) is a true ocular emergency. The intraocular pressure can rise over 1-2 hours to 35 to 80 mmHg causing severe pain and irreversible loss of vision. AACG usually occurs monocularly, but the risk exists in both eyes. The primary predisposing factor is an anatomically narrow angle (Fig. 3 & 4) which is more common in hyperopes, women, and people of Asian, Eskimo and Middle Eastern heritage. Age, cataract and pseudoexfoliation are also risk factors since they are associated with enlargement of the lens and crowding or narrowing of the angle. Dark environments (movie theaters, looking at the stars) and episodes of physical or emotional stress may precipitate an attack by partially dilating the pupil (angle closure usually occurs when the pupil is mid-dilated - Fig 5). Pharmacologic dilation of the pupil may rarely cause angle closure so this should only be done under the supervision of a physician.

Mechanism: A physiologic obstruction to aqueous flow occurs where the pupillary border touches the lens ("pupillary block"). The aqueous trapped in the posterior chamber forces the middle portion of the iris forward ("iris bombé" - Fig 6) so that the peripheral iris touches and blocks the trabecular meshwork (angle closure).

Symptoms:

• Ocular pain - severe deep pain, associated headache, may radiate from eye to teeth or jaw
  
• Nausea/vomiting - may be misdiagnosed as an intestinal problem
  
• Decreased vision - from corneal edema and decreased blood flow to optic nerve
  
• Haloes around lights - important symptom since it may precede an attack
  - caused by corneal edema

Signs:

• Elevated IOP
  
• Red eye with focal redness around limbus ("limbal flush"), may have lid and conjunctival edema
  
• Hazy "steamy" cornea - from corneal edema
  
• Deep central anterior chamber with very shallow periphery - caused by iris bombé
  
• Mid-dilated, irregular pupil with little or no reaction to light (fixed or sluggish) - the high IOP decreases blood flow to the iris, impairing its function
  
• Edema of the optic nerve head - like the iris, the nerve is deprived of blood - a form of Anterior Ischemic Optic Neuropathy (AION). Later the nerve becomes pale and cupped.

Treatment: Medications are used to lower the IOP so that the definitive procedure, Laser Peripheral Iridotomy (LPI), can be performed (surgical iridectomy is rarely needed).

• Standard medical management - Beta blockers (timolol), carbonic anhydrase inhibitors (Diamox - oral or IV), Iopidine. Cholinergics are used once the IOP has been lowered somewhat by the other medications.
  
• Hyperosmotic agents - Glycerin by mouth (given with ice and juice because it is so sweet that it may cause nausea) or Mannitol intravenously.
  
• Laser peripheral iridotomy (LPI) - creates a hole in the iris through which aqueous can escape from the posterior chamber into the anterior chamber. This eliminates iris bombé, thus opening the angle and allowing the aqueous to exit the eye through the trabecular meshwork. Some of these patients continue to require chronic medical therapy and a few later require surgery. In most cases, LPI is also done in the other eye to prevent subsequent angle closure in that eye.
  
• Surgery - patients who cannot sit at the laser (mentally retarded, physically handicapped) may require a surgical iridectomy. Trabeculectomy may be necessary if medications and laser do not control the pressure.

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Mixed or Combined Mechanism Glaucoma

As the name indicates, this glaucoma is a mixture or combination of open and closed angle glaucoma. It includes patients with acute ACG whose angle opens after laser iridotomy, but who continue to require medications for IOP control. It also includes patients with POAG or pseudoexfoliative glaucoma who gradually develop narrowing of the angle (this is common with aging and with pilocarpine use). It is treated with standard medical, laser and surgical therapy.

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Chronic Angle Closure Glaucoma (CACG)

Like acute angle closure glaucoma (AACG), the underlying mechanism is pupillary block with iris bombé which narrows the angle. Unlike AACG, the iris gradually obstructs the angle by sticking to the trabecular meshwork. These adhesions, called "peripheral anterior synechiae" (PAS), interfere with aqueous outflow. Similar to POAG, the IOP rises slowly and without symptoms. Treatment is similar to POAG but includes a laser iridotomy.

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Secondary Glaucoma

Secondary glaucoma is caused by another ocular or systemic disease or condition. It is also divided into open and closed angle forms. Treatment is aimed at the causative factor (for example, panretinal photocoagulation for neovascular glaucoma), along with standard glaucoma therapy. Examples of secondary glaucoma are given below:

• Trauma: damage to the trabecular meshwork
  
• Inflammation: In conditions like uveitis, inflammatory cells may clog the meshwork and decrease aqueous outflow. Peripheral anterior synechiae (PAS) may form closing the angle. Posterior synechiae (adhesion of the pupillary border to the lens) may create secondary pupillary block with iris bombé and angle closure.
  
• Steroid induced: long term use of topical steroids increases the resistance to aqueous outflow through the trabecular meshwork and may produce severe glaucoma. The mechanism of this effect is not fully understood.
  
• Pseudoexfoliation/exfoliative glaucoma: very common in Saudi's and Scandinavian's. An abnormal material is produced in the eye that coats the lens capsule, ciliary body and iris. This substance rubs off and obstructs the trabecular meshwork causing a glaucoma that is often unilateral in its early stages.
  
• Hemorrhage: blood in the anterior chamber (hyphema) may clog the meshwork thus decreasing aqueous outflow.
  
• Neovascular: retinal ischemia (lack of blood flow to the retina) causes the retina to produce a chemical that results in the growth of new, abnormal blood vessels. This can happen in diabetic retinopathy and following central retinal vein occlusion. Small new blood vessels on the iris surface (rubeosis iridis) may grow across the angle structures, blocking aqueous outflow. They may also contract, pulling the iris up over the trabecular meshwork to further decrease outflow (PAS and secondary angle closure).
  
• Lens induced: A mature cataract may grow so large that it pushes the iris forward against the trabecular meshwork (phacomorphic glaucoma - a form of angle closure). Hypermature cataracts leak lens protein across their wrinkled lens capsule. These proteins may obstruct or damage the trabecular meshwork (phacolytic glaucoma). Subluxated (loose and mobile) lenses may move forward to cause pupillary block and angle closure.
  
• Intraocular tumors: large tumors may push the iris forward against the angle structures causing secondary angle closure.

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Congenital Glaucoma

Congenital (present at birth) or Infantile (after birth to one year) glaucoma is much less common than the adult forms of glaucoma. It may affect multiple children in one family. A malformation of the anterior chamber angle causes poor aqueous outflow. There may be other associated ocular and systemic anomalies.

Signs:

• Tearing/epiphora: corneal edema and photophobia cause tearing
  
• Photophobia: cannot tolerate light because of corneal edema
  
• Blepharospasm: unable to open eyes because of photophobia
  
• Enlarged eye and cornea: under the age of two years, elevated IOP can cause the eyeball to grow resulting in very large eyes (buphthalmos = "ox eye" - Fig. 8).
  
• Corneal edema: cornea appears steamy or hazy. stretching of the cornea causes tears in the back of the cornea (Descemet's membrane) which allow aqueous fluid to enter the corneal stroma producing edema.

Treatment: Medications work poorly in congenital glaucoma so the treatment of choice is surgery to open or create drainage channels.

• Goniotomy: when the cornea is clear enough for the angle structures to be seen by gonioscopy, a knife or needle is used to open the angle from inside the eye.
  
• Trabeculotomy: if the cornea is too hazy, Schlemm's canal is found outside the eye and a probe is passed into Schlemm's and then rotated into the anterior chamber to open a channel.
  
• Trabeculectomy and trabeculotomy are often combined in one procedure for a higher success rate.

In very young children, some of the glaucoma damage may be reversible. Some degree of myopia, caused by stretching of the globe, is often reversed after surgery. Optic nerve cupping may also reverse once the IOP is lowered. However, just like in adult glaucoma, once optic nerve fibers are lost they can never be regained.

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Low or Normal Tension Glaucoma

Low tension glaucoma is relatively uncommon and can be very difficult to manage. Progressive optic nerve damage and loss of visual field occur despite IOP's in the normal range (10-21mmHg). There are probably several different mechanisms that produce the picture of low tension glaucoma. One theory is that the optic nerve is abnormally sensitive to pressure induced damage (mechanical theory). Another theory is that blood flow to the optic nerve head is impaired resulting in repetitive small "strokes" of the nerve. Optic disc hemorrhages are common in this condition. Surgery is often required to produce IOP's less than 12 mmHg in an attempt to stop the damage.

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Ocular Hypertension

Some eyes tolerate IOP's higher than the normal range without developing optic nerve damage or visual field loss. These patients are referred to as ocular hypertensives or glaucoma suspects. These patients are at increased risk of glaucoma, but therapy is only indicated when evidence of damage develops. Close observation is required.

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Absolute Glaucoma

The endstage of glaucoma is a blind (NLP = "no light perception") eye, called absolute glaucoma. If the pressure remains highly elevated the eye may also become painful. Traditional glaucoma surgery is not indicated since the vision has already been lost. Atropine and steroid drops are given for comfort only. If the eye remains painful, a retrobulbar alcohol injection may relieve the pain. Enucleation is often the ultimate procedure for these blind, painful eyes.

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Clinical Evaluation of Glaucoma

The diagnosis of glaucoma is made on the basis of examination findings, so a careful clinical evaluation is essential. Full evaluation may take several visits to establish the diagnosis and the progression of the disease.

History: A careful history is important on the initial visit as well as on follow up visits. Specific information to be asked includes the following: family history of glaucoma, trauma, steroid use, colored haloes around lights, asthma, congestive heart failure, sickle cell, diabetes, hypertension, other diseases, current medications, sulfa or other medication allergies, and prior ocular surgeries.

Tonometry: Tonometry is the measurement of IOP. There are several methods of measuring IOP: indentation (with the Schiotz tonometer), applanation (with the Goldmann tonometer, Tonopen, and pneumotonometer), non-contact tonometry (air-puff - a form of applanation), or tactile tonometry (estimation of IOP by feeling the hardness of the eye with one's fingers). Applanation with the Goldmann tonometer is the most reliable method. IOP measurements should be taken at different times of day at different visits since the IOP fluctuates during the day (diurnal variation). Sometimes a patient is asked to stay at the clinic for many hours to assess the degree of this fluctuation (a diurnal curve). A difference of 3-6mmHg between readings is considered normal, but more than 10 mmHg is suggestive of glaucoma. In normal eyes the IOP peaks at midday.

Tonography: This test is performed with a Schiotz tonometer or a pneumotonometer. It determines the rate of aqueous outflow per minute. Reduced outflow suggests a risk for glaucoma. This test is rarely used in modern ophthalmic practice.

Ophthalmoscopy: Direct stereo visualization of the optic disc to estimate the size of the optic cup (C/D ratio) and to describe any focal damage is an important part of any glaucoma exam. The findings must be documented, either with photographs or with careful drawings, so that comparisons can be made from visit to visit. Photographs are the most reliable method since one ophthalmologist's estimation and drawing may differ from another ophthalmologist's.

Pupils: Pupil evaluation should be done at the initial visit. Irregular pupils are suggestive of posterior synechiae caused by inflammation or drugs like pilocarpine. A semi-dilated, poorly reactive pupil is suggestive of past or current acute angle closure. An afferent pupillary defect (APD) indicates severe damage to one optic nerve with less damage to the other nerve.

Estimation of Anterior Chamber Depth: This procedure can easily be performed by the assistant with a penlight , See section on special testing procedures.

Gonioscopy: Visualization of the angle structures is performed with a mirrored lens at the slit lamp (indirect gonioscopy - Zeiss 4-mirror or Goldmann 3-mirror lens) or with a non-mirrored lens in the operating room or exam chair (direct gonioscopy - Koeppe lens, etc.) Gonioscopy is necessary to determine if the patient has open or closed angle, if there are peripheral anterior synechiae and if a secondary glaucoma is present. These findings may greatly alter the treatment used for a given patient.

Perimetry: This is the evaluation of the visual field which should be done at the initial exam and every 3 to 6 months thereafter. Visual field testing is important to establish the extent of visual loss, to follow the progression of visual loss and to correlate with any observed change in the optic disc. Visual fields may be crucial in deciding if additional medications or surgery are necessary to achieve a lower IOP and prevent further damage.

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GLAUCOMA MEDICATIONS

Medical management of glaucoma involves reducing the IOP with drugs that decrease aqueous production or increase aqueous outflow. These drugs are often used in combination to achieve the greater reductions in IOP. These drugs are presented in the order that they are commonly used. One drug is added to another until the IOP is controlled or maximum medical therapy is reached (usually 4 medications: a beta blacker, an adrenergic, a cholinergic and a carbonic anhydrase inhibitor).

Systemic side effects of topical drops are caused by drainage of the drops through the tear ducts into the nose. Some of the medication is absorbed into the blood stream in the nose and some is swallowed (this is the reason that eye drops "taste" bad). After a drop is instilled, closing the eyes and occluding the puncta are two ways to decrease systemic absorption. All drops in bottles (instead of minims) have preservatives. Many cases of drug-related ocular allergy are due to the preservatives and not the drug itself.

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BETA BLOCKERS

These drugs are the usual first choice and are well accepted due to few side effects. They lower IOP by blocking beta adrenergic receptors which decreases aqueous production. All used twice a day (BID).

Side effects: slowing of heart rate (bradycardia), lowering of blood pressure, male impotence, depression, cardiac irregularities, worsening of asthma.
Contraindications: asthma (see below), congestive heart failure, third degree heart block

• timolol maleate 0.25% or 0.5% (Timoptic, Betimol)
  
• levobunolol 0.5% (Betagan) - packaged in Liquifilm Tears, so good for dry eyes
  
• betaxolol 0.5% (Betoptic S) - slightly less effective but cardioselective so may be used with mild asthma
  
• metipranolol (Optipranolol)

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SYMPATHOMIMETICS

These adrenergic drugs mimic the sympathetic ("fight or flight") effect. They reduce IOP by both reducing aqueous production and increasing outflow. All used twice a day (BID).

Side effects: high incidence of allergy/toxicity, increased blood pressure, tachycardia (increased heart rate), blurred vision from slight pupil dilation, elevation of lid, initial whitening of eye followed by significant reddening.

• epinephrine 1% or 2% (Glaucon, Epinal, Epifrin, Eppy) - primarily increases aqueous outflow. Rarely used today. With chronic use, frequently causes allergic blepharoconjunctivitis. Can cause macular edema in aphakic patients (probably not in pseudophakic patients).
  
• dipivalyl epinephrine or dipivefrin hypochloride 0.1% (Propine) - Propine is a prodrug which is converted into epinephrine by an enzyme as it penetrates into the eye. The dipivalyl portion of the drug facilitates absorption and penetration through the cornea so that 12 times more drug gets into the eye than with epinephrine. There are also milder side effects than with epinephrine. Mostly used as a single agent if beta blockers cannot be used or as a second agent in addition to beta blockers if the IOP only needs to be a little lower (2-4 mmHg lower).
  
• apraclonidine 0.5% (Iopidine) - primary effect is a decrease in aqueous production. Given before and after laser procedures to prevent post-laser IOP elevations. Also used on a chronic basis in addition to maximum medical therapy to try to delay surgery. Chronic use limited by allergy.
  
• brimonidine 0.5% (Alphagan) - same uses and effect as Iopidine, but less allergy with chronic use. Newest formulation is Alphagan P with Purite, a dissolving preservative - may induce less allergy.

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CHOLINERGICS

Sometimes called "miotics" (because they produce a small pupil), these drugs cause contraction of the ciliary body muscle and the pupillary sphincter muscle. The ciliary muscle pulls on the scleral spur which opens the trabecular meshwork and increases aqueous outflow. It also shifts the lens and iris forward,, shallowing the anterior chamber and inducing myopia (all undesirable side effects). The pupillary sphincter muscle constricts the pupil (undesirable) and pulls the iris root away from the trabecular meshwork (desirable).

Side effects: browache, headache, decreased vision (especially at night), induced myopia, increased risk of retinal detachment and cataract

Direct acting miotics (parasympathomimetic):

• pilocarpine: 1% to 4% most common - given QID
  
  
• carbachol: 1.5% , 2.25%, 3% - given TID
  Mechanism: combination of direct and indirect effect
  
  
• Miochol (acetylcholine): Used during surgery to constrict the pupil and provide some IOP control in the immediate post-operative period.

Indirect acting miotics (anticholinesterases): These are very strong, long-acting medications and can cause problems with general anesthesia.

• physostigmine (Eserine): 0.5% solution or ointment. Usually used as ointment (BID) since the drug is extremely unstable in water. Rarely used.
  
  
• demecarium bromide (Humorsol): 0.125% and 0.25%. Given BID.
  
  
• echothiophate (Phospholine Iodide): 0.03%, 0.06%, 0.125%, 0.25%. Induces cataracts in adults so used in pseudophakic or aphakic patients. In children causes iris pigment cysts. Given BID.
  
  
• diisopropyl fluorophosphate = DFP (Isofluorophate): 0.25% ointment only. Intense ciliary spasm. Rarely used.

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CARBONIC ANHYDRASE INHIBITORS

These drugs block the enzyme (carbonic anhydrase) which is responsible for aqueous secretion. They are all sulfa drugs and therefore should not be used in patients with sulfa allergy and G6PD deficiency. Because they cause acidosis, they should not generally be used in sickle cell patients.

Topical

• dorzolamide 2% (Trusopt): Used as second drug in addition to a beta blocker ( BID) or as initial therapy in patients who cannot take a beta blocker (TID). Slightly less effective than oral drugs, but much less systemic side effects than oral drugs.
  Side effects: stinging, blurring of vision, systemic effects (see below under oral)

• brinzolamide (Azopt) - may have less stinging than dorzolamide with similar efficacy

Oral

Side effects: tingling and numbness or lips and extremities, gastric upset, general malaise & fatigue, carbonated drinks taste metallic, metabolic acidosis, electrolyte imbalance in some patients (decreased potassium), blood disorders, kidney stones.

• acetazolamide (Diamox) - 125mg & 250mg tablets - given QID, 500mg sustained release capsules (Sequels) - given BID, and 500mg IV infusion - for acute IOP reduction, especially in patients too nauseated to take pills.
  
  
• dichlorphenamide 50mg (Oratrol, Daranide): given TID. Headaches and prolonged diuresis are unique side effects to this drug.
  
  
• methazolamide 50mg (Neptazane): less side effects but slightly less effective, given BID to TID

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HYPEROSMOTIC AGENTS

These medications are given orally or intravenously (IV) for acute control of highly elevated IOP when standard medications have failed to reduce the IOP enough. Commonly used in acute angle closure glaucoma and preoperatively in any form of glaucoma with a very high IOP. These drugs draw water from the vitreous body into the bloodstream and out of the eye. This decreases the IOP by shrinking the vitreous and decreasing the volume of intraocular fluid. If the patient drinks too much water after the drug is given, the drug will be less effective at lowering IOP.

Side effects: Thirst, headaches, nausea, vomiting, dizziness, agitation, seizures, disorientation, intracranial hemorrhage. Use extra caution in patients with cardiovascular, pulmonary or renal disease. Also use caution in elderly patients.

Oral:

• glycerine 50% solution (Glycerol, Osmoglyn, Glyrol): Dose is 1 to 1.5 grams/Kg of oral solution. Because this medication is sickeningly sweet and nauseating, it is usually mixed with citrus juice (lemon) and ice to reduce the sweetness. In diabetics can cause highly elevated blood sugars - don't use.

• isosorbide 50% solution (Ismotic): same dose as glycerine, but safe in diabetics.

Intravenous:

• mannitol 5% to 25% solution: dose is 1 to 1.5 grams/Kg infused slowly over 30 to 60 minutes.
  
  

• urea: no longer used due to a rebound increase in IOP following the initial decrease.

Hyperosmotic agents are only used in emergency situations where a quick reduction of IOP is needed prior to laser or surgical intervention.

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PROSTAGLANDIN ANALOGS

These medications are the current cutting edge of glaucoma therapy. They work by increasing uveoscleral (nonconventional) outflow. This means that the aqueous escapes the eye through the iris and ciliary body instead of through the trabecular meshwork.

• latanoprost 0.005% (Xalatan): Given once daily (bedtime). Well tolerated.

Side effects: darkening of iris color (in medium pigmented eyes - blue eyes and dark brown eyes do not seem to be affected), increase in the number, length and curvature of eyelashes. May cause uveitis or cystoid macular edema in predisposed individuals.

• bitmatoprost (Lumigan): Given once daily. Well tolerated.

Technically a "prostamide"

Side effects: eye color and eyelash changes similar to Xalatan , may cause significant redness of eyes

• travoprost (Travatan): Given once daily. Well tolerated.

Side effects: eye color and eyelash changes similar to Xalatan , may cause significant redness of eyes

• unoprostone (Rescula): Given twice daily. Well tolerated, but less effective

Technically a "docosanoid"

Side effects: similar to Xalatan.

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