How Do Prostaglandin Analogues Work?

Increase the outflow of aqueous through the non-conventional uveoscleral pathway.

What Are the Prostaglandin Analogues?

This drug class is generally the first-line drop treatment, given its relative superior efficacy, once daily dosing, and relatively low systemic side effect profile. The most common commercially prescribed versions are:

• Xalatan
• latanoprost (generic)
• Lumigan
• bimatoprost (generic)
• Zioptan (preservative-free)
• tafluprost (generic)
• Travatan Z
• travoprost (generic)
• Xelpros (preservative-free)

Possible Side Effects of Prostaglandin Analogues

All medications, including eye drops, can have side effects. Some people taking prostaglandin analogue eye drops may experience

• Increase in eyelash length, thickness, pigmentation
• Misdirected eyelashes rubbing on the cornea (trichiasis)
• Darkening of iris color, most commonly hazel, green, or blue irides
• Darkening of eyelids
• Ocular allergy with a red eye or red eyelids
• Ocular inflammation (iritis or uveitis)
• Herpes keratitis reactivation
• Macular edema (fluid in the retina)

How Do Beta Blockers Work? Beta-blocker (beta adrenergic antagonist) medications are reliable for lowering intraocular pressure. They work by decreasing the amount of fluid that the eye continually produces, called the aqueous humor. For many years, beta blockers were the mainstay of treatment. Thus, we have a lot of experience with this medication for the treatment of glaucoma.

Types of Beta-Blocker Medications

There are two general classes of beta blockers: non-selective and selective. Non-selective beta blockers have more effects on the body’s beta receptors system-wide and are associated with more side effects. The non-selective beta blockers are also more effective at lowering IOP. The non-selective beta blockers include

• timolol (Timoptic, Betimol, Istalol)
• timolol gel (Timoptic XE)
• levobunolol (Betagan, AKBeta)
• carteolol (Ocupress)
• metipranolol (Optipranolol)

The only available selective beta-blocker medication is

• betaxolol (Betoptic, Betoptic S)

While a selective beta-blocker eye drop has a better safety profile, especially in terms of respiratory symptoms, it still must be used with caution in patients with asthma or emphysema. The eye pressure-lowering effect is slightly less with selective beta blockers. There is only a minimal additive effect in terms of lowering eye pressure in patients already taking oral beta blockers, and there is the risk of further additive side effects. If you are already taking a beta-blocker medication by mouth or if your primary care doctor newly prescribes a beta blocker, please notify your ophthalmologist.

Possible Side Effects of Beta Blockers

All medications, including eye drops, can have side effects. Some people taking beta-blocker eye drops may experience

• wheezing or difficulty breathing;
• slow or irregular heart beat or decreased response of heart rate to exercise;
• increased risk for heart failure;
• depression;
• impotence;
• headache, dizziness or weakness;
• in diabetics, difficulty sensing blood glucose changes; and
• eye irritation or allergy.

How Do Alpha Agonists Work?

Alpha agonist medications are reliable for lowering the intraocular pressure. They have a dual mechanism: they work by decreasing the production of the fluid that the eye continually makes, called the aqueous humor, as well as by increasing the outflow facility of the aqueous humor from the eye.

What Are the Alpha Agonists?

The most common commercially prescribed versions are:

• Alphagan, Alphagan P
• brimonidine (generic)

Possible Side Effects of Alpha Agonists

All medications, including eye drops, can have side effects. Some people taking alpha agonist eye drops may experience

• dry mouth;
• ocular allergy with a red eye or red eyelids;
• tiredness or fatigue;
• low or high blood pressure and possible slowing of heart rate (less than with beta blockers);
• blurred vision;
• sensitivity of the eyes to bright light; and
• headache.

How Do CAIs Work?

CAI medications are very reliable at lowering the intraocular pressure. They work by decreasing the production of the fluid that the eye continually makes, called the aqueous humor.

What Are CAI Medications?

Topical drugs:

• dorzolamide (Trusopt)
• brinzolamide (Azopt)

Oral medications:

• acetazolamide (Diamox, AK-Zol)
• acetazolamide sustained-release (Diamox Sequels)
• methazolamide (Neptazane, GlaucTabs)
• Generic versions of the eye drop formulations are not yet available.

Possible Side Effects of CAIs

All medications, including eye drops, can have side effects. Some people taking topical carbonic anhydrase medications (eyedrops) experience:

• blurred vision
• bitter taste in the mouth
• dry eyes
• eye irritation or allergy with a red eye or red eyelids
• headache or dizziness
• upset stomach

The oral (pill) form of these medications has more side effects, including:

• increased need to urinate
• tingling sensation in fingers and toes
• rarely, severe allergic reactions or blood disorders can occur
• change in taste (especially with carbonated beverages)
• unusual tiredness or weakness

WARNING

These medications are sulfonamides. If you are allergic to sulfa antibiotics, the same types of adverse reactions MAY occur with carbonic anhydrase inhibitors. Also, rare adverse drug interactions have occurred in patients taking high doses of aspirin and carbonic anhydrase inhibitors.

How Do Nitric Oxide Donors Work?

Nitric oxide induces cell relaxation in the trabecular meshwork by activating the nitric oxide–cyclic guanosine monophosphate signaling pathway, which is thought to lead to a widening of the intercellular spaces in the trabecular meshwork, thereby increasing the conventional outflow.

What Are the Nitric Oxide Donors?

The only commercially available medication is Vyzulta (latanoprostene bunod) which is metabo­lized into two moieties, latanoprost (a prostaglandin analogue) and butanediol, and therefore regulates IOP through both the trabecular outflow and uveoscleral outflow pathways.

Possible Side Effects of Vyzulta are very similar to the side effect profile of the prostaglandin analogue class:

All medications, including eye drops, can have side effects. Some people taking latanoprostene bunod eye drops may experience:

• Increase in eyelash length, thickness, pigmentation
• Misdirected eyelashes rubbing on the cornea (trichiasis)
• Darkening of iris color, most commonly hazel, green, or blue irides
• Darkening of eyelids
• Ocular allergy with a red eye or red eyelids
• Ocular inflammation (iritis or uveitis)
• Herpes keratitis reactivation
• Macular edema (fluid in the retina)

How Do Rho Kinase (ROCK) Inhibitors Work?

These have the potential to lower IOP through three mechanisms of action: lower the resistance to outflow through the trabecular meshwork, decrease production of fluid, and decrease episcleral venous pressure.

What Are the ROCK Inhibitors?

The only commercially available medication is Rhopressa (netarsudil) which also comes in combination form with latanoprost (Rocklatan).

Possible Side Effects of ROCK Inhibitors:

All medications, including eye drops, can have side effects. Some people taking ROCK inhibitor eye drops may experience:

• Eye redness
• Discomfort with drop administration
• Corneal verticillata (whorls on the surface layer of the cornea only evident under the microscope)

With each new medication that your ophthalmologist prescribes, make sure you understand the following:

• the name of the medication
• how to take it
• how often to take it
• how to store it
• if you can take it with your other medications (make sure all of your doctors know about all the different medications you take, including nonprescription medications)
• what the possible side effects may be
• what you should do if you experience side effects
• what you should do if you miss a dose

Infections, inflammation, glaucoma, and many other eye disorders often are treated with medicated eye drops.

It is important to remember that all medicines can have side effects. Surprisingly, even the small amount of medication in an eye drop can create significant side effects in other parts of the body. There are ways to decrease the absorption rate of the eye drop into the system and to increase the time the eye drop is on the eye, making the medicine safer and more effective.

Instilling eye drops may seem difficult at first but becomes easier with practice. To place an eye drop in your eye, first tilt back your head. Then create a “pocket” in front of the eye by pulling down on the lower with an index finger or by gently pinching the lower lid outward with the thumb and index finger. Let the drop fall into the pocket without touching the dropper tip to your eye, eyelid, or fingers, so as to prevent contaminating the bottle.

Immediately after instilling the drop, press on the inside corner of the eyelids next to the bridge of your nose for two to three minutes with your thumb and forefinger. This prevents most of the drop from traveling down the tear duct to the back of the throat, where it then is absorbed by the rest of the body. Keep your eyes closed for three to five minutes after instilling eyedrops.

Before opening your eyes, dab unabsorbed drops and tears from the closed lids with a tissue.

If you are taking two different types of eye drops, wait at least five minutes before instilling the second drop. Because the volume of a single drop exceeds the capacity of the surface of the eye, it serves no purpose to use two drops at the same time.