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THE GLAUCOMA THERAPY TOOLBOX

A look at the IOP-lowering drugs and when to refer for surgery and co-management

Glaucoma treatment is focused on lowering IOP via medication, laser and/or surgery. No universal management recipe exists, so each patient must have their therapy personally tailored. When medication alone is insufficient, patients are referred for surgery, and they’re co-managed.

Here, I discuss the currently available glaucoma drugs (in alphabetical order), when to refer patients and co-management.

 

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ALPHA-ADRENERGIC AGONISTS

These lower IOP by decreasing aqueous production, as well as increasing uveoscleral outflow. They are often used as adjunctive therapies with beta-blockers or prostaglandin analogues (PGAs).

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Ideal patients. Anterior segment laser surgery patients, as these drugs reduce the risk of an IOP spike (apraclonidine). These drugs are also to be used as adjunct therapy in open angle glaucoma patients (brimonidine).

Current formulations. Apraclonidine (iopidine 0.5% and 1%, Novartis and generic) and brimonidine. Because of tachyphylaxis, apraclonidine use is limited to preventing post-laser IOP spikes. Brimonidine is used for chronic therapy, but has reduced nocturnal efficacy. The available brimonidine products: generic formulations (0.2% preserved with BAK and 0.15% non-BAK preservative) and 0.1% (Alphagan P, Allergan, preserved with Purite). Writing a prescription for “Alphagan P” may result in the generic 0.15% concentration, so specify the concentration.

Contraindications/adverse events. The most common side effect with brimonidine is allergic conjunctivitis, which appears concentration-related. Other side effects: dizziness, drowsiness, dry mouth, hypotension and central nervous system (CNS) depression. Brimonidine is not recommended in children of any age due to the possibility of severe CNS and respiratory depression.

Dosing. First-line therapy: t.i.d. Adjunctive therapy: b.i.d., off-label fashion (brimonidine). One drop pre- and post-laser (apraclonidine).

BETA-BLOCKERS

Beta-adrenergic receptor antagonists, or beta-blockers, lower IOP by decreasing aqueous production. The effect is rapid.

Ideal patients. Those who require rapid IOP reduction, such as acute angle closure or post-op IOP spike, often in combination with brimonidine. These can also be used in open angle glaucoma patients who have PGA contraindications. Current formulations. levobunolol hydrochloride 0.5% (Betagan, Allergan) and 0.25% and 0.5% (generic), timolol hemihydrate 0.25% and 0.5% (Betimol, Akorn) and timolol maleate 0.25% and 0.5% (Timoptic, Timoptic Ocudose and Timoptic XE, Valeant Ophthalmic) and 0.5% (Istalol, Bausch + Lomb, and generic). Also, the beta-1 selective betaxolol hydrochloride 0.5% (generic) and 0.25% (Betoptic-S, Novartis), which has reduced efficacy, but an improved pulmonary side effect profile.

Contraindications/adverse events. Asthma, chronic obstructive pulmonary disease, uncompensated congestive heart failure and symptomatic bradycardia, as beta-blockers have the potential to cause serious cardiovascular and pulmonary side effects.

In terms of adverse events, concurrent use of a systemic beta-blocker may reduce topical beta-blocker therapy efficacy in glaucoma. Another important consideration: As with brimonidine, the IOP-lowering effect is significantly reduced during sleeping hours.

Dosing. As monotherapy: b.i.d., but clinical studies reveal q.d. dosing is also effective. If used q.d., early morning instillation is critical, based on the reduced nocturnal effect.

CARBONIC ANHYDRASE INHIBITORS

These, also known as CAIs, lower IOP by reducing aqueous production. They are available orally or topically. As with alpha-adrenergic agonists, topical CAIs are often used as an adjunctive therapy with beta-blockers and PGAs.

Ideal patients. Those who have an acute, extreme elevation of IOP (40mmHg or higher) may need oral CAI therapy. Topical therapy is typically adjunct for open angle glaucoma.

Current formulations. Acetazolamide 125mg and 250mg tablets (generic) and 500mg sustained-release capsules (generic and Diamox Sequels) are the most commonly used oral CAI. Topically, brinzolamide 1% (Azopt, Novartis) and dorzolamide 2% (generic and Trusopt, Merck)

Contraindications/adverse events. Oral therapy can result in fatigue, paresthesia and more serious conditions, such as metabolic acidosis. Topical therapy can produce stinging and a bad taste post-instillation. Also, CAIs can reduce the function of the corneal endothelial pump, contraindicating them in patients who have corneal endothelial dysfunction. Controversy exists regarding the use of CAIs in patients who have reported sulfonamide allergy, so cautious use in patients with reported sulfa allergy is advised.

Dosing. Acetazolamide in-office use is typically two 250mg tablets; for longer use, 500mg sustained-release capsule b.i.d. Topicals: FDA recommended dosing: t.i.d., adjunctive therapy: b.i.d. (off label).

FIXED COMBINATION

Fixed combination medications provide patient convenience and have the added benefit of decreasing the preservative load.

Ideal patients. Those who need more than one medication to achieve rapid IOP reduction and who may become confused by using multiple bottles, which could lead to poor adherence. Fixed combination medications are often used as adjunct therapy in combination with a PGA; a typical scenario might be to add a topical CAI to a PGA as initial adjunct therapy. If additional IOP-lowering is needed, the CAI is switched to a fixed combination to achieve a therapy of three medications but with only two bottles. Brinzolamide/Brimonidine 1%/0.2% (Simbrinza, Novartis) is ideal as an adjunct therapy in patients who have beta-blocker contraindications, as the other two fixed combinations contain timolol.

Current formulations. Simbrinza, brimonidine 0.2%/timolol 0.5% (Combigan, Allergan) and dorzolamide 2%/timolol 0.5% (generic, Cosopt, and Cosopt PF, Akorn). (Compounding pharmacies Ocular Science and Imprimis recently began offering customized drops, which may contain as many as four agents (brimonidine, dorzolamide, latanoprost and timolol). These drops are not commercially available at pharmacies, and they do not copy commercially available combinations. Compounded drugs are not FDA approved.)

Contraindications/adverse events. Listed above. The main disadvantage of fixed combination medications is an increased side effect profile, as each combination has the potential side effects of its respective components.

Dosing. Timolol-containing fixed combination drugs: b.i.d., Simbrinza: t.i.d., adjunctive therapy: b.i.d. (off label).

NETARSUDIL

The newest glaucoma medication is netarsudil ophthalmic solution 0.02% (Rhopressa, Aerie Pharmaceuticals). Rhopressa, FDA approved in December, is believed to reduce IOP by increasing the outflow of aqueous humor through the trabecular meshwork, Aerie Pharmaceuticals says.

Ideal patients. TBD.

Contraindications/adverse events. Reported side effects include conjunctival hyperemia and corneal verticillata.

Dosing. Q.d. in the evening.

PGAS

Many practitioners opt for PGAs first, due to the medication’s excellent efficacy, 24-hour IOP control and minimal side effects. They lower IOP by increasing aqueous outflow through the uveoscleral pathway.

Ideal patients. Those who do not have an acute IOP elevation, such as those with acute angle closure or postop IOP spike.

Current formulations. Bimatoprost 0.03% (generic), bimatoprost 0.01% (Lumigan, Allergan), latanoprost 0.005% (generic and Xalatan, Pfizer), latanoprostene bunod 0.024%, (Vyzulta, Bausch + Lomb), tafluprost 0.0015% (Zioptan, Akorn) and travaprost 0.004% (generic and Travatan Z, Novartis). The latter two are ideal for patients who have ocular surface disease or sensitivity to BAK, as the former is preservative free and the latter offers an ionic-buffered preservative. Vyzulta, FDA approved in November, is a nitric oxide-donating PGA that provides an added mechanism of increased conventional outflow through the trabecular meshwork, Bausch + Lomb says. Choosing the right PGA can depend on patient cost, preservative and side effect profile.

Contraindications/adverse events. Conjunctival hyperemia and eyelash growth, potential for reversible periorbital skin pigmentation changes and, rarely, irreversible iris color changes. Another common side effect: prostaglandin analogue periorbitopathy. These side effects are more noticeable with monocular use, so consider other medications in cases of unilateral glaucoma therapy. Further, there are reports of increased inflammation and cystoid macular edema with PGA use, but several studies have reported no increased risk. Caution should be used in these cases.

PILOCARPINE

Pilocarpine and other cholinergic agonists were used extensively prior to the development of newer medications, such as PGAs. They work by increasing aqueous outflow through the conventional (trabecular) pathway. They have fallen out of favor in the management of open angle glaucoma, due to undesired side effects and four times a day dosing, but remain important in the management of acute angle closure with pupillary block.

Ideal Patients. Patients with acute angle closure with pupillary block.

Current Formulations. Generic pilocarpine in 1%, 2% and 4%. O.D.s should keep a bottle of 1% pilocarpine in their offices for emergency use.

Contraindications/adverse events. Miotic therapy can cause pain and headache due to accommodative spasm, and is not well tolerated by people younger than 50 years old. In addition, the miosis may cause dim vision; with chronic use, the miosis may become permanent, making diagnostic mydriasis difficult or impossible. Redness, tearing and ocular irritation are common. Respiratory side effects may occur in patients with a history of asthma.

WHEN TO REFER PATIENTS

When glaucoma progresses despite maximum tolerated medical therapy, laser trabeculoplasty (LTP) or incisional surgery may be needed.

LTP is relatively non-invasive and can be performed by optometrists in some states. That said, O.D.s in all states can provide post-laser care immediately following the procedures. (See: http://bit.ly/2Cd2ZNl for post-op guidelines.) Given its excellent safety profile, LTP is often considered as early adjunct or even first-line therapy rather than waiting until maximum medical therapy has been reached. Incisional surgery includes traditional filtering surgery, as well as the new minimally invasive glaucoma surgeries (MIGS). Filtering surgery post-operative care is more complex, as it involves carefully titrating the appropriate amount of aqueous filtration, sometimes involving suture lysis or even a return to the operating room. Therefore, many surgeons prefer to follow their patients for several weeks before returning the patient to their optometrist. MIGS are typically performed at the time of cataract surgery, and post-operative care is essentially the same as cataract post-operative care.

KNOWLEDGE IS POWER

By knowing the ideal patients, current formulations, contraindications/adverse events and dosing of the available glaucoma drugs, as well as when to refer for surgery and the related co-management, we play an important role in reducing the vision loss associated with glaucoma. OM