Last week I attended a continuing education course in which we reviewed several difficult glaucoma patient cases. These were all patients with moderate to advanced glaucoma who showed progression and the subsequent need for adjustment of their current glaucoma treatment plans.

Additionally, most of these patients also presented with complicated medical histories, had allergies to certain classes of medications, responded poorly or ineffectively to prior topical glaucoma treatments, and had difficulties with compliance when multiple medications were needed. 

I have had several complicated patients like the ones presented in our lecture in my chair before, and determining the next steps to take for the patient to properly manage their situation can be quite difficult. However, I have found that as long as I know each topical glaucoma medication, its mechanism of action, dosage, side effects, contraindications, and expected treatment effect, I can more easily make my way through the complicated thought process of what to do next. 

In case you feel a little rusty on these medications, I have put together a review of the most important concepts to know for each topical glaucoma medication. 

 Prostaglandin Analogs

 This class of IOP lowering agents is typically the first-line treatment for most patients with open-angle glaucoma or ocular hypertension due to its once-daily dosage, superior efficacy, good 24-hour IOP control, long-term clinical usefulness, and excellent safety profile. 

Mechanism of action:

• Xalatan® (latanoprost) and Travatan® (travoprost) both increase aqueous humor outflow exclusively through the uveoscleral route
• Lumigan® (bimatoprost) promotes outflow of aqueous through both the uveoscleral and trabecular meshwork routes
• Rescula® (unoprostone isopropyl) appears to increase aqueous outflow solely through the trabecular meshwork 

Dosage: Most prostaglandin analogs are prescribed once daily at night (QHS) as they have been shown to have a sustained IOP-lowering effect during the nocturnal period, providing a more controlled diurnal curve. 

Side Effects:

• Conjunctival hyperemia and foreign body sensation are the most common side effects
• Thickening, lengthening, and hyperpigmentation of the eyelashes (reversible)
• Hyper pigmentation of the iris (irreversible); the highest incidence occurs in green-brown irides and the lowest in blue-grey or brown irides
• Hyperpigmentation of the periorbital skin (reversible)
• Cystoid macular edema may occur in eyes that have other risk factors (e.g. capsular rupture or vitreous loss associated with cataract surgery)
• Anterior uveitis is a rare side-effect; therefore, prostaglandins should be cautioned in patients with uveitic glaucoma
• There has been shown to be an increase risk for herpetic keratitis (rare)
• Systemic side effects of prostaglandins are rare, but headaches, skin rashes, and mild upper respiratory tract symptoms have occurred
• Prostaglandins should not be used during pregnancy because of possible teratogenic effects

Preparations:

• Xalatan® (latanoprost): Xalatan® has been shown to be at least as (if not more) effective than timolol (beta-blocker) in reducing IOP. The ocular hypotensive effect for Xalatan® is expected to be about 27-30% (whereas timolol is approximately 20%). The hypotensive effect of Xalatan® appears to be independent of race, gender, iris color, age, type of glaucoma, or previous glaucoma therapy. 
• Travatan® (travoprost): The early formulations of Travatan® were preserved with BAK which demonstrated an increase in potential for corneal epithelial toxicity and subsequent ocular surface disease. Travatan-Z® was later introduced with a unique ionic buffering compound which decreased its associated toxic effects and eliminated the need for a preservative. IOP-lowering effects of Travatan® are similar to Xalatan® except in African Americans, where Travatan® appears to be more effective. 
• Lumigan® (bimatoprost): Lumigan® is considered to be part of the prostaglandin family but has been shown to differ sufficiently from the other prostaglandins and is sometimes referred to as a prostamide. As with the other prostaglandin analogs, studies have proven that Lumigan® used once daily is more effective than timolol twice daily. The mean IOP reduction from baseline is approximately 33% (this is slightly greater than Xalatan® and Travatan®). 
• Rescula® (unoprostone isopropyl): Rescula® is the only prostaglandin that has a twice-daily (BID) dosage. It has also not been shown to be as effective as the other prostaglandins and is arguably not suited as a first-line monotherapy. 

Beta-Blockers

 Beta-blockers are IOP-lowering drugs that antagonize the effects of catecholamines and beta-adrenergic receptor sites. Remember that there are four main types of adrenergic receptors: alpha-1 (arterioles, pupil dilator, and Muller’s muscle), alpha-2 (ciliary epithelium), beta-1 (myocardium), and beta-2 (bronchi and ciliary epithelium). Non-selective beta-blockers are equally potent at beta-1 and beta-2 receptors, while cardioselective beta-blockers are more potent at beta-1 (to reduce the bronchoconstrictive effect of beta-2 blockade). 

Mechanism of action: Beta-blockers reduce IOP be decreasing the secretion of aqueous humor. This is important in that beta-blockers can be utilized in all types of glaucoma treatment, irrespective of the state of the anterior chamber angle. In about 10% of cases, the efficacy of beta-blockers in IOP reduction may decrease over time. This can occur within days of starting treatment (short-term escape) or months/years later (long-term drift). Beta-blockers have been shown to work best when used in the morning, as aqueous production at night is usually less than half of that produced during the day. 

Dosage: Most beta-blockers are recommended to be dosed twice-daily (BID); however, when used as adjunctive therapy, beta-blockers are often used once-daily in the morning (QAM) for the reason stated above. 

Side Effects: 

• Ocular allergies and corneal punctate epithelial erosions; this may cause itching and foreign body sensation for the patient
• Reduced aqueous tear production
• Systemic side effects tend to occur within the first week of initiation of treatment; they are rare but can be potentially serious
• Bradycardia and systemic hypotension can occur due to the effect on beta-1 receptors; therefore, it is very important to evaluate a patient’s pulse before starting treatment with a beta-blocker
• Bronchospasm may be induced secondary to the beta-2 receptor blockade; this can be fatal in patients with asthma or severe chronic pulmonary obstructive disease
• Sleep disorders, confusion, depression, fatigue, headache, hallucinations, decreased libido, and dizziness have also occurred in patients taking beta-blockers

Preparations:

• Timolol (Timoptic®, Timpotic® in Ocudose, Timoptic-XE®, Betimol®, Istalol®): Timolol is a noncardioselective beta-blocker. The mean decrease in IOP is approximately 25% (this is greater than pilocarpine and topical carbonic anhydrase inhibitors, but typically less than prostaglandin analogs). Timolol is usually prescribed twice-daily (BID) as it has been shown that the IOP-lowering effect lasts for at least 12 hours once instilled. However, timolol also works well as a once-daily therapy, and the IOP reduction ranges from about 17-28% with a single drop. There is limited proof that the 0.5% preparation of timolol provides a greater hypotensive effect than the 0.25% preparation. 
• Levobunolol (Betagan®): Levobunolol is similar to timolol in that it is also a noncardioselective beta-blocker. The potency of this medication is also similar to timolol (the mean reduction of IOP given twice-daily is equivalent to the BID dosage of timolol). Levobunolol can also be used as a once-daily medication with a similar IOP-lowering effect as a twice-daily dosage. 
• Betaxolol (Betoptic®): Betaxolol is the only cardioselective beta-blocker, exhibiting greater specificity for the beta-1 receptor, and at the ocular beta-2 receptor it shows about half the potency as timolol (and is therefore less effective at decreasing IOP when compared to timolol and levobunolol). Betaxolol has also been shown to block sodium and calcium channels in the microvascular tissue of the optic disc, which may increase optic disc blood flow and protect critical nerve tissue. Because of this possible added neuroprotection, studies have shown that the preservation of the visual field appears to be superior with betaxolol.
• Metipranolol (OptiPranolol®): Metipranolol is a noncardioselective beta-blocker. Retinal perfusion pressure and blood flow appear to increase when topical metipranolol is administered; however, it has been shown to occasionally cause granulomatous anterior uveitis.
• Carteolol (Ocupress®): Carteolol is a noncardioselective beta-blocker; however, it appears to have more selective action on the eye than on the cardiopulmonary system (may induce less bradycardia than timolol). Carteolol shows a similar IOP-lowering effect to timolol, and also appears to cause less ocular irritation than timolol and may even produce some moderate corneal anesthesia as well. 

Knowing everything there is to know about the most commonly used topical glaucoma medications will help you become more confident when presented with challenging glaucoma patients (which you will encounter many times!). Stay tuned for the next blog post where we will review alpha-agonists, carbonic anhydrase inhibitors, miotics, and the combination medications. 

 -Dr. Dexter 

The Top 15 Tips and Tricks for Studying for Part I of NBEO^®

We’ve put together a ton of great tips and tricks for studying for Part I of NBEO along with two tailored study programs that will help you thoroughly prepare for the big day. Remember, you’ve made it this far and you can totally do this!

Some of the Top 15 Tips include:

• Familiarize Yourself with the Test Format
• Tackle the Weak Subjects Early
• Start Sooner and Ease Into It
• ...and 12 more!