Published in Glaucoma

The Drop Debate: Patient Considerations and Conundrums

This is editorially independent content
12 min read
In this talk from Eyes on Glaucoma 2022, Dr. Y. Shira Krecsh explains how to choose the most effective and safest glaucoma drops for each specific patient and, conversely, which drops should be avoided.
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On June 10-11, eyecare practitioners from all over the world gathered online for Eyes On Glaucoma 2022, a two-day educational event all about glaucoma disease diagnosis, treatment, and management.
With so much fantastic education happening at once, we knew that people had to choose which sessions to attend. So over the next few months, we'll be releasing much of the excellent content from Eyes On Glaucoma for you to watch at your leisure—whether for the first time or to review important learnings!
Scroll down to unlock this recording of Dr. Y. Shira Kresch's full discussion on glaucoma eye drops, and don't forget to check out our list of future events!
Please note that these videos are provided for review only.
Glaucoma is a progressive optic neuropathy that can lead to blindness if left uncontrolled. Glaucoma affects over 80 million people globally. Optometrists and ophthalmologists are responsible for detecting, treating, and managing those at risk of glaucoma and patients with glaucoma.
Treatment is often tricky with topical, oral, laser, and surgical options. Within each of these forms of treatment, there are several categories. This Eyes On Glaucoma session focused on the various forms of medical treatments using an easy-to-follow, case-by-case approach. You will learn about the most effective options for your patients, and perhaps more importantly, understand why certain drops should not be used on specific patients.
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Watch the full discussion on glaucoma eye drops!

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The four Cs of topical medications

When choosing a topical medication for your glaucoma patient, remember the four Cs: Cost, Compliance, Comorbidities, and Cosmesis. Each of these considerations can have a major impact on the effectiveness of your chosen prescription.
Often, many doctors will take standardized measures, but every patient is unique and requires a thoughtful approach. Glaucoma treatment is as much an art as it is a science—but the science is still very important.
To begin with, here are some important definitions:
  • Contraindication: a pre-existing condition that renders a drug neither safe or effective. Depending on the condition and the medication, contraindications can require a loose or a hard stop.
  • Side effects: undesirable effects of a drug that are predictable by the drug’s MOA.
  • Adverse events: undesirable effects of a drug that are not predictable by the drug's MOA. These can range from dose-dependent adverse events, such as toxic drug effects, to non-dose-dependent adverse events, such as allergic reactions.
A crucial step in choosing the right medication for your patient is weighing the clinical benefit versus the potential harm. To reach your treatment goal with glaucoma, look for the hypotensive agent with the highest likelihood of reaching the target IOP with the lowest risk profile—for each patient.

Mechanisms of action

Aqueous is produced by the non-pigmented epithelium of the ciliary body and is controlled by several factors, including enzymes and blood flow. A simple analogy would be blowing up a balloon. There are two ways to control the pressure inside the balloon: you can decrease the production of air or open the end of the balloon to release some of the air that’s already inside.
Topical medications for treating glaucoma fall under these categories. Their mechanisms of action work by lowering the amount of aqueous production or increasing the outflow of produced aqueous. Many drugs target both of these methods, while others focus on one or the other. As eyedrops, these medications don’t get metabolized in the liver; rather, they are absorbed through the mucosa of the nasal cavity.
There are many different topical medications on the market for glaucoma treatment these days:
  • Beta blockers
  • Alpha agonists
  • Prostaglandins (including nitric oxide)
  • Carbonic anhydrase inhibitors
  • Rho kinase inhibitors
  • Miotic or cholinergic agents
  • Combination therapies
This session will cover each major category and the considerations to remember when prescribing them to your patients.

Watch the full recorded session!

Beta blockers

Beta blockers used to be the primary first-line treatment in topical medications for glaucoma. However, they have many possible systemic contraindications and side effects, including (but not limited to) bradycardia, asthma, COPD, and considerations for athletes as well as known side effects like conjunctivitis, blepharitis, hypotension, depression, and impotence—to name only a few.
When prescribing beta blockers, keep the following considerations in mind:
  • Is there respiratory or heart disease in this patient?
  • Is the patient at high risk for hypoglycemia?
  • Is there depression, anxiety, fatigue, or impotence?
  • Does the patient have thyroid disease or myasthenia gravis?
Make sure to watch the recorded session for the full discussion and patient case!

Alpha agonists

Alpha agonists target alpha-2 receptors, decreasing aqueous production and increasing aqueous outflow. They’re often favored for younger patients, as some evidence suggests they’re neuro-protective.
However, there are substantial contraindications for alpha agonists: they cannot be prescribed to those with orthostatic hypotension, depression, or Raynaud’s phenomenon, nor can they be prescribed to children under 4 years of age. Additional considerations for alpha agonists include any oral medications your patient may be taking, as they have the potential to interact poorly with digoxin, anti-depressants, and oral beta blockers.
Alpha agonists are also notorious for their side effects, the most well-known of which is conjunctival blanching.
When prescribing alpha agonists, keep the following considerations in mind:
  • Is this a child under 3-4 years old?
  • Is the patient hypersensitive?
  • Does the patient have low blood pressure?
Make sure to watch the recorded session for the full discussion and patient case!

Prostaglandin analogues

Prostaglandin analogues are a highly popular category of topical medications for glaucoma, and it’s easy to see why. They have no systemic contraindications. However, the side effects of this category of topicals are substantial and can include pigmentation changes, periorbital fat atrophy, hypertension, and other side effects.
It’s especially important to note with this category of medications that their dosage is limited to once per day. There are studies indicating that increased dosage leads to decreased effectiveness. Prostaglandin analogues are standardly dosed at night, so the immediate redness often experienced upon instillation has time to fade. However, for patients who must take it in the morning for any reason, such as lifestyle considerations, make sure to impress upon them to take the medication at the same time every day.
When prescribing prostaglandin analogues, keep the following considerations in mind:
  • Does the patient have active inflammation or are they prone to inflammation?
  • Is this for unilateral use?
  • Does the patient have hazel or light-colored eyes?
Make sure to watch the recorded session for the full discussion and patient case!

Carbonic anhydrase inhibitors

Carbonic anhydrase inhibitors are another important category of drops with both standalone and combination possibilities. They’re commonly prescribed, but there isn’t a strong understanding of their mechanism of action. Carbonic anhydrase inhibitors are direct antagonists to the ciliary epithelial carbonic anhydrase, the enzyme important for producing aqueous humour. More than 90% of that enzyme must be inhibited to lower IOP.
Carbonic anhydrase inhibitors, for this reason, are extremely potent. Oral CAI are even more potent than drops, but can have significant systemic side effects and should only be prescribed in collaboration with a medical team. However, drop CAI can result in up to a 20% reduction in IOP, which is still immensely significant for many glaucoma patients.
The main contraindications for carbonic anhydrase inhibitors are hypersensitivity to sulfonamides. Side effects can include punctate keratitis, burning, headaches, and kidney stones, to name a few.
When prescribing carbonic anhydrase inhibitors, keep the following considerations in mind:
  • Is the cornea healthy, specifically endothelial function (e.g., Fuchs' dystrophy)?
  • Does the patient have hepatic or renal issues? (systemic use)
Watch the recorded session for the full discussion and patient case!

Rho kinase inhibitors (Rhopressa)

Rho kinase inhibitors can improve the outflow of trabecular meshwork by around 35% and can improve episcleral venous pressure by around 10%, leading to a nice reduction in IOP. They are dosed once daily, usually at night, in the hopes that any conjunctival hyperemia will fade by morning.
Like prostaglandin analogues, there are no contraindications for rho kinase inhibitors. Regarding side effects, however, the biggest one is conjunctival hyperemia, which occurs in over 50% of patients. Also, in my experience, another 20% can expect to see corneal verticillata and potentially other side effects. However, there are no known systemic side effects with rho kinase inhibitors.
When prescribing rho kinase inhibitors, keep the following considerations in mind:
  • Can the patient tolerate the hyperemia?
  • Is this for unilateral treatment?
Watch the recorded session for the full discussion and patient case!

Miotic or cholinergic agents

Miotic or cholinergic agents work by stimulating ciliary muscle contraction, which pulls on scleral spur and increases aqueous outflow. Pilocarpine has declined in popularity in recent years but is still frequently used with patients who need it, particularly patients who have had glaucoma surgery and are maxed out on their other medications.
With miotic or cholinergic agents, you can expect a decrease in IOP of around 20%. Contraindications include asthma, acute iritis, and perhaps most importantly, retinal detachment, which is a common known side effect of miotic agents. Other known side effects include but are not limited to blurred vision, accommodative spasm, nausea, and bronchospasm.
I don’t recommend miotic agents as a first-line treatment for my younger patients, since they tend to be uncomfortable with the cosmetic side effects. Miotics make the pupil smaller and your patients won’t dilate well, meaning that you’ll have an increased risk of retinal events and a more difficult time checking for the same.
When prescribing miotic or cholinergic agents, keep the following considerations in mind:
  • Is the patient myopic?
  • Does this patient have lattice degeneration?
  • Is there a history of retinal detachment?
  • How high is this patient’s accommodation?
  • How will a small pupil affect this patient?
Watch the recorded session for the full discussion and patient case!

Combination therapy

Our last category is combination therapies. These drugs will have a combination of side effect profiles. While they often make for easier scheduling, they are also potentially more expensive.
With combination therapies, I recommend a slow, conservative approach. Remember, glaucoma is a long-term, chronic disease and you will be dealing with these patients for a long time. It’s helpful to get as much information as possible, so start slow and ramp up. You’ll see all of the effects of the drugs—positive and negative—before you start combining them.
Sometimes you’ll see slightly better IOP reduction from separate medications, but usually, the combinations are pretty effective.

General questions to keep in mind

  • How does age factor into the treatment plan?
  • Which drops might you avoid in a young person?
  • Which drops might you avoid in an elderly person?
  • How about pregnant patients?
  • What can we know/deduce about adherence?

How do you decide?

Ultimately, the decision is down to you and your patient. When discussing branded medications, don’t be afraid to present the options and let your patients make the decision.
One last note on preservative-free medications: it’s good to have them on hand when preserved options fail and your patient has concurrent dry eye symptoms. Dry eye syndrome and glaucoma go hand in hand.
As always, asking about systemic conditions is crucial before moving to treatment. Discuss the side effects with your patients, and set guidelines for yourself for when to consider changing course.

Watch the full recorded session!

Y. Shira Kresch, OD, MS, FAAO
About Y. Shira Kresch, OD, MS, FAAO

Dr. Shira Kresch is a primary care optometrist who specializes in the non-surgical treatment and management of glaucoma as well as myopia control. After obtaining her BS in Nutrition and Food Science from Wayne State University Honors College with a co-major in University Honors, she received her OD/MS degrees from the State University of New York and completed her residency in primary care and ocular disease at the NY VA Harbor Healthcare System under the supervision of Dr. Murray Fingeret and Dr. Evan Canellos.

Following residency, Dr. Kresch underwent further training with Dr. Jeffrey Liebmann and Dr. Jack Cioffi in the glaucoma service at Columbia University Medical Center where she is currently an Instructor of Optometric Sciences in Ophthalmology and the clinic lead of the myopia control clinic.

In addition to her clinical work, Dr. Kresch pursues research in the areas of early detection of glaucoma and technological advances in patient education.

Y. Shira Kresch, OD, MS, FAAO
Eyes On Eyecare Editorial Team
About Eyes On Eyecare Editorial Team

Led by Editor-in-Chief Eleanor Gold, PhD, Eyes On Eyecare is a digital publication that provides clinical and career education to the young generation of optometrists and ophthalmologists. We work with eyecare professionals to create compelling, educational content available for free to all those in the eyecare industry. To learn more about our team, values, and other projects, visit our About page.

Eyes On Eyecare Editorial Team
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