Do you know that among the top 100 best-selling drugs in the US, 22 of them can cause dry eye? In fact, 62% of dry eye cases in the elderly can be attributed to systemic medications, including nonsteroidal anti-inflammatory drugs (NSAIDs), diuretics, vasodilators, analgesics/antipyretics, antiulcer agents, sulfonylureas, cardiac glycosides, anxiolytics/benzodiazepines, anti-infectives, antidepressants/antipsychotics, hypotensive agents, and antihistamines. “TFOS DEWS II iatrogenic report” has summarized research data in this area and compiled a very nice table below.

Table 1.  Systemic medications that contribute to dry eye.

 

The reason why these drugs cause dry eye is not completely known, but it is thought that many of them have anticholinergic activity, which means they target intentionally or unintentionally a class of proteins on cells, and these proteins are important for the secretion of tear, mucous and lipid.

Another reason why drugs can cause dry eye is that some drugs are secreted and form crystals in the tear, including amiodarone, aspirin, bisphosphonates, chloroquine, ibuprofen and clofazimine.

Eye drops, can they make your eyes dry?

The answer is yes.

We all know that artificial tear eye drops alleviate dry eye, but some other eye drops can actually cause dry eye or make it worse. One such example is glaucoma eye drops. It is estimated that they cause burning sensation and dry eye in up to 47% of patients. The reason is that most glaucoma eye drops contain a preservative called benzalkonium chloride (BAK), which is a known toxin for cells and causes inflammation on the surface of the eye, as we talked about previously (link here). Interestingly, once switched to preservative-free glaucoma eye drops, dry eye sensation reduce to 16%. It is noteworthy that because of the common dry eye issues associated with glaucoma eye drop use, eye doctors often prescribe artificial tears to be used while patients are using glaucoma drops. However, if patients use an artificial tear that contains preservatives such as BAK, their dry eye may be worse.

For people with significant dry eye, it is recommended that preservative-free forms of glaucoma eye drops be used, and preservative-free artificial tears regularly supplemented as well. If you have such issues, ask your eye doctor about the preservative-free versions of glaucoma drops.

Of note, the medicated eye drops that make dry eye worse can also be due to the active medication itself, in addition to the preservatives.

Again, “TFOS DEWS II iatrogenic report” compiled a table of eye drops that may cause dry eye. A great reference to patients and doctors both.

Table 2. Topical eye drops that cause dry eye.

In the end, while we know that a number of systemic medications as well as topical eye drops can cause or make dry eye worse, this is not to say that we should discontinue these medications. However, it is helpful that doctors and patients are aware of the dry eye side effect of certain medications, and take measures to treat dry eye while on them, or switch to different medications if necessary.

The most common first-line treatment for dry eye is to use artificial tears (ATs), and these are available OTC. I talked about how to select ATs last time. Eye doctors will also recommend warm compress and lid scrub a couple of times a day, which I also talked about previously. These are really effective for majority of dry eye, which is mild to moderate. If you continue to be bothered by dry eye, there are other treatments available. This article will be about the other treatments your eye doctor may recommend or prescribe. Some of these are products you can buy in store or on the web, others have to be done in a doctor’s office. I have also provided additional links to some of the resources at the end of the article.

Rx eye drops for dry eye

Currently there are two FDA-approved medicated eye drops for dry eye disease, Restasis and Xiidra. The active ingredient for Restasis is Cyclosporine Ophthalmic Emulsion 0.05%. It is an immune suppressant that dampens inflammation on the surface of the eye in chronic dry eye. It was approved by FDA in 2003 based on findings that 15% patients showed increased tear production vs 5% patients in the control group. Caveat with Restasis is that it usually takes 2-3 months of regular using to show an effect.

Xiidra is a Lifitegrast 5% ophthalmic solution, approved by FDA in 2016. Lifitegrast blocks T cell functions, reducing inflammation, and improving dry eye signs and symptoms.

Autologous serum

This is a topical treatment using a patient’s own serum. Your blood is drawn, blood cells are removed, leaving the clear liquid portion called serum.  The serum contains numerous growth factors and hormones, which may promote healing in severe dry eye. However, because of laws and regulations related to blood products, as well as lab processing and storage issues, this is not a popular treatment at the moment; but it is effective, and may gain more insurance coverage in the future.

Intense pulsed light

This was initially used in dermatology to treat acne, skin pigmentation, hair removal and rosacea. Studies have shown that it is safe and effective in treating MGD and improving dry eye. The mechanism of action is not well understood, but may be partially due to the thermal heating of the meibum as well as effects on local blood vessels. It is recommended this procedure carried out multiple times over several months in the doctor’s office.

Punctal occlusion

This is a physical way to block the tear drainage thereby conserving the tears on the eye. Tears are naturally drained via upper and lower tear ducts, which join together and drain into the nasal cavity eventually (Figure 1). By applying a plug to the lower and/or upper puncta (Figure 1), tear will no longer drain easily and therefore stay on the eye for longer. This is a quick and easy in office procedure, and there are plugs that are permanent or temporary based on patients’ need. This treatment is most effective for aqueous deficient dry eye, where the water part of the tear is deficient.

Figure 1. Punctal plug blocking the lower puncta of tear drainage. Image source: http://www.allaboutvision.com/conditions/punctal-plugs.htm

 

Moisture chamber spectacles

Moisture chamber spectacles are eyeglasses that provide a humid environment and minimizing airflow over the ocular surface. These have been shown to be effective in some case reports.

Tear stimulation

A number of topical eye drops containing medication have been developed in the hope of stimulating tears, some failed clinical trials, others still in development. There is one device that is currently available, called the TrueTear™ Intranasal Tear Neurostimulator (by Allergan), that temporarily stimulates tear production. This product uses a weak electrical stimulation by two probes in the nasal cavities where the nerves are stimulated, resulting in nasal lacrimal reflex (meaning the stimulation of nerves in the nose causes tearing reflex).

Warm compress and its derivatives

Warm compress using a wet towel can be tedious as you have to repeatedly warm it up. There are a variety of microwave heatable products that maintain the temperature for 10 min so no reheating needed.

In addition to these products, a device called LipiFlow® accurately delivers heat to the Meibomian glands to therapeutic levels of 42.5 C. Clinical trials show that the single 12-min procedure of the LipiFlow® system is safe and effective for treating MGD and that the effect can be sustained for 6 months. This treatment is however very expensive and not yet covered by insurance.

Rigid gas permeable scleral lenses

These are hard, large contact lenses worn with saline bathing the entire cornea. Some patients will severe dry eye or other ocular surface diseases find this to be the last resort to alleviate their symptoms. There are a variety of scleral lens designs and brands. One of them is called PROSE (Prosthetic Replacement of the Ocular Surface Ecosystem), which has been around for quite a while and has helped thousands of severe dry eye patients.

One word about new drugs in development

Multiple drugs are in research from various approaches. I have personally been involved in research on hormones that promote Meibomian gland health and thereby have potential to be used as novel therapies to treat dry eye, including growth hormone, insulin-like growth factor-1 and testosterone. In addition, ECF843, a recombinant human protein, lubricin, has recently been licensed by Novartis for up to $ 1 billion. Large scale clinical trials are anticipated.

References and more resources

• TFOS DEWS II Management and Therapy Report
• Intense pulsed light: https://www.reviewofoptometry.com/article/feel-the-burn
• PROSE scleral lens: http://www.bostonsight.org/PROSE/PROSE-Treatment/About-PROSE
• LipiFlow: http://tearscience.com/en/the-tearscience-system/treatment/
• TrueTear™ Intranasal Tear Neurostimulator: https://www.truetear.com/

 

 

A patient’s guide to artificial tears

The new TFOS DEWS II report provides the latest understanding of dry eye disease (Click here to know more about TFOS DEWS II, the most authoritative literature review worldwide on dry eye disease). How are eye doctors treating dry eye? It turns out, artificial tears are still the first line of treatment. Go to any drug store, and you will find dozens of different bottles of artificial tears. What are in them, what are the differences, and how can you pick out one that is good for you? Let’s take a look. Much of this article is based on information from “TFOS DEWS II Management and Therapy Report”.

There are two major types of artificial tears, one that supplements the aqueous, or water part of the tear, and the other that supplements the lipid part of the tear. We know from my previous post (link here) that majority of dry eye is actually caused by Meibomian gland dysfunction (MGD) which results in lipid deficit and rapid evaporation of the tear. Therefore some of the newer artificial tears contain lipid.

Aqueous supplementing artificial tears

To provide lubrication, viscosity enhancing agents are used. These are often referred to as the ‘active ingredient’ in the artificial tears. They include carbomer 940 (polyacrylic acid), carboxymethyl cellulose (CMC), dextran, hyaluronic acid (HA), HP-guar, hydroxypropyl methylcellulose (HPMC), polyvinyl alcohol (PVA), polyvinylpyrrolidone (PVP) and polyethylene glycol. You don’t have to memorize these names at all. I have listed them here in case you want to read the ingredient list on a product and wonder what that weird name means. What matters is that they prolong the time the artificial tear stays on your eye, and that most of these viscosity agents work similarly well.

Some examples: Carboxymethycellulose is used in Refresh and TheraTears; Hydroxypropyl Cellulose is used in Genteal; Hydroxypropyl Guar is used in Systane; and Sodium hyaluronate is used in Blink.

Lipid supplementing artificial tears

These are emulsions where small lipid droplets are suspended in the water base. For example, Systane Balance contains a polar phospholipid, DMPG (dimyristoylphosphatidylglycerol), in addition to Propylene Glycol which is a lubricant; and Retaine MGD contains mineral Oil 0.5% as a lipid.

 

Gels and ointments

These are thick tears that will stay on the eye for longer, but will cause blurry vision while they stay on the eye, so mostly used at night or before bedtime. They contain high concentration of the viscosity agent, and/or mineral oil. Examples include Genteal Night time gel, Refresh PM and Refresh Lacrilube. These are good choices to use especially if you suffer from dry eyes in the morning or when waking up.

 

Preservatives vs preservative-free

Preservatives are essential these days to prolong the shelf-life of food, cosmetics, medication, as well as artificial tears. For a ½ oz (15 ml) drop bottle, it will take about a month to finish if you put 4 drops in each eye daily. Of course you will try to avoid touching the tip with finger or eye or anything except for air, and replacing the lid immediately after each use. Still, as soon as you open that sterile bottle, bacteria or fungus free-floating in the air will inevitably get in, let alone the accidental touching of hand, eyelids or other objects. In addition, many people use artificial tears in an as needed manner, this will make each bottle last longer, increasing risk of contamination. A good practice I would recommend is that once you open a bottle, label it with date of opening, and discard after 3 months even if it’s not finished.

So, preservatives allow us to store artificial tears for longer. However, they are known to cause adverse effects on the surface of the eye. The most commonly used preservative in eye drops is called benzalkonium chloride (BAK). “BAK can induce corneal and conjunctival epithelial cell death, damage the corneal nerves, delay corneal wound healing, interfere with tear film stability and cause loss of goblet cells”. To prevent these adverse actions, you should not use preserved artificial tears more than 6 times a day.

Of course, the far better alternative is to use preservative-free (PF) artificial tears. You will know if an artificial tear is PF when you see it is individually packaged in small vials. Once you open one vial, it is good for 24 hours and you should discard it after that. Examples of PF artificial tears include Refresh Celluvisc, TheraTears Liquid Gel, and Retaine MGD.

The problem with these is that they are expensive. A number of new products are now available that use one-way valve dispensers which avoid contamination and allow multiple-use of a PF bottle. I am awaiting for artificial tears to be packaged this way, and hopefully it will be cheaper than the PF tears individually packed. If you know of such a product, let me know by leaving a comment.

Another alternative to the BAK issue is to develop alternative “softer preservatives” which are less harmful to the eye. These are used in eye drops such as glaucoma medications and not just limited to artificial tears. These include oxidative preservatives (sodium chlorite; Purite® and OcuPure™ and sodium perborate; GenAqua™), polyquaternium-1 (Polyquad®) and Sof-Zia™. They cause less adverse reactions on the eye, but still, PF is better, especially if you are using the eye drops multiple times for long-term.

 

Be careful with redness relief

Some OTC eye drops provide a quick redness relief, such as Visine, ClearEye, Rohto. While they do contain lubricants for dry eye, the redness relief ingredients, which include Tetrahydrozoline or Naphazoline, should not be used long-term. These redness relief ingredients are vasoconstrictors that restrict tiny blood vessels in the eye, making the redness disappear; when used long-term, can actually cause rebound redness, making red eyes worse.

With chronic dry eye, the irritation on the surface of the eye can lead to dilation of the tiny vessels in the conjunctiva, which is the white part of the eye. Therefore the root cause of redness in this case is dry eye itself. Regular use of artificial tears helps to restore normal ocular surface environment, this will get rid of the redness. Forcing the blood vessels to constrict with medication without treating dry eye itself, such as using a vasoconstrictor, will make redness worse if you stop the medication.

In practice, we routinely recommend lubricating artificial tears, but suggest patients to use redness relief only in temporary or emergent situations, such as going to a party in a few hours. In the long term, please control your dry eye, the cause of redness in many cases.

Summary

I have given a brief guide to the various artificial tears available over-the-counter. There are artificial tears that are primarily lubricating via supplementing the water part of the tear, there are also ones that supplement the lipid part. Some are more viscous than others, and the gels and ointments are so thick that they will blur vision for hours, so they are best used before bedtime. Most artificial tears in regular eye drop bottles contain preservatives, which are harmful for the surface of the eye when used in long-term. I would like all patients to use PF artificial tears if possible, but cost is a significant impeding factor.  Finally, watch out for quick redness relief, and do not rely on these long-term, as you will find redness coming back worse once you stop using them. In reality, you may find one particular eye drop to be soothing to you while others are not so great. Don’t be afraid to try a few ones and find the best for you.