The Dry Eye

Are we underdiagnosing allergy?

Whether you are speaking at or listening to a CME lecture or a sponsored dinner program, the number of dry eye disease patients in the U.S. is given as either 16 million or 30 million patients. I have long held that both are underestimates. From my experience in the clinic and chatting with other eye docs around the country, DED is vastly underdiagnosed. My working number of likely DED sufferers in the U.S. has been 50 million. It has been my contention that dry eye symptoms have been ascribed to other diagnoses by both patients and doctors. While working on a new presentation, I learned that 60 million Americans are diagnosed with allergic conjunctivitis, which confirms my suspicion.

Or does it?

There is no question that DED is underdiagnosed in the U.S. All manner of symptoms that ultimately turn out to be due to DED are routinely misdiagnosed, most commonly blurred vision. Countless patients come to SkyVision Centers with a diagnosis of allergic conjunctivitis, on a perfectly reasonable allergic conjunctivitis treatment regimen, with no discernable reduction in their symptoms. A basic examination reveals obvious signs of DED, and switching to a standard DED treatment regimen usually produces results.

It seems as if every patient who comes to the office with a red eye thinks they have an allergy. Or “sinus,” but I still have no idea what “sinus” is. Clearly there are an awful lot of eye doctors (and likely primary care doctors) out there who agree with those patients if 60 million people are diagnosed with allergic conjunctivitis. I am utterly convinced that DED is diagnosed less frequently than it exists out in the wild. It is hard to treat, and when you add in all of the health insurance nonsense you must deal with to get your patients treated, this is no surprise.

It always seemed to me that “allergy” was the copout diagnosis. Your patient already thinks they have symptoms due to allergies; there are a number of older medicines on the market, some of them generic; many of the patients who actually have an early dry eye may receive a bit of relief from the vehicle in the allergy drop. On top of that, there is no real controversy about whether or not allergic conjunctivitis is a real clinical entity. Honestly, though, that 60 million number shook my confidence enough that perhaps it is time to reexamine allergies and the eye.

Rather than trust my memory, I decided to seek some help from my long-time buddy and fellow OG Mark Milner. When talking about DED, Mark has long described allergic conjunctivitis as one of the great “co-conspirators” in the creation of ocular surface inflammation. Indeed, anyone who takes care of DED patients knows that there is an uptick in visits from symptomatic patients during the local allergy season. As an aside, I once asked a colleague from SoCal when their allergy season began. He replied: “Sunrise.”

None of us is missing the diagnosis of vernal conjunctivitis or giant papillary conjunctivitis. When we are discussing allergic conjunctivitis, we are talking about seasonal or perennial allergies. Unfortunately, we do not as yet have a point-of-care test that would allow us to make an objective diagnosis. Patients typically present with bilateral symptoms and signs. The most common ocular symptom is itching, and they will often describe both tearing (clear) and a runny nose (also clear). And redness. They also complain that their eyes are always red.

Of course, all of this can also be seen in all kinds of DED patients. What separates the allergy patient from the DED patient is swelling. These folks often have obvious chemosis that can be striking. It behooves us to evert the lower lid and look for subtler signs of swelling of the conjunctiva in the inferior cul-de-sac. My diagnostic accuracy seems to improve if I see these patients earlier in the day; they tend to have lid edema and periocular “puffiness” that is more prominent in the morning.

An environmental allergen (pollen, mold, animal dander) comes in contact with the ocular surface. From there it is presented to mast cells. This triggers degranulation and the release of histamine, chemokines and cytokines. H1 receptors on sensory nerves are activated, leading to itching. Histamine binding with H2 receptors on blood vessels results in increased permeability and swelling. Chemokines attract more inflammatory cells, and the cytokines that have been released activate these cells once they arrive on the scene.

Treating allergic conjunctivitis is an old story. Prescribe a topical steroid, and you will be simultaneously a genius and your patient’s new best friend. Every single corticosteroid will work, and of course you have all of the potential side effects and complications (increased IOP, cataract formation) that come along with your new Mensa membership. The histamine story is well known, though, and the rest of the anti-allergy armamentarium stems from that knowledge.

Mast cell stabilizers were first approved in the ’80s. Opticrom (cromolyn sodium ophthalmic solution) is used four times per day. Alocril (nedocromil sodium ophthalmic solution) is both more effective and more convenient; it only needs to be instilled twice a day. The problem with both of these medications is that it takes weeks for them to have any effect on symptoms. Because of this, the ’80s and ’90s were a time of intense competition. Big pharma raced to develop effective topical antihistamine drops that would prevent histamine that was already released from causing symptoms.

With the exception of epinastine, which blocks both H1 and H2 receptors, all of the presently available antihistamine drops are H1 blockers. Believe it or not, there has not been a new antihistamine molecule approved or launched in the U.S. since Lastacaft (alcaftadine, Allergan), and that was nearly 10 years ago. There are branded versions of prescription-only medications, such as Pazeo (olopatadine hydrochloride ophthalmic solution) and Optivar (azelastine hydrochloride ophthalmic solution), but at the moment Bepreve (bepotastine besilate ophthalmic solution, Bausch + Lomb) is the only medication that is brand-only. (Note: Zerviate (cetirizine ophthalmic solution, Nicox/Eyevance), a topical formulation of the medication best known as Zyrtec, will soon be available.)

So, if you are convinced that your patient does have allergic conjunctivitis, how do you go about treating them? Dr. Milner suggests simultaneously starting both a mast cell stabilizer and an antihistamine, only using a steroid in the most severe cases. Which ones should you prescribe? That depends on your experience with the various options as well as your stomach for battling pharmacy benefit managers for coverage. The “easy button” is Zaditor (ketotifen fumarate) because it is over the counter. Sadly, Zaditor is the least effective of all the options in my experience. Far better to fight the fight for the first prescription to more effectively and efficiently treat your patient’s symptoms with a more effective drop and then perhaps “step down” to the OTC option for maintenance.

Unless your patient also happens to have DED, and the allergic conjunctivitis is also kicking up a sandstorm there. But, of course, you already know how to take care of that.

Disclosure: White reports he is a consultant to Allergan, Shire, Sun, Kala, Ocular Science, Rendia, TearLab, Eyevance and Omeros; is a speaker for Shire, Allergan, Omeros and Sun; and has an ownership interest in Ocular Science and Eyevance.

Whether you are speaking at or listening to a CME lecture or a sponsored dinner program, the number of dry eye disease patients in the U.S. is given as either 16 million or 30 million patients. I have long held that both are underestimates. From my experience in the clinic and chatting with other eye docs around the country, DED is vastly underdiagnosed. My working number of likely DED sufferers in the U.S. has been 50 million. It has been my contention that dry eye symptoms have been ascribed to other diagnoses by both patients and doctors. While working on a new presentation, I learned that 60 million Americans are diagnosed with allergic conjunctivitis, which confirms my suspicion.

Or does it?

There is no question that DED is underdiagnosed in the U.S. All manner of symptoms that ultimately turn out to be due to DED are routinely misdiagnosed, most commonly blurred vision. Countless patients come to SkyVision Centers with a diagnosis of allergic conjunctivitis, on a perfectly reasonable allergic conjunctivitis treatment regimen, with no discernable reduction in their symptoms. A basic examination reveals obvious signs of DED, and switching to a standard DED treatment regimen usually produces results.

It seems as if every patient who comes to the office with a red eye thinks they have an allergy. Or “sinus,” but I still have no idea what “sinus” is. Clearly there are an awful lot of eye doctors (and likely primary care doctors) out there who agree with those patients if 60 million people are diagnosed with allergic conjunctivitis. I am utterly convinced that DED is diagnosed less frequently than it exists out in the wild. It is hard to treat, and when you add in all of the health insurance nonsense you must deal with to get your patients treated, this is no surprise.

It always seemed to me that “allergy” was the copout diagnosis. Your patient already thinks they have symptoms due to allergies; there are a number of older medicines on the market, some of them generic; many of the patients who actually have an early dry eye may receive a bit of relief from the vehicle in the allergy drop. On top of that, there is no real controversy about whether or not allergic conjunctivitis is a real clinical entity. Honestly, though, that 60 million number shook my confidence enough that perhaps it is time to reexamine allergies and the eye.

PAGE BREAK

Rather than trust my memory, I decided to seek some help from my long-time buddy and fellow OG Mark Milner. When talking about DED, Mark has long described allergic conjunctivitis as one of the great “co-conspirators” in the creation of ocular surface inflammation. Indeed, anyone who takes care of DED patients knows that there is an uptick in visits from symptomatic patients during the local allergy season. As an aside, I once asked a colleague from SoCal when their allergy season began. He replied: “Sunrise.”

None of us is missing the diagnosis of vernal conjunctivitis or giant papillary conjunctivitis. When we are discussing allergic conjunctivitis, we are talking about seasonal or perennial allergies. Unfortunately, we do not as yet have a point-of-care test that would allow us to make an objective diagnosis. Patients typically present with bilateral symptoms and signs. The most common ocular symptom is itching, and they will often describe both tearing (clear) and a runny nose (also clear). And redness. They also complain that their eyes are always red.

Of course, all of this can also be seen in all kinds of DED patients. What separates the allergy patient from the DED patient is swelling. These folks often have obvious chemosis that can be striking. It behooves us to evert the lower lid and look for subtler signs of swelling of the conjunctiva in the inferior cul-de-sac. My diagnostic accuracy seems to improve if I see these patients earlier in the day; they tend to have lid edema and periocular “puffiness” that is more prominent in the morning.

An environmental allergen (pollen, mold, animal dander) comes in contact with the ocular surface. From there it is presented to mast cells. This triggers degranulation and the release of histamine, chemokines and cytokines. H1 receptors on sensory nerves are activated, leading to itching. Histamine binding with H2 receptors on blood vessels results in increased permeability and swelling. Chemokines attract more inflammatory cells, and the cytokines that have been released activate these cells once they arrive on the scene.

Treating allergic conjunctivitis is an old story. Prescribe a topical steroid, and you will be simultaneously a genius and your patient’s new best friend. Every single corticosteroid will work, and of course you have all of the potential side effects and complications (increased IOP, cataract formation) that come along with your new Mensa membership. The histamine story is well known, though, and the rest of the anti-allergy armamentarium stems from that knowledge.

PAGE BREAK

Mast cell stabilizers were first approved in the ’80s. Opticrom (cromolyn sodium ophthalmic solution) is used four times per day. Alocril (nedocromil sodium ophthalmic solution) is both more effective and more convenient; it only needs to be instilled twice a day. The problem with both of these medications is that it takes weeks for them to have any effect on symptoms. Because of this, the ’80s and ’90s were a time of intense competition. Big pharma raced to develop effective topical antihistamine drops that would prevent histamine that was already released from causing symptoms.

With the exception of epinastine, which blocks both H1 and H2 receptors, all of the presently available antihistamine drops are H1 blockers. Believe it or not, there has not been a new antihistamine molecule approved or launched in the U.S. since Lastacaft (alcaftadine, Allergan), and that was nearly 10 years ago. There are branded versions of prescription-only medications, such as Pazeo (olopatadine hydrochloride ophthalmic solution) and Optivar (azelastine hydrochloride ophthalmic solution), but at the moment Bepreve (bepotastine besilate ophthalmic solution, Bausch + Lomb) is the only medication that is brand-only. (Note: Zerviate (cetirizine ophthalmic solution, Nicox/Eyevance), a topical formulation of the medication best known as Zyrtec, will soon be available.)

So, if you are convinced that your patient does have allergic conjunctivitis, how do you go about treating them? Dr. Milner suggests simultaneously starting both a mast cell stabilizer and an antihistamine, only using a steroid in the most severe cases. Which ones should you prescribe? That depends on your experience with the various options as well as your stomach for battling pharmacy benefit managers for coverage. The “easy button” is Zaditor (ketotifen fumarate) because it is over the counter. Sadly, Zaditor is the least effective of all the options in my experience. Far better to fight the fight for the first prescription to more effectively and efficiently treat your patient’s symptoms with a more effective drop and then perhaps “step down” to the OTC option for maintenance.

Unless your patient also happens to have DED, and the allergic conjunctivitis is also kicking up a sandstorm there. But, of course, you already know how to take care of that.

Disclosure: White reports he is a consultant to Allergan, Shire, Sun, Kala, Ocular Science, Rendia, TearLab, Eyevance and Omeros; is a speaker for Shire, Allergan, Omeros and Sun; and has an ownership interest in Ocular Science and Eyevance.