July is Dry Eye Awareness Month! To commemorate and help raise awareness for the disease, Harbir Sian is joined by no other than Dr. Bruce Jackson. Dr. Jackson has a long list of accolades with his research interests covering bacterial and viral infections of the external eye, new antibiotics, antivirals, and ocular surface disease, especially dry eye disease. In this episode, he educates us on the history of the condition and the development of the different treatments for it. Dr. Jackson also discusses the different diagnoses associated with the disease and how to approach them with your doctor to develop a dry eye plan that works for you. Tune in for a very insightful and informative episode.
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Pharmaceuticals In Dry Eye With Dr. Bruce Jackson
Thank you so much for taking the time to join me here, to learn, and grow. As always, I am truly appreciative of all the support. Everybody I speak to who gives me feedback on the show, all the comments and reviews online are incredibly supportive. I always ask a little favor right off the top. If you do get some value out of the show from any episode that you've read, please do share it. Tell a friend, throw it up online on social media, wherever you can.
Again, I appreciate all the support. It has really been helping the show grow and helping me bring on amazing guests like our guest, Dr. Bruce Jackson. Before I get into the introduction for Dr. Jackson, if you didn't know, July is Dry Eye Awareness Month. We are going to do this show digging into the ins and outs of dry eye to commemorate this special month. I didn't know that until recently. I want to make sure that we do this Dry Eye Awareness Month justice here.
Dr. Jackson is the perfect guest for this conversation. He obtained his MD in 1967 at the University of Western Ontario, and he completed his residency in Ophthalmology at McGill University in 1972. In 1986, he became the Ophthalmologist in Chief at Royal Victoria Hospital, which is the hospital at McGill University. In 1987, he became the Chairman of the Department of Ophthalmology.
Since then, there has been a lot happening in Dr. Jackson's career. In particular, he started the Excimer Laser Program at The Eye Institute in 1992, carrying out clinical research in the treatment of myopia, myopic astigmatism, hyperopia, hyperopic astigmatism, and PresbyLASIK from 1993. His research interests are in bacterial and viral infections of the external eye, new antibiotics, antivirals, and ocular surface disease, especially dry eye disease.
Dr. Jackson has a huge list of accolades. I want to mention a few of them because it's important to recognize these types of achievements. Here are a few of them, the Eye Physicians and Surgeons of Ontario Lifetime Achievement Award in 2017 and the Canadian Ophthalmological Society Lifetime Achievement Award in 2012. The Ottawa Life Sciences Council Career Achievement Award in 2006, the Queen's Golden Jubilee Medal Recipient in 2002, and a few more. I feel like the only thing that's missing, Dr. Jackson, is the queen tapping you on each shoulder with a sword here to give you a knighthead. What do you think? Is that due at some point soon?
No, I don't think so.
Thank you, Dr. Jackson, for joining me. Honestly, it's truly an honor to have you. I have had some pretty special guests but to have someone as distinguished as yourself is wonderful, especially when we are going to be talking about this condition, dry eye that you are truly an expert in. Thank you for taking the time.
I'm delighted to.
Dry Eye Awareness Month is in July. Why don’t we start with a little introduction for yourself from your perspective of who you are and what you do?
I started in ophthalmology. In fact, I thought that I would probably not do much in the way of clinical but be more on the research side. However, once I got into the program and then did a fellowship at the Proctor Foundation in California, I returned to McGill. I enjoyed the practice, teaching residents, and ultimately starting a fellowship program.
I tried to get involved in research but it was when I moved to become Director General at the University of Ottawa Institute we had a chance to develop a good corneal unit with basic scientists and also be able to start the excimer laser program. At that time, that was the most controversial of anything to have a new Eye Institute start into something that was only in the private world.
The question was, "Does it work or not?" Our research for all those years was to show that it was a great benefit, and there was a tremendous amount of spinoff that we got learning about dry eye, ocular surface disease, and refractive changes. It was a great tool for training residents, fellows, and ophthalmic technicians.
You have this amazing experience in the research realm but also refractive surgery, dry eye, and ocular surface disease, and all of that does come together in many of our patients. I was interested to know the perspective on treating dry eyes in preparation for refractive surgery. Is that becoming more important over time? How important is that now?
It’s always nice to have options.
Let me take you back to 1995, when we started to do hyperopic PRK. What we soon saw was that these patients, who were perimenopausal women predominantly who wanted to get rid of their glasses so that they could put on their makeup more easily, basically had a fluctuating vision after surgery. If you put in an artificial tear and had them blink a few times and read the chart again, you often got 1 or 2 more lines of vision.
We realized that by steeping the cornea, these eyes were drying and had tear instability. That was the first recognition that refractive surgery could change the ocular surface. We started to look much more carefully at patients preoperatively to make sure that they did not have a rapid tear breakup time and didn't have corneal standing or other signs of dry eye.
That's a lot longer ago than I expected. 1995 is taking me back to high school. Since we are talking about its history of it, is that when we started to recognize dry eye more? Was it an earlier stage when the medical community as a whole recognized dry eye as an actual disease?
When I first did my training, we looked at the dry eye as a lack of tears or an inadequate volume of tears. We understood that Sjogren's syndrome was autoimmune and that there was T-cell infiltration that shut down. The lack of accessory lacrimal glands in this group but we didn't recognize this as an inflammatory condition.
Allergan did the clinical studies with Restasis. The associated research after that showed that we were dealing with an inflammatory ocular disorder. By 2007, the first Dry Eye Workshop included that this was a multifactor disease of the tear film ocular surface, and so it took that time for us to realize that it wasn't an adequate number of tears. It was the composition of the tears and that this was an inflammatory process that was driving this.
When was the Allergan study conducted?
The Allergan study was done around 1998 in that realm. We took part in that at McGill. Fortunately, we had a number of patients that did well in that study. The government gave us this special access program so that we could continue to use cyclosporine or RESTASIS on these patients. The supply was come and go. Sometimes we have it, sometimes not. Some of these patients would be doing great, and then we couldn't get it for two months. You could see the regression that occurred. When they got back on again, they were happy with the symptom, signs, and improvements.
It drove home the point that properly selected patients did improve on anti-inflammatory treatment. Cyclosporine was the first one that we had. Up until that point, we used some steroids for severe cases but they had to be short-lived because of pressure and cataract concerns. When cyclosporine came along, we had a safe drug that we could use long-term.
Dry Eye: We looked at the dry eye as a lack of tears or an inadequate volume of tears. We didn't recognize this as an inflammatory condition.
I'm a little bit of a historian or at least I enjoy learning about the history of certain things. A couple of my questions have been like, "When did this start?" Where did cyclosporine even come from? We are saying that perhaps doctors or the medical community started to recognize dry eyes toward the late ‘90s as an actual inflammatory type of condition. Was it being used somewhere else where they said, "This could be reapplied on the eye?"
There is a spontaneous dry eye that occurred in dogs. I'm not quite sure why the veterinarians got involved but they started to use it. We picked up on it. One of the chaps in New York, Hank Henry, and myself started to formulate cyclosporine and try it on some of the dry eye patients. It was interesting that the discussions with Allergan and Paragon chairlift at Snowmass Colorado prompted them to take a real serious look at what cyclosporine might be able to do in the treatment of the dry eye.
From that, we've learned a ton of information regarding this inflammatory cycle. Again, we are recognized for refractive surgery and its importance, and then cataract surgery became a refractor procedure. With premium IOLs with toric lenses, we realized that we had to have accurate keratography. If you took topography, for example, you could see some patients with severe dry eyes in the images. It became an important part of patient satisfaction and getting a good post-op result.
The other interesting thing was that there was a study called a PHACO study. Although it was done in 2013 and 2014, it didn't get published by Will Trattler until 2017. What was interesting in that study was that about 60% had no symptoms when they were going for cataract surgery or dry eye but in fact, about 63% had a rapid tear breakup of less than five. Fifty percent had central corneal staining, almost 3/4 had some form of corneal staining, and close to 20% had decreased Schirmer's.
That put a perspective of what problem they had in patients going for cataract surgery, who are older may not have symptoms but do have evidence of ocular surface disorder. You compound that with patients who are on glaucoma drops with preservatives. You have the perfect storm, where you might get toxicity from the preservatives in the glaucoma drops on top of a dry eye. This is why it has become so important if we are going to have patient satisfaction after cataract surgery.
Circling back to that initial question, especially when it comes to, and I lumped them together, to be honest, laser surgery, cataract surgery or refractive surgeries, as far as I’m concerned. Surgeons can have fantastic visual or refractive outcomes with cataract surgery if it's all done well. That's why it's so important. Often the patients who are getting cataract surgery have this perfect storm of the deteriorating ocular surface plus the medications, oral and topical medications that can cause more dry eye and all of that needs to be addressed. You are telling me that Restasis came into eyecare because of a conversation that you had on a chairlift.
Yes, we were pushing them to take a good look at it. Fortunately, they did. We didn't understand a lot about the symptoms and signs of dry eye in those early days. When you look at those early studies, they were aimed at more severe patients. They were using Restasis twice a day but with no other drops. There was no other therapy. We know you can't treat dry eyes with cyclosporine twice a day. It's multiple treatments to achieve a good result.
The fact that they could demonstrate improvement, and it took until 2003 for the FDA to approve it in the states based on increased year production. Canada didn't accept that. It took a subgroup analysis to show that both symptoms and signs improved. It got approved in Canada by 2010 but again, properly selected patients were the key. When it first comes out, everybody gets on it, and then there are failures. You say, "Why didn't this patient improve?" You then have to look, "What these patients do benefit from anti-inflammatory treatment?
We're getting much more efficient drug delivery to the eye.
Early in my career, I felt some of those failures as well because I thought, "This is the magic drug. I'm going to put every dry eye patient on." That's not how it works. Since we are doing the history of pharmaceuticals here, Restasis was the first one of these pharmaceutical agents to treat the inflammatory side of dry eye. What came after that?
Interestingly, Restasis was approved in 2010, and seven years later, in 2017, lifitegrast or Xiidra was approved in Canada. This was a little different immunomodulatory drug. It acted differently than cyclosporine around the LFA-1 to ICAM binding but it acted on the T-cells, decreasing recoupment cytokine release. It did help a number of patients with their symptoms more than signs.
I call it my love or hate drop, either patient loves it and will hug you for putting them on it or else they will return the box and say that the side effects were too bad of the dysacousia, the stinging, and the blurred vision that they couldn't continue with it, even though it might have made a little improvement. I found it more useful in the evaporative dry eye than the deficient dry eye. Again, more for the symptoms.
In 2021, CEQUA by Sun Pharma was approved as a new formulation of cyclosporine. The exciting part is that it's almost double the concentration at 0.09%. It's like using Restasis four times a day when we only have to use it twice a day. The formulation is novel where they use this nanomiceller technology to encapsulate the cyclosporine as a core with a shell of a water-soluble polymer such that it gets into the tear film much more quickly. It looks like it penetrates the cornea and conjunctiva considerably faster.
We are getting much more efficient drug delivery to the eye. We've started to use it. I certainly have had a few patients now that were unable to use Restasis. They are finding it more comfortable and showing some good results. It's always nice to have options. We did have another one. Santen had Ikervis, which is now approved for vernal, which is Verkazia, and it was also 0.1% cyclosporine but again, an emulsion, a little different vehicle. That didn't get approved by Health Canada. At this point in time, CEQUA is our newest one to use.
You mentioned with Restasis and any of these medications that you can't simply use the medication on its own and expect that to fix all of the symptoms and everything that the patient is dealing with. Usually, there's a multifaceted approach, as we know from the DEWS definition. It's a multifactorial disease. We will get into that a little later about what would be the holistic approach.
Speaking about the pharmaceutical agents, you touched on it already but what would be the benefits of CEQUA versus the traditional cyclosporine Restasis of 0.05% versus 0.09%. You mentioned the higher concentration. Are you finding that patients are tolerating it better? Are they not getting as many of those symptoms or the side effects that they were getting with Restasis?
It's pretty early for me to make a comment. The ones that I have put on at this point are patients that have failed on Restasis. For those that are doing well on Restasis, I leave them on it but for those that have failed, I have had to discontinue. I'm having some good success in getting them started on CEQUA. For some of the new patients coming in, I will put on CEQUA. So far, they have been doing quite well.
Dry Eye: The different formulations may make a big difference.
The different formulations may make a big difference. Another point to be made is that generic cyclosporine was approved in Canada. To a lot of people's surprise because we have no idea what the emulsion is. I had a number of patients that were switched by the pharmacy and came in, and they weren't doing as well and had a lot more symptoms. I then realized that they were on the generic form, not on the brand name form.
Once we switched back to the brand, they improved. There is a group that may not do as well on the generic. I just point that out when people say they are on cyclosporine, and what they are on is important. Allergan has a multidose bottle. That one is not genericized. That is one that can be prescribed and not get the generic for.
That's an important point to confirm if your patients are not doing well on Restasis to confirm whether they are on the generic or the branded one. Is the multidose available in Canada? I didn't even notice that.
It was around 2018, it was approved. I was on the advisory for that and we thought, “This was going to be great,” that patients are going to love the multidose one bottle that they can carry around and use for a month. Interestingly enough, patients like the vials. They could carry them around. They could leave them all over the place, in the office or at home so that they didn't forget them.
A number of them did vial spare, so they could get more out, whereas there was enough for one month in a bottle, especially when patients didn't have insurance and we are paying for it. I have a few of the multidose but I must say that the majority are still back to the minims, and that's the way CEQUA is as well.
I've got similar feedback from a lot of patients when I'm trying to switch them over from the single-dose or single-use preservative-free drops, whichever preservative-free artificial tears, over to a multidose. Initially, they say, "That sounds like a great idea, except I like to keep a couple of my pocket, a couple over there," and then reuse them so they get a little more out of them. That does make sense. That would be a common issue there.
We are moving on and understanding that this is a multi-factorial condition that we are talking about. You and I talked in the past and wanted to stress the importance of recognizing the relevance and the role that lid disease has to play on ocular surface disease and dry eye. I would love it if you could go into where blepharitis and other types of lid conditions come in and how we can recognize them?
One of my mentors at the Proctor Foundation, Dr. Richard O'Connor, used to give a lecture. He starts on blepharitis by saying it was poorly diagnosed and treated, and it's still exactly the same now. If a patient comes in with crusted eyelids, scurf, and debris sleeves on the lashes, we recognize that as blepharitis. We know that cleaning the lids using an antibiotic, occasionally an antibiotic steroid, will settle these down. That hasn't changed much over the years for interior blepharitis. In adulthood, you get a history that as a child, they had crossed either some styes.
Patients look for that quick relief or improvement and when it doesn't come then they quit.
It really did change with meibomian gland dysfunction. We did recognize the role of the meibomian glands, especially when patients came in with frequent chalazia and you could see obstructed glands. I used to remember at the Royal Vic, patients would come in, and we would do meibomian gland expression after warm compresses and put these patients on tetracycline, for example. We didn't recognize the role of lipids in the tear film. In the same way, as we did eventually how lid disease probably accounts for 50% or 60 of dry eye with the tear instability. Only about 10%, 15% have an aqueous deficiency, and the rest are basically a mixture.
We now know a lot more about the role of meibomian gland dysfunction, and also the role that rosacea plays within this, and atopic dermatitis are all added risk factors for it. It's that tear instability that starts this whole inflammatory cycle. The lids play such a major role. I remember, at one point, we used to talk about conjunctivitis and meibomian. Conjunctivitis from the old days where the eye would get red and inflamed a bit, and you would look and find nothing, except that there may be a few little changes on the lid margin. We didn't recognize that there was that inflammation that was going on that was the cost of this.
That's such a key factor. For so many patients, the underlying issue is this meibomian gland dysfunction, leading to the tear film instability and then the inflammation. This is a conversation I have so many times every day with patients. They come in, and their complaint is they are getting a sharp pain a few times throughout the day. I'm like, "Let me rewind the clock here and tell you how this all started, and then it got to this point." I try my best to show them visuals and all these things but they will be like, "No, it just started a couple of days ago." "Trust me. This has been going on for a long time. Your symptoms started a few days ago."
It's interesting to know that physicians at that particular time connected the dots but now we know that it's so vital. When we talk about a more rounded approach to treating dry eye, what would you say on the average patient that you've seen who has these mixed causes of dry eye, the aqueous and evaporative? What treatments are you seeing most commonly for these patients?
At the moment, I'm practicing in a community. We don't have a lot of some of the new technologies available. We are back to almost where we were. We have been able to show that warm compresses are done effectively, lid massage, keeping the lid margin clean, and now we have pre-moistened wipes and some with tea tree oil if we suspect Demodex.
We've got the use of antibiotics but azithromycin, a lot of the staff are resistant to it. I tend to use Fucithalmic or fusidic acid for some of these patients and a discussion on Omega-3s. We also have eye drops that have oil in them to help the tear film. We used to use lid-scrubs with baby shampoo but I worked out better ways to do it than that, so I discourage that.
If you look at the combination of things, including the artificial tears, I have a discussion on the omega-3s with patients, we know some do well on them, and others have found no effect. I give the patient the choice of using a medical-grade one to see if that will make a difference for about three months. In about 80% of patients, that alone will make an improvement if they do it. What happens? It's like flossing your teeth. They start to feel better and then gradually drop off. Men don't like doing warm compresses, so I have them do it in the shower and let the warm water hit the closed eyelids and massage in the shower. That's a little bit better way for doing that.
That's the basic treatment that we need, and then depending upon whether they have more rosacea, I will often put these patients on doxycycline or low-dose doxycycline. It's amazing some will improve with that. Their symptoms of dry eye almost completely disappear with that as an anti-inflammatory. In some patients, it doesn't seem to make a difference. For those unable to take tetracycline, I use azithromycin, and occasionally, you can use compounded azithromycin on the lid margin to help as well. That, to me, is the basic approach to the lids.
Dry Eye: We didn't recognize the role of lipids in the tear film in the same way as we eventually did how lid disease probably accounts for 50% or 60%, of dry eye with the tear instability. Only about 10%, 15% have an aqueous deficiency and the rest are basically a mixture.
We will then get into those that don't respond to that. For that group, we've got a lot of new technology. The first one was the LipiFlow which showed thermal pulsation. If you warm those lids up to about 42.5 degrees, you were able to express the meibomian glands that these patients did have symptomatic improvement. We did see parameters change in the tear film. The problem is it was expensive, and it didn't last. It wasn't a permanent cure.
Other procedures came along like that. For example, for rosacea, we have been using intense pulsed light, and dermatologists have for many years. That has an anti-inflammatory effect and Demodex. That shows improvement. I gained not a cure but often has to be repeated and/or combined with meibomian gland expression.
We have a number of these techniques where we are trying to warm the lid, essentially expressing the meibomian glands. We know that meibomian glands get keratinized, so therefore, there are a number of procedures to try and debride the surface, whether it's mechanical, and even gone to the point of Maskin developed little probes for meibomian probing.
I did spend a few hours probing meibomian glands but decided this was not going to be a procedure that I was going to continue with. It goes back to that same concept. We've got to warm up the lids, try to open up the meibomian glands, express them, and then hopefully change that LipidFlow, so we got better stability of the tear film. At the moment, things like doxycycline and azithromycin are certainly ways that seem to alter the meibomian gland function.
If you wouldn't mind sharing the mechanism of action for something like a doxy when you give somebody an oral doxy, what do we understand is happening?
I tell patients, and they are always concerned. I said, "We are not using it for its antimicrobial effect. In the low dose, it probably does have a little but it inhibits MMP-9. MMP-9 is a product of IL-6, and it is responsible for causing apoptosis and corneal cells. I use it pretty extensively on patients who have a corneal disease because it does inhibit the MMP-9s. On patients with lid disease, you could do the InflammaDry and show that they are positive for MMP-9.
Using doxycycline reduces that. I use it as an anti-inflammatory, and then I try to use it in a lower dose as possible. Certainly, Apprilon is a good one for those that have insurance. For those that don't, I will take doxycycline, use the pill, have them cut it in half, and take half a pill a day. That's often enough to maintain their symptom-free level of comfort.
There are other conditions that will mimic a dry eye. We call them a masquerade. In different areas of medicine, we will have Masquerade syndromes or conditions. Are there some for dry eye, and what types of conditions are they? How do we distinguish those from your typical dry eye type of condition?
If you're treating dry eye, you have to spend the time with the patient.
I have a fun practice because I get the referrals of the patients who've not done well on a lot of the routines. It's interesting that when they come into me, they have all been advised by their eye care provider to use all of the things that we've talked about and the warm compresses and everything but by the time they get to me, they've forgotten all of that. We are starting back from scratch. I always look at each one of them from the point of view of being a detective. "What can I find that's really going on? Why didn't they respond?" You go through everything and look.
I have had a number that have an anterior basement membrane dystrophy or epithelial basement membrane dystrophy. They come in with symptoms of fluctuating vision. It's not an obvious one but when you put fluorescein in and they have to have enough fluorescein, and then watch the epithelium breakup time, you start to see the lines. For some of those patients, that's the cause of their tear instability. I've done some of them a superficial keratectomy to relieve their symptoms.
Same thing as for Salzmann's nodular dystrophy. Treating that made the world of difference and made them comfortable because it altered tear distribution. That is what leads to that tear instability. Conjunctivochalasis is the same, and that's inflammatory. That's usually inferior, and we have SLK, Superior Limbic, both friction-related disorders but also in the superior limbic can gets filaments. By identifying that you are dealing with SLK that you can treat that one and conjunctival resection for both of those tends to work well.
I have had a number of patients with Floppy Lid syndrome that have been referred in. The realization that those are lax lids, and when you elevate the upper lid, it flips over, and you see that papillary reaction. A lid shortening procedure and a lot of these patients who have sleep apnea can make the world a difference. I have had a number with Mucus Fishing syndrome where a little bit of mucus and then they start going after it. They start this cycle.
I had one young lawyer who would take her finger and go right into the upper and the lower fornix to remove it. It's the most dramatic you have ever seen in a video. She's coming in with symptoms of dry eye but until you asked, "You have mucus but what do you do?" They then show you and you say, "I didn't realize that people were doing this," whether it's Kleenex or their finger.
There's a lot, even things like the epiphora tearing. I get a number that is referred and isn't dry eye with reflects teary, and that gives them epiphora because we know that tearing is a part of the symptoms of dry eye or is it punctal stenosis or nasolacrimal duct obstruction. What drugs are they? Is it toxicity from a medication they are taking? That's the cause.
A lot of these patients with keratitis, and it looks like dry eye. The other thing that I've done is check for corneal sensation. That's something that we've neglected to do. I have been surprised at the number that has reduced corneal sensation. We know this can be on the basis of dry eye. For example, the Sjogren's is a very severe disease. They almost have no symptoms and yet complete corneal staining. There's an element of neurotrophic there in a number of our dry eye patients. Recognizing that, changes a lot of our treatment approach.
Those are a few of those masquerade ones. I have had a couple that has been essential like blepharospasm, that I have been referred in because of frequent blinking due to dry eye, and they are basically blepharospasm patients. That Botulinum will make a big difference. I always try to put on my detective hat and see if I can find something that's there that has been missed that we can address.
Dry Eye: They've taught us to recognize conjunctivochalasis as a cause of symptoms where we looked at it as almost an aging process and ignored it as a cause when it can be significant.
There's a lot. I was thinking that you might give us 3 or 4 but there are 10. There are probably others that you maybe see a little less frequently. The conjunctivochalasis, I feel like I see many in the aging population. If I see a little bit, should I refer it out to see potentially if it could be repaired or improved? Does it need to be like hanging out over the eyelid? In your opinion, as a surgeon, how soon would you want me to send that over to you?
I'm in exactly the same position as you are. Some patients can have a lot of conjunctivochalasis and have no symptoms. Some patients have a very mild amount and have a tremendous number of symptoms. It's interesting that if you do an InflammaDry, a lot of them will have a positive MMP-9. That gives you an idea that, for some of these patients is more of an inflammatory process. What I've done and others have taught me is that if you have patients that you've done everything else, they have conjunctivochalasis and are not improving. One of the simple things you can do is cautery virtually at the slit lamp and basically shrink down the conjunctiva. That can be a very simple procedure.
On the other hand, you can do a resection, and a lot of times, with glue, you can seal these up very quickly. It's a minor procedure, and they do well. We are always surprised at how much improvement when you finally make the decision to do something that they get. We are under-treating but no one knows how to predict which is going to do well and which is not.
It is tricky in that sense but I have one small comparison that I can make, which is when I was doing my clinical rotation in my fourth year, I was at an ophthalmology clinic in Florida. This is maybe a distinction between Canada and the US. If they saw a little bit, they were like, "We are going to fix that," and they will do a resection like this.
Here, I've sent patients over to the ophthalmologist and they say, "We are not going to touch that." I remember seeing not that much conjunctivochalasis before when they were doing the surgery in the US. There's an obvious distinction there. I still have those thoughts in my mind that maybe the surgeon will go ahead and repair this but they are not as easy or not as open to invasive procedures here.
I agree. They've taught us to recognize conjunctivochalasis as a cause of symptoms where we looked at it as almost an aging process and ignored it as a cause when it can be significant. What's interesting is that when an SLK, Superior Limbic Keratoconjunctivitis, where you get that loose conjunctiva up above, what amazed me was that they had been resected. The next day, the patient feels comfortable, and yet you have this bare area up above. You flip the lid, and there's still a papillary reaction. They should be more uncomfortable but they said, "At last, I have relief." That always amazed me as to what symptoms they can get from that redundant conjunctiva.
Dr. Jackson, if there are three words that make me uncomfortable, and I'm sure many other people frustrated, who are treating ocular surface disease, it's a pain without stain. We have a lot of patients coming in. There are no obvious signs or staining, there's nothing showing up under the slit lamp but they are complaining constantly of this pain.
Whether they've maybe had laser surgery or cataract surgery, perhaps they haven't and are still constantly complaining of this discomfort. Some of them come in with pretty severe pain. This neuropathic issue, how do we pick it up? How do we treat it? Help me with this because I have a bunch of patients who could benefit from me learning a little more about this.
Dry Eye: Those with chronic pain syndromes, fibromyalgia, osteoarthritis, diabetics, atopic, or any of that group, even those with migraines can have an exaggerated ocular response and you don't see anything.
I can't agree more. Returning back to my days of refractive surgery and I was referred to patients that had perfect results but were in agony. When you looked, there were no signs of ocular surface disease, and yet they would be crying because of the discomfort in the waiting room. We soon learned that this was a nerve problem. It's not an ocular surface problem but it may start as an ocular surface problem.
In other words, these patients may be in that pre-sign stage of dry eye, where they have hyperalgesia. Their corneal surface is sensitive to wind, cold, and light, and yet you see no signs. Ultimately, they develop more of a dry eye. In that group, if you put in a topical anesthetic, they feel comfortable but when you get into the true neuropathic pain patient, you put in a drop of anesthetic, and they don't notice any difference. I say, "I'm putting a drop in to see if it makes any difference." They think I'm putting an artificial tear in. If they say, "That feels so much better," we are dealing with something on the ocular surface. If they say, “It didn't make much difference,” then this is neuropathic pain.
We do know that a number of patients have an exaggerated response. Those with Chronic Pain syndromes, fibromyalgia, osteoarthritis, diabetics, atopics, or any of that group. Even those with migraines can have an exaggerated ocular response, and you don't see anything. There is this discordance that occurs with that. When you get a patient, and you suspect that they have neuropathic pain and may or may not have other risk factors, you have to go through the whole gamut of dry eye treatment. I look at the lids and the surface. I try them on various things.
It's only at the end that you can sit down with them and say, "We've tried everything from drops to cyclosporine to serum tears, and none of it has made a difference. Sometimes a scleral lens or PROSE type of lens can make the difference too but in the end, it's a pain management. Sometimes, I referred them to a psychiatrist, and I have had amazing results with a few of the psychiatrists treating these patients over a period. They've come back and have been smiling in the office where they were crying before.
It's one of the pain management but it's recognizing and they need reassurance. They've gone to see five other people, and they have all said, "I don't see anything wrong." They think they are crazy but you have to reassure them. You know what's going on, "This is a problem. We don't have effective treatment for it.” It's to manage pain is the key.
In many cases, we can say, "Here's an eye drop. Here's a pill," or whatever. For this, there's not really anything that we know works. I've read different things about serum like autologous serum drops or an amniotic membrane, even something as simple as Omega-3 potentially helping. Would you find those are more for the ones that respond to the anesthetic that you know it's more of a topical or surface-level thing or would you think those potentially could work for the deeper neuropathic type patients as well?
I have been fooled on both. I go through it for all of them. I don't usually go for the amniotic membrane but I go through to the rest, the serum tears, even cyclosporine, can increase nerve growth in that. There may be some function for it as well. I try all the things but I tell the patient up front what is going on. If they are willing, we will go through it and try this. I have had some patients that do find some relief. We haven't cured them but are able to function. While there are a few patients after refractive surgery, some have gone on to suicide. It could be like the zoster or postherpetic neuralgia. It couldn't be that severe.
Before I go to my last question, I wanted to go back to the Omega-3 thing. You mentioned a medical grade. I was curious to know what type of Omega-3 if you have something specific that you recommend, and what dosage? How many milligrams of Omega-3 are you recommending daily for patients?
Dry Eye: The studies have shown some have had benefits and the more recent ones show that it didn't. It's a hard thing to assess. Patients should at least be given the option and the knowledge of the types of omega-3s out there.
When I first heard about Omega-3s, I must say that I wasn't very convinced that that would help. A number of studies were published. The first one, a medical-grade one, was PRN which I was introduced to. The difference between an ester and a triglyceride, in other words, most of the lower priced ones that you can get are in the ester form to take out impurities but they are not very efficient and not well-absorbed. You can get that fishy taste. If you go the extra mile, you convert it back to a triglyceride. That's the medical-grade one.
With that, somewhere around 1,500 to 2,000 EPA DHA seems to make a difference if you look at the blood levels and the thing that people have done. Systane makes an omega-3 PRN. There are a number of them that make a good run. I tell patients to use it if they would like for about a three-month period and see if it makes a difference.
I have had patients that have faithfully felt it did and stayed on it. I have others that didn’t. I have a lot of patients come in and they say, "I'm taking an Omega-3." That's where we have a little discussion and say, "You can continue. That's fine. If you want to see if it makes more of a difference, then there are options to upgrade what you are taking and see if it does make a difference." The studies have shown some have had benefits, and the more recent ones show that they didn't. It's a hard thing to assess. Patients should at least be given the option and the knowledge of the types of Omega-3s out there.
Education is where it starts. I have a similar conversation as you with my patients, educating them on the difference between ethyl ester and a triglyceride and roughly recommending about the same amount dosage-wise as you do as well. It's nice to see that patients when they get the education, they understand why you are sharing this information, and a lot of them do come onboard with it. Especially these days, many patients are looking for more of a natural approach versus a pharmaceutical necessarily or other invasive processes.
If they can do a holistic approach like taking an Omega-3, that's systemically going to be healthy for them and open to that conversation. This is going to be my last question for you. This includes myself. I find a lot of eye care providers or optometrists are hesitant to maybe prescribe or maybe unsure even to how to prescribe or if they should prescribe something like CEQUA, for example. Are there any words of encouragement or anything that you might want to share that might help someone like me to become more comfortable with prescribing these medications?
It's interesting because a lot of my referrals come from optometrists. They will put patients with dry eye or a fairly severe dry eye with keratitis on a topical steroid for a few weeks, one of the FML or fluorometholone, and notice some improvement or maybe not notice any improvement and then refer the patient. They stopped short of putting them on anti-inflammatory, whether Restasis or CEQUA.
I look at those drugs as being the safest. They are steroid-sparing. I tend to use them with induction with steroids. A 2 or 3-week induction with steroids, sometimes if the severe ones that I see, I will start them on a topical steroid 3 or 4 times a day. After a week, I will add Restasis, CEQUA or cyclosporine, and then taper off the steroids. They get an initial good improvement with the steroid because we know that it's going to take 2 or 3 months for cyclosporine to have its full effect. As far as a safe drug, it couldn't be a safer one, much safer than steroids. No hesitation there.
You have to warn the patient of the side effects that it will sting and burn. We haven't been able to get away from that. If they put it in the fridge, sometimes putting it in the cold helps. Ten minutes later, they put in an artificial tear that can be very helpful. I would tell the patients that they are not going to notice an immediate benefit. In fact, when you back and see me in 2 to 3 months, you may not feel much better but if it's working, I will notice an improvement on the surface. Gradually, there will be some improvement but patients look for that quick relief or improvement, and when it doesn't come, then they quit.
Dry Eye: It's the technicians and the help that can go over how they use the drops, what to use, timing, all of that, that makes a real difference in whether there's good compliance or not.
One of the ophthalmologists used to say, "I make them swear that they are going to use it for three months or I won't prescribe it," because you've got to give it a chance. From the point of view of safety for spending a few minutes talking to the patient and if it's purely an evaporative dry eye and they got tons of tears, then I don't go that route initially. I will look at other things to try but for those that have that mix, they have some decrease in tear volume but also have some lid disease, then certainly, I will go to that when they have corneal staining.
Oftentimes, it will be part of your initial dry eye plan to start them on a drop like that.
By the time I see the patient referred to me, they usually have had a lot of the basics but they have stopped whatever. We go over that but then this is what I will add next. If they don't have much keratitis, then I may wait and reinforce a lot of the other things, see them back again and how much improvement we've got from that alone, and then start them on the drug. For those that have severe keratitis and have been struggling, that's my next approach.
Thank you so much, Dr. Jackson. There was a lot of valuable information here, whether it's the history of dry eye, refractive surgery, and pharmaceuticals or your more practical advice on a clinical approach to treating dry eye. It has been helpful for me in this conversation. I'm going to go back and read it again because there are parts I can implement right away in our office. Any other final words of wisdom? Any other thoughts you would like to share before we wrap up?
If you are treating dry eye, you have to spend the time with the patient. The chair time is important because most of the time, they are given drops and then out the door. It does take time. As providers like ourselves, we only need 3 or 4 minutes with the patient to assess where they are. It's the technicians and the help that can go over how they use the drops, what to use, timing, all of that, that makes a real difference in whether there's good compliance or not. That's the big thing that I find. Make sure the patient feels that you understand their condition and can inform and give them a rationale of how you are going to approach treatment. See them back 2 or 3 months later to follow up on that. I find that this goes a long way in getting compliance from the patients.
I would have to agree with you on that one. In fact, for that reason, I find there are more than a few practitioners out there who choose not to dive into the dry eye because they know how much chair time, handholding, empathy, and all this that it requires. That's fine if they choose to practice a certain way but those of us who dive into it, learn pretty quickly. That's a big part of it. Thank you for that.
Thanks again, Dr. Jackson. It's a pleasure to have you on. I'm excited to share this with everybody, and don't forget everyone, July is Dry Eye Awareness Month. Make sure you get out there and spread the good word about treating dry eye and its importance of it. Thanks again for reading. If you got some value out of it, don't forget to share it with your friends. I will see you again in the next episode.
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About Dr. Bruce Jackson
Dr. Jackson obtained his MD in 1967 at the University of Western Ontario and completed his residency in Ophthalmology at McGill University in 1972. After a fellowship in Cornea and External Disease at the Francis I. Proctor Foundation for Research in Ophthalmology, University of California, San Francisco in 1973, he returned to the Royal Victoria Hospital at McGill University in Montréal, Québec where he was geographical full-time at the hospital, involved in clinical care, research and teaching residents medical and surgical cornea. He developed a Cornea and External Disease Fellowship Program, graduating twelve fellows and initiated the McGill Low Vision Clinic.
In 1986, he became Ophthalmologist-in-Chief at the Royal Victoria Hospital and in 1987, Chairman of the Department of Ophthalmology at McGill, Program Director, and Research Director, a position he held until he moved to the University of Ottawa in1991 where he became Chairman of the Department of Ophthalmology and Director General at the University of Ottawa Eye Institute, The Ottawa Hospital until the end of his mandate, in June 2008. He started the excimer laser program at the Eye Institute in1992 carrying out clinical research in the treatment of myopia, myopic astigmatism, hyperopia, and hyperopic astigmatism and PresbyLASIK from 1993. Over his academic career he has trained many residents, fellows and technology students.
His research interests are in bacterial and viral infections of the external eye, new antibiotics and antivirals, and ocular surface disease especially dry eye disease. He has led and been an expert consultant on teams formed to investigate clusters of endophthalmitis cases following cataract surgery and helped develop best practice strategies for prevention.
Dr. Jackson moved from Ottawa in December 2014 and continues his subspecialty consult practice in Cornea and External Disease with an emphasis on ocular surface disease - lid disease and dry eye and new therapies at the Peterborough Clinic in Dr. Kylen McReelis’s office. He is a participant on several pharmaceutical advisory boards and presents clinical and research studies at major meetings. He has published numerous peer reviewed articles and chapters related to refractive surgery, dry eye disease blepharitis and new therapies.