There is a lot of marketing spin regarding the medical treatment of dry eye. We propose to set forth a rational, scientifically sound and clinically successful, literature- based protocol for truly helping patients who suffer from ocular surface dryness.
Bear with us as we set the foundation for our clinical approach. Two of the most respected clinicians in this field of study are Michael A. Lemp, M.D., and Gary N. Foulks, M.D. Dr. Lemp is widely regarded as one of the pioneers in dry eye research and has been with the Georgetown University School of Medicine for many years. Dr. Foulks has chaired the cornea service at Duke University and the University of Pittsburgh, and is currently at the University of Louisville, in Kentucky. He is editor- in-chief of the authoritative journal, The Ocular Surface (www.theocularsurface.com), a journal we highly recommend to all practicing eye doctors.
Now, let us examine some pertinent quotes from these clinician/ scientists from the peer review literature. In the July-August 2007 issue of Survey of Ophthalmology, Dr. Foulks states:1
• “Increasing the thickness of the tear lipid layer improves the stability of the tear film, suggesting that in selecting a dry eye therapy, an important feature would be the ability of the treatment to mimic the lipid layer of the tears.”
• “One drop containing Restoryl, the active ingredient of Soothe XP [Bausch & Lomb], more than doubled lipid layer thickness.”
• “Restoryl has been shown to replenish the aqueous layer of the tear film. When applied to the eye, Restoryl differentiates into neutral oils (helping to rebuild the lipid layer), interfacial molecules (stabilizing the interface between the lipid and aqueous layers, and supporting the mucin layer), and water (helping to restore the aqueous layer).”
• “Overall, decades of research have shown a strong correlation between dry eye symptoms and the state of the tear film lipid layer, as well as a clear connection between the status of the lipid layer and the osmolarity of the tear film.”
In the September 2008 American Journal of Ophthalmology, Dr. Lemp states: “Tear osmolarity is considered ‘the central mechanism causing ocular surface inflammation, damage and symptoms, and the initiation of compensatory events in dry eye’.”2
We have learned from Dr. Foulks that Soothe XP stabilizes the lipid layer, thus protecting the tear layer from becoming hyperosmotic. Dr. Lemp established the (hyper) osmotic tear film as the prime cause of ocular surface inflammation. We believe these two foundational cornerstones establish Soothe XP as a key element in helping patients with dry eye. Dr. Lemp continues:
“Although the exact place of inflammation in the stream of events leading to ocular surface distress is not clear, its role is unmistakable.” He goes on to say, “In the use of cyclosporine (Restasis) to modulate immune activity and to suppress inflammation in dry eye, there is increasing evidence that the use of topical corticosteroids as temporary or pulsed therapy can be useful in reducing the damaging effect of inflammation.”
Furthermore, the Report of the International Dry Eye WorkShop (DEWS), published in 2007, clearly established that “corticosteroids are an effective anti-inflammatory therapy in dry eye disease.”3
Now, let’s talk about the use of the steroids in ocular surface inflammatory disease. This is very simple and very straightforward. Steroids continue to suffer from the myth that they are dangerous. Cars have the potential to be dangerous; in fact, 38,000 people die in them every year. The truth is that Americans love their cars and, while cognizant of this statistic, they confidently get in their beloved vehicles on a routine basis with great confidence they will return home safely. Well, steroids have the potential to cause harm, but many thousands of people are helped by steroids every day. It is so important to keep the enormous beneficial attributes of steroids in focus. As intensely busy clinicians, we have been able to help thousands of patients over the decades, and we cannot recall a single therapeutic misadventure with corticosteroids.
There are two types of steroid molecules: ketone-based, such as prednisolone and dexamethasone; and one that is ester-based, loteprednol. Human systems do not possess “ketonases,” but have an abundance of esterases. It is this reality that sets loteprednol apart as a very safe and very effective molecule. In fact, the loteprednol molecule is nearly identical to the prednisolone molecule except that a ketone moiety is replaced with an ester moiety. So, for 10 years, the world has had extensive experience with loteprednol and it is authoritatively established as a highly effective, yet very safe, anti-inflammatory medicine. Obviously this makes Lotemax the best available choice in the management of ocular surface inflammation.
Now, the stage is set so we can care for our dry eye patients in an enlightened manner. Here is how we have approached these patients since the formulation of Soothe XP came to market a few years ago:
• First, we do a therapeutic trial with Soothe XP for a month. We encourage our patients to use the drops as often as they would like, but at least four times a day. At the one-month follow-up, if they are happy, our goal is met, and the patient is encouraged to continue to consistently use the Soothe XP as needed. We stress here that Soothe XP, being a mineral oil emulsion, is radically different from other artificial tears and cannot intelligently be grouped as “just another artificial tear” due to its completely different molecular design.
• If the patient is only partially improved, we recommend adding Lotemax q.i.d. for two weeks, being sure to separate the two eye drops by about 30 minutes. We have found that most, but not all patients, achieve relief with this approach. If there is a clinically significant inflammatory component to the patient’s dry eye, then it is our opinion that a twoweek course of q.i.d. loteprednol is sufficient to suppress the ocular surface inflammation.
• Assuming clinical success, we now decrease the Lotemax to b.i.d. for two more months and allow the patient to try to reduce the frequency of instillation of the Soothe XP.
• At the two-month follow-up (assuming we have a satisfied patient, which is typically the case), we are at another decision tree. By this time, most patients are using Soothe XP two to three times a day, and we can try to stop the Lotemax. Remember that Drs. Lemp and Foulks have showed us that tear osmolarity is “the central mechanism causing ocular surface inflammation.” So, via Soothe XP, we have bolstered the lipid layer, thus reducing tear osmolarity, and with Lotemax, we have addressed whatever hyperosmolarity-induced inflammation preexisted. At this juncture, there should be little or no clinically significant ocular surface inflammation.
• Now, back to the decision tree: Following the two to three-month “inflammation suppression” phase, we stress the importance of consistent ocular surface lubrication to help prevent any reestablishment of inflammation, and we generally stop the Lotemax. Keep in mind that we prescribed it q.i.d. for two weeks and b.i.d. for two months, which we think is ample time to suppress any ocular surface inflammation. Now, we are in a “maintenance phase,” using only artificial tears. Some doctors continue the Lotemax once daily for a few more months, and while we have no issue with this, we do not feel it is necessary in most cases.
We must now considerably digress. Obviously, one cannot treat every patient with a rigid protocol. It is incumbent upon us to attentively treat every patient on an individual basis, so we offer the following perspectives: it is well established that omega-3 supplementation can be helpful in cardiovascular disease, rheumatologic disease and meibomian gland dysfunction. It may be that most adults would be well served to take such supplementation. Regardless, neither the exact amount nor the ratio of DHA to EPA has been established in prospective clinical trials. And, even if such data existed, one would still have to treat each patient on an individualized basis. Our approach is generally to suggest supplementation early on in the treatment with the goal of using the least amount of topical eye drops to maintain comfort.
It is our impression that oral doxycycline most potently and more quickly enhances meibomian gland function than the omega-3s, so we often prescribe doxycycline 40mg to 50mg per day for three to four months and then replace the doxycycline with one of the omega- 3 products for enduring use. (It may be that 20mg each day of doxycycline would be effective, but we can find no authoritative support for this.) Any antibiotic can cause gastrointestinal upset and, in women, vaginal candidiasis can be problematic, so discuss these issues proactively. Doxycycline can be taken with food, and doing so generally solves the GI issue.
There is some chatter about using azithromycin (either topically or orally) in place of oral doxycycline. Remember, doxycycline is being used at sub-antimicrobial dosages to reduce meibomian gland inflammation and to enhance the fatty acid metabolism within the meibomian glands. We have now consulted several dermatologists and they have unequivocally stated that doxycycline has a vastly more beneficial clinical effect than azithromycin in this setting. We encourage you to have a similar conversation with dermatologists in your community.
Punctal plugs can be very beneficial once any ocular surface inflammation has been controlled. To “plug first and steroid later” can actually exacerbate ocular surface inflammation initially. In our opinion, it is senseless to monkey around with dissolvable collagen plugs “to see if the patient is helped temporarily.”
We believe the need, or lack thereof, of punctal occlusion should be profoundly evident to a seasoned clinician. “Just do it,” if in your judgment the patient can benefit. Whether you choose to plug the more symptomatic eye as a trial (to see how much relief is obtained), or plug both lower puncta simultaneously, is a judgment call.
We always employ punctal plugs, and never use intracanalicular devices. This is mainly so we, and our patients, can monitor whether the plug is still there or not. (See “New Insights Into Punctal Plugs,” page 37A, on why replugging is often unnecessary should the initial plug become extruded and lost.)
Our experiences have demonstrated to us and our patients that the approach that we have set forth here works well and leaves precious few patients unsatisfied.
We close this discussion with an example of the success of this approach. A very pleasant, 65-yearold white female had been leaving our general area and driving a few hours away every three months for the past five years to a highly prestigious medical center for treatment of her dry eyes. After trying to help her for five years, she was still symptomatic and unhappy, but was told everything that could be done for her had been done. They suggested she find a local ophthalmologist to continue to care for her and save her all these time-consuming and expensive trips.
She found one of us, and here is what our records can document. Yes, she had tried every artificial tear (except Soothe XP); yes, she had properly placed punctal plugs; yes, she was on Restasis; and yes, she was using omega-3 supplementation. Here is what we did to enable this lady after two months to say, “This is the best my eyes have felt in years.” We replaced her artificial tears with Soothe XP, we added 50mg of oral doxycycline (and continued her omega-3), and replaced the Restasis with Lotemax, as we described earlier.
As we have clearly set forth, caring for patients with dry eyes is not all that challenging—if we wisely use the good medicines at our disposal.
- Foulks GN. The correlation between the tear film lipid layer and dry eye disease. Surv Ophthalmol. 2007 Jul-Aug; 52(4):369-74. Review.
- Lemp MA. Advances in understanding and managing dry eye disease. Am J Ophthalmol. 2008 Sep;146(3):350-356. Epub 2008 Jul 2. Review.
- Management and therapy of dry eye disease: report of the Management and Therapy Subcommittee of the International Dry Eye WorkShop (2007). Ocul Surf 2007 Apr;5(2):171.