The dysfunctional tear syndrome opus: Review and interpretation

One expert breaks down the strengths, weaknesses and bottom line of this recent publication.

My friend Mark Milner and I have spent countless hours together on various stages in venues across the country talking about dry eye disease. A couple of years ago, he mentioned that he was working on a comprehensive DED diagnostic and treatment protocol that would be published “pretty soon.” I am not Jewish, but I am now fully aware of what my Jewish brothers and sisters mean when they say “next year in Jerusalem.” We have been waiting for the arrival of the CEDARS/ASPENS opus on the evaluation and treatment of dysfunctional tear syndrome for longer than Didi and Gogo waited for Godot. It arrived in my inbox recently, all 1,127 pages signed by each of the 93 authors.

Just kidding. It is only 45 pages long.

Fear not. I, your trusted DED scribe, am here to give you an overview of this very important contribution to the DED canon. What follows is an examination of the strengths and weaknesses of the article. The purpose of The Dry Eye is in part to distill large amounts of information into an easily digestible morsel that can be put into action in your DED clinic. I will do my best to give you a “bottom line” take-home message as well.

Nomenclature and subcategories

Review articles of broad topics are meant to be comprehensive in scope, and the review by Milner and colleagues in the January issue of Current Opinion in Ophthalmology certainly qualifies. Multiple authors mean that you are unlikely to end up with any bold statements about the disease or entity in question. In order to complete the project (see paragraph one above), it is necessary to reach consensus. The peer-review process, as well as the fact that the article is eligible for CME credit, also magnifies this phenomenon. We get an exhaustive review but little in the way of an ordering of our options.

From 30,000 feet, the authors open by declaring that we would do well to change our basic nomenclature. Rather than referring to “dry eye,” it would be more accurate to call all of the various subtypes “dysfunctional tear syndrome,” or DTS. Among friends and colleagues, I agree, and because this is a communiqué to us, I think it is appropriate to use this new term as our foundation. (Note: Your patients will still want to call it dry eye.) Others may prefer “ocular surface disease” because that includes infections and allergy as well. Call that the umbrella term under which DTS is the largest bucket.

The 3,000 foot view is an entity that is broken down into four distinct subcategories: aqueous deficient, meibomian gland disease/blepharitis, exposure-related DTS and goblet cell deficiency. Taking them in reverse order, we can dispense with goblet cell, or mucin deficiency, right away because it is of academic interest only. There is no diagnostic test available to label any case of DTS as a primary mucin deficiency, and there is no true goblet cell-targeted treatment out there for us to use. For all that we know about DTS, all of which is right here in this review, including goblet cell deficiency reminds us that we still have a huge hole in our understanding of what is actually happening at the 0.3 mm view on the ocular surface. While hardly ignored, mucin treatment remains the “Ghost of DTS Future.”

Every time I read about exposure DTS (E-DTS), I am chagrined anew at how infrequently I consider it in the clinic. E-DTS and its cousin, the floppy eyelid syndrome, are actually incredibly common, and this review does us all a significant service by reminding us to put E-DTS closer to the top of both our diagnostic and therapeutic radar screens. Unlike mucin-associated disease, E-DTS lends itself quite readily to both accurate diagnosis and easily accessible treatment. Indeed, the section on treating E-DTS is the most helpful in the review because it is rather pointed and direct.

Which leaves us looking down from our 3,000-foot perch at the two most common causes of DTS, aqueous deficient (AD-DTS) and meibomian gland/blepharitis associated (MG-DTS). The community of doctors who willingly treat DED is emerging from a period of upheaval in how we think about the disease, one in which our traditional emphasis on reduced tear production has been replaced by the concept of dysfunction associated with abnormal oil production. We continue to hew to the concept that underlying both general categories is a single culprit: inflammation in the tear production system. This is undoubtedly the strongest part of the review. The explanation of the primacy of inflammation and its effect on both aqueous and lipid production should be required reading for initiates and experts alike.

Diagnosis and treatment

It gets awfully messy as we descend to 300, 30 and 3 feet, though. Think 15 Michelin-starred chefs sitting around a table putting together a review article meant to contain the collective information in everything ever written by Julia Child and M.F.K. Fisher, and you start to get an idea of what it must be like to have a group of mostly fellowship-trained cornea specialists writing on a topic that each and every one of us will deal with every single time we enter the kitchen, er, clinic. The sheer volume of information presented makes it somewhat challenging to winnow down our options and target them so that we can effectively treat the most common cases that fill our lanes. Indeed, a careful re-reading (or re-re-reading, as was the case for me) will show that there is much more commonality in the diagnostic and treatment approach across subtypes than not.

After all, one butters one’s toast the same way most of the time whether the bread be white or wheat, and the nuance of upland (Child) vs. lowland (Fisher) Irish butter seldom influences the nutritional value of either.

As a lifelong athlete who participated in team sports, I am genetically wired to be a good team player. However, unlike the roster of superstar “athletes” in the list of authors, I am unencumbered by the need to either achieve a consensus or please a reviewer. Let me therefore distill the ingredients jammed into the review article’s pantry into a concise recipe to follow, one that will be true to both the letter and the spirit of this very important contribution. Note that you really should read the review.

Despite the fact that the majority of the authors practice in a referral setting, it is clear from the review that every encounter with a DTS patient begins with a careful history of that particular patient’s symptoms. These are clinical signs-driven doctors, and yet there is a very strong emphasis on making patients feel better as a primary endpoint. A simple, straightforward exam is always a part of the process, and it includes taking the patient’s visual acuity and doing a slit lamp exam. Really basic stuff like fluorescein staining and tear breakup time are mandatory elements. The authors make a point that you can stop right here and treat.

I would have preferred a stronger statement about including point-of-service tests as well as a bolder, more definitive statement about how to interpret the results. My strong bias, obvious in my prior writing, is that you should be testing tear osmolarity as a minimum, and assessing objective evidence for the presence of inflammation on the ocular surface is valuable if available. The more information you have at 3 feet and 30 feet, the more success you will have at 0.3 mm.

Treat DTS when it is diagnosed. Treat it like a disease with real, honest-to-goodness medicine. On this the authors and I strongly agree. It does not matter whether you use Restasis (cyclosporine ophthalmic emulsion 0.05%, Allergan), Xiidra (lifitegrast ophthalmic solution 5%, Shire) or your favorite steroid, treat inflammation if it is present, especially in the symptomatic patient. While there are all kinds of esoteric treatments out there (dapsone gets a lot of love, for example), commonly available treatments work uncommonly well in the treatment of common problems. For most of us it is not necessary to get fancy (Irish butter) in order to successfully treat the majority of our patients.

You will notice an enormous amount of overlap in the suggested treatment of both AD-DTS and MG-DTS. You could certainly use that insight from this very accomplished group to create a “boilerplate” first treatment program for most of your patients. Among other variables, your template could be driven by the local regulatory/insurance environment (it is illegal to sell Irish butter in Wisconsin). The majority of your patients will likely improve over time using this approach. This brings up a final gem from the article, one that in itself is worth the effort put in by the authors: Sometimes choosing to give a partially successful treatment program more time to succeed is the best “new” course.

If your toast pops out of the toaster and it is too light, you do not have to buy a new toaster — you just have to toast your bread a little longer.

“Dysfunctional tear syndrome: dry eye disease and associated tear film disorders — new strategies for diagnosis and treatment” was a massive undertaking, long in the making, but well worth the effort on the part of its authors. Everyone in the DED space owes Mark Milner and his colleagues an enormous debt of gratitude for pulling together this opus. Each of us, and by extension all of our patients, would benefit from a careful reading and thoughtful application of its contents. – by Darrell E. White, MD

Reference:

Milner MS, et al. Curr Opin Ophthalmol. 2017;doi:10.1097/01.icu.0000512373.81749.b7.

For more information:

Darrell E. White, MD, can be reached at SkyVision Centers, 2237 Crocker Road, Suite 100, Westlake, OH 44145; email: dwhite2@skyvisioncenters.com.

Disclosure: White reports he is a consultant for Bausch + Lomb, Allergan, Shire and Eyemaginations; is on the speakers board for Bausch + Lomb, Allergan and Shire; and has a financial interest in TearScience.