As ophthalmologists know all too well, dry eye is a notoriously complex disease, with multiple risk factors and causes. Adding to the diagnostic and treatment headaches is the fact that the signs and symptoms are often disparate — many patients have numerous symptoms and minimal signs, and vice versa. Further, DED, like glaucoma or hypertension, may need several concurrent treatments to control the disease.

And that is the disease itself. Dry eye also has what I call co-conspirators, diseases that masquerade as or contribute to DED. It’s no wonder that patient and physician alike use words like exasperating, annoying and hopeless in association with this disease.

Before we turn to co-contributors — what they are, what the symptoms are, and how to treat them — we’ll first explore the reasons why and how you should diagnose DED patients in the first place.

Why embrace DED?

• Prevalence. DED is probably the most prevalent diagnosis in our practices. Upwards of 30 million Americans have dry eye¹; most dry eye experts believe this is probably an underestimate.
• Practice builder. Embracing these patients can build your practice. As mentioned, these patients are extremely frustrated and, when treated, can be the most appreciative and refer their sisters who need cataract surgery, their nieces who want LASIK, and so on.
• Financial stability. While practices performing discretionary services such as LASIK and premium IOLs may be affected by a recession, dry eye practices grow in any economy.
• CL tolerance and happy postsurgical patients. A healthy tear film is critical to contact lens tolerance and surgical outcomes. Trattler et al showed that 80.9% of patients from nine sites presenting for routine cataract screening had level 2 DED or higher, based upon the ITF guidelines,² while half had central corneal staining.²

As a cornea specialist, I have received countless referrals for patients with 20/20 to 20/30 vision after cataract surgery with a premium IOL who were not happy with their vision because the previous physician did not adequately treat the tear film.

A DIAGNOSTIC-BASED APPROACH

Let’s assume that you are now sold on the importance of taking the tear film more seriously. What can you do to limit the frustration and make it easier to take care of these patients? As I see it, one problem is that many of the algorithms available to treat DED use a severity-based approach. This means that you treat mild dry eye differently than moderate or severe dry eye, regardless of the subtype or cause of the DED, which may limit your success.

I believe a diagnostic-based approach makes more sense. Your approach will be more directed and your patients will likely have better outcomes if you can separate them into four basic subtypes:³

1. The aqueous deficient
2. Those with blepharitis/meibomian gland dysfunction (evaporative; nonevaporative);
3. Goblet cell deficient/mucin deficient
4. Those with exposure keratopathy (Figure 1).

If you direct your treatments based upon one or more of these DED classifications, which often overlap, it will more than likely help the patient (Figure 2).

GUILT BY ASSOCIATION

Colleagues have told me that they followed this approach and, although it helped, they still have the occasional patient who is no better despite multiple treatment trials (often from multiple physicians). When this happens, it is important to think about what I call the dry eye “co-conspirators,” those diseases that masquerade as or contribute to DED. These are ocular surface diseases that sound like dry eye based upon the patient’s complaints or “fuel the fire” of DED by exacerbating the dysfunctional tear syndrome with its course and/or treatments. A co-conspirator could leave you feeing like you’re “spinning your wheels.”

The list of DED co-conspirators includes:

• Superior limbic keratoconjunctivitis (SLK). SLK is basically a chaffing of the upper bulbar and tarsal conjunctiva from a redundant superior bulbar conjunctiva. This may occur due to a loss of Tenon’s capsule along with a potential association with thyroid eye disease. These patients may vehemently complain of dry eye symptoms. However, you will not make the proper SLK diagnosis until you move the slit lamp away and witness the superior injection by having the patient look down and raise the upper lid, or use rose Bengal or lissamine green to see the superior staining (Figure 3). Treatments may include topical lubrication, anti-inflammatory drops, chemical or thermal cautery, or excision, with or without amniotic membrane, to name a few.
• Allergic or atopic conjunctivitis. This is an important co-conspirator because it is so common. It acts as a co-conspirator for several reasons. First, allergic conjunctivitis causes inflammation to the ocular surface, which can lead to tear deficiency and instability and goblet cell loss. Atopic/vernal conjunctivitis may also cause stringy mucus prompting mucus fishing. Additionally, the symptoms of allergic/atopic conjunctivitis, such as grittiness, burning and itching, are often confused with DED. Treatment for allergic/atopic conjunctivitis often includes antihistamines, both topically and orally, notoriously exacerbate DED. An excellent example of allergy as a co-conspirator is a patient I treated for DED for almost six months with limited success. She had mild aqueous deficiency, trace meibomian gland dysfunction and no history of allergies. None of my directed approaches helped, so I began to suspect a co-conspirator. After the patient repeatedly denied having any environmental allergies, I performed allergy skin testing and the results surprisingly showed an allergy to Aspergillus — tests later revealed high levels in her bedroom and basement. Upon cleaning the mold from her house, her symptoms resolved.
• Conjunctivochalasis. Often under-diagnosed, conjunctivochalasis is a redundant conjunctiva inferiorly (almost like an “inferior SLK”) that mimics the dry eye symptoms of irritation from exposed, externalized conjunctiva or increased tearing from the conjunctivochalasis blocking the tears from filling the fornix, ultimately coming onto the lid and cheek. Treatment is similar to SLK, but, in my experience, symptoms often persist until the redundant conjunctiva is excised with or without amniotic membrane.
• Medicamentosa. This co-conspirator is often missed when a patient takes multiple topical medications (such as glaucoma drops) and the preservatives and/or medications themselves cause toxicity and symptoms of irritation similar to DED. The treatment here is often to simply stop the meds and “start over from scratch” if possible. Many times, a patient will be helped by using preservative-free drops when available commercially or compounded.
• Thygeson superficial punctate keratitis (SPK). This is an intra-epithelial keratitis of unknown etiology; the diagnosis is one of exclusion with similar symptoms as DED. Topical steroids and topical cyclosporine (off label) work well with Thygeson SPK.
• Mucus fishing syndrome. This is another underdiagnosed co-conspirator. The patient often digs into her inferior fornix with a tissue, cotton swab or a fingernail to remove mucus or stop the itching. Mucus-fishing patients commonly “spin their wheels” with further DED treatments because the symptoms never abate until they stop the fishing. The diagnosis is made more easily with a thorough history and rose Bengal or lissamine green staining showing uptake in the inferior fornix (Figure 3). The treatment here, in addition to treating the inciting causes for the mucus, is to convince the patient to stop the fishing. Until the patient stops, the patient often will never feel or look better.
• Contact lens-related toxicity. This may also sound like dry eye to the treating physician. It is imperative for the physician to check the fit of the contact lens, look for solution toxicity, and check for giant papillary conjunctivitis (GPC) by flipping the upper lid. The treatment here is to refit the contacts if needed, change the solutions, or treat the GPC. Treatment of GPC, in addition to CL “holidays” and switching to daily disposables, is to treat the inflammation. Often steroids are used with success, but come with the obvious risks of infection, ocular hypertension and cataracts. GPC has both a type I (IgE mediated) and type IV (T-cell mediated) hypersensitivity response. I believe that a good long-term treatment includes antihistamine/mast cell stabilization to treat the IgE response and treat with topical cyclosporine or lifitegrast (Xiidra, Shire off label) to address the T-cell response.
• Chemical or UV keratitis. This is a rare but often missed co-conspirator. Exposure to chemicals or fumes (such as hair spray) or UV light may lead to a keratitis in the interpalpebral fissure and to complaints similar to DED. For example, a patient presented to me with persistent keratitis for months despite several treatments. Then, I realized that his hair was perfect and motionless at every visit, so I asked him if he used hair spray. He admitted that he used it in front of the mirror — with his eyes open. A simple suggestion to close his eyes solved the problem. In other situations, the remedy is to identify the offending chemical and limit its exposure.
• Floppy lid syndrome. This can confound a DED diagnosis because these patients can have chronic symptoms of irritation, burning and grittiness similar to dry eye. The patient usually sleeps with his/her face buried in the pillow and inadvertently mechanically irritates the eye. A trial of an eye shield at bedtime can often help clarify the situation and improve the symptoms. Eye shields at bedtime may be a simple treatment to improve the signs and symptoms of floppy lid syndrome. Ultimately, however, the patient may need an oculoplastics remedy. Also, patients with floppy lid syndrome should be checked for sleep apnea due to its association.
• Corneal hyperalgesia. Some have referred to this as a “fibromyalgia of the eye.” A patient with corneal hyperalgesia following the classic history and course of corneal hyperalgesia has complaints that are not relieved with many treatments and has symptoms often out of proportion to the findings. One finding to differentiate this from DED is the lack of (or minimal) improvement in symptoms with topical anesthetic. In addition, the diagnosis may also be made with a confocal microscopy showing neuromas; a decrease in the density of the corneal nerves; and the triad of hyperalgesia, allodynia (the experience of pain from a non-painful stimulus) and spontaneous pain.^4,5 The treatment for corneal hyperalgesia, in addition to treating the DED categories present, includes oral treatments that help other syndromes with similar pain such as nortriptyline or naltrexone, diet and exercise or ultimately scleral lenses.⁶

CONCLUSION

Undiagnosed and/or untreated DED co-conspirators can cause persistent, relentless signs and symptoms of DED and delay successful treatment. Uncovering these co-conspirators starts with thinking about whether the patient could have other ocular surface diseases that confuse the picture or limit improvement. There is no substitute for a careful history and thorough examination. Assessing the rose Bengal (or lissamine green) or fluorescein staining pattern may aid in making the diagnosis of these co-conspirators.

While the list on page 22 is comprehensive it is, by no means, a complete tally of co-conspirators. Keep these co-conspirators in mind to help in successfully treating the patient and easing the frustration of all involved. OM

REFERENCES

1. Paulsen AJ, Cruickshanks KJ, Fischer ME, et al. Dry eye in the beaver dam offspring study: prevalence, risk factors and health-related quality of life. Am J Ophthalmology. 2014;157:799-806.
2. Trattler, WB, et al. Clinical study report: Cataract and dry eye: prospective health assessment of cataract patients ocular surface study. 2010. (Unpublished study).
3. Milner MS, Beckman KA, Luchs JI, et al. Dysfunctional tear syndrome: dry eye disease and associated tear film disorders - new strategies for diagnosis and treatment. Curr Opin Ophthalmol. 2017 Jan;27 Suppl 1:3-47.
4. Goyal S, Hamrah P. Understanding neuropathic corneal pain—gaps and current therapeutic approaches. Semin Ophthalmol. 2016;31:59-70.
5. Hamrah P, Qazi Y, Shahatit B, et al. Corneal nerve and epithelial cell alterations in corneal allodynia: an in vivo confocal microscopy case series. Ocul Surf. 2017;15:139-151.
6. Hamrah P, Qazi Y, Shahatit B, et al. Corneal nerve and epithelial cell alterations in corneal allodynia: an in vivo confocal microscopy case series. Ocul Surf. 2017;15:139-151.

About the Author

Mark S. Milner, MD, specializes in cornea, external disease, uveitis and refractive surgery. He practices at the Eye Center of Southern Connecticut, Hamden, CT.