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Achieving the premium ocular surface
Determining the type of dry eye a patient has is crucial to ensuring a proper treatment regimen.
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The arena of dry eye disease has become its own area of expertise, requiring a thorough knowledge of the etiologic, diagnostic and therapeutic approaches to achieve the premium ocular surface.
There are various reports indicating that up to between 25 million and 30 million Americans suffer from dry eye, with at least 50% of the patients visiting eye care professionals for a primary or secondary complaint of dry eye. A Gallup survey in 2012 further showed that 66% of patients seen at a formal eye exam have tried three or more artificial tears for 2 or more years before the exam.
The definition of dry eye disease has changed from the original Pflugfelder definition in 2004, which said that the lacrimal unit created a dysfunctional tear film, to that of the International Dry Eye WorkShop (DEWS) in 2007, which says that dry eye is a multifactorial disease of the ocular surface that results in discomfort, visual disturbance and tear film disability accompanied by increased inflammation and osmolarity of the tear film and ocular surface.
The tear film is the most important refracting surface of the eye and involves a complex interaction of the environment, the aging process, systemic diseases, systemic medication, osmolarity, inflammatory processes and lacrimal gland neuroregulation. As a result of these interactions, ocular surface abnormalities are clinically relevant as a crossover or combination of evaporative dry eye (posterior blepharitis, meibomian gland dysfunction or lid margin disease), aqueous deficiency (dry eye syndrome or primary/secondary Sjögren’s syndrome) and/or ocular allergy.
Recognizing, treating blepharitis
Posterior blepharitis, or meibomian gland dysfunction, is a chronic, recurrent and progressive disease of the meibomian glands in the eyelids. It can be obvious, in cases such as plugged meibomian glands, gland dropout or inflammation on slit lamp evaluation, or non-obvious, such as with the expression of meibomian glands needed to view the quality and quantity of secretions. Acne rosacea causes meibomian gland dysfunction 50% of the time.
Mitchell A. Jackson
Therapeutic options include any combination of warm compresses or goggles; lid massage; lid scrubs; topical eye medications; artificial tears that replace the lipid layer; systemic medications, such as low-dose doxycycline at 50 mg/day or nutritional supplements that offer anti-inflammatory benefit; and/or eyelid procedures, such as the Maskin Meibomian Gland Intraductal Probe (Rhein Medical) or the LipiFlow Thermal Pulsation System (TearScience) aided by diagnostic evaluation of the lipid layer with the LipiView Interferometer (TearScience).
Aqueous deficiency
Aqueous deficiency is typically most common in postmenopausal women older than age 50 years, affecting approximately 12 million individuals in the U.S. Other risk factors for this category of dry eye disease include prior corneal refractive surgery; autoimmune diseases, with diabetes mellitus as the No. 1 cause and thyroid as No. 2; patients with low blink rate, such as those with computer vision syndrome and Parkinson’s disease; prior cosmetic facial surgery, such as blepharoplasty; and contact lens users. Medications such as antihistamines, diuretics, beta-blockers, tricyclic antidepressants, anxiolytics, antispasmodics, hormone replacement therapy and birth control pills are among the many that can contribute to dry eye and aqueous deficiency.
With the new DEWS definition, the tear film in aqueous deficiency typically has elevated electrolytes measurable as osmolarity, decreased protective enzymes and antibodies, and elevated inflammatory cytokines.
Current clinical measures to evaluate dry eye include tear secretion tests such as Schirmer, corneal and conjunctival staining, tear breakup time, impression cytology, tear osmolarity, LipiView analysis and patient questionnaires, such as the Ocular Surface Disease Index and SPEED. Other in-office quick tests not yet approved in the U.S. to detect inflammatory mediators include InflammaDry (RPS), which detects elevated levels of matrix metalloproteinase-9, with a level greater than 40 ng/mL indicative of ocular surface damage.
Tear osmolarity
Quantifying tear osmolarity is a reliable method to diagnose aqueous deficiency and monitor a patient’s response to treatment. A tear osmolarity reading greater than 308 mOsm/L and/or a difference of greater than 8 mOsm/L between the two eyes is a hallmark of tear film instability. Like hemoglobin A1c is a measure of blood glucose control in diabetes, tear osmolarity is a good measure of dry eye severity and therapeutic response.
Lastly, newer devices such as the Keratograph 5M (Oculus) can assess the tear lipid layer in a more quantitative format as an initial diagnostic tool by measuring tear breakup time, tear volume and meibomian gland dropout in the tarsus in a noninvasive manner.
The International Task Force (ITF) created consensus guidelines in terms of diagnostic signs and treatment considerations. ITF level 1 reveals conjunctival staining (best seen with lissamine green), level 2 adds corneal staining and poor tear breakup time, level 3 adds filamentary corneal findings, and level 4 adds conjunctival scarring. The DEWS diagnostic template for staining recommends dividing the cornea into five regions and the interpalpebral conjunctiva into six regions, with a grading scale of 0 to 3 in each region.
To simplify the process clinically, at the minimum it is best to grade the central cornea and inferior cornea staining and be consistent with your ITF classification and grading between exams. The central cornea is the hallmark of severe disease, and the inferior cornea is the most common location of staining. As for the conjunctiva, I consistently measure just nasal or temporal regions at each exam unless it is for clinical study purposes. Staining is maximized on the corneal and/or conjunctival surface if you allow for 60 to 90 seconds after dye instillation.
The ITF recommends using topical Restasis (cyclosporine ophthalmic emulsion 0.05%, Allergan) for level 2 and above, with the addition of punctal plugs at level 3 and above. Topical cyclosporine is believed to inhibit T cell activation, recruit additional T cells and reduce cytokine production in the inflammatory process of dry eye.
Sanjay N. Rao, MD’s, 2011 follow-up to the publication of his original study in 2010, which compared cyclosporine and Refresh Endura artificial tears (Allergan), showed continued increased tear production with cyclosporine use at 2 years compared to tear production control patients with chronic dry eye due to ocular inflammation. Because cyclosporine takes approximately 3 to 6 weeks before having a therapeutic effect, I prefer to use topical steroids such as Lotemax gel (loteprednol etabonate ophthalmic gel 0.5%, Bausch + Lomb) during the induction phase for cyclosporine. Hypotonic artificial tears, such as Blink (Abbott Medical Optics) and TheraTears (Advanced Vision Research), have also been shown to reduce osmolarity and can be useful in patients with elevated osmolarity.
Newer topical treatments on the horizon but not yet approved by the U.S. Food and Drug Administration include topical interleukin-1 receptor antagonists, such as Kineret (anakinra 2.5%, Amgen); topical lifitegrast (Shire), a small-molecule integrin antagonist believed to reduce inflammation over a 12-week period; and topical RU-101 (recombinant human serum albumin-containing ophthalmic solution, R-Tech Ueno) as a 12-week treatment to enhance mucin production in the tear film. Autologous serum tears are already part of the dry eye armamentarium. By centrifuging the patient’s blood, the serum component is combined with sodium chloride typically in a 20% concentration, and used topically, but not in recombinant form.
Ocular allergy
Ocular allergy completes the triad that can affect the ocular surface. Patients may have perennial allergies caused by dust mites and/or animal dander, or they may have seasonal allergies caused by tree, grass and/or ragweed pollens.
All forms of allergy treatment will typically cause dry eye as a side effect of treatment, complicating an already complex ocular surface. Fortunately, the newest topical allergy eye medications are combination agents blocking H1 receptor activity at the corneal nerve level to prevent itching, as well as blocking mast cells from releasing histamine and other inflammatory mediators responsible for chemosis, vasodilation, edema and hyperemia.
The newest topical combination agents on the market that have the highest specificity for the H1 receptor and without the muscarinic side effects of dry eye are Bepreve (bepotastine besilate ophthalmic solution 1.5%, Bausch + Lomb) and Lastacaft (alcaftidine ophthalmic solution 0.25%, Allergan).
In summary, the ocular surface is a complex array of environmental influences, meibomian gland disease and inflammatory mediators. Deciphering whether the patient has evaporative dry eye or an aqueous-deficient dry eye, or both, with or without an additional allergy insult is important in paving the way to a proper treatment regimen as described by the DEWS report and other current and future treatment modalities.
Stay tuned for my next column on achieving the premium patient experience, which will include perspective from my own recent surgery.