In the early 1980s, while working on my master’s degree in biology, I decided to become an optometrist. I had taken on an ophthalmic technician job with an ophthalmologist, Jack M. Dodick, MD, to understand the eyecare professions.

At that time, Dr. Dodick was chief at Manhattan Eye, Ear and Throat Hospital, and his practice enjoyed informative visits from many pharmaceutical and device representatives. Famous actors and artists, princes and politicians, and a host of other high-profile New Yorkers were patients of the practice.

Rarely a day went by without one of us in the practice mentioning a patient’s pre- or post-operative vague or specific complaints of blurred vision, ocular discomfort in its many forms, fatigue, and/or fluctuating vision. Often, patients characterized their eyes as “feeling dry,” especially after cataract surgery.

The go-to solution at the time (no pun intended) for these patients was a hypotonic artificial tear drop that is no longer commercially available. Most boots-on-the-ground clinicians were comfortable with “adding wet if a patient complained of dry.”

In the ’80s, one of our forward-thinking drug representatives would always say to me, “Katherine, dry eye treatment is going to be big. Really big.” Then he would arm me with a dozen units of his “Patient Dry Eye Treatment Kits” that consisted of a blue box containing a travel-sized bottle of baby shampoo, some 2-by-2-inch gauze pads, a tube of antibiotic ointment, and a bottle of hypotonic artificial tears. In retrospect, this simple kit addressed a number of ocular surface disease (OSD) concerns for which we now have better understanding and treatments.

Fast forward to 2022. Experts from around the world share knowledge and evidence-based strategies through workshops, panels, reports, and summits. Eyecare practices around the globe are adding ocular surface specialty care to their practice offerings. Novel technologies, therapeutics, and treatments for “dry eye” allow us to better manage this ubiquitous concern.

CONTENTS OF THE BLUE BOX

Instilling hypotonic “artificial tears” was an attempt to balance the patient’s dysfunctional natural tears, restoring a more normal osmolar environment. Hyperosmolar tears contribute to a cycle of damage and inflammation to the ocular surface.¹ This is a pure and simple explanation for a complex disease. Yet, the main objective of restoring ocular surface balance, or homeostasis, is core to the deliverables that most of our dry eye practices choose to alleviate the multiple triggers of ocular surface inflammation. With an explosion of dry eye research and treatment alternatives, every practice can successfully build a dedicated OSD specialty. Let’s explore the evolution of dry treatment from the contents of the blue box.

The Basics Including baby shampoo in the dry eye blue box is a nod to the understanding that lid margin hygiene is paramount to a healthy tear film and ocular surface. Bacteria, allergens, mites, skin care products and cosmetics, environmental pollutants, and the residue from ocular medications all have deleterious effects on both the structure and function of the lids, lashes, and glands that contribute to the manufacturing of tears.

We now have a host of preparations specifically designed for eyelid hygiene, including an array of hypochlorous acid or other active ingredient cleansing solutions. Hygiene products are available in foams, gels, sprays, wipes, and pads, an upgrade from the blue box gauze squares. In-office microblepharoexfoliation of the lid margins can “jump-start” a home eyelid care regimen with a prescribed product, and an adjunct fibered brush or silicone tool may be used for patient eyelid maintenance at home.

Antibiotic Ointment The blue box also included an antibiotic ointment that had the dual purpose of reducing bacteria (think biofilm, bacterial exotoxins, lipases, and blepharitis, which compromise lid surface and tear integrity and precipitate inflammation) and adding an oily layer to reduce tear evaporation. Although not an ideal therapy for chronic management, the rationale is in the right direction for approaching normalization of the tear/tear-producing environment. Now in 2022, there is more than one technology that encourages the production of the lipid layer of the tear film; most include a meibomian gland-warming element and a form of gentle gland expression or massage with varying degrees of eyecare practitioner involvement in the processes.

These technologies have a range of investment price points and footprints. At the lowest end of this modality, a wraparound or wearable eyelid-warming mask followed by gentle gland expression, often aided by a hand-held paddle or forceps, may be employed at the slit lamp. Patients can continue at-home gland-warming therapy with a warming device that complements and fits into their lifestyle.

Practitioner-directed intense pulsed light (IPL) warms the meibomian glands and has a number of other patient benefits that include making for a more consistent skin tone and reducing telangiectatic blood vessels on the face. IPL promotes collagen synthesis that can improve lid apposition and tear-spreading, modulates epithelial cell apoptosis, stimulates mitochondria, which decreases inflammation, reduces free radicals that promote inflammation, and kills Demodex species that are associated with blepharitis and meibomian gland granulomas.²

Low-level light therapy (LLLT) is an adjunct form of photobiomodulation. Either as an in-office or at-home therapy, combined with IPL or as a stand-alone treatment, LLLT involves applying red, or near infrared, radiation using low-power light sources. LLLT applied as a treatment for dry eye can stimulate lacrimal gland and meibomian gland function.³

Alternately, radiofrequency therapy delivers high-frequency electrical current onto the eyelid tissues to produce heat. The generation of superficial and deep heat stimulates collagen production and skin regeneration. Radiofrequency provides uniform bulk heating at an optimal temperature to treat meibomian gland dysfunction (MGD).⁴

From basic eyelid warming tactics to higher technology devices, heat delivered around the meibomian glands melts the obstructing oils and consistent pressure from the application movement allows for expression. Light therapies have an aesthetic bonus for patients and can promote patient therapeutic recommendation uptake.

Of course, having a view of the meibomian glands (MGs) can guide diagnosis and encourage patient compliance with therapy. From simple Finhoff transillumination of the glands to sophisticated slit lamp-mountable or freestanding unit infrared technologies, every practitioner has the capability to appreciate the structure of these glands.⁵ Similarly, quality and quantity of the oils produced by the MGs can be characterized by slit lamp expression or via interferometry.

Many clinical units now combine corneal topography, tear meniscus height measurements, conjunctival redness analysis, noninvasive tear film breakup, and other data points for MGD imaging and can generate proprietary dry eye analysis and reports. Of course, providers can build their own patient profiles utilizing information obtained from careful slit lamp examination and observation.

Vital dyes enhance the examiner’s clinical skill at identifying changes/abnormalities of the tear film or ocular surface, as well as to the cornea, conjunctiva, lid and lid margins, puncta, and caruncles. A simple yet more integrative assessment of the tear film—the Ocular Protection Index (OPI)—is a ratio of blink rate over breakup time. Ideally, blinks replenish a healthy tear film prior to significant breakup, and an unstable tear film can prompt blinking at a faster rate, one of the known consequences of dry eye. The OPI score reflects this anomaly: in a subject who has an OPI < 1, breakup time is shorter than blink rate, leading to an exposed, compromised ocular surface. Conversely, a subject who has an OPI score > 1 reflects a healthy tear dynamic in which blinks precede the breakup of the aging tear film.⁶

The Blue Box Bottle of Artificial Tears Tear substitutes are commonly used as a first line of defense for patients who have OSD. As in any iteration of “technology,” “eye lubrication” has evolved and improved to counter the deleterious effect of a desiccating ocular surface. The primary types of ingredients used in the composition of tear substitutes are viscosity-enhancing agents (demulcents or lubricants that increase tear film thickness and have hygroscopic properties), electrolytes (to maintain osmotic balance), osmoprotectants (oily agents in the form of liposomes and oil nanodroplets that maintain surface tension of the tear film and in the humectation of the ocular surface), antioxidants, and preservatives. Interestingly, some effects on wound healing and inflammation have been identified for certain ingredients (such as hyaluronic acid [HA]).^7,8 Eye lubricants can be in drop, gel, or ointment form.

Another artificial tear option contains a proprietary cationic oil-in-water nano-emulsion that has novel bio-adhesive properties. It is thought that electrostatic interactions between the positively charged oil nanodroplets and the negatively charged ocular surface epithelium increase the residence time on the ocular surface.⁹ Novel preservative-free bottles allow multi-dosing from a bottle; alternatively, preservative-free, unit-dose vials are available. Ingredients of tear substitutes not only have significant effects on symptomatic relief, but they can also play a significant therapeutic role in addressing the underlying mechanisms involved in DED.

WHAT ELSE TO CONSIDER

1. Anterior segment optical coherence tomography (AS-OCT) is a useful and reproducible instrument to measure the cross-sectional area of conjunctiva prolapsing into the tear meniscus of patients who have conjunctivochalasis (CCh).¹⁰ The presence of age-related CCh¹¹ is associated with dry eye symptoms as well as abnormal tear parameters, and impacts quality of life.¹²Plasma skin regeneration is gaining popularity as a cosmetic procedure.¹³ This noninvasive procedure is especially used in the treatment of mild upper dermatochalasis and lower eyelid lines and wrinkles.¹⁴ It is also known as “fibroblast skin tightening” or “plasma pen.” The exact mechanism of its action is debated. An ultra-high-frequency generator ionizes inert atmospheric nitrogen into an active plasma that delivers controlled thermal energy to the skin via a handpiece. The Plasma Assisted Noninvasive Surgery (PANIS) method can be used as a quick and easy method for the treatment/tightening of CCh (early reports, individual state scope of practice may apply).¹⁵
2. Therapeutic reformulations of antibiotics and steroids, drug advances, and/or novel molecules such as cyclosporine and lifitegrast, have given practitioners advantages in managing DED. Nasal spray stimulation of tear production can augment other therapies, including temporary or semipermanent punctal occlusion. Amnion and amnion-derived or blood-derived products are also a consideration when managing recalcitrant OSD.
3. The most effective contact lens option for patients who have severe DED is scleral lenses. Scleral lenses are fluid filled and vault over the cornea, resting over the limbus, hence providing the ocular surface with constant lubrication. Several studies using scleral lenses have shown improved comfort, decreased dry eye symptoms, and improved visual acuity with a good safety profile in patients who have severe ocular surface disease.¹⁶ Advancements in scleral lens technology and design have made these lenses easier to fit than their predecessors. In addition, sclerals are more readily available commercially, which allows practitioners to consider them earlier when contemplating DED management options.^17,18 Scleral lenses not only provide vision correction, but they also protect the eye and serve a therapeutic purpose by lubricating the ocular surface. In recent years, the U.S. Food and Drug Administration (FDA) has included keratoconjunctivitis sicca as a therapeutic indication in the labeling of scleral lenses.¹⁹ In light of these new standards, scleral lenses are now more commonly used by specialty contact lens fitters and dry eye specialists.
4. Point-of-care diagnostics (e.g., osmolarity and inflammatory biomarkers) are available and can be useful in diagnosis and/or monitoring therapy in OSD. Two commercially available objective dry eye tests include tear film matrix metalloproteinase-9 (MMP-9) and tear film osmolarity, can be used to diagnose dry eye. Inflammation is increasingly recognised as a fundamental element in the pathogenesis of dry eye disease. MMP-9 and osmolarity are known players in the inflammatory pathways that are involved in dry eye disease. Studies suggest that MMP-9 and tear film osmolarity evaluations may be used to easily and conveniently identify inflammation in patients who have dry eye.^20-24
5. One study looked at nutritional supplements that promote dry eye comfort. These supplements include gamma-linolenic acids (GLA) and omega-3 fatty acids (EPA and DHA), antioxidants, and other key vitamins and minerals that work together to support a healthy tear film and soothe the ocular surface.²⁴
6. A battery of dry eye questionnaires to detect/characterize/monitor OSD can help practitioners determine the best options for a specific patient.
7. Educational resources are available from several eyecare provider and patient support groups, blogs, programs, online product shops, and disease state information websites.
8. Digital health media, social media, wearable technology, and artificial intelligence (AI) can be leveraged to generate OSD awareness. Eyelid, eyelash, and ocular surface images are powerful teaching tools for both staff and patients, and a good slit lamp photography system can capture the proverbial “thousand-word” pictures of pathology. Images have a profound, resonating impact on patient understanding and adherence to therapy recommendations. Images elevate the patient experience and can be digitally connected, consumer-centric, and focused on wellness.

THE BEAUTY OF TREATING DRY EYE

Dry eye is a dynamic disease, and its associated signs and symptoms can wax and wane. Patients and providers should appreciate that therapy targets and treatments may vary seasonally and may fluctuate with changing patient medical history, medications, lifestyle, and environmental differences. A patient’s dry eye profile requires regular updating to clue the provider in to symptom concerns. Queries can include changes in diet, weight, cosmetic procedures or products, nutritional supplement use, sleeping patterns, use of continuous positive airway pressure (CPAP) units, and home climate control.

Empower your staff to initiate the dry eye conversation with patients. Educate them to recognize patient complaints that drive the dry eye diagnosis.

Engage and elevate ancillary staff in your dry eye care model by allowing care-extending staff freedom to perform standing order baseline dry eye testing. Cultivate relationships with eye surgeon providers who rely on a healthy ocular surface for successful ocular surgeries (anterior or posterior segment procedures, anti-VEGF therapy, etc.).

Promote your expertise on your website and social media. Emphasize the health-aesthetic relationship of OSD management from clearing red eyes to improving skin tone and texture, as well as eyelash growth and rehabilitation. Recruit the assistance of your vendors in generating a fee schedule for non-covered services and execute non-covered benefit/liability agreements for non-medically covered services (state, local, and legal conditions apply).

An in-office supply of products prescribed for your patients’ therapy will increase patient adherence to care directives and generate additional office income. Consider bundling products to extend in-office treatments into the patient home, as well as enhancing self-care and proactive disease management.

Our industry partners are busily developing exciting new dry eye products—a treatment for Demodex, a water-free drop, and a keratolytic to unblock stagnant meibomian glands are on the horizon. Artificial intelligence has a high potential for use in many different applications related to DED, including automatic detection and classification of DED, investigation of the etiology and risk factors for DED, and the detection of potential biomarkers.²⁵

Keeping up with professional continuing education and paying attention to patient blogs, support groups, and email groups for those suffering from dry eye will elevate your practice and enhance your patients’ lives. Keep your finger on the pulse of the developments and best practices in OSD. Finally, be a dry eye warrior! CLS

REFERENCES

1. Baudouin C, Aragona P, Messmer EM, et al. Role of Hyperosmolarity in the Pathogenesis and Management of Dry Eye Disease: Proceedings of the OCEAN Group Meeting. Ocul Surf. 2013 Oct;11:246-258.
2. Cote S, Zhang AC, Ahmadzai V, et al. Intense pulsed light (IPL) therapy for the treatment of meibomian gland dysfunction. Cochrane Database Syst Rev. 2020 Mar 18;3:CD013559.
3. Park Y, Kim H, Kim S, Cho KJ. Effect of low-level light therapy in patients with dry eye: a prospective, randomized, observer-masked trial. Sci Rep. 2022 Mar;12:3575.
4. el-Domyati M, el-Ammawi TS, Medhat W, et al. Radiofrequency facial rejuvenation: evidence-based effect. J Am Acad Dermatol. 2011;64:524-535
5. Alsuhaibani AH, Carter KD, Abràmoff MD, Nerad JA. Saudi J Ophthalmol. 2011 Jan;25:61-66.
6. Abelson MB, Lafond A. 3,500 Years of Artificial Tears. Rev Opthalmol. 2014 Dec 8;13:110-113. Available at reviewofophthalmology.com/article/3500-years-of-artificial-tears . Accessed May 24, 2022.
7. Labetoulle M, Benitez-Del-Castillo JM, Barabino S, et al. Artificial Tears: Biological Role of Their Ingredients in the Management of Dry Eye Disease. Int J Mol Sci. 2022 Feb;23:2434.
8. Moshirfar M, Pierson K, Hanamaikai K, Santiago-Caban L, Muthappan V, Passi SF. Artificial tears potpourri: a literature review. Clin Ophthalmol. 2014 Jul;8:1419-1433.
9. Lallemand F, Daull P, Benita S, Buggage R, Garrigue, J-S. Successfully Improving Ocular Drug Delivery Using the Cationic Nanoemulsion, Novasorb. J Drug Deliv. 2012;2012:604204.
10. Gumus K, Crockett CH, Pflugfelder SC. Anterior segment optical coherence tomography: a diagnostic instrument for conjunctivochalasis. Am J Ophthalmol. 2010 Dec;150:798-806.
11. de Paiva CS. Effects of Aging in Dry Eye. Int Ophthalmol Clin. 2017 Spring;57:47-64.
12. Chhadva P, Alexander A, McClellan AL, McManus KT, Seiden B, Galor A. The impact of conjunctivochalasis on dry eye symptoms and signs. Invest Ophthalmol Vis Sci. 2015 May;56:2867-2871.
13. Elsaie ML, Kammer JN. Evaluation of plasma skin regeneration technology for cutaneous remodeling. J Cosmet Dermatol. 2008 Dec;7:309-311.
14. Patel S, Shamdas M, Cobb C. Plasma fibroblast skin tightening treatment resulting in bilateral chemical eye injury secondary to EMLA cream: a case report. BMC Ophthalmol. 2020 Aug;20:342.
15. Jadidi K, Nabavi N-S, Nejat MA, et al. Evaluation of plasma assisted noninvasive surgery (PANIS) as a new approach for the treatment of conjunctivochalasis; a clinical case series. Expert Rev Ophthalmol. 2021;16:225-230.
16. Bavinger JC, DeLoss K, Mian SI. Scleral lens use in dry eye syndrome. Curr Opin Ophthalmol. 2015 Jul;26:319-324.
17. Thulasi P, Djalilian AR. Update in Current Diagnostics and Therapeutics of Dry Eye Disease. Ophthalmology. 2017 Nov;124:S27-S33.
18. Jackson WB. Management of dysfunctional tear syndrome: a Canadian consensus. Can J Ophthalmol. 2009 Aug;44:385-394.
19. Art Optical. Amplyeye™ Scleral Now FDA Approved for Ocular Surface & Dry Eye Disease Management. Available at artoptical.com/news-events/ampleye-scleral-now-fda-approved-for-ocular-surface-dry-eye-disease-managem?msclkid=208bb7f0afac11ecb138e3a38ffd36d9 . Accessed March 29, 2022.
20. Bron AJ, de Paiva CS, Chauhan SK, et al. TFOS DEWS II pathophysiology report. Ocul Surf. 2017 Jul;15:438-510.
21. VanDerMeid KR, Su SP, Ward KW, Zhang J-Z. Correlation of tear inflammatory cytokines and matrix metalloproteinases with four dry eye diagnostic tests. Invest Opthalmol Vis Sci . 2012 Mar 21;53:1512-1518.
22. Mathews PM, Karakus S, Agrawal D, Hindman HB, Ramulu PY, Akpek EK. Tear osmolarity and correlation with ocular surface parameters in patients with dry eye. Cornea. 2017 Nov;36:1352-1357.
23. Kang MJ, Kim HS, Kim MS, Kim EC. The Correlation between Matrix Metalloproteinase-9 Point-of-Care Immunoassay, Tear Film Osmolarity, and Ocular Surface Parameters. J Ophthalmol. 2022;2022:6132016.
24. Sheppard JD Jr., Singh R, McClellan AJ, et al. Long-term Supplementation With n-6 and n-3 PUFAs Improves Moderate-to-Severe Keratoconjunctivitis Sicca: A Randomized Double-Blind Clinical Trial. Cornea. 2013 Oct;32:1297-1304.
25. Storas AM, Strumpke I, Riegler MA, et al. Artificial Intelligence in Dry Eye Disease. Ocul Surf. 2022 Jan;23:74-86.