ESCRS 2024: How to Choose Correct Artificial Tear for Our Patients
Speaker: Jutta Horwath-Winter
Dry eye patients often experience dissatisfaction and frustration, frequently consulting multiple practitioners and trying numerous eye drops. The market offers a range of artificial tears with varying ingredients and compositions, leading to a trial-and-error approach that can result in mounting costs. The objective of dry eye management is to restore tear film and ocular surface homeostasis to improve quality of life. However, a universal artificial tear suitable for all patients is unlikely due to the multifactorial nature of dry eye disease. Effective management requires customized treatment based on an accurate diagnosis. Individualized treatment involves understanding the patient's history, subjective symptoms, and ocular surface status. Tests are used to determine the underlying cause and dominant subtype of dry eye. Additionally, environmental factors, such as digital screen use, must be considered. To select the most suitable artificial tear, knowledge of ingredient characteristics, properties, performance, and patient satisfaction is essential.
Tear supplementation is the primary treatment for dry eye, and it can be used alone or with other therapies. Historically, artificial tears provided temporary relief by adding to the natural tear film but did not address the underlying causes of dry eye. Modern formulations, however, contain biologically active ingredients that target various mechanisms of dry eye, offering both palliative and therapeutic benefits. Artificial tears differ in their composition, ingredients, and properties such as viscosity, mucoadhesion, and biological effects. Viscosity-enhancing agents, mainly hydrophilic polymers, increase the residence time of artificial tears on the ocular surface by mimicking the viscoelastic behavior and shear-thinning properties of natural tears. These agents should provide stability when the eyes are open and reduce viscosity during blinking. Hyaluronan is a popular viscosity-enhancing agent with over 30 years of clinical use. Its water-binding capacity, high mucoadhesion, and biological effects, such as modulation of wound healing and inflammation, make it effective for dry eye. Hyaluronan formulations vary in concentration (0.1% to 0.4%) and molecular weight (below 100 kDa to 3,000 kDa), with higher molecular weight providing better effects. Ideal artificial tears often include high molecular weight hyaluronan and may combine it with other polymers or molecules, and can be chemically modified or cross-linked.
Artificial tears should mimic natural tears in terms of electrolytes, tonicity, and pH. Electrolytes are crucial for maintaining the epithelial barrier and corneal integrity. These products are typically formulated as isotonic or hypertonic solutions to counterbalance tear film hyperosmolarity through dilution, though this effect lasts only 5 to 15 minutes post-application. Buffering agents stabilize pH at physiological levels. Osmoprotectants, such as trehalose, are small soluble molecules that protect ocular surface epithelial cells against osmotic and oxidative stress by modifying cellular water uptake. Trehalose also promotes autophagy and stabilizes the lipid layer. Lipid-containing products aim to further mimic natural tears by replenishing the lipid layer, stabilizing the tear film, increasing lipid layer thickness, and preventing evaporation. These products can include bola lipids or non-lipids and are formulated as liposomes or oil-in-water emulsions with amphiphilic lipids or surfactants. Caution is needed with high concentrations of certain surfactants and cationic agents due to potential ocular toxicity. Perfluorohexyl octane, a water-free liquid with low surface tension, is used but has limited long-term safety and biocompatibility data. Preservatives, especially benzalkonium chloride, are known to be toxic to the ocular surface and should be avoided. While soft preservatives are safer, they can still have toxic effects. Therefore, preservative-free formulations are recommended, available in single-dose units or multi-dose preservative-free systems. Studies have shown that switching from preserved to unpreserved products improves ocular surface health and reduces symptoms, a finding applicable to both glaucoma medications and artificial tears. Additionally, antioxidants, such as vitamins, lipid acids, coenzymes, and polyphenols, are included in artificial tears to address oxidative stress, with many of these still in development.
Artificial tears often contain agents that promote wound healing and reduce inflammation. High molecular weight hyaluronan, for example, accelerates wound healing and exhibits anti-inflammatory effects. Carboxymethylcellulose enhances epithelialization, while emulsions aid in wound healing and decrease pro-inflammatory factors. Corneal nerve support is also vital in dry eye treatment, and high molecular weight hyaluronan has been shown to reduce sensitivity to mechanical stimulation and increase nerve fiber length in the sub basal nerve plexus after eight weeks. Additionally, coenzyme Q10 and vitamin E have positive effects on sub basal nerve anatomy. Due to these benefits, the term "wetting agent" is now preferred over "tear substitute" to reflect their broader roles in lubrication and tissue support. Selecting the appropriate artificial tear involves considering disease severity, dry eye subtype, and the affected tear film layers. Low-viscosity drops are generally used for mild cases, while higher-viscosity drops are recommended for more severe cases. The frequency of application should be adjusted based on severity, with gels and ointments suggested for nighttime use. It may also be necessary to switch between different lubricant types or move from simple to more complex formulations. For aqueous tear-deficient dry eye, osmolarity-balanced hypertonic artificial tears are favored, whereas lipid-containing products are more beneficial for evaporative dry eye. Given the overlap of symptoms, a combination of aqueous and lipid-based artificial tears is often effective.
Studies show that different types of ingredients in artificial tears impact various layers of the tear film and address key mechanisms of dry eye, such as tear instability, hyperosmolarity, ocular surface cell apoptosis, and inflammation. Non-preserved artificial tears are recommended for all patients, with considerations for the type of delivery system and its squeezability. Initially, these should be applied 4 to 6 times daily for the first 1 to 3 months, with adjustments based on severity. Using a drop diary helps track usage, and patients should be informed that symptom relief may take at least a month, with clinical improvement requiring several months. Regular follow-ups are crucial to adjust treatment if needed. Not all patients respond to artificial tears, with one-third potentially not responding at all. In such cases, address anatomical disturbances, underlying systemic diseases, and Meibomian gland dysfunction with appropriate treatments. For neuropathic corneal pain, target nerve dysfunction, and ensure preservatives are removed if they haven't been. Educating patients on the importance of adherence to treatment is vital for successful outcomes.
Artificial tears relieve symptoms and address dry eye's underlying causes. Early and effective lubrication can prevent worsening of the condition. Long-term, adaptable treatment is necessary, tailored to individual needs and environmental factors. Since artificial tears vary, detailed information is important. Future innovations include low-dose cortisone and NAGA, with ongoing research needed to assess new ingredients, safety, and effectiveness for different dry eye types, and to determine the best management strategies.
42nd Congress of the European Society of Cataract and Refractive Surgeons, 6 – 10 September 2024, Fira de Barcelona, Spain.
