According to various research findings, it is estimated that more than four million people in the United States suffer from dry eyes. Research on keratoconjunctivitis sicca (dry eye syndrome) has advanced significantly in recent years, allowing for a better understanding of the pathophysiology, mechanisms, and progression of the disease. This progress has led to more targeted treatments and new therapies aimed at addressing the underlying pathophysiology of the condition. While previous treatments for dry eye aimed to replace lost fluids with tears, today there are treatments targeting the inflammatory process identified as part of dry eye syndrome.
Traditionally, dry eye treatment focused primarily on providing relief and soothing effects, mainly by using artificial tear substitutes without addressing the root causes of the disease. Over the years, improvements have been made in the composition of tear substitutes, enhancing viscosity and lubrication, as well as developing preservative-free formulations to prevent corneal damage. However, despite their widespread use and improvements in alleviating dryness and improving vision clarity, these substances do not replicate natural tears, do not replace a steady tear flow, and do not address the underlying issue or potential long-term damage caused by dryness.
It is now understood that dry eye syndrome originates from cytokines and receptors that participate in inflammatory processes and affect tear production. This inflammatory process can reduce tear production or alter the composition of tears, thereby affecting the balance of the eye's surface and causing dryness. This knowledge has led to treatments that target these inflammatory processes.
Tear Substitutes:
The most common treatment for dry eyes involves the local application of tear substitutes. While this treatment provides soothing effects, the use of artificial tears for dry eyes can be effective in mild cases to alleviate dryness and grittiness. These formulations often contain polymers that spread across the eye's surface to maintain moisture. Tear substitutes are available in liquid, gel, or ointment forms, with differences primarily in viscosity, composition, and preservative content. Lower viscosity formulations are typically used in mild cases to minimize visual blurring, while more severe dryness may require higher viscosity formulations, albeit with the potential for visual blurring.
Despite the importance of treating the mucin layer in dry eyes, few devices address this layer of tears. In cases where patients have severely mucinous dry eyes that cause painful thread-like strands on the eye's surface, 10% mucolytic agents can be used for temporary relief.
Lipid-based formulations are available primarily in ointment form. These ointments are designed to provide relief overnight and upon waking up in the morning. Castor oil, derived from the seeds of the Castor oil plant (Ricinus communis), is present in the Refresh Endura eye drop formulation.
A notable drawback of preservative-containing artificial tear formulations is their potential to worsen surface damage in dry eyes. Long-term use of these formulations can exacerbate the condition. Thus, some formulations are available without preservatives to address this concern.
Buffering agents are also included in artificial tear formulations to maintain the natural pH of tears around 7.4, which is important for the health of ocular surface cells. Buffered formulations counteract the tendency of hypertonic solutions to draw fluid out of cells.
Therapeutic Stimulation of Tear Production:
Medications that stimulate tear production, such as mucolytics (Bromhexine, Ambroxol), cholinergic agents (Pilocarpine), and Eledoisin, are used to encourage the lacrimal gland to produce more tears. However, these medications may have side effects that limit their use. Medications that increase cAMP and cGMP levels are generally effective in promoting tear secretion.
In conclusion, the treatment landscape for dry eye syndrome has evolved over the years, with a greater understanding of the underlying inflammatory processes and the development of more targeted therapies. These treatments range from tear substitutes to medications that encourage tear production, each with its own set of benefits and considerations. The choice of treatment depends on the severity of the condition and the specific needs of the patient.
Inflammatory Modulation Treatments
Recognizing inflammation's role as a cause of dry eye due to damage to the tear glands and mucous membrane has led to the conclusion that anti-inflammatory treatment is needed for dry eye disease. Treatment with steroids without a preservative is an effective approach to reducing inflammation and improving the ocular surface in patients with dry eyes. Unfortunately, prolonged local treatment with steroids has side effects such as thinning and cataract formation, limiting extended use of this medication. Steroids are highly effective as short-term treatment during episodes of inflammation.
In long-term use, Cyclosporin A (CsA) might be effective. CsA is an immunosuppressive substance that affects T cells and suppresses inflammatory activity. Various studies have shown that local treatment with cyclosporine A 0.05% (Restasis by Allergan Pharmaceuticals) had a positive impact on symptoms and signs in patients with dry eye. Other studies demonstrated a decrease in inflammatory cells and inflammatory markers and an increase in the number of goblet cells. No systemic side effects were reported, and the substance was not detected in the blood. However, CsA has two major issues: the poor solubility of CsA (Refresh Endura) is almost as effective as the drug itself (leading to a prolonged FDA approval process), and CsA affects T cells, which has a half-life of 110 days, suggesting an effect only after around three months of usage.
Protopic ointment is another treatment with a mechanism of action similar to that of cyclosporine and is effective, although its use exceeds the indication for which the medication was registered, namely for treating skin inflammation.
Androgens play a crucial role in tear production and anti-inflammatory mechanisms on the ocular surface. Various studies suggest that androgen deficiency in women with dry eyes contributes to meibomian gland dysfunction, instability of the tear surface, and increased tear evaporation. Clinical trials with testosterone eye drops are ongoing.
Alternative medicine offers another approach to reducing inflammation associated with dry eye. The essential fatty acids linolenic acid (omega-6) and gamma-linolenic acid (omega-3) are crucial. Omega-6 fatty acids found in milk, ice cream, pizza, beef, and butter promote inflammation, whereas omega-3 fatty acids found in flaxseed and fish are anti-inflammatory and improve meibomian gland secretion. Omega-3 fatty acids are metabolized into eicosapentaenoic acid, which has various anti-inflammatory effects. Currently, no well-established studies demonstrate the efficacy of omega-3 fatty acid treatment.
Since no single anti-inflammatory treatment is universally effective, future anti-inflammatory treatment for dry eyes might involve a combination of short-term steroid use, long-term immunosuppressive drug use, hormonal therapy, and nutritional supplements.
Autologous Serum
Autologous serum treatment for dry eyes might be helpful when other treatments fail. The exact mechanism of how serum affects the eye is unknown, but proteins, vitamin A, and growth factors in the serum might protect and heal the ocular surface. Care must be taken to avoid contamination, as preservatives are not present in the serum. Serum can be instilled without dilution or diluted with tear substitutes.
Vitamin A
Vitamin A is present in tears and has been shown to be deficient in dry eyes. The effectiveness of local vitamin A treatment has not yet been proven. A deficiency of this vitamin in tears causes keratinization and thinning of goblet cells. Vitamin A treatment might address these issues.
In summary, while we await treatments targeting the underlying causes of dry eye disease, the primary treatment currently available for patients with dry eye remains symptomatic relief and improvement through the use of emerging tear substitutes. Understanding that inflammatory processes underlie dry eye due to damage to tear glands and the ocular surface has led to a new strategy of immunomodulation and hormonal balance preservation in the environment of the meibomian glands and ocular surface.