Alternative therapies for dry eye disease

Abstract

Purpose of review: Dry eye disease (DED) is a multifactorial disease affecting approximately 5-50% of individuals in various populations. Contributors to DED include, but are not limited to, lacrimal gland hypofunction, meibomian gland dysfunction (MGD), ocular surface inflammation, and corneal nerve dysfunction. Current DED treatments target some facets of the disease, such as ocular surface inflammation, but not all individuals experience adequate symptom relief. As such, this review focuses on alternative and adjunct approaches that are being explored to target underlying contributors to DED.

Recent findings: Neuromodulation, stem cell treatments, and oral royal jelly have all been studied in individuals with DED and lacrimal gland hypofunction, with promising results. In individuals with MGD, devices that provide eyelid warming or intense pulsed light therapy may reduce DED symptoms and signs, as may topical Manuka honey. For those with ocular surface inflammation, naturally derived anti-inflammatory agents may be helpful, with the compound trehalose being farthest along in the process of investigation. Nerve growth factor, blood-derived products, corneal neurotization, and to a lesser degree, fatty acids have been studied in individuals with DED and neurotrophic keratitis (i.e. corneal nerve hyposensitivity). Various adjuvant therapies have been investigated in individuals with DED with neuropathic pain (i.e. corneal nerve hypersensitivity) including nerve blocks, neurostimulation, botulinum toxin, and acupuncture, although study numbers and design are generally weaker than for the other DED sub-types.

Summary: Several alternatives and adjunct DED therapies are being investigated that target various aspects of disease. For many, more robust studies are required to assess their sustainability and applicability.

Fig 1.. Mapping of alternative therapies for DED based on present underlying pathologies.

Alternative and adjunct therapies have been developed to treat various underlying causes of DED. Patients with aqueous deficient DED due to lacrimal gland hypofunction may benefit from transcutaneous electrical nerve stimulation (TENS), transcranial magnetic stimulation (TMS), stem cell therapy, or royal jelly therapy. Alternatively, those with evaporative DED due to meibomian gland dysfunction may be treated with office-based eyelid warming and massage devices, intense pulsed light therapy, and topical antibacterial agents, such as Manuka honey. Several therapies are currently available to target DED associated ocular surface inflammation. Trehalose and intense pulsed light therapy are two adjuvant therapies that are also being studied for this purpose. Lastly, nerve dysfunction may also be present in DED. Treatments for neurotrophic keratitis include nerve growth factor (NGF), platelet rich products (PRP), corneal neurotization, and polyunsaturated fatty acids (PUFA). In patients with neuropathic pain, cutaneous nerve blocks, TENS, botulinum toxin, and acupuncture have been used to treat pain of central origin, while autologous serum tears (AST) and amniotic membrane transplant (AMT) have been used to treat pain of peripheral origin.