La dry eye syndrome (DED), as defined by the Tear Film and Ocular Surface Society (TFOS) DEWS II, is 'a multifactorial disease of the ocular surface, characterised by a loss of tear film homeostasis and accompanied by ocular symptoms, in which tear film instability and hyperosmolarity, ocular surface inflammation and damage, and neurosensory abnormalities play an aetiological role'. It is therefore a pathology with multiple causes, which arises due to either reduced tear production (hyposecretive DED) or excessive tear evaporation (evaporative DED) or both conditions (mixed DED). DED is characterised by symptoms such as eye burning, photophobia, blurred vision and eye discomfort or pain.
What pain looks like in DED
The ocular pain associated with dry eye syndrome is a factor that significantly impairs patients' quality of life. DED can present with various symptoms and these symptoms, including pain, can be subjectively perceived with an intensity that varies from person to person.
The symptoms of ocular discomfort or pain reported by patients with dry eye syndrome are supported by several clinical conditions, such as epithelial damage of the ocular surface, inflammation and neurosensory abnormalities. The consequence is the presence of variable symptoms for each individual patient, ranging from a mild sensation of ocular discomfort (often referred to as a 'foreign body sensation') to pain made intolerable even by harmless stimuli such as light or wind.
DED and ocular pain: what mechanisms
The cornea is one of the most innervated tissues in the human body and has many nociceptors (i.e. receptors designed to pick up painful stimuli), which are activated by mechanical, chemical and thermal stimuli.
The rupture of the tear film during the blinking interval, hyperosmolarity of the tears, rubbing between the eyelid and the eyeball in the presence of reduced tearing, as well as the presence of inflammation, are all stimuli present in dry eye syndrome, which are able to activate the nociceptors and, thus, the sensation of pain.
Furthermore, corneal neurosensory changes play a fundamental role in both the development and maintenance of DED. From the initial inflammatory phase, in fact, an evolution towards neurogenic inflammation is possible, which is at the basis of actual nerve damage, with the reduction of nerve fibre density and branching, up to the formation of neuromas (i.e. fibrosis of the affected nerves).
These phenomena can lead to the onset of neuropathic-type pain, amplified in intensity and persistent over time. As the neuropathic component in dry eye syndrome increases, so does the presence of typical perceptions, such as ocular heat sensation, burning, stinging pain and the sensation of having granules in the eyes. Usually, in these cases, traditional treatment of dry eye tends not to be effective, since the damage is at the level of the nerves.
The treatment of pain in DED
The first line of intervention to provide relief with regard to the painful symptoms of dry eye syndrome are artificial tears, particularly water- and/or lipid-based ones, applied topically.
Artificial tears act by increasing the aqueous layer on the ocular surface and, at the same time, temporarily reducing the osmolarity of the tear fluid. In addition, to provide relief, artificial tears are often formulated with macromolecules that create viscosity. These substances not only allow artificial tears to remain on the ocular surface for longer and perform their action, but also create a protective layer, reducing dryness, friction and epithelial cell death.
Among the different formulations of artificial tearsthose containing sodium hyaluronate (hyaluronic acid, HA) and/or xanthan gum (xanthan gum, XG) have also shown a synergistic effect on corneal abrasions, which are often characterised by acute ocular pain.
If painful symptoms persist after treatment with artificial tears, it may be necessary to resort to second-line treatment with medicated topical eye drops containing antibiotics and anti-inflammatory agents, corticosteroids, omega-3 fatty acids or tear secretagogues.
- Yoshikawa Y, Yokoi N, Kato H, Sakai R, Komuro A, Sonomura Y, Ikeda T, Sotozono C. Evaluation of Eye-Pain Severity between Dry-Eye Subtypes. Diagnostics (Basel). 2021 Jan 25;11(2):166.
- Giannaccare G, Ghelardini C, Mancini A, Scorcia V, Di Cesare Mannelli L. New Perspectives in the Pathophysiology and Treatment of Pain in Patients with Dry Eye Disease. J Clin Med. 2021 Dec 25;11(1):108.
- Priyanka Agarwal et al. Formulation Considerations for the Management of Dry Eye Disease. Pharmaceutics. 2021 Feb 3;13(2):207. https://pubmed.ncbi.nlm.nih.gov/33546193/