How dry eye disease can become a complex vicious cycle

I spoke with Prof. Christophe Baudouin, president of the European Dry Eye Society to find out more about the complex nature of dry eye disease.

Could you tell me more about the pathogenesis of dry eye disease?

Dry eye is a very complex disease. It is not just a question of lack of water and so it is impossible to treat patients just by lubricating the eye with water. It is a disease that involves a series of self-stimulating biological events, and the lack of tears, insufficient tear quality or their instability results in direct mechanical and/or osmotic stress, which causes further damage.

In addition, goblet cell loss results in further tear film instability or imbalance and thus, dryness. The drier the eyes become, the more inflammatory they become and the greater the inflammation, the more the eyes continue to dry out, i.e., a vicious cycle occurs (see Figure 1).

To give more context on the vicious cycle theory, the dryness of the eye stimulates the nerves, the inflammatory reaction and inflammatory cells, and those act as stimulation for further damage, and so tears and their quality are reduced further, resulting in the disease becoming chronic.

Overall, the disease is very complex, with many risk factors, causes and aetiologies having been defined. As a result, it is difficult to resolve.

How are primary and secondary inflammatory processes involved in the disease?

There is a constant state of inflammation with the most severe dry eye cases, and this can be primary; for example, as seen with Sjogren syndrome, where inflammatory cells infiltrate and block the lacrimal glands, as well as the conjunctiva and cornea, and thus invade the whole ocular surface. Secondary processes are also involved: the various types of stress including mechanical and osmotic factors also stimulates inflammatory cells and results in a chronic inflammatory state.

What do you think future treatment strategies need to focus on?

The increasing interest in the idea of the vicious cycle allows us to discriminate between different levels of events: the mechanical stress, the osmotic stress and the inflammatory stress, for example. This new way of understanding the disease may allow the physician firstly to try to prevent the patient from entering the cycle, which is important and can be made possible by controlling the environment, improving the eyelid and decreasing inflammation. Secondly, each part of the loop can be targeted with a specific approach such as lubrication, eyelid hygiene, anti-inflammatory strategies and maybe even Omega-3.

And so there are different complementary approaches that can improve the patient’s symptoms. That said, sometimes it is very difficult to help the patient and they can suffer a lot.

To discuss a further complication of dry eye, we are increasingly starting to understand the concept of neuropathic pain in dry eye disease. Sometimes, the overstimulation of the nerve causes chronic pain and so even when the cornea and tears have been improved, patients can continue to suffer.

And once neuropathic pain has been stimulated, it can be very difficult to control it. Therefore, a good future treatment approach would be to find the best ways of relieving pain symptoms either locally or systemically.

Another consideration is in how we treat and control inflammation. In Europe, there is only one ciclosporin formulation indicated for severe dry eye disease with corneal damage, Ikervis (Santen), whilst the United States market has the prescription eyedrop Restasis (Allergan).

Another medication for the treatment of signs and symptoms of dry eye, which is available in some countries, is lifitegast (Xiidra, Takeda Pharmaceutical), which blocks the activation of lymphocytes. Unfortunately, this drug is not available in Europe and so other anti-inflammatory strategies are needed here.

In addition, the eyelids are likely to be the location of a lot of inflammation and so represent potential targets. In fact, various strategies to treat the eyelids have been developed, based on pulse light or warming and massaging devices, and are certainly a good way of relieving the patient’s symptoms.

Has the incidence of dry eye disease increased during the COVID-19 pandemic as screen time has increased?

We do not yet have epidemiological data to assess, however, it is clear that long hours working at, or reading on, a computer do affect dry eye and there is a clear association between the two. So, most likely, patients who have dry eye are suffering more during this time.

Furthermore, it has also been found that wearing a mask seems to interfere with eyelids and lead to meibomian gland dysfunction, perhaps by blocking the lymphatics at the level of the eyelids or by focusing an air flow on the eyes, so some people are finding that their dry eyes have been worsening due to their mask use.

Figure 1: The vicious cycle theory of dry eye disease. (Image courtesy of Prof Christophe Baudouin)

Christophe Baudouin, MD, PhD, FARVOE
E:cbaudouin@15-20.fr
Prof. Baudouin is professor and chair of ophthalmology at Quinze-Vingts National Eye Hospital & Vision Institute, University Paris Saclay, Paris, France. He has no financial interest in the subject matter.