Dry eye and chronic fatigue: what connection?

Dry eye syndrome (DED) may be among the causes of Chronic Fatigue Syndrome (CFS).

This is the finding of a study conducted in Taiwan on almost 900 DED patients.

Ocular surface and dry eye syndrome

The ocular surface is a delicately balanced system, made up of various components, interconnected both structurally and functionally.

Structure

The ocular surface includes the cornea, conjunctiva and ocular adnexa such as the eyelids, eyelashes, tear film, main and accessory lacrimal glands and meibomian glands.

The set of structures that make up the ocular surface system participate in the production and distribution of the tear film on the anterior surface of the eye.

The structures that contribute to the production of the tear film include:

- the main and accessory lacrimal glands,

- the mucipar calycephalic cells of the conjunctiva

- the Meibomian glands

The distribution and excretion of the tear film are ensured by the aeyelid crinkling.

The secretory activity of the glands is finely organised thanks to the control exerted by the nervous system, the endocrine system (thanks to sex hormones and, above all, testosterone, which has a trophic effect on the glands) and the immune system, which regulates the inflammatory response and the reaction against possible infectious agents.

Functions

The ocular surface represents a direct connection between the eye and the external environment and, therefore, all its components act synergistically to keep the eye healthy and protect key structures of vision from external pathogens.

Both of these goals are achieved, inter alia, through the production of an efficient tear film.

Any factor that disrupts thehomeostasis of the ocular surface system can alter the stability and osmolarity of tears, leading to tissue damage through osmotic, mechanical and inflammatory processes.

Dry eye syndrome

One of the conditions in which ocular surface homeostasis is altered is dry eye syndrome, a multifactorial ocular surface disease that affects up to 30% of individuals over the age of 50. A higher incidence has been found in older people, postmenopausal women, contact lens wearers and patients with autoimmune diseases.

Type of dry eye

Dry eye syndrome can be due to decreased tear production or increased evaporation. Both of these conditions lead to hyperosmolarity and subsequent inflammation of the ocular surface.

Hyposecretion

Hyposecretory forms, in which there is a reduced functioning of the lacrimal glands, include forms related to autoimmune diseases, such as primarily Sjögren's syndrome, but also rheumatoid arthritis, systemic lupus erythematosus, polyarthritis nodosa, Wegener's granulomatosis, systemic sclerosis and other connective tissue diseases.

Then there are the hyposecretive 'non-Sjögren' forms of dry eye, the most important of which is age-related.

Excess evaporation

Dry eye due to excess evaporation can be classified according to the conditions that cause it, into 'intrinsic' (e.g. in case of Meibomian gland dysfunction or eyelid and orbital abnormalities) and 'extrinsic' (due to contact lens use or topical drugs with preservatives; eye diseases such as allergy and conjunctivitis; vitamin A deficiency).

Symptoms of dry eye syndrome, such as blurred vision, photo-sensitivity, irritation, burning and itching, can limit daily activities and have a negative impact on quality of life.

Risk factors

The main risk factors can be summarised as follows:
1. Age: ageing causes progressive atrophy of the lacrimal glands.
2. Gender: women between 40 and 60 are more affected by dry eye, probably due to the new hormonal balance following the menopause.
3. Use of certain drugs: hormones, immunosuppressants, antihypertensives, antihistamines, antidepressants and others.
4. Climatic-environmental factors: air conditioning, dry climate, cigarette smoke, wind, smog.
5. Prolonged use of computers and television.
6. Nutritional deficiencies: insufficient vitamin A intake.
7. Use of contact lenses.

In this regard, it has been established that the wearing of all types of contact lenses leads to alterations of the ocular surface and the tear film.

The magnitude of these effects varies depending on the lens material, the way it is worn and the characteristics of the wearer.

Silicone hydrogel lenses generally result in fewer harmful effects.

However, the risk of corneal infection and inflammation remains high, especially in the case of recurring night-time lens wear.

In the case of predominantly daytime use, damage to the ocular surface can also result from the use of certain solutions for daily lens cleaning, to which the eye can be or become particularly sensitive.

Chronic fatigue syndrome: what it is 

Chronic fatigue syndrome is a complex disorder that negatively affects quality of life.

CFS is characterised by severe and disabling fatigue and other symptoms, including muscular and skeletal pain, sleep disturbances, reduced concentration and headaches.

It is a long-term and persistent condition, difficult to diagnose, in which fatigue persists even after periods of rest.

The underlying factors of this condition are not yet known, and several studies have been devoted to understanding the aetiology of CFS.

CFS and dry eye syndrome, a possible correlation?

The dry eye syndrome (DED) is a multifactorial ocular surface disorder, characterised by impairment and loss of tear film homeostasis and ocular surface dryness and pain. Several studies have shown that CFS is often correlated with dry eye symptoms and the Sjögren's syndrome.

The Taiwanese study

In particular, a clinical study that was carried out in Taiwan reported that dryness symptoms were present in about 70% of patients with chronic fatigue syndrome.

However, the relationship between DED and the risk of developing CFS is still not well defined.

Therefore, a study conducted in Taiwan sought to shed light on the correlation between chronic fatigue syndrome and dry eye syndrome.

The results of the study

I results of the Taiwanese study have shown that patients with any comorbidity have an increased risk of developing CFS.

Moreover, being affected by a severe form of DED seems to be directly related to the development of CFS.

In particular, patients with dry eye syndrome showed a 2-fold higher risk of developing CFS, compared to the control group without DED.

The risk remains higher (about 1.6 times) even after normalising the data by age, gender and comorbidity.

The study also examined the correlation between the frequency of DED-related doctor visits and the risk of developing chronic fatigue syndrome.

The results showed that those who see a specialist once or twice a year for dry eye syndrome run an almost five times higher risk of developing CFS in their lifetime.

Basically, the results showed that the cumulative incidence rate of developing chronic fatigue syndrome was significantly higher in the group of patients with DED, compared to patients without dry eye syndrome.

In addition, the cumulative incidence rate of CFS increases with follow-up time, so the disease may also occur later in life than DED.

According to the researchers, the possible correlation between dry eye syndrome and chronic fatigue syndrome could reflect a dysfunction of the immune system, further complicated by the presence of chronic diseases.

CFS would, therefore, be a complication of these conditions.

In fact, dysregulated ocular immune responses cause damage to the ocular surface and are one of the factors contributing to the pathogenesis of DED.

Conclusions

In conclusion, the results of the study showed that the risk of developing chronic fatigue syndrome is associated with both dry eye syndrome and other comorbidities.

Moreover, the onset of DED also seems to be correlated with the incidence of CFS in later life years. Therefore, DED could also be considered as a marker in clinical practice to improve the diagnosis of CFS, which to date is still based on patient-reported symptoms.

The researchers also recommend that physicians take adequate account of the increased risk of chronic fatigue syndrome among patients with dry eye syndrome and adequately assess the impact of these conditions on patients' general health.

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3. Periman LM, Perez VL, Saban DR, Lin MC, Neri P. The Immunological Basis of Dry Eye Disease and Current Topical Treatment Options. J Ocul Pharmacol Ther. 2020 Apr;36(3):137-146.