OVERVIEW on …

HOW WE GET Dry Eye Disease

BASIC Causative Factors

• Deficiency of Tear SECRETION

• Deficiency of Tear FILM FORMATION

• RISK FACTORS for Dry Eye Disease

BASIC CAUSATIVE FACTORS lead to a Deficiency of the Tear Film

These are termed BASIC CAUSATIVE FACTORS because they lead to the (Primary Pathology of) a Deficiency of the Tear Film in either volume or quality.

Once a tear film is formed, other secondary factors become important

• SECONDARY Pathology/ pathogenetic factors occur, such as e.g. an increased evaporation,

  • typically due to a lack of oil secretion in Meibomian Gland Dysfunction (MGD) ... which is a basic secretion problem

  • but also an intact tear film on the eye may become deficient . This can occur when desiccating Influences from the environment (termed as external environmental RISK FACTORS), such as high wind and/or low humidity are present.

• Secondary Pathogenic factors typically form cascades, e.g. increased evaporation typically causes hyper-osmolarity of the tear film. So, in a ´causative´/ pathophysiological view on Dry Eye Disease, a hyper-osmolarity occurs pretty much downstream of other earlier factors ... even though it may, or may not, be considered as ´important´.

... THEREFORE, on the present page,  FIRST the BASIC Causative Factors are discussed and THEN  External and Internal RISK FACTORS that are of influence 

Dysfunctions of tear secretion and of tear film formation are the basic causative factors for the onset of dry eye disease

IMPAIRMENT of the Basic Functional Complexes of Ocular Gland SECRETION and Tear FILM FORMATION means ...

• ... that the Ocular Surface can no longer provide the permanent moisture in the pre-ocular zone of the bulbar surface ...

  • ... that lies in the lid aperture (palpebral fissure) where the Ocular Surface is exposed to the ambient dry environment.

When this situation becomes chronic, it necessarily leads to the development of Dry Eye Disease.

Various alterations of the Ocular GLANDS and of the Eye LIDS can be involved as CAUSATIVE FACTORS.

(1) A deficiency in tear secretion by the ocular glands appears as the most frequent reason for dry eye disease

´Deficiency´ is a relatively general term because it describes quantitative and also qualitative deficiency of the secretion by the ocular glands.

Both of these types of gland dysfunctions are typically caused by an alteration or failure of the underlying regulatory factors, such as innervation, endocrine hormones or the immune system. ... and influenced by factors such as age or sex

A deficiency in tear secretion, of any kind, is the most frequent causative factor for Dry Eye Disease.

This explains the two main types of Dry Eye Disease due to tear film deficiency

• the AQUEOUS deficient type and

• the LIPID deficient/ evaporative type.

A primary deficiency of tear film lipids is the most frequent cause for dry eye disease

In recent years it was found that the most frequent cause of Dry Eye is a LIPID deficiency of the tear film

This occurs due to the mainly obstructive Dysfunction of the Lipid-Producing Meibomian Glands in Meibomian Gland Dysfunction MGD  (for details please see there).

Due to the obstructive process, the amount of delivered lipids on the lid margin and on the tear film is typically decreased - which causes increased evaporation of the aqueous phase. 

On the other hand, also the qualitative composition of the lipids is altered in disease, because

• lipids with increased melting point are formed that tend to solidify inside the glands contribute to the obstruction process of the terminal gland duct and orifice

• also irritant lipid species, such as free fatty acids, occur that may cause irritation of the lid margin tissue and decrease of the stability of the remaining tear film.

(2) A deficiency in tear film formation can occur due to eye lid and blinking dysfunction (lbd) – even when the tears are sufficient

Important for clear vision is not only that we have quantitatively enough tears with qualitatively correct composition. This is not even good enough for an intact ocular surface and for a clear cornea.

The FORMATION of the thin pre-ocular Tear FILM is produced by the blink movement of the eye lids.

During the down-phase the ´old´tear film is compressed towards the lower eye lid and all irregularities in the film including shed epithelial cells are removed.

The upper eye lid then spreads out a new tear FILM while it moves back up after a typically short eye closure.

The relatively fragile film must be frequently renewed because it is unstable. It is renewed typically every ten seconds by a new eye blink.

A deficiency in Tear FILM FORMATION from sufficient tears, therefore occurs when the eye lid function is altered in any way. 

This constitutes a deficiency that members of the Ocular Surface Center Berlin have termed as Eye "LID and BLINKING DYSFUNCTION", abbreviated as LBD. The terminology is in line with other types of tear deficiency, such as Meibomian Gland Dysfunction (MGD) and Lacrimal Gland Dysfunction (LGD).

The type of LGD can be:

• QUANTITATIVE when the blinking frequency is too low, typically lower than the tear film stability

• QUALITATIVE

  • when the blink movement is not full and results in partial blinks or

  • when the congruity between the eye lid and the surface of the eye balls is lost, whichoccurs typically due to deformations of the lid and lid margin

The reason can be

• morphologic for any reason, including changes with advancing age which may be most frequent, or due to scarring, traumatic, inflammatory, neoplastic, inherited etc.

• neurologic for any reason with a deficiency, for any reason, of the neural ´command structures´ that regulated blinking

Eye lid deformations can impair an efficient eye blink

A qualitative deficiency occurs when the eye lids and blink movement are morphologically NOT intact.

This may typically arise during the normal aging process but can also occur due to trauma, neoplasm, inherited or other diseases.

Morphological lid alterations can occur as part of the normal aging process by a laxity of the eye lids due to decreased elasticity of connective tissue. This leads to Ectropion where parts of mainly the lower lid are no longer fully in touch with the globe. The lower eye lid can thus no longer stabilize the pre-ocular tear film that normally rests on the ´Line of Marx´ of the posterior lid border (for details please see there).

A somewhat ´reverse´ lid condition, Entropion, can also occur due to the aging process. In contrast to ectropion, in entropion the eye lid rolls inward. In addition to dripping of the tears, that can no longer be held at the ocular surface, over the outer lid border, termed epiphora, in entropion the eye lashes typically wipe and scratch on the ocular surface which can distinctly alter the normal structure and cause severe irritation and downstream inflammation (for details please see the section on ´Hierarchy of Pathogenetic Factors´).

Many risk factors for Dry Eye Disease exist, that can increase the likeliness of onset and progression of Disease

The ocular surface and in particular the tear fluid, is exposed to a large number of influence factors. When they influence the function of the ocular surface negatively they are RISK factors for Dry Eye Disease.

RISK Factors for Dry Eye Disease are plenty and they are either of internal systemic nature inside the body or they are due to external environmental influences that impair in one or the other way the ability of the ocular surface functional unit to remain constantly moist.

Thereby the ´RISK FACTORS´ obey the explained pathways of functional complexes, causative factors and resultant pathology and act on them as additional factors of influence on the described pathophysiology.

Internal and External Risk factors

INTERNAL risk factors influence the organs and therefore typically the secretion of tear components - whereas EXTERNAL environmental risk factors typically act on the readily produced tears on the ocular surface and particularly on the tear film. 

Therefore, the EXTERNAL environmental factors can often be influenced, minimized or even abolished in order to improve the ocular dryness - whereas this is difficult for the INTERNAL risk factors ... but still it is important to be informed about some basic issues.

Internal risk factors act on the tissues and are difficult to prevent

It becomes obvious that typically the main risk factors for the onset and worsening of dry eye disease are internal and thus difficult to influence - these are mainly based on age, sex and chronic disease. 

• AGE, in the sense of advanced age, refers to the general decline of body functions and tissue properties that also affects the ocular tissues in terms of gland activity with decreased secretion or connective tissue laxity that can lead to morphological lid deformations with resulting impairment in the formation of a tear film in front of the cornea.

• Endocrine Hormones, in particular Sex Hormone levels are certainly included as an important factor of age as they typically decrease with advancing age. But sex hormones as such are also an independent and important factor for the differentiation and integrity of the ocular tissues.

  • Androgens are shown as an important protective factor for ocular surface health by several studies by David SULLIVAN and colleagues, Their levels are generally lower in females, who also represent the highest proportion of dry eye patients. Females also experience perturbations of the hormone levels in menopause which is a typical age for the onset of Dry Eye Disease.

• The Genetic Background and Inherited Disease appear as internal factors of importance. Some genetic diseases like ectodermal dysplasia syndromes, intensely studied by Thomas KAERCHER and colleagues, have clear significance for development of Dry Eye Disease. A genetic background may also be of importance to explain the typically higher prevalence of Dry Eye in Asian Populations - but is yet unclear.

• Some Chronic Systemic Diseases such as skin diseases, like seborrheic dermatitis or rosacea, are associated with increased rate of Dry Eye Disease.

• Mental affections like depression also have a certain correlation with increased rate of Dry Eye Disease.

• Such diseases may also be influenced by above named factors of age and sex.

• Such interactions between different influence factors makes it often difficult to clearly identify causative relations.

  • Also the therapy and medication that is required for certain certain systemic diseases may negatively influence the ocular surface.

    • This applies to anti-androgen therapy or to bone marrow transplantation that can lead to very difficult to treat graft-versus-host inflammatory disease at the ocular surface. Therapy for systemic disease certainly introduces external factors into/onto the body but since it typically influences primarily the tissues (and act less on the tear fluid) it may therefore still be considered as "internal" risk factors.

• Various medications that are given systemically (i.e. oral or as an infusion) can favor dry eyes. Often underestimated internal risk factors are, apart from systemic diseases themselves, the medications that are administered as a therapy against them.

• Medication favors Dry Eye Disease if the influence the internal milieu of the body in a way that negatively affects e.g. the production of tear fluid or tear fluid components, or the regular eyelid blink and thus the formation of a stable tear film, or influence the maturation and homeostasis of the tissue at the ocular surface.

• The TFOS DEWS II Report (2017) lists such negative influences of medication under “Iatrogenic Dry Eye“.

• Many classes of medication are well known for some time to favor Dry Eye Disease. Among them are e.g.  

  • Antihypertensive drugs, such as Beta-Blockers

  • some Anti-Cholinergics such as

    • Anti-Histaminics for allergies

    • some Antiarrhythmics for heart disease

    • some bronchiodilatators for lung disease

  • some Anti-Depressants, Sedatives

  • some Anti-Parkinson medications

  • some Pain killers (Canabinoids, Opioids)

  • Hormones and Hormone antagonists (e.g. Östrogenes, Anti-Androgenes)

• In case it is thought, that a medication may negatively influence ocular health and favor dry eyes, this must (1) be verified and (2) it must always be weighted against the intended positive and potentially live-saving actions of the medication. Therefore, medication that is administered by a doctor should never be discontinued without further advice from a doctor in order to secure your health !

External risk factors are mainly desiccating environmental factors that negatively influence the tear film … and can often be improved

External Factors with negative influence on the tear fluid that is already secreted onto the Ocular Surface pose an increased risk for the onset and worsening of Dry Eye Disease. There are plenty of such risk factors in our daily private life and work environments. Due to the increased occurrence of desiccating environmental factors in or ´" modern life" environments with stressful screen work in air-conditioned rooms the desiccating external risk factors appear to increase in epidemiological importance for dry eye disease.

This concerns every e.g. desiccating environments with high ambient temperature and a low humidity which both increase the rate of water evaporation from the Ocular Surface. Similarly higher wind speed as is intended by using fans in the summer have the same effect. Contact lenses have higher requirements for tear volume and may also increase the evaporation of tears.

Visual tasks such as concentrated reading, in particular from video display terminals also distinctly reduces the blink frequency and thus the risk for drying an existing tear film out before it is refreshed by a blink.

With the above in mind it is no surprise, that concentrated work at computer screens associated with air condition and low humidity is often associated with a dry eye condition termed as ´office eye´). This affects also younger age groups who are increasingly occupied by concentrated viewing of video-screens of any kind.