Dry Eye Concept 5 -

BASICS on Function & Pathology

The BASIC ENTITIES of the Ocular Surface are Anatomical Construction & Functional Collaboration - both is dictated by the eventual aim ...

Lets start with the AIM ... which is VISION ...

Along with the present construction principle of the eye, the eventual AIM of Optical Function requires Moisture for the Ocular Surface.

Therefore basic functional complexes of the Ocular Surface are there to secure that the Ocular Surface Tissues can be kept constantly moist.

In order to secures this, the BASIC FUNCTIONAL COMPLEXES are:

• Gland Tear SECRETION
• Eye LID Tear FILM FORMATION

The Ocular Surface has some requirements - one is an anatomical unit of suitable organs

In order to provide moisture, the Ocular Surface is composed of a

• mucous membrane including the adherent glands
  • for the production of moisture in the form of tear fluid and
• a lacrimal drainage system for disposal of the "used" fluid after is has bathed the mucosa for a while.

The organs that constitute this complete Ocular Surface are an ANATOMICAL UNIT.

Another requirement is that the organs work properly together and thus constitute a FUNCTIONAL UNIT

Together with the regulatory systems that provide their maturation and their functional regulation the tissues become a Functional Unit for the provision of moisture

- for details please see also the Section ´Ocular Surface´.

Only when the regulatory systems such as the:

• nervous system
• endocrine hormonal system
• immune system

work properly, they can realized a functional unit at the Ocular Surface ... necessary to achieve their aim.

When the regulatory systems to not work properly, which leads to dysfunctions of the tissue, this is a typical cause for the development of pathology - typically in the form of Dry Eye Disease.

Moisture means nothing ... when it is not equally distributed and permanently present - BLINKING is necessary

The Ocular Surface does not only consists of areas that are constantly hidden in the depth of the conjunctival sac and elsewhere, but also has areas at the anterior surface of the eye ball that are exposed to the ambient dry air and therefore prone to desiccation- the cornea and the conjunctiva.

In order to keep the cornea and conjunctiva constantly moist (and also for refraction of incoming light) a FILM of tears must cover these tissues even when they are exposed during the period between two blinks - the inter-blink period. 

This sets another requirement apart from tear fluid - a mechanism for spreading the tears into a tear FILM is necessary ... and this is the LID APPARATUS with its different accessory structures.

Eye Lid BLINKING is a highly regulated process that depends on the nervous system

Since the tear film, that is spread by the lid apparatus, unluckily has only a limited stability of some (around 10 to 20) seconds - it must be frequently renewed.

In order to do that, a servo system composed of different parts of the nervous system is necessary - it can therefore be termed as a neural reflex arc as we have so many of the in different parts of the body.

- in high-tech language: external sensors, some hard wiring and a CPU

The neural reflex arc consists of

• peripheral receptors at the ocular surface,
• afferent nerve fibers,
• a central processing unit in the brain stem (that can communicate with higher brain centers)
• efferent nerve fibers that give respective contractile stimuli to the muscles of the lid apparatus

The Brain Stem communicates with, and is influenced by, higher centers in the brain, that can regulate the lid apparatus according to what ´higher knowledge´ of superior e.g. cortical centers deems necessary. Such individual wishes of higher centers are however not always welcome to the periphery because they are one reason for rare blinking in concentrated visual tasks ... that may lead to a Dry Eye condition. 

The Patho-Physiology of Disease Onset and Progression develops along the Dysfunction in the tracks of anatomy and physiology

... so, by now we have a nice and more or less complete collection of tissues and functional mechanisms the are necessary to provide the Ocular Surface Function.

In return, when any of the involved organs or any of the trophic and regulatory mechanism is impaired, becomes dysfunctional or is completely lost ... this will also deteriorate the most basic function of the Ocular Surface which is the provision of moisture.

Therefore, Dry Eye Disease is a prototypic disease of the Ocular Surface that may always eventually occur when any of the parts of the ocular surface is altered by organ-specific, systemic or external environmental conditions.

When Basic FUNCTIONAL COMPLEXES of the Ocular Surface are COMPROMISED ... their LACK turns into Basic CAUSATIVE FACTORS for Disease

hmmm, that sound complicated ... but it is actually very easy:

When basic functional complexes of the Ocular Surface for moisture are COMPROMISED ... this leads to a deficiency or lack of:

• a LACK  of Tear SECRETION
  • - at least of one component such as
    • water
    • mucin or
    • lipid
• OR
• a LACK   of Tear FILM FORMATION

Even a lack of only one of these two functions is sufficient to endanger the health of the Ocular Surface.

A lack of tear secretion or a lack of tear film formation are Basic CAUSATIVE FACTORS for Dry Eye Disease

The lack of such basic functions for moisture is a pathologic factor for the Ocular Surface Mucosa and thus necessarily constitutes a Basic CAUSATIVE FACTOR for the onset and progression of pathology of Dry Eye Disease.

For a mucosa it is a question of life or death to have the pre-requisite of being moist fulfilled ! ... this may remind us of a citation by WELLINGTON

Basic causative factors CAUSE  PRIMARY PATHOLOGY of the Tear Film and Ocular Surface

The LACK of basic causative factors causes the PRIMARY PATHOLOGY of the ocular surface that is already known from the early days of dry eye research:

• Tear Film Deficiency
• Surface Tissue Damage

Tear Film Deficiency is A Typical PRIMARY Pathology In Dry Eye

When a dysfunction of gland secretion of at least one component - mucins, water or lipids -  of the tear film occurs this leads to Pathology of the Tear Film- termed Tear Film Deficiency. This is one PRIMARY Pathology on Dry Eye Disease.

Tear Film Deficiency typically leads to negative influences- mainly mechanical friction and hyper-osmolarity - on the underlying epithelium of the ocular surface.

• Tear Film Deficiency defines the type of Dry Eye Disease ... and its respective therapy

The pathology of Tear Film Deficiency is indeed so important that the different forms of Dry Eye Disease are classified/ termed according to the type of Tear Film Deficiency, as either:

• Aqueous-deficient Dry Eye                     or... most frequently
• Lipid-deficient/ evaporative Dry Eye     or  ... more rarely
• Mucin-deficient Dry Eye

Surface Tissue Damage is a typical downstream alteration of tear film deficiency - BUT can also occur as a primary issue

Surface Tissue Damage is a typical downstream alteration due to a tear film deficiency of any kind and the question may arise why Surface Damage is then not designated as a ´secondary pathology´ in the present Concept on Dry Eye Disease.

Tissue Damage can actually very well arise as a first alteration of the ocular surface due to various negative influences directly on the tissue, such as a nerve damage, lack of hormones or to a lack of trophic factors such as Vitamin A. Graft-versus-host disease after bone marrow transplantation can lead to very difficult to treat inflammatory reactions against the ocular surface tissues.

Such factors that lead to a primary tissue damage are less frequent in "typical" Dry Eye Disease as seen every day in every ´typical´ ophthalmological practice.

Surface Damage and Tear Film Deficiency are interdependent primary Pathologies

The interaction of the Tear Film and the Surface Tissue is more complex, as explained in more detail in the ´Overview on Dry Eye Disease´ and acts in both directions.

It is thus not surprising that Tear Deficiency and Surface Damage are linked via vicious circles. Tear Deficiency induces, e.g. by instability and dry spots in the tear film, downstream epithelial surface damage that, in return, further reduces the binding of the tear film to the surface which then leads to even more surface damage.

Since pathogenetic factors act back onto themselves and thereby amplify the disease process the described interaction of Tear Film and Surface Pathology can be termed a Vicious Circle.

Surface Damage and Tear Film Deficiency are so closely inter-related that it appears justified and makes most sense from a more general patho-physiological perspective on Dry Eye Disease, when Tear Film and Tissue Pathology are both designated as "Primary Pathology".