- Gewebestörung an der Augenoberfläche
Hauptursachen für Epithelstörungen und Oberflächenschädigung
Epithelistörungen entstehen typischerweise wenn die normale Gesundheit der Augenoberfläche eingeschränkt wird in einem Ausmass, dass dies zu Symptomen führt. Epithelstörungen entstehen vor allem durch zwei Hauptursachen, nämlich erhöhte Mechanische Reibung durch die Trockenheit, also den Mangel and ´Schmiermittel´ zwischen Augapfel und Augenlidern, und durch erhöhte Osmolarität, also eine erhöhte Konzentration der Salze in den Tränen wenn das Tränenwasser bei Olmangel verdunstet.
Chronic Mechanical Friction and Hyperosmolarity presently appear as the main Secondary Pathogenetic Factors due to and downstream of Tear Film Deficiency. Surface Damage, starting with the Epithelium, induces another sequence of downstream secondary pathogenetic factors, that lead to inflammatory reactions. In chronic stages this can lead to chronic destruction of the Ocular Surface Tissue in severe Dry Eye Disease. This Pathophysiology of Dry Eye Disease is explained in more detail in the Animation on the HOLISTIC DYNAMIC CONCEPT on the PATHOPHYSIOLOGY in Dry Eye Disease.
Going along the Pathophysiology of Disease ... makes the understanding of pathology and of therapy much easier
Even though chronic mechanical friction and hyper-osmolarity are certainly important factors in Dry Eye Disease, in a pathophysiological view on this disease condition, they are no primary events but they arise due to other prior events such as tear film deficiency ... and that in turn is again based on other basic causative factors such as gland dysregulation etc.
A pathophysiological view in medicine is however not an academic fooling around ... but instead is the approach that leads to understanding of the causative relations of the condition and thus of likely successful therapy approaches.
This is the reason, why the new HOLISTIC DYNAMIC CONCEPT on the PATHOPHYSIOLOGY of DRY EYE DISEASE is strictly based on the pathophysiological course... and, also, what is thought to be ´important´ today may very well change already by tomorrow.
an unusually strong mechanical friction
typically between the bulbar mucosa (cornea and bulbar conjunctiva) and the palpebral conjunctiva of the eye lids
that exceeds the normal level of friction
which necessarily occurs by eye movements and blinking
but is limited to a tolerable degree by several lubrication systems
due to additional influence factors such as e.g.
a lack of tear water (aqueous tears) as e.g. in Dry Eye Disease, desiccating environments etc.
a lack of mucins due to squamous metaplasia as e.g. in Dry Eye Disease
additional external factors such as e.g. a contact lensthat can lead e.g. to Dry Eye Disease
CHANGES in OSMOLARITY - typically Hyper-Osmolarity
an unusually strong deviation of the osmolarity of the luminal tear fluid from the normal value of just under 300mosm/l (MilliOsmol per liter) - => as explained there
typically by increased evaporation of aqueous tears
due to a lack of tear film lipids
in obstructive Meibomian gland dysfunction (MGD)
in low blinking frequency with low delivery of lipids from the glands
in desiccating environments
with subsequent concentration of salts and osmotically active functional proteins
that may occurs at least in local spots of hyper-osmolarity
this exerts a hyper-osmolar stress on the epithelium
that drags out the water of the epithelial cells and can lead to surface damage and activation with onset of an inflammatory reaction.
Increased FRICTION and Increased OSMOLARITY are the two main secondary pathogenetic impact factors for the occurrence of EPITHELIAL DEFECTS.
Epithelial defects in Dry Eye Disease typically occur
at the BULBAR surface, as explained, but also occur
in the PALPEBRAL region of the Lid Wiper
at the posterior lid margin where the frictional forces of the upper lid appear to be concentrated. Lid Wiper Epitheliopathy (LWE) with pathological vital staining was observed to be the most sensitive indicator for increased friction at the ocular surface.
This little collection of the main pathogenetic factors does not include more severe impacts such as dramatic changes of the external milieu e.g. in ocular burns due to aggressive chemicals or all sorts of accidents or serious infections that can all happen but are less frequent than chronic mechanical friction and local hyper-osmolarity.
Die Darstellung von Beschädigungen der Augenoberfläche durch Vitalfarbstoffe ist eine etablierter Eckpfeiler der in der Diagnostik der Augenoberfläche generell und speziell beim Trockenen Auge.
Verschiedene Farbstoffe (z.B. meist Fluoreszein, seltener Lissamingrün) werden in der Klinik am Patienten direkt auf das lebende vitale Gewebe gegeben ohne Schaden anzurichten - ausser gelegentlich einer möglichen kleinen Irritation bei Bengalrosa. Da diese Farbstoffe topisch an der Augenoberfläche verwendet werden werden sie gelegentlich auch als ´Topische Farbstoffe´ bezeichnet.
Die Bezeichnung als ´Vitafarbstoff´ steht in Kontrast zu ´Histologischen Farbstoffen´, die im Labor auf avitale, fixierte und daher tote Zellen gegeben werden. Der Begriff ´Vital´ bezieht sich also auf die Zellen und nicht auf den Farbstoff selbst, denn einige Farbstoffe können sowohl bei vitalem Gewebe wie auch in der Histologie bei fixiertem Gewebe angewendet werden - dies betrifft z.B. Lissamingrün.
Das Färbungsprinzip besteht darin, dass die Farbstoffe von intakten lebendem Gewebe nicht gebunden werden sondern von der Augenoberfläche einfach abperlen durch die Schutzschicht der Muzine an der Zelloberfläche und den Wascheffekt der Tränen.
Die Vitalfarbstoffe können nur an geschädigten Stellen binden, die z.B. durch Oberflächenschäden beim Trockenen Auge entstehen. Dort ist entweder die Muzinschicht defekt, so dass die Zelloberfläche frei liegt, oder sogar die Zelloberfläche selbst defekt ist.
Das Anfärbungsmuster der Vitalfarbstoffe zeigt also die Regionen an, in denen die Gesundheit der Augenoberfläche gestört und das Gewebe beschädigt ist. Die Menge der Anfärbung entspricht dem Schweregrad der Störung, meist eines Trockenen Auges.
Die Oberflächenstörung kann, wie beschrieben, entweder auf zellulärem Niveau bestehen oder (nur) die extrazelluläre Muzinschicht.
Die Vitalfärbung erscheint typischerweise in der Form kleiner Färbungspunkte, die meist nur bei entsprechender Vergrösserung an der Spaltlampe gut erkennbar sind. Klinisch ist dies eine Keratitis superficialis punctata (KSP).
The general concept is that increased staining corresponds to increased alteration of the surface integrity and thus corresponds to and indicates an increased pathological impact and increased disease severity. The more stained dots occur after vital staining the more the ocular surface damage and thus the disease severity is.
As explained in the chapters on the ´Basics of Function and Disease´ and on ´How Dry Eye Disease gets Worse´ the pathological alterations of the epithelium are basically negative effects of desiccation and they occur mainly by the Secondary Pathogenetic Events of:
to chronic mechanical friction due to decreased lubricative activity of the reduces tear film
chemical irritation of a hyper-osmolar type due to increased evaporation of aqueous tears
It can be assumed that most of the surface cell destruction will occur in the region that is exposed to the ´dry´ ambient air in the bulbar area of the inter-palpebral fissure, where we have to open our eye lids in order to let the light in, that we need for the primary function of the eye ... which is of course vision.
Indeed most staining occurs in the inter-palpebral fissure area of the eye ball and therefore affects mainly the cornea and a part of the bulbar conjunctiva.
It may further be assumed that the tissue destruction, that is based on desiccation, occurs preferably where least tears occur on the ocular surface.
This would be away from that side where the excretory ducts of the lacrimal gland enter the conjunctival sac (temporal side) and thus more surface damage may be assumed on the nasal side.
Indeed experienced ophthalmologists seem to verify this assumption, because, e.g the group of James McCULLEY from Dallas reported in the Ophthalmology Newsmagazine 2008, that vital staining in the nasal area occurs more frequently and is not necessarily specific for Dry Eye Disease but the occurrence of a temporal vital staining indicates a more severe dry condition and is relatively specific for Dry Eye Disease.
BULBAR Epithelial Defects - Vital STAINING
Staining Scores - Oxford ScORE
The amount and often distribution of staining is estimated according to different scoring systems, of which the OXFORD Score is probably most frequently used.
The Oxford Score records the intensity of staining, i.e. the amount of stained dots, separately for the nasal and temporal conjunctiva and for the cornea.
The severity of staining is then scored in six grades of increasing severity from 0 to 5 with the assumption that the staining is expressed more or less uniformly over the three mentioned areas.
The evaluation is done in a semi-quantitative fashion by comparing the staining in a individual patient with the six grades of the scoring chart that shows a schematic representation of each of the different staining images - the closest match between the patient´s result and the chart does then determine the classification. This system is relatively reliable and easy to perform and is often used for studies.
Disparity of Signs and Symptoms in Dry Eye Disease
... sooo easy could be the life of a clinician and of a patient IF this was already the full picture. In Dry Eye Disease, however, it often occurs that there is a certain disparity between such objective clinical signs as vital surface staining and the subjective symptoms of an individual patient. This may be based on aspects of neurobiology on any level that may influence the uptake, transmission, or central computation and reception of neural signals ... as discussed elsewhere.
PALPEBRAL Epithelial Defects - Vital STAINING - Lid Wiper Epitheliopathy (LWE)
Friction also occurs at the palpebral posterior lid border
Vital staining of epithelial alterations does not only occur at the bulbar surface which is the typical region for evaluation of ´ocular surface´ vital staining, e.g. according to the Oxford Score.
In conditions with increased friction at the ocular surface, such as e.g. in Dry Eye Disease and in Contact Lens Wear, also the palpebral conjunctiva suffers epithelial defects that can be visualized by vital staining.
This concerns specifically the marginal conjunctiva at the palpebral aspect of the posterior lid border - termed the LID WIPER. This zone is apposed and directly in contact to the globe whereas the rest of the tarsal conjunctiva is separated from the eye ball by the narrow tear lake of "Kessing´s space".
The elevated epithelial lip of the Lid Wiper is that part of the eye lid, that wipes over the bulbar bulbar surface during a blink. Thereby the Lid Wiper compresses the ´old´tear film, that frequently already has thin areas or even disruptions, during the down-stroke of the upper eye lid. During the up-stroke of the lid the lid wiper spreads out a new tear film (please see the animation below).
The frictional forces during the blink concentrate on the Lid Wiper
Therefore most or almost all of the frictional forces of the eye lid rest on the lid wiper zone whereas the friction of the bulbar conjunctiva is distributed over a wide area. In conditions with increased friction at the Ocular Surface the Lid Wiper is consequently the zone where most alteration and wounding will occur.
In fact vital epithelial staining of the lid wiper zone - termed as LID WIPER EPITHELIOPATHY and abbreviated as LWE - was reported as a very sensitive first indicator of increased friction in patients with Dry Eye Disease and in Contact Lens Wearers by KORB and colleagues in several reports since about the millennium years.
LEW already occurred when conventional markers for Dry Eye Disease, such as short Tear Film Break-Up Time (BUT) or Schirmer´s Test were still normal or borderline normal. Patients with Dry Eye Disease, which includes respective symptoms, overwhelmingly (about four fifth) have LEW whereas patients without respective dry eye symptoms only rarely have LEW of any degree. LEW therefore represents an important and very specific indicator for elevated mechanical friction at the Ocular Surface.
GRADING of Lid Wiper Epitheliopathy is made according to the extension of alterations
The severity of LWE is graded according to the extension of the vital staining in two dimensions - vertical hight and horizontal width - in 4 Grades from 0 to 3 - as explained by KORB and colleagues 2010 in the Cornea Journal:
the vertical height is graded as:
in parts of the LW height
25% 0 (normal)
25% to 50% 1 (mild)
50% to 75% 2 (moderate)
75% 3 (severe)
the horizontal width is graded as:
< 2 mm 0 (normal)
2–4 mm 1 (mild)
5–9 mm 2 (moderate)
> 10 mm 3 (severe)
The mean value for both dimensions makes up the total grade of LWE.
OPTIMAL VITAL STAINING of LWE
LWE stains with all ordinary chromophores that are discussed here - Fluorescein, Lissamine Green and Rose Bengal.
The intensity of vital staining can be optimized by mixing 2% fluorescein with 1% Lissamine Green and for applying one drop (40µl) for each eye two times with 5 minute interval. The staining can be analyzed one minute after the second drop.
Different Vital STAINS
There are different vital stains that are often used interchangeably even though the have slightly different staining principles.
Most often used in ophthalmological practice is probably Fluorescein a fluorescent molecule with blueish-green color in the slit lamp. A major advantage is certainly that Fluorescein is a multi-purpose stain that can be used:
for the observation of ocular surface integrity in terms of epithelial alterations - often simply called ´vital staining´
Fluorescein is better suitable for the study of corneal alterations whereas the bulbar conjunctiva, that equally suffers from the pathology e.g. in Dry Eye Disease, stains more weakly
the visibility of Fluorescein can however be improved by using specific filters for excitation (blue) and for observation (orange)
for observation of the tear film integrity in the Fluorescent Break-Up Time Test (F-BUT)
for assistance in contact lens fitting ... which is however safest for RGP since soft hydrogel lenses may pick up the stain
for easier observation of the tear meniscus hight (TMH) ... when it is made sure that the applied volume is minute enough inorder to avoid erroneous reading of a high TMH although this is in fact low
A TRIPLE APPROACH is possible with flUOrescein:
Since fluorescein stains EPITHELIAL ALTERATIONS and also the TEAR FILM it can be used for several investigations:
first for evaluation of the tear film with respect of BREAK-UP TIME (BUT) and
Tear MENISCUS Height (TMH) and afterwards, when fluorescein is immersed for some minutes, typically 5min, it can be used for
evaluation of EPITHELIAL ALTERATIONS ´vital staining´
... this is a time saving practical approach in ophthalmological clinics.
Lissamine stains, as its name says, in green color and binds to altered and dead cells e.g. in Dry Eye Disease
it stains the bulbar conjunctiva better than fluorescein
for tear film analysis Lissamine green is not of much use and therefore basically restricted for cellular alterations
Rose Bengal has a reddish to pink color and it is probably best known by the patients because its topical application leads to a distinct stinging sensation
it has a similar staining spectrum as Lissamine green, i.e. it is more suitable for conjunctival alterations
in contrast to Lissamine, Rose Bengal also stains mucins and healthy cells in addition to altered ones, when it has access to healthy cells due to gaps in the mucin layer. These characteristics can make Rose Bengal staining interpretation somewhat more difficult compared to lissamine green and fluorescein.
Summary Vital Stains:
Fluorescein is the multi-purpose vital stain for the ocular surface and tear film whereas Lissamine Green is preferable for investigation of the conjunctiva, because it stains conjunctival alterations more intensely. Due to the stinging sensation of Rose Bengal, this may only be necessary for very specific purposes.
The intensity of vital staining can be optimized (e.g. for vital staining of Lid Wiper Epitheliopathy of the marginal conjunctiva) by mixing 2% fluorescein with 1% lissamine green and for applying one drop (40µl) for two times with a 5 minute interval. The staining can then be analyzed one minute after the second drop was given.
Since Fluorescein is described as a more intense stain for Cornea whereas Lissamine Green is preferred for the Conjunctiva the described combination of both stains should reveal optimal vital staining results in both epithelia.
A potential challenge may occur because the illumination may need to be switched because fluorescein is best seen with blue light whereas Lissamine Green is best seen in normal white light.
MUCOSAL Status - Conjunctival STROMA
Konjunktiva Status - LId-Parallele COnjunctivale Falten (LIPCOF)
Lid-Parallele Conjunctivale Falten, meist abgekürzt als LIPCOF sind ein wichtiges Zeichen eines chronischen Trockenen Auges.
Diese Falten würden entdeckt und benannt von Frank SCHIRRA während seiner Promotionsarbeit Mitte der 1990er Jahre.
LIPCOF Falten entstehen durch die chronische Gewebeschädigung beim chronischen Trockenen Auge
Die LIPCOF Falten zeigen eine Auflockerung des Bindehautgewebes an, die als ´Conjunctivochalasis´ bezeichnet wird (von dem Griechischen Wort χάλασις ("chalasis") für auflockern).
Die Auflockerung entsteht durch die chronische Entzündung beim Trockenen Auge, bei der andauernd grosse Mengen von Kollagen auflösenden Enzymen feigesetzt werden. Es handelt sich dabei um Matrix-Metalloproteinasen (MMP), vor allem vom Typ MMP9.
Wenn die Bindehaut durch eine Zerstörung ihres normalen Kollagenfasernetzwerks aufgelockert ist, dann schlägt sie Falten bei allen Bewegungen des Augapfels gegenüber den Augenlidern und vor allem durch die häufige Bewegung des Augenlides über den Augapfel beim Lidschlag.
Die Bildung der Falten wird begünstigt durch die erhöhte Reibung, die typischerweise beim Trockenen Auge besteht durch den Mangel der Tränen in ihrer Menge und/oder Qualität und ihre dadurch verminderter ´Schmierung-Wirkung´ zwischen Augenlidern und Augapfel.
LIPCOF Falten treten vor allem parallel zum Lidrand auf und lassen sich vor allem am Unterlid in temporaler Position beobachten. Mit zunehmender Zerstörung nimmt die Zahl der Falten, die sich am Lidrand übereinander lagern zu (siehe schematische Abbildung).
WHEN THE OCULAR SURFACE BECOMES DRY THIS CAN LEAD TO THE ONSET OF A PATHOGENETIC CASCADE OF TISSUE DESTRUCTION AND LIPCOF FORMATION
When the ocular surface becomes dry with the onset and progression of Dry Eye Disease the normal gliding of the eye lids over the eye ball may gradually transform into a ´rubbing´ ... and several problems of ´ocular surface mathematics´ occur that lead to the onset of conjunctivochalasis and LIPCOF folds:
tear film deficiency => decreased lubrication => increased friction => epithelial cell wounding and activation
increased activation of proteases => conjunctival stroma destruction => conjunctivochalasis
conjunctivochalasis + increased friction = conjunctival folds ... among which LIPCOF are the most prominent
LIPCOF folds are, as the term behind the abbreviations tells, a very specific form of conjunctival folds - they are ´Lid Parallel Conjunctival Folds´.
The destroyed and loosened (´chalatic´) conjunctival tissue tends to be moved by the posterior eye lid margin during every blink and gradually forms conjunctival folds in front of the advancing lid margin.
Since conjunctival LIPCOF folds are a typical and obvious consequence of conjunctivochalasis these two terms are occasionally used as synonyms, which may not be quite correct.
Depending on the progression of Dry Eye Disease also the degree of conjunctival destruction increases and the number and size of LIPCOF folds increases. First there is only one small fold that is barely detectable but later the folds increases in size, they protrude onto the mucocutaneous junction of the posterior lid border i.e. at the bottom of the tear meniscus. In advanced stages several folds are superimposed - one on the other.
Since the degree of LIPCOF folds increases with increasing severity of disease and the fold are thus an important sign, several classifications use LIPCOF folds as a marker criterion for the staging of Dry Eye Disease.
LIPCOF FOLDS ON THE POSTERIOR LID BORDER CAN PUSH UP THE TEAR MENISCUS AND LEAD TO AN ERRONEOUS HIGH ESTIMATION OF TEAR VOLUME
LIPCOF folds are lying on the posterior lid border and in advanced stages they are superimposed on each other. The lowest, i.e. first fold is typically the largest and protrudes widest in anterior direction whereas the following folds tend to decreased in size with each fold.
Thereby LIPCOF are lying within the tear meniscus and fill it increasingly and thus push up the apparent upper end (height) of the meniscus.
Since the apparent Tear Meniscus Hight (TMH) is measured or just semi-quantitatively evaluated in order to have an impression of the meniscus filling and thus of the volume of the pre-ocular tears the presence of at least extensive LIPCOF can lead to wrong, i.e. erroneously high readings of tear volume. These observations were published by Pult and Pult.
Diagnose von Entzündungsfaktoren
MMP9 (Matrix-Metalloproteinase 9) Tissue Protein degrading Enzyme
Chronic inflammation in chronic Dry Eye Disease can typically induce progressive destruction of the tissue. When such destruction has not yet occurred tissue degrading inflammatory mediators may already be diagnosed by more elaborated but still convenient clinical tests in order to have more precise information on the status of an individual patient. This has become available for an important ocular surface tissue degrading enzyme termed Matrix-Metalloproteinase 9 (MMP9)
The schematic structure of the conjunctiva is depicted in the figure that shows
the surface epithelium and
the underlying lamina propria.
Alterations of the epithelium are explained in the chapter for "VITAL STAINING" of epithelial alterations.
Destruction of the lamina propria is covered in the present chapter.
The figure to the right shows the structure of the conjunctiva together with the alterations that occur after a pathogenic insult and during the inflammation that is initiated as a protective answer when proteases such as MMP9 are massively activated.
MATRIX-METALLO-PROTEINASES ARE IMPORTANT INFLAMMATORY MEDIATORS
Tissue degrading enzymes such as Matrix Metallo-Proteinases (MMP) are important inflammatory mediators that cleave proteins.
They are produced and activated downstream of the primary inflammatory mediators such as inflammatory lipids, including eicosanoids, histamine, and inflammatory cytokines that are produced due to the influence of a pathogenic insult onto the tissue.
The pathogenic insult comes typically from the outside in the form of e.g. mechanical friction, hyper-osmolarity or possibly infection. Mechanical friction due to low lubrication and hyper-osmolarity due to increased aqueous evaporation typically occur in Dry Eye Disease and hit the epithelial cells that appear to be the first producers of inflammatory mediatory such as cytokines.
MATRIX-METALLOPROTEINASES DISSOLVE THE COLLAGEN MATRIX OF THE TISSUE
Since an inflammatory reaction is a basic protective answer of tissues, it is necessary to mount downstream mechanism in order to promote this answer.
Apart from up-regulation of adhesion molecules e.g. on vascular endothelial cells to get more ´helpful inflammatory cells´ into the tissue
there is also more space needed within the narrow tissue clefts of the collagen fiber matrix to accommodate the large amount of incoming cells in order to do their job as good as they can.
Proteases are thus activated that can degrade the matrix of the stromal connective tissue of the ocular surface which is mainly formed of proteins, overwhelmingly of collagen fibers (as shown in the figure. Collagen fibers form the structural meshwork in which the stromal cells and support structures such as blood and lymph vessels and nerves reside. At the ocular surface in Dry Eye Disease mainly the Matrix-Metalloproteinase MMP9 is of importance and shown e.g. by Steven PFLUGFELDER´s group, by MELLER and TSENG, and by others.
CONJUNCTIVAL LIPCOF FOLDS ARE A CLINICAL SIGN OF CHRONIC MMP9 ACTIVATION AND TISSUE DESTRUCTION
Chronic activation of proteases such as mainly the subtype termed Matrix-Metalloproteinase MMP9 leads to progressive tissue destruction alternating with frustrate attempts for tissue repair, which is the final step of the physiological inflammatory process.
The repair attempts with reformation of collagen is unluckily frustrate since the tissue destruction by activation of MMP9 is chronically ongoing.
This typically leads to a loose conjunctival lamina propria due to the destroyed internal structure, that is termed conjunctivochalasis from the Greek word χάλασις ("chalasis") for loosening. Conjunctivochalasis refers to a general loosening of the conjunctiva. It typically leads to conjunctival LIPCOF folds because these are formed when the advancing lid margin wipes over the bulbar surface during the frequent blink movements and thereby ´shovels up´ the loose conjunctiva ... similar to a snow plough ... into the shape of folds. Since conjunctival folds are a typical consequence of conjunctivochalasis these two terms are occasionally used a synonyms.
A Convenient CLINICAL MMP9 TEST IS AVAILABLE THAT MAY OFFER A PREVENTIVE APPROACH IN DRY EYE CLINICS
Recently a diagnostic test became available that can show the presence of active MMP9 exceeding a certain normal concentration, This is an easy to perform test that can be performed directly besides the patient in the clinical setting and only requires to collect some tears with superficial cell material from the inferior conjunctival palpebral tissue.
The MMP9 test works with an immune reaction that is made visible by occurrence of a line if the test is positive - similar to a pregnancy test. It does however not show pregnancy but the presence of increased amounts of tissue degrading enzymes that are distinctly harmful for the ocular surface.
This handy new test could probably offer to detect elevated levels of MMP9 before other distinct clinical sings have occurred, such loosening of the conjunctival tissue and formation of conjunctival folds.
Such a clinical MMP9 test could therefore provide a chance for a preventive aspect in Ocular Surface Clinics.
Meibomian Gland Status - MEIBOGRAPHY
The interest in the Meibomian Glands has strongly increased after it was publicly realized that a deficiency in Tear Film LIPIDS due to a mainly obstructive Dysfunction of the Meibomian Glands in fact appears presently as the main causative factor for Dry Eye Disease. This may appear a a surprise for many since the term ´Dry Eye´ seems to point to a primary lack of water. Many dedicated Dry Eye Specialists, however, have long realized that alterations of the lipid phase are often involved as indicated e.g. by foam on the tear film and lid margin from saponification of tear film lipids or lipid containing encrustations on the lid margin and around the base of eye lashes (collarettes).
MEIBOGRAPHY WAS MAINLY A RESEARCH LAB TECHNIQUE DURING THE 20TH CENTURY
The ocular surface specialist is generally blessed compared to many other medial professions, in that most anatomical structures and pathological events in his interest can be easily seen.
In this respect the Meibomian Glands certainly represent an unexpected challenge because they are hidden in the depth of the tarsal plate inside the eye lids. From the front they cannot be seen through the anterior lid lamella with the skin and lid muscles. From the back of the lids through the relatively transparent conjunctiva the Meibomian Glands can be seen seen much better as whitish streaks of individual glands under suitable conditions, but this image does not reveal too many details (please see figure).
In a first wave of interest in the Meibomian Glands during the 1980s following the discovery of ´Meibomian Gland Dysfunction´(MGD) by KORB and HENRIQUEZ, a group around a man named James JESTER, performed early experiments that focused on hyper-keratinization of the gland epithelium. They visualized the glands by trans-illumination of the lids with infrared light from the frontal skin side and observation occurred from the back side through the conjunctiva. When such a visualization of Meibomian glands is only seen, it is termed ´Meiboscopy´and when the image is recorded it is termed ´Meibography´.
NON-CONTACT MEIBOGRAPHY WITH INFRARED ILLUMINATION AND CCD CAMERA HAS GREATLY REVOLUTIONIZED CLINICAL OBSERVATION OF THE MEIBOMIAN GLAND
More recently a novel technique for MEIBOGRAPHY was developed by Reiko ARITA and colleagues in Tokyo that is termed Non-Contact Infrared Meibography and was described in a seminal paper in 2008. This technique also:
uses infrared light because this appears to show the lipid content of the Meibomian Glands particularly well and it also
observes the glands from the conjunctival side, which certainly makes much sense, with an infrared digital camera attached to a slit-lamp.
this setting was custom-tailored by Topcon Japan Inc. and became later available to all interested clinicians as a commercial package.
In contrast to previous Meibography techniques the illumination is from the same side as the observation, i.e. from the posterior conjunctival side. Since relatively more light intensity reaches the Meibomian Glands the contrast of the image and thus the clarity is much better. ARITA and colleagues have meanwhile formed a Research Group termed the ´Lid and Meibomian Gland Working Group´(LIME, http://www.lime.jp/en/), they have made many advancements in the field of Meibomian Gland Dysfunction and also organize annual international research meetings.
The term non-contact refers to the fact that neither the lamp nor the camera is in contact with the eye - but since the eye lids must be everted in order to see the conjunctival surface some kind of device or the clinicians fingers must be in touch with the eye to perform the lid eversion.
A KEY FINDING IN MEIBOGRAPHY IS THE DEGREE OF GLAND DROP-OUT
Meibomian Gland Drop-Out describes the disappearance of parts of the gland tissue in the Meibography observation which suggests a disappearance of functional gland tissue. This assumption appears correct as the degree of gland drop-out generally correlates with the gland function and with the degree of Dry Eye Disease.
Therefore Meibography this has become a valuable new diagnostic parameter in Dry Eye Diagnostics. The gland drop-out typically starts from the end of the Meibomian Glands, i.e. from that part which is away from the orifice on the posterior lid margin.
Apparently different pathogenetic influence factors may cause gland-drop because this is drastically increased in long-term contact lens wear, independent of the lens type, and gland drop-out also occurs in inflammatory conjunctival allergy as discussed in the chapter for Meibomian Gland Dysfunction (MGD).
Grading Scales are available for clinical use
Several semi-quantitative GRADING SCALES are available for Gland Drop-Out which basically all evaluate the relative amount of drop-out in different grades of differentiation.
A large number of visualization devices can nowadays display the Meibomian Glands and their drop-out including the class of so-called ´Topographers´ that are described in this chapter, and several more basic instruments that provide infrared imaging. Still, there is presently apparently no software available that can determine the exact degree of gland dropout fully automatic. The more basic devices just provide visualization and photography of the glands whereas more advanced systems often allow a manual tracing of the disappeared gland tissue that works with different degrees of exactness, particularly in potentially stressful clinical service situation.
Höchste Bild-Qualität bei der Meibographie ist möglich … aber sie benötigt eine spezielle Beleuchtungs- und Auswertungstechnik
Ein häufiges Problem bei der Darstellung der Meibomdrüsen im Augenlid des Patienten direkt in der Praxis des Arztes beruht darauf, dass Augenoberfläche eine natürliches ´Feuchtgebiet´ ist - eine Schleimhaut - und daher eine feuchte Oberfläche hat, die bei der Beleuchtung viele Reflexionen produziert.
Störende Reflexionen verschiedenen treten typischerweise auf den meisten Meibographiebildern auf und es erfordert einen gewissen Grad von Erfahrung des Untersuchers die Reflexionen möglichst gering zu halten um eine aussagekräftiges Foto für die klinische Verlaufs-Dokumentation anzufertigen.
Andererseits erlaubt es eine Fotodukumentation mit perfektem Kontrast und Auflösung die Meibomdrüsen so darzustellen, als wären sie freiiegend und nicht bedeckt von dem darüberliegenden Gewebe der Lidplatte und der Augenbindehaut. Dadurch ist die Struktur der Drüsen unmittelbar erkennbar für den Arzt … und auch für den Patienten.
Man darf annehmen, dass diese realistische Darstellung der Meibomdrüsen auch dem Patienten erlaubt unmittelbar zu verstehen, wie der Zustand ´seiner´ Meibomdrüsen mit dem Beschwerdebild des Trockenen Auges zusammenhängt und wie wichtig z.B. eine konsequente heimische Physikalische Lidrand Therapie für die Verbesserung der Erkrankung ist.
Die perfekte und störungsfreie Darstellung solch schwieriger Objekte wie der Meibomdrüsen erfordert eine anspruchsvolle Systeme für die Beleuchtung und für die elektronische Bildverarbeitung die kombiniert werden müssen um eine perfekte Bildqualität zu erzielen. Aktuell gibt es nur einen Gerätetyp, der diese Anforderungen erfüllt und es daher erlaubt Meibomdrüsenbilder von ungekannter Klarheit und Präzision in fast histologischer Auflösung zu erzeugen - das Lipiview und das Lipiscan (Fa. TearScience Inc.) siehe Abbildungen anbei.