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Endothelial Blebs: Part VIII Corneal Endothelium
Endothelial Blebs: Part VIII Corneal Endothelium
Endothelial Blebs: Part VIII Corneal Endothelium
28 CHAPTER
Endothelial blebs
Prior to 1977, it was thought that contact lenses could only research commenced into understanding the endothelial
affect the cornea by direct mechanical influence or oxygen response to lens wear.
deprivation. Because the endothelium is located on the pos-
terior surface of the cornea and is known to obtain all of its
required oxygen from that dissolved in the aqueous humor,1 Prevalence
this tissue layer was thought to be immune from the effects
of contact lenses. The prevalence of endothelial blebs is thought to be essen-
The first clue that contact lenses could alter the corneal tially 100% among contact lens wearers.2 That is, blebs can
endothelium came from Zantos and Holden,2 who noted be observed in all patients within 10 minutes of lens inser-
that the endothelial mosaic undergoes a dramatic alteration tion. There is a large variation in the intensity of the response
in appearance within minutes of inserting a contact lens. between patients.2,6,7 Asian subjects have a significantly
Specifically, they reported observing a number of black, higher degree of endothelial bleb formation than the non-
non-reflecting areas in the endothelial mosaic – which they Asian population for closed eye lens wear.8
called blebs – and an apparent increase in the separation
between cells. These changes can be observed under high
magnification (×40) using the slit lamp biomicroscope Signs and symptoms
(Figure 28.1).
The black, non-reflecting areas observed in the endothelial
mosaic correspond with the position of individual cells or
groups of cells. The initial impression one gains is that cells
have ‘fallen off’ the posterior surface of the cornea, leaving
behind gaps or black holes.2 In corneas displaying a marked
blebbing response, it also appears as if all endothelial cells
throughout the field of view have become more separated
and the endothelial surface takes on a more textured and
three-dimensional appearance.2
The ‘bleb response’ displays a characteristic time course
(Figure 28.2). Blebs can be observed within 10 minutes of
lens insertion. The number of blebs peaks in 20 to 30
minutes, then subsides to a low level after about 45 to 60
minutes. A low-level bleb response can be observed
throughout the remainder of the wearing period.2
Hydrogel lenses cause a greater bleb response than well-
fitting rigid lenses. Lenses of greater average thickness
induce a greater response than thinner lenses. However, the
design and fit of hydrogel lenses have little effect on the
Figure 28.1 Contact lens-induced blebs (arrow) in the endothelial mosaic bleb response.6 Ohya et al.7 observed that blebs are confined
observed in specular reflection with the slit lamp biomicroscope. (Courtesy to the central regions of the cornea beneath rigid lenses, but
of Arthur Ho, Brien Holden Vision Institute.) occur throughout the cornea with soft lenses; that is, blebs
are seen in all corneal areas covered by contact lenses.
The contact lens fraternity remained sceptical for some Williams and Holden9 observed two additional endothe-
time, and it was not until (a) the appearance of blebs was lial phenomena in patients wearing soft lenses on an
verified independently3; and (b) reports of contact lens- extended wear basis. First, there appears to be an increase
induced endothelial polymegethism were published by in the number of blebs in the late evening, prior to going to
Schoessler and Woloschak4,5 in the early 1980s, that serious sleep. Second, the overall magnitude of the bleb response
© 2012 Elsevier Ltd
Endothelial blebs
10
*
Rigid (Dk/t = 16)
0.8 8 Soft (Dk/t = 15)
(% area of endothelium affected)
6
0.6
*
Lens 4 *
0.4 on *
Lens off 2 *
* *
0.2 0
0 5 10 15 20 25 30 35 40 45 50 55
A Time (minutes)
0
0 30 60 90
10
Time (min) Rigid (Dk/t = 49)
8 Soft (Dk/t = 49)
No lens (control)
that were enucleated (because of melanomas); and (b) (×680).14,15 Kaufman et al.14 observed the corneas of three
corneas of beating-heart, brain-death cadavers. The patients wearing high water content hydrogel contact
‘blebbed’ endothelium displayed oedema of the nuclear lenses for the first time. In one patient, endothelial changes
area of cells, intracellular fluid vacuoles and fluid spaces consisting of irregularly shaped, round or oval, dark
between cells. Thus, endothelial blebs appear to be the regions were observed within the endothelial mosaic. These
result of a local oedema phenomenon, whereby the poste- changes were most evident 20 minutes after lens insertion,
rior surface of the ‘blebbed’ endothelial cell is bulged and by 30 minutes the changes were fewer and less promi-
towards the aqueous. The endothelial cell bulges in the nent. Kaufman et al.14 suggested that their results con-
posterior direction because this represents the path of least firmed the ‘localized oedema’ theory of endothelial bleb
resistance; that is, the posterior stromal surface (Descemet’s formation.
membrane) provides much greater resistance to endothelial Efron et al.15 obtained images from each eye of 15 normal
cell swelling than the aqueous humor. subjects (age range 19–36 years; mean 26 ± 6 years) before
and after 20 minutes’ wear of a +5.50 D 58% water content
hydrogel lens in one eye. The extent of the bleb response
Slit lamp biomicroscopy was determined using the grading scales shown in Appen-
A simple optical model can be constructed to explain the dix A of this book (see ‘Observation and grading’); the
appearance of blebs as seen with the slit lamp biomicro- images were also assessed qualitatively. After 20 minutes
scope (Figure 28.4). When the endothelium is viewed using of lens wear, the mean bleb response in the lens-wearing
specular reflection, light rays reflect from the tissue plane eye was grade 1.0 (range 0.0 to 3.2). Two subjects did not
corresponding to the interface between the posterior surface display blebs. No blebs were observed in the non-lens-
of the endothelium and the aqueous humor. This interface wearing eyes. Individual blebbed cells comprised of a
acts as the reflective surface because it represents a signifi- bright central spot, surrounded by a darker annulus, were
cant change in tissue refractive index. The light rays that observed in the endothelium of most subjects.
are reflected from this interface give rise to an observed In one subject, the endothelium was imaged at baseline
image of an essentially flat (or slightly undulating) mosaic and over a time sequence of 5, 10, 15 and 20 minutes of
of largely hexagonal endothelial cells. lens wear (Figure 28.5). The time sequence reveals the
initial appearance of a dark border around some cells,
which broadens into a thick, dark annulus after 15 to 20
minutes of lens wear (Figure 28.6).
A B
Stroma
Light rays which strike ‘blebbed’ endothelial cells will be Figure 28.5 (A–E) Confocal
deflected away from the observation path, leaving a cor- microscope images of the
responding area of darkness. Thus, an endothelial bleb is development of endothelial blebs
simply an individual endothelial cell (or group of adjacent E over a 20-minute time period.
cells) that has become swollen and bulged in the direction (Courtesy of Haliza Mutalib.)
of the aqueous humor, giving rise to the compelling optical
illusion that the cell (or cells) has disappeared.
An optical model is used to illustrate the appearance of
endothelial blebs using confocal microscopy (Figure 28.6).
Confocal microscopy This model employs normal light reflection because light
The confocal microscope has been used to observe the rays pass to and from the endothelium through the confocal
endothelial bleb response at very high magnification microscope objective lens via a pathway of light directly
280
Endothelial blebs
Aetiology
The aetiology of endothelial blebs has been explained by
Holden et al.16 These authors attempted to induce blebs
using a variety of stimulus conditions, and concluded that
one physiological factor common to all successful attempts
to form blebs was a local acidic pH change at the
endothelium.
Two separate factors induce an acidic shift in the cornea
during contact lens wear: (a) an increase in carbonic acid
due to retardation of carbon dioxide efflux (hypercapnia)17
by a contact lens; and (b) increased levels of lactic acid as a
result of lens-induced oxygen deprivation (hypoxia)17 and
Figure 28.6 Enlargement of a confocal microscope image of blebs (arrows), the consequent increase in anaerobic metabolism (Figure
each showing a bright centre surrounded by a thick dark annulus. The 28.8). When silicone elastomer contact lenses are worn,
surrounding unaffected endothelium reflects brightly. (Courtesy of Haliza such metabolic changes do not take place because of the
Mutalib.) extremely high oxygen permeability of such lenses.
HCO3–
HCO3–
HCO3–
endothelial bleb response, whereby more blebs can be automated specular endothelial microscopes are available
observed immediately upon awakening following sleep. for viewing the endothelium;23 these instruments offer
The question arises as to the precise mechanism by which higher magnification and superior resolution compared
acidosis causes endothelial cells to swell. All cells in the with slit lamp observation. As discussed previously, the
human body function optimally when surrounded by confocal microscope provides an even higher level of mag-
extracellular fluid that is maintained within an acceptable nification that allows detailed examination of individual
range of pH, temperature, tonicity, ion balance etc. Car- cells. Endothelial specular microscopes7,8 and confocal
bonic acid and lactic acid may alter the physiological status microscopes14,15 are invaluable as research tools when it is
of the environment surrounding the endothelial cells by necessary to quantify endothelial changes and understand
shifting pH in the acidic direction. This may induce changes the pathology of this phenomenon; however, a general
in membrane permeability and/or membrane pump activ- appraisal of the endothelial bleb response can still be
ity, resulting in a net movement of water into endothelial obtained satisfactorily with a good quality, high magnifica-
cells. The resultant cellular oedema is observed as tion slit lamp.2
‘blebbing’. The extent of endothelial bleb formation can be graded
using the grading scale for this response provided in
Appendix A; however, the usual connotation that is associ-
ated with contact lens grading scales concerning the urgency
Observation and grading for clinical action (see Chapter 29) does not apply here
because contact lens-induced endothelial blebs are thought
The corneal endothelium can be viewed by specular reflec- to be innocuous, irrespective of the level of severity of bleb-
tion using a slit lamp biomicroscope at ×40 magnification. bing. The 0 to 4 scale of the bleb response shown in Appen-
In order to observe the endothelium using this technique, dix A can be considered as being approximately linear.
the angle between the illumination and observation systems High magnification slit lamp photographs of endothelial
must be symmetrical about a plane extending normally blebbing of grades 0 (normal), 2 (slight) and 4 (severe) are
from the cornea, and will typically be between 75° and 90°. shown in Figure 28.9.
The endothelial mosaic can be seen adjacent to a bright
reflex from the corneal surface (Figure 28.1). Using this
technique, only the mid-peripheral nasal or temporal endo- Management
thelium are viewed; this does not pose a problem because
changes in these regions are representative of changes Whilst the phenomenon of endothelial blebs is of immense
elsewhere in the cornea.9 interest from a physiological standpoint, there are no
Although individual endothelial cells can only just be readily apparent clinical ramifications. The bleb response
resolved at ×40 magnification, blebs have a stark appear- occurs to a greater or lesser degree in most patients, and
ance and are easily recognizable. A variety of sophisticated displays a characteristic time course. It is not known
A B C
Figure 28.9 High magnification slit lamp photographs of contact lens-induced endothelial blebs: (A) grade 0 (Courtesy of Steve Zantos, Brien Holden Vision
Institute); (B) grade 2 (Courtesy of Lewis Williams, Brien Holden Vision Institute); and (C) Grade 4. (Courtesy of Brien Holden, Brien Holden Vision Institute.)
282
Endothelial blebs
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