ENDOTHELIAL SYNDROMES (ICE)
The patient with
ICE syndrome is typically a younger female. It is most common in Caucasians,
and there typically is no family history of this disease. It is most commonly
a unilateral phenomenon, but bilateral cases have been documented.1 It
tends to manifest in early to middle adulthood.2 Common findings
include a beaten bronze appearance to the corneal endothelium, corneal
edema, iris atrophy and hole formation, corectopia, prominent iris nevus,
and peripheral anterior synechiae with progressive angle closure and secondary
closed-angle glaucoma. Vision may be unaffected or may be reduced due to
endotheliopathy or glaucoma. The patient may occasionally complain of monocular
diplopia secondary to an exposed area of full thickness iris atrophy creating
another entrance for light to enter the eye (polycoria).
The ICE syndromes
represent a continuum of disease involving three distinct entities:
essential iris atrophy, Chandler syndrome, and
Cogan-Reese (iris nevus) syndrome. Essential iris atrophy is characterized
by progressive iris atrophy and hole formation, corectopia, and marked
peripheral anterior synechiae. The iris and pupil are pulled in the
direction of the peripheral anterior syn-echiae. Chandler syndrome,
the more common of the three, manifests greater corneal changes and
edema but fewer iris abnormalities. Cogan-Reese syndrome presents
with iris atrophy, corneal endotheliopathy, corneal edema, and prominent
iris nevi. Patients with Chandler's syndrome typically have worse
corneal edema than the rest of the group, while secondary glaucoma
is more severe in the other syndromes.3
in essential iris atrophy.
anterior synechiae in essential iris atrophy.
All the ICE
syndromes share a common underlying pathophysiology and can all be
considered to be primary proliferative endothelial degenerations.4 The
corneal endo-thelium has a fine beaten-silver appearance. This, along
with ensuing corneal edema, is a cause of vision reduction in these
patients. The endothelium is most affected in essential iris atrophy.
Some endo-thelial changes such as migration and reparative processes
are identifiable, as is the presence of cell necrosis and chronic
inflammation.5 It appears that the endothelial cells undergo
a metaplastic transformation into "epithelial-like" cells that migrate
in a membrane form over the anterior chamber angle to the iris.6 Subsequent
contraction of the membrane pulls the iris toward the cornea with
a chronic progressive synechial closure of the angle. This can result
in secondary angle closure without pupil block. The cellular membrane
may also cause aqueous outflow blockage in the absence of peripheral
ICE syndromes is case specific and should be dictated by the degree
of corneal edema and severity of the secondary glaucoma. Topical
aqueous suppressants are the medical mainstay for management of glaucoma
secondary to ICE syndromes. Medications that stimulate aqueous outflow
are typically less effective and should not be used. Also, laser
trabeculoplasty is not seen as effective. In severe cases, trabeculectomy
may be necessary, though there is a risk of closure of the sclerotomy
site by the abnormal membranes, with subsequent surgeries required.7,8 Glaucoma
surgical implant devices may be necessary for this reason. Despite
adequate IOP control, corneal edema may persist due to the endotheliopathy.
In these cases, penetrating keratoplasty may be necessary to restore
vision, though this procedure will not affect abnormalities in the
iris or anterior chamber angle.9
iris atrophy, Chandler's syndrome, and Cogan-Reese syndrome are all
in the same clinical disease spectrum of ICE syndromes
is unpredictable, and many patients have a good outcome.
- The iris is
dragged in the direction of the peripheral anterior synechia.
- Huna R, Barak A, Melamed S. Bilateral iridocorneal endothelial
syndrome presented as Cogan-Reese and Chandler's syndrome. J
- Shields MB. Progressive essential iris
atrophy, Chandler's syndrome, and the iris nevus (Cogan-Reese)
syndrome: a spectrum
of disease. Surv Ophthalmol. 1979;24(1):3-20.
- Wilson MC,
Shields MB. A comparison of the clinical variations of the iridocorneal
endothelial syndrome. Arch Ophthalmol. 1989;107(10):1465-8.
- Langova A, Praznovska Z, Farkasova B. Progressive essential atrophy
of the iris as a form of the iridocorneal endothelial
(ICE) syndrome. Cesk Slov Oftalmol. 1997;53(6):371-80.
- Alvarado JA, Murphy CG, Maglio M, et al. Pathogenesis of Chandler's
syndrome, essential iris atrophy and the Cogan-Reese
syndrome. I. Alterations of the corneal endothelium.
Invest Ophthalmol Vis Sci. 1986;27(6):853-72.
- Howell DN, Damms
T, Burchette JL Jr, et al. Endothelial metaplasia in the iridocorneal
endothelial syndrome. Invest Ophthalmol
Vis Sci. 1997;38(9):1896-901.
- Halhal M, D'hermies
F, Morel X, et al. Iridocorneal endothelial syndrome. Series
of 7 cases. J Fr Ophtalmol. 2001;24(6):628-34.
- Kidd M, Hetherington
J, Magee S. Surgical results in iridocorneal endothelial syndrome.
Arch Ophthalmol. 1988;106(2):199-201.
- Buxton JN, Lash RS. Results
of penetrating keratoplasty in the iridocorneal endothelial syndrome.
Am J Ophthalmol. 1984;98(3):297-301.
TECHNOLOGY: GDx VCC
THE EARLIEST clinically identifiable changes occurring in glaucoma
is damage to the nerve fiber layer (NFL). Nerve fiber layer
damage typically precedes visual field loss, often by several
years. Thus, a careful examination of the NFL is essential
to identify early patients who have developed glaucoma. Focal
NFL defects, particularly when they are juxtaposed against
healthy NFL, are easily detected ophthalmoscopically. However,
diffuse or subtle NFL damage is more difficult to appreciate.
The need to objectively and accurately quantify the NFL and
differentiate normal patients from those with glaucoma led
to the development of the GDx Nerve Fiber Layer Analyzer.
utilizes scanning laser polarimetry (SLP) to measure the thickness
of the NFL for comparison against a normative database. The
principles of SLP utilize birefringence and retardation. Briefly,
the NFL is birefringent due to the parallel arrangement of
microtubules within NFL axons. Birefringence changes the polarization
of the incident light into orthogonal planes. The time delay
between the return of these fast and slow axes is called retardation.
Polarized light passing through a birefringent medium (NFL)
is split into two rays. Rays of laser light that travel perpendicular
to fibers passes through at a speed different from those rays
passing through in parallel. The phase shift results in retardation
and provides the basis for which to measure the thickness of
the cornea and, to a lesser extent, the lens are also birefringent
structures that essentially can contribute to signal noise
that can artifactually alter the analysis, much the same way
a cataract can affect the results of a visual field. Early
iterations of SLP utilized a fixed corneal compensator that
assumed a set corneal polarization magnitude and axis. While
this fixed corneal compensator corrected for anterior segment
aberration in the vast majority of patients, there were patients
whose corneal polarization magnitude and axis did not conform
to that of the general population, and their anterior segment
birefringence was not eliminated.1 This led to artifacts
in the analysis with the true retrolenticular birefringence
not being accurately measured.
this problem, variable corneal compensation (VCC) has been
incorporated into the scanning laser polarimeter (GDx VCC).
This device now measures the corneal polarization axis and
magnitude in all eyes, then sets the device to cancel individual
corneal birefringence so that the true retrolenticular (retinal
NFL) birefringence is accurately measured. The method that
the GDx VCC employs is quite simple. For the initial exam on
all patients, a macular scan is first obtained. Birefringence
around the fovea is known to be uniform due to the absence
of ganglion cells, and hence NFL in this region. A non-uniform
pattern at the fovea must be caused by the cornea, and an hourglass
pattern indicates the axis and magnitude of the corneal birefringence.
When the variable compensator is set to cancel the corneal
birefringence, the hourglass disappears, indicating successful
of scanning laser polarimetry is to objectively and accurately
discriminate between normal patients and those with glaucoma.
Previously reported poor diagnostic precision of SLP with a
fixed corneal compensator was likely attributable to inflated
intersubject variability resulting from ineffective corneal
birefringence compensation. New research using variable corneal
compensation has demonstrated success at differentiating normal
patients from those with glaucoma. The variable corneal birefringence
compensation has significantly narrowed the range of normals
and much more accurately allows for differentiation between
those with and without glaucoma. The sensitivity of this discrimination
has increased greatly due to the removal of artifact stemming
from improperly compensated corneal polarization axis and magnitude.3-5 It
appears that the GDx VCC accurately measures the true retrolenticular
birefringence and provides a reproducible measurement of the
thickness of the NFL. The VCC now allows for accurate measurement
of the NFL, which correlates well with both structure as measured
by optical coherence tomography6 and function as
measured by SITA perimetry.7 A normative database,
which also represents patients of African descent as well as
other races prone to glaucoma, allows for a statistical comparison
of the NFL.
- Weinreb RN, Bowd C, Greenfield DS, et al. Measurement of the magnitude
and axis of corneal polarization with scanning laser polarimetry.
Arch Ophthalmol. 2002 Jul;120(7):901-6.
- Zhou Q, Weinreb RN. Individualized
compensation of anterior segment birefringence during scanning
laser polarimetry. Invest
Ophthalmol Vis Sci. 2002 Jul;43(7):2221-8.
- Weinreb RN, Bowd
C, Zangwill LM. Glaucoma detection using scanning laser polarimetry
with variable corneal polarization
compensation. Arch Ophthalmol 2002; 120:218-24.
DF, Greaney MJ, Caprioli J. Correction for the erroneous compensation
of anterior segment birefringence
with the scanning laser polarimeter for glaucoma diagnosis.
Invest Ophthalmol Vis Sci. 2002 May;43(5):1465-74.
FA, Zangwill LM, Bowd C, et al. Fourier analysis of scanning
laser polarimetry measurements with variable corneal
compensation in glaucoma. Invest Ophthalmol Vis Sci.
- Bagga H, Greenfield DS, Feuer W, et al.
Scanning laser polarimetry with variable corneal compensation
and optical coherence tomography
in normal and glaucomatous eyes. Am J Ophthalmol. 2003
- Bowd C, Zangwill LM, Weinreb RN.Association
between scanning laser polarimetry measurements using variable
compensation and visual field sensitivity in glaucomatous
eyes. Arch Ophthalmol. 2003 Jul;121(7):961-6.
TECHNOLOGY: CONFOCAL SCANNING LASER TOMOGRAPHY
CONFOCAL SCANNING LASER TOMOGRAPHY is not exactly a "new" technology,
its widespread use in clinical practice today merits special
mentioning. The Heidelberg Retinal Tomograph II (HRT II) offers
a combined approach for detection of both glaucoma and macular
detection, the HRT II obtains a series of optical section images
of the optic disc and peripapillary retina at several depths.
This series of images is combined layer-by-layer into a three-dimensional
image remarkably similar to a CT scan. The HRT II gives both
a pictorial image of the disc and cup as well as numerical
values of several disc parameters. Data obtained from a patient
is compared against a normative database in the Moorfields
Regression Analysis. The Moorfields Regression Analysis classifies
eyes based upon the relationship between the cup and rim area,
among other parameters. The fact that the HRT II linear regression
analysis takes into account the overall disc area makes the
device more sensitive than clinical assessment of stereoscopic
optic disc photographs in distinguishing between healthy patients
and those with early glaucoma.1
intervals are set at 95% and 99.9%. That is, if the data obtained
on a patient shows that the area of the neuroretinal rim is
larger than or equal to that found in 95% of the patients in
the normative database, the patient is classified as "within
normal limits." If the area of the neuroretinal rim for the
patient falls between 95% and 99.9% of the area for the neuroretinal
rim of patients in the normative database, the patient is classified
as "borderline." If the patient's obtained data indicates that
99.9% of the patients in the normative database have more area
to the neuroretinal rim, the patient is labeled as "outside
normal limits." These analyses are performed for several areas
of the disc. Following a patient for change over time can be
done either with the stereometric parameters or by using the
Progression and Change Probability program, which is the preferred
an image is obtained, the operator must manually plot the edge
of the disc with a "contour line." This can be seen as a source
of introduced error, as the analysis is highly dependent upon
the correct determination of the disc contour. Further, the
delineation between the cup and rim is accomplished through
a reference plane. The average thickness of the papillo-macular
bundle located at 350º to 356º has been found to
be, on average, 50µm. This is the bundle that remains
intact through disease progression. The separation of rim from
cup is set 50µm below the average thickness of this area.
Essentially, everything above the reference plan is rim, and
everything below is cup. This has been argued to be another
source of introduced error.
importing the reference plane and contour line into successive
analyses compensates for any introduced error. The Progression
and Change Probability program negates any sources of introduced
error and remains a powerful feature of the HRT II. Further,
the Progression and Change Probability program can operate
without the operator ever defining a contour line. Built-in
software automatically, objectively compares subsequent patient
exams against the original baseline exam and identifies significant
changes. Measurement of disc stereometric parameters is highly
reproducible.2 There are sensitive parameters to
indicate the quality of captured images and follow-up exams
that are unfocused by more than 1.00D are easily identified.
Thus, the HRT II remains an outstanding device to measure changes
in disc parameters over time.3 Further, the HRT
II can meet or exceed the disc topographic change detection
performance of even the most experienced clinicians.4 The
ability to detect subtle change in the disc topography over
time is critical because this pathological alteration frequently
occurs prior to the onset of visual field progression and may
be one of the first indications of glaucomatous deterioration.5,6 The
ability to detect change over time remains the greatest strength
of the HRT II.
II also provides an objective way to measure retinal edema.
The macular edema module of the HRT II analyzes signal width.
It then takes into account signal width and retinal reflectance
at each retinal location obtained in the optic slices to generate
an index that is sensitive to the presence of retinal edema.
- Wollstein G, Garway-Heath DF, Fontana L, et al. Identifying
early glaucomatous changes. Comparison between expert clinical
assessment of optic disc photographs and confocal scanning
ophthalmoscopy. Ophthalmology. 2000;107(12):2272-7.
S, Albé E, Guareschi M, et al. Intraobserver
and interobserver reproducibility in the evaluation of optic
disc stereometric parameters by Heidelberg retina tomograph.
Ophthalmology 2002; 109:1072-7.
- Burgoyne CF, Mercante DE,
Thompson HW. Change detection in regional and volumetric
disc parameters using longitudinal
confocal scanning laser tomography. Ophthalmology. 2002
- Ervin JC, Lemij HG, Mills RP, et al. Clinician
change detection viewing longitudinal stereophotographs compared
to confocal scanning laser tomography in the LSU Experimental
Glaucoma (LEG) Study. Ophthalmology. 2002 Mar;109(3):467-81.
- Scheuerle AF, Schmidt E, Kruse FE, et al. Diagnosis and follow-up
in glaucoma patients using the Heidelberg retina
tomograph. Ophthalmologe. 2003 Jan;100(1):5-12.
BC, McCormick TA, Nicolela MT, et al. Optic disc and visual
field changes in a prospective longitudinal
study of patients with glaucoma. Comparison of scanning
laser tomography with conventional perimetry and optic disc
Arch Ophthalmol 2001; 119:1492-9.
INSIGHT ON TREATING GLAUCOMA
GLAUCOMA HAS LONG BEEN considered a pressure- sensitive optic
neuropathy, only recently has the benefit of intraocular pressure
reduction been scientifically proven.1-5 Recently,
a study has been published that may be the only study to include
an untreated study arm of patients known to have the disease.
The Early Manifest Glaucoma Trial (EMGT) was a controlled clinical
trial that evaluated the effectiveness of reducing IOP in patients
with newly detected, previously untreated, early glaucoma.6 Results
from this landmark study have shed light on managing this condition.
randomized 255 patients, aged 50 to 80 years with early stage
glaucoma in at least one eye, into either a treated arm or
an observational arm of the study. Patients were detected through
population-based screenings at two cities in Sweden and were
included if they had a new diagnosis of early manifest primary
open-angle glaucoma (POAG), normal-tension glaucoma, or pseudo-exfoliative
glaucoma. Patients were excluded if they had advanced visual
field defects, poor acuity in either eye, mean IOP greater
than 30mm Hg or any IOP greater than 35mm Hg, or any condition
that would interfere with serial observation for progression.
Thus, the patients in the study truly had early glaucoma only.
in the treated arm received standard therapy consisting of
betaxolol and argon laser trabeculoplasty. While there was
not a target pressure or desired IOP reduction, the standard
treatment lowered IOP by 25%, which was maintained throughout
the study. The patients in the observational arm were followed
closely with very sensitive indicators designed to detect progression.
While some wondered whether it was ethical to not treat patients
with glaucomatous damage, the study was designed carefully
so that any untreated patient who demonstrated progression
was immediately offered treatment. Thus, no patient was allowed
to lose a significant amount of visual field while undergoing
were somewhat surprising. After fours years of follow-up, 30%
of patients in the treated arm demonstrated progression, while
49% of the untreated patients progressed. After six years of
follow-up, 45% of the patients in the treated group had progressed,
compared to 62% of the untreated patients. While this clearly
demonstrated a benefit of treatment, it was apparent that glaucoma
progressed in a large percentage of treated patients. The time
that it took for glaucoma to progress varied greatly among
patients and was sometimes rather short, even in the treated
group. However, many patients remained stable throughout the
course of the study, even in the untreated group. Results of
this study showed that each mm Hg of pressure reduction conferred
approximately a 10% reduction of risk for glaucoma progression.
This may force doctors to reevaluate what constitutes a "clinically
significant" pressure reduction, as small reductions in IOP
may be critical.
clearly shows that treatment for newly diagnosed early glaucoma
should be individualized and tailored to the needs of the patient.
One option could include no initial treatment, but observation
with treatment commencing if progression is seen. The decision
not to treat patients in the early stage may postpone or obviate
the need for medications.
of this study must be viewed in context with the limitations
of this study. Virtually all patients were Caucasian. Thus,
it may not be prudent to apply the results of this study to
patients of African descent, who may have an entirely different
form of the disease. Over half of the patients had normal-tension
glaucoma, which has been shown to be largely a non-progressive
disease.5 Also, there is no data on patients with
very high IOP or advanced visual field loss, and there is no
long-term follow-up of patients beyond EMGT progression.
- Lichter PR, Musch DC, Gillespie BW, et al. Interim clinical
outcomes in the Collaborative Initial Glaucoma Treatment
Study (CIGTS). Comparing initial treatment randomized to
medications or surgery. Ophthalmology 2001; 108:1943-53.
- Sommer AS, Tielsch JM, Katz J, et al. Relationship
between intraocular pressure and primary open angle glaucoma
White and Black Americans. The Baltimore Eye Survey. Arch
- Kass MA, Heurer DK, Higginbotham
EJ. Et al. The Ocular Hypertension Treatment Study. A randomized
that topical ocular hypotensive medication delays or
prevents the onset of primary open angle glaucoma. Arch Ophthalmol
- The Advanced Glaucoma Intervention
Study Investigators. The Advanced Glaucoma Intervention Study
(AGIS): 7. The relationship
between control of intraocular pressure and visual
field deterioration. Am J Ophthalmol 2000; 130:429-40.
Normal Tension Glaucoma Study Group. Comparison of glaucomatous
progression between untreated patients with
normal tension glaucoma and patients with therapeutically
reduced intraocular pressures. Am J Ophthalmol 1998;126:487-97.
- Heijl A, Leske MC, Bengtsson B, Hyman L, Bengtsson B, Hussein
M, for the Early Manifest Glaucoma Trial Group. Reduction
of intraocular pressure and glaucoma progression.
Arch Ophthalmol 2002;120:1268-79.
reports in this section