Download Retinal nerve fiber layer analysis in idiopathic intracranial

Original Article
Retinal nerve fiber layer analysis in idiopathic intracranial
hypertension
Tan Funda Uysal, Akarsu Cengiz*, Gullu Reyhan*, Doner Hatice
Departments of Neurology and *Ophthalmology, Kirikkale University, Faculty of Medicine, Kirikkale, Turkey
Background: The chronic nature of idiopathic intracranial
hypertension (IIH) represents a risk factor for progressive
optic nerve damage and structural abnormalities of the
retina. Aim: We measured the retinal nerve fiber layer
(RNFL) thickness in patients followed with the diagnosis
of IIH who had no or mild visual impairment to search for
possible structural alterations in the retina for diagnostic
and prognostic purposes. Settings and Design: Casecontrol prospective study. Materials and Methods: The
study group consisted of 12 women followed and treated
with the diagnosis of IIH in our clinic. The selection criteria
were the, normal optic nerve, normal visual fields or mild
visual field defects (Grade 1-3) by Humphrey perimeter.
Randomly assigned, age-matched 12 healthy women were
taken as the control group. Retinal nerve fiber layer
thickness was evaluated with scanning laser polarimetry
and both eyes were studied for each case in both groups.
Statistical Analysis Used: Mann-Whitney U test. Results:
The mean ages of the patient and the control groups were
34.58±4.2 and 34.42±5.7 years respectively (P=0.87). The
mean duration of disease was 5.5±3 years. Some
parameters related to RNFL thickness were found to differ
significantly between patients with IIH and control subjects.
Namely superior ratio (P=0.007), inferior ratio (P=0.039),
superior-nasal ratio ( P=0.025), maximum modulation
(P=0.01) and symmetry (P=0.006) were lower in the patient
group than controls. Conclusion: Scanning laser
polarimetry might be a good adjunct for determining
possible structural affects of IIH on the retina in patients
with no or mild visual impairment.
Key words: Idiopathic intracranial hypertension, retinal
nerve fiber layer thickness, scanning laser polarimetry.
Introduction
Idiopathic intracranial hypertension (IIH) is a disorder
characterised by increased intracranial pressure (ICP) in the
absence of intracranial disease such as space occupying lesion or
ventriculomegaly, abnormal cerebrospinal fluid (CSF) composition
and cerebrovascular disease. Although the disorder was described
more than a century ago, its pathogenesis remains unclear.[1] It is
known to be associated with significant visual morbidity even
blindness in up to 10% of the cases.[2,3] Although the papilledema
and symptoms might be transient the chronic nature of the disease
represents a risk factor for progressive optic nerve damage and
structural abnormalities of the retina.[2,4] Visual field testing is
considered to be a reliable method to assess the optic nerve damage
in patients with IIH. [2,5] Visual field defects in IIH are similar to
glaucoma and usually include an enlarged blind spot, nasal steps,
arcuate defects, inferior altitudinal loss and generalised
constriction.[5,6]
Scanning laser polarimetry is a device designed for objective
and quantative measurement of retinal nerve fiber layer (RNFL)
thickness.[7,8] The validation of the instrument was confirmed in
animal models[7,8] and the device was used for various purposes
in ophthalmology like the detection and follow up of glaucoma,
documentation of optic neuropathy and assessment of diabetic
retinopathy.[9-13] The present study was designed to investigate
whether measurement of RNFL thickness with scanning laser
polarimetry might yield additional benefit for searching
ophthalmologic complications of IIH and provide quantitative
information for follow up during the course of the disease. A
selected group of IIH patients were included to the study who had
no or mild visual impairment to search for possible structural
alterations in the retina for diagnostic and prognostic purposes.
Materials and Methods
Subjects
This study was conducted during May 2004 and December
2004 in a group of 12 consecutive female patients with no or mild
visual impairment selected among patients followed and treated
with the diagnosis of IIH in our clinic. The selection criteria were
the absence of papilledema (resolved papilledema), normal optic
nerve (no atrophy), normal visual fields or mild visual field defects
Funda Uysal Tan
Elçi Sokak 19/18, Y.Ayranci 06550, Ankara, Turkey. E-mail: [email protected]
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Uysal et al.: Idiopathic intracranial hypertension and retinal thickness
(Grade 1-3) by Humphrey perimeter during follow up. Patient
characteristics are given at Table 1. In all patients the diagnosis of
IIH was made previously by using the modified Dandy criteria by
Smith which requires the presence of: signs and symptoms of
increased ICP (headache, papilledema etc.), no localizing
neurological sign other than sixth nerve palsy, increased CSF
pressure (≥ 250 mmH2O for all patients) with normal composition
(normal protein and glucose levels and number of cells) no evidence
for hydrocephalus (small-normal and symmetric ventricles) or
mass lesion confirmed by CT scan or MRI and no other cause of
IIH.[14,15] The lumbar puncture was performed in the lateral
decubitus position from the L3-L4 intervertebral space using a
standard 20G spinal lumbar puncture needle. Randomly assigned
12 healthy women of similar age and sex were taken as the control
group which was not subjected to lumbar puncture. After
neurological evaluation all patients with IIH and control subjects
underwent a complete ocular examination including history taking,
measurements of visual acuity and refraction, ocular motilities,
intraocular pressure measurement, visual field examination with
Humphrey automated perimeter and bio-microscopy of the
anterior and posterior segments. Patients were excluded from the
study if they had a neurological disease other than IIH, any
systemic disorder or medication that could cause papilledema or
IIH; any previous eye disease particularly surgery, glaucoma,
retinal disorders or systemic disorder affecting vision such as
diabetes mellitus, hypertension etc. Same exclusion criteria were
also applied to the control group. In accordance with the ethical
standards each participant was adequately informed, agreed
participation and a written informed consent was obtained from
all of the patients that had entered to the study.
Scanning laser polarimetry
Retinal nerve fiber layer thickness was evaluated with scanning
laser polarimetry (Nerve Fiber Analyzer, GDx VCC:5.3.3, Laser
Diagnostic Technologies, San Diego, California, U.S.A) for both
IIH and control groups. The measurement of RNFL thickness
was carried out by the same examiner, who was unaware of the
patient and control status. Examinations were done in the same
room for all subjects and the pupils were undilated. After
ophthalmological evaluation and test for exclusion criteria, for
each case, both eyes were evaluated in both the patient and control
groups as IIH is expected to affect both. As all subjects and eyes
fulfilled the inclusion criteria a total number of 48 eyes (24 from
the patient and 24 from the control groups) were taken to the
study. The technique of scanning laser polarimetry was described
elsewhere previously.[7-13] When the polarised laser beam
illuminates the retina it passes through the birefringet RNFL
that changes the state of polarisation of the light source. The
amount of change in polarisation (retardation) is correlated with
RNFL thickness.[7,8] The polarisation detection unit provides
digital real time images of the ocular fundus. The operator initially
marks an ellipse at the rim of the optic disc [Figure 1]. The
machine generates a 10-pixel wide second ellipse (the RNFL
thickness measurement ellipse) around the first one that is situated
at 1.75 disc diameters apart from the center of the optic disc. The
laser beam is directed over 256x256 pixel (each corresponding a
retinal point) retinal locations and a colour coded retardation
image(map) is produced such that blue represents less
birefringence (thinner area)while the red/yellow represents areas
of greater birefringence (thicker area) [Figure 1]. The device
measures and gives a series of parameters related to RNFL
thickness. For each subject more than one good quality images
were acquired to obtain the best image that would be used for the
measurement of RNFL thickness. For all patients mean RNFL
thickness values were computed for all of the retina as well as
superior (120°), inferior (120°), temporal (70°) and nasal (50°)
segments [Figure 1] and compared with the control group.
The used parameters were previously defined as:[10-12]
Average Thickness (µm): The average thickness for all pixels
in the image outside the disc margin
Symmetry: The ratio of the average 1500 thickest pixels in the
superior quadrant divided by the average 1500 thickest pixels in
the inferior quadrant.
Superior (Inferior) Ratio: The ratio of the average 1500 thickest
pixels in the superior (inferior) quadrant divided by the average
1500 thickest pixels in the temporal quadrant.
Superior-Nasal Ratio: The ratio of the average 1500 thickest
Table 1: Patient characteristics. Age is the age at the time of study, Humphrey perimeter (P) grades are assigned from
the reference by Wall and George [3] and the visual acuity is the best corrected visual acuity according to Snellen chart.[17]
Age
40
41
39
32
29
32
34
32
34
35
28
39
Disease
duration
3
6
10
8
8
6
3
6
3
2
10
1
Intracranial
pressure (mmH 2 O)
335
300
270
400
450
290
295
260
300
300
300
250
Neurology India | June 2006 | Vol 54 | Issue 2
Humphrey P.
right eye
1
0
0
3
1
1
0
1
0
0
2
1
Humphrey P.
left eye
1
1
0
3
0
1
0
2
0
0
2
2
Visual acuity
right eye
10/10
10/10
10/10
10/10
10/10
10/10
10/10
10/10
10/10
10/10
10/10
10/10
Visual acuity
left eye
10/10
10/10
10/10
10/10
10/10
10/10
9/10
10/10
10/10
10/10
10/10
10/10
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Uysal et al.: Idiopathic intracranial hypertension and retinal thickness
thickest pixels in the superior (inferior) RNFL.
Ellipse Average (µm): The average thickness of RNFL beneath
the measuring ellipse along its circumference.
Maximum Modulation: Gives an index of the difference between
the thickest(superior, inferior quadrants) and thinnest parts
(temporal, nasal quadrants) of all RNFL.
Ellipse Modulation: Gives an index of the difference between
the thickest and thinnest parts beneath the measurement ellipse.
Statistics
The statistical analysis was done by the Statistical Package for
Social Sciences (SPSS) program. The Mann-Whitney U test was
used to compare numeric variables between headache and control
groups and P values <0.05 were considered as statistically
significant.
Results
A
B
Figure 1: (A) The operator initially marks the rim of the optic disc.
The machine generates a second ellipse (the RNFL thickness
measurement ellipse) around the first one that is situated at 1.75
disc diameters apart from the center of the optic disc (Upper
image). The laser beam is directed over retina and a colour coded
retardation image(map) is produced (Lower image). Blue represents
less birefringence (thinner area) while the red/yellow represents
areas of greater birefringence (thicker area). (B) Graphic illustration
for total retinal polarisation and related thickness given in µm. The
shaded area represents the normal range. S: Superior,
I: Inferior, T: Temporal and N: Nasal segments
pixels in the superior quadrant divided by the average 1500
thickest pixels in the nasal quadrant.
Superior (Inferior) Average (µm): The average thickness of
RNFL beneath the measuring ellipse in the superior (inferior)
sector.
Superior (Inferior) Maximum (µm): The mean of the 1500
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The mean ages of the patient and the control groups were
34.58±4.2 and 34.42±5.68 years respectively (P=0.87). The
mean duration of disease was 5.5±3 years and the mean
intracranial pressure as 312.5 mmH2O. At the time of study 66.7%
of the patients and 14 eyes (58.33%) had visual defects assessed
by Humphrey perimeter [Table 1]. However most visual field
defects were of mild grades and visual acuity was excellent in all
cases. None of the patients had papilledema. All cases received
acetazolamide in a dose of 750-1000 mg/day and weight loss was
encouraged especially in obese patients. Briefly, although
measurements were usually similar, some parameters related to
RNFL thickness were found to differ significantly between patients
with IIH and control subjects [Table 2]. Namely superior ratio
(P=0.007), inferior ratio (P=0.039), superior-nasal ratio
(P=0.025), maximum modulation (P=0.01) and symmetry
(P=0.006) were lower in the patient group than controls.
Finally the relationship between the level of intracranial pressure
and parameters of RNFL layer was investigated using Spearman
correlation analysis. This test revealed a negative correlation
between superior average (coefficient -0.53, P=0.008), superior
maximum (coefficient -0.51, P=0.011) parameters and
intracranial pressure meaning that the higher is the pressure the
thinner is the RNFL in the superior sector.
Discussion
The most important complication of IIH is severe visual
morbidity. Although fundus images obtained at certain periods
are helpful for objective documentation and comparison of the
disease process, visual field testing especially with Humphrey
perimeter is considered as a reliable method to assess the optic
nerve damage in patients with IIH.[2,5,6] In a series of 50 patients,
visual field defects were found in 96% of the cases at initial
evaluation by Goldmann perimetry that were improved after
treatment in 60% of the patients but visual function deteriorated
Neurology India | June 2006 | Vol 54 | Issue 2
Uysal et al.: Idiopathic intracranial hypertension and retinal thickness
Table 2: Comparison between idiopathic intracranial hypertension patients (12 patients, 24 eyes) and controls (12
women, 24 eyes) for retinal nerve fiber layer (RNFL) thickness parameters.
RNFL thickness parameter
Age
Tsnit. av (µm)
Symmetry
Sup. ratio
Inf. ratio
Sup. nasal ratio
Sup. average (µm)
Inf. av (µm)
Sup. max (µm)
Inf. max (µm)
Elp. Average (µm)
Max. mod.
Elp. mod.
Patient (n. eyes=24)
Mean ± Std. deviation
34.58 ± 4.22
59.96 ± 4.85
0.92 ± 0.15
3.31 ± 1.16
3.53 ± 1.1
2.3 ± 0.59
71.18 ± 5.96
69.87 ± 10.21
81.34 ± 9.74
90.37 ± 13.41
59.96 ± 4.85
2.65 ± 1.26
4.23 ± 1.82
Control (n. eyes=24)
Mean ± Std. deviation
34.42 ± 5.68
57.61 ± 3.83
0.99 ± 0.11
3.93 ± 0.94
3.98 ± 0.87
2.67 ± 0.58
70.43 ± 4.56
68.65 ± 5.03
81.07 ± 6.89
82.72 ± 8.46
57.61 ± 3.83
3.17 ± 0.86
4.53 ± 1.53
P value*
0.87
0.06
0.006
0.007
0.039
0.025
0.86
0.59
0.65
0.07
0.06
0.011
0.17
*Mann-Whitney U Test, TSNIT.AV: Average thickness. SUP: Superior. INF: Inferior. MAX: Maximum. MOD: Modulation. ELP: Ellipse
in 5 cases (10%).[3] Similarly Rowe and Sarkies assessed the
visual function in 35 IIH patients prospectively over a 3 year
period.[6] Although visual field defects still persisted in 75% and
56% of the cases by Goldmann and Humphrey perimetries
respectively the visual status improved significantly throughout
the follow-up period and the final visual outcome was excellent or
good in the majority of the patients. This was attributed to the
fact that most visual field defects were of mild grades (grade 1 or
2) thus most patients were unaware of the defect. Though
uncommon, the gradual and insidious development of severe visual
loss necessitates periodic monitoring of visual fields and acuity in
IIH. New visual field defects or progression of previous defects
are accepted as indicators of progressive optic damage and imply
a more aggressive treatment approach.[5,16] However fluctuations
might be possible thus a repeat analysis might be prudent in case
of suspect.[5] In a small number of patients with IIH Mullholland
et al. used confocal scanning laser ophthalmoscopy (SLO)
acquired optic disc images to monitor papilledema.[17] The authors
reported that SLO had a high sensitivity for detecting small
changes in disc volumes and correlated closely with visual field
changes in the short term.
Test-retest variability might make perimetry somewhat
problematic in deciding when progressive loss is occurring and
when to recommend invasive treatments. If test-retest variability
for the nerve fiber layer measurement could be shown better than
that of perimetry, it may be the preferred way to follow them for
deciding on intervention even when field loss and thinning is well
established. However in patients without or with mild visual
improvement like our study group, RNFL analysis with scanning
laser polarimetry might also provide early valuable information.
Our data revealed that superior ratio, inferior ratio, superiornasal ratio, maximum modulation and symmetry were lower in
the patient group than controls. These parameters are indicators
of differences between thickest (superior and inferior) and thinnest
parts (nasal and temporal) of the retina [Figure 1]. The difference
between ratios might represent an early change not reflected by
other indices like superior-inferior average, superior-inferior
Neurology India | June 2006 | Vol 54 | Issue 2
maximum or total-ellipse average. Previously Hedges et al. analyzed
RNFL changes in patients with IIH from photographs of RNFL
and used visual field tests to determine the clinical usefulness of
RNFL analysis in the clinical management of patients with
papilledema.[18] The location of the nerve fiber layer changes
correlated with corresponding sites of visual field loss and superior
regions within the nerve fiber layer were affected 5.4 times more
frequently than inferior regions. Similarly we found that the RNFL
in the superior sector was more adversely affected with increased
pressure.
In conclusion scanning laser polarimetry might be a good
adjunct for determining possible structural affects of IIH on the
retina in patients with no or mild visual impairment. It might
supply additional measurable indices for follow up. As the series
is small this report provides only preliminary information that
might lead clinical research in this field and further data with
larger series are necessary to clear the subject adequately.
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Accepted on 28-03-2006
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