Download Low ocular rigidity in patients with osteogenesis imperfecta.

Volume 20
Number 6
Reports
6. Ham WT Jr, Ruflblo JJ Jr, Mueller HA, Clarke AM,
and Moon ME: Histologic analysis of photochemical
lesions produced in rhesus retina by short-wavelength light. INVEST OPIITIIALMOL VIS SCI 17:1029,
1978.
7. Zuclich JA: Cumulative effects of near-UV induced
corneal damage. Health Phys 38:833, 1980.
Table I
Measurement
Technique
Corneal diameter
Central corneal thickness
Anterior chamber depth
Horizontal and vertical
keratometry
Pupil size
Millimeter ruler
Haag-Streit pachymeter
Hagg-Streit pachymeter
American Optical keratometer
Millimeter ruler at ambient light
Millimeter ruler in primary position
A-scan ultrasonography
Indentation technique
with two weights on the
Schiotz' tonometer
Retinoscopy and manifest
refraction
Masked grading of external photographs on
scale 0 - 4 +
Palpebral fissure size
Low ocular rigidity in patients with os-
Length of globe
Ocular rigidity
teogenesis imperfecta. MURIEL I. KAISERKUPFER, LESSIE M C C A I N , JAY R.
MARVIN
J.
PODCOR,
CARL
SHAPIRO,
Sixteen patients with osteogenesis imperfecta (01) have
undergone a thorough eye examination. These patients
had statistically significantly lower ocular rigidity measurements than a group of normal oolunteers matched on
age, sex, and, refractive error. In addition, the corneal
diameter and. length of the eyeball was smaller in 01
patients than that in controls. Possible correlations of
low ocular rigidity with biochemical changes in scleral
collagen await further investigation.
Osteogenesis imperfecta (01) is an inherited
disease of bone affecting between 10,000 and
20,000 persons in the United States. OI is usually
inherited as an autosomal dominant, but cases of
sporadic or recessive inheritance have been reported. Given the variability in clinical and genetic expression, the term OI probably represents
several clinically similar but genetically distinct
disorders. Although blue sclera, along with fractures and deafness, have been identified as cardinal clinical features of OI, there has been poor
correlation of the presence or absence of blue
sclera with the other features of the disease.1' 2
This may be because of subjectivity in estimating
the presence or absence of blue sclera as well as
grading the color. A more quantitative assessment
of the properties of sclera could be of value in
determining the functional characteristics of this
tissue in OI patients. The purpose of this presentation is to report the findings of a complete ocular
evaluation of sixteen patients with OI as compared
with age-, sex-, and refractive error-matched
controls.
Materials and methods. Sixteen patients with
OJ ranging in age from 9 to 56 years underwent a
complete ocular examination, including measurement of corneal diameter, corneal thickness centrally, anterior chamber depth, horizontal and
vertical keratometry, pupil size, palpebral fissure
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Refractive error
KUPFER, AND
DAVID ROVVE.
807
Scleral color
size, length of globe, ocular rigidity, refractive error, and scleral color. Table I presents the- techniques used for each of these measurements.
These patients represented the broad clinical and
genetic spectrum of OI. Each had a lifelong history of multiple fractures, compatible radiologic
findings, and no chemical abnormality indicative
of another cause for the brittle bone disease.
Skeletal deformities, scoliosis, and hernias were
associated findings. A control group consisted of
16 normal volunteers matched on age, sex, and
refractive error to the patients with OI. All ages
matched within 2 years. This control group also
had the complete eye examination. For each variable, first the right eye then the left eye of each
person was measured. Statistical analysis involved
the paired t test and calculation of the intraclass
correlation coefficient.'
Results. Because each patient was matched to a
control, the paired t test provided a sensitive procedure for identifying differences between the patient group and the control group. For each variable, a value for each person was determined by
averaging the two eyes. The appropriateness of
this averaging was investigated by the intraclass
correlation coefficient, a measure of relatedness of
the two eyes, which accounts for the variation in
measurements between persons. An intraclass
correlation coefficient close to 1 indicated similar
measurements between eyes.
Only two variables (length of globe for patients
and corneal thickness for controls) had low (0.4)
intraclass correlation coefficients. This indicated
considerable variation between eyes (when compared with the variation between persons) and
808
Invest. Ophthalmol. Vis. Sci.
June 1981
Reports
Table II. Comparison of 0 1 patients and age-, sex-, and refractive error-matched
controls (16 pairs)*
Patients (N = 16)
Controls (N = 16)
Pair difference
(patient — control)
(N = 16)
Variable
Mean
S.D.
Mean
S.D.
Mean
Pupil size (mm)
Corneal diameter (mm)
Horizontal keratometry (diopters)
Vertical keratometry (diopters)
Corneal thickness (mm)
Anterior chamber (mm)
Applanation tomometry (mm Hg)
Palpebral fissure (mm)
Length of globe (mm)
Ocular rigidity (I" 1 )
4.5
10.7
42.9
44.7
0.58
3.3
14.7
21.3
22.8
0.015
1.2
0.6
1.7
1.5
0.11
0.3
2.3
1.1
1.0
0.004
4.1
11.4
43.5
44.7
0.58
3.6
13.5
22.1
24. Of
0.020
1.2
0.5
1.8
2.0
0.02
0.5
2.5
2.0
1.6
0.006
0.4
-0.6
-0.6
0.0
0.00
-0.3
1.2
-0.8
-1.2t
-0.005
S.D.
1.3
0.8
2.8
2.4
0.10
0.5
3.1
2.0
1.3
0.005
Significance
level
(two-sided
p value)
0.23
0.007
0.39
0.99
0.97
0.05
0.14
0.13
0.003
0.001
* Values for each person were determined by averaging the measurements of the two eyes.
t Length of globe for one control was unavailable; therefore calculations were based on a sample size of 15.
Table III. Ocular rigidity and blueness of
sclera in OI patients
Ocular rigidity*
Group 1. Blue sclera 0
to 2+
N = 7
Mean = 0.017
S.D. = 0.004
Group II. Blue sclera
3+ to 4 +
N = 13
Mean = 0.014
S.D. = 0.003
p = 0.04
* Ocular rigidity value for a person is the average of the two
eyes.
thus suggests caution in averaging values from the
eyes for these two variables. Therefore, with these
cautions, we were satisfied in averaging eyes.
Table II summarizes the comparison between
the patient group and the control group by the
paired t test with the average of the two eyes.
The mean ocular rigidity value was significantly
lower in the OI patients than that in the normal
controls (p = 0.001). The corneal diameter was
smaller in patients than that in controls (p =
0.007), and the A-scan for length of the globe indicated a small eye in patients as compared with controls (p = 0.003). No other values were significantly different between the two groups.
We also compared the scleral color (with respect
to blueness) to the ocular rigidity measurements of
12 of the 16 patients above and eight additional OI
patients (Table III). The 20 OI patients were divided into two groups; group I had sclera graded
blue from 0 to 2+ on external photographs,
whereas group II had sclera graded blue from 3+ to
4+. In group 1 the average ocular rigidity was
0.017, and in group II it was 0.014. This difference
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in ocular rigidity was significantly different at
p = 0.04 as determined by the Student's t test,
although the correlation of ocular rigidity and blueness of sclera (R = 0.25) was not significantly different from zero (p = 0.29).
Discussion. Ocular rigidity is a measurement of
the distensibility of the coats of the eye when the
cornea is indented with a weight, in this case a
Schiotz tonometer. Low ocular rigidity is sometimes associated with myopia. Thus it was most
important to have as controls normal volunteers
matched not only for age and sex but also for refractive error. Because there was a highly significant
difference between patients and controls, myopia
does not seem to explain the low ocular rigidity in
these patients.
It was of particular interest that the eyes in OI
patients tended to be smaller, as determined by
A-scan ultrasonography, which showed a decreased
corneal diameter and decreased overall globe
length. Since a smaller eye requires less fluid to
raise the intraocular pressure (IOP) the same
amount as a normal-sized eye, the low ocular rigidity in OI patients is even lower than measured. If a
small eye and a normal eye have the same elasticity
of the ocular coats, the small eye will require less
injected fluid than the large eye to produce the
same elevation oflOP. In the OI small eyes the low
ocular rigidity is indicated by the larger corneal
indentations produced by the tonometer. Therefore the decreased ocular rigidity cannot be the
result of the small eyeballs but rather is the result of
increased distensibility of the ocular coats. Although these data demonstrate the increased extensibility of the sclera, they contain no information
about the tensile strength of the ocular coats and
Volume 20
Number 6
should not be interpreted to indicate that these
eyes are more easily ruptured by internal pressure
than are normal eyes. What can be concluded is
that the decreased ocular rigidity and smaller eye
may be related to the developmental aspect of the
globe, reflecting an underlying biochemical abnormality in either the type of collagen produced or
the ratio of aj and a2 chains in type I collagen. These
determinations must await further investigation.
We detected no correlation between ocular
rigidity and blueness of sclera in patients with 01.
This may be the result of a number of factors such
as true independence between ocular rigidity and
blue sclera, the difficulty of having a truly linear
scale for blueness of sclera, or the small sample
size. Efforts continue to improve the measurement of scleral color and to increase the sample
size.
From the Clinical Branch, National Eye Institute,
National Institutes of Health, Bethesda, Md. (M.I.K.,
L.M., C.K.) Office of Biometry and Epidemiology, National Eye Institute, National Institutes of Health,
Bethesda, Md. (M.J.P.), Clinical Center, National Institutes of Health, Bethesda, Md. (J.R.S.), and Department of Pediatrics, University of Connecticut, Farmington, Conn. (D.R.). Submitted for publication Dec.
19, 1980. Reprint requests: Muriel I. Kaiser-Kupfer,
M.D., National Eye Institute, Building 10, Room
12S235, National Institutes of Health, Bethesda, Md.
20205.
Key words: ocular rigidity, osteogenesis imperfecta,
blue sclera
REFERENCES
1. Bell J: Introduction. In The Treasury of Human Inheritance, Pearson K, editor. Vol. II. Anomalies and
Diseases of the Eye. (Nettleship Memorial Volume).
Part III. Blue Sclerotics and Fragility of Bone. London, 1928, Cambridge University Press.
2. Smith R, Francis MJA, and Sykes B: The eye and
collagen in osteogenesis imperfecta. Birth Defects
13:563, 1976.
3. Snedecor GW and Cochran WG: Statistical Methods,
ed. 6. Ames, Iowa, 1967, Iowa State University
Press.
Flicker: a "decay" effect after light deprivation. ANNE CHRISTAKE CORNWELL.
The "decay" effect resulting from repetitive light stimulation at different flicker rates was investigated. Adult
cats were visually deprived monocularly or binocularly
for I or 2 weeks. The results showed a progressive decrease in the b-wave of the electroretinogram during the
Reports
later flashes in a train. The data are presented as percent
of the initial response to a flash. In the control eye the
b-wave stabilized rapidly after the initial flash in a train
of stimuli. Partial recovery occuired after 1 week of normal stimulation.
Monocular light deprivation over a brief period
causes changes in the b-wave of the electroretinogram (ERG). The b-wave is decreased in amplitude
to a single flash and wanes to a train of flashes. l~4
The deprived eye is sensitive to both the frequency
and intensity of the stimuli. The b-wave of the
nondeprived eye, however, does not show a similar
progressive decrease. After the initial rapid rise in
amplitude, it stabilizes to a constant fraction of the
initial response at slow flicker rates. 5
Light deprivation for 1 week or longer clearly
affects certain retinal response properties. These
ERG changes reflect the sensitivity of the eye to
restrictions of light input and the subsequent inability of the retina to sustain a normal response
during flicker.
A lack of resolution of intermittent light flashes
was shown in the normal all-rod skate retina.(> A
decreased ERG b-wave and reduced ganglion cell
activity were recorded during flicker. In the cat,
however, the retinal neural structures or their
mechanism of action may differ. Cats have both
cones and rods, although the latter predominate
(rod-cone ratio = 10.5:1 in area centralis, 66:1 in
periphery, and 100:1 in ora serrata).' It can be
hypothesized from these findings that the normal
activity of the photoreceptors in the cat retina may
be disrupted by light deprivation and result in a
"decay" effect during flicker.
This decay effect after light deprivation was investigated in this study with different flicker rates.
This would maximize the b-wave reduction in the
deprived eye but would leave the normal eye virtually unaffected. The progressive decrease in
b-wave amplitude during flicker was also studied,
since this decay phenomenon is affected by the
cumulative effects of light input.
Materials and methods. The data are based on
the averaged ERG b-wave from the right and left
eye of two adult cats deprived monocularly for 2
weeks and of two cats deprived binocularly for 1
week. The ERG was recorded from both eyes simultaneously before and immediately after deprivation. Recovery was tested 1 week after the end
of monocular deprivation.
The procedure followed in the present study
was previously described. 1 The monocularly deprived animals were anesthesized with pentobarbital (Nembutal) and were deprived of all light by
means of a black plastic bulbous disc sutured to
0146-0404/81/060809+04$00.40/0 © 1981 Assoc. for Res. in Vis. and Ophthal., Inc.
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809