Download Diabetic short-wavelength sensitivity: variations with induced

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Diabetic Short-Wavelength
Sensitivity: Variations With Induced
Changes in Blood Glucose Level
VickiJ. Volbrecht,* Marilyn E. Schneck,*
Anthony J. Adams,* John A. Linjoot,\
and Everett Ai%
Purpose. To investigate variations in diabetic shortwavelength sensitivity with acute, induced changes in
blood glucose level.
Methods. Increment threshold measures were obtained
for short-wavelength-sensitive and middle/longwavelength-sensitive cone pathways after an induced,
acute change in blood glucose level in diabetic observers.
Results. Diabetic observers showed an increase in shortwavelength sensitivity, but no change in middle/longwavelength sensitivity, with a rapid drop in blood glucose level.
Conclusions. Experimentally induced changes in diabetic blood glucose levels can directly affect diabetic
short-wavelength sensitivity. Invest Ophthalmol Vis Sci.
1994;35:1243-1246.
At is well documented that individuals suffering from
diabetes display color vision losses. This color vision
loss is substantiated by spectral sensitivity measures
that show diabetic short-wavelength (SW) sensitivity
lower than that of nondiabetics.1"4 Furthermore, SW
sensitivity fluctuates across days of measurement,
whereas middle- and long-wavelength (M/LW) sensitivity remains relatively stable.4 Others have demonstrated similar color vision variations with the FM 100hue test. For example, Harrad et al5 administered the
FM 100-hue test at three different blood glucose levels. When subjects with diabetes were hypoglycemic
(low blood glucose level), their performance on the
FM 100-hue test was poor; but as their blood glucose
increased, their performance improved. This suggests
that the fluctuations in SW sensitivity may be attributable to differences in blood glucose levels across test
sessions.
From the *School of Optometry, University of California, Berkeley, the -\Diabetes
ami Endocrine Institute, Summit Medical Center, Oakland, and the ^Department
of Ophthalmology, California Pacific Medical Center, San Francisco, California.
Supported by National Institutes of Health grant EY02271 (AfA), Bethesda,
Maryland.
Submitted for publication May 20, 1993; revised August 23, 1993; accepted
August 24, 1993.
Proprietary interest category: N.
Reprint requests: VickiJ. Volbrecht, Department of Psychology, Colorado State
University, A21A Clark, Fort Collins, CO 80523.
The current study systematically investigated the
relationship between blood glucose level and SW sensitivity in subjects with diabetes. Measurements of SW
sensitivity and M/LW sensitivity were made under
conditions of induced hyperglycemia (high blood glucose level) as well as during a 2-hour period in which
blood glucose level was rapidly decreased. Diabetic
SW sensitivity was directly affected by changes in
blood glucose level, whereas M/LW sensitivity was not.
MATERIALS AND METHODS. Subjects. Eighteen patients with diabetes at the Diabetes and Endocrine Institute of Providence Hospital in Oakland, California, participated in this study. The volunteers were
either recently diagnosed as diabetic or had a history
of poor metabolic control under conventional treatment. Table 1 summarizes the characteristics of these
patients. Mean visual acuity as assessed with the highcontrast Bailey-Lovie eye chart was 0.0 log MAR
(range: —0.24 to 0.19 log MAR). All but one observer,
a congenital deutan, were color normal according to
the FM 100-hue test, D-15 test panel test, and the
Adams desaturated D-15 test, and thus showed no evidence of a tritan color loss.
Informed consent was obtained from all subjects
with diabetes after information was provided as to the
nature and purpose of the experiment. The experimental methods followed the guidelines established by
the Declaration of Helsinki, and was approved by the
University of California and Providence Hospital human subject committees.
Stimulus and Apparatus. A portable, two-channel, rear-view projection optical system interfaced
with a Macintosh SE computer (Apple, Cupertino,
CA) was used to make threshold measures. One channel of the optical system projected a 6°, 200 cd/m2
yellow adapting background (Xd = 586 nm; xx = 0.55,
yx = 0.45) onto the viewing screen. This adapting
background was divided into two equal parts by a
narrow horizontal black line. The second optical channel randomly presented a 1.5°, 300 millisecond test
stimulus either above the black line or below the black
line. The distance from the edge of the test stimulus to
the black line was approximately 1° of visual angle. A
Wratten 47B broad-band filter defined the spectral
properties of the SW test stimulus; the dominant wavelength as specified by the manufacturer's guidelines
for a tungsten source used in this optical system was
452 nm. The spectral composition of the M/LW test
stimulus was the same as the adapting background.
Procedure. Threshold measures were obtained
for diabetic subjects at varying blood glucose levels.
Investigative Ophthalmology & Visual Science, March 1994, Vol. 35, No. 3
Copyright © Association for Research in Vision and Ophthalmology
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Investigative Ophthalmology & Visual Science, March 1994, Vol. 35, No. 3
1244
TABLE l.
Patient
No.
Diabetic Observers
Gender
Age
(yr)
Diabetes
Type
Duration of
Diabetes (yr)
1
2
F
M
18
33
I
I
12
22
3
M
45
I
26
4
5
6
7
8
9
10
11
12
13
14
M
F
F
M
F
M
F
M
M
F
M
26
47
31
36
47
48
49
50
53
55
61
I
I
II
II
II
II
II
II
II
II
II
0
12
1
5
8
0
1
3
6
6
17
15
16
F
M
61
65
II
II
27
17
18
M
M
66
41
II
II
7
0
The specific methods used to measure threshold and
to manipulate blood glucose level are outlined below.
Threshold Measures. Observers monocularly
adapted for 1 minute to the yellow background. After
this initial adaptation, a single-staircase, two-alternative, forced-choice procedure was used to measure the
M/LW threshold, followed immediately by a measurement of the SW threshold. Because each threshold
measurement took approximately 2 minutes, at least 3
minutes of adaptation to the yellow background preceded measurement of the SW threshold. Adams et
al,6 using a variant of this procedure, demonstrated
that this particular adaptation period successfully isolated the short-wavelength-sensitive (SWS) mechanism. Initial step size for stimulus intensity in the staircase was 1 log unit, and was continuously decreased by
one half over a series of reversals to the smallest step
size of 0.125 log unit. At the larger step sizes (1.0 and
0.5 log unit), one correct answer decreased the stimulus intensity and one incorrect answer increased the
stimulus intensity. At the smaller step sizes (0.25 and
0.125 log unit), three correct answers made the test
stimulus dimmer, and one incorrect answer made the
test stimulus brighter.
Observers were instructed to fixate on the center
of the horizontal dividing line on the adapting field
and respond whether the test stimulus appeared above
or below the black line by pressing the appropriate
button. The staircase continued until four reversals
were obtained at the smallest step size. A mean threshold was computed from the four threshold values
8
Status of
Retinopathy
None
Moderate background
No macular edema
Mild background
Minimal macular edema
None
None
Not available
None
None
None
None
Not available
None
None
Mild background
No macular edema
None
Mild background
Minimal macular edema
None
Not available
ascertained at the last four reversals. A mean value was
accepted only if the standard deviation was less than
0.25 log unit. Whenever possible, the staircase was repeated for standard deviations greater than or equal
to 0.25 log unit; however, time constraints sometimes
precluded repeated testing.
The same procedure was repeated to obtain SW
and M/LW thresholds for the other eye. Only data
from one eye of an observer were used in the analyses.
Whenever possible, data from the right eye were used;
however, data from the left eyes of four diabetic subjects were used because the standard deviations of the
critical measurements of the right eye exceeded the
criterion for inclusion (standard deviation > 0.25 log
unit), only the left eye was tested, or technical problems occurred during testing of the right eye.
Insulin Administration. Twenty-four hours before
an experimental session, the observers with diabetes
refrained from taking their medication, maintaining
their restricted diet, or both, thereby inducing hyperglycemia. At the start of the experimental sessions, the
diabetic subject's hyperglycemic blood glucose level
was determined, followed by measurements of M/LW
and SW thresholds.
After these measurements, insulin administration
commenced. Each diabetic subject received a bolus
injection of insulin and a continuous, intravenous infusion of insulin for up to a 2-hour period. The
amount of insulin varied for each individual, depending on his or her high blood glucose value at the start
of the session, known sensitivity to insulin, and past
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1245
medical history. (The amount of insulin received by
injection ranged from 6 to 25 units of insulin. The
amount of insulin received by infusion ranged from 4
to 25 units per hour). Diabetic subjects were monitored continuously by medical personnel, who determined when the subject's blood glucose level had
reached a level sufficiently low to terminate infusion.
Ten minutes after insulin injection and commencement of infusion, a blood glucose measure was taken,
followed by M/LW and SW threshold measurements
for each eye. This procedure of blood glucose and
threshold measurements was repeated 20, 30, 45, 60,
90, and 120 minutes after the initial insulin administration.
RESULTS. To examine the effect of acute, rapid
changes in blood glucose on visual function in subjects
with diabetes, the SW and M/LW sensitivity values obtained at the highest blood glucose level were compared to the corresponding measures obtained at the
lowest blood glucose level, which, depending on the
individual, occurred 30 to 120 minutes after insulin
administration. The high and low blood glucose values
are specified in Table 2. For inclusion in the data analysis, the high and low blood glucose values needed to
differ by at least 100 mg/dl, or the low blood glucose
value needed to fall below 150 mg/dl, a blood glucose
level considered to be the upper limit of the normal
range for nondiabetic people. It was expected that if
either criterion was not attained, a significant physio-
TABLE
2. Blood Glucose Levels of Diabetics
Blood Glucose
Levels (mg/dl)
Patient
No.
Log Differences
High
Low
sws
M/LWS
1
>500
2
384
261
356
397
204
395
347
207
362
213
323
216
310
242
153
85
34
-0.12
0.47
-0.10
0.19
0.04
0.03
0.11
-0.49
0.56
0.01
0.10
0.53
0.16
-0.01
0.17
0.05
0.08
0.32
0.28
0.40
0.30
0.25
0.07
-0.07
0.05
-0.05
-0.12
-0.23
0.16
-0.33
0.14
0.00
0.00
0.22
3
4
5
6
7
8
9
10
11
12
13
14
15
16
17
18
>500
418
277
77
315
64
149
90
40
85
64
151
130
73
49
126
277
57
The high blood glucose readings of two of the patients exceeded
the maximum reading (500 mg/dl) of the glucometer used in this
study. Their values are denoted as >500.
srenc
Reports
0.8
0.6
0.4
D)
0.2
0.0
5 o
-0.2
w
-0.4
c
<D
CO
O>
-0.6
-0.8
SWS
M/LWS
FIGURE l. Log differences in short-wavelength sensitivity
(middle/long-wavelength sensitivity) obtained at high and
low blood glucose levels are shown on the left (right) side of
the figure. The horizontal line represents no difference.
logical change would not occur, and subsequently visual sensitivity would not be influenced. As a result of
these criteria, the data from one observer (patient No.
5) were excluded from this analysis.
When more than one sensitivity measure was
taken at a given time, a mean was computed from
those values with a standard deviation less than 0.25
log unit. The mean standard deviations across observers was 0.13 log unit (range: 0.02 to 0.23 log unit).
The log sensitivity differences are specified in Table 2, and the results are presented in Figure 1; differences are plotted on the left side of the figure and
M/LW sensitivity differences are plotted on the right.
Positive values indicate higher sensitivity at the low
blood glucose level than at the high blood glucose
level, whereas negative values indicate higher sensitivity at the high blood glucose level than at the low blood
glucose level. For the diabetic observers, most of the
SWS differences fall above the horizontal line, indicating an increase in sensitivity with a decrease in blood
glucose. These SW sensitivity differences are statistically significant as determined by a one-tail, paired /
test (*16 = 3.92, P < 0.0005). The M/LW sensitivity
differences show no systematic change in sensitivity
with changes in blood glucose, as demonstrated by an
approximately even number of points falling above
and below the horizontal line (t16 = -0.28, P > 0.39).
The familywise error for the two multiple tests was
0.05, with a significance level of 0.025 for each individual test.7
DISCUSSION. This study demonstrates that the
SWS cone pathway of the visual system is dynamically
responsive to transient changes in blood glucose level.
To our knowledge, this is the first reported selective
increase in diabetic SW sensitivity with an acute reduction in blood glucose level.
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Investigative Ophthalmology 8c Visual Science, March 1994, Vol. 35, No. 3
Although it is now well established that a variety of
ocular and systemic diseases, including diabetes, are
harmful to the SWS cone pathway, causing a decrease
in SW sensitivity,2"4-9 the site(s) of the loss is not well
known. The loss in SW sensitivity in diabetes has been
variously attributed to changes in the lens, loss of SWS
cone receptors due to their greater vulnerability to
insult, the reduced response range of normal SWS
cones relative to LWS cones,8 and postreceptoral SWS
functional losses either at the opponent site9 or
beyond the opponent site.910
The acute and reversible nature of SW sensitivity
observed in this study constrains the choice of potential sites and mechanisms to explain this effect.
Clearly, the current results imply that at least part of
the SWS loss in diabetes cannot be ascribed to increased lens density or photoreceptor loss, because
neither of these events is likely to be reversible. The
current results, however, may reflect functional
changes at the receptoral level or at a postreceptoral
site(s) at or beyond the opponent site, but the exact
locus still needs to be isolated. The results do suggest
that the changes in SW sensitivity are directly related
to the transient metabolic state of diabetes and immediately tied to diabetic blood glucose levels, rather
than to structural damage of vascular or neural tissues
presumed to be involved in the SWS pathway loss in a
variety of retinal diseases.
Key Words
diabetes, blood glucose, short-wavelength sensitivity, metabolic control
Scotopic Optokinetic Nystagmus
Thresholds in 10-Week-Old Infants
Ronald M. Hansen and Anne B. Fulton
Purpose. To compare psychophysical and reflexive optokinetic nystagmus (OKN) estimates of dark-adapted
scotopic thresholds mediated by the posterior retina in
10-week-old infants and adults.
Methods. A staircase procedure was used to determine
the stimulus intensity needed to produce an OKN response to a moving 19° X 19° grating. In the same sub-
From the Department of Ophthalmology, Children's Hospital, and the Department
of Ophthalmology, Harvard Medical School, Boston, Massachusetts.
Supported by National Eye Institute grant EY05325
Submitted for publication July 6, 1993; revised August 23, 1993; accepted August
24, 1993.
Proprietary interest category: N.
Reprint requests: Dr. Ronald M. Hansen, Department of Ophthalmology,
Children's Hospital, 300 Longwood Avenue, Boston, MA 02115.
References
1. Greenstein V, Sarter B, Hood D, Noble K, Carr R.
Hue discrimination and S cone pathway sensitivity in
early diabetic retinopathy. Invest Ophthalmol Vis Sci.
1990;31:1008-1014.
2. Adams AJ. Chromatic and luminosity processing in retinal disease. Am J Optom Physiol Opt. 1982; 59:954960.
3. Greenstein VC, Hood DC, Ritch R, Steinberger D,
Carr RE. S (blue) cone pathway vulnerability in retinitis pigmentosa, diabetes and glaucoma. Invest Ophthalmol Vis Sci. 1989;3O:1732-1737.
4. Zisman F, Adams AJ. Spectral sensitivity of cone mechanisms in juvenile diabetics. Doc Ophthalmol Proc Ser.
1982;33:127-131.
5. Harrad RA, Cockram CS, Plumb AP, et al. The effect
of hypoglycemia on visual function: a clinical and electrophysiological study. Clin Sci. 1985;69:673-679.
6. Adams AJ, Schefrin B, Huie K. New clinical color
threshold test for eye disease. Am] Optom Physiol Opt.
1987;64:29-37.
7. Keppel G. Design and Analysis. 3rd ed. Englewood
Cliffs, NJ: Prentice Hall; 1991.
8. Hood DC, Benimoff NI, Greenstein VC. The response range of the blue-cone pathways: a source of
vulnerability to disease. Invest Ophthalmol Vis Sci.
1984;25:864-867.
9. Greenstein VC, Shapiro A, Zaidi Q, Hood DC. Psychophysical evidence for post-receptoral sensitivity
loss in diabetics. Invest Ophthalmol Vis Sci. 1992;
33:2781-2790.
10. Schefrin BE, Adams AJ, Werner JS. Anomalies
beyond sites of chromatic opponency contribute to
sensitivity losses of an S-cone pathway in diabetes. Clin
Vis Sci. 1991;6:219-228.
jects, a two-alternative, forced-choice procedure was
used to obtain thresholds for detecting 10° diameter,
50 ms duration stimuli.
Results. Both OKN and psychophysical thresholds of infants are 0.9 log unit higher than those of adults.
Conclusion. The infant-adult difference in thresholds
mediated by retina at the posterior pole is greater than
the infant-adult difference in thresholds for full-field
stimuli. It is possible that delayed maturation of the posterior retina is the primary determinant of infants' high
OKN and psychophysical thresholds. Invest Ophthalmol Vis Sci. 1994; 35:1246-1249.
1 he dark-adapted, rod-mediated thresholds of young
human infants are significantly higher than those of
adults.1"5 However, the magnitude of the threshold
elevation is not constant across procedures. At age 10weeks, dark-adapted infants' scotopic ERG 235 and
VEP4 thresholds for full-field stimuli are only about
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