ACTA 0 P H T H A L M 0 L O G I C A 70 (1992) 659-664

Visual dysfunction in type II diabetic patients revealed by a hyperacuity test

Russell Watkins’ and Terry Buckingham’

Department of Ophthalmology’, Clinical Sciences Building, Leicester Royal Infirmary, Leicester, Department of Optometry*, University of Bradford, Bradford, U.K.

Abstract. Displacement thresholds for an oscillating bar, which fall into the hyperacuity range, were deter- mined in 21 subjects with non-insulin dependent diabetes mellitus and 19 age-matched visually normal controls. The diabetic subjects were classed as either hav- ing minimal or no retinopathy. Whilst thresholds for the diabetic group were significantly raised above those of the normal group, there were no significant differences in thresholds between the diabetic subgroup with retino- pathy and the subgroup without. Greater thresholds tended to be found at higher frequencies of oscillation as the known duration of the diabetes increased.

Key words: psychophysics - hyperacuity - NIDDM - diabetic retinopathy.

Patients with diabetes mellitus often show evi- dence of abnormal central vision before they de- velop overt diabetic retinopathy (Trick et al. 1988). Abnormalities of colour vision, contrast sensitivity, the electroretinogram (ERG) and the visual evoked response (VER) have been reported in these pa- tients (Lakowski et al. 19721’73; Ghafour et d. 1982; Puvanendran et al. 1983; Bresnick et al. 1985; Sokol et al. 1985; Jenkins 8c Cartwright 1990; Hardy et al. 1992). Although the underlying pathophysiology of these visual abnormalities is unknown, they are considered to be evidence of neurosensory dys- function that may precede the development of diabetic retinal microangiopathy (Bresnick 1986). There is no doubt, however, that the retinal micro- angiopathy itself is a significant factor in the visual dysfunction of patients with diabetes mellitus.

Nevertheless, the exact interrelationship between the nature of the visual dysfunction and the state of the retinopathy remains poorly defined.

Recently, the psychophysical investigation of various visual system disorders using hyperacuity tasks has attracted much interest. This is because hyperacuity tasks, which produce thresholds much smaller than resolution acuity (hence the term ‘hyperacuity’ (Westheimer 1975)), behave differ- ently to resolution acuity. For instance, some hyperacuity tasks are resistant to the effects of image degradation and blur (Essock et al. 1984; Enoch et al. 1985a,b; Williams et al. 1985; Whitaker & Buckingham 1987). Likewise, in the presence of visual dysfunction, hyperacuity thresholds are raised in spite of visual acuity being normal (Wat- kins & Buckingham 1991; Watkins et al. 1991). Hyperacuity tasks must, therefore, be processed in a different way to resolution acuity.

One task that produces thresholds in the hyper- acuity range in normal vision is the oscillatory movement displacement threshold (OMDT) which can be defined as the smallest amplitude of dis- placement that elicits the perception of movement for a given temporal frequency of oscillation. The oscillation is usually sinusoidal but can be square- wave or triangular-wave. OMDT are thought to be mediated primarily by the magnocellular pathway (Watkins & Buckingham 1992) and have the property of being unaffected by image degrada- tion (Buckingham & Whitaker 1987).

We measured OMDT in subjects with non in-

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sulin dependent (or Type 11) diabetes mellitus (NIDDM). The aim of this experiment was to examine the interrelationships between known duration, level of retinopathy, visual acuity and OMDT to see if this particular hyperacuity task re- vealed a detectable abnormality in patients with NIDDM and normal visual acuity both with and without retinopathy.

Age (years)

Subjects

Diabetic subjects were included in this study if they met the following strict criteria:

1) LogMAR score of less than 0.00 (6/6 Snellen equivalent);

2) no history of previous eye disease other than diabetic retinopathy;

3) no concurrent other eye disease or amblyopia in either eye;

4) no systemic disease, other than NIDDM, con- sidered likely to affect results;

5) no visual field defect detected using the Fried- mann VFA MkII;

6) IOP less than 22 mmHg using the Goldmann Applanation Tonometer;

7) no lens opacity in the undilated pupil area visible with a direct ophthalmoscope;

8) hypermetropia less than + 6.00 DS and myopia less than -4.00 DS with no cylindrical compo- nent greater than - 2.50 DC.

Twenty-one subjects with NIDDM and minimal or no retinopathy fulfilled the criteria and were re- cruited to the study from the Diabetic Eye Disease Screening Service and an antiretinopathy drug trial (before the subjects began the trial), both based at the University of Bradford. Informed con- sent was obtained from all subjects. The age of this group ranged from 46 to 64 years. The known dur- ation of the diabetes ranged from 2 years to 27 years. The known duration of NIDDM was inde- pendent of age. The retinopathy in each subject was graded according to the Modified Airlie House Classification System described by Davis et al. (1985). The subjects reported in the present ex- periment were graded as level 10 if no retinopathy was present and level 20 if one or more microaneu- rysms only were present. Accordingly, 13 subjects were graded as level 10 and 8as level 20. The clini- cal details of these patients are given in Table 1.

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Duration Retinopathy LogMAR (years) level score

1 46 3 2 49 4 3 51 27 4 53 8 5 54 20 6 55 10 7 55 2 8 57 5 9 58 1 1

10 58 4 11 58 8 12 64 3 13 64 8

14 50 15 51 16 54 17 57 18 58 19 58 20 61 21 61

26 12 8

10 21 3 8 8

10 10 10 10 10 10 10 10 10 10 10 10 10

20 20 20 20 20 20 20 20

-0.06 -0.10 -0.06 -0.04 -0.10 -0.02 -0.08 -0.10 -0.08 -0.06

0.00 -0.06 -0.08

-0.08 0.00

-0.06 -0.12

0.00 -0.10 -0.08

0.00

Nineteen age-matched non-diabetic controls were also recruited to the study using the same in- clusion criteria. These subjects were gathered from the spouses of the NIDDM subjects and staff of the University of Bradford. Their ages ranged from 40 to 68 years.

Apparatus

An oscillating stimulus and two stationary ref- erence lines were generated onto a Kikusui Cos 1711 CRT (P31 phosphor; frame rate 200 Hz) using an Innisfree ‘Picasso’ CRT Image Synthesiser. Os- cillatory movement was programmed using a Qubie HR39 ‘Basic Time’ microcomputer. The ob- server viewed the CRT screen through a mirror such that the effective distance was 6 m. The aver- age luminance of the CRT screen was 63 cd/m2. The luminance of the stimulus and stationary ref- erences was 135 cd/m2 whilst the luminance of the background was 15 cd/m2. This resulted in Michel- son contrast of 80%. The stimulus was 30 min arc vertically by 5 min arc horizontally and the station- ary references were 1 degree vertically by 14 min arc horizontally. The stimulus was situated midway

OMDT (” arc)

0 2 4 6 8 10 12 14

Temporal Frequency (Hz)

Fig. 1. OMDT plotted on a log scale as a function of temporal frequency for the group of subjects with NIDDM and no visible retinopathy (open squares), those with minimal retinopathy (open circles) and the age-matched control group (solid

circles). SEMS are shown. See text for details.

between the two stationary references such that the distance from the edge of the stimulus to the edge of the reference was 4.5 min arc.

Test principles and procedure

At the start of the testing session, subjects adapted for 7 min to the dimmed ambient light level. OMDT were measured using a two-alternative temporal forced-choice staircase, which measured the 71% correct detection level on the psychome- tric function. The displacement amplitude was in- cremented following each incorrect response and decremented following two correct responses. Am- plitude was initially changed in 32 sec arc steps but after the second, third and fourth reversal, ampli- tude changed in 16,s and 4 sec arc steps, respec- tively (Levitt 1970). Each trial was ended after six reversals and threshold was estimated from the mean of the last four reversals.

Table 2. LogMAR scores.

I I I

Age-matched control group -0.09 0.01 0.06 NIDDM group -0.07 0.01 0.04

The stimulus was oscillated horizontally be- tween the stationary references for two 3 sec inter- vals, indicated by a single or double tone. During one randomly selected interval, the stimulus oscil- lated sinusoidally between the stationary referen- ces. During the other interval, the stimulus did not oscillate. The subject denoted in which interval the stimulus was oscillating, by answering with ‘one’ or ‘two’. The answer was entered into the computer by the experimenter and feedback was provided. The temporal frequencies of oscillation investigated were 1,4, 7, 10 and 13 Hz.

Visual acuity was measured on the LogMAR chart. Any necessary refractive correctionwas worn and OMDT and LogMAR scores were determined monocularly in the dominant eyes (determined by the ‘sighting‘ method) of the controls and the eyes with the better visual acuity of the diabetics. In- variably, the dominant eyes of the controls had the better visual acuity. Natural pupils were used in all cases.

Results

A Mann-Whitney test confirmed that the ages of the diabetics and of the age-matched group were not significantly different and those with level 10 retinopathy were age-matched with those with level 20 retinopathy. The group of subjects with

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OMDT lOHz (" arc)

20 +----A 0 10 20 30

DURATION (YRS)

Fig. 2. A scattergram of OMDT at 10 Hz plotted as function of duration of diabetes for the group of diabetics as a whole. The

equation of the regression line is y = l .lx+ 41.2. r = 0.4408. See text for details.

level 20 retinopathy tended to have been known diabetics for longer. This, of course, is to be ex- pected since the development of diabetic retino- pathy is duration dependent. A t-test confirmed that the LogMAR scores of the age-matched con- trol group (see Table 2) were not significantly dif- ferent to those of the diabetics. A chi-squared test for normality indicated that the OMDT and known duration data could be considered as being nor- mally distributed and so parametric methods were used to evaluate the results. A Bartlett test for ho- mogeneity of variances indicated that the OMDT data were homoscedastic.

From Fig. 1, it appears that OMDT for the diabe- tics both with no and minimal retinopathy are raised above those of the age-matched group. This is confirmed by a two-way analysis of variance that reveals a signifcant effect of NIDDM (F2,185 = 11.87, p<O.OOl) and temporal frequency (F4,185 = 20.53, p<O.OOl). There was no significant interaction ef- fect which indicates that the functions are of simi- lar shapes. An analysis of variance also revealed that there was no significant difference between the diabetics with no (level 10) retinopathy and those with minimal (level 20) retinopathy (F,,,,= 0.99, p = ns).

For the group of diabetics as a whole, there were no significant correlations between the level of re- tinopathy and the known duration, LogMAR score or OMDT at any temporal frequency. Likewise, LogMAR score did not correlate significantly with known duration or OMDT at any temporal fre-

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quency. These observations highlight the dif- ference in processing mechanisms of resolution acuity on the one hand and hyperacuity tasks on the other. Whilst there were no signifcat correla- tions between the known duration and OMDT at 1, 4 and 7 Hz, there were significant correlations (see Figs. 2 and 3) between known duration and OMDT at 10 Hz (r = 0.4408, p = 0.045) and OMDT at 13 Hz (r = 0.5440, p = 0.011).

Individual OMDT measurements were classed as abnormal if they fell more than 2 standard devia- tions beyond the age-matched control mean. On the basis of this criterion, 62% of the diabetics with no retinopathy and 75% of the diabetics with mini- mal retinopathy exhibited a signifcant increase in OMDT for at least one temporal frequency. In- creases in OMDT were observed at all temporal fre- quencies and were apparent most often at a tempo- ral frequency of 4 Hz and least often at a temporal frequency of 10 Hz. All except one subject exhibited an increase in OMDT at more than one temporal frequency of oscillation. Of the age-matched con- trols, only one subject (0.5%) exhibited significant increase in OMDT.

Discussion

OMDT are raised in subjects with NIDDM com- pared to visually normal subjects of equivalent age. This is evident in those with no retinopathy as well as those with minimal retinopathy and, per-

OMDT 13Hz (” arc)

3

A scattergram of OMDT at 13 Hz plotted as function of duration of diabetes for the group of diabetics as a whole. The equation of the regression line is y = 2.9x+ 48.4. r = 0.5440. See text for details.

haps surprisingly, OMDT are raised to a similar ex- tent in level 10 and level 20 retinopathy. The two subgroups of diabetics presented here are too small to make any firm conclusions on this matter but it is interesting that a recent paper (Hardy et al. 1992) described colour vision abnormalities in Type 1 diabetics with angiopphically normal reti- nae. Significant increases in OMDT were noted in 67% of the NIDDM subjects with no retinopathy and 75% of the subjects with minimal retinopathy. These are somewhat higher percentages than is seen in reports on hue discrimination and contrast sensitivity. For example, Bresnick et al. (1985) noted that 41% of subjects with background retino- pathy exhibited scores that fell outside the 95” percentile of the published norms for the FM 100 Hue Test. Furthermore, this result was obtained for severe (preproliferative) background retino- pathy. Trick et al. (1988) observed significant con- trast sensitivity reductions in 24% of diabetics with no retinopathy and 45% of diabetics with ‘mild-to- moderate’ retinopathy. Della Salla et al. (1985) noted contrast sensitivity reductions in 41% of diabetic subjects with no retinopathy and 30% of diabetic subjects with background retinopathy. Sokol et al. (1985) found significant contrast sensi- tivity abnormalities in 28% of their level 10 diabe- tics and 59% of their diabetics with retinopathy. OMDT, it appears, are more sensitive to diabetic visual changes than contrast sensitivity and hue discrimination.

Whilst hyperacuity tasks are processed at higher levels of the visual cortex, a healthy retina (Watkins 1991) and optic nerve (Watkins & Buckingham 1991; Watkins et al. 1991) are necessary to transmit visual information ot visual cortex. Neuronal de- generation in the retinal ganglion cell layer and re- tinal nerve fiber layer is one of the earlies changes in diabetic retinopathy (Bloodworth 1962) and these degenerative changes are independet of vas- cular changes (Adams 1963). Since the retinal gan- glion cells and their axons carry the sampled reti- nal image information it is understandable that OMDT are raised in NIDDM.

It is interesting that OMDT for 10 Hz and 13 Hz tend to increase with the duration of NIDDM. Two subsystems are involved in the detection of relative oscillatory movement (Tyler & Torres 1972; Buck- ingham & Whitaker 1986; Buckingham et al. 1991) and it seems that the subsystem responsible for the detection of the higher oscillation frequencies becomes more sensitive to diabetic visual change as time goes by. However, this can only be speculative because of the dficulty in determining the exact duration of NIDDM as many NIDDM subjects are diabetic for some years before being diagnosed.

In conclusion, a hyperacuity task in the form of OMDT reveals a visual abnormality in subjects with NIDDM whether they have started to develop visible retinopathy or not. Further studies are on- going to determine the potential clinical applica- tions of such tasks.

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Acknowledgments

The authors would like to thank Nick Strong PhD FCOphth for his comments on an earlier draft of this manuscript. We are also grateful, as ever, to the subjects seen in this study. This work was supported by the Dol- lond and Aitchison Group.

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Received on December 19th 1991.

Author's address:

Dr Russell Watkins, Department of Ophthalmology, Clinical Sciences Building, PO Box 65, Leicester Royal Infirmary, Leicester, LE2 7LX.