- Email: [email protected]
Visual acuity of low- and high-risk neonates and acuity development during the first year
Behavioural Brahl Research, 49 (1992) 107-I 14 9 1992 Elsevier Science Publishers B.V. All rights reserved. 0166-4328/92/$05.00
107
BBR 01320
Visual acuity of low- and high-risk neonates and acuity development during the first year A.E. Ipata a, G. Cioni a, A. Boldrini b, P. B o t t a i a a n d J. v a n H o f - v a n D u i n c a Institute of Child 1Veurology and Psychiatry, Unirersity of Pisa and Stella Maris Foundation, Calambrone. Pisa (ltal)9, t'Neonatal Intensive Care Unit, University of Pisa, Pisa (Italy} and ~Department of Physiology I, Erasmus Unirersity Rotterdam, Rotterdam (The Netherlands) (Received 11 March 1992) (Accepted 15 April 1992)
Key words: Visual acuity; Preterm; Fullterm; Neonate; Risk factor; Acuity card; Neonatal injury; Ultrasound; EEG; Leukomalacia
Binocular grating acuity of 65 neonates was measured using Teller acuity cards/At the time of testing, age corrected for prematurity ranged from - 3 weeks to 2 weeks. On the basis of clinical data, serial ultrasound scans and EEG recording newborns were divided in!o 4 subgroups: fullterm low-risk (FLR, n - 22); preterm low-risk (PLR, n = 20); preterm medium-risk (PMR, n = 9) and preterm high-risk (PHR, n = 14). Mean visual acuity of PLR infants (0.86 cy/deg; S.D. 0.34 oct) was not significantly different from that of FLR newborns (0.80 cy/deg; S.D. 0.71 oct); the lower variability of the PLR infants might possibly be caused by their longer postnatal experience. Within the preterm groups, mean visual acuity of PLR newborns was found to be significantly higher than that of PMR (0.73 cy/deg; S.D. 0.26 oct) and PHR infants (0.73 cy/deg; S.D. 0.35 oct). This difference can not be explained by dissimilarities in postnatal or corrected"age. Brain impairment, as documented by US scans and EEG recording could account for these findings. Longitudinal data are needed in order to substantiate these findings and correlate them with later neurological and neuro-imaging outcome. Preliminary results of an ongoing longitudinal study suggest acuity development of most, but not all, PHR infants, in whom a cystic-periventricular leukomalacia had been diagnosed, to be worse than that Of low- and medium-risk infants.
INTRODUCTION
Although there is general agreement that visual acuity is very poor at birth, actual values reported by various authors differ. There are not only large quantitative differences between behavioural and electrophysiological data, but also within techniques diverging acuity values have been reported. The mean visual acuity, estimated in healthy newborns during the neonatal period with the forced-choice preferential looking procedure (FPL), ranges across various laboratories between 0.25 and 1.1 cycles per degree (cy/deg) 2'3'8't2'a~ Using the acuity card procedure 19, these values were found to range between not-testable 5 and 1.1 cy/ deg 9"17'22 during the neonatal period, and when acuity was assessed by means of a modified version of the acuity cards (the so-called one-aperture acuity card) between 0.705 and 1.1 cy/deg 9. The variability range
Correspondence: G. Cioni, Institute of Child Neurology and Psychiatry, University of Pisa and Stella Maris Foundation, 56018 Calambrone, Pisa, Italy.
reported in these various studies lies between 0.4 and 0.8 octaves. Electrophysiological studies have yielded neonatal acuity estimates varying between 0.25 cy/deg 3, 0.85 cy/deg 2, 3 cy/deg 4 to 4.523 and 5 cy/deg 24. Discrepancies between acuity values obtained with behavioral and electrophysi010gical techniques have been reported earlier. However, some studies claimed to find no significant differences between FPL and VEP acuity estimates obtained at term age 3, and even from birth to 3 months of age t. It is generally accepted that visual experience before the expected term date has no measurable effect on the normal development of behavioural acuity 3'7'11"12"14'17"18'22'29"30"31"33'34.Whereas visual acuity of healthy preterm infants lies within the range for fullterm infants of comparable conceptional age, preterm infants with birthweights less than 1,500 g, and those who suffered perinatal insults are at risk of developing impaired visual acuity t~ For high-risk preterm infants, the relationship between intracerebral haemorrhage and development of visual functions is still unclear. Minor intracerebral haemorrhage may be transient and without effect on acuity development; larger
108 intracranial insults such as periventricular haemorrhage and periventricular leucomalacia may result in severe v i s u a l d e f e c t s 11'26'3~ U p till now, visual acuity deficits in high-risk preterms have not been demonstrated at term age, the earliest reports being at 6 weeks of corrected a g e 1~ Assessment of differences in acuity estimates between low- and high-risk neonates appeared to be complicated both by the high neonatal variability, and the slow progress in acuity development during the neonatal period ~7. However, these former studies often lacked serial ultrasound scanning, as a result ofwhich data on the severity of neonatal pre- and perinatal neurological lesions are not fully comparable. The aim of the present study was to investigate the effects of pre- and perinatal complications on the development of visual acuity in preterm infants during the neonatal period and in the first months of life. The study includes high-risk, medium-risk as well as lowrisk preterm infants, divided on the basis of clinical neurological data, serial ultrasound scans and EEG recording. Acuity estimates obtained during the neonatal period were compared to those of healthy fullterm infants. The long-term aim is to follow the development of visual functions over several years, and to assess the prognostic value of early neuro-imaging techniques, EEG recording and visual assessment.
SUBJECTS
Binocular grating acuity was tested in 90 newborn infants (25 fullterms and 65 preterms) born at the Department of Obstetrics or admitted to the N I C U of the Pisa University Hospital between January 1990 and May 1991. Criteria required for inclusion in this study were: postmenstrual age at the time of neonatal visual assessment between 37 and 42 weeks; no retinopathy
of prcmaturity or other ophthalmological abnormalities; no respiratory, infectious, metabolic or haematological complications at the time of testing. Low-risk fullterm infants (FLR) were selected on the basis of an uncomplicated delivery after an uneventful pregnancy of 37-42 weeks, and normal neurological examination after birth. Preterm neurological condition was graded according to the results of serial cranial ultrasound (US) scans, neonatal EEG, and neurological examination both before discharge from the N I C U and at follow-up examinations until at least 6 months of corrected age. Cranial US scans (with 5 and 7.5 MHz transducers) were carried out within the first 24 tl, repeated during the preterm period and after discharge from the Hospital until fontanel closure. EEGs, lasting at least 1 h, were performed in the first 2 weeks of life, by means of computer-aided portable recorders, using 8 active electrodes on the scalp. Ictal and background activities were assessed visually and submitted to spectral analysis. Neurological clinical assessment was carried out by means of classical neurological examinations 25'27, qualitative assessment of spontaneous motility 13 and developmental scales ~5"2s. Further details of the examination procedures in our Unit are given elsewhere 6. According to the outcome of these examinations and using criteria as indicated in Table I, preterm infants were divided into three different groups: lox~,,-,mediumand high-risk. Twenty-five infants (3 fuliterms and 22 preterms) were excluded from the study because of excessive crying or drowsiness during visual testing, or unreliability of the results due to a testing time of more than 5 rain. Moreover, results obtained from infants assessed within the incubator were not included, in order to standardize testing conditions. The main characteristics of the remaining 65 infants
TABLE I Criteria o f risk-grading hl preterm hlfants IVH = intra-/periventricular haemorrhage graded according to Volpe, 1987; T F = transient flare ( < 15 days); PF = prolonged flare; PVL = cystic periventricular leukomalacia; par haem = parenchymal haemorrhage; EEG and neurological examination graded as in Cioni et al., 1992. Group
Neurological examh2ation at term and at follow-up
Serial US-scan
Neonatal EEG
PLR low-risk
normal
and
normal, IVH I or T F
and
normal
PMR medium-risk
moderate or transient signs
or
PF, 1VH 1I or IVtt III
or
moderate abnormality
PHR high-risk
severe and persistent signs
or
PVL or par haem
or
severe abnormality
109 (22 fullterms and 43 preterms) are indicated in Table II. Of the preterms, 20 appeared to be at low-risk (PLR); 9 at medium-risk (PMR) and 14 at high-risk (PHR). One FLR, 2 PLR, 1 PMR and 1 P H R infants were classified as small for gestational age (SGA) according to Lubchenco et al. TM. (As discussed elsewhere33 visual acuity development of SGA infants has been found to be comparable to that of appropriate for age infants.) US scanning of the 20 PLR infants showed no abnormalities in 15 infants, whereas a transient flare was demonstrated in 4, and an intraventricular haemorrhage (IVH grade I according to Volpe 35) in one infant. These last 5 infants were graded 'low-risk', because of a normal neonatal EEG (or with very occasional sharp waves) and normal neonatal neurology; in addition, at 6 months of age neurological and developmental outcome was found to be normal. In 8 PLR infants visual acuity development could be followed during the first 50 weeks of corrected age. Serial US scans of PMR infants (n = 9) showed a prolonged flare in all of them; in 2 cases this was associated with an intraventricular haemorrhage (IVH grade II according to Volpe35). Neonatal EEG showed moderate abnormalities in 6 out of the 9 PMR infants. Neurological follow-upexamination at 6 months and more, showed 6 infants to be normal, whereas in 3 infants moderate neurological signs were found. Visual acuity follow-up of 5 PMR infants, including the case with the IVH grade II (case 1), will be presented. Neonatal EEG of the 14 preterms graded as highrisk (PHR) was found to normal in 4, moderately abnormal in 4 others and severely abnormal in 6 infants. Early neuro-imaging revealed in 3 out of the 14 P H R
infants a prolonged flare; at neurological follow-up, one showed severe, and 2 moderate neurological abnormalities. Visual follow-up of all 3 infants is available. Neonatal ultrasound scanning of the 11 other P H R infants revealed a cystic-periventricular leukomalacia (PVL), associated with a haemorrhagic infarction in 2 of them; 5 of these infants showed at 6 months of corrected age a severe neurological outcome (cerebral palsy), whereas 6 had mild, but persistent neurological signs. MRI was carried out at around 12 months of age in 5 of the P H R infants with PVL; the results confirmed US findings. Visual acuity development could be followed in 9 of the 11 PVL infants, including one of the cases with associated haemorrhagic infarction (case 7).
METHODS
Binocular grating acuity was tested by means of the acuity card procedure 19,zl, using Teller acuity cards (Vistech Consultants, Inc.). This method is based on the inborn preference for a pattern over a uniform comparison field. The infant was held in front of a uniform grey screen, containing on one side a black and white striped pattern. An observer watched the infant's face from behind the screen through a peephole located between the stimulus positions. Gratings of stripe-widths ranging from 0.23 to 26 cy/cm, were presented in . 1/2octave steps, with the left/right position of the pattern varied randomly from trial to trial. The observer, who was unaware of the left/right position of the grating stimulus, was required to judge the stimulus position on the basis of the infant's eye and head movements. The
T A B L E II
Main clinical, US and EEG fmdings hi the study gro,tp 9 G A = gestational age; m o d = moderate; sev = severe; abn = abnormality; other abbreviations as in Table I.
Group
n
GA hz wks
Birthweight (g)
US scan
Neonatal EEG
Neurological outcome (> 6 nO
FLR
22
mean S.D. range
39.5 1.1 37-41
mean S.D. range
3,065 820.5 2,200-4,990
-
-
-
PLR
20
mean S.D. range
35 1.4 30-36
mean S.D. range
2,183 513 950-3,450
15 n o r m a l 4 TF 1 IVH I
18 n o r m a l 2 m o d . abn.
20 n o r m a l
PMR
9
mean S.D. range
31.1 2.9 25-36
mean S.D. range
1,452 465 960-2,325
7 PF 2 P F + IVH II
3 normal 6 m o d . abn.
6 normal 3 mod. normal
PHR
14
mean S.D. range
31.7 1.5 30-35
mean S.D. range
1,567 324 960-2,050
3 PF 9 PVL 2 P V L + par h a e m
4 normal 4 m o d . abn. 6 sev. abn.
8 m o d . abn. 6 sev. abn.
110 Teller test-set consists of 17 two-aperture cards, 16 of which containing on one side a vertical square wave grating in a uniform grey surrounding. One of the cards contained blank grey cardboard. Testing started with the presentation of a coarse grating (0.32 cy/cm), followed by the presentation of the blank grey card, in order to familiarize the observer with the infant's looking behaviour in the presence or absence of a visible stimulus. Subsequently, cards with gratings of decreasing stripe widths were presented in rapid succession, with each card rotated by 180 ~ by the observer at least once, until the region of the acuity threshold appeared to be reached. At this point, the infant was shown a grating near or at threshold in alternation with a grating 1/2 octave finer, and judged to be above threshold, at least 3 times each. The threshold of acuity was taken as the finest stripe-width for which the infant consistently responded correct according to the observer, and was expressed as cycles per degree of visual angle (cy/ deg). Infants were tested at a distance of 40 cm. The number of trials ranged between 15 and 25; testing time was about 3-5 min. Tests taking more than 5 minutes were considered unreliable, and discarded. Testing of newborns took place in the Neonatal Intensive Care Unit rooms. The newborns were tested out of bed, when they were awake spontaneously; they were held in an upright position, with their head supported by an experienced holder. Testing was carried out without a surrounding screen. Acuity cards were illuminated by diffuse and indirect daylight (mean luminance ranged from 12 to 16 cd/m2). Older infants were tested in the Children's Hospital, where they came for neurological and developmental check-ups. Testing was carried out with a surrounding screen, and the distance was increased to 57 cm for infants between 6 and 12 months.
RESULTS
.Binocular visual acuity was assessed in the neonatal period in 22 out of 25 fuilterms and 43 out of 65 preterm
infants (success rate 7 2 ~ ) . For each infant, the first confident acuity estimate obtained between 37 and 42 weeks of postmenstrual age was used for further analyses. Mean acuity, variability, and mean postnataland corrected age of each of the four different groups of neonates are given in Table III. No significant differences in mean visual acuity were observed between fullterms (0.80 cy/deg; S.D. 0.71 oct) and preterms (0.79 cy/deg; S.D. 0.34 oct). Within the preterms, statistical analysis using Student's t-test showed mean visual acuity of low-risk preterms to be significantly better than that of the combined groups of medium and high-risk preterms (P= 0.026), whereas the mean acuity of PLRs (0.86 cy/deg; S.D. 0.34 oct) was only slightly better (P = 0.058) than that of either PMR (0.73 cy/deg; S.D. 0.26oct) or PHR infants (0.73 cy/deg; S.D. 0.35 oct) (P=0.064). Analysis of variance revealed a significant difference at the 0.05 level between acuities of PLR and PHR infants but not between PLR and P M R infants. Multiple regression analysis within the preterm groups, showed mean acuity of preterms at low-risk to be significantly related to the degree of risk (P<0.02). A significant correlation between mean visual acuity and gestational age (P = 0.01) was found, but can be explained by the fact that both PMR and P H R infants had lower gestational ages than PLR infants. No relationship between visual acuity and birthweight could be demonstrated. Fig. 1 shows the development of binocular visual acuity during the first year after term of 8 PLR, 5 PMR, and 12 P H R infants. Ophthalmological examination revealed no clear refractive errors in these infants. Data of PHR infants are divided into three groups; infants with a prolonged flare (n = 3), infants with PVL, showing mild neurological abnormalities at follow-up (n = 5), and infants with PVL and severe neurological outcome (cerebral palsy) at 6 months after term 07 = 4). During the first weeks after term age the majority of infants of all groups showed a positive acuity development. However, in comparison to normative acuity values obtained in control preterm and fullterm infants as described by Mohn et al. 22, visual acuity development of all preterms
TABLE 11I Mean binocular gratblg acuiO', mean postnatal- and corrected ages of testblg in four groups of neonates Group
FLR PLR PMR PHR
n
22 20 9 14
Bhzocular visual acuiO, cy]deg
Corrected age (wks)
Posmatal ag~ (wks)
mean
S.D. (ocO
mean
S.D.
mean
S.D.
0.80 0.86 0.73 0.73
(0.71) (0.34) (0.26) (0,35)
0.45 -0.98 -0.53 -0.98
'1.1 1.2 1.2 1.2
0.8 3.9 8.3 7.3
1.8 2.0 2.7 2.1
111 PLR infants
100
PHR i n f a n t s ( w i t h
g~ 100
~
PVL and s e v e r e n e u r a l , obn.)
"o
10
f~y.'"2"2"'-~
10
D
u o
D v
o
p -. _ , r
.....
,..Z,-.y.- ~
1
D
g
I
m
D U
"
ffl
0.1
6
20
1;
310
50
AfO
~'o ;o
80
0.1
lb
Corrected oge P5
- -
P50
- -
o 17
- -
0 14
x 10
Corrected P95.
--
~ 16
v 1B
I15
4 24
x7
a26
P5
,~o
~o
6'o
7'o
~o
age
--P50
--P95
o13
425
"02
Fig. 1, Development of binocular visual acuity during the first year after term in 8 low-risk (PLR), 5 medium-risk (PMR), and 12 highrisk preterms (PHR) in comparison to normative acuity values obtained in control prcterm and fullterm infants as described by Mohn et al.zz (thin lines enclose the 9 0 ~ confidence interval). Results of PHR infants withoutand with cystic-periventricular leukomalacia (PVL) are given separately. Data of PVL infants are divided according to the neurological outcome at 6 months.
PMR i n f a n t s
~ 100
~o
2'0
o "0
1C o
"5 v o c: 111
O
6
i~
2b
3b
Jo
~
5'o go
80
Corrected cge --P5
~PSO
x6
m
o9
--P95
ol
411
121
PHR i n f a n t s w i t h PF
10C
"o
1c o
.=o_ al o.1
lb
2b
3b
4'0 5b
go
7'o
80
Corrected nge --P5
--PSO
PHR
"& 10C
--P95
x 27
v 22
23
i n f a n t s w i t h PVL and mild n e u r a l obn.
D
b
was found to be rather slow. Although the first values were within normal ranges, acuity estimates of most P L R and P M R infants appeared to lie within the l o w normal range from 10 to 20 weeks after term, whereas acuities of one P L R infant (case 17) and one P M R (case 21) became clearly low for age. Visual acuity development of the 3 non-PVL P H R infants was found to be similar to that of P L R and P M R infants. As can be seen in Fig. ld and e visual acuity values of many of the P H R infants with PVL were found to be within the low-normal range, and often clearly impaired. I n the group of infants with mild neurological outcome at follow-up, only one infant showed a normal visual acuity during the first 26 weeks of corrected age. Visual development of 2 infants was rather low during the first weeks and clearly impaired from 20 weeks onward, whereas 2 other infants had impaired acuities at 16 weeks, despite normal values at term age. Visual outcome of PVL infants with severe neurological outcome (Fig. le) seemed not to be clearly different from that of PVL infants with mild neurological signs. In 3 out of the 4 eases followed up till now, visual acuity development was impaired. However, visual acuities of case 7 (PVL associated with parenchymal haemorrhage) were within normal ranges up till 40 weeks of age, and only slightly below normal at 70 weeks.
o cO
x
1;
2b
3b
2o
go
6'0
7'o
80
DISCUSSION
C o r r e c t e d age --P5 *3
--P50
--P95
x 5
412
z 4
o
19
At term age, the mean visual acuity of at-risk neonates was found to be significantly lower than that of
112 low-risk preterms. Up till now, visual acuity deficits have not been demonstrated in medium- and high-risk preterms before 6 weeks of corrected age 1~ In these former studies ~7 it was suggested that no differences could be demonstrated between acuities of lowand high-risk neonates, because of the high standard deviations. However, in the present study the acuity variability of preterm infants appeared to be remarkably low, both in comparison to that of fullterms and to reported values 9'17'22'31. This might possibly be explained by the longer postnatal experience of preterms compared to that of fullterms. The main difference between low-risk preterms and fullterms at the time of visual assessment is their postnatal age (for PLR 3.9 weeks; for FLR 0.8 weeks), whereas corrected ages were similar, since all infants were tested between 37 and 40 weeks of postmenstrual age. So it seems that 3 weeks of postnatal experience in the newborn period helps to stabilize the attentional level in otherwise healthy preterms. Surprisingly, the at-risk preterms showed low variabilities of visual acuity estimates too. Although their postnatal ages (8.3 weeks for P M R and 7.3 weeks for PHR infants) were considerable longer than that of FLR infants, one would have expected higher variabilities because of their peri- and postnatal medical complications. In fact, in other studies much higher variabilities are reported 9't7"22'3~. Our results suggest that the combination of serial ultrasound scanning, neonatal EEG and neurological examination allows a well-defined selection of neonates as to the severity of neonatal pre- and perinatal neurological lesions. The mean visual acuity of 0.80 cy/deg obtained in low-risk fuIlterms at term age and the S.D. of 0.71 octave are comparable with previous behavioral studies 8"9'1~ NO significant difference in mean visual acuity could be demonstrated between low-risk fullterms and low-risk preterms, which confirms the generally accepted opinion that visual experience before the expected term date has no measurable effect on the normal development of behavioural acuity. Visual acuity of low-risk fullterms was also not significantly different from that of medium- and/or high-risk preterms, possibly because of the high variability of the results obtained in fullterms. 9The mean acuity of low-risk preterms at term age of 0.86 cy/deg is at the low range of earlier reports 9'22'31, but higher than recently described by Hermans et al. 17. U sing the acuity card procedure, these authors reported a mean visual acuity of 0.58 cy/deg and a standard deviation of 0171 octave in preterms during the neonatal period. The discrepancies with our results might possibly be explained by the selection criteria of t h e
infants and by differences in the testing procedure. In the present study infants were not tested in bed or incubator; all neonates were held in an upright position and kept alert during testing, which lasted 5 rain or less. Within the preterms, visual acuity of low-risk neonates was found to be significantly better than that of at-risk infants. Although the mean acuity of both medium-risk and high-risk preterms amounted to 0.73 cy/deg, analysis of variance revealed the difference between PLR and P H R to be significant, but not between PLR and PMR infants. This might be explained by the small number of medium risk neonates (n = 9). The reason for dividing preterms into 3 instead of 2 separate risk groups is that, according to the neonatal signs, the PMR infants did not belong to either lowrisk, or high-risk infants. Neurological outcome at 6 months of age supported and confirmed the decision to consider medium-risk preterms as a separate group. Since gestational ages of both PMR and P H R infants were lower than those of low-risk preterms, the factor gestational age as such can not be considered a risk factor for low mean visual acuity at term age. No significant correlation between birthweight and neonatal visual acuity could be demonstrated. The low visual acuity of medium- and high-risk neonates compared to that of low-risk preterms cannot be accounted for by differences in postnatal age or corrected age, since these were similar across the groups. In the absence of ophthalmological abnormalities, low visual acuities of at-risk preterms seem more likely to be due to pre- and perinatal brain lesions; in fact, mild to severe hypoxic and]or haemorrhagic insults were detected by means of US and EEG. These lesions often involve parts of the brain relevant for visual processing such as optic radiations and occipital lobes 6. However, no differences were observed between the mean visual acuity of P M R and P H R infants, despite the more severe lesions in the latter group. This could be due to the small number of P M R neonates, or that neuroimaging techniques fail to demonstrate (some of the) lesions. Visual acuity development of individual preterms was found to vary across the various risk groups. One P L R infant (case 17) showed a n impaired visual acuity at 50 weeks of corrected age, despite normal neonatal EEG and ultra sound scans, and normal neurology at all times. One PMR infant,(case 21) with a prolonged flare but otherwise no EEG or neurological abnormalities had normal actiity values during the first 13 weeks, but a low acuity at 30 weekL On the other hand, ease 1, a P M R infant with in the neonatal period a prolonged flare combined with an intraventricular haemorrhage
113 grade II, moderate EEG and neurological abnormalities, developed visually and neurologically normal. Visual and neurological follow-up after discharge from the hospital, has been carried out in 12 out of the 14 PHR infants. Visual development of the 3 P H R infants with a prolonged flare was similar to that of the PLR and the PMR infants; they showed normal acuities during the first 20 weeks and, although 2 of them showed a low acuity at around 40 weeks, repeated testing at 70 weeks showed one of them to be within the normal range again. This infant (case 27) had been classified PHR based on a severely abnormal neonatal EEG, and moderately abnormal neurological signs at term and at 6 months. The other infant with a low acuity at 40 weeks (case 23) had shown a moderately abnormal neonatal EEG and developed cerebral palsy at 6 months. Visual development of PHR infants with a cystic PVL was often slow during the first 20 weeks, with acuity values lying within the low-normal range, and from 20 weeks onward clearly impaired in some of the infants. However, acuity development was not found to be clearly related to the severity of the brain lesion as demonstrated by serial US, neonatal EEG, or early and follow-up neurological abnormalities. Visual acuity estimates obtained in PVL children, who developed moderate neurological abnormalities at follow-up (Fig. ld), seemed to be even worse than those of the children who developed a cerebral palsy (Fig. le). The last group included 2 infants whose visual development was found to be normal to 50 weeks, despite the fact that both ultrasound and MRI had revealed cystic-PVL combined in one case with a haemorrhagic infarction; the neonatal EEG had been normal in case 13 and severely abnormal in case 7. Visual acuity of case 7 was found impaired at 70 weeks. In summary, high-risk preterms were found to have a lower mean visual acuity than low-risk preterms. Confirming earlier reports 11'z8'3~ individual visual acuity development of PHR infants, especially those with cystic-PVL, was often found to be worse than that of low- and medium-risk infants, but appeared not to be related to the severity of neurological outcome. Some of the infants with a cystic-PVL, showed a (nearly) normal visual acuity development. The first results of the longitudinal study suggest that for high-risk preterm infants the relationship between the development of visual functions and the severity of cerebral damage as demonstrated by way of neuro-imaging is still unclear. However, early visual assessment in combination with serial US, EEG and neurological assessment seems to have a high prognostic value for later outcome. More data are needed in order to substantiate these findings, and to clarify which early brain lesions have transient
effect and possibly result in a delayed but otherwise normal visual development, and which ones are leading to permanent visual impairment.
ACKNOWLEDGEMENTS
The authors gratefully acknowledge the contribution to this study of C. Romano, M.D. for ophthalmological examination, P. Salvadori, M.D. for visual acuity testing, L. Bartalena, M.D. for US examinations, E. Biagioni, M.D. for EEG recording, Prof. C. Cipolloni and the staff of the N.I.C.U. of the University of Pisa for their assistance. We also thank A. Mura for computer and statistical analysis and C.W. Eveleens Maarse-Havermans for administrative help. This research was supported by grants of the Italian Ministry of Health (current research project 1989) and of Scientific Research and University.
REFERENCES 1 Atkinson, J. and Braddick, O~J., Newborn contrast sensitivity measures: do VEP, O K N and FPL reveal differential development of cortical and subcortical streams? Invest. OphthahnoL Vis. Sci., 30 (1989) Suppl. 313. 2 Atkinson, J., Braddick, O. and French, J., Contrast sensitivity of the human neonate measured by the visual evoked potential, hzrest. OphthahnoL Vis. Sci., 18 (1979) 210-213. 3 Baraldi, P., Ferrari, F., Fonda, S. and Penne, A., Vision in the neonate (full-term and premature). Preliminary result of the application of some testing methods, Doc. OphthahnoL, 51 (1981) 101-112. 4 Birch, E.E., Birch, D.G., Petrig, B. and Uauty, R., Retinal and cortical function of very low birth weight infants at 36 and 57 weeks postconception, Clin. Vision Sci., 5 (1990) 363-373. 5 Brown, A.M. and Yamamoto, M., Visual acuity in newborn and preterm infants measured with grating acuity cards, Am. J. OphthahnoL, 102 (1986) 245-253. 6 Cioni, G., Bartalena, L., Biagioni, E., Boldrini, A. and Canapicchi, R., Neuroimaging and functional outcome of neonatal leukomalacia, Behav. Bra#z Res., 49 (1992) 7-19. 7 Dobson, V., Mayer, D.L. and Lee, C.P., Visual acuity screening ofpreterm infants, hn'est. Ophthahnol. Vis. Sci., 19 (1980) 14981505. 8 Dobson, V., McDonald, M.A. and Teller, D.Y., Visual acuity of infants and young children: forced-choice preferential looking procedures, Am. Orthopt. J., 35 (1985) 118-125. 9 Dobson, V., Schwartz, T.L., Sandstrom, D.J. and Michel, L., Binocular visual acuity of neonates: the acuity card procedure, Dev. Med. Child NeuroL, 29 (1987) 199-206. I0 Dobson, V., D'Antonio, J.A. and Bonvalot, K., Grating acuity in early infancy predicts grating acuity at age 1 year with perinatal complication, hlrest. OphthabnoL Vis. Sci., 30 Suppl. (1989) 142. 11 Dubowitz, L.M.S., Mushin, J., Morante, A. and Placzck, M.,
114
12 13
14
15 16
17
18
19
20
21
22
23
The maturation of visual acuity in neurologically normal and abnormal newborn infants, Behav. Braht Res., 10 (1983) 39-45, Fantz, R.L., Visual perception from birth as shown by pattern selectivity, Ann. N.Y. Acad. Sci., 118 (1965) 793-814. Ferrari, F., Cioni, G. and Prechtl, H.F.R., Qualitative changes of general movements in preterm infants with brain lesions, Earl)' Hum. Dev., 23 (1990) 193-231. Getz, L., Dobson, V. and Luna, B., Full-term acuity card norms can be used for preterm children 0-3 years of age, hlvest. Ophthahn. Vis. Sci., 32 Suppl. (1991) 962. Griffiths, R., The Ability of Babies. University London Press, London, 1954. Groenendaal, F., Van Hof-van Duin, J., Baerts, W. and Fetter, W.P.F., Effect"of perinatal hypoxia on visual development during the first year of (corrected) age, Earl), Hum. Dev., 20 (1989) 267-279. Hermans, A.J.M., Van Hof-van Duin, J. and Oudesluys-Murphy, A.M., Visual acuity in low birth weight (1550-2500) neonates, Early Human Dev., 28 (1992) 155-167. Lubchenco, L.O., Hansman, C. and Boyd, E., Intrauterinegrowth in length and head circumference as estimated from live birth at gestational ages from 26-42 weeks, Pediatrics, 37 (1966), 403408. McDonald, M.A., Dobson, V., Sebris, S.L., Baitch, L., Varner, D. and Teller, D.Y., The acuity card procedure: a rapid test of infant acuity, hlvest. Ophthahnol. Vis. ScL, 26 (1985) 11581162. b,liranda, S.B., Visual acuity and pattern preferences of premature infants and fullterm neonates, J. Exp. Child Psychol., 10 (1970) 189-205. Mohn, G. and Van Hof-van Duin, J., Rapid assessment ofvisual acuity in infants and children in a clinical setting, using acuity cards, Doc. OphthahnoL Proc. Ser., 45 (1986) 363-372. Mohn, G., Van Hof-van Duin, J., Fetter, W.P.F., De Groot, L. and Hage, M., Acuity assessment in non-verbal infants and children. Clinical experience with the acuity card procedure, Dev. Med. Child NeuroL, 30 (1988) 232-244. Norcia, A.M. and Tyler, Ch.W., Spatial frequency sweep VEP:
24
25
26
27 28 29
30
31
32
33
34
35
visual acuity during the first year of life, Vision Res., 25 (1985) 10 1399-1408. Porciatti, V., Temporal and spatial properties of the patternreversal VEPs in infants below 2 months of age, Hum. NeurobioL, 3 (1984) 97-102. Prechtl, H.F.R., The neurological examination of the full term newborn infant, In Clinics hi Developmental Medichw, 63, 2nd edn., Heinemann Medical Books, London, 1977, 65 pp. Scher, S.M., Dobson, V., Carpenter, A.N. and Guthrie, R.D., Visual and neurological outcome of infants with periventricular leukomalacia, Dev. Med. Child NeuroL, 31 (1989) 353-365. Touwen, B.C.L., Neurological development in infancy, In Clinics in Developmental Medichw, 58, Heinemann, London, 1976. Uzgiris, I. and Hunt, J.McV., Assessment in hfancy, University of Illinois Press, Urbana, IL, 1985. Van ttof-van Duin, J. and Mohn, G., Vision in the preterm infant. In H.F.R. Prechtl (Ed.), Continuity of Neural Fwwtionsfrom Prenatal to Postnatal Life, Clinics hz Developmental ~Iedic#te, Spastics Int. Med. Publications, London, 1984, pp. 93-115. Van Hof-van Duin, J. and Mohn, G., Th.e development of visual functions in preterm infants, Ergebn. Exp. Med., 46 (1985) 350362. Van Hof-van Duin, J. and Mohn, G., The development of visual acuity in normal fullterm and preterm infants, Vision Res., 26 (1986) 909-916. Van Hof-van Duin, J., Evenhuis-van Leunen, A., Mohn, G., Baerts, W. and Fetter, W.P.F., Effect of very low birth weight (VLBW) on visual development during the first year after term, Earl), 'Hum. Dev., 20 (1989) 255-266. Van Hof-van Duin, J., Heersema, D.J., Groenendaal, F., Baerts, W. and Fetter, W.P.F., Visual field and grating acuity development during the first 21# years after term, Behav. Brain Res., 49 (1992) 115-122. Van H0f-van Duin, J., Mohn, G., Fetter, W.P.F., Mettau, J.W. and Baerts, W., Preferential looking acuity in preterm infants, Behav. Brahl Res., 10 (1983) 47-51. Volpe, J.J., Neurology of the newborn, 2nd edn., W.B. Saunders, Philadelphia, 1987.
107
BBR 01320
Visual acuity of low- and high-risk neonates and acuity development during the first year A.E. Ipata a, G. Cioni a, A. Boldrini b, P. B o t t a i a a n d J. v a n H o f - v a n D u i n c a Institute of Child 1Veurology and Psychiatry, Unirersity of Pisa and Stella Maris Foundation, Calambrone. Pisa (ltal)9, t'Neonatal Intensive Care Unit, University of Pisa, Pisa (Italy} and ~Department of Physiology I, Erasmus Unirersity Rotterdam, Rotterdam (The Netherlands) (Received 11 March 1992) (Accepted 15 April 1992)
Key words: Visual acuity; Preterm; Fullterm; Neonate; Risk factor; Acuity card; Neonatal injury; Ultrasound; EEG; Leukomalacia
Binocular grating acuity of 65 neonates was measured using Teller acuity cards/At the time of testing, age corrected for prematurity ranged from - 3 weeks to 2 weeks. On the basis of clinical data, serial ultrasound scans and EEG recording newborns were divided in!o 4 subgroups: fullterm low-risk (FLR, n - 22); preterm low-risk (PLR, n = 20); preterm medium-risk (PMR, n = 9) and preterm high-risk (PHR, n = 14). Mean visual acuity of PLR infants (0.86 cy/deg; S.D. 0.34 oct) was not significantly different from that of FLR newborns (0.80 cy/deg; S.D. 0.71 oct); the lower variability of the PLR infants might possibly be caused by their longer postnatal experience. Within the preterm groups, mean visual acuity of PLR newborns was found to be significantly higher than that of PMR (0.73 cy/deg; S.D. 0.26 oct) and PHR infants (0.73 cy/deg; S.D. 0.35 oct). This difference can not be explained by dissimilarities in postnatal or corrected"age. Brain impairment, as documented by US scans and EEG recording could account for these findings. Longitudinal data are needed in order to substantiate these findings and correlate them with later neurological and neuro-imaging outcome. Preliminary results of an ongoing longitudinal study suggest acuity development of most, but not all, PHR infants, in whom a cystic-periventricular leukomalacia had been diagnosed, to be worse than that Of low- and medium-risk infants.
INTRODUCTION
Although there is general agreement that visual acuity is very poor at birth, actual values reported by various authors differ. There are not only large quantitative differences between behavioural and electrophysiological data, but also within techniques diverging acuity values have been reported. The mean visual acuity, estimated in healthy newborns during the neonatal period with the forced-choice preferential looking procedure (FPL), ranges across various laboratories between 0.25 and 1.1 cycles per degree (cy/deg) 2'3'8't2'a~ Using the acuity card procedure 19, these values were found to range between not-testable 5 and 1.1 cy/ deg 9"17'22 during the neonatal period, and when acuity was assessed by means of a modified version of the acuity cards (the so-called one-aperture acuity card) between 0.705 and 1.1 cy/deg 9. The variability range
Correspondence: G. Cioni, Institute of Child Neurology and Psychiatry, University of Pisa and Stella Maris Foundation, 56018 Calambrone, Pisa, Italy.
reported in these various studies lies between 0.4 and 0.8 octaves. Electrophysiological studies have yielded neonatal acuity estimates varying between 0.25 cy/deg 3, 0.85 cy/deg 2, 3 cy/deg 4 to 4.523 and 5 cy/deg 24. Discrepancies between acuity values obtained with behavioral and electrophysi010gical techniques have been reported earlier. However, some studies claimed to find no significant differences between FPL and VEP acuity estimates obtained at term age 3, and even from birth to 3 months of age t. It is generally accepted that visual experience before the expected term date has no measurable effect on the normal development of behavioural acuity 3'7'11"12"14'17"18'22'29"30"31"33'34.Whereas visual acuity of healthy preterm infants lies within the range for fullterm infants of comparable conceptional age, preterm infants with birthweights less than 1,500 g, and those who suffered perinatal insults are at risk of developing impaired visual acuity t~ For high-risk preterm infants, the relationship between intracerebral haemorrhage and development of visual functions is still unclear. Minor intracerebral haemorrhage may be transient and without effect on acuity development; larger
108 intracranial insults such as periventricular haemorrhage and periventricular leucomalacia may result in severe v i s u a l d e f e c t s 11'26'3~ U p till now, visual acuity deficits in high-risk preterms have not been demonstrated at term age, the earliest reports being at 6 weeks of corrected a g e 1~ Assessment of differences in acuity estimates between low- and high-risk neonates appeared to be complicated both by the high neonatal variability, and the slow progress in acuity development during the neonatal period ~7. However, these former studies often lacked serial ultrasound scanning, as a result ofwhich data on the severity of neonatal pre- and perinatal neurological lesions are not fully comparable. The aim of the present study was to investigate the effects of pre- and perinatal complications on the development of visual acuity in preterm infants during the neonatal period and in the first months of life. The study includes high-risk, medium-risk as well as lowrisk preterm infants, divided on the basis of clinical neurological data, serial ultrasound scans and EEG recording. Acuity estimates obtained during the neonatal period were compared to those of healthy fullterm infants. The long-term aim is to follow the development of visual functions over several years, and to assess the prognostic value of early neuro-imaging techniques, EEG recording and visual assessment.
SUBJECTS
Binocular grating acuity was tested in 90 newborn infants (25 fullterms and 65 preterms) born at the Department of Obstetrics or admitted to the N I C U of the Pisa University Hospital between January 1990 and May 1991. Criteria required for inclusion in this study were: postmenstrual age at the time of neonatal visual assessment between 37 and 42 weeks; no retinopathy
of prcmaturity or other ophthalmological abnormalities; no respiratory, infectious, metabolic or haematological complications at the time of testing. Low-risk fullterm infants (FLR) were selected on the basis of an uncomplicated delivery after an uneventful pregnancy of 37-42 weeks, and normal neurological examination after birth. Preterm neurological condition was graded according to the results of serial cranial ultrasound (US) scans, neonatal EEG, and neurological examination both before discharge from the N I C U and at follow-up examinations until at least 6 months of corrected age. Cranial US scans (with 5 and 7.5 MHz transducers) were carried out within the first 24 tl, repeated during the preterm period and after discharge from the Hospital until fontanel closure. EEGs, lasting at least 1 h, were performed in the first 2 weeks of life, by means of computer-aided portable recorders, using 8 active electrodes on the scalp. Ictal and background activities were assessed visually and submitted to spectral analysis. Neurological clinical assessment was carried out by means of classical neurological examinations 25'27, qualitative assessment of spontaneous motility 13 and developmental scales ~5"2s. Further details of the examination procedures in our Unit are given elsewhere 6. According to the outcome of these examinations and using criteria as indicated in Table I, preterm infants were divided into three different groups: lox~,,-,mediumand high-risk. Twenty-five infants (3 fuliterms and 22 preterms) were excluded from the study because of excessive crying or drowsiness during visual testing, or unreliability of the results due to a testing time of more than 5 rain. Moreover, results obtained from infants assessed within the incubator were not included, in order to standardize testing conditions. The main characteristics of the remaining 65 infants
TABLE I Criteria o f risk-grading hl preterm hlfants IVH = intra-/periventricular haemorrhage graded according to Volpe, 1987; T F = transient flare ( < 15 days); PF = prolonged flare; PVL = cystic periventricular leukomalacia; par haem = parenchymal haemorrhage; EEG and neurological examination graded as in Cioni et al., 1992. Group
Neurological examh2ation at term and at follow-up
Serial US-scan
Neonatal EEG
PLR low-risk
normal
and
normal, IVH I or T F
and
normal
PMR medium-risk
moderate or transient signs
or
PF, 1VH 1I or IVtt III
or
moderate abnormality
PHR high-risk
severe and persistent signs
or
PVL or par haem
or
severe abnormality
109 (22 fullterms and 43 preterms) are indicated in Table II. Of the preterms, 20 appeared to be at low-risk (PLR); 9 at medium-risk (PMR) and 14 at high-risk (PHR). One FLR, 2 PLR, 1 PMR and 1 P H R infants were classified as small for gestational age (SGA) according to Lubchenco et al. TM. (As discussed elsewhere33 visual acuity development of SGA infants has been found to be comparable to that of appropriate for age infants.) US scanning of the 20 PLR infants showed no abnormalities in 15 infants, whereas a transient flare was demonstrated in 4, and an intraventricular haemorrhage (IVH grade I according to Volpe 35) in one infant. These last 5 infants were graded 'low-risk', because of a normal neonatal EEG (or with very occasional sharp waves) and normal neonatal neurology; in addition, at 6 months of age neurological and developmental outcome was found to be normal. In 8 PLR infants visual acuity development could be followed during the first 50 weeks of corrected age. Serial US scans of PMR infants (n = 9) showed a prolonged flare in all of them; in 2 cases this was associated with an intraventricular haemorrhage (IVH grade II according to Volpe35). Neonatal EEG showed moderate abnormalities in 6 out of the 9 PMR infants. Neurological follow-upexamination at 6 months and more, showed 6 infants to be normal, whereas in 3 infants moderate neurological signs were found. Visual acuity follow-up of 5 PMR infants, including the case with the IVH grade II (case 1), will be presented. Neonatal EEG of the 14 preterms graded as highrisk (PHR) was found to normal in 4, moderately abnormal in 4 others and severely abnormal in 6 infants. Early neuro-imaging revealed in 3 out of the 14 P H R
infants a prolonged flare; at neurological follow-up, one showed severe, and 2 moderate neurological abnormalities. Visual follow-up of all 3 infants is available. Neonatal ultrasound scanning of the 11 other P H R infants revealed a cystic-periventricular leukomalacia (PVL), associated with a haemorrhagic infarction in 2 of them; 5 of these infants showed at 6 months of corrected age a severe neurological outcome (cerebral palsy), whereas 6 had mild, but persistent neurological signs. MRI was carried out at around 12 months of age in 5 of the P H R infants with PVL; the results confirmed US findings. Visual acuity development could be followed in 9 of the 11 PVL infants, including one of the cases with associated haemorrhagic infarction (case 7).
METHODS
Binocular grating acuity was tested by means of the acuity card procedure 19,zl, using Teller acuity cards (Vistech Consultants, Inc.). This method is based on the inborn preference for a pattern over a uniform comparison field. The infant was held in front of a uniform grey screen, containing on one side a black and white striped pattern. An observer watched the infant's face from behind the screen through a peephole located between the stimulus positions. Gratings of stripe-widths ranging from 0.23 to 26 cy/cm, were presented in . 1/2octave steps, with the left/right position of the pattern varied randomly from trial to trial. The observer, who was unaware of the left/right position of the grating stimulus, was required to judge the stimulus position on the basis of the infant's eye and head movements. The
T A B L E II
Main clinical, US and EEG fmdings hi the study gro,tp 9 G A = gestational age; m o d = moderate; sev = severe; abn = abnormality; other abbreviations as in Table I.
Group
n
GA hz wks
Birthweight (g)
US scan
Neonatal EEG
Neurological outcome (> 6 nO
FLR
22
mean S.D. range
39.5 1.1 37-41
mean S.D. range
3,065 820.5 2,200-4,990
-
-
-
PLR
20
mean S.D. range
35 1.4 30-36
mean S.D. range
2,183 513 950-3,450
15 n o r m a l 4 TF 1 IVH I
18 n o r m a l 2 m o d . abn.
20 n o r m a l
PMR
9
mean S.D. range
31.1 2.9 25-36
mean S.D. range
1,452 465 960-2,325
7 PF 2 P F + IVH II
3 normal 6 m o d . abn.
6 normal 3 mod. normal
PHR
14
mean S.D. range
31.7 1.5 30-35
mean S.D. range
1,567 324 960-2,050
3 PF 9 PVL 2 P V L + par h a e m
4 normal 4 m o d . abn. 6 sev. abn.
8 m o d . abn. 6 sev. abn.
110 Teller test-set consists of 17 two-aperture cards, 16 of which containing on one side a vertical square wave grating in a uniform grey surrounding. One of the cards contained blank grey cardboard. Testing started with the presentation of a coarse grating (0.32 cy/cm), followed by the presentation of the blank grey card, in order to familiarize the observer with the infant's looking behaviour in the presence or absence of a visible stimulus. Subsequently, cards with gratings of decreasing stripe widths were presented in rapid succession, with each card rotated by 180 ~ by the observer at least once, until the region of the acuity threshold appeared to be reached. At this point, the infant was shown a grating near or at threshold in alternation with a grating 1/2 octave finer, and judged to be above threshold, at least 3 times each. The threshold of acuity was taken as the finest stripe-width for which the infant consistently responded correct according to the observer, and was expressed as cycles per degree of visual angle (cy/ deg). Infants were tested at a distance of 40 cm. The number of trials ranged between 15 and 25; testing time was about 3-5 min. Tests taking more than 5 minutes were considered unreliable, and discarded. Testing of newborns took place in the Neonatal Intensive Care Unit rooms. The newborns were tested out of bed, when they were awake spontaneously; they were held in an upright position, with their head supported by an experienced holder. Testing was carried out without a surrounding screen. Acuity cards were illuminated by diffuse and indirect daylight (mean luminance ranged from 12 to 16 cd/m2). Older infants were tested in the Children's Hospital, where they came for neurological and developmental check-ups. Testing was carried out with a surrounding screen, and the distance was increased to 57 cm for infants between 6 and 12 months.
RESULTS
.Binocular visual acuity was assessed in the neonatal period in 22 out of 25 fuilterms and 43 out of 65 preterm
infants (success rate 7 2 ~ ) . For each infant, the first confident acuity estimate obtained between 37 and 42 weeks of postmenstrual age was used for further analyses. Mean acuity, variability, and mean postnataland corrected age of each of the four different groups of neonates are given in Table III. No significant differences in mean visual acuity were observed between fullterms (0.80 cy/deg; S.D. 0.71 oct) and preterms (0.79 cy/deg; S.D. 0.34 oct). Within the preterms, statistical analysis using Student's t-test showed mean visual acuity of low-risk preterms to be significantly better than that of the combined groups of medium and high-risk preterms (P= 0.026), whereas the mean acuity of PLRs (0.86 cy/deg; S.D. 0.34 oct) was only slightly better (P = 0.058) than that of either PMR (0.73 cy/deg; S.D. 0.26oct) or PHR infants (0.73 cy/deg; S.D. 0.35 oct) (P=0.064). Analysis of variance revealed a significant difference at the 0.05 level between acuities of PLR and PHR infants but not between PLR and P M R infants. Multiple regression analysis within the preterm groups, showed mean acuity of preterms at low-risk to be significantly related to the degree of risk (P<0.02). A significant correlation between mean visual acuity and gestational age (P = 0.01) was found, but can be explained by the fact that both PMR and P H R infants had lower gestational ages than PLR infants. No relationship between visual acuity and birthweight could be demonstrated. Fig. 1 shows the development of binocular visual acuity during the first year after term of 8 PLR, 5 PMR, and 12 P H R infants. Ophthalmological examination revealed no clear refractive errors in these infants. Data of PHR infants are divided into three groups; infants with a prolonged flare (n = 3), infants with PVL, showing mild neurological abnormalities at follow-up (n = 5), and infants with PVL and severe neurological outcome (cerebral palsy) at 6 months after term 07 = 4). During the first weeks after term age the majority of infants of all groups showed a positive acuity development. However, in comparison to normative acuity values obtained in control preterm and fullterm infants as described by Mohn et al. 22, visual acuity development of all preterms
TABLE 11I Mean binocular gratblg acuiO', mean postnatal- and corrected ages of testblg in four groups of neonates Group
FLR PLR PMR PHR
n
22 20 9 14
Bhzocular visual acuiO, cy]deg
Corrected age (wks)
Posmatal ag~ (wks)
mean
S.D. (ocO
mean
S.D.
mean
S.D.
0.80 0.86 0.73 0.73
(0.71) (0.34) (0.26) (0,35)
0.45 -0.98 -0.53 -0.98
'1.1 1.2 1.2 1.2
0.8 3.9 8.3 7.3
1.8 2.0 2.7 2.1
111 PLR infants
100
PHR i n f a n t s ( w i t h
g~ 100
~
PVL and s e v e r e n e u r a l , obn.)
"o
10
f~y.'"2"2"'-~
10
D
u o
D v
o
p -. _ , r
.....
,..Z,-.y.- ~
1
D
g
I
m
D U
"
ffl
0.1
6
20
1;
310
50
AfO
~'o ;o
80
0.1
lb
Corrected oge P5
- -
P50
- -
o 17
- -
0 14
x 10
Corrected P95.
--
~ 16
v 1B
I15
4 24
x7
a26
P5
,~o
~o
6'o
7'o
~o
age
--P50
--P95
o13
425
"02
Fig. 1, Development of binocular visual acuity during the first year after term in 8 low-risk (PLR), 5 medium-risk (PMR), and 12 highrisk preterms (PHR) in comparison to normative acuity values obtained in control prcterm and fullterm infants as described by Mohn et al.zz (thin lines enclose the 9 0 ~ confidence interval). Results of PHR infants withoutand with cystic-periventricular leukomalacia (PVL) are given separately. Data of PVL infants are divided according to the neurological outcome at 6 months.
PMR i n f a n t s
~ 100
~o
2'0
o "0
1C o
"5 v o c: 111
O
6
i~
2b
3b
Jo
~
5'o go
80
Corrected cge --P5
~PSO
x6
m
o9
--P95
ol
411
121
PHR i n f a n t s w i t h PF
10C
"o
1c o
.=o_ al o.1
lb
2b
3b
4'0 5b
go
7'o
80
Corrected nge --P5
--PSO
PHR
"& 10C
--P95
x 27
v 22
23
i n f a n t s w i t h PVL and mild n e u r a l obn.
D
b
was found to be rather slow. Although the first values were within normal ranges, acuity estimates of most P L R and P M R infants appeared to lie within the l o w normal range from 10 to 20 weeks after term, whereas acuities of one P L R infant (case 17) and one P M R (case 21) became clearly low for age. Visual acuity development of the 3 non-PVL P H R infants was found to be similar to that of P L R and P M R infants. As can be seen in Fig. ld and e visual acuity values of many of the P H R infants with PVL were found to be within the low-normal range, and often clearly impaired. I n the group of infants with mild neurological outcome at follow-up, only one infant showed a normal visual acuity during the first 26 weeks of corrected age. Visual development of 2 infants was rather low during the first weeks and clearly impaired from 20 weeks onward, whereas 2 other infants had impaired acuities at 16 weeks, despite normal values at term age. Visual outcome of PVL infants with severe neurological outcome (Fig. le) seemed not to be clearly different from that of PVL infants with mild neurological signs. In 3 out of the 4 eases followed up till now, visual acuity development was impaired. However, visual acuities of case 7 (PVL associated with parenchymal haemorrhage) were within normal ranges up till 40 weeks of age, and only slightly below normal at 70 weeks.
o cO
x
1;
2b
3b
2o
go
6'0
7'o
80
DISCUSSION
C o r r e c t e d age --P5 *3
--P50
--P95
x 5
412
z 4
o
19
At term age, the mean visual acuity of at-risk neonates was found to be significantly lower than that of
112 low-risk preterms. Up till now, visual acuity deficits have not been demonstrated in medium- and high-risk preterms before 6 weeks of corrected age 1~ In these former studies ~7 it was suggested that no differences could be demonstrated between acuities of lowand high-risk neonates, because of the high standard deviations. However, in the present study the acuity variability of preterm infants appeared to be remarkably low, both in comparison to that of fullterms and to reported values 9'17'22'31. This might possibly be explained by the longer postnatal experience of preterms compared to that of fullterms. The main difference between low-risk preterms and fullterms at the time of visual assessment is their postnatal age (for PLR 3.9 weeks; for FLR 0.8 weeks), whereas corrected ages were similar, since all infants were tested between 37 and 40 weeks of postmenstrual age. So it seems that 3 weeks of postnatal experience in the newborn period helps to stabilize the attentional level in otherwise healthy preterms. Surprisingly, the at-risk preterms showed low variabilities of visual acuity estimates too. Although their postnatal ages (8.3 weeks for P M R and 7.3 weeks for PHR infants) were considerable longer than that of FLR infants, one would have expected higher variabilities because of their peri- and postnatal medical complications. In fact, in other studies much higher variabilities are reported 9't7"22'3~. Our results suggest that the combination of serial ultrasound scanning, neonatal EEG and neurological examination allows a well-defined selection of neonates as to the severity of neonatal pre- and perinatal neurological lesions. The mean visual acuity of 0.80 cy/deg obtained in low-risk fuIlterms at term age and the S.D. of 0.71 octave are comparable with previous behavioral studies 8"9'1~ NO significant difference in mean visual acuity could be demonstrated between low-risk fullterms and low-risk preterms, which confirms the generally accepted opinion that visual experience before the expected term date has no measurable effect on the normal development of behavioural acuity. Visual acuity of low-risk fullterms was also not significantly different from that of medium- and/or high-risk preterms, possibly because of the high variability of the results obtained in fullterms. 9The mean acuity of low-risk preterms at term age of 0.86 cy/deg is at the low range of earlier reports 9'22'31, but higher than recently described by Hermans et al. 17. U sing the acuity card procedure, these authors reported a mean visual acuity of 0.58 cy/deg and a standard deviation of 0171 octave in preterms during the neonatal period. The discrepancies with our results might possibly be explained by the selection criteria of t h e
infants and by differences in the testing procedure. In the present study infants were not tested in bed or incubator; all neonates were held in an upright position and kept alert during testing, which lasted 5 rain or less. Within the preterms, visual acuity of low-risk neonates was found to be significantly better than that of at-risk infants. Although the mean acuity of both medium-risk and high-risk preterms amounted to 0.73 cy/deg, analysis of variance revealed the difference between PLR and P H R to be significant, but not between PLR and PMR infants. This might be explained by the small number of medium risk neonates (n = 9). The reason for dividing preterms into 3 instead of 2 separate risk groups is that, according to the neonatal signs, the PMR infants did not belong to either lowrisk, or high-risk infants. Neurological outcome at 6 months of age supported and confirmed the decision to consider medium-risk preterms as a separate group. Since gestational ages of both PMR and P H R infants were lower than those of low-risk preterms, the factor gestational age as such can not be considered a risk factor for low mean visual acuity at term age. No significant correlation between birthweight and neonatal visual acuity could be demonstrated. The low visual acuity of medium- and high-risk neonates compared to that of low-risk preterms cannot be accounted for by differences in postnatal age or corrected age, since these were similar across the groups. In the absence of ophthalmological abnormalities, low visual acuities of at-risk preterms seem more likely to be due to pre- and perinatal brain lesions; in fact, mild to severe hypoxic and]or haemorrhagic insults were detected by means of US and EEG. These lesions often involve parts of the brain relevant for visual processing such as optic radiations and occipital lobes 6. However, no differences were observed between the mean visual acuity of P M R and P H R infants, despite the more severe lesions in the latter group. This could be due to the small number of P M R neonates, or that neuroimaging techniques fail to demonstrate (some of the) lesions. Visual acuity development of individual preterms was found to vary across the various risk groups. One P L R infant (case 17) showed a n impaired visual acuity at 50 weeks of corrected age, despite normal neonatal EEG and ultra sound scans, and normal neurology at all times. One PMR infant,(case 21) with a prolonged flare but otherwise no EEG or neurological abnormalities had normal actiity values during the first 13 weeks, but a low acuity at 30 weekL On the other hand, ease 1, a P M R infant with in the neonatal period a prolonged flare combined with an intraventricular haemorrhage
113 grade II, moderate EEG and neurological abnormalities, developed visually and neurologically normal. Visual and neurological follow-up after discharge from the hospital, has been carried out in 12 out of the 14 PHR infants. Visual development of the 3 P H R infants with a prolonged flare was similar to that of the PLR and the PMR infants; they showed normal acuities during the first 20 weeks and, although 2 of them showed a low acuity at around 40 weeks, repeated testing at 70 weeks showed one of them to be within the normal range again. This infant (case 27) had been classified PHR based on a severely abnormal neonatal EEG, and moderately abnormal neurological signs at term and at 6 months. The other infant with a low acuity at 40 weeks (case 23) had shown a moderately abnormal neonatal EEG and developed cerebral palsy at 6 months. Visual development of PHR infants with a cystic PVL was often slow during the first 20 weeks, with acuity values lying within the low-normal range, and from 20 weeks onward clearly impaired in some of the infants. However, acuity development was not found to be clearly related to the severity of the brain lesion as demonstrated by serial US, neonatal EEG, or early and follow-up neurological abnormalities. Visual acuity estimates obtained in PVL children, who developed moderate neurological abnormalities at follow-up (Fig. ld), seemed to be even worse than those of the children who developed a cerebral palsy (Fig. le). The last group included 2 infants whose visual development was found to be normal to 50 weeks, despite the fact that both ultrasound and MRI had revealed cystic-PVL combined in one case with a haemorrhagic infarction; the neonatal EEG had been normal in case 13 and severely abnormal in case 7. Visual acuity of case 7 was found impaired at 70 weeks. In summary, high-risk preterms were found to have a lower mean visual acuity than low-risk preterms. Confirming earlier reports 11'z8'3~ individual visual acuity development of PHR infants, especially those with cystic-PVL, was often found to be worse than that of low- and medium-risk infants, but appeared not to be related to the severity of neurological outcome. Some of the infants with a cystic-PVL, showed a (nearly) normal visual acuity development. The first results of the longitudinal study suggest that for high-risk preterm infants the relationship between the development of visual functions and the severity of cerebral damage as demonstrated by way of neuro-imaging is still unclear. However, early visual assessment in combination with serial US, EEG and neurological assessment seems to have a high prognostic value for later outcome. More data are needed in order to substantiate these findings, and to clarify which early brain lesions have transient
effect and possibly result in a delayed but otherwise normal visual development, and which ones are leading to permanent visual impairment.
ACKNOWLEDGEMENTS
The authors gratefully acknowledge the contribution to this study of C. Romano, M.D. for ophthalmological examination, P. Salvadori, M.D. for visual acuity testing, L. Bartalena, M.D. for US examinations, E. Biagioni, M.D. for EEG recording, Prof. C. Cipolloni and the staff of the N.I.C.U. of the University of Pisa for their assistance. We also thank A. Mura for computer and statistical analysis and C.W. Eveleens Maarse-Havermans for administrative help. This research was supported by grants of the Italian Ministry of Health (current research project 1989) and of Scientific Research and University.
REFERENCES 1 Atkinson, J. and Braddick, O~J., Newborn contrast sensitivity measures: do VEP, O K N and FPL reveal differential development of cortical and subcortical streams? Invest. OphthahnoL Vis. Sci., 30 (1989) Suppl. 313. 2 Atkinson, J., Braddick, O. and French, J., Contrast sensitivity of the human neonate measured by the visual evoked potential, hzrest. OphthahnoL Vis. Sci., 18 (1979) 210-213. 3 Baraldi, P., Ferrari, F., Fonda, S. and Penne, A., Vision in the neonate (full-term and premature). Preliminary result of the application of some testing methods, Doc. OphthahnoL, 51 (1981) 101-112. 4 Birch, E.E., Birch, D.G., Petrig, B. and Uauty, R., Retinal and cortical function of very low birth weight infants at 36 and 57 weeks postconception, Clin. Vision Sci., 5 (1990) 363-373. 5 Brown, A.M. and Yamamoto, M., Visual acuity in newborn and preterm infants measured with grating acuity cards, Am. J. OphthahnoL, 102 (1986) 245-253. 6 Cioni, G., Bartalena, L., Biagioni, E., Boldrini, A. and Canapicchi, R., Neuroimaging and functional outcome of neonatal leukomalacia, Behav. Bra#z Res., 49 (1992) 7-19. 7 Dobson, V., Mayer, D.L. and Lee, C.P., Visual acuity screening ofpreterm infants, hn'est. Ophthahnol. Vis. Sci., 19 (1980) 14981505. 8 Dobson, V., McDonald, M.A. and Teller, D.Y., Visual acuity of infants and young children: forced-choice preferential looking procedures, Am. Orthopt. J., 35 (1985) 118-125. 9 Dobson, V., Schwartz, T.L., Sandstrom, D.J. and Michel, L., Binocular visual acuity of neonates: the acuity card procedure, Dev. Med. Child NeuroL, 29 (1987) 199-206. I0 Dobson, V., D'Antonio, J.A. and Bonvalot, K., Grating acuity in early infancy predicts grating acuity at age 1 year with perinatal complication, hlrest. OphthabnoL Vis. Sci., 30 Suppl. (1989) 142. 11 Dubowitz, L.M.S., Mushin, J., Morante, A. and Placzck, M.,
114
12 13
14
15 16
17
18
19
20
21
22
23
The maturation of visual acuity in neurologically normal and abnormal newborn infants, Behav. Braht Res., 10 (1983) 39-45, Fantz, R.L., Visual perception from birth as shown by pattern selectivity, Ann. N.Y. Acad. Sci., 118 (1965) 793-814. Ferrari, F., Cioni, G. and Prechtl, H.F.R., Qualitative changes of general movements in preterm infants with brain lesions, Earl)' Hum. Dev., 23 (1990) 193-231. Getz, L., Dobson, V. and Luna, B., Full-term acuity card norms can be used for preterm children 0-3 years of age, hlvest. Ophthahn. Vis. Sci., 32 Suppl. (1991) 962. Griffiths, R., The Ability of Babies. University London Press, London, 1954. Groenendaal, F., Van Hof-van Duin, J., Baerts, W. and Fetter, W.P.F., Effect"of perinatal hypoxia on visual development during the first year of (corrected) age, Earl), Hum. Dev., 20 (1989) 267-279. Hermans, A.J.M., Van Hof-van Duin, J. and Oudesluys-Murphy, A.M., Visual acuity in low birth weight (1550-2500) neonates, Early Human Dev., 28 (1992) 155-167. Lubchenco, L.O., Hansman, C. and Boyd, E., Intrauterinegrowth in length and head circumference as estimated from live birth at gestational ages from 26-42 weeks, Pediatrics, 37 (1966), 403408. McDonald, M.A., Dobson, V., Sebris, S.L., Baitch, L., Varner, D. and Teller, D.Y., The acuity card procedure: a rapid test of infant acuity, hlvest. Ophthahnol. Vis. ScL, 26 (1985) 11581162. b,liranda, S.B., Visual acuity and pattern preferences of premature infants and fullterm neonates, J. Exp. Child Psychol., 10 (1970) 189-205. Mohn, G. and Van Hof-van Duin, J., Rapid assessment ofvisual acuity in infants and children in a clinical setting, using acuity cards, Doc. OphthahnoL Proc. Ser., 45 (1986) 363-372. Mohn, G., Van Hof-van Duin, J., Fetter, W.P.F., De Groot, L. and Hage, M., Acuity assessment in non-verbal infants and children. Clinical experience with the acuity card procedure, Dev. Med. Child NeuroL, 30 (1988) 232-244. Norcia, A.M. and Tyler, Ch.W., Spatial frequency sweep VEP:
24
25
26
27 28 29
30
31
32
33
34
35
visual acuity during the first year of life, Vision Res., 25 (1985) 10 1399-1408. Porciatti, V., Temporal and spatial properties of the patternreversal VEPs in infants below 2 months of age, Hum. NeurobioL, 3 (1984) 97-102. Prechtl, H.F.R., The neurological examination of the full term newborn infant, In Clinics hi Developmental Medichw, 63, 2nd edn., Heinemann Medical Books, London, 1977, 65 pp. Scher, S.M., Dobson, V., Carpenter, A.N. and Guthrie, R.D., Visual and neurological outcome of infants with periventricular leukomalacia, Dev. Med. Child NeuroL, 31 (1989) 353-365. Touwen, B.C.L., Neurological development in infancy, In Clinics in Developmental Medichw, 58, Heinemann, London, 1976. Uzgiris, I. and Hunt, J.McV., Assessment in hfancy, University of Illinois Press, Urbana, IL, 1985. Van ttof-van Duin, J. and Mohn, G., Vision in the preterm infant. In H.F.R. Prechtl (Ed.), Continuity of Neural Fwwtionsfrom Prenatal to Postnatal Life, Clinics hz Developmental ~Iedic#te, Spastics Int. Med. Publications, London, 1984, pp. 93-115. Van Hof-van Duin, J. and Mohn, G., Th.e development of visual functions in preterm infants, Ergebn. Exp. Med., 46 (1985) 350362. Van Hof-van Duin, J. and Mohn, G., The development of visual acuity in normal fullterm and preterm infants, Vision Res., 26 (1986) 909-916. Van Hof-van Duin, J., Evenhuis-van Leunen, A., Mohn, G., Baerts, W. and Fetter, W.P.F., Effect of very low birth weight (VLBW) on visual development during the first year after term, Earl), 'Hum. Dev., 20 (1989) 255-266. Van Hof-van Duin, J., Heersema, D.J., Groenendaal, F., Baerts, W. and Fetter, W.P.F., Visual field and grating acuity development during the first 21# years after term, Behav. Brain Res., 49 (1992) 115-122. Van H0f-van Duin, J., Mohn, G., Fetter, W.P.F., Mettau, J.W. and Baerts, W., Preferential looking acuity in preterm infants, Behav. Brahl Res., 10 (1983) 47-51. Volpe, J.J., Neurology of the newborn, 2nd edn., W.B. Saunders, Philadelphia, 1987.