Abstract
Purpose:
We investigated the pattern of meridional anisotropies, if any, for pattern onset–offset visual evoked potential (POVEPs) responses and psychophysical grating acuity (GA) in children with normal letter visual acuity (20/20 or better).
Methods:
A total of 29 children (aged 3–9 years), nine of whom were astigmatic (AS), were recruited. Orientation-specific monocular POVEPs were recorded in response to sinewave grating stimuli oriented along the subjects' principal AS meridians. Horizontal and vertical gratings were designated Meridians 1 and 2, respectively, for nonastigmatic patients (Non-AS). Binocular POVEPs in response to the same stimuli, but oriented at 45°, 90°, 135°, and 180°, were recorded. Psychophysical GAs were assessed monocularly and binocularly along the same meridians using the same stimuli by a 2-alternative-forced-choice staircase technique. The C3 amplitudes and peak latencies of the POVEP and GAs were compared across meridians using linear mixed models (monocular) and ANOVA (binocular).
Results:
There were significant meridional anisotropies in monocular C3 amplitudes regardless of astigmatism status (P = 0.001): Meridian 2 (mean ± SE Non-AS, 30.13 ± 2.07 μV; AS, 26.53 ± 2.98 μV) was significantly higher than Meridian 1 (Non-AS, 26.14 ± 1.87 μV; AS, 21.68 ± 2.73 μV; P = 0.019), but no meridional anisotropies were found for GA or C3 latency. Binocular C3 amplitude in response to horizontally oriented stimuli (180°, 29.71 ± 3.06 μV) was significantly lower than the oblique (45°, 36.62 ± 3 .05 μV; P = 0.03 and 135°, 35.95 ± 2.92 μV; P = 0.04) and vertical (90°, 37.82 ± 3.65 μV; P = 0.02) meridians, and binocular C3 latency was significantly shorter in response to vertical than oblique gratings (P ≤ 0.001).
Conclusions:
Meridional anisotropy was observed in children with normal vision. The findings suggest that horizontal gratings result in a small, but significantly lower POVEP amplitude than for vertical and oblique gratings.
Astigmatism is a relatively common type of refractive error that affects approximately 20% of school-aged children.
1 If present with other refractive errors, it accounts for approximately 47%
1 of correctable visual impairments (defined as visual impairment that is correctable to 20/20 with optical correction). Although normally-developing infants have a relatively high prevalence of low-to-moderate astigmatism (1.00–2.00 diopters cylinder [DC]) with their principal meridians typically lying close to the cardinal orientations (i.e., vertical and horizontal),
2–5 they are unlikely to be negatively affected by the retinal blur caused by this degree of astigmatism.
6 In fact, retinal blur most likely contributes to the development of the accommodative feedback system.
7 Additionally, there is a sharp decline in the magnitude of astigmatism over the first year of life.
2,3
High magnitudes of childhood astigmatism (>2.50 DC) are less common.
8 Previous studies indicated that only 5% to 20% of 4-year-old children have astigmatism between 1.00 to 2.00 DC
9 and fewer than 5% have ≥2.00 DC.
9 Astigmatism (≥1.50 DC) at ages 5 to 6 years is approximately 11% in Singapore.
10 Some astigmatic children may suffer neural deficits corresponding to the astigmatic meridians,
11 a condition known as meridional amblyopia.
12 The onset of refractive amblyopia is approximately 3 to 4 years of age
13 and is less likely to develop for the first time beyond the age of 7 years.
14,15 Young children with astigmatism may be adapted to the optical aberration and may not actively complain about blurred vision, so astigmatism sometimes may be undetected without clinical examination or screening
8 leading to extended durations of uncorrected astigmatism. Thus, astigmatism may be an amblyogenic factor. Factors thought to influence the development of meridional amblyopia include age at astigmatism onset,
16 duration of astigmatic blur,
16 magnitude of astigmatic blur,
17,18 type of astigmatism,
19 and the accommodative state that regulates astigmatic blur.
20,21
A study of 1682 Singaporean children ages 30 to 72 months demonstrated that 85% of amblyopic cases were related to uncorrected refractive errors and only 15% were related to strabismus.
10,22 In addition, 29% of the amblyopes had isometropic astigmatism >2.50 DC and 42% had aniso-astigmatism ≥1.50 DC.
22 Meridional amblyopia also has been found previously in two small-scale experimental visual evoked potential (VEP) and psychophysical studies.
20,23 Freeman and Thibos
20 found that meridional amblyopes had reduced VEP amplitude at the meridian that experienced the greatest retinal blur and that this was not an optical effect. However, the number of subjects investigated was small (
n = 9) with no details about the age of or treatment undertaken by the subjects. Fiorentini and Maffei
23 reported meridional anisotropies along the astigmatic meridians in five of seven highly astigmatic children (defined as 3.00–4.00 DC) whereas low astigmatic children (
n = 16; defined as 0.50–1.50 DC) did not have significant meridional anisotropy. However, the report was confounded by mixed results in two subjects: one highly astigmatic subject who did not have meridional anisotropy and one who had highly irregular waveforms. Additionally, they were unable to establish whether the astigmatic children were previously amblyopic.
Another well-known meridional anisotropy is the oblique effect,
24 where stimuli oriented at the cardinal meridians (horizontal and vertical) tend to have stronger responses than those at the oblique meridians.
25 Other anisotropies observed in people with normal vision include two kinds of horizontal effect. One study found poorer contrast sensitivity to horizontal than vertical square-wave gratings of very low spatial frequencies (SF; 0.06–0.10 cycles per degree [cpd]) in newborn infants.
26 In that study, refractive errors, such as astigmatism, were not considered. It is unclear whether similar meridional anisotropies are expected in preschool and school-aged children. Another type of horizontal effect was found psychophysically in adults viewing natural scenes
27–29 containing broad SF and orientation content, whereby sensitivity was less for horizontal than for vertical and oblique stimuli. Studies have found that meridional anisotropies may be spatial frequency dependent
30 and may be dependent on: (1) contrast,
31 (2) type of stimulus (e.g., natural image
32,33 versus grating),
34–38 (3) mode of stimulus presentation (e.g., simultaneous or successive),
39 (4) time for neural adaptation (e.g., sustained or transient stimulus),
40 and (5) age of the subject.
41
While individuals with meridional amblyopia are likely to have meridional anisotropy aligned with the astigmatic meridians, it is not clear whether nonamblyopic children with and without astigmatism will have any meridional anisotropy. It is important to understand the normal pattern of anisotropy of orientation-specific psychophysical and electrophysiologic responses in young children before evaluating children with amblyopia for the presence of meridional amblyopia. Therefore, we investigated whether meridional anisotropies exist in children with normal vision (letter acuity), using orientation-specific pattern onset–offset visual evoked potential (POVEP) and grating acuity (GA). We hypothesized that no meridional anisotropy would be demonstrated other than the oblique effect for the stimuli used.
Children of preschool and school age with normal letter visual acuity (VA; defined as ≤0.05 logMAR in each eye) were included in the study. Nonastigmatic children (Non-AS) were defined as having <0.50 DC and astigmatic children (AS) were defined as having ≥0.50 DC. Spectacle correction, if required, was as prescribed by subjects' own attending clinicians to reflect real-life conditions. Children with amblyopia, strabismus, ocular diseases or abnormalities were excluded. All subjects underwent ocular health examination, logMAR VA (HOTV chart, Good-lite Co, Elgin, IL, USA), binocular vision, retinoscopy, autorefraction, and manifest subjective refraction assessments using age-appropriate refraction techniques. The decision to conduct cycloplegic refraction was made by the clinician, and not the researchers. Six out of 29 subjects did not have cycloplegic refraction. All subjects were able to read the English alphabet fluently due to education level.
The POVEPs were recorded using the Espion System (Diagnosys, Cambridge, UK) at a sampling rate of 5 kHz and a band-pass filter of 0.312–100 Hz and a recording window of 1 second per sweep. The stimuli were generated using the ViSaGe Mk II (Cambridge Research Systems, UK) and presented on a calibrated Sony CPD-G500 21-inch Trinitron cathode ray tube (CRT) monitor. The ViSaGe stimulus generator is a 14-bit system that was able to generate the stimulus specified at the viewing distances used and with the high-performance CRT monitor (Maximum Resolution, 2048 × 1536 at 75 Hz; horizontal and vertical scan range, 30–121 kHz and 48–160 Hz, respectively). It presented 35.2 cpd gratings without aliasing at the viewing distance of 2.2 m. If the resolution of the monitor was insufficient to present the stimulus without aliasing, the solution would have been to increase the viewing distance to increase the physical size of the stimulus while maintaining the angular size of the stimulus. Impedance was monitored to be below 8 kΩ before each recording.
Psychophysical GA was measured monocularly using the same orientation-specific POVEP sine wave gratings with 54% contrast presented pattern-onset–offset (100 msec on and 400 msec off) for 2500 msec as described previously except a smaller field size of 3° was used to allow a spatial forced choice task within the display size. The stimulus was presented for 100 msec only five times and the task was to determine the location of the grating stimulus, on the left or right side of the screen, which were located either 2° left or right from the fixation target. Subjects indicated the location of the stimulus either verbally or by pointing at the stimulus location and they had ample time to make a decision, but usually within 5 to 10 seconds at most. If they were unable to detect the grating, they were encouraged to guess to make a decision. Threshold GA was estimated as the average of the last four reversals of a psychophysical staircase; two-alternative spatial forced-choice method with a 1 down 1 up staircase technique with 3-dB step size ranging from low to high SF (maximum presented at 35 cpd). Incorrect responses resulted in the SF being decreased and correct responses resulted in SF being increased. Custom-designed software (School of Optometry and Visual Science [SOVS]–Centre For Eye Health [CFEH] Psychophysical Testing Suite, Sydney, Australia) written using Matlab (Version R2017a, MathWorks, Inc., Natick, MA, USA) was used to generate the stimuli and assess threshold. Subjects were tested with room lights turned off at a viewing distance of 2.2 m.
There were no significant differences between the AS and Non-AS groups. Across the entire group of subjects, the average C3 amplitudes of the obliques (average of 45° and 135°, 34.62 ± 2.11 μm; 95% CI, 30.28–38.95) were significantly (P = 0.017) greater than the average cardinal meridians (average of 90° and 180°, 31.35 ± 1.66 μm; 95% CI, 27.94–34.77) by a mean difference of 3.27 ± 1.28 μm (95% CI, 0.63–5.90).
Additionally, there was a small but statistically significant effect of meridian on POVEP C3 log(amplitude;
P = 0.03;
F3,24 = 3.56). There was no effect of meridian or age on log(GA). Pairwise comparison of the binocular dataset shows that the horizontal (180°, 29.71 ± 3.06 μV; 95% CI, 3.00–3.48) was significantly lower in log(amplitude) compared to the rest of the meridians tested (45°,
P = 0.030; 36.62 ± 3.05 μV; 95% CI, 3.33–3.68; 135°,
P = 0.035; 35.95 ± 2.92 μV; 95% CI, 3.27–3.66; 90°,
P = 0.02; 37.82 ± 3.65 μV; 95% CI, 3.40–3.71). The mean differences between the horizontal and the rest of the meridians were 6.90 ± 1.53 μV (95% CI, 0.02–0.52), 6.24 ± 1.74 μV (95% CI, 0.01–0.45), and 8.11 ± 1.95 μV (95% CI, 0.03–0.59) for the 45°, 135°, and 90° meridians, respectively (
Fig. 5a).
C3 log(latency) was significantly shorter in response to vertical than oblique gratings (
P ≤ 0.001;
Fig. 5b).
We investigated whether meridional anisotropies exist in astigmatic and non-astigmatic children with normal vision using POVEP and psychophysical GA. It was hypothesized that no meridional anisotropy would be demonstrated other than the oblique effect. In the study, the only effect that might be similar to an oblique effect was for binocular C3 latency, in which longer latencies were observed for oblique stimuli compared to the vertical meridian (
P ≤ 0.001). However, this may not be clinically significant if we consider 10% of the longest latency as being within the acceptable limits of repeatability.
45,47
What could account for these findings? WTR astigmatism is known to have greater prevalence than other types (i.e., against-the-rule [ATR] or oblique astigmatism) in preschool/kindergarten and school-aged children older than 4–5 years,
48,49 so the finding that eight of nine AS subjects in our study had WTR astigmatism is reflective of such a population trend. In this study, the POVEP grating stimuli for the monocular recordings were matched exactly to the principal astigmatic meridians of each child. Each meridian was considered separately in the AS cohort to identify which focal line lay closest to the retina when uncorrected for refractive error. AS patients may have to accommodate preferentially to one focal line, such that one orientation is imaged more clearly on the retina than the perpendicular orientation. Since the majority of the AS cohort had either simple (three of nine) or compound myopic (five of nine) WTR astigmatism (example: −1.00/−1.00 × 180), the more myopic focal line is horizontal. Given that accommodation tends to favor the situation in which one focal line lies on the retina,
21 it is expected that horizontal lines will be more frequently out-of-focus with distance viewing tasks. However, either line could become out-of-focus during near tasks (e.g., 40 cm).
Consensual accommodation (equal for each eye) is the typical response to consensual accommodative stimuli,
50 with the qualifier that the binocular accommodative response is biased towards the dominant eye's response.
51 However, an aniso-accommodative stimulus of 1 D can generate 0.19 to 0.38 D of aniso-accommodation. This may act to partially or fully preserve binocular summation in contrast sensitivity, stereo acuity, and provide efferent feedback about each eye's refractive error that may guide isometropization.
50 In the chick model of myopia, induced astigmatic refractive error can result in complex compensatory changes to the retina that result in astigmatism when the inducing astigmatism is removed, despite the ability to accommodate. However, it is unclear how the human visual system may resolve accommodation in the case of bilateral astigmatic refractive errors or whether meridional amblyopia will arise.
52
Meridional amblyopia may be one consequence if the astigmatic blur occurs during the critical period.
20,21,53 The degree of astigmatic blur is strongly dependent on its accommodative demand. Depending on the accommodative status of the individual,
54 there may be greater variability for either one of the focal planes to be clear when viewing a near object.
15 As there is no significant difference in the meridional anisotropies when comparing AS and Non-AS groups, it may be deduced that the meridional anisotropies in this AS cohort are not related to their principal astigmatic meridians.
Alternatively, the finding of monocular meridional anisotropy may be attributed to a horizontal effect whereby the horizontal meridian is less sensitive than the rest of the meridians. The binocular POVEP data also supported this interpretation since the horizontal meridian's C3 amplitudes were significantly reduced compared to the oblique and vertical meridians. Furthermore, this phenomenon is unlikely to be induced by luminance artefacts from raster-scan CRT monitors, since such artefacts would have resulted in horizontal gratings being presented more precisely than vertical gratings.
55–58
As our subjects were young children, it was postulated that these findings may be a continuation of the horizontal effect, as has been previously observed in infants in relation to contrast sensitivity to oriented gratings, but scaled to higher SF in line with improved spatial resolution acuity with increasing age.
26 Although horizontal effects have not been previously investigated electrophysiologically, data from a study by Arakawa et al.
30 in young adults (
n = 9) aged 19–25 years may be useful to review as they found higher VEP amplitudes in response to oblique rather than cardinal gratings at 4 cpd. Higher SF (>5 cpd) tended to exhibit the oblique effect (oblique orientations were poorer than the horizontal orientation by approximately 1 μV). Arakawa et al.
30 suggest a SF dependency of meridional anisotropies. Therefore, our finding of a horizontal effect may reflect normal, albeit immature, findings.
Young children may have more limited visual experiences than adults and, hence, less opportunity to develop biases against oblique meridians, which is perhaps why binocular latency findings are equivocal in relation to the oblique effect, and may reflect a developing oblique effect with respect to binocular C3 peak latency. The form of horizontal effect that has been described in response to viewing natural stimuli
27–29 is unlikely to explain our study data, as the stimuli used in our study were not broadband natural scenes. However, no meridional anisotropies were observed for psychophysical GA in either the AS or Non-AS groups.
While POVEP C3 amplitudes and psychophysical GA did not differ significantly between the AS and Non-AS groups, the Non-AS group had a trend for better GA, by 0.43 octaves (equivalent to approximately nine letters on the logMAR chart), than astigmatic children. Although childhood astigmatism was expected to have some deleterious effect on the visual resolution of the gratings, the astigmatic subjects in this cohort did not have as high magnitudes of astigmatism that have been described previously in other studies as causing negative effects on GA in nonamblyopic children <3 years old.
13 Age improvements in GA may be related to improvements in contrast sensitivity with age as the gratings were presented at moderate, rather than high contrast.
59
Our study established the presence of meridional anisotropies that are consistent with trends that have been found in other studies, specifically a horizontal effect. However, it is acknowledged that where no significant effects were found, this may be due to insufficient statistical power or low magnitudes of astigmatism. This is because the original sample size for the study was powered to detect the oblique effect, but not to assess the secondary exploratory aim of an effect due to astigmatic refractive error. While a larger sample size may help to clarify these observations, this would be a very small effect size based on the current study results. Other limitations of the study include: (1) not having a full history of the subject's refractive status, (2) being unable to track whether spectacles were worn regularly or consistently, (3) the assumption that vergence/accommodative demands were normal in this cohort, and (4) the results relate to the present sample and its generalizability to a larger population with a wider range of refractive errors or ages is unclear.
The authors thank the parents and children for their participation, the colleagues at the Visual Electrophysiology Laboratory at Singapore National Eye Centre and Eye Clinic at KK Children's and Women's Hospital, and the Guide Dogs NSW/ACT for funding the development of the SOVS-CFEH Psychophysical Test Suite.
Supported by the ARVO Publications Grant.
Disclosure: T.P. Yap, None; C.D. Luu, None; C.M. Suttle, None; A. Chia, None; M.Y. Boon, None