Abstract
Purpose:
To investigate the characteristics of retinal electrophysiological activity in relation to early myopia development in children.
Methods:
Fifty-six children aged 6 to 9 years with emmetropic refractive error (defined as ≥ −0.5 diopter [D] and ≤ +0.5 D) were recruited. Cycloplegic refraction, axial length, and global flash multifocal electroretinogram (MOFO mfERG) at 49% and 96% contrast levels were recorded in all children at their first visit. The refraction and axial length measurements were repeated after 1 year. The amplitudes and implicit times of the direct component (DC) and the induced component (IC) of the MOFO mfERG obtained at the initial visit were analyzed. Correlations between the MOFO mfERG parameters and changes in refractive error and axial length were investigated.
Results:
The mean spherical equivalent refractive error and axial length of the eyes of the children at the first visit were +0.19 ± 0.33 D and 23.14 ± 0.6 mm, respectively. After 1 year, the mean refractive error increased by −0.55 ± 0.53 D, whereas axial length increased by 0.37 ± 0.22 mm. The changes in refractive error and axial length were significantly correlated with the central IC amplitudes at 49% contrast level measured at the initial visit (ρ = 0.46, P < 0.001 and ρ = −0.34, P = 0.01, respectively).
Conclusions:
The prospective changes we have shown are believed to derive from central inner retina. These changes appear to precede myopia and could be a potential reference for juvenile myopia development.
Excessive eyeball elongation causes myopia. In severe cases, it may result in retinal stretching, thinning, and changes in retinal cell morphology and pathology. Application of the ERG technique has provided ample evidence to confirm that myopia results in impaired retinal function. It has been reported that myopia in adults was associated with decreased nonlinear components of ERG responses,
1 multifocal ERG (mfERG) responses,
2,3 retinal adaptation response,
4 and inner retinal function.
5–7 Axial length was shown to be linearly related to ERG amplitudes,
8 first-order kernel, and the first slice of second-order kernel of mfERG responses.
9 The reduction in mfERG responses in myopic adults is believed to be due to the deterioration in retinal function associated with long-standing myopia. However, this explanation cannot be applied to myopic children, and discrepancies of ERG characteristics have been noted between myopic adults and children.
2,7 Luu and his colleagues
2 conducted a cross-sectional study of mfERG measurement in 104 children and 31 adults with a range of refractive errors. They found a significant correlation between refractive error and mfERG response in adults, but this correlation was not observed in children. Ho et al.
7 also demonstrated different characteristics of retinal electrophysiological activities in adults and children in terms of retinal regions and mfERG components.
To the best of our knowledge, no study has previously investigated retinal function in young children with emmetropic refractive status, nor the correlation between retinal function and subsequent myopic change. The current study sought to use global flash mfERG (MOFO mfERG) parameters to predict early myopic development in children. We hypothesized that emmetropic children with decreased retinal response measured by the global flash mfERG would subsequently develop myopia.
The MOFO mfERG was recorded with Dawson-Trick-Litzkow fiber acting as the active electrode (located on the cornea of the right eye) and gold-cup surface electrodes as reference (located at the outer canthus of the right eye) and ground (located at the forehead). The recordings were commenced after the pupil of the subject's right eye was dilated to at least 7 mm diameter. The stimulus pattern was generated by the Visual Evoked Response Imaging System (VERIS Science 6.0.6d19; EDI, San Mateo, CA, USA) and displayed on a 22-inch LED monitor (model VG2239M-LED; ViewSonic, Walnut, CA, USA). The stimulus pattern consisted of 61 hexagons subtending 37 degrees horizontally and 33 degrees vertically at a working distance of 40 cm. Full correction was provided to compensate for a subject's sphero-cylindrical refractive error and working distance.
The global flash paradigm was composed of four video frames as shown in
Figure 1A: starting with a frame of multifocal flashes, followed by a dark frame, a full-screen flash frame and a second dark frame in each slice of the pseudorandom binary m-sequence (2
12–1). Frame frequency of the monitor was set at 75 Hz. The luminance of the multifocal flash stimulus in light and dark states was 185 and 4 cd/m
2, respectively, for 96% contrast level, and at 140 and 48 cd/m
2, respectively, for 49% contrast level. The mean luminance of the multifocal flashes and the background was approximately 94 cd/m
2 for both contrast levels. The recording time of 4 minutes for each contrast level was divided into 16 segments to allow the subject to rest between runs. A central cross was used for fixation. The signal was monitored using the real-time response provided by the VERIS program and any segment contaminated by blinks or fixation loss was re-recorded. An amplifier (model 15A54, Physiodata Amplifier System; Grass Technologies, Astro-Med, Inc., West Warwick, RI, USA) was used with a signal gain of 100,000 times and the band pass filter between 10 and 300 Hz.
Groups of responses from the MOFO mfERG trace arrays were averaged to five successive rings from the center to the periphery as shown in
Figure 1B. The peak-to-peak amplitudes of the direct component (DC) and the induced component (IC) responses were calculated. The implicit times of DC and IC response were counted from the onset of multifocal flash and global flash, respectively, to the peak of the response (
Fig. 1C). Refractive error and axial length changes were calculated by subtracting the results of the initial visit from that of the follow-up visit.
The normality of the variables was determined by the Shapiro-Wilk Test (SPSS 23.0; IBM Corporation, Chicago, IL, USA). As the data of the changes in refractive error and axial length were not normally distributed, nonparametric tests were used for the statistical analysis. Wilcoxon signed ranks test was used to compare the refractive error and axial length between the two visits and to compare the amplitudes and implicit times between the DC and IC of mfERG response within the same subject. The correlation between refractive error change and axial length change was tested by the Spearman test. Spearman's rank correlation was also used to analyze the relationship between the MOFO mfERG responses and the myopic development in terms of changes in refractive error and axial length. Bonferroni adjustment was applied, as there were five retinal regions within each subject's right eye for comparison, and thus the adjusted significance level was set to 0.01.
Intra-sessional measurement variability of MOFO mfERG responses at 49% contrast level was tested on 11 children (7 girls and 4 boys) aged from 8 to 11 years. The method of Bland and Altman was used to calculate the coefficient of repeatability (COR), defined as 1.96 times the SD of the differences between the paired measurements. The confidence interval was 95%. The COR results and Bland-Altman plots are shown in the Appendix (
Fig. A1;
Table A1).
The authors thank Paul Lee for his valuable advice in the statistical analysis.
Supported by the General Research Fund (PolyU 5605/13M) from Research Grants Council, HKSAR, and the Internal Research Grants (G-YBBS) from The Hong Kong Polytechnic University.
Disclosure: S.Z.-C. Li, None; W.-Y. Yu, None; K.-Y. Choi, None; C.H.-I. Lam, None; Y. Lakshmanan, None; F.S.-Y. Wong, None; H.H.-L. Chan, None