Purpose To determine the choroidal thickness (CT) in the macular area of eyes of children with hyperopic anisometropic amblyopia and to compare the thickness with that of fellow eyes and age-matched controls.
Materials and methods Twenty-five patients (6.6±2.2 years, mean±SD) with hyperopic anisometropic amblyopia and twenty age-matched controls (6.7±1.9 years) were studied. The CT was measured with the enhanced depth imaging programme of a spectral domain optical coherence tomographic instrument in all patients and controls. The CT of the subfoveal area and at 1 mm and 3 mm diameter around the fovea was determined. In addition, the correlation between the CT and axial length was calculated.
Results The mean subfoveal CT was 351.3±54.7 µm in the amblyopic eyes, 283.5±55.2 µm in the fellow eyes and 282.7±73.3 µm in the control eyes. The subfoveal choroid in amblyopic eyes was significantly thicker than that of the fellow eyes and control eyes (p=0.001). There was a significant negative correlation between the subfoveal CT and the axial length in the amblyopic eyes (amblyopic eyes: r=−0.51, p=0.01) and the control eyes (r=−0.46, p=0.01).
Conclusions The subfoveal choroid of eyes with hyperopic anisometropic amblyopia is significantly thicker than that of the fellow eye and the age-matched controls. The profile of the CT in the amblyopic eyes was different from that of the fellow eyes and control eyes.
- Child health (paediatrics)
- Optics and Refraction
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Amblyopia is a developmental disorder of the visual system that is characterised by reduced visual acuity unilaterally or bilaterally in the absence of any ocular pathology. Amblyopic eyes are structurally normal on clinical examinations,1 and the best evidence is that it is caused by a deprivation of clear vision in the period of neural plasticity early in life. This can be caused by anisometropic amblyopia, high bilateral refractive errors, or visual deprivation, for example, cataracts, ptosis.2 ,3 Of these, hyperopic anisometropia is the most frequent risk factor for amblyopia.4
Experimental evidence indicates that the amblyopia is caused by abnormalities in the visual cortex,4–6 and whether the retina and choroid are altered in eyes with amblyopia is controversial. The introduction of optical coherence tomography (OCT) has allowed clinicians to examine the retinal morphology of human eyes and to answer the question of whether the retina is structurally normal in eyes with amblyopia. A large number of studies have been recently performed to assess the thickness of the retinal nerve fibre layer,7 ,8 macular volume9 ,10 and retinal thickness11–13 in eyes with amblyopia. However, a consensus of whether the retina is abnormal has not been reached.
New information on choroidal anatomy and physiology have been recently published.14 It was reported that the choroidal thickness (CT) in healthy eyes decreases with increasing age,15–20 but there have been only a few studies on CT in children.15 ,21–23 In addition, whether the choroid is altered in children with amblyopia has not been determined. There is evidence, primarily from research with young animal models24–27 that the choroid plays an important role in the modulation of refractive state and may be involved in the development of refractive errors. In chicks,26 ,27 marmosets25 and macaque monkeys24 a choroidal compensation was found, and myopic defocus caused choroidal thickening and decreased scleral growth. Eyes of young animals receiving frequent brief episodes of plus lens-induced myopic defocus had a decrease in the rate of growth in the absence of long-term choroidal thickening.24–27 However in human children, the relationship between CT and ocular growth has not been determined.
Thus, the purpose of this study was to determine the CT in the macular area of eyes with hyperopic anisometropic amblyopia and to compare it with that of the fellow eyes and with the eyes of age-matched controls. We also determined whether choroidal compensation was present in human children as it does in young animals.
Patients and methods
This was a cross-sectional comparative, non-interventional study conducted at the Nara Medical University from April 2012 to October 2012. The protocol of this study conformed to the tenets of the Declaration of Helsinki, and it was approved by the Internal Review Board of the Nara Medical University. Consent was obtained from all of the patients and controls or parents to perform the original measurements and to review their medical records. All examinations were performed between 13:00 to 15:00 to avoid diurnal variations.28 ,29
An eye was classified as being amblyopic when the best-corrected visual acuity (BCVA) was ≤20/30 in one eye or was at least two Snellen visual acuity lines worse than the fellow eye. Anisometropia was defined as a difference of 2.00 dioptres (D) or more in the two eyes.
Twenty-five eyes with hyperopic anisometropic amblyopia and their fellow eyes were studied. The mean age of the patients was 6.6±2.2 years (±SD) with a range of 3–11 years. All of the patients and controls had dilated funduscopic examinations. Patients with strabismus, organic eye diseases, history of intraocular surgery, laser treatment, cataract, glaucoma or any other retinal disorders were excluded. In addition, patients who could not cooperate for the OCT examinations were also excluded.
Twenty right eyes of 20 age-matched controls (6.7±1.9 years) who had normal or corrected-to-normal visual acuity (0 logarithm of the minimal angle of resolution (logMAR) units or better) in both eyes were studied. We recruited the controls from subjects who visited Nara Medical University because of the compulsory visual screening of 3–8-year-olds, and all had good visual acuity and no retinal diseases. The parents were also informed about the study and procedures, and an informed consent was obtained from all.
The visual acuity was measured with a standard Snellen chart, and the decimal visual acuity was converted to logMAR units for the statistical analyses.
The axial length of the eye was measured with the IOL Master (Carl Zeiss Meditec, Dublin, California).
Optical coherence tomography (OCT)
The CT was measured on the images obtained by a Heidelberg Spectralis spectral domain OCT (Heidelberg Engineering, Heidelberg, Germany; SD-OCT) with the enhanced depth imaging programme from all patients and controls. All images were recorded by an experienced ophthalmologist and by one of the authors. The CT was measured manually as the distance between the basal edge of the retinal pigment epithelium and the chorioscleral border. It was measured at 9 points; directly beneath the fovea or the subfoveal area, and at the superior, inferior, temporal and nasal points of 1 mm and 3 mm diameter (figure 1). Three measurers who were masked as to whether the eye was amblyopic, selected the best scan and independently measured the CT at the nine regions in all of the OCT images. The final thickness was calculated as the arithmetic mean of the calculations of the three measurers. The intermeasurer reproducibility was evaluated using an intraclass correlation coefficient.
The results are expressed as the means± SD. One way analysis of variance (ANOVA) was used to determine the significance of differences in the values in the three groups. The CT at each of the sectors in the amblyopic eyes was compared with the corresponding sectors of the fellow eyes and control eyes by Tukey tests. The significance of the correlation between the subfoveal CT and age, refractive error and axial length was determined by Pearson's correlation coefficient. A p<0.05 was taken to be statistically significant. Statistical analysis was performed using licensed statistical software (SPSS V.21.0; SPSS, Chicago, Illinois, USA).
The demographic data of the patients and controls are shown in table 1. There were no significant differences in the age and sex distribution among the two groups of subjects (ANOVA). The mean BCVA was 0.29±0.16 logMAR units in the amblyopic eyes, −0.03±0.05 logMAR units in the fellow eyes and −0.09±0.06 logMAR units in the control eyes. The mean BCVA was significantly worse in the amblyopic eyes than in the fellow and the control eyes (p=0.01, ANOVA). The mean BCVA in the amblyopic eyes was significantly worse than that of the fellow eyes (p=0.01, Tukey) and the control eyes (p=0.01, Tukey).
The mean refractive error was +3.97±1.86 D with a range of +2.0 D to +7.0 D in the amblyopic eyes, +1.92±1.56 D with a range of 0 D to +5.0 D in the fellow eyes and +2.75±2.38 D with a range of +0.5 D to +7.5 D in the control eyes (p=0.001, ANOVA). The mean refractive error was significantly more hyperopic than that of the fellow eyes (p=0.005, Tukey), but the difference between amblyopic eyes and control eyes was not significant (p=0.34, Tukey).
The mean axial length was 21.55±0.86 mm in the amblyopic eyes, 22.14±0.93 mm in the fellow eyes and 21.72±1.12 mm in the age-matched control eyes. The mean axial length was not significantly different in the three groups (p=0.07, ANOVA).
Case report of a patient with amblyopia
The findings in a representative 5-year-old patient with amblyopia are shown in figure 2. Our initial examination showed that his BCVA was 0 logMAR units in the right eye and 0.5 logMAR units in the left eye. Slit-lamp and fundus examinations showed that both eyes were completely normal. Figure 2A shows the enhanced depth image for the fellow eye and figure 2B shows that of the amblyopic eye. The thickness of the subfoveal choroid in the amblyopic eye was 365 µm (figure 2B) which was much thicker than the 294 µm of the fellow eye (figure 2A).
Choroidal Thickness (CT)
The mean subfoveal choroidal thickness (CT) was 351.3±54.7 µm in the amblyopic eyes, 283.5±55.2 µm in the normal fellow eyes and 282.7±73.3 µm in the control eyes. The subfoveal choroid in the amblyopic eyes was significantly thicker than that of the fellow eyes and the control eyes (p=0.001, ANOVA; p=0.01, respectively, Tukey test).
The interobserver reproducibility was excellent (intraclass correlation coefficient=0.91).
The subfoveal choroid of the amblyopic eye was significantly thicker than that of the fellow eyes and control eyes. At 1 mm diameter, the temporal and nasal choroidal sectors of the amblyopic eye were thicker than that of the fellow eyes (Tukey test; p<0.05; table 2). In the amblyopic eyes, the choroid was thickest in the subfoveal area followed by the temporal, superior, inferior and nasal sectors for the 1 mm and 3 mm diameter sectors (figure 3A,B). The subfoveal CT was significantly thicker than that of the nasal sector for the 1 mm diameter sector (Tukey test, p=0.008). For the 3 mm sector, the subfoveal CT was significantly thicker than the superior, inferior, temporal and nasal sectors (Tukey test, superior, p=0.03; inferior, p=0.00001; temporal, p=0.02; and nasal, p=0.00001). In the fellow and control eyes, the choroid was thickest in the temporal sector. For the 1 mm diameter sectors, the temporal choroid was significantly thicker than the nasal sector (Tukey test, fellow eye, p=0.02; control eye, p=0.0001). For the 3 mm diameter sectors, the temporal choroidal sector was significantly thicker than the nasal sector (Tukey test, fellow, p=0.00001; control, p=0.0001; figure 3A and B).
Coefficients of correlation
There was a significant negative correlation between the subfoveal CT and the axial length in amblyopic (r=−0.51, p=0.01) and control eyes (r=−0.46, p=0.01) but not in the fellow eyes (r=−0.24, p=0.14; Pearson's correlation coefficient; figure 4). There were no significant correlations between the subfoveal CT and age, refractive error in amblyopic eyes, fellow eyes and control eyes (p>0.05; Pearson's correlation coefficient).
Differences of choroidal thickness of amblyopic eyes
Our analyses showed that the subfoveal choroid was significantly thicker in amblyopic eyes than in fellow eyes and normal control eyes. A number of studies have examined the topography of eyes with amblyopia, but they examined only the retinal topography and not the choroidal topography. In addition, these studies compared the findings in the amblyopic eyes with that of the fellow eyes and did not include normal control subjects.7–13 A search of Medline with keywords ‘choroidal thickness and amblyopia’ did not extract any articles. Thus, our study is the first to evaluate the CT of amblyopic eyes and compare it with fellow eyes and with normal control eyes.
In normal eyes, there is a progressive thinning of the choroid with increasing age,16–21 ,30 although Ruiz-Moreno et al15 reported that the CT beneath the macula in children was not significantly thicker than that of healthy adults. Fujiwara et al21 and Ruiz-Moreno et al15 reported that children less than 10 years of age had a thicker choroid compared with children older than 10 years of age and adults. However neither of these studies stratified their paediatric subjects any further to examine age-related changes in early childhood. Read et al23 reported that the subfoveal choroid of 4–6-year-old children (312±62 µm) was significantly thinner than that of 7–9-year-old children (337±65 µm). Ruiz-Moreno et al15 and Read23 reported that the profile of the choroid was different in the paediatric population, namely that the choroid was thickest on the temporal sector followed by the subfoveal and the nasal sectors. Our results of the fellow eyes and control eyes are consistent with these reports.15 ,23
However in amblyopic eyes, the choroid was the thickest in the subfoveal area followed by the temporal sector, and was thinnest in the nasal sector. In the fellow eyes and control eyes, the choroid was thickest in the temporal sector of the macular area. Overall, our findings showed that the profile of the choroid thickness in amblyopic eyes was different from that of the fellow eyes and control eyes.
We found a significant negative correlation between the subfoveal CT and the axial length of the amblyopic eyes and control eyes. Ruiz-Moreno et al15 reported a negative correlation between the CT and the refractive error in children (ages 3–17 years), however they did not examine whether there was an association between the CT and the axial length. Ikuno et al18 reported that there was a significant negative correlation between the CT and the refractive error or the axial length in the normal eyes of adult Japanese. We also found a significant negative correlation between the CT and the axial length in amblyopic eyes.
Functional significance of structural differences
The primary role of the choroid is to nourish and thermoregulate the retina; however, it is also believed to play a role in emmetropisation and refractive error development in young animals.24–27 It is well established that a variety of young animals undergo rapid changes in CT in response to imposed defocus, which in turn adjusts the position of the retina to maintain clear vision. Although our results showed that the subfoveal choroid was significantly thicker in amblyopic eyes than that of the fellow eyes or that of normal eyes, we do not know if there is a cause and effect relationship between the thicker choroid and the amblyopia. Hung et al24 reported that in young monkeys changes in the effective refractive state led to rapid compensating changes in the CT. Hyperopic defocus promoted choroidal thinning, myopic defocus promoted choroidal thickening, and anisometropia produces interocular differences in the CT. From our study, the subfoveal CT of the fellow eyes and control eyes was thinner compared with the amblyopic eyes. Troilo et al25 hypothesised that the thickening of the choroid observed during the normal development of primate eyes may function to slow the growth of the eye during development, either by providing a barrier to diffusion of growth factors or as a mechanical buffer to limit the eye's elongation. We hypothesised that in young children hyperopic defocus caused choroidal thinning in fellow eyes and control eyes; however, in amblyopic eyes, this choroidal compensation does not occur, so the subfoveal CT was thicker and the ocular growth was limited. The thickening of the choroid observed in our amblyopic children has a function of slowing eye growth. If amblyopic eyes wear plus lenses and causes more myopic defocus, choroidal thickening by myopic defocus may inhibit ocular growth. We plan to follow these patients, and determine the changes of the CT.
We studied only hyperopic anisometropic amblyopia and did not study the CT in other kinds of amblyopia. The CT was determined manually because there is no commercially available automated software. In addition our findings of the CT in Japanese children were made on a small number of subjects. Further studies including a larger number of subjects will be necessary to confirm our findings.
In conclusion, the subfoveal choroid was thicker in amblyopic eyes than in the fellow eyes and normal control eyes. The profile of the CT was different in the amblyopic eyes from the fellow eyes and control eyes.
Contributors Duco Hamasaki.
Competing interests Yes.
Patient consent Obtained.
Ethics approval Ethics Committee of Nara Medical University.
Provenance and peer review Not commissioned; externally peer reviewed.