Hong Sheng Bi

Refractive Error, Visual Acuity and Causes of Vision Loss in Children in Shandong, China. The Shandong Children Eye Study

Purpose To examine the prevalence of refractive errors and prevalence and causes of vision loss among preschool and school children in East China. Methods Using a random cluster sampling in a cross-sectional school-based study design, children with an age of 4–18 years were selected from kindergartens, primary schools, and junior and senior high schools in the rural Guanxian County and the city of Weihai. All children underwent a complete ocular examination including measurement of uncorrected (UCVA) and best corrected visual acuity (BCVA) and auto-refractometry under cycloplegia. Myopia was defined as refractive error of ≤−0.5 diopters (D), high myopia as ≤−6.0D, and amblyopia as BCVA ≤20/32 without any obvious reason for vision reduction and with strabismus or refractive errors as potential reasons. Results Out of 6364 eligible children, 6026 (94.7%) children participated. Prevalence of myopia (overall: 36.9±0.6%;95% confidence interval (CI):36.0,38.0) increased (P<0.001) from 1.7±1.2% (95%CI:0.0,4.0) in the 4-years olds to 84.6±3.2% (95%CI:78.0,91.0) in 17-years olds. Myopia was associated with older age (OR:1.56;95%CI:1.52,1.60;P<0.001), female gender (OR:1.22;95%CI:1.08,1.39;P = 0.002) and urban region (OR:2.88;95%CI:2.53,3.29;P<0.001). Prevalence of high myopia (2.0±0.2%) increased from 0.7±0.3% (95%CI:0.1,1.3) in 10-years olds to 13.9±3.0 (95%CI:7.8,19.9) in 17-years olds. It was associated with older age (OR:1.50;95%CI:1.41,1.60;P<0.001) and urban region (OR:3.11;95%CI:2.08,4.66);P<0.001). Astigmatism (≥0.75D) (36.3±0.6%;95%CI:35.0,38.0) was associated with older age (P<0.001;OR:1.06;95%CI:1.04,1.09), more myopic refractive error (P<0.001;OR:0.94;95%CI:0.91,0.97) and urban region (P<0.001;OR:1.47;95%CI:1.31,1.64). BCVA was ≤20/40 in the better eye in 19 (0.32%) children. UCVA ≤20/40 in at least one eye was found in 2046 (34.05%) children, with undercorrected refractive error as cause in 1975 (32.9%) children. Amblyopia (BCVA ≤20/32) was detected in 44 (0.7%) children (11 children with bilateral amblyopia). Conclusions In coastal East China, about 14% of the 17-years olds were highly myopic, and 80% were myopic. Prevalence of myopia increased with older age, female gender and urban region. About 0.7% of pre-school children and school children were amblyopic.

Effect of cycloplegia on the refractive status of children: the Shandong children eye study.

Purpose To determine the effect of 1% cyclopentolate on the refractive status of children aged 4 to 18 years. Methods Using a random cluster sampling in a cross-sectional school-based study design, children with an age of 4–18 years were selected from kindergardens, primary schools, junior and senior high schools in a rural county and a city. Auto-refractometry was performed before and after inducing cycloplegia which was achieved by 1% cyclopentolate eye drops. Results Out of 6364 eligible children, data of 5999 (94.3%) children were included in the statistical analysis. Mean age was 10.0±3.3 years (range: 4–18 years). Mean difference between cycloplegic and non-cycloplegic refractive error (DIFF) was 0.78±0.79D (median: 0.50D; range: -1.00D to +10.75D). In univariate analysis, DIFF decreased significantly with older age (P<0.001;correlation coefficient r:-0.24), more hyperopic non-cycloplegic refractive error (P<0.001;r = 0.13) and more hyperopic cycloplegic refractive error (P<0.001;r = 0.49). In multivariate analysis, higher DIFF was associated with higher cycloplegic refractive error (P<0.001; standardized regression coefficient beta:0.50; regression coefficient B: 0.19; 95% confidence interval (CI): 0.18, 0.20), followed by lower intraocular pressure (P<0.001; beta: -0.06; B: -0.02; 95%CI: -0.03, -0.01), rural region of habitation (P = 0.001; beta: -0.04; B: -0.07; 95%CI: -0.11, -0.03), and, to a minor degree, with age (P = 0.006; beta: 0.04; B: 0.009; 95%CI: 0.003, 0.016). 66.4% of all eyes with non-cycloplegic myopia (≤-0.50D) remained myopic after cycloplegia while the remaining 33.6% of eyes became emmetropic (18.0%) or hyperopic (15.7%) under cycloplegia. Prevalence of emmetropia decreased from 37.5% before cycloplegia to 19.8% after cycloplegia while the remaining eyes became hyperopic under cycloplegia. Conclusions The error committed by using non-cycloplegic versus cycloplegic refractometry in children with mid to dark-brown iris color decreased with older age, and in parallel manner, with more myopic cycloplegic refractive error. Non-cycloplegic refractometric measures lead to a misclassification of refractive error in a significant proportion of children.

Intraocular Pressure and Associated Factors in Children: The Shandong Children Eye Study

PURPOSE We examined the distribution of intraocular pressure (IOP) and its associated factors in children. METHODS Using a random cluster sampling from kindergartens, primary schools, and junior and senior high schools from rural Guanxian County and the city of Weihai, the school-based cross-sectional Shandong Children Eye Study included children aged 4 to 18 years. All participants underwent an ocular examination, including ocular biometry, cycloplegic refractometry, and noncontact tonometry. RESULTS Mean IOP was 17.6 ± 2.7 mm Hg (range, 10-28 mm Hg). The IOP increased up to an age of 10 years and subsequently decreased with older age. In multivariate regression analysis, higher IOP was associated with female sex (P < 0.001; standardized correlation coefficient β, 0.06; regression coefficient β, 0.34; 95% confidence interval [CI], 0.18, 0.50), higher body mass index (P < 0.001; correlation coefficient β, 0.09; regression coefficient β, 0.07; 95% CI, 0.04,0.09), younger age (P < 0.001; correlation coefficient β, -0.15; regression coefficient β, -0.13; 95% CI, -0.17,-0.10), maternal myopia (P < 0.001; correlation coefficient β, 0.05; regression coefficient β, 0.34; 95% CI, 0.15,0.53), and more time spent indoors with reading/writing (P = 0.002; correlation coefficient β, 0.05; regression coefficient β, 0.07; 95% CI, 0.03,0.11), and with the ocular parameters of longer axial length (P < 0.001; correlation coefficient β, 0.14; regression coefficient β, 0.29; 95% CI, 0.21,0.37) and smaller corneal horizontal diameter (P < 0.001; correlation coefficient β, -0.06; regression coefficient β, -0.31; 95% CI, -0.46,-0.15). CONCLUSIONS In children aged 4 to 18 years, IOP showed an M-shaped association with age. Higher IOP was associated with the nonocular parameters of female sex (P < 0.001), higher body mass index (P < 0.001), younger age (P < 0.001), maternal myopia (P < 0.001), and more time spent indoors with reading/writing (P = 0.002), and with the ocular parameters of longer axial length (P < 0.001) and smaller corneal horizontal diameter (P < 0.001).

Macular Choroidal Thickness in Children: The Shandong Children Eye Study.

PURPOSE To examine the thickness of the macular choroid and its associations in school children aged 6 to 18 years. METHODS The school-based cross-sectional Shandong Children Eye Study included 6026 (94.7%) of 6364 eligible children fulfilling the inclusion criterion of an age from 4 to 18 years. Spectral-domain optical coherence tomography (SD-OCT) was performed for a subgroup of 972 school children aged 6+ years. All participants underwent ocular examinations, including measurement of visual acuity, cycloplegic refractometry, biometry, and SD-OCT (enhanced depth imaging mode) for measurement of choroidal thickness. RESULTS The study included 972 children (501 girls) with a mean age of 11.3 ± 3.3 years (range, 6-18 years) and mean axial length of 24.10 ± 1.56 mm (range, 16.57-28.82 mm). Mean choroidal thickness was thicker (P < 0.001) at 500 μm temporal to the foveola (290 ± 67 μm) than in the subfoveal region (283 ± 67 μm; range, 113-507 μm) and the region 500 μm superior to the fovea (283 ± 66 μm), where it was thicker (P < 0.001) than at 500 μm inferior of the foveola (281 ± 66 μm), and it was thinnest (P < 0.001) at 500 μm nasal of the foveola (268 ± 67 μm). In multivariate analysis, thicker SFCT was (overall correlation coefficient r: 0.51) associated with shorter axial length (P < 0.001; standardized correlation coefficient β: -0.48; B: -23.7; 95% confidence interval [CI]: -27.2 to -20.3), male sex (P = 0.006; β: -0.08; B: -10.7; 95% CI: -18.3 to -3.11), and younger age (P = 0.04; β: -0.07; B: -1.46; 95% CI: -2.85 to -0.07). CONCLUSIONS As in adults, thicker SFCT in children and teenagers was markedly associated with shorter axial length, and to a lesser degree with male sex and older age. As in adults, increasing axial myopia in teenagers is associated with choroidal thinning and development of a leptochoroid.

Education-Related Parameters in High Myopia: Adults versus School Children

Purpose Since high myopia in the younger generation may differ etiologically from high myopia in older generations, we examined whether education-related parameters differ between high myopia in today´s school children and high pathological myopia in today´s elderly generation. Methods The investigation included the adult populations of the population-based Beijing Eye Study (BES) (3468 adults;mean age:64.6±9.8years;range:50–93years) and Central India Eye and Medical Study (CIEMS) (4711 adults;age:49.±13.2years;range:30–100years), and the children and teenager populations of the Shandong Children Eye Study (SCES) (6026 children;age:9.7±3.3years;range:4–18years;cycloplegic refractometry), Gobi Desert Children Eye Study (1565;age:11.9±3.5years;range:6–21 years;cycloplegic refractometry), Beijing Pediatric Eye Study (681 children;age:7.7±1.6years;range:5–13 years;non-cycloplegic refractometry,calculation of axial length to corneal curvature radius ratio), Beijing Children Eye Study (15066 children;age:13.2±3.4years;range:7–18years;non-cycloplegic refractometry), Beijing High School Teenager Eye Study (4677 children;age:16.9±0.7years;range:16–18years;non-cycloplegic refractometry). Results In the BES and CIEMS, educational level did not differ significantly between, or was significantly lower in the highly myopic group (myopic refractive error ≥6 diopters) than in the non-highly myopic group. In all non-adult study populations, higher prevalence of high myopia was significantly associated with higher degree of education related parameters such as attendance of high-level schools, and more time spent for indoors near work versus time spent outdoors. Conclusions Comparing associations of old or genetic high myopia in adults with new or acquired high myopia in school children revealed that education-related parameters did not show a clear association with old or genetic high myopia, while in contrast, new high myopia showed strong associations with education. It confirms previous studies that the two forms of high myopia not only differed in age of onset, but also in associations with education as well. The data support the notion of two types of high myopia. Future studies may assess whether the risk of pathologic myopic maculopathy and high myopia associated open-angle glaucoma differs between both types of high myopia.

Amphiregulin Antibody and Reduction of Axial Elongation in Experimental Myopia

To examine the mechanism of ocular axial elongation in myopia, guinea pigs (age: 2–3 weeks) which either underwent unilateral or bilateral lens-induced myopization (group 1) or which were primarily myopic at baseline (group 2) received unilateral intraocular injections of amphiregulin antibody (doses: 5, 10, or 15 μg) three times in intervals of 9 days. A third group of emmetropic guinea pigs got intraocular unilateral injections of amphiregulin (doses: 0.25, 0.50 or 1.00 ng, respectively). In each group, the contralateral eyes received intraocular injections of Ringers solution. In intra-animal inter-eye comparison and intra-eye follow-up comparison in groups 1 and 2, the study eyes as compared to the contralateral eyes showed a dose-dependent reduction in axial elongation. In group 3, study eyes and control eyes did not differ significantly in axial elongation. Immunohistochemistry revealed amphiregulin labelling at the retinal pigment epithelium in eyes with lens-induced myopization and Ringers solution injection, but not in eyes with amphiregulin antibody injection. Intraocular injections of amphiregulin-antibody led to a reduction of lens-induced axial myopic elongation and of the physiological eye enlargement in young guinea pigs. In contrast, intraocularly injected amphiregulin in a dose of ≤ 1 ng did not show a significant effect. Amphiregulin may be one of several essential molecular factors for axial elongation.

Axial Length and Associated Factors in Children: The Shandong Children Eye Study

Purpose: To investigate ocular axial length (AL) in Chinese children. Methods: The Shandong Children Eye Study included 6,364 children aged 4-18 years. Results: Longer AL (mean 23.45 ± 1.20 mm, range 18.80-28.59 mm) was associated (multivariate analysis; correlation coefficient r2: 0.61) with older age (p < 0.001, standardized correlation coefficient β = 0.35, unstandardized regression coefficient B = 0.13, 95% confidence interval [CI] 0.12, 0.15), male gender (p < 0.001, β = -0.24, B = -0.10, 95% CI -0.29, -0.19), urban region (p < 0.001, β = 0.10, B = 0.25, 95% CI 0.20, 0.31), body height (p < 0.001, β = 0.22, B = 0.02, 95% CI 0.01, 0.02), maternal education (p < 0.001, β = 0.07, B = 0.07, 95% CI 0.05, 0.10), paternal myopia (p < 0.001, β = 0.09, B = 0.26, 95% CI 0.20, 0.33), maternal myopia (p < 0.001, β = 0.08, B = 0.23, 95% CI 0.17, 0.30), more time spent indoors reading/writing (p < 0.001, β = 0.05, B = 0.03, 95% CI 0.02, 0.04), less time spent outdoors (p = 0.005, β = -0.03, B = -0.01, 95% CI -0.02, -0.003), longer corneal curvature radius (p < 0.001, β = 0.36, B = 1.63, 95% CI 1.53, 1.74) and higher intraocular pressure (p = 0.008, β = 0.03, B = 0.01, 95% CI 0.004, 0.02). High axial myopia (AL ≥26.0 mm) present in 202 children (3.4 ± 0.2%, 95% CI 2.92, 3.84) was associated with less time spent outdoors (p = 0.002, odds ratio 0.92, 95% CI 0.87, 0.97) in multivariate analysis. Conclusions: In children in the less developed Eastern Chinese province of Shandong, the prevalence of high axial myopia was >10% among 16-year-olds. A modifiable factor associated with higher prevalence of high axial myopia was less time spent outdoors.

Myopia in China: a population-based cross-sectional, histological, and experimental study

BACKGROUND The prevalence of myopia has markedly increased within the past three decades, in particular in China. Because of myopic retinopathy and myopia-associated glaucoma, myopia has become one of the leading blinding disorders. METHODS Conducting population-based studies and school-based investigations, we assessed prevalence and incidence of myopia and associated factors in children, university students, and adults in urban and rural regions of different Chinese provinces. We performed histomorphometric studies on human eyes, and examined whether the intraocular application of an antibody to amphiregulin was associated with a reduction of experimentally induced myopic axial elongation of eyes in guinea pigs. This study was approved by the ethics committee of the Shandong University of Traditional Chinese Medicine. FINDINGS In nine population-based studies with up to 560 000 child and adult participants, the prevalence of myopia was about 80% in 18-year-old school children and 17% in adults aged 40 years and older. These figures were significantly higher in urban regions than in rural regions (OR 1·63, 95% CI 1·51-1·75, p<0·0001). Myopic retinopathy and myopia-associated glaucoma were the most common causes for irreversible visual loss in adults. In children, the most common myopia-associated modifiable factor was less time spent outdoors/more time spent indoors with studying. Histological studies revealed that the density of retinal pigment epithelium cells and retinal thickness decreased with longer axial length in the retinal midperiphery, while retinal cell density and thickness in the macula were statistically independent (p>0·40) of axial length, as was Bruchs membrane thickness. Intraocular application of amphiregulin antibody reduced axial elongation in guinea pigs in a dosage-dependent manner (p=0·002; regression coefficient -0·58, 95% CI of difference 0·20 to 0·63). INTERPRETATION These findings suggest that the increase in prevalence of myopia in the young Chinese generation is associated with lifestyle factors. The histological findings indicated that myopic axial elongation was associated with formation of Bruchs membrane in the midperiphery. Since the retinal pigment epithelium has receptors for amphiregulin, a member of the epithelial growth factor family, this hypothesis fits with the finding that amphiregulin antibody was associated with a dosage-dependent reduction in axial elongation. Further studies are warranted on the medical reduction of axial myopisation by amphiregulin antibody. FUNDING None.

Prevalence and Associations of Anisometropia in Children.

PURPOSE To describe prevalence and associations of anisometropia in children. METHODS The cross-sectional school-based study included children aged 4 to 18 years. RESULTS The study included 6025 (94.7%) of 6364 eligible children. Mean refractive anisometropia was 0.37 ± 0.57 diopters (median: 0.25 diopters; range: 0-7.88 diopters; prevalence [≥1 diopter]: 7.0% ± 0.3%). In multivariate analysis (regression coefficient r: 0.66), higher refractive anisometropia was associated with older age (P < 0.001; β: 0.07; B: 0.01; 95% CI: 0.01-0.02), higher maternal education level (P < 0.001; β: 0.04; B: 0.02; 95% CI: 0.01-0.03), more total time spent indoors reading or writing (P = 0.001; β: 0.04; B: 0.01; 95% CI: 0.01-0.02), larger intereye difference in axial length (P < 0.001; β: 0.57; B: 1.20; 95% CI: 1.15-1.24), shorter mean axial length of both eyes (P = 0.03; β: -0.03; B: -0.02; 95% CI: -0.03 to -0.001), larger intereye difference in best corrected visual acuity (BCVA) (P < 0.001; β: 0.14; B: 1.83; 95% CI: 1.54-2.12), and lower stereoacuity (P < 0.001; β: 0.08; B: 0.31; 95% CI: 0.22-0.39). Refractive anisometropia showed a U-shaped correlation with refractive error. Higher anisomyopia was associated (r: 0.57) with older age (P = 0.001; β: 0.05; B: 0.006; 95% CI: 0.002-0.009), higher level of paternal education (P = 0.001; β: 0.01; B: 0.01; 95% CI: 0.01-0.02), more total time spent indoors reading or writing (P = 0.01; β: 0.03; B: 0.01; 95% CI: 0.00-0.01), larger intereye difference in axial length (P < 0.001; β: 0.22; B: 0.26; 95% CI: 0.23-0.29), greater myopic refractive error (P < 0.001; β: -0.46; B: -0.07; 95% CI: -0.08 to -0.07), and lower corneal astigmatism (P < 0.001; β: -0.10; B: -0.06; 95% CI: -0.08 to -0.05). In the same multivariate model, hyperopic anisometropia was not significantly associated with time spent indoors with reading (P = 0.18). Cylindrical anisometropia (mean: 0.30 ± 0.32 diopters; prevalence [≥1 diopter]: 3.7% ± 0.2%) increased with higher refractive anisometropia (P < 0.001; β: 0.16; B: 0.09; 95% CI: 0.08-0.11), greater myopic refractive error (P < 0.001; β: -0.06; B: -0.01; 95% CI: -0.01 to -0.01), higher corneal astigmatism (P < 0.001; β: -0.22; B: -0.15; 95% CI: -0.17 to -0.13), and lower mean BCVA (P < 0.001; β: 0.11; B: 0.90; 95% CI: 0.68-1.17). CONCLUSIONS In 4- to 18-year-old children, refractive anisometropia and anisomyopia increased with systemic parameters such as age, parental education level, and lifestyle of the children, for example, more time spent indoors reading or writing. In contrast, hyperopic anisometropia and cylindrical anisometropia were not related with lifestyle parameters.

Parapapillary Diffuse Choroidal Atrophy in Children Is Associated With Extreme Thinning of Parapapillary ChoroidParapapillary Diffuse Choroidal Atrophy in Children

Purpose To analyze morphologic features of segmental parapapillary diffuse choroidal atrophy (PDCA) in children. Methods The study group included children (age ≤15 years) with high myopia who attended the Tokyo High Myopia Clinic. Control groups comprised participants of the population-based Gobi Desert Children Eye Study (GobiDCES). Fundus photographs were examined for presence of PDCA and choroidal thickness (CT) was measured by optical coherence tomography. Results The study group included 41 eyes of 21 children with PDCA (mean age: 9.4 ± 3.7 years; mean refractive error: -11.5 ± 3.1 diopters) and the GobiDCES included 1463 children (age: 11.8 ± 3.5 years). In the study group, all eyes showed an extreme and abrupt thinning of the temporal parapapillary choroid. At 2500 μm nasal to the foveola, CT was <60 μm in 31 (76%) eyes of the study group but in none (0/1463) of the GobiDCES (P < 0.001), except for one child with PDCA. Conclusions Parapapillary diffuse choroidal atrophy in children is associated with abrupt segmental thinning of the choroid in the temporal parapapillary region, in addition to the thinning of the subfoveal choroid after adjusting for refractive error and age.