Refractive errors in a large dataset of French children: the ANJO study

Undetected refractive errors (REs) in children can lead to irreversible vision loss. This study aimed to show the proportions of REs in French children using cycloplegic refraction. Multicentre cross-sectional retrospective study including children with cycloplegic refraction and without associated ocular conditions from 2015 to 2018 in French eye clinics. The following data were collected: age, symptoms of eye strain, best-corrected visual acuity (BCVA), cycloplegic refraction. The analysis included 48,163 children (mean age: 7.75 years, range: 2 to 12 years). The proportion of each RE was as follows: emmetropia (− 0.50 < Spherical Equivalent (SE) ≤  + 2.0; 58.3%), hyperopia (+ 2.0 \documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$$<$$\end{document}< SE \documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$$\le$$\end{document}≤+5; 17.2%), myopia (− 6 \documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$$\le$$\end{document}≤ SE \documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$$\le$$\end{document}≤− 0.50; 15.5%), high myopia (SE < − 6; 0.5%), high hyperopia (SE >  + 5; 3.6%), mixed astigmatism (4.9%). Anisometropia (SE difference ≥ 1.5) was found in 5.0%. Functional amblyopia in children attending primary school (aged over 6 years) was encountered in 2.7%. Symptoms of eye strain were frequent (70%) but not specific to any RE. REs are frequently found in French children and may remain undetected in the absence of symptoms of eye strain. Few studies have investigated REs in children using cycloplegic refraction, which has been shown to be the gold standard for RE assessment.


Methods
Study framework. This is a multicentre cross-sectional retrospective study including French children aged 2 to 12 years. Clinical data were collected from January 2015 to December 2018 from seven eye clinics (Versailles, Antony, Créteil, Poitiers, Troyes, Lyon Montrochet, Nice) considered as primary care centres and dedicated to REs. Appointments are mainly given online. First, patients are evaluated by an orthoptist who asks the parents for any general or ophthalmological personal history and then performs a best-corrected visual acuity (BCVA) assessment. Second, the ophthalmologist performs slit-lamp and fundus examination. All children are examined using cycloplegic drops as recommended by the French Association for Paediatric Ophthalmology and Strabismus. The exclusion criteria were as follows: children over 12 years of age, which corresponds to the mean age of puberty in France 13 ; consultations with a possibility of ocular disorder (e.g. retinal pathology, cataract, dyschromatopsia); missing autorefraction data; absence of cycloplegia; ophthalmic symptoms other than those of eye strain (e.g. red eye, painful eye, ophthalmic pruritus, ptosis).
This study was approved by the Ethics Committee of the French Society of Ophthalmology (Institutional Review Board: 0008855) and was conducted in accordance with the ethical principles of the Declaration of Helsinki. Data were anonymized for study purposes. Informed consent was not required for this study according to French law.
Database composition and characteristics. The following data were extracted automatically from each patient data file (Ophtix© software, OPHTEL®): demographic characteristics including age at examination, any ophthalmological medical history, symptoms of eye strain (blurry vision, asthenopia, headache), the use of cycloplegic drops (cyclopentolate, Skiacol©, Alcon®, USA or Atropine®), autorefraction on both eyes (Tonoref©, Nidek®) after cycloplegia, and prescription of glasses at the end of the consultation. Patients were included if cycloplegic refraction was performed at the first visit, or within 6 months after the first visit in the case of delayed cycloplegic refraction.
The database contained anonymised administrative and ophthalmological data which were divided into quantitative (BCVA, cycloplegic refraction, refraction of prescribed glasses) and qualitative sections (ophthalmological medical history, reason for consultation, symptoms, slit-lamp and fundus examination). Quantitative variables were analysed directly, while for qualitative data, being textual, all words referring to ophthalmic disorders were excluded.
Visual acuity measurement and refractive data. REs were classified according to the criteria described in Table 1, in accordance with a previous study 8 . Refractive status was defined according to SE. Anisometropia was defined as a difference in SE ≥ 1.5 D between both eyes 14 .
BCVA was assessed using decimal scales suitable to the child's age using autorefraction or subjective refinement, where possible (Pigassou symbols in preschool children and Monoyer chart for schoolchildren). Decimal scale visual acuity was converted to logarithmic values using the following formula: log(1/BCVA). Amblyopia was defined as a difference in BCVA between both eyes for children above 6 years old as follows: mild (difference in logarithmic lines > 1 and < 3), moderate (difference in logarithmic lines ≥ 3 and < 10) and severe (difference in logarithmic lines ≥ 10) 15 .
Each child was first examined by an orthoptist who reported in each data file if there were any symptoms. If symptoms such as blurry vision (e.g. sensation of decreased visual acuity at distance or near fixation, difficulties in seeing the blackboard or reading) were reported, data was included in the "symptoms" section of each medical record.
Statistical analyses. Statistical analyses were performed using the R software package version 3.6.0 (Rstu-dio®, Inc., Boston, MA, USA). Data were reported as the mean (SD) or median (interquartile range), as appropriate. For statistical independence purposes and based on the absence of significant differences between SEs for the two eyes, only right eyes were analysed, except for anisometropia for which both eyes had to be taken into account.

Results
In total, 48,163 records met the inclusion criteria (mean age: 8 years, range: 2-12 years) (Fig. 1). Table 1. Classification of refractive errors. Absolute value * Negative cylinder notation was used to apply this classification. a Including hyperopia and hyperopic astigmatisms. b Including myopia and myopic astigmatisms, SE spherical equivalent. Visual acuity and amblyopia. Age-specific BCVAs, with 5th, 50th, and 95th percentiles, are described in Fig. 4. From 2 to 4 years of age, the median BCVA increased to logMAR 0. At 6 years of age, 97.5% of the population had a BCVA higher than 20/32. At 9 years of age, 97.5% of the population had a BCVA higher than 20/25. In subjects over 6 years old, mild amblyopia was found in 815 (1.8%) children, moderate amblyopia in 447 (0.9%) children, while no severe amblyopia was reported.
A sensation of blurry vision was the most frequent symptom for all types of REs, from 62.3% for high hyperopia to 79.3% for myopia. Headache was the second most common symptom experienced by patients but much more rarely (ranging from 6.2 to 11.6%). Even in the emmetropia group, symptoms were not uncommon.

Discussion
To our knowledge, this is the first study of a large dataset of French children using cycloplegic refraction. REs were found frequently, especially hyperopia and anisometropia, which are major risk factors for amblyopia.
It is now established that accommodation is an important interpretation bias when studying REs in paediatric populations. In studies without cycloplegic drops, accommodation can lead to overestimation of myopia and under-detection of hyperopia. Sankaridurg et al. highlighted the importance of considering cycloplegia to better describe each RE 11 . Hashemi et al. showed that cycloplegic refraction is more sensitive than subjective refraction in measuring REs 12 . Thus, the use of cycloplegic refraction in the current study is consistent with the recommendations of previous publications in order to reduce interpretation bias.
In this study, hyperopia (SE ≥ 2.0 D, including hyperopia and high hyperopia) was reported in 20.8% of children. The prevalence of hyperopia is highly heterogeneous within literature owing to the SE threshold value used for the definition. A review of 7 studies with systematic cycloplegia in Indian children from 0 to 15 years of age reported a prevalence of 4.7% for hyperopia (defined as SE > 2.0 D) 16 . In a literature review of 29 studies which included children over 5 years of age, the prevalence of hyperopia (> 2.0 D) ranged from 2.1% to 19.3%. In Denmark, significant hyperopia (≥ + 3.0 D) was found in 7.9% of children aged 4.5 to 7 years old 17 . When considering the criteria > + 3.50 D for hyperopia at risk for amblyopia, proposed in the guidelines of the American   14 . The methodological characteristics of each study tend to make comparisons difficult. Moreover, it has been reported that populations with a Caucasian origin have the highest prevalence of hyperopia 18 . Hyperopia can be asymptomatic when mild but can also be responsible for symptoms of eye strain, independently of its severity. It is therefore mandatory to consult an ophthalmologist if symptoms are present. In the current study, no symptom was specific to any RE. They are therefore all non-specific. Uncorrected hyperopia can cause amblyopia and impact vision-related quality of life or school performance 19 . Studies show that a wellcorrected child performs better in school than an uncorrected child 9,20 . Hence systematic screening is necessary, and not only following the child's complaints.
Myopia (SE ≤ − 0.50 D, including myopia and high myopia) was found in 16.0% of children, which is lower than those reported in Asian studies 4,21 . In a study performed in Shanghai, 52% of the children aged 10 had myopia 22 . Ethnic group can therefore have a significant impact. In the Netherlands, myopia prevalence was 11.5% at 9 years old 23 . Another study performed in 2015 in French children aged 9 years or younger reported a prevalence of 19.6% for myopia, which is consistent with our findings 24 . In our study, myopia was found in almost 1 out of 7 children, suggesting that it represents a public health issue. This is a major concern considering the potential increase of myopia in those children during puberty, especially with increasing time dedicated to indoor activities and a marked reduction of outdoor activities in developed countries 25 . Screening for myopia in children is very important in order to control environmental factors associated with myopia progression. There is currently an almost universal consensus that increasing outdoor activities is a protective factor. However, this does not occur with near-work activities, and although many researchers have confirmed the association with myopia, various epidemiological studies have not found such an association 26 .
Several studies have reported a prevalence of anisometropia ranging from 3.0% to 8.5% (in Australia, Afsari et al. . Thus, the anisometropia prevalence of 5.0% in the current study is within the range of previous studies. The pathophysiological mechanisms underlying the development of anisometropia are still poorly understood. Yet, it is well known that anisometropia represents a major risk factor for amblyopia and impaired binocular vision and needs to be corrected 14 . The prevalence of functional amblyopia in children attending primary school (6 years and older) was found to be 2.0%, which is consistent with previous findings (Faghigi et al.: 2.2% in children aged 5 to 15 years) 30 . In the absence of organic pathology, this represents a significant percentage of avoidable vision loss. Efforts have yet to be made to detect any RE at risk for amblyopia and we believe that systematic screening in pre-school children would be helpful.  www.nature.com/scientificreports/ Indeed, the representativeness of the subjects included is of great importance. To enable further comparisons with other countries, the characteristics of each healthcare system must be known. Specifically concerning the French vision healthcare system, children can be examined in private clinics, which represent primary care, or public hospitals, which represent secondary or tertiary care. Therefore, most children are examined by private ophthalmologists and then referred to public hospitals for further investigations for difficult cases. Second, visual screening is performed at the age of 3, which corresponds to the youngest children in the study population. Finally, these consultations are reimbursed by social security and mutual insurance and therefore the cost of care does not represent an obstacle to visual screening by an ophthalmologist. Any patient can make an appointment directly with an ophthalmologist for a visual examination in the current refractive centres, even without visual symptoms. Yet we cannot rule out that children with symptoms were more likely to be examined, as this study was retrospective. Further prospective studies with systematic screening would be relevant but it would hardly be possible to obtain such a large dataset. We also have to acknowledge that definitions of refractive errors are highly variable between studies, making comparisons difficult. Still, there is an increasing effort towards standardisation 31,32 , which remains an unmet need.
In conclusion, REs are frequently found in our cohort of French children, whether symptomatic or not. Symptoms of eye strain are non-specific, and the current findings highlight the need for systematic screening for REs in pre-school children in order to prevent irreversible vision loss and avoid low school performance. This is the largest public health study of REs using cycloplegic refraction in children.

Data availability
The datasets generated and/or analysed during this study are available from the corresponding author on reasonable request.