Shanghai Child and Adolescent Large-scale Eye Study -High Myopia Registration

1. introduction 1.1 Overview of myopia and high myopia Myopia is the most common eye disease in the world . Among them, the incidence and prevalence of myopia are highest in developed countries and regions in East and Southeast Asia. It is predicted that by 2050, global myopia patients would reach 5 billion, 1 billion of which were high myopia. In developed countries and regions in East and Southeast Asia, the prevalence of myopia in high school graduates is as high as 80% to 90%. A study in Taiwan showed that more than 80% of adolescents suffered from myopia when they graduated from high school, 10% of whom were high myopia. Another study which focused on university students in Shanghai showed that 95.5% of college students suffered from myopia, and 19.5% of them were high myopia. In stark contrast, the prevalence of myopia in the same age in western developed countries is between 20% and 40%. In less developed countries and regions of the world, the incidence of myopia in young people is about 5% to 10% due to the low level of education.

At present, the etiology and pathogenesis of myopia and high myopia are still unclear. Environmental and genetic factors are involved in the development of myopia and high myopia. Among them, the level of education and outdoor activity time are closely related to the development of myopia and high myopia. At present, most studies believe that the higher the education level, the higher the incidence of myopia and the deeper the degree of myopia. In addition, most studies suggest that outdoor activities was a protective factor for myopia, and increasing outdoor activity time could reduce the incidence of myopia. Also, some studies have shown that the age of onset of myopia was closely related to high myopia. Furthermore, genes may also be closely related to the occurrence of myopia and high myopia. At least 19 myopic loci have been identified through family studies and twin studies till now. With the completion of the Human Genome Project, genome-wide association analysis technology is becoming more and more mature, and more and more related genes and mutation sites have been elucidated, but the pathogenic genes of myopia are still not completely clear. In addition, the genes related to pathological myopia and fundus lesions are currently unclear. In recent studies, high myopia and pathological myopia are not strictly differentiated (pathological myopia is defined by diopter or axial length alone). Therefore, genes related to pathological myopia need further research, in order to judge whether high myopia and pathological myopia are two different diseases at genetic level or different states controlled by the same genes.

1.2 Relationship between high myopia and pathological myopia The fundus of patients with high myopia is often accompanied by a series of pathological changes, such as posterior scleral staphyloma, retinal choroidal atrophy, lacquer crack, choroidal neovascularization（CNV）, macular hemorrhage, Fuchs plaque, retinal palpebral fissure, retinal tear, retinal detachment. These pathological changes are important causes of decreased vision and even blindness. Some studies have shown that macular degeneration caused by myopia has become a major cause of blindness and low vision. In Jing'an District of Shanghai, high myopia with macular degeneration has leapt to the first place in adult blindness. A study in Beijing showed that pathological myopia has become the leading cause of blindness and visual impairment in the 40-49 age group.

Although high myopia is closely related to pathological myopia, and most patients with pathological myopia are highly myopic, high myopia is not equivalent to pathological myopia. The change of diopter and axial length do not fully reflect the characteristics of pathological myopia. Some patients with high myopia have no definite fundus lesions, and some non-high myopia patients may also have posterior scleral staphyloma, retinochoroid atrophy and other complications. At present, Ohno-Matsui K et al define pathological myopia as: myopic macular degeneration ≥ 2 (diffuse retinochoroid atrophy), or additional lesions (lacquer cracks, choroidal neovascularization, Fuchs plaque), or posterior scleral staphyloma. In this definition of pathological myopia, we focus on fundus lesions caused by myopia, and do not emphasize diopter and axial length.

At present, there are still many unknowns about the relationship between high myopia and pathological myopia. The process of developing simple high myopia in children and adolescents as pathological myopia is still unclear. Does high myopia eventually evolve into pathological myopia? Are pathological myopia and high myopia different stages of the same disease or two different diseases? Which fundus changes can predict the occurrence of pathological myopia? These problems need further exploration.

1.3 Morphology and visual function changes in fundus of children with high myopia At present, there are few studies on the changes of fundus morphology and visual function in children with high myopia. And long-term follow-up studies are also lacking.

Morphological studies suggest that the common fundus changes in children with high myopia include β-peripapillary atrophy（β-PPA）, optic disc tilt, etc., but the incidence of posterior scleral staphyloma and retinochoroid atrophy is low in childhood. Furthermore, some studies have suggested that diffuse retinochoroid atrophy around the optic disc in childhood could easily develop into pathological myopia in adulthood. In addition, thinning of the retina, choroid, and sclera is also present in children with myopia and high myopia. In addition to the fundus of the posterior pole, there are also multiple lesions in the peripheral fundus. Some studies considered that peripheral fundus lesions such as lattice-like degeneration, non-compressive whitening, and retinal tears are more common in children with high myopia.

Corresponding to structural changes, there are also changes in micro-field and electrophysiology of patients with high myopia. However, there is few studies focusing on children and adolescents with high myopia, and no long-term follow-up studies has been reported. There are still many unknowns in the early morphological changes, evolution process and visual function of high myopia, which deserve further exploration.

1.4 The direction of this research A． Follow-up study of morphological changes in the fundus of children with high myopia; B． Follow-up study of visual function changes in children with high myopia; C． Etiological studies related to high myopia in children; D． Follow-up study of quality of life, psychology, behavior, and social interactions in children with high myopia. 2. Data collection 2.1 Preparatory work A． Establish Shanghai Children and Adolescents High Myopia Registration Information System and Workflow: a set of information function modules including appointment, real-time collection of exam data, online feedback of exam results, daily consultation contact and data management analysis. And then establish the workflow SOP file; B． Train physicians, optometrists and other relevant staff responsible for the research; C． Print promotional materials, questionnaires, informed consent forms and examination flow charts; D． Contact the children and adolescents in the Shanghai Children's Refractive Development Archives Information Database System through their school and use science lectures, WeChat（a kind of APP） official accounts, Weibo(Chinese version of Twitter), paper leaflets to promote the harm of high and pathological myopia to children, adolescents and their parents, as well as introduction of the content of this study, the participants' benefits and potential risks; E． Sign an informed consent form to collect information on the participants; F． The appointment is registered through the information system.

2.2 Examination process The brief process is as follows: Identity information registration \> height, weight \> naked eye vision \& wearing vision \> axial length \> intraocular pressure \> slit lamp anterior segment examination \> Microperimetry (selected) \> cycloplegia \> Autorefraction and subjective refraction \> Pentacam, Swept-source optical coherence tomography（SS-OCT，Topcon), wide-angle optical coherence tomography angiography(OCTA,Zeiss-9000), fundus color photography + autofluorescence(Topcon), Ultra wide Angle fundus photography(Optos), mfERG (optional), wavefront aberrations \> blood sample collection / saliva specimens \> fill out the questionnaire.

The specific flow chart is as follows.

2.3 Ophthalmology inspection project operation rules 2.3.1 Vision test The eyesight examination used the ETDRS visual acuity chart (LCD backlit lamp, WH0701), the test distance was 4 meters, and the visual target at 20/20 was the same height as the eye of the examinee. The recognition time of each visual target is 2\~3s; the eye of the subject is required to be opened normally for examination, and the blinking, hoeing, neck stretching and peeking are strictly prevented. Vision is converted to a decimal count record. Visual acuity examination includes two parts: uncorrected visual acuity (UCVA) and corrected visual acuity (CVA). Children who are not wearing glasses are only examined by UCVA, and children who wear glasses are required to check CVA after completing the UCVA test.

2.3.2 Axis measurement The axial measurement was performed using an IOL Master (version 5.02, Carl Zeiss Meditec, Germany). Simulated eye calibration was needed before measurement. Each eye was measured repeatedly for 3 times, and the difference was less than 0.02 mm each time. For those who still have large fluctuations in multiple measurements, the examiner needs to record it.

2.3.3 Intraocular pressure measurement Intraocular pressure was measured using a non-contact tonometer (NT-4000, Nidek, USA). Each eye was repeatedly measured 3 times and averaged, and the difference between each two was less than 5 mmHg. Those with an intraocular pressure higher than 24 mmHg should be recorded and added for visual field examination.

2.3.4 Ophthalmologist examination Ophthalmologist examinations included anterior segment slit lamp examination (66 Vision. Tech, Suzhou,China) and ophthalmoscopy examination(66 Vision. Tech, Suzhou,China). The examination of the anterior segment slit lamp includes the eyelid, conjunctiva, cornea, anterior chamber, iris, pupil, lens and anterior vitreous body, which is completed by the investigator's senior ophthalmologist. For patients with peripheral anterior chamber depth less than 1/2 corneal thickness, or acute inflammation of the anterior segment of the eye and other related diseases, it is not suitable for cycloplegia afterwards. It should be registered by the examining physician and suspended or excluded from the study. In addition, the ophthalmologist should use corneal reflection, occlusion-de-covering, etc. to determine whether the subject has strabismus (hidden strabismus or strabismus). Those who were strabismus should be excluded from the study. For those suspected of having fundus diseases, ophthalmoscopy (direct ophthalmoscope or 90D) can be performed after cycloplegia, and the nature of fundus disease is judged by an ophthalmologist. Participants with myopia-related fundus lesions can be registered and included in the study, while participants with other fundus lesions need to be excluded after recorded. Those who had other organic eye diseases were also excluded after recording.

2.3.5 Microperimetry Microperimetry examinations were performed in the darkroom and needed to be performed prior to OCT and fundus photographic examinations to avoid influence by bright light. Microperimetry was performed using an MP1 micro-perimeter (MP-1, Nidek, Japan), and the Goldman III, 4-2-1 mode was selected to detect retinal light sensitivity wi

• uncorrected visual acuity [Срок оценки: June 31, 2038]
• corrected visual acuity [Срок оценки: June 31, 2038]
• best corrected visual acuity [Срок оценки: June 31, 2038]
• spherical power [Срок оценки: June 31, 2038]
• cylindrical power [Срок оценки: June 31, 2038]
• intraocular pressure(IOP) [Срок оценки: June 31, 2038]
• height [Срок оценки: June 31, 2038]
• weight [Срок оценки: June 31, 2038]
• BMI [Срок оценки: June 31, 2038]