1.1 General information
Using the method of randomized controlled clinical trial, 231 children with myopia ametropia treated in the eye hospital of Tianjin Medical University from June 2016 to June 2017 were included. All subjects wore myopia fully corrected monocular frame glasses. Inclusion criteria: (1) age 6 ~ 14 years; (2) The spherical equivalent refraction (SER) of binocular myopia was -0.75 ~ -6.0 D, and the astigmatism was < 2.00 D; (3) Best corrected visual acuity (LogMAR) 0.1; (4) Binocular ser difference < 1.00 D; (5) The intraocular pressure was 10 ~ 21 mmHg (1 mmHg = 0.133 kPa). Exclusion criteria: (1) allergic reaction or intolerance to atropine eye drops; (2) Long term use of low concentration atropine eye drops, rigid breathable corneal contact lenses or corneal shaping lenses for myopia prevention and control; (3) Unable to ensure regular follow-up; (4) Those with other eye diseases, eye surgery and trauma; (5) Have other systemic diseases. The subjects were randomly divided into 110 cases in 0.02% atropine group and 121 cases in 0.01% atropine group. During the study, 18 cases in the 0.02% atropine group were abandoned, accounting for 16.4%, of which 6 cases were lost to follow-up, 7 cases stopped the drug due to fear of adverse reactions, 4 cases failed to review on time, 1 case stopped the drug due to photophobia, and finally 92 cases completed one-year follow-up. In the 0.01% atropine group, 20 cases were abandoned, accounting for 16.5%, of which 9 cases were lost to follow-up, 7 cases stopped the drug on their own for fear of side effects, 2 cases failed to review on time, 2 cases stopped the drug on their own due to photophobia, and finally 101 cases completed one-year follow-up. All subjects took right eye data for analysis. There was no significant difference in baseline data between the two groups (all P > 0.05) (Table 1). This study followed the declaration of Helsinki, was approved by the ethics committee of ophthalmic hospital of Tianjin Medical University (approval No.: 2020-35) and registered in the national clinical trial registration center (Registration No.: chictr-ipd-16008844). All subjects and their guardians understood the purpose of the study and signed informed consent.
Table 1
Comparison of baseline data before intervention between 0.02% and 0.01% atropine groups
Groups
|
cases
|
Age (mean ± SD, years) a
|
Gender (male/female, n) b
|
BMI(mean±SD,kg/m2)a
|
Sphericity (mean ± SD, D) a
|
Cylindricity (mean ± SD, D) a
|
SER(mean±SD,D)a
|
0.02% atropine group
|
92
|
9.5±1.9
|
44/48
|
17.62±2.46
|
-2.31±1.27
|
-0.42±0.41
|
-2.57±1.37
|
0.01% atropine group
|
101
|
9.4±1.8
|
50/51
|
17.43±3.54
|
-2.39±1.60
|
-0.41±0.38
|
-2.68±1.59
|
t/χ2 value
|
|
0.986
|
0.054
|
1.401
|
-0.397
|
-0.046
|
-0.403
|
P value
|
|
0.191
|
0.816
|
0.178
|
0.702
|
0.987
|
0.712
|
Groups
|
cases
|
Intraocular pressure(mean±SD,mmHg)a
|
Corneal curvature(mean±SD,D)a
|
ACD(mean±SD,mm)a
|
PD(mean±SD,mm)a
|
AMP(mean±SD,D)a
|
AL(mean±SD,mm)a
|
Parental myopia(0/1,n)b
|
0.02% atropine group
|
92
|
16.58±2.80
|
43.07±1.24
|
3.65±0.21
|
6.09±0.53
|
16.12±6.15
|
24.32±0.77
|
30/62
|
0.01% atropine group
|
101
|
16.97±2.82
|
42.89±1.28
|
3.69±0.19
|
6.13±0.69
|
15.56±4.97
|
24.51±0.76
|
28/73
|
t/χ2 value
|
|
0.886
|
-0.554
|
1.375
|
0.021
|
1.214
|
1.271
|
0.547
|
P value
|
|
0.612
|
0.599
|
0.186
|
1.125
|
0.723
|
0.446
|
0.460
|
Note:(a:Independent sample t test;b: χ2 test) BMI:body mass index;SER:spherical equivalent refraction;ACD:anterior chamber depth;PD:pupil diameter;AMP:amplitude of accommodation;AL:axial length;1 mmHg=0.133 kPa;corneal curvature was calculated by the mean of the flattest and steepest meridian curvature;myopic parents:''0'' meant that neither parent was myopic;''1'' meant that at least one parent was myopic |
1.2 Method
1.2.1 Preparation of test drug
Atropine eye drops with different mass fractions were prepared by professional pharmacists in the drug research room of Henan Provincial eye hospital. Place atropine sulfate powder on the super clean workbench, prepare atropine sulfate into 0.01% and 0.02% atropine eye drops with normal saline, adjust the pH value to 5.4 ~ 5.6, add ethyl paraben preservative, put it into a 3ml eye drop bottle, store it away from light at 15 ~ 25 ℃, and discard it one month after opening the bottle.
1.2.2 Ophthalmic examination of subjects before medication
The axial length (AL), anterior chamber depth (ACD) and corneal curvature were measured by IOL master 500 (Carl Zeiss, Germany). The pupil diameter (PD) was measured by AR-1 computer optometer (Nidek company of Japan). During the measurement, the subjects were completely relaxed, adapted indoors for 5 minutes under the condition of naked eyes, and the illuminance value of the tested eye plane was 300 ~ 310 LX; Intraocular pressure was measured by TX-10 non-contact tonometer (Canon company, Japan); The amplitude of accommodation (AMP) was measured by the approach method. Compound tropicamide eye drops were used once every 10 min for 4 times. After 40 min of paralysis of ciliary muscle, AR-1 automatic computer optometry was used for objective optometry, then retinoscopy and subjective optometry. The spherical and cylindrical degrees were obtained according to the principle of the highest positive mirror of the best vision, and ser = spherical mirror + cylindrical mirror / 2 was calculated. The above inspections are completed by the corresponding technicians of the same fixed.
1.2.3 Application method of atropine eye drops with different mass fractions
All eye drops shall be kept and distributed by the same pharmacist who does not participate in the auxiliary examination. The subject's Guardian received the eye drops. The 0.02% atropine group used the alternate day eye pricking scheme, and the 0.01% atropine group used the daily eye pricking scheme. Both groups received eye drops once before going to bed at night, 1 drop / time, lasting for 1 year.
1.2.4 Evaluation index and follow-up
The observation indexes included visual acuity, intraocular pressure, PD, amp, Ser and al. The changes of SER, Al, PD and amp were the difference between 1 year after treatment and before treatment. All follow-up examinations were performed in the morning. The newly prepared eye drops for the next stage shall be distributed after each review.
1.2.5 Observation and evaluation of adverse reactions
When signing the informed consent form, explain in detail the possible local or systemic adverse reactions to the tested children and their guardians, and inform the response measures. During each follow-up, the subjects (assisted by the guardian) were asked about the total adverse reactions since the last review in the form of questionnaire and recorded. The ocular adverse reaction questionnaire includes the following three aspects: (1) whether there is photophobia (never, occasionally, often, always), under which circumstances (no, indoor normal light, daily outdoor light, bright sunlight) and duration; (2) There is ambiguity (never, occasionally, often, always) and severity (none, mild, moderate, severe) and duration of near reading; (3) Whether there is eye itching, eye swelling or other discomfort (never, occasionally, often, always) and the severity (no, mild, moderate, severe) and duration. The observation contents of systemic adverse reactions include tachycardia, dry mouth, nose and throat, fever, facial flushing, etc.
1.3 Statistical methods
Statistical software was used for statistical analysis. The normal distribution of measurement data is confirmed by Kolmogorov Smirnov test, expressed as mean ± SD. The differences of SER, Al and other parameters in the two groups at different time points before and after medication were compared by repeated measurement two-way ANOVA, and multiple comparisons between groups were compared by LSD-t test. The counting data were expressed in percentage, and the differences of gender composition and parental myopia rate between the two groups were compared χ 2 inspection. P < 0.05 was statistically significant.