After her child Xuanxuan was diagnosed with myopia in the first grade of elementary school, Zhang Lin, who is nearly forty years old, has mastered all kinds of ophthalmology knowledge proficiently.
She counted the ways to prevent myopia: ensure at least two hours of outdoor activities every day; every 20 minutes of close study, you need to look far away; the child should have an eye examination every six months during the growth process. ; Compared with white light, warm light can protect eyesight better.
However, Zhang Lin often regrets that she learned these ophthalmological knowledge too late, and she failed to prevent and control her son Xuanxuan's myopia in time.
In March of this year, Zhang Lin bought three boxes of low-concentration atropine eye drops from the small program of Shenyang Xingqi Eye Hospital on the advice of her doctor, hoping to control Xuanxuan's myopia.
The colorless atropine eye drops were packed in a single transparent plastic tube. At first, it dropped into the eyes. Xuan Xuan said that there was a slight dazzling feeling, but after a long time, the dazzling feeling gradually disappeared.
After three months of re-examination, Zhang Lin was delighted to find that Xuanxuan's myopia and axial length had hardly increased.
However, on the evening of July 21, Xingqi Eye Medicine suddenly announced the closure of the Internet sales channel of low-concentration atropine eye drops.
He's Ophthalmology, Opcon Vision and other companies have also announced that they have suspended the sales of low-concentration atropine eye drops in Internet hospitals, and patients need to buy them with a prescription when they go to the hospital.
The suspension of Internet sales originated on May 9 this year. The State Food and Drug Administration publicly solicited opinions on the Implementation Regulations of the Drug Administration Law of the People's Republic of China (Draft for Comments), and for the first time formulated regulations for the management of drug online sales.
Among them, Article 82 points out that the drugs for sale shall be the varieties held by the holder of the drug marketing license or the varieties licensed by the drug distributors.
However, atropine has not been officially launched as an in-hospital preparation and will no longer be sold through online channels.
Atropine eye drops were once known as the "magic medicine" for myopia.
The sudden suspension of sales left parents at a loss for a while.
Some people have grabbed enough atropine, others are anxiously looking for medicine, and the purchasing of atropine has also become active on various platforms.
Behind the search for medicine, a battle to protect the eyesight against the younger age of myopia is quietly going on in the parent group.
ask for medicine
The news of the online suspension came suddenly.
On the evening of July 20, Zhang Lin learned from her colleagues that the sale of low-concentration atropine eye drops would be suspended on the Internet.
When she woke up the next morning, she clicked into the Xingqi Eye Hospital's applet to try to make a registered purchase, but the doctor hadn't been online yet, so Zhang Lin couldn't buy it.
At five or six o'clock in the evening, Zhang Lin opened the applet again, and the announcement on the suspension of the sale of low-concentration atropine eye drops appeared on the homepage.
Originally, Zhang Lin had two ways to buy low-concentration atropine eye drops.
One is to go to a hospital with in-hospital preparations and buy them with a doctor’s prescription. However, only a few hospitals in the country, such as Shandong Eye Hospital, Shanghai Children’s Hospital, and Fudan University Affiliated Eye, Nose and Throat Hospital, can prescribe in-hospital preparations.
The other way is through the Internet hospital: after she took her child to the eye clinic of Beijing Tongren Hospital, the doctor would write a prescription for low-concentration atropine eye drops on the medical record. Zhang Lin took the medical record and went to Shenyang Xingqi Ophthalmology Department. After the consultation on the hospital mini-program, provide the child's eye examination report within three months to purchase.
Like Zhang Lin, Gao Rui, who lives in Beijing, didn't have time to stock up on atropine.
Seeing that there were only ten pieces of atropine left at home, Gao Rui searched for information on atropine on major platforms, and by "seeking medicine" on social platforms, "compounded three boxes" from other parents.
At the doctor's advice, Gao Rui split another atropine into two days for use - atropine eye drops have no added preservatives and only have a 24-hour shelf life.
Now it can only be divided into two uses: put it in the refrigerator in an airtight bag, and give it to the child before the 24-hour expiration.
With the supply cut off, various social platforms have emerged more and more posts asking for medicine, and there have also been many purchasing agents for atropine eye drops.
There are purchasing agents who will usually sell a box of atropine eye drops at 298 yuan, an increase of 40 yuan, an additional 8 yuan registration fee, 10 yuan express fee, and a minimum order of six boxes.
She claimed that customers only need to provide their name, address and phone number, and do not need a prescription from the hospital.
But she couldn't tell the specific purchase channels, only said, "It's all genuine, don't worry."
Another purchasing agent said that he ordered atropine from the person in charge of the hospital. Because parents have stockpiled a lot of stock recently and the supply is tight, he can only open three boxes at a time, and each box needs to be added 20 yuan.
Parents are flocking to atropine.
Wang Lei thinks she is much luckier: she managed to grab ten boxes of atropine before the sale of atropine on the Internet was officially discontinued.
Wang Lei felt that compared with other prevention and control measures, it is much more convenient to use atropine eye drops for her son: gently twist the cap of the plastic tube, drop the eye drops into the eyes, and then discard the single package after use.
Wang Lei calculated that the annual cost of atropine eye drops is about 3,600 yuan.
But compared to the price, Wang Lei felt that she valued more: the growth of the child's eye axis and myopia after three months of using atropine was significantly slower.
Is it a "magic medicine for myopia", or is it one of the prevention and control measures?
When Xuanxuan was 7 years old, after a routine physical examination at the beginning of school, the teacher suddenly found Zhang Lin and said that Xuanxuan was short-sighted.
Zhang Lin took Xuanxuan to the hospital for a check, only to find that he had 100 degrees of myopia in his left and right eyes.
Although Zhang Lin was prepared for her son's myopia: her husband was 900000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000,000.
But she still couldn't believe it: Xuan Xuan was only in the first grade, which was five or six years earlier than her expected short-sighted age.
At first, Zhang Lin spent more than 4,000 yuan to equip Xuan Xuan with a pair of defocusing mirrors.
But after reexamination half a year later, her eyes were 50 degrees deeper, so she had to spend more than 3,000 to get a new pair.
At the beginning of this year, seeing that Xuanxuan's myopia was getting deeper and deeper, the doctor suggested Zhang Lin to try atropine sulfate eye drops with a concentration of 0.01% for Xuanxuan.
This is the first time Zhang Lin has heard that there are drugs that can be used for the prevention and control of myopia.
When she was young, there were not many people with myopia around her, and there was no other means of prevention and control except wearing glasses.
After high school, the number of people with myopia gradually increased.
Myopia has become an "epidemic" in China.
According to the survey results of the "China Eye Health White Paper" released by the National Health and Medical Commission, the overall myopia rate of children and adolescents nationwide in 2018 was 53.6%.
Among them, 14.5% of 6-year-old children, 36.0% of primary school students, 71.6% of junior high school students, and 81.0% of high school students.
"53.6%" - this means that one in two children is short-sighted.
On August 30, 2018, the "Implementation Plan for Comprehensive Prevention and Control of Myopia in Children and Adolescents" jointly issued by the Ministry of Education and other eight departments pointed out that in recent years, the myopia rate of children and adolescents in my country has remained high and rising, and myopia has become younger and more severe. , has become a major issue related to the future of the country and the nation.
The plan puts forward the goal of implementing the prevention and control of myopia in my country: by 2030, the rate of new-onset myopia among children and adolescents nationwide will be significantly reduced, the rate of myopia among 6-year-old children will be controlled at about 3%, the rate of myopia among primary school students will be reduced to below 38%, and the rate of myopia among junior high school students will be reduced to below 38%. It has dropped to below 60%, the myopia rate of high school students has dropped to below 70%, and the national student physique and health standard has reached the standard and excellent rate of over 25%.
It is also against this background that in October 2019, the National Health and Health Commission released the document "Guidelines for Appropriate Technical Guidelines for the Prevention and Control of Myopia in Children and Adolescents", which first mentioned the use of "low-concentration atropine" in the prevention and control of myopia in adolescents.
The guidelines point out that when myopic children and adolescents use low-concentration atropine or wear orthokeratology lenses to slow down the progression of myopia, they need to go to a regular medical institution, under the guidance of a doctor, and follow the doctor's order.
Qu Jia, director of the National Clinical Research Center for Eye, Nose and Throat Diseases, said that under the current reality that there are few measures to prevent and control myopia, low-concentration atropine preparations in the hospital have become one of the main means to delay myopia. The other two means are daily outdoor Two hours of activity, wearing orthokeratology lenses (OK lenses) or defocusing lenses.
"Outdoor activities are the best way to prevent and control myopia." Qu Jia said that many schools do not allow students to leave the classroom between classes for safety reasons. In the reality that the time for outdoor activities cannot be guaranteed, many parents have to seek medical help. means to prevent myopia.
Atropine was originally a drug used to relieve visceral colic, and has also been used in ophthalmology for mydriatic optometry for many years.
The article "Expert Consensus on the Application of Low-Concentration Atropine Eye Drops in the Prevention and Control of Myopia in Children and Adolescents (2022)", which was participated by 86 ophthalmologists across the country, pointed out that as early as the 1970s, there have been international concerns about atropine eye drops. A report on the application of myopia prevention and control.
In 2005, the National Eye Research Center of Singapore released the clinical research results of atropine eye drops.
The study used high concentration (1%) atropine eye drops on 400 children aged 6 to 12 years, and the clinical data for two years showed that 1% atropine eye drops could delay the progression of myopia by 77%, confirming its effectiveness. Effective role in delaying the progression of myopia in Asian children.
However, due to a series of adverse reactions in high-concentration atropine eye drops, such as severe photophobia for users and decreased visual acuity caused by decreased ocular accommodation, the rebound effect is strong after drug withdrawal, and high-concentration atropine has not been widely used in the world. It is used in the prevention and control of myopia in adolescents.
The transition happened in 2016.
The National Eye Research Centre of Singapore has released a five-year clinical trial report on atropine eye drops.
The center launched a clinical trial of different concentrations of atropine eye drops in 400 children.
The results showed that the use of atropine eye drops at a concentration of 0.01% can slow the development of myopia by 50%, and the rebound reaction after drug withdrawal is less severe, and there are fewer visual side effects.
However, the trial report also pointed out that in the first two years of the 0.01% group of the trial, 9.3% of the children's myopia increased by 150 degrees, proving that some children did not respond well to atropine.
The completion of this clinical trial has made 0.01% atropine eye drops the mainstream choice for myopia prevention and control. Countries including Singapore, Japan and Malaysia have started using 0.01% atropine eye drops in hospitals and eye clinics.
Difficulty in listing atropine
Although the role of atropine in the prevention and control of myopia is recognized, the road to the market of atropine eye drops seems to be a bit long.
According to public information, in China, from 2005 to 2018, a number of companies have applied for clinical studies of atropine eye drops that have not been approved or that the Phase III clinical trials have not been completed due to unknown reasons.
Internationally, even in the National Eye Research Center of Singapore, which has made a major breakthrough in the clinical trial of low-concentration atropine eye drops, its low-concentration atropine preparation has not yet been officially launched.
The latest development is that the low-concentration atropine preparation "Myopine" developed by the center was first approved by the Singapore Health Sciences Authority on October 30, 2018, and is used clinically in various hospitals and myopia clinics in Singapore. As of now, the preparation is still in the third phase. clinical trial stage.
It was not until September 2021 that the world's first low-concentration atropine eye drops specifically used to alleviate the development of myopia in children was approved for marketing in Australia.
The low-concentration atropine eye drops developed by the United States and other countries are still in the phase III clinical trial stage.
The first in China to open the situation is Shenyang Xingqi ophthalmic medicine.
In January 2019, Shenyang Xingqi Eye Hospital, a subsidiary of Xingqi Eye Medicine, obtained the "Medical Institution Preparation Registration Approval" and was approved to prepare atropine eye drops with a concentration of 0.01% in the form of in-hospital preparations.
In-hospital preparations refer to fixed prescription preparations prepared and used by medical institutions upon approval according to the clinical needs of the unit.
At present, there are more than ten hospitals in China that prepare low-concentration atropine eye drops in the form of in-hospital preparations.
Chu Renyuan, a professor of ophthalmology at the Eye and ENT Hospital Affiliated to Fudan University, introduced that in-hospital preparations are prepared by the pharmacy departments of various hospitals and are mainly used for clinical trials in hospitals.
Different from marketed drugs, in-hospital preparations need to be approved by the national or provincial drug administration and approved by the ethics committee of a medical institution. They can only be used for clinical trials in hospitals and cannot be sold in the market.
"After prescribing the in-hospital preparations, the hospital should also regularly contact the patient to check back on the use effect and whether there are side effects, and form a clinical research report."
While conducting clinical trials using in-hospital preparations, the State Food and Drug Administration also agreed to Xingqi ophthalmic drug clinical trials to delay the progression of children's myopia.
According to the National Drug Clinical Trial Registration and Information Publicity Platform, up to now, there are 9 clinical trials of atropine eye drops related to myopia in progress, among which Zhaoke Eye, Xingqi, Santian, Ouconvision and Chengdu Shengdi (Hengdi). Rui Medicine subsidiary) and other companies have reached the third clinical stage.
The application process of an innovative drug requires the completion of relevant research work such as pharmacy, pharmacology and toxicology, and phase I, II, and III clinical trials of the drug before applying for marketing registration.
The phase III clinical trial is the confirmation stage of the effect of drug treatment, and it is the key stage to provide the basis for the approval of the drug registration application.
Dr. Liu Liekui, president and chief scientific officer of Zhaoke Ophthalmology, said that the main difficulty in the marketing of low-concentration atropine eye drops lies in its instability and the short validity period of the drug.
Liu Liekui said that due to commercialization considerations, the shelf life of a drug is too short (for example, less than 6 months), and it is difficult to meet the purchase requirements of general pharmacies.
"The pharmacy itself is under a lot of business pressure, so people don't sell drugs with a very short shelf life."
Liu Liekui said that many companies at home and abroad are still in the phase III clinical trial stage, and even the pharmaceutical companies that started earlier abroad did not officially launch the trials until 2017.
As for the two Phase III clinical trials currently underway by Zhaoke Ophthalmology, the subjects have been enrolled, and it is expected to become one of the first drugs to be marketed in China to delay the progression of myopia in children and adolescents.
On August 23, Gu Hong, the head of the clinical trial of Shenyang Xingqi Eye Drug Company, said that the Phase III clinical trial of Xingqi Atropine Eye Drops was in progress, and it was inconvenient to disclose the specific progress.
Yang Xiao, a professor at the Zhongshan Ophthalmology Center of Sun Yat-sen University, participated in the Phase III clinical trials of several domestic pharmaceutical companies on low-concentration atropine eye drops.
She pointed out that in accordance with the "Technical Guidelines for Clinical Research on Drugs for Controlling Myopia Progression" issued by the Drug Evaluation Center of the State Food and Drug Administration in December 2020, a drug that controls the progression of myopia requires at least two years of effectiveness in Phase III clinical trials. Sexual investigation and one-year drug withdrawal observation period, plus the first and second phase clinical trials, the time for children to be enrolled, and the time for drug approval, "We calculate that it will take seven or eight years for this type of drug to complete the registration."
Controversial "in-hospital preparation + Internet hospital"
In Wang Lei's view, although atropine eye drops have not been officially launched, her son's myopia "can't wait".
She said that her son is only ten years old this year, and the degree of myopia has reached more than 100 degrees. After wearing OK glasses for a year, the degree is still increasing.
After three months of atropine use, both visual acuity and axial growth were under control.
Therefore, she intends to drip her son for a long time.
"Maybe we can wait, but a child's eyes can't wait," Wang Lei said.
In December 2019, Shenyang Xingqi Eye Medicine announced that Shenyang Xingqi Eye Hospital has received the "Medical Institution Practicing License" issued by the Shenyang Municipal Health Commission and has the ability and conditions to carry out Internet diagnosis and treatment.
Afterwards, Xingqi Eye Medicine launched the model of "in-hospital preparations + Internet hospital", which issued in-hospital preparations in the form of Internet diagnosis and treatment.
In addition to Xingqi ophthalmic medicine, Aier Ophthalmology, He's Ophthalmology, Opcon Vision and other companies have adopted this model to sell in-hospital preparations of atropine eye drops in their Internet hospitals.
This model has also brought constant controversy over whether the sales method of low-concentration atropine eye drops in the hospital complies with the regulations.
The "Administrative Measures for the Registration of Pharmaceutical Preparations in Medical Institutions (Draft for Comment)" issued by the Legislative Affairs Office of the State Council on January 26, 2015 pointed out that the preparations of medical institutions can only be used in the medical institution with the prescription of a licensed physician or a licensed assistant physician, and shall not be used in the medical institution. Medical preparations are marketed or sold in disguised form.
The "Administrative Measures for Internet Hospitals (Trial)" issued by the National Health and Health Commission only stipulates that special management drugs such as narcotic drugs and psychotropic drugs shall not be prescribed for Internet diagnosis and treatment. Regarding whether in-hospital preparations can be issued through Internet hospitals, the above-mentioned administrative measures There are no specific regulations.
There have been voices questioning on the Internet: If it is possible to sell in-hospital preparations to all parts of the country through Internet hospitals, why bother to do drug registration?
In Chu Renyuan's view, the drug regulatory department needs to have a strict basis to approve the listing of a drug.
Only after a drug has been officially approved as a commodity can it be sold online.
The form of Internet hospital sales is easy to cause drug abuse.
"At present, the production in various hospitals is only provided for clinical research use."
Qu Jia believes that the sales model of "in-hospital preparations + Internet hospitals" has no violations.
He believes that atropine, an in-hospital preparation prescribed by various hospitals, is produced under the strict review of the provincial drug regulatory authorities, and the drug sales process of Internet hospitals is also strictly regulated.
After prescribing atropine eye drops, the hospital's clinical research will also closely track the use of the testers. "Especially during the epidemic, Internet hospitals have played a great role."
Regarding the reason behind the suspension of the sale of atropine in the Internet hospital, the most discussed is the rectification of the Internet hospital.
On May 9 this year, the State Food and Drug Administration publicly solicited opinions on the "Regulations on the Implementation of the Drug Administration Law of the People's Republic of China (Draft for Comments)", in which Article 82 of the regulations on the management of drug online sales pointed out that sales of drugs should be It is the variety held by the holder of the drug marketing license or the variety licensed by the drug distributor.
According to the regulations, low-concentration atropine eye drops that have not yet been marketed can no longer be sold on Internet hospitals.
On July 22, the online hospital applet of Shenyang Xingqi Eye Hospital issued an announcement on the suspension of the sale of atropine.
Network screenshot
In response to the Internet suspension of sales, on August 4, Xingqi Eye Medicine responded on its investor interaction platform, "At present, the company's main business is operating in a healthy manner. As for preparations in medical institutions, patients can go to Xingqi Eye Hospital if necessary. Get a prescription from a brick and mortar hospital."
Qu Jia believes that the sudden stop of Internet hospital sales has made doctors and parents who originally prescribed and used atropine in accordance with the regulations a little overwhelmed.
In his view, because low-concentration atropine is aimed at adolescents and has been used for a long time, it is usually continued to be used until the age of 16. "It is right to take a cautious attitude at the national level."
But he is also worried: the formal channels are suspended, and the informal channels are inevitably flooded.
"We have all seen illegal reselling at high prices offline and online, and even changed their name to 'Antropine'."
Qu Jia said that due to different indications, some children have no obvious reaction to the use of atropine eye drops, "but for doctors and parents, there are always several methods to choose from."
"At present, the review of Internet hospitals is in place. Before prescribing medicine, a doctor will evaluate it to determine whether the child's age and situation are suitable for using atropine." Yang Xiao believes that regular Internet hospitals and irregular ones should be differentiated. Separate online sales.
"Some informal online shopping does not require prescriptions and doctor evaluations, these are the purchase channels that need to be regulated."
Yang Xiao introduced that in the use of non-registered drugs such as low-concentration atropine in Singapore, the United States and other countries, the risk of drug use is borne by the doctor who prescribes the drug. For some drugs that are urgently needed but not yet on the market, this method is relatively flexible.
In China, the risk of drug use is mainly borne by the Food and Drug Administration, which is more cautious in approval, but it is also prone to a "one size fits all" situation.
After the Internet hospital stopped selling atropine, Yang Xiao's hospital did not make any in-hospital preparations, and Yang Xiao could only use other methods to prevent and control children's myopia.
"The effect is not as good as the combined use of atropine. The period of myopia prevention and control is only a few years when children grow up. I hope there will be a compliant way for clinicians to use it rationally as soon as possible," Yang Xiao said.
Wang Kai, chief physician of the Eye and Optometry Center of Peking University People's Hospital, also said that there is clear evidence-based medical evidence that atropine can control myopia, "and the level of evidence is very high." At the moment when myopia is getting worse and younger, low-concentration atropine has also become a It is one of the main measures for preventing and controlling myopia by ophthalmologists in the national ophthalmology clinics.
He also believes that the prevention and control of myopia is a comprehensive problem and cannot rely on a single means such as atropine.
"Including eye habits, sitting posture, eye distance, indoor light brightness, outdoor activity time, atropine, etc., need comprehensive means to control. If you only use atropine, you will not pay attention to other aspects, and you will not be able to control it. Shortsighted."
After the Internet hospital channel was shut down, Zhang Lin counted the low-concentration atropine eye drops left in a box and a half in several homes. "It can last for more than a month." She considered whether to go from Beijing to Shenyang Xingqi specially. Eye hospital to buy?
But she also felt that the time and money cost of this method was too high, and "the cost is too high." Even though there are certain risks in purchasing on behalf of others, Zhang Lin still inquired around, hoping to find a relatively reliable purchasing agent.
Talking about the longer-term plan, Zhang Lin looks forward to the early launch of low-concentration atropine eye drops, and that she can purchase atropine eye drops in a compliant way.
Since her daughter Qianqian was diagnosed with myopia, Gao Rui told her friends with children one by one: If you haven't checked your eyes after birth, you must take them to check them immediately.
After that, Gao Rui will keep tracking the progress of her friends' inspections.
She took this as some kind of compensation for not paying attention to her child's eye health earlier.
"If someone at the time had gone to the trouble of telling me when the child was three or four years old that she should pay special attention to her eye health, set up a file for her, and keep track of her, maybe I would have paid more attention, and maybe she would not be at the age of 8. Such a young age is myopic.”
After her daughter was short-sighted, Gao Rui felt that she had done everything she could: first, she replaced all the lights at home with eye protection lamps, and replaced all the tables that Qianqian would use for her reading at home to the one facing the window sill. As soon as you look up, you can see the trees outside.
After that, she stopped all of Qianqian's extracurricular tutoring, went to picnics and bikes outdoors on Saturdays and Sundays, and took Qianqian to skiing or playing tennis throughout the winter and summer vacations.
Even at noon at school, Gao Rui asked Qianqian to go home for dinner. With a few minutes' walking distance on the way home, she could take a look at the outdoors and relax her eyes.
Every time during the reexamination, Gao Rui sorted out Qianqian's axial length, diopter, intraocular pressure, and uncorrected visual acuity according to the hospital's optometry data, and took the trouble to enter the data into her mobile phone.
She plans that if the atropine eye drops are effective for her daughter long-term, she intends to keep her on until adulthood.
Even so, Gao Rui knew that once she relaxed, the degree of Qianqian's eyes would deepen irreversibly.
She is ready for this: to fight a protracted battle with myopia.
(At the request of the interviewee, Zhang Lin, Wang Lei, Xuan Xuan, Gao Rui, and Qianqian are pseudonyms)
Beijing News reporter Zhou Siya editor Chen Xiaoshu proofreads Liu Jun