During this live webinar, we will discuss all the evidence of using low concentration atropine eye drops for myopia control in children. Topics will include: the concentration-dependent response, age-dependent response, washout out and rebound effect, long term efficacy, and when to start and stop treatment.
Lecturer: Dr. Jason Yam, Department of Ophthalmology and Visual Sciences, The Chinese University of Hong Kong
I’ve no financial interest to disclose. Before going to the webinar, I have a few warm up questions to ask about our participants to get an idea of what is our audience looking for. The question one is, are you using low concentration atropine drops for myopia control in children? Please indicate whether yes or no. Okay. About 40% of our audience are using the atropine drops while 60% are not. Okay.
Next questions. If you are using, what concentration of atropine drops are you using? Please indicate your choice. 40% of those answering is using 0.01 and 25% is using 0.05. And almost another 20% using 0.1% and 10% about using 0.025 and less than 10% using 1%. Okay, thank you.
The third questions. What factor will you consider for the dosage when you start the atropine drops? Age of myopia onset, the current age of the child while you are starting, the parental myopia, baseline myopia, or all of these above factor? Okay, 60% of answering all of the above. And the current age of child another 20%.
Number four, at what age would you start atropine drops for myopia children? That means how young you would start? Four, six, eight, or 10? 40% are four years old, another 40% are about six years old.
Okay, number five. How long will you continue? Use it one year and then stop, use it two years, three years, four years, or until teenage when the myopia progression slow down? 60% of answer indicating they will use until teenage.
Are you combining the atropine drop with other optical method? If yes, A OK lens, B the multifocal contact lens, or C some defocus spectacles? 44% are using OK lens and another 41% is using defocus spectacle. Only about 15% using multifocal contact lens. Okay.
Thank you for answering all these few questions and I hope our talk will go over some of these aspects to talk about the low concentration atropine drops for myopia control. Lots of the wonderful work come by our dear colleagues in Taiwan because the use of atropine drops are very prevalent in Taiwan, using from 1%, 0.5%, to 0.1% atropine drops.
Another very important line master, of course that we all know is the ATOM1 and ATOM2 study by Singapore colleague. In particular the ATOM2 study. They used 0.5%, 0.1%, and 0.01% using over five years time in clinical trial on 400 children. Phase 1 intervention for two years and then washout for one year and then restart treatment for another 2 years. In the phase three, they restarted treatment of .01%. They found that number one, the myopia rebound are less in the 0.01% while greater in 0.5% and 0.1%. And seemed that 0.01% is more sustainable. And over five years time, after this switching, 0.01% had an even better efficacy in the 0.5% and 0.1% group. And however there is a lack of placebo control group. Therefore, the efficacy, the real efficacy of the low concentration atropine is still not known after the ATOM2 study.
Afterwards a meta-analysis suggests atropine is dosed, the efficacy probably is dose independent within a certain range, whereas adverse effects are dose dependent. Therefore our group has started the LAMP study. Based on because there’s number one, a placebo group. We are not quite sure whether it is concentration-dependent response, what are the optimal concentration, what other factors associated with the treatment response, and the rebound phenomenon.
Today I’m going to share some of our work based on the LAMP study and discuss with you some of the perspective. Based on the LAMP study, we have published about six reports and this is a randomized controlled trial in the four group, in the first year of placebo, 0.05%, 0.025%, 0.01%. We included about 438 subject. And the form schedule is similar to the ATOM2 study for better comparison.
This is the first year result. We demonstrate in fact there is a concentration-dependent response along the SE and the axial length. We found that on 0.05%, comparing to the placebo group, roughly there is a 67% reduction in the myopia progression and 51% reduction in the axial length elongation. And whereas in 0.025% it’s about 43% and 0.01% is about 27 to roughly 30%. It is a clear concentration-dependent response.
Accommodation the size, in fact, in terms of the accommodation there is about two diopter loss comparing in 0.05%, comparing to the placebo group. And the pupil size about one millimeter increase in the 0.05%. Whereas 0.05% is about 0.5 millimeter increase and accommodation loss is only about 0.3 diopter loss. The VA distant VA area I’m not going to talk about it.
Adverse effect, in terms after one year’s time, roughly is less than 10% of the children who complain photophobia and other progressive glasses among all the four group are similar. It’s about 1%. And we also use the visual function questionnaire and they found that the VIQ, or vision related quality of life as similar among all the four groups.
We demonstrate comparing to the placebo group, atropine eye drops, low concentration atropine eye drop is effective in 0.05%, 0.025%, and 0.01%. Of course, in particular, 0.01% comparing to the placebo group, the axial length is not clinically significant. It’s not statistically significant and also there is a concentration-dependent response. Subsequently another trial in mainland China has looked into atropine 0.01% about 76 versus 83 control. And find that the relative reduction is roughly about 34% in the myopia progression and 22% in the axial elongation. The research is quite consistent to what we have been reported in Chinese children.
In the Japanese trial, the ATOM-J study, multi-center clinical trial in Japan. About 171 school children six to 12 years of age, 0.01% compared to placebo group, the effect is a bit less. It’s about 15% reduction in the SE progression and 18% reduction in the axial length elongation.
After the first year, in the second year ATOM2 study has noted there is much better pinnacle response during the second year time. Here you can see to that. Over first year is 0.43 diopter progression but in the second years, overall is only 0.49.
It raised a question whether in longer term, after we use the atropine drops, the second year or third year become much better and better resulting. The lower concentration efficacy can catch up with a higher concentration.
And therefore, we look into our second year result in the second phase, its second year, all the group maintained the same group, whereas the placebo group because of the ethical reason, we have to switch over to the 0.05%. Here we can see that that concentration-dependent response are quite consistent. This is 0.05, 0.025, 0.01 and the switch over group. Here is the axial length and here’s the SE.
In number one we see that the 0.05% in two years time, it remained the most efficacious among all the group. We see compared to 0.025 and then 0.01%. And also in two years time point, 0.05% efficacy is roughly double than that of the 0.01% because in 0.05% is -0.5 diopter whereas 0.01% is -1.12 diopter. Switch over group for 0.05% was similar, over two years time was similar to the 0.01% in two years time.
Comparing to the ATOM2 in our LAMP study, the second year, we found that the efficacy of the second year clinically is not very significantly different, in terms of the 0.025, 0.05. 0.01% it has a slightly better efficacy but clinically it’s not very significant. And switch over group also we found that comparing to the self-control group, it is very effective. And all concentration number one, less than three millimeter increase in the photopic pupil size. Study has used this as a cutoff for not tolerable or significant side effect. 0.05%, 0.025% and 0.01%, the pupil size increase still acceptable. And 0.05% accommodation loss is about two diopter. And two diopter means that when a child read they can read at about usually they have accommodation power of 12 diopter they can read at eight centimeters roughly. And loss of two diopter they still maintain about 10 diopter accommodation, they need to lengthen two to three centimeter only. After considering, we encourage our children to read at 30 centimeter. Usually it doesn’t affect their near work, near reading.
In the second year we demonstrate that 0.05% effect was double than the 0.01% over two years time. And the concentration dependent response persistently maintained during the two years.
However, there are also another questions. We can see the discrepancy between the SE progression and the axial length elongation. In ATOM2 study the SE progression is about 60% but the axial elongation is no effect. In the LAMP study, also 27% in the SE progression but only 12% in the axial elongation.
Study researcher has been speculating whether the anti-myopic effect of the atropine is mediated other than the axial length elongation in addition with associated biometric changes. This is important because we want it for myopia control, we want to be due to axial elongation retardation. But not the other parameter.
We want to answer this question and we look into other ocular biometrics by 0.05%, 0.025%, 0.01%. What we look into, we use the first year data to look into the four group and then we look into other parameter including in addition to SE, axial length, we look into the average K, lens power, anterior chamber depth, and also the corneal curvature and corneal astigmatism.
And here you show that the SEs are along concentration dependent and the SE length is also along the concentration dependent. But the change in the corneal power, lens power, and anterior chamber depth are similar. Changes in corneal power, lens power are not significantly different among the groups.
And we also look into the model accounting for these changes. We found that the axial length alone contribute about 70-80% variation. Therefore the other parameter including the corneal power, lens power, contribute in the remaining.
That explain why the SE progression and axial elongation will have a different effect because axial length alone contribute only about 0.7 to 0.8 diopter differences, in terms of the ratio. The remaining variance are accounted by the lens and corneal power. But however, the change in the corneal power, lens power in the atropine group are similar and are not different. Therefore the axial length changes follow a concentration-dependent effect. And is also mainly due to the axial length effect.
And also the children axial length elongation apart from the myopia-associated growth and also include a very, very small amount of normal age-related growth. Therefore the SE changes correlate only part of the axial elongation and therefore will not be, axial elongation will be less than SE progression.
Our study, this report, we found that the low concentration atropine has no significant effect on corneal power and lens power. And the contribution and the SE progression from the axial length, corneal, and lens power from each concentration and placebo were similar. And the anti-myopia effect mainly reducing via the axial elongation and therefore can reduce the risk of myopia complication in futures.
We also want to look into the factors associated with treatment response. Because when we consider the atropine drops or myopia control, we want to identify what are the factors that can enhance the treatment or factors that we need to change, switch, or even increase the dosage.
In other reports we looked into the LAMP study, is to look into other factor, in particular the age. Along the various eye factor, the age, gender, baseline SE, outdoor activity, near work, parental myopia, and the treatment compliance, we found that among all this factor, age, the age at the time the child is using the treatment is the most important factor that are correlated with treatment response. In both the SE and also the axial length elongation.
Here is an important graph to show you the treatment effect. This is a 0.05, 0.025, 0.01 and placebo group. All these along a concentration-dependent response. Here is a poorer response, here is a better response. At each age, you can see a concentration-dependent response. The higher concentration, the better response. But however you can also see that the younger age, the poorer response, the older the age, the better the response. This is quite a clear age-dependent event.
And here is the spherical equivalent, here is the axial length elongation. And also we found that here you can see at the same treatment effect, we use this as a cutoff. At younger age, 0.05% at the younger age, in fact if we used 0.025, it is a older age. And also 0.01 is an even older. What does it mean? It means that we also look into the efficacy using 0.05% at an age of six is roughly to a child, using 0.025% at the age of eight, and is also roughly to a child using 0.01% at the age of 10. And it’s roughly equal to the child using placebo group at the age of 12.
What we know today is that age-dependent effect in each treatment group 0.05%, 0.025%, 0.01% along the concentration-dependent response. The higher concentration the better response. And the younger children require higher concentration to achieve similar reduction in the amount of progression that the older child and children on the low concentration. And therefore higher concentration when we start a treatment if the child is very young age. And then we tend to use a higher concentration. There’s a few reasons. Number one, because the young children, they will have a faster progression because of the inherent progression rate. Myopia progression is age-dependent. The younger the child, the faster the progression. And it will slow down with age. Number two is the younger child, in fact, they can tolerate the treatment better. Their eyes got better. They have a stronger accommodation power and they have less side effect of photophobia.
In this way, a higher concentration administered as a starting dose for younger children given they have a greater risk of myopia progression. And treatment on these children should be aggressive in order to reduce the burden of high myopia.
We also want to know are there any biomarker for the treatment response to low concentration atropine? This is a report we published last year. We looked into the choroidal effects, the choroidal response from the atropine. And here is a chart to show you, in fact it is 0.05%, this is 0.025, here’s a 0.01%, and this is the switch over group. And in fact there is a choroidal thickening. Once you use atropine, your choroid will become thicken. And the thickening is roughly about 20 micron for the 0.05 and also is less than 10 micron for the 0.025 and it’s minimal for the 0.01%.
In this foveal choroidal thickness, there is also a concentration-dependent response. The higher concentration, here you can see that the higher concentration, the more thicken of the effect. And we also in using a mediation analysis we found that the concentration, the treatment concentration and the choroidal thickening can also contribute to the SE progression.
Concentration, low concentration atropine induced a choroidal thickening effect along a concentration-dependent response. The higher concentration, the more thicker of the choroid. Also the choroidal thickening was associated with a slower progression and axial length elongation. Therefore we believe the choroidal response is an important treatment biomarker for long term treatment outcome and as a guide for us to concentration titrations for the atropine. Meaning that when you use the atropine and if you notice any choroidal thickening effect, its treatment outcome and treatment response will be better. On the other hand, if there is poor choroidal response, the treatment outcome will be suboptimal or would be less optimal.
Also in the recent trial we looked into the three-year clinical trial of our LAMP study. In particular at this time we want to answer whether we need to stop the treatment after three years, or we need to continue the treatment. And also what are the factor affecting the rebound? Are there any rebound as demonstrated in the ATOM2 study and what are the factor associated with this rebound?
What we do, our approach is in the phase three, that is after two years, in each of the treatment group we randomized each group into continue group and washout group. In 0.05, 0.025, and 0.01%. In the placebo group, we just keep it as the 0.05% after the first year.
Here is showing you the results. Here is the 0.05%, here is the continue group, here is the washout group. Here is the 0.025%, here’s the continue group, here’s the washout. 0.01%, washout and here is the switchover group. Here’s the axial length.
Number one, what we found is, we found that the washout group, during the third year time, regardless of which concentration you are using, you continue the treatment in fact is significantly better than if you stop the treatment. Meaning that we can just use two years atropine drops and then we stop it. We need to continue at least in the third year time. And number two, we also looked into the washout group. The washout group, in fact, you can see that the 0.05% after stopping the treatment, the rebound is 0.6 diopter. 0.025 is 0.5 diopter, 0.01% is another 0.5 diopter. Clinically, also there is a concentration-dependent response but it is clinically not very significant.
And in the regression model we looked into the factor that determine this rebound phenomenon and we found that age and also the concentration is the two most important factor. What does it mean that the older the age, one age older and then you will roughly have .08 diopter less of the rebound during the third year time. And also the treatment group. You used 0.025 and in fact the rebound is similar to the 0.01%. But if you switch from 0.05% to comparing to the 0.025% in fact there is a significant difference and is about 0.2 diopter.
Overall, in the three years time, here you can see from baseline to 36 months or three years, 0.05%, 0.025%, 0.01% in the continue group, 0.05% over three years is better than 0.025% and better than 0.01%. Also the washout is similar. Therefore our conclusion is during the third year we advise to continue the treatment and can achieve a better effect across all concentration compared to the washout regimen group. And 0.05% remain an optimal concentration over three year time in Chinese children. Stopping treatment at an older age and lower concentration will be associated with a rebound. However, the rebound effect were clinically small across 0.05%, 0.025%, and 0.01%. The atropine drops were all well-tolerated without apparent adverse effect on the vision-related quality of life. Taken into this account we suggest 0.05% atropine over three years, the efficacy is more than double of 0.01% atropine with only minor rebound effect. And therefore, for those fast progression group we suggest to use 0.05% atropine in Asian children.
For my practice, I will also start treatment at the age of four. Seldom we have children at the age of two to three, for those kids, very early onset and very high myopia, these will probably be categorized into congenital myopia. These children tend not to progress and I will observe for a while before starting any treatment. And also number two, for these congenital myopia cases, there’s not much evidence to suggest whether it will response or not.
But what we are talking about is school myopia or those with very high myopic parents. At the age of four if they have two diopter and then I will start atropine drops. And the younger the age onset, the more aggressive the treatment need to be. That is to use a higher concentration. And use the drop once nightly, wear photochromic glasses for those are needed, and follow every four to six months. And the treatment age, we are still analyzing and follow up our LAMP study. We want to determine what are the age that is optimal to, we know the treatment, we still don’t have the answer yet, but I will suggest to continue until 14 or 15 when the progression of myopia becomes slowed down. Of course it’s individualized. For those who are still progressing, of course, they still need the treatment.
In the 10 minutes time afterwards, in the subsequent 10 minutes, I will just go over some of the other method for myopia control and then to bring for discussion. Of course, increased outdoor time is an important measure to prevent myopia. Based on the ROC, the school custom ROC in Taiwan and also in Guangzhou. And we now know that the increase in outdoor time can reduce myopia progression and also reduce myopia onset. And especially in Taiwan, Professor Wu Pei-Chang has conducted a study which is the whole city using a campaign for myopia to increase outdoor activity two hours per day. And then you see the visual acuity of the children which is possibly for the myopia rate, is increasing. But after they launched the activity public health program of two hours per day and it plateau and then it slowed down, it dropped. They reversed the long term trend to reduce the visual acuity in the primary student.
How much is important? At least the current evidence suggests two hours per day, accumulated 14 hours per week is important.
Another method includes the optical method. Optical method roughly it can be defocus spectacles, contact lens, orthokeratology. I would go over this a little bit. Of course, recently there is using the red light therapy but the evidence, many trials are still ongoing so I will not touch on this path in this talk.
The defocus spectacle, what is the rationale? The rationale is using defocus. The light ray focus on the retina is focused, but if the light ray beyond, behind the retina, it induces a hyperopic defocus and it will increase the myopia flow. But if we can induce a myopic defocus, the focus is being in front of the retina, the growth of the eyeball becomes slower. These are based on the animal study and therefore there is several different defocus spectacle in the market and also is using now. Number one is the DIMS technology. They incorporate multiple segment of myopic defocus along the crucial area. And each zone has a +3.5 myopic defocus. And while the central part is normal lens for distant vision, for normal vision.
A two-year double-masked RCT in 183 Chinese children 8-13 years of age, showing over two years there is roughly 52% SE progression slowering and 52% axial length elongation. One point is to look at this cohort, this RCT recruited a population of relatively slow progressing. Because you can see the single vision lens over two years time it only progressed .8 diopter. Given the rational that slow progressing cohort, the efficacy will become better. But fast progressing cohort, the efficacy may become weaker. This has to be taken into consideration.
Just a few days ago there is another report coming up with aspherical lenslet for myopia control done by Huang, Bao colleagues. Rationale using there is a concentric ring configuration with aspherical lenslet along also in the mid-center part of the lens. And it can induce providing a volume of myopic defocus along this. Of course this study also using a highly aspherical lenslet and also slightly aspherical lens to test on the dose-dependent effect.
At two years time, 157 children and using HAL, SAL, and single vision lens, over two years there is, in fact, a 55% SE progression slower and 51% axial length elongation less in the HAL treatment group comparing to the single vision lens. Also you can see there is also a concentration-dependent response. The more highly aspherical lens, the more myopic defocus the better the treatment efficacy. And also at this time, you can see the single vision lens over two years time, it is 1.5 diopter progression. This RCT is progressing faster, this cohort is progressing faster.
Another one is the multifocal contact lens published in JAMA in 2020. It’s an RCT, three years time, using different dosage of multifocal contact lens: high power, medium power, and single vision lens. Over three years time, you can also see there is a concentration–dependent response. The higher dose-dependent effect. The higher end can reduce about 43% comparing to the single vision lens over three years time.
And also other contact lens including the MiSight contact lens, also three years multi-center RCT and also shows that over three years time, the efficacy is about 59% reduction and the axial length is about 52% reduction in these MiSight contact lens.
Finally, it’s the OK lens. OK lens is orthokeratology. It is worn overnight and then during the daytime, you do not need to wear the contact lens. And then temporarily for myopia control and correction. With the study, various study has demonstrated the use of the OK lens can also reduce the axial length elongation compared to control group. In this ROMIO study, there is about 43% reduction comparing to the single vision lens. These are some of the literature suggesting the different method that can help with myopia control.
And combined therapy, nowadays and also in our survey just now we conducted, many of us are using combined therapy already. Combining with OK lens, combining with the defocus spectacle or contact lens. But the evidence are still emerging. I just summarized here is that the atropine combined with orthokeratology, it seems that combining atropine, the current evidence suggesting that combining the OK lens with the orthokeratology may result in better treatment response.
I will end here to leave some time for the Q&A. I would like to thank my support from the funding agency and my department, my team. And also my colleagues here for all the work I presented, in particular the Hong Kong Children Eye Study and the LAMP study. Professor Calvin Pant, Professor Clement Than, Dr. Zhang, the whole team, for we worked together on this.
I would like to take some question and discussion in the following 10 to 20 minutes.
In the Q&A box, okay. To what age is it recommended to continue usage of topical atropine? I hope my powerpoint and my talk has answered this question. Currently, in fact, we don’t know. We don’t have the exact target of stopping the treatment yet. But what we know is, number one, the myopia progression is age-dependent. The older the age, the slower the progression. And number two, the rebound phenomenon is also age-dependent. The older age you stop the treatment, the less rebound. Therefore, I would suggest you stop the treatment at the older age whereas the progression rate is slower and even though you stop the treatment, the rebound is less. I would suggest about 14-15. Some child, if they still have an ongoing progression of course we need to stop it at an older age.
What would objectively constitute atropine-driven failure? I would say that atropine-driven failure… Of course you need to consider several factor. The high risk of failure, including the age, the younger the age, second one is the parental myopia. Our previous cohort has demonstrated that parental myopia is a very strong indicator for myopia progression or myopia development. If you have both parents highly myopic, the odds of developing myopia is about tripled. Considering all these and then you need to consider whether the treatment response is good enough. I would say I would consider within 0.5 diopter for one year acceptable. If it is more than 0.5 diopter, we need to consider number one, stepping up the dosage. Number two, combining with other treatment. In fact, if they are really not responding, we need to consider switching treatment or using other method.
Is it advisable to use atropine to African children with congenital myopia? Thank you for this very excellent question. I would say I do not have the data and I don’t have the answer for this. But I would say because African children having a pigment iris, I would say they would be more tolerable to the atropine side effect. What I have gathered understanding is that for atropine treatment or for all myopia control for a fast progression cohort, the effect would be weaker. For slow progression cohort the effect would be much better. I would expect the treatment in Asian will be even better in Caucasian given the fact that the Caucasion child tend to progress slower than the Chinese. And also in African children, it depends on the progression rate. If the progression rate is slow, atropine will definitely, the efficacy will be even better. I would say if the African children, they are progressing, I would suggest to try to use the atropine drops and it will be helpful.
How best myopia in children can be treated? How? I would put it this way, based on our LAMP study, in fact, we can reduce about 67-70%. To note that in better LAMP study, we include quite a fast progression cohort. Because we include age 4-5, compared to the ATOM1 and ATOM2 study, and many other studies. ATOM1 and ATOM2 study is using the age of 6-12. And also the other spectacle, optical method usually is 8-13. Now our study include a very fast progression cohort because of the young children and we have achieved about 67-70% reduction.
And if a child progression annually is about one diopter, or .8 diopter, after six to seven to eight years it become highly myopic. But if you start the treatment early and then you can maintain within .3-.4 diopter and then the child will not become highly myopic for the rest of their life and much reduce the complication. Because having high myopia, the complication of myopic macular degeneration is 850 times higher than normal optic eyes. The treatment can help prevent the future of blinding complication for our next generation.
What bring you to look at the choroidal thickening as biomarker? I’m not sure whether I get the question correctly. But what we do is we use the OCT to measure the choroid. I would say now we understand in using, having understand the atropine response can partially be reflected by the choroidal response. Whether the choroidal thickening is in addition to biomarker, whether it is the mechanism to reduce the myopia we are still investigating. But at least it is a biomarker. We can see that a higher concentration shares a thicker choroid. Dense choroid becomes thickening. And this choroid laid where the treatment effect, therefore when we have a child and after a few months and then the choroid’s not thickened, we can consider to step up the treatment until there’s a choroidal thickening. Until there’s a choroidal response. And then to have this can probably pave the way for individualized atropine titration approach, using the choroidal response. I hope this can answer the question.
Hello. Can you tell us a bit about the side effects you see in practice? The side effect is majorly the side effects, there’s two side effects. Number one is the blurred near vision. Number two is the photophobia. I have been, to be very frank, I have very little experience on Caucasian group, so I do not know the tolerance of light pigmented iris.
But in Chinese, in Chinese, they’re total in dark pigmented iris, they tolerate quite well. Having 0.01%, usually the child do not counter anything. They don’t feel photophobia, they don’t have blurred near vision. Up to 0.025, they are also very good in terms of the side effect. In 0.05%, some of the children may feel a bit bright outside. But they are still acceptable, they feel it is acceptable, it doesn’t affect their daily activity. And for the reading, most of them do not complain of the blurred near vision. I would say 1-2% they have a very sensitive response or the accommodation reserve is much less. They will have blurring difficulties in reading, they need to lengthen 2-3 centimeter in order so they can read. But all these are acceptable at least to Chinese children and to Chinese parents. They are very used to having all these concentration, especially on 0.05%.
Is there a digital software to monitor and calculate progression? I would say there is different formula in the past and also nowadays people are using AI, artificial intelligence, to monitor progression. But what I would suggest is to look into two factor. To me, the two important things to factor is number one, the age of onset. And number two is parental myopia. Because these two are very important baseline factors that can predict the progression of the children. You can see it is a fast progressor or slow progressor. Say, for example, if a child come to you at the age of 10 and they only start to have myopia just to have the myopia at the age of 10 or 12, and then the parents are both not myopic, I would tend to use a lower concentration. To parents of acceptance and also the treatment efficacy. But if a child come to you at the age of four, already 2 diopter, and both parent is -8 and then I would use 0.05% or even higher concentration because we expect the progression rate’s much faster.
How does increased outdoor time help with reducing myopia progression? This is done by a lot of various group. The first has to be credited to Professor Kathy Rose from the Sydney Myopia Study in 2008. In the Sydney Myopia Study shows that the increased outdoor time can be associated with a lower myopia prevalence in Australian children. And a lot of other studies have been followed up to confirm this association. And then in Taiwan Professor Wu Pei-Chang, using the classroom, the ROC study, to show that it’s reducing myopia prevalence and incidents. And also the Professor He Mingguang published in JAMA in about 2016 in GUANTO OCT study.
Increased outdoor time probably still to the dopamine. Because the increase in the outdoor light it luminate our retina to release the ocular dopamine which is an axial length inhibitor. The ocular eyeball inhibitor that can reduce eyeball elongation. I can roughly, what we are quoting now, is roughly outer activity about 30% efficacy. You can argue that 30% efficacy is not much. But if the whole country, whole region is doing this in a public health approach, we can bring a significant impact. But for those who are fast progressor, after outdoor activity, for them it can help them to reduce but they still need atropine, they still need other method to help them.
How does atropine help with reducing myopia? What is the mechanism of action? I would say we are still not one hundred percent sure about the atropine mechanism. It is based on the pinnacle evidence that it is really working comparing to the placebo group. Number one, we know that it is not related to the accommodation. Because in animal check, atropine can still work for myopia progression. I would say our study also provide more evidence, additional evidence or supporting the other evidence that in fact atropine can induce a choroidal response. Whether the call to response can induce more choroidal circulation, that can maybe helping the atropine to expand atropine effect. Also the atropine can work on the retina, the sclera, the structure that may help to remodel all this. But they’re still under a lot of different investigation and experiment and study and we don’t have a very definite answer to this yet. Thank you for the question.
How do we measure choroidal thickness, how can we show both measurements pre and for comparable? Now we use OCT. And if you use a Triton OCT the medial measurement, Triton OCT, the medial measurement is not very dependent. It’s quite autonomous, semi-autonomous. And also for measurement you need to be aware of the diurnal variation for the choroidal effect. Usually you measure at the same time. For the length it’s almost all the children measure at the three to four PM, all of them. This you need to consider. And also the cycloplegic agent can also have the effect on the choroidal. You need to measure under the same protocol. We use it after the cycloplegic. Although the cycloplegic agent may affect the choroid, but if you measure both the pre and post measurement are the same, it will still give you the answer whether there’s any thickening or not.
What is the acceptance rate of myopia treatment by parents? In Chinese, especially in fast progressing children, the acceptance rate is excellent. I would say it’s more than 95%.
Is several CBI can use local agent atropine? If they have myopia progression, I would say there’s no, I don’t have the data and I don’t have the answer yet. But using local agent atropine in fact it is very, very safe on one hand because the concentration is very minimal. I would say you can consider as a trial and also to see whether the effect can be used.
What approach would you recommend for a four-year-old girl with right eye 10 diopter, left eye atropine 0.1% denature defocus? This is also somewhat on an offer we sometimes see these children. Now, four years old with 10 diopter, I would say whether it is a congenital myopia or not. If it is a congenital myopia, I’ll observe for a moment yet. Because some of the cases with congenital myopia they don’t progress. Some of them they regress a little bit even. Especially if it’s four years old, of course we also need to concern about amblyopia. Four years old with -10 diopter, that’s going to leave the girl have amblyopia. I would probably go for treating the amblyopia first with the glasses. Sometimes they may also need the contact lens to improve the visual rehabilitation and then observe at least for half year to see whether it’s really progressing. If yes, then we will start the atropine. Atropine 0.05% is maybe even not enough and then I would talk to 0.1% or even higher concentration. And using defocus spectacle may help. But given this fast progressor we need to have a combined treatment. I agree with this.
Control. How do you set your control? You mean in the study? In the study we used a control as placebo group. We used a placebo is a randomized controlled trial. We used a placebo group with normal saline drops.
What do you think it would make a difference if used 0.01% five times a day compared to 0.05% once a day? Very good questions. I don’t have the answer yet, but in fact we don’t have, certainly what concentration that we want all the times. What I will use is, I also use a fifth approach. Say, for example, a kid’s come to me, I don’t want to start 0.05% because it’s slow progressor, age of 10 or even 12, and now we start at 0.01% and then three drops, two or three drops. What I suggest to do is one drop after a few minutes, another drop, another three minutes, another drop. I won’t use it in the daytime because we want to avoid using the drops at the daytime to reduce the photophobia. All at nighttime.
How effective is it when you have atropine lenses and other activity combined? I personally think it would be better. We are still looking forward to have more clinical data to come out to see.
For age one years old, parents are high myopia, for age one can I use atropine? I would say we need to consider the hyperopia research. How much is your hyperopia? I would say if the hyperopia research is less than 0.5 diopter, then we can consider starting atropine for prophylaxis.
How should we treat a progressive boy for one year’s old, I would still wait a bit longer. At least three to four or five.
How should we treat progressive myopia in adulthood? Is it the same protocol? I don’t have the answer because there’s no data for this. We understand that progressive myopia in adulthood the progression rate is not very fast. And atropine is not helping in adult. I’m not saying it’s not helping, but it is very disturbing because you use even 0.01% as an adult they feel very blurry. Only children, only kids with strong accommodation power can tolerate the atropine drops.
What dosage would you consider? I think this has been covered.
What’s the priority of myopia concentration you prefer lowest to highest? It depends on the age. If a young aged children come to me, I would go from highest to lowest because we need to prevent progression fast. If a older children comes to me, slightly varied slow progression. I may go from lowest to highest. I would start it first and see the side effect and then gradually titrate up.
Do you take accommodation therapy? I would also use defocal spectacle for some of the kids if they are progressing.
Any increase in your patient? I don’t have a lot of experience on all of these.
Early onset, still progression with higher concentration. Yes, I would say, I would take up a higher dose.
What do you suggest to wear together atropine therapy? Eyeglasses or soft contact lens? It really depends on the parents preference. In general, parents prefer glasses more than contact lens. But of course if some parents prefer contact lens, combining atropine with contact lens, especially the multifocal lens, should be a good idea.
Can we prepare 0.05% atropine concentration? We usually ask that pharmaceutical manufacturer to prepare for us. It may be safer and you can ensure the concentration be better.
There’s still quite some of the questions. Maybe I choose a few more to answer.
Is it beneficial over 15 years of age? If it is still progressing, yes.
What’s the criteria to step down the dosage of treatment? I would say the older age, slower progression, then you can start to step down the treatment.
Any role for low concentration atropine in the amblyopia in mild? In amblyopia, in myopia children, this is another about amblyopia. Amblyopia using low concentration for amblyopia treatment is not working because it doesn’t affect the vision at all. But for myopia progression, I would say it is still a role for preventing myopia progression.
In your LAMP study how do you measure the refraction, subjective refraction or cycloplegic? I use both but for the data represented we used cycloplegic refraction. Cycloplegic was more objective measurement and also the axial length.
Any study about atropine effect on corneal thickness that could have affected treatment? Our study data we haven’t shown here, atropine should not have any effect on the corneal thickness.
Does atropine affect academic achievement? We don’t have any data on that.
Bifocal help to reduce progression of myopia? The use of bifocal is very modest, very mild. Previous study our city had showed that it can have a mild effect. But the effect is not very significant.
At what amount of myopia can use atropine? Any amount. Even though for some of the children with very high myopia parents, they have very low hyperopia observed. Some of them may also use atropine for prevention.
What is the mechanism? I have answered this.
Should we have treatment for under eight years old is suitable? Under eight years of age I would say 0.05%.
What last action will decrease chronicity and benefit? Lifestyle change, of course, number one, increase outdoor time, two hours per day, 14 hours per week. Number two is encourage a good reading habit. Not too long, every 30 minutes take a break, not too close and at least 30 centimeter, not too dim. We need to have adequate light for reading.
What happens in case of noncompliant period spent using drops? Can you restart treatment? Yes, for those noncompliant we would restart the treatment. It doesn’t ever too much as long as you use the atropine drops and then the treatment efficacy can happen there.
And then the other question is combination, I believe I have covered in the talk.
And how to manage low vision in short distance? Reading, writing. Now there’s a few approach. Number one, you can use progressive glasses if the seven years old children using 0.05% is really complaining in short reading problem, you may consider progressive glasses or they can help for this.
Higher dose of atropine can cause reading blurry, should we prescribe glasses? That is the same question. For those who are really cannot tolerate then it’s about a few percent, we can use progressive glasses. That can definitely help and also may have added value.
Do you use atropine in primary children? Yes, I have answered this question.
Is it effective more than age of 20? Some of the group in Taiwan they advocate to use until the age of 18. Our LAMP study is now following up to the age about 17-18 now. I would say when the progression rate’s slower then we can consider to start to slow down. Because the progression is very slow. Of course the older the age, the more, the better the efficacy, I would say in this way.
Accommodation role in the progression of myopia. Currently the hypothesis or the theory is based on the defocus, is less about accommodation, it’s about the defocus. The defocus inducing the eyeball growth, therefore the defocus may be the main role in the development of myopia.
Any eventful heart rate if use atropine for a long time. Using low concentration atropine it doesn’t affect the heart rate as long as the eye can, in my experience.
Thank you very much. I seem to have go over, very quickly, all the questions and hope that this can help answer in some of your query. And I hope that this talk can help you to understand a little bit more about the use of atropine eye drops for myopia control. Thank you very much, once again, for attending this lecture. Thank you.
April 8, 2022