Lecture: Myopia in Children Treated for Retinopathy of Prematurity

Good morning, everybody. I’m Dr. Neelam Pawar, pediatric ophthalmologist for Aravind Eye Hospital in India. Welcome to Cybersight live webinar. I will be presenting on myopia and treatment of retinopathy of prematurity. I’m an ophthalmologist at Aravind Eye Hospital in India. I’m having no financial interest in this presentation. And during my presentation, I will have a few poll questions for you. And it will be my pleasure to answer any queries at the end of the presentation. ROP is a global health problem. And because of increased care and improved ICU setting, we are seeing increasing incidence of ROP. And geographic differences do occur in the epidemiology of ROP because of disparities in care. And recently, there has been surge in publications and research on ROP. So here is the poll question one. What is your current position? A pediatric ophthalmologist, comprehensive ophthalmologist, pediatric fellow, retina fellow, medical student or resident or optometrist? Let’s see all who have joined us today for this webinar. Yes. So it’s great to see that most of you are optometrists, 37 percent. And next are the pediatric ophthalmologists and comprehensive ophthalmologists. Few are pediatric fellow and retina fellow. And most of them are medical students. It’s great to see all of you. This talk is from the perspective of pediatric ophthalmologist. This article in journal of pediatric ophthalmology and trauma bis muscles reported that ROP is second most written about and top 100 cited articles in pediatric ophthalmology followed by myopia. This lecture will focus and explore on the dynamics of myopia development in treated and untreated cases of ROP. It will highlight recent findings on the myopia development and evaluation of the various factors which are associated with preterm babies who are not only treated with anti-VEGF or laser photocoagulation. We will also see what happens in untreated patient. And we will have discussion on latest research findings, clinical insights, and potential strategies in context of myopia related to ROP. This is the global map that shows the burden of vision impairment due to retinopathy of pre-maturity. If you see, sub-Saharan Africa, North Africa and Middle East have a higher percentage of visual impairment and blindness due to ROP. While high-income countries have least prevalence of visual impairment due to ROP. The most important risk factor for developing ROP prematurity and low birth weight. 50 separate risk factors have been identified and associated with ROP. And if — factors are taken care, the prevalence of ROP and severity of ROP can be reduced. The vascularization of the retina begins approximately 15 to 16 weeks at optic disc and later on it goes into peripheral retina. It is completed by 32 weeks. And by 40 weeks at temporal retina. So in case of preterm birth, there is initial relative hyperoxia and later on because of the depleted fluctuations of supplemented oxygen, there is dysregulated signaling pathway that leads to — ROP where there is compromised physiologic vascularity and later on phase two, where there is vaso proliferation and a fibro vascular cyst. So there are various studies on screening of ROP which are based on different algorithms and different countries. And the maximum sensitivity and specificity for detection of ROP. Will are oxygenation target studies to set an oxygenation target for ROP babies and there are treatment studies with different landmark studies like C are yours YO-ROP and ETROP and BEAT-ROP. We will focus on these studies. Dr. Good in this article in ophthalmology, reemphasized the fact that genetic factors play an important roll in ROP. It’s the post conceptional and gestational timing which is more important than the post natal. So here again, reemphasizing that people should undergo and read this early report of incidence and early growth of retinal myopia of prematurity with this remarkable trial, the cryotherapy study for ROP. The world has seen three epidemics of ROP. The first epidemic was seen in 1940 in the US and western Europe because of unmonitored supplemented oxygen. And second epidemic seen in 1980s because of greater survival of increasingly preterm infants. In the late 80s and early 90s, the third epidemic was seen in eastern Europe and Latin America and then in southeast Asia and 2020 in sub-Saharan Africa because of the expansion of intensive neonatal care which is often because of poor quality services and low coverage of ROP. This recent surge in cases of ROP in Africa and it raises the alarm whether we are stepping into the fourth epidemic of ROP. Now poll question 2, are you aware of different weight or gestational age guidelines of various countries for ROP screening? Yes, no, or not sure? It’s good to see that most of you are aware of different weight and gestational age guidelines of various countries for ROP screening. Each and every country is having its own criteria for ROP screening. Gilbert et al. in their study found that countries with high levels of development have low birth weight and gestational age criteria compared to low and moderate levels of development in various countries. And if you see this box plot, median birth weight and median gestational age is less is high income countries. And variations occur in different Asian countries also. This is the comprehensive list of ROP screening guidelines across the world. And if we look in this table, countries like Columbia, Costa Rica, Cuba, Mexico, Philippines and Nicaragua are having higher birth weight criteria and higher gestational age criteria. The current guidelines in the US is the screen babies of less than 15 grams or less than or equal to 30 weeks as well as to screen those infants who are having unstable clinical course. Why in UK criteria, there is no additional criteria of screening in — unstable clinical course. So next question comes whether we should screen infants with unstable clinical course. Most of the time we see cases from neonatologists who have a — referred to us for screening of ROP. So this study done in Colorado with a very long-term — from 2006 to 2021 on unstable clinical course, the authors reported that only 6.9 percent of the babies referred with unstable clinical course developed ROP. 6.2 developed type two. While none of the babies had treatment requiring ROP. But still, it is good to screen all the babies with unstable clinical course, because if we can save even one eye with ROP, it is worth to screen all the babies with unstable clinical course. In 2005, the earlier classification of ROP and event modification including severity of disease into stages and progressive ROP. In 2021, the ICROP3 edition came that changed the lexicon because of the increasing use of anti-VEGF in the treatment of ROP. There is a description of reactivation and one has to see if there is a physiologic vascularization of the anti-VEGF treatment or any other pathologic extra retinal neovascularization going on. Reactivation after anti-VEGF includes vascular dilation, tortuosity, and extra-retinal neovascularization. Clarification of regression with reduced dilation of the veins and — or arterials and veins. This definition of persistent avascular retina and addition of posterior zone 2 which is just outside the zone one. There is new subclassification for stage 5. Along with 5A and B, we have 5C that includes the anti-disegment manifestation and the broader definition of plus (ph) disease and long-term sequelae like strabismus and retinal detachment. This is the stage one ROP. We can see there is a very fine demarcation line. In stage two there is a ridge formation. This is stage 3 with extra retinal fibro vascular proliferation. Stage 4 with retinal detachment not involving fovea. This is 4B where fovea is involved. Stage 5, there is open ROP and stage 5b is closed ROP. And stage 5C along with retinal detachment is shallowing of the anterior chamber and involvement of the anterior segment. I’m grateful to Dr. Shah for sharing this picture and he was one of the eminent pediatric retinal specialists involved in IC ROP classification. These are pictures of stage 1, stage 2, stage 3 and stage 4. This picture is of stage 4 which is suggestive of pars plana retinopathy and thanks to Dr. Syed for sharing this. It’s important to have a good and collaborative relationship with pediatric people and retinal specialists because pediatric ophthalmologists usually follow these cases for long term. Next is poll question 3, do you use the term myopia of prematurity in your clinic or hospital? Yes, sometimes, never, frequently, not aware of this term? Do people really use this term or not at all? It’s great to see that most of you responded that sometimes they use the term myopia of prematurity in their clinical practice. And some of them, very few percentage of them are not aware of this term. So what is myopia of prematurity? It’s a form of refractive error related to alterations in the development of anterior segment that occurs in individuals born prematurity. Quite often this term is underestimated. Though it is different from pathologic or school-aged myopia. But ICD classification doesn’t have a code for this. So unfortunately, we have to always report or code it as simple or high myopia. And unfortunately, there is even no term, no med terms to search in databases like PubMed or other scholarly systems. So myopia of prematurity can be broadly divided — this is just for understanding — it can be divided as myopia of prematurity where only prematurity is responsible. And then myopia of prematurity without treatment or in cases where there is spontaneously regressed, that is ROP without treatment. And then myopia of ROP which is a result of sequelae of ROP with treatment and myopia of adult retinopathy which is known as adult ROP. So Longback, Felder, and Quinn published this paper in the British Journal of Ophthalmology of myopia of prematurity, nature, nurture or disease. They stated that myopia is probably the normal refractive state in infants before full term with the eye becoming more hypertrophic in early infancy. Comparing these eyes with full term baby, this myopia are of shorter axial length, flatter anterior chamber and more spherical length. So there are several theories associated with myopia of prematurity but none-over them are 100% conclusive. But still, these theories are postulated to be responsible for myopia of prematurity. The first is the arrest theory that states that ROP and prematurity lead to blocked development of the anterior segment of the eye, which affects the process of orthokeratology and refractive status. And if then dysfunctional retina alters the eye growth signals. The bone deficiency theory says that MOP could be attributed to post-natal bone mineral deficiency. And temperature theory states that preterm neonates experience usually hypothermia and they experience temperature deficit at a time when the corneal growth is especially active. There is a light, visual, and deprivation theory, that says that light exposure can act as a myogenic factor. ROP induced myopia cannot be fully explained by increased axial length. There is always a nonlinear refractive development associated with ROP. And the prevalence of myopia rises as stage 3 is achieved and so the prevalence of anisometropia and astigmatism. To summarize, two types of myopia are associated with premature birth. First is physiological and temporary myopia, which is nature. And second is myopia without ROP, MOP or nurture. And third is myopia induced by ROP, that is disease. So this is the white paper published by the International Myopia Institute and they focus in this article on investigation and management of high myopia in infants and young children that biometric evaluation including excellent and corneal curvature is very important to distinguish myopia from refractive myopia. Because refractive myopia is associated with abnormal development of anterior segment. This is the famous curve by Gordon. If we see most of the length increases in 0 to 2 years in normal children. While lens power decreases sharply in 0 to 2 month age. In another longitudinal study of biometric and refractive changes in full-term infant during first year of life, the regression analysis showed that excellent change is curvilinear, the anterior chamber depth is linear. And while there was no change in length thickness in children in first year of life. So Gordon et al. in their very small subset of patients with retinopathy of prematurity found in 1986, they reported that children with retinopathy of prematurity have higher lens diopter value, which was found to be statistically significant compared to full-term babies. So the longitudinal studies of the development of MOP indicate that degree of myopia is not static from birth, but it develops over time and most rapid changes occur during the first year of life. Quinn et al. in their study reported that distribution of refractive errors changed between 3 months and 1 year with little change after 1 year. Other studies report that Mr. Continues to increase until 3 years of age and even beyond that. So what about refractive data in untreated ROP? As we know ROP is a complex and multifactorial phenomenon. So this is influenced by severity and duration of acute ROP. Even in untreated cases we can see significant trend of sphere toward mosquito and increased magnitude of astigmatism and an isometropia. There is a significant trends towards myopia that increases in severity at 6 months of follow up. In this paper published in the journal of [inaudible] the authors reported outcomes for nontreatment requiring infants evaluated for ROP and reported that out of 304 patients, most of them had hyperopia and astigmatism followed by myopia and strabismus and other manifestations. And the author, again, stressed the fact that all the children, even with nontreatment requiring infants with ROP, they should be checked by ophthalmologist at 4 to 6 months after discharge from their hospital. These are even the guidelines given by American association of pediatric ophthalmology and strabismus. So what is the epidemiology of MOP. The risk of myopia is higher with treatment of posterior ROP with cryotherapy or laser. In cryo ROP trial, there was a natural history population group. In that group, the overall prevalence of myopia was 21 percent among all subjects at one year. While subgroup with severe ROP had myopia prevalence of 80 percent. And overall prevalence of high myopia in untreated group was 3.9 percent at one year. But it was 43 percent among those with severe ROP. Each 100-gram decrease in birth weight correlated with a 10 percent increase in the prevalence of myopia. The ET-ROP studied published in 2001, had participants with ROP and high myopia was 65 percent and 35 percent representatively. And about 70 percent of high risk pre-threshold ROP eyes, which were treated with laser, were myopic by the age of 4 to 6 years. The BEAT study which is bevacizumab, eliminates the angiogenic threat of retinopathy of prematurity. The study compared the effect of bevacizumab over laser therapy for zone 1 disease in infants with stage 3 plus ROP. And this study found that children with zone 1 ROP, the mean SE was minus 1.5 with a standard deviation of 3.2 diopters in the intravitreal bevacizumab group. And it was minus 8.4 for the standard deviation of 7.57 diopter in the laser group. The question arises why the myopia is less with bevacizumab? The intravitreal bevacizumab allows for minimal disruption of the local growth factor and signaling pathways which are necessary for the development of anterior segment. And it stays for a few weeks in the body. In the case of laser, there is a larger confluent area which is destroyed by laser and therefore it disrupts more signaling pathway and alters the anterior segment and leads to more myopia. The rainbow trial which is Ranibizumab compared with laser treatment therapy. Used Ranibizumab 0.2 mg and 0.1 mg which is cleared more rapidly in the blood compared to laser treatment. And even this study compared the alternate Ranibizumab dosage for safety efficacy. What the study found? It found that at 24 weeks post treatment, the success was 80 percent in infants with 0.2 mg Ranibizumab. And 75 percent with 0.1 mg of Ranibizumab. And 66.2 percent following the laser treatment. And at 2 years, there was no new structural abnormalities with the 0.2 mg dose. And it was superior to laser therapy in terms of myopia and it causes less spherical equivalent of myopia. So this Cochrane database of the systemic review included 5 trials which compared intravitreal bevacizumab and Ranibizumab with a laser therapy and even one trial comparing — with laser therapy. And this Cochrane Systematic Review pointed the fact that the mono-therapy with Avastin and Ranibizumab should be taken with caution. This causes less refractive error but still the chances of reactivation and retinal detachment are high with mono therapy alone. These are the anti-VEGF used for the treatment of ROP. And bevacizumab is more commonly used more widely for treatment of ROP. And recently, there are various trials going on with the Aflibercept on ROP management. What about this anti-VEGF? We don’t know the long-term safety effects. This correct dose established and long-term outcomes like systemic effect and effect on neuro development with this anti-VEGF treatment is not clearly understood. There is no consensus regarding the frequency of exam, the length of follow up after treatment, when to discharge the patient, and whether to treat or not to treat the persistent avascular retina. Whether to add insurance laser or not. There is always a dilemma. The long-term follow up studies including the five-year extension of rainbow as well as butterfly eye and firefly eye which is having — using Aflibercept versus laser ROP will give a more conclusive result in the future. What is the pathophysiology of myopia and high myopia associated with the ROP. So until now we have seen that myopia of prematurity whether it is associated with the ROP or not, the myopia result due to abnormal development of anterior segment there is increased lens thickness and power. These patients have increased corneal curvature and steepness. And axial length compared to myopia, axial length is shorter. If you see the position of the lens center, it’s a more forward position of the lens center and 50 percent, there is 50 percent higher in ROP eyes that contribute to the development of high myopia with shallow anterior chambers. So, here is poll question 4. Do you perform biometry in ROP patient? Yes, no, or sometimes? 41 percent of you do not perform biometry in ROP patient. And some of you do sometimes. And 33 percent of you are saying that they perform biometry in ROP patient. So it is very important to do biometry in ROP patient because then only we can rule out and differentiate it from axial myopia. So how the treatment modalities may affect structural changes in ROP eyes. In this study, comparing full term eyes and ROP treated eyes, they found that refractions were almost similar. No significant differences in the refractions. But ROP eyes who were treated with cryo or laser had increasing myopia which was associated with lens thickness and lens power with lesser contributions from corneal steepness, axial length, and more forward position of the lens center. They found that ROP eyes had lens thickness by anterior chamber depth ratio almost 50 percent higher than full term babies. While they found no differences in axial length between the laser treated eyes, compared to matched full term eyes or regressed ROP in a followup of limited duration. But most of the studies report that axial length in laser treated eyes in ROP eyes with spontaneous regressed ROP, they have shorter axial length compared to matched full term eyes. So this is a very interesting study which did biometric evaluations of variations in high myopia associated with different underlying and ocular conditions and the authors found that patients with treated ROP have significantly higher lens thickness. And higher K values and lesser anterior chamber depth and lesser axial length compared to the other groups with high myopia. And if you see on comparing with the isolated high myopic group, ROP patients have excellent range with a standard deviation of 1.9 mm which is quite less than high myopic eyes and the steepness of the cornea increased with 45.7 with a standard deviation of 1.9 diopter. The anterior chamber was shallow. A range of 3 with a standard deviation of 0.5 mm. And lens thickness was high. With a standard deviation of 0.6 mm. The author stated that ROP group had significantly shorter axial length, shallow anterior chambers and thicker lenses compared with isolated high myopic group. And they concluded that retinopathy of prematurity associated high myopia with primarily lenticular. So this study is the longest longitudinal study which has ever been reported in the literature. And this study was, showed that higher prevalence of myopia and astigmatism was observed in laser treated threshold ROP eyes on comparison with age-matched control eyes and myopia and astigmatism in laser treated ROP eyes typically progress through adolescence after school age. So this paper tells us that it is not only the school age which requires followup for this ROP patient but even at adolescence also, these patients require followup. What is pattern in lasered ROP. The longitudinal SEQ in the severe ROP group were best fit with the bilinear model. Before 1.3 years old, the rate of myopic shift was minus happy.7 diopters. And after 1.3 years the rate slowed to minus 0.15 diopter per year. Longitudinal SEQ in the mild or no ROP group had a best fit linear model with the rate of minus 0.004 diopter per year. So whether the development of myopia is because of prematurity or laser photocoagulation. So in this study they found that in a multivariable linear regression analysis, they reported that the stage of ROP, stage 3 and number of laser spots count applied in laser photocoagulation was significantly correlated with the degree of myopia. Solas spot count, laser type, area, affects the severity of refractive error? The higher number of laser spot, the more myopia. The larger the area of avascular retina ablated, the greater risk of myopia. Whether the laser is done with diode or argon laser doesn’t matter. And if you see the disease stage, instants with advanced ROP, they are more likely to develop myopia after laser photocoagulation. And what about myopia progression. The stage and zone of ROP have significant effect on myopia progression. More severe the disease, faster is the myopic progression. Anterior posterior location of the active ROP also correlates with the myopia as well as the extent of final vascularization. And the risk of myopia is higher after spontaneous regression of posterior ROP, nah is zone 2, compared to anterior ROP, zone 3. And in Asian country where aggressive posterior ROP is found in higher rate and higher gestational age babies, it has a particularly strong risk factor for the high myopia. Does the number of spots resulted to amount of myopia. So again, this study reported that for every 100 increase in the number of laser spot applied, the degree of myopia increased by minus 0.14 diopter. Degree of myopia increased minus 0.26 for every increase in 100 laser spots. For every 100 increase in the number of laser spots, the degree of myopia decreased. So Mr. in children born prematurely without ROP, is negatively correlated with birth weight and gestational age. Tends to be of low magnitude and lessens with age. Myopia of spontaneously regressed ROP is negatively correlated with birth weight and gestational age but also with the ROP severity. And myopia usually plateaus at age of 2 and a half years. It is of higher magnitude. And does not decrease with age. So this here we will see a couple examples. In this patient, this patient is in followup with us. Right now she is 20 years old. If you see she is having in both eyes minus 2 diopter sphere and minus two cylinder. And if you see her biometry — 25.84 in the left eye which is less — myopia of minus 12 should correspond to — 27 to 28 mm. And anterior chamber depth is shallow compared to high myopia. It’s 2.5. And 2.83 in left eye. This is another example of a girl who had laser photocoagulation at 1 month. If you see, she is having in right eye minus 7.5 and cylinder of minus 4.5 at 10 degree. In left eye, she is having just minus 0.5 and high cylinder of minus 3 at 165. You see the biometry, right eye is having 24.09. Again doesn’t correspond to a myopia of 7.5. She is having high astigmatism. And left eye, it’s less that doesn’t correspond to the spherical equivalent. It’s 21.59. The anterior chamber depth is okay. And lens thickness is slightly high. 3.96 in left eye and 3.86 in right eye. This patient is of post avastin. At five years, if you see he had a minimal astigmatism of .5 diopters at 180-degree. If you see he is excellent in the right eye, 22.28 and left eye is 22.86. The anterior chamber is shallow in the left eye. And he is having pretty high lens thickness that is 4.29 in left eye. So what about patients who undergo surgery. Some studies have shown that patients with 3 port LSV develop less myopia than fellow eyes treated with the laser alone. Some studies show they have high myopia. One study showed that at 2 years of age, eyes treated with the bevacizumab had a mean refraction of minus 0.98D. As compared to minus 14.38D. In eyes treated with lens sparing vitrectomy. And excellent but not significantly different. With different anti-VEGF doses the refractive profile changes. If you see in the literature, there are various papers that study the myopia development with the various anti-VEGF. Most of the studies show that anti-VEGF causes less myopia than laser. So this recent paper studied and reported — outcomes of ocular and developmental outcomes for infants that received the decreasing dose of Avastin. And the authors reported at the end of 2 years there was no statistically significant differences in the neuro developmental status and even there was no significant differences in the myopia development. This is another study which compared IVR and IVB and showed that IVB is associated with the shallow anterior chamber and higher prevalence compared to IVR. And the reason postulated behind this is — stays for less time and the prolonged suppression by bevacizumab can have greater impact on the development of anterior chamber. Poll question five, do you see differences in spherical equivalent in laser treated ROP and post anti-VEGF? Always, yes, sometimes, never? 65 percent say yes, sometimes they are able to see the difference and 14 percent of you are stating they never see any differences. The prevalence of myopia is quite high in the laser group compared to IOP group and the rate of change is minus 5D in the laser group but 3.5D in the — group after one year of age. So SE shows that it is higher in laser. In a longitudinal study, showed that 100% of patients develop myopia in zone one in laser treated group. And while 88 percent develop high myopia in laser group. And on comparison with various landmark studies done in, comparing IVB is and laser, the prevalence of myopia was more in laser treated group compared with IVB group. And zone one had higher prevalence of myopia than laser treated group. This group did a study on children treated with ROP. And among 134 eyes with 67 study subjects, the major refractive error was myopia seen in 93 eyes with a spherical equivalent range of minus 2.89 with a standard deviation of 3.21D. So these are studies. And this table shows various retrospective and prospective studies comparing laser and IVB. Most of the studies, if you see the spherical equivalent in laser group is quite high than IVB. So biometry in these eyes can be done by conventional or optical biometry and optical is the preferred one. What about treatment for ROP myopia? We have to always give optical correction for these children and these are the guidelines for the refractive correction in infants and young children. Sometimes we have to give classes in this ROP patient even (glasses) even if they’re having less myopia than this. Those who are treated, they never [inaudible] What about myopia progression treatment in myopia of prematurity. There is little justification for routine use of currently available optical and pharmacological treatments. Still, atropin treatment and various myopia controlled glasses is questionable. And in the white paper; it says that if axial growth is observed, active myopia management would be reasonable approach. But because all the major interventional trials are excluded ROP group, all the major trials like ATOM one and two and other trials that have used myopia controlled glasses have not included the ROP group. So parents should be informed of lack of evidence of efficacy. So the world has seen changes from oxygen management to molecular manipulation. At the same time decreasing the effective management and decreasing the myopia. So there is a long way to go. We have to balance and reduce the dose. At the same time we have to see the neuro developmental effects. And we have to aim for lesser myopia. So the important points are that in ROP babies and infants, it’s important to monitor the refractive status and eye health of children regularly and provide them appropriate optical correction and they need a long-term followup. Because it’s a multi-complex disease and there is variability of dosing and changing different anti-VEGF and laser treatment, close monitoring and long-term followup is required for these children. And biometry is an essential armamentarium in the management of ROP patients. So to conclude, these patients are small subset of your pediatric patients. And these children are undergone a strong course in early life. They need long-term follow up and the follow up is simple but one needs a slight medical — approach and long-term followup is required to see any occurrence of glaucoma and retinal detachment and strabismus. And keep on evaluating. Now with the advances in — and artificial intelligence, one has to update himself or herself regularly. So thank you very much for joining me. And if any questions, I am happy to answer. There is one question, thousand treat amblyopia in high ROP myopia. The management is same as that in the normal patient. We have to do rue teen [inaudible] early. There is one question, optometrists can examine ROP? These ROP patients are very precious baby and it takes a lot of effort by neonatologist and pediatrician and a lot of support from parents to bring patients for screening. And already they have such a strong — and bad course, I will not advocate that any optometrist should examine even a general or comprehensive ophthalmologist should — they can examine but I don’t think so they should, optometrist should examine ROP. The field should be limited to pediatric ophthalmologist, pediatric retina and retinal specialists. There is another question, there may be hypermetropia ROP patient. Yes. There can be hypermetropia. Even in our publication, we had 15 children with hypermetropia. So you can get it in ROP patients. If you have an axial progression in ROP baby 21 to 22 but doesn’t explain the degree of myopia, you still advocate atropin? The role of atropin is really controversial. I don’t prefer to give atropin in my ROP patients. Rather most of the time I keep on stopping atropin which is usually given to patients by some other general ophthalmologist. These children, they don’t [inaudible] so in my opinion, there is no point in giving this. Until and unless it’s progressing beyond the 25 or 26 mm of axial length. There is another question, what do you do biometry in the OPD or under anesthesia and how many times do you do it? If child is cooperative, if it’s four or five years with no neuro developmental issue, a normal child, we can do contact biometry. And for, if child is not cooperative, you can do examination under anesthesia. And then you can do biometry. What is your follow up guideline for premature infant? Do you review all infants with or without ROP at 4 to 6 months: Irrespective of whether they are treated or not treated, we give them a followup period and we counsel parents that they need 6 month recheck and at least up to 5 years of age, just like treated ROP, we advise them to have routine follow up. Another question. Do you consider that 0.01 percent atropin is suitable as pharmacological treatment? As I stated earlier, we don’t have any dosage-related atropin treatment. We are not having any published study, no literature on the dosage of atropin which is ineffective in ROP babies. Another question. Are the glasses meant to stop the progression of the myopia in children? As I mentioned, these children, whatever optical correction you can giving, it itself will stop the progression of myopia. And these children are, behave quite differently from normal children. If you are under correcting them, they progress faster. But in this ROP baby, there is no process of — and myopia progression is so variable. And it is not so much after five or six years of age. So usually they don’t progress so much. If there is progression, better to give them full correction. There is no point of giving under-correction, under-correcting their glasses. Another question. What is the difference between myopic ROP patient treated by anti-VEGF versus laser therapy? Laser is a more destructive therapy because we are treating a very large area and we are literally burning the retina with this laser ablative therapy. So we are disrupting the various signaling cascade pathway. And it causes more myopia. While in anti-VEGF, we are just injecting this agent and it stays for just 20 days. So it doesn’t disrupt the signaling pathway. And therefore the difference in myopia arises. I had a very interesting question which was sent to me in email. And that was about how to create the awareness for ROP screening. So it is very important for pediatric ophthalmologist and retina specialists that you have to educate and have a good collaborative relationship with the neonatologist and pediatrician who can send ROP babies to you. At the same time you have to educate the staff of the pediatric hospitals. You have to create awareness among parents. You can show videos and have podcast and You Tube presentations for parents. You can display posters and distribute pamphlets in pediatric hospitals. And a collaborative approach between general ophthalmologists, retina specialists will help you to create ROP awareness. It’s very important to give feedback to pediatrician and neonatologist and even to retina specialist also that what other ophthalmic changes or other complications you are seeing on followup. You can have various programs on awareness, on either international ROP day or world prematurity day. I think we are done now. Thank you again for joining us, me today. And thank you Cybersight for providing me this opportunity to present. Thank you very much. Have a great day.