An excellent opportunity to learn from an enthusiastic world class trainer in Retinopathy of prematurity, this time discussing current concepts of systemic therapy available for preemies who have this avoidable condition. Join Nigerian pediatric ophthalmologists to learn more.
Lecturer: Dr. Subhadra Jalali, Vitreoretinal surgeon and ROP specialist , L V Prasad Eye Institute , Hyderabad, India
Panelist: Adedayo Adio FWACS, Consultant Pediatric Ophthalmologist
University of Port Harcourt teaching hospital, Nigeria.
Chairperson, Nigerian Pediatric Ophthalmology and Strabismus Society (NIPOSS)
[Adio] You are very welcome to today’s transmission from NIPOSS from Nigeria. Very welcome, I’m transmitting from Port Harcourt. And today we’ll be talking about systemic therapy during ROP management.
I’m the Chairperson of NIPOSS in Nigeria. That is the Society of Pediatric Ophthalmologist. We are committed to ensure the overall eye health of the Nigerian child. And we’re all based in Africa, as you know. This is the world’s second largest and most populated continent after Asia. We’re about 1.3 billion people, for those who don’t know. And that is where I am in Nigeria on the west coast.
We have about 36 states in the country, our capital is in Abuja. To give you a brief rundown on what Nigeria is and what we are, the population is about 205.7 million which is the estimate for 2020. We have about 40 pediatric ophthalmologists in all, which gives about 8% of the total number of ophthalmologists. We are spread out all over 21 centers. You’ll see those black dots there, that is mostly in the southern part as well. In the northern part we have fewer pediatric ophthalmologists.
We have featured several topics so far. The goal of last year we had five. This is the second one for this year 2020. And so we’ll like to appreciate Cybersight for this collaborative education package that they are helping us with.
So by way of introduction, we want to be focusing on retinopathy of prematurity, because it’s one of the leading causes of preventable blindness in the developing world. We have about 32,000 cases from an estimate that was done in 2013. I’m sure the numbers would have increased by now. Because of this, epidemic levels have been predicted. Because over the years, over the decades, there is now greater access to neonatal intensive care units. And because of this there’s improved survival rates. And to let you know, it’s one of the major causes of blindness in a blind school study that was done in a middle-income country.
But in Africa, we don’t have studies just yet. We have studies but the ROP, retinopathy of prematurity, is not a major cause of blindness, because they don’t grow up to that level to come into a blind school. But in other places where they’ve been seeing ROP for decades, now it’s a major cause of up to 35% of those who are in the blind schools.
And what are the reasons why this could be so? We find that we don’t have enough sophisticated oxygen regulation and because of the fewer numbers of pediatric ophthalmologists there’s relative lack of routine screening. There’s a relative lack of trained personnel, very few people have had this full training. And of course, because we don’t have enough pediatric ophthalmologists, that’s 500 for a population of 205. And there are fewer pediatric ophthalmologists and retina surgeons to initiate treatment for those who develop severe ROP is quite difficult.
So for this reason, Africa has been described as the new frontier for ROP. Since the quality of neonatal inpatient care and appropriate, well-monitored oxygen determines now many will develop ROP, when we are scaling up neonatal services we must be sure that we’re also implementing high standards of care. And of course this includes anticipating and managing conditions, systemic issues that are predisposed to ROP.
This is my ROP screening team in my hospital where I’m working in the University of Port Harcourt Teaching Hospital. Before we introduce our speaker, Dr. Subhadra Jalali, we have a short poll that we’re going to give to you, so please share the poll now. We want to know a few things so that when we’re discussing, you want to know. So this first question says, what is your profession? If you are there, you can please vote and indicate which one it is, we have about five questions.
The first question says, most of them are residents. We have very few pediatricians, those who are managing, but I’m sure they will join along the line. We have some nurses also. All right, the next questions. Have you had ROP training? Okay, so the majority have not had ROP training. Thank you.
Now, do you screen ROP babies? Okay, now do you screen ROP babies? Most of them do that. In the last six months have you had any child blind from ROP? We’ve seen at least 20% have seen a child blind. Wow, okay. What systemic problems is commonest among those you have screened? First option is apnea, necrotizing enterocolitis, anemia, juvenile jaundice, necrotizing fasciitis, which of them have you been seeing? Apnea is the most common, okay.
Great, so this is very useful and it will help Dr. Subhadra exactly how to approach this.
I will introduce her now to you. Dr. Subhadra Jalali, she’s going to be talking to us about systemic therapy. I’ll just give a brief biography. She finished her MBBS in 1986 and her MS in 1989. Completed a two year fellowship in LVPEI in 1993. She has four fellowships in ocular genetics, visual electrophysiology, posterior uveitis, and ROP, of course. So since she’s been working in LVPEI since 1993, she’s been a director of the Newborn Eye Health Alliance of the 200 facilities of LVPEI. It’s interesting to know that she’s one of those who pioneered retinal surgery as an Indian woman, which was an exclusive male domain at that time.
And she’s a prolific writer, she’s very passionate about presenting, having given several hundred presentations, including orations, 165 publications, and she’s also a co-investigator in various international studies. She has received numerous awards and she has trained so many fellows, including myself, in LVPEI. She loves dancing, she’s especially cosmopolitan, she can relate to anyone. She’s married to a doctor also. And her slogan “Thirty days to vision” has saved thousands of babies from blindness across the globe. I present to you, Dr. Subhadra Jalali, to talk to you about systemic therapy. I’m sure we’re going to learn a lot. Sit back and enjoy it, thank you.
I’ll stop screen share now and then if you can take over Subhadra, thank you.
[Subhadra] Okay, thank you, Adio, I think it’s just amazing that I can talk to all of you from such a long distance. Greetings to everyone and it was very nice to see that there are people who have been trained or there are people who are doing the screening there, seeing some problems and have seen ROP. Because previously people thought that ROP doesn’t happen in Africa.
Let’s get going. I’m just going to talk a little bit about systemic therapy, but I will also give a little overview of ROP because we have residents and nurses there.
These publications generally, most of the publications they will color the countries into one color. Like you can see the whole of India is blue and all of Africa has been shown as dark green and some parts are light green. To say that you know, where is this ROP happening?
It shows that there’s a lot of ROP in some parts of the world, there’s very little ROP in other parts. But really, if you look at a country like India, or Nigeria for that matter, any of these big countries, there’s a lot of people and populations, they’re not homogenous. So why the publications show it that everything is same, but if you see India we have states or regions which have as good care as the best. And we have things, what we call as the model stage, these states in red where there’s lots of mortalities or they don’t see that much of ROP.
But here, where I am, in Hyderabad, there’s very good medical care. So we see a lot of ROP. So really, to color one country in a single color for ROP I don’t think that’s good. Because I’m sure in Nigeria, there would be NICUs, maybe one, two, maybe 20, where really high-end care is happening, and the assisted fertilization is happening, and babies are surviving. And then there will be regions where babies are dying because there’s no good care. This is for premature babies.
So if you look at India, this is 2004, we have 26 million births. Out of which 1.2 million will die within the first one month. But you see over a period of time, under five mortality, our infant mortality, neonatal mortalities, everything is for very tiny babies, the change in mortality has started showing a downward trend. And this is because we are aspirational countries, whether it is NIgeria or India or Ghana, we want to become developed, we want to move upwards, we want our economy and our aspirations moving upwards and that is what is called a middle-income country.
So this baby was the 10,000th baby that was seen in our program, our program started in 1998. And she came from this amazing SNCU, or NICU, or what we call as newborn care unit, which have been set up by the government in remote parts of the country. And she was 33 weeks, 1800 grams and within three months of birth she came to us with leukocoria. And she had stayed 25 days in the government hospital, this hospital with everything being there. And these hospitals have been set up with the help of international NGOs especially UNICEF, to attend the sustainable development goals of reducing neonatal mortality in our country. And it’s not that whether they’re saving all these babies, but when these NICUs were set up, there was no ROP program along with that, which should have been there.
So this whole thing about sustainable development goals, these are being set up in all the countries. Whether it’s Philippines, I’m sure it’s been set up in Nigeria, and in so many countries. And I think because of that, while it is heartening to see these babies not dying, but we have made conditions that we promote blindness because now they are surviving. Why it is so is because ROP is a sort of iatrogenic disease in the sense that it’s not an ancient disease like retinoblastoma or cataract, which has been described in 2000 year B.C. It is a disease which was started in 1942.
The first incubators were set up in Boston, in USA in 1941. And within a year, the first retinal fibroplasia was seen in 1942. So this lesson has not been transferred to other places. So to my mind, if we have already learned this lesson in 1940s, then why we are setting up an incubator and not setting an ROP plan right there? Because the moment the NICU center is set up, the ventilators are set up, the babies start surviving, the ROP will come, it’s not that it will not come, it will always come.
I think it’s very important for every center to know that wherever newborn care center is set up, the ROP will happen. And if you’re doing a good job as a pediatrician, or as a nurse and you’re surviving these babies, then the smallest survivors will have the highest risk. And if we have suboptimal care, these are all three ICUs in my city, in Hyderabad, so you can see here there is unblended oxygen. There are multiple babies in one bed because we don’t have beds. And here, this room heater is supposed to keep all these seven, eight babies warm, because there are no warmers. And here we have the best care, which can compete with any care in USA or UK or anywhere where everything is there.
So we have all types of care. And so these are the places where we’ll get more ROP because there is unblended oxygen, moderate care or no care. And here also they’re going to get more ROP because here we are surviving the tiniest babies.
So this is my city, what we call as a middle-income country, we are a 400 year old city, we have a lot of old civilization, old culture, old habits. And then we have this very modern cyber city, IT professionals. So we are in the middle. And this is what will happen and this is the story of my city. That in ‘98 I started my program, you can see here in 1996, less than 5% of deliveries were premature. And even if they happened, they used to die, they were in villages they never came to the city. But you see by 2000, almost 15% and now almost 25% of babies born in this tertiary care center are premature. Which means every fourth baby is a premature baby. And you can see that 20% of babies would die and now hardly anybody dies, even small babies survive. And you can see here, this is my hospital data which started in 1987, my hospital. Until 1997, we almost never saw ROP, we didn’t know what it is, we read in the books there’s something called ROP, there’s something called therapy study. But there was no ROP in Hyderabad city at all.
But it was in ‘95-97 you can see here, as these babies started surviving, we started seeing ROP. And very soon, in ‘98 after I came back from my training in the USA, you can see how high the numbers went. So this is what is going to be the story of every city where aspiration and new technology’s happening. It will be repeated again and again. And this is our data, you see in 2000 we used to see vitamin A deficiency, keratomalacia, we hardly see it now.
We used to see a lot of congenital cataracts, and we still see a lot of congenital cataracts. We were seeing congenital glaucoma, we still see. So these numbers have increased because the population has increased. Otherwise there’s nothing in the population or in the epidemiology which has changed in numbers, so they’re almost stable.
But look at what has happened to preterm babies, tenfold increase in these 13 years. So we used to see 87 in that year and now we see almost 1000 babies a year. So this is what I wanted to highlight that the ROP menace is increasing and it is becoming a very important cause of newborn blindness in our communities and this is actual data.
And in this data, I also put the hereditary retinal dystrophies that we’ll see in other things because that was a control group. What type of children come to us because we are a growing hospital? But as you can see, there is no comparison of how the ROPs growing as compared to other things.
And previously only 15% of our babies came from smaller towns and districts because they did not have this as a SNCU or NICU. But now in 2014, almost 28% to 30% are coming from those places. And this is a very difficult thing because the ROP program is not available in the remote areas and the rural areas. Where now we’re seeing more ROP. So it has shifted from urban centers to smaller towns.
Good news for the residents, there is an international classification on how we talk about ROP. What is the area involved, the more posterior the most severe the disease and the location is decided by the zones, three zones. And then we talk about clock hours, how many clock hours that the disease is. And most important is the severity. The severity is from stage one to five. One being the least severe and five being blindness because of detachment. And then there’s a plus disease. Plus disease refers to dilation and tortuosity, I will show that.
So this is how we draw the drawings. That zone I is centered on the disc, and zone II around the optic equator and touching the nasal aura, and then temporal present. So any disease which is in the posterior part is much more severe and has almost 80% chance of leading to blindness. If it is the time zone here then it will have a 50 to 60% chance of blindness.
This is just to show these pictures, usually not in books, what is a mature retina. So a newborn baby who’s born at term should have a retina something like this. Baby seems pink colored, there are a significant number of vessels, density’s good. The vessels are dicontomously branching, this is most important sign to see that are the vessels are branching?
And then generally happens, some modulation in these tiny babies because the vessels are still growing. And here we can see what we call are the immature line. Immature line you will see the same thing, but you will see less number of vessels, less density. The retina will have a greyish appearance and not the bright shining appearance or a succulent appearance of a mature retina because the intralimbal membrane is still not laid out here. And you will see that the vessels will just disappear and they will just be a little dilation and tortuosity, not much. And the pupil will dilate very nicely and the media will be fully cleared.
So once the ROP happened, that means these vessels which are growing branching and going forward, they branch but they don’t move forward, they just bunch up at one place and that is what creates this demarcation line so you can see this is the retina with no vessels and these are the vascular retina and they’re demarcated by a line which forms because the vessels dividing but they are not moving forward. So this is stage one.
And in stage two there’s a fibrous tissue laid over it, there’s a thickness so this is stage two. In stage three, the new vessels happen and this is the stage where we want to treat because you all know if there are new vessels in there they’ll bleed and obstruction. And these are the stages which are controlled. And once it goes beyond stage three, that is the detachment develops, either macula involved or macula not involved. Then we are almost on the road for non recovery.
The plus sign is for the tortuous dilated vessels, which I will show you. So everybody should be able to make a difference about ROP and no ROP. But this is what a normal retina will have fewer cells like dicotonmousy branching, nice clear medium, you can see what happens the moment the disease becomes active. Then it will start dilating tortuous. So then the veins are enlarged, dilated, tortuous at the posterior pole. We call it plus sign. And in these cases usually the pupil will not dilate very well or it will dilate very slowly so you will know that something is wrong there. And you can see here, something, they will have new vessels or tortuous vessels, media will become hazy. This is a very advanced disease where there’s too much of new vessels and the dilated plus disease.
ROP is an ideal condition to screen. The reason for this is as you saw in the baby which I showed you, 10,000 babies at the top. Population risk is already in the hospital, so you don’t have to do door to door surveyor campaigns in the community to find and get them out of their house and come to you, like you would need to do for congenital cataract or trachoma. But here they’re already in the hospital. So they’re already with the medical doctor and the parents are quite motivated to meet the doctor and talk to them. And if the doctor explains something, then they’ll be more receptive.
There is no disease, but at birth they will be normal. At birth the macula is normal, there’s a potential for success vision. So unlike congenital cataract, glaucoma, or other congenital disorders of the eye, this newborn disease is perfectly normal retina at birth. It’s normal for their age, because it is immature.
And then the next stage is very normal, we know, we know the immature retina, we go either into a mature retina or after 20 to 30 days it will start bleeding. If we don’t treat in the next six to seven weeks the retina will be in that stage 4B. If we still do detect it because in all these stages the child is asymptomatic, there’s nothing from the outside. And then it will go into stage five at three months of age. And then it’s going to be permanent, irreversible blindness. So that is when somebody will notice the leukocoria or the nystagmus or the white eye. And so we know the child cannot see.
The ETROP, that is the early treatment for ROP study, it has given us guidelines when to treat and when not to treat. But 80% of the disease can go away on its own and doesn’t need treatment. It just needs an observation that it is going. It’s like a fire, if there’s a small fire you don’t call the fire brigade. If you burn a small paper in your room, you don’t call the fire brigade, you just watch it. That it’s not blowing in the wind, it’s not burning a curtain or something, the fire will stop on it’s own. But if the curtain starts burning then obviously you’d start finding your fire extinguisher. And of course, if there’s a fuel tank, then you know it’s doomed.
Some people get very confused when we ask them the question, “What degree, what stage, zone?” Just forget about it, it’s very easy to remember. That what you need to treat are new vessels, which you always treat in a retinal disease, that is stage three. And any plus, because that means active. So even if you can’t remember the zones and the stages, it doesn’t matter. You can see here, everything that you treated, either plus or three and here also everything that you treat is plus or three. And there’s only one stage one plus where it says follow. But stage one plus is a critical stage, because it never happens. Whenever there’s stage one and it is plus, it will go into two, it will not remain in one. So really, we never see clinically a stage one plus, it has to be followed. So all new vessels and all plus have to be treated. All eyes which are not plus, or no new vessels, they can be followed.
So we come back to this baby who’s asking in 2017, who stole my vision when the natural history was known since 1960s? We said the first case was diagnosed in 1940s and then by 1960 there was a huge epidemic of these ROP babies and there was a lot of studies done. We found that oxygen worsened the disease or there are various things that we can do and more studies were done in 1980s. And nearly the ROP in the West started coming down. But unfortunately, in other countries, including in India, we did not face this epidemic because we did not have these incubators at that time. So we were not aware. And now we are facing the first epidemic here.
But we’re also facing the second epidemic which happened in the West in 1990s, when the tiny babies started being saved like the 25 weekers, 26 weekers, 800 grams, 700 gram babies. So in the West they’re only seeing ROP in these tiny babies, not in the bigger babies. But we, in developing countries, are having both of these and this is called the third epidemic. And we can see here, that the third epidemic which we are facing now, is very huge because now there’s less mortality. The smaller babies are surviving, the bigger babies are surviving. And the huge numbers, the number of babies born in our country is huge. The ROP that we are seeing is just exponentially increased.
So this is very important that every country should have its own national guidelines. It took us almost 10 years but finally we do have, we are very proud of this that we have this Universal Eye Screen National Guidelines. Anybody who wants a copy can write to me or it’s available on the Ministry of Health and Family Welfare website. And all the doctors involved in pediatrics, gynecology, nursing, ophthalmology, retina specialists, pediatric ophthalmologists, a huge number of people and the public health specialists, and the government officials, we all got together. It took us one year, we debated a lot and finally this is what we came up with. That you should screen before 30 days of birth. That is the “Tees din roshni ke,” or the 30 days to vision. We must screen big babies in our country, so less than 2,000 grams and less than 35 weeks. Just to compare, in the USA it’s about 1500 grams and 30 weeks or 32 weeks. And also in our countries, because a lot of mothers don’t know their gestational age, so all preterm who’s gestational age is not well known, they must be screened. If the parents don’t know when this baby was supposed to be born, when was the last menstrual date, then we must screen these babies. Because we never know how old these babies are. The mothers don’t know, they’ll just say seven month, eight month, which is not good enough for us.
The important thing is that when we are screening these babies, you must make sure that you have a written MOU with the hospital and the onus of getting the baby to the eye specialist for the legal and moral responsibility is of the physician, or the pediatrician, or neonatologist. So that has to be explained very clearly. That I’m not responsible, I don’t know where the baby is, baby may be in the sick unit, or it maybe in-
Okay, I think we lost connection, I’ll connect again.
Okay, Adio, where did we lose? Were we here? Should I go back one slide?
[Adio] Go back to the slide before.
[Subhadra] Should we go back one slide?
[Adio] One slide.
[Subhadra] Okay, this one we had done.
[Adio] Yes, this one, yes.
[Subhadra] Okay, sorry. This is what we want to say that the Western countries, that is Canada, USA, UK, you can see here. Every child was less than 1500 grams or less than 31 weeks if they needed treatment. But you can see here, that in the developing countries where we have data from various units of Argentina, various units in India, Hyderabad, India, Delhi, India, Madras, between here. You can see we don’t have any of the African countries here because this was done in 2005 and at that time they thought, I’m sure there must have been babies isolated at some point of time, but I think we can data from African countries. A simple study to do and compare it to this study, which is already there, already data was collected. And you can see all the babies almost 16 to 18% babies are outside the Western criteria. That’s why we should not use the Western criteria for our countries, we should have broader criteria and then over the years we can always narrow them down.
So the good thing about ROP is that many times some doctors tell you your child has ROP or somebody and the parents are very worried, “Will my child see?” The good thing is we get very good outcomes, almost 90% babies will see very well if we treat early. Because as I’ve said, they’re born with normal retina, normal pupils, so they don’t get amblyopia, they don’t have a congenital problem, and they have normality there. So if you just treat with laser as soon as the baby starts, you can see here, everything goes away. And of course, many of them need glasses, myopia is an integral part of ROP. But then they see well and they don’t remain blind.
How to screen? This is important that the added eyedrops with 5% Phenylephrine should not be used in babies. You should use dilute drops that is 2.5% Phenylephrine and 1% Tropicamide. Or you can use .5% Cyclopentolate and this should be put in three times. And then we must wipe the eyelids nicely because the drug can get absorbed through the skin and cause tachycardia, breathing problems, feeding problems, even deaths have been reported. But in correct use of the eye drops, the nursing staff has to be taught how to use these eye drops correctly. And you can see that within 15 minutes the pupil will dilate very, very nicely. So if the pupil doesn’t dilate it means there is severe ROP behind.
We must make sure that the child is not hypothermic, because they cannot maintain their temperature so they’re well wrapped. The mothers will just get them unwrapped, we must wrap them in a blanket or in a bedsheet, and make sure that the child is fed nicely or has had some glucose because we won’t want the glucose to go low.
Sometimes even trained people miss ROP. This is one of my earliest cases which I missed. I saw this and I said, “There’s no line, there’s no demarcation line, so there’s no ROP.” But actually, this is what is called aggressive posterior ROP, here we don’t see a line. We don’t see stage one, two, three, four, five. Not the staged ROP here. We see these quadrants, what has changed? You can see is another pattern of non dichotomous branching retina has changed. So here you can see this retina with non dichotomously branching vessels and then suddenly they have changed their character and they’ll become all this shine and round her also. It seemed everything was normal and it seems everything is normal but if you look carefully, then you can see here the vessels are not sprouting but they are starting curling on themselves, which is happening here.
So this is the earliest stage of aggressive posterior ROP and if you don’t treat it immediately, then it will directly go to stage five within a week or two. This condition has to be recognized by everybody because it’s something very dangerous. And now we recognize it just because of the changed patterns. And when we treat them, we must treat all these pockets of avascular retina. All these abnormal pockets we have to treat, not just beyond the reach which is done for this APROP.
Here again I’m showing these pictures. We should not miss them. So whenever we are looking at ROP we should place the vessels and see what is happening to the vessels and otherwise we might miss these certain findings.
And of course the laser is very effective, we can see here we’ve done laser, there’s some blood and we’ve lasered this eye. And when we see these white centered hemorrhages, that the blood has gone away and the blood is cleared, not quite central, this is clearing of blood in the centers, that means this area is now empty and it is not going to worsen. But in the same eye, you can see this area, there’s still no removal of the blood from the center, it’s still a big blood clot, so this is still active. And the reason for this is we have not lasered in between these pockets. So in the second sitting we have to go and laser this whole area right up to here and then the disease will go. If you don’t do that then it will start reattaching from here.
This is one of the reasons why laser doesn’t work or the laser failures are there because people don’t realize which area to laser, especially in non stage ROP.
But there are many other conditions that now we come to this issue of systemic therapy in ROP. Many people don’t realize that ROP is not just an ocular disease, it’s a systemic disease. There are various factors which are causing the ROP and also worsening the ROP. And when we are trying to treat it just the eye and if we don’t treat the systemic part, then our treatment will not do well. Or even if we’re waiting for spontaneous regression of the disease, the disease will not regress well. Because the system is showing up certain conditions because of which the ROP’s worsening.
As I said, we can have what is called a risk-reduction strategies. And these strategies depend on quality care. You need high quality care, simple things, and sophisticated things, both of them are there. There are some simple measures, which every unit can put in place and then of course there’s some costly things that need to be put in. I will be going through some of these and what I want to highlight is that the nurses are a major player who will reduce the ROP. Both the occurrence of ROP and the severity of ROP directly depends on what the nurses are doing and how they are handling the baby.
The other thing is that if we have large for gestational age babies, like babies born to diabetic mothers, baby with hydrocephalus, who may be 2.5kg , 3 kg, so they’re also at very high risk. So it’s the prematurity which is important, not just the weight.
So let’s look at prevention of ROP. So why can’t we prevent ROP? Yes, if we could prevent premature births, then we could prevent ROP. But as you saw in my data, the premature births, a lot of them reducing have actually increased a lot. And the reason for this, of course, in our country is the assisted fertilization or what we call test tube babies, or taking tablets. And because of that you get twins, triplets, and everybody wants to have a baby and they use all these methods. So yes, that leads to premature births, all the assisted fertilization techniques will lead us in premature births.
Then of course, in our countries, we also have both the ends of the spectrum, we have early teenage pregnancies, unwed mothers, or even they get married at 13, 14, 15. The official age in our country is 18, but there are many girls in the rural area who get married at 15 and by 16 they are pregnant. And then we also have the highly urban working mothers who don’t want to get pregnant now, they want to postpone their pregnancies so they become elderly primis and they also land up with premature deliveries. So both ends, depending on where the woman is, they can land into these premature deliveries.
And the maternal education levels matter, how well they are nourished, what is their socioeconomic condition, how much they know about their body and pregnancy and fertility. And take proper decisions. So that is again very low in our country, so that leads to a lot of premature births. And of course there’s lack of access to care in a lot of our area. I’m sure it’s there also. If somebody’s in premature condition or is prone to a premature delivery, they don’t have access to care which can help to prolong the pregnancy.
On the other side, we also have the opposite where in our high-end centers, there’s very close fetal monitoring and the moment somebody thinks the child is going to respiratory distress, or the child is a UGR, or if there’s a risk to the baby, no obstetrician wants to deliver stillbirth. And stillbirths are not accepted by the community now as they were 30, 40 years ago. So everybody does early cesarean sections, so at least a live baby is delivered and handed over to the pediatrician. So they can just say that we delivered a live baby. So because of all these reasons, actually the premature births are increasing and they will continue to increase.
But yes, what we can do for ROP is that all these high-risk pregnancies where we suspect they will land into a premature delivery, we must give antenatal steroids, intramuscular. And this is the protocol there that between 24 to 34 weeks, two doses of Betamethasone must be given. Previously they were giving routine weekly doses but these are contraindicated. But a good system of antenatal steroid care from the obstetricians, not only prevents ROP but it also reduces the risk for respiratory distress, the intraventricular hemorrhage, and perinatal morbidity. Currently in India, there’s a national program where there’s a national guideline for all the obstetricians to give antenatal steroids to all the high-risk pregnancies. This was put in place about four, five years ago.
Then most importantly is oxygen. So many times in the early era people thought this was an oxygen-induced retinopathy, oxygen caused ROP. But now we know that oxygen, it’s not like it causes ROP, but it worsened the ROP more level stage ROP, because you need an immature retina for this oxygen to cause the damage. If you have mature retina, then the oxygen would not cause that much damage. So the oxygen management is very critical. And you can see here, if the mother is going to preterm labor, it’s good if they can be there for tertiary care center, what we call in-utero transfer. So that the baby, when it is delivered, it is in the best circumstances. This is very difficult to attain, I know in your country and in my country. But that is what is ideal.
Then there’s something called the first golden hour of care. So as soon as the baby is born in many places is what happens, is they’re so worried that this child will survive or not, it’s a preterm baby. So they clean the baby. And in India we put on oxygen, 100% oxygen. Whether the baby needs or doesn’t need. So what is required is that you put the pulse oximeter and watch the baby. And at birth, preterm babies can have a saturation of 70%, it will build up over the next few minutes. So you don’t have to push oxygen immediately and that oxygen causes damage. So the first golden hour how it is taken care of matters.
When start with CPAP, that is continuous positive airway pressure, so use air rather than oxygen, so again, this requires some sophisticated training and equipment. But oxygen is easy, you can just take a tube and just put in the nose.
The monitoring of oxygen is very, very critical. So in the 1940s to 1960-70, it was very clearly shown both in animal models and human data that you should not give pure oxygen. One, you should always give blended oxygen. And the pulse oximeter reading should not cross 94. So in very tiny babies it should be at 87 to 91 at the time of birth. And then within one or two week you can go up. You don’t know exactly how much to give, but in general, it should not cross 94. And we should also recognize that not having 100% on pulse oximeters. But if we don’t measure we’ll not know.
More important than the total oxygen is also the fluctuation of oxygen. So what happens in many places we saw, this happened in my country, we saw it in Mexico, I’m sure it’s happening in other places. Is that there’s so many babies and there’s only a few nurses. So they just put the oxygen full so that the baby doesn’t desaturate. And then sometimes when they’re told eh, the child will get ROP, okay. So they will switch off the oxygen. Or when they’re feeding they will give oxygen, when they’re not feeding, they will not give oxygen. In the night they will keep high oxygen and in the morning they will reduce it because now the doctor’s coming on round and will scold if they give high oxygen.
So this fluctuation of oxygen, this is the most damaging. It’s the eye doesn’t know what to do, should I drink oxygen or should I not drink oxygen? So this fluctuation of oxygen has been shown to be the most damaging than steady flow of oxygen. So please, I request everybody to watch this and make sure that the child is under steady oxygen, there’s a monitoring of oxygen and it is blended oxygen, it’s filled with air and oxygen mixture, which is delivered to the baby.
This is, of course, very challenging in our countries because of pulse oximeters are costly, the blenders are costly, they are not manufactured in our country. The education of nurses to understand how to monitor the oxygen and how to change the oxygen saturation. Again, this is lacking. And we don’t have that many nurses who can monitor every baby, so for this to work, you need one nurse for one baby or one nurse for two babies. In my country, there’s one nurse for 40 babies. I don’t know how many it is in your country, but I’m sure it is like that.
But at least what the nursing staff can do is hand washing and asepsis. So this is definitely doable. This is a cost effective thing, it doesn’t require anything except a cake of soap or some solution to wash hands. Frequent handwashing, aseptic techniques is something which all doctors and nurses have to practice. And this brings down the ROP because every time there’s infection, there is more ROP.
One of the things we can definitely do is weight gain. It has been found that poor weight gain is a very high risk factor for our ROP and it’s almost a biomarker of ROP. Any child who’s not gaining weight will have more severe ROP. So here we need to again educate the nurses, the families, that right from birth we have to give expressed breast milk, feed every two hourly. And it’s not easy because I had a preterm baby and I know it was so difficult, I had a pump out the milk and by the time I fed that milk and tried to sleep it was the next second hour. And again, I was back to pumping out milk. So it’s not easy. But if you do that, and you can give that breast milk every two hourly, whether by tube or by a spoon or whatever, or drop by drop with a dropper, then these babies will gain weight very well. And they will also be less sepsis.
Kangaroo mother care, again, helps the baby to gain weight and to avoid sepsis because so many nurses are not touching the baby. Sometimes there needs to be supplemented feed mixed with the breast milk to be given. But really children need total parenteral nutrition but I think the most important thing is asepsis. If we can wash the hands, if we cannot touch the baby, without washing hands or without using alcohol rub in our hands, and we are wearing the mask and we maintain good asepsis, I think it will do a huge thing for these babies.
The other important thing which I think every ophthalmologist should look at is the lungs immaturity, we talked about apnea. So these children, they can have pneumonia, underlying pneumonia they may not look very sick, but they’ll have some breathing problem. They may have an underlying chronic lung disease or oxygen dependency. So these things matter because the lungs require VEGF, that is vascular endothelial growth factor to grow. And whenever they’re immature, they will produce lots of VEGF in the lungs. And this goes into the eye. And any high VEGF in the eye will cause ROP. So there’s a direct connection of what is happening to the lungs and what is happening to the ROP.
If we can afford and we’re given surfactant, again the expertise has to be there, then the lungs mature faster, but then you need to know about chest physiotherapy. So if the child is not responding to your laser or you saw the baby, has ROP, and you want this to go away, look at the chest and suggest to them that the child needs chest physiotherapy. The nostrils are very small and if there’s little cough, cold, their nostrils will get blocked. So they’ll be hypoxia happening there and hypoxia worsens ROP. So make sure that the parents know to clean the nose, they can use some nasal clear drops that keeps their nose lubricated and their nose is not blocked. They can do nebulization. All these things have to be done in consultation with the pediatrician and bring to their notice that the child is not doing well in ROP, we want the lungs to be taken care of.
Of course the excessive resuscitation should not be done in the first golden hour because that will cause lung injury and permanent chronic lung disease. And sometimes when there’s an underlying pneumonia, then of course it can be seen on x-ray, they will need systemic antibiotics rather than oral antibiotics because it doesn’t go in. So all these things when we are doing the laser, we’re starting the laser, we’re going to take treatment or no treatment. All the ROP babies we must have a lot of attention to always their breathing, are they grunting, (grunting) so then you know their nose is blocked, something is happening.
The other important thing is anemia. Most of the preterm babies, they have anemia lasting almost seven to eight months and that is normal for them. So most of the pediatricians don’t like to give transfusion, which is correct. But if they get ROP then we need the hemoglobin should be at least 10. We don’t want anemia during the phase of active ROP because anemia, as you know, is a hypoxic stimulus and it will cause more ROP, it also causes bleeding and vitreous hemorrhage. So we should watch the platelets, we should watch the hemoglobin. So every time a new baby comes to my center and I see there’s an ROP, I start the treatment. But same night I will tell them please get your hemogram done, and talk to the pediatrician, and we want a transfusion in case the hemoglobin is seven, eight, six. And almost 50% of babies have six, seven, eight hemoglobin when they come to us. And once we give the transfusion, the response to laser or the spontaneous regression, and the severity of the disease starts coming down.
On the other hand, if we give too many transfusions that is also a problem because we are transfusing adult blood into a baby. So baby has what we call is a fetal blood which doesn’t give off oxygen so easily from the blood. Whereas the adult blood gives off a lot of oxygen into the system. So again, we should not just over transfuse these babies. So there has to be a balance, a balance whether we need to transfuse or not need to transfuse so the protocols up there and the literature, I’m not a pediatrician. So these things should be kept in mind.
And I think what is most important is now all this might fail. We may not have the experts there, we may not have enough nursing, so all this can fail that we’re not able to give transfusion, we’re not able to monitor oxygen. But we cannot fail is sepsis control. Once again, education and counselling of parents and nurses and doctors, that ROP screening can be done. So even if baby gets ROP, but we have screened on time and treated on time, still we can save that eye. Even if everything else went wrong, even if the child got sepsis, had all these systemic conditions could not have been taken care of for one reason or the other. But still, if we could have screened this baby between 20 to 30 days of life, and the parents did not miss all of appointments, we could still salvage these babies.
The other thing, of course, is when the baby’s gone, we should not ignore open eye torchlight examination. I’ve had babies like this where the child is having some redness and nobody opened the eye. They said, “Oh, your baby has some conjunctivitis,” and without opening the eye, they give antibiotics and next time we saw, actually child has endogenous and ophthalmicus from sepsis. See this child, she has groundless corneas and this was not detected until the child was 6 months old. Sometimes in a chemical emergency, there can be an exposure. But what I want to say is that every newborn baby on the day of birth, must have at least a torchlight examination. We don’t get this information from the pediatricians whether on the day of birth the eyes were okay or not.
This of course, congenital glaucoma. Somebody should open the eyes.
If the child has redness, watering, 99% it is normal conjunctivitis but you could have seen this problem like retinoblastoma, endophthalmitis or something else happening there. So always open the eye with a torchlight, just see is the cornea here, is it bright shining, is there something else there for which I need to send to the pediatric ophthalmologist or an ophthalmologist. You don’t want all watering and redness to come to ophthalmology hospital, most of them can be taken care of low key. But it’s important to know the protocol, what we need to check before we just arbitrarily give an antibiotic to these babies.
Of course, all these children, we should also find a good family history, we still have lots of childhood blindness because of congenital cataract, this is one shameful thing which just keeps on repeating in my country. I’m sure it’s happening in other countries. All these three elder children were in a blind school. And it was only this one who was picked up by a health worker and found to have congenital cataract. We operated and when we asked the history we could get all these children at this age to get congenital cataract surgery done. So this is shameful, I think if they had a torchlight examination at birth, or a red glow examination, we didn’t have to face this so many years of blindness because of cataract which is treatable.
And here we have another child, this girl developed metastatic retinoblastoma because nobody told this mother who had enucleation done, almost 30 years ago, that if you have retinoblastoma your child needs screening for retinoblastoma. So actually the mother received better treatment than what this child received. So these are important things that when we are dealing with children in pediatric hospitals we must know that these things can happen and we need to keep ready for this.
Every newborn baby, in addition to a torchlight exam, must get a red glow done. For that just take into a dark room, all newborn babies, just put a drop of Tropicamide, and from your direct ophthalmoscope, or from your cell phone camera, just look. Is the glow red or is it not red? A torchlight and a red glow examination can be done in all babies at the time of birth and then in the next health checkups whenever they come in for follow up through the pediatrician.
Now there’s also some cameras which are there, so usually we screen ROP with indirect ophthalmoscopy so it’s difficult. You need a lot of trained people to do indirect ophthalmoscopy. So what about using cameras? If the cameras are there, you can see their result, it’s very expensive. Now from India we have a new camera which is almost ⅓ or ¼ of the cost of this machine. It has to be approved. So this is an option, but still it’s quite expensive. Now people are using smartphones and indirect lens, or they’re using the nasal endoscope. Various options are there and more and more people are trying to use their smartphone to take the pictures of the retina. I’m sure that there is a propension for much inexpensive cameras to take pictures. Because taking picture is easy, so any health worker anywhere or nurse in the NICU, can take a picture and then it can be transmitted through Zoom or WhatsApp. And then the doctor can see and they can make out that something is wrong. And so I think that is there.
But I want to end by saying that this child, we come back to this child, because there’s thousands of such children. Where it is like, who owns my vision? Is my vision owned by the ophthalmologist, by the nurse, by the pediatrician, by the gynocologist? Why did I go blind? They saved my life but they didn’t save my vision?
I think again, I come back to this point that every newborn facility should have an eye screening program. I think other pediatricians did a great job in eradicating polio from our country. I’m sure that polio could not have been eradicated if it was owned by neurologists and orthopedicians because it is affecting the leg or the arm. It could only have been done by pediatricians because the babies are with them. And same thing for ROP, childhood blindness, ROP, it cannot be eradicated or taken care of by ophthalmologists. The babies are with the pediatricians. The pediatricians have to own this disease, take care of it and do all the things which are possible to prevent prematurity, to prevent ROP. And then get it screened on time. And of course, the ophthalmologists need to have proper training and proper equipment to manage these cases.
ROP is a race against time. The center of this program must always be the premature baby, not my ego or your ego, or my hospital, or the pediatrician, or the ophthalmologists. The center of this program must be the red glow of the baby. We must not lose it, it takes a lot of effort for this whole team to set up a safety net. Most of the net is with the neonatologists, the parents, and the eye care professional. We need little help of anesthetics, not most of the times, we don’t need the help of. Of course we need pediatric glasses and the rehabilitation people who will take care of the low vision. And the social workers. The social worker is the nurse or the receptionist who’s been giving appointments, or the person who’s talking to the parents. Somebody who’s coordinating this whole things so that the baby does fall through.
The main challenge, of course, is logistics. How to reach little babies that are in some hospitals, we are somewhere else. And so we should fix one/day time of the week to visit in an NICU. There should be a contact person in the NICU who will maintain a diary knowing which babies are to be screened today, whether they have come or not. Previously we had a lot of problems because we could not contact the parents. But now with the cellphone, the mobile, we are able to call the parents and connect to them and say, “Please come, your time is today,’ send them an SMS.
And on the Day of Birth Front Sheet must be stamped. What are the ROP screening date? If the child is born on 4th of March, okay, 4th of April you must finish your ROP check. And this must be conveyed to the parents. The discharge summary should not just scribble something, go for an ROP check. It should tell that the eye check up is urgent, it is compulsory, it has to be done on such and such date at such and such place. It should not be something which is told very hurriedly, by somebody, “Give milk, give heat, go for ROP, go for this thing, this thing, okay, goodbye, thank you.” No, then it doesn’t register. The parents have told us time and again, that I said it was written in your case sheet, why didn’t you go for ROP screening? They said, “No, but it was not told to us. It was told, ‘If you have time, you can go for eye checkup. Why don’t you go for eye check up?’So it was told very casually, we didn’t realize the importance.” So that is very, very important.
I want to recapitulate what we talked about in the last 30 minutes or so. “Tees din roshni ke,” which in Hindi means “30 days to vision.” That is the most important. If people want to sleep in this talk, please just remember this one line. Within 30 days of birth, the eye checkup of a preterm baby must be done. That’s the crux.
And all preterms who are less than 2000 grams or less than 35 weeks. 35 weeks again, because mothers don’t know the dates, so you can just arbitrarily, if it is one month from the due date. If it was born one month before due date, it is preterm. And if you don’t know the dates, then definitely you must screen if the baby looks premature. And those who have a family history must be screened, not after 30 days, but even before they are pregnant or during pregnancy they should be counseled that your child can get problems and what type of problem and at one time the screening has to happen for retinoblastoma or cataract or if there be other things.
Systemic factors which were the crux of these topics. The systemic factors are very critical to our ROP prevention and ROP management. and these have to be done by the nurses, the pediatrician, and ophthalmologist working together as a team to make sure that the ROP which is not just an ocular disease, but a system disease. And we can really bring down the amount of ROP that we see.
I am reminded that one day there are two big hospitals in my city and one of the hospitals said, “How’s the ROP in my hospital? Am I having less ROP or more ROP than the other hospital?” So they’re competing with each other. And I said, “I can’t tell you all the information, but I can definitely tell you that I’m doing more lasers in your hospital than the other hospital.” And he was shocked! He said, “No, no, I can’t believe it, how can it happen? My hospital is so good, how can I be doing more lasers in my hospital, how can I have so much ROP? Maybe they don’t survive small babies?” I said, “No, they survive small babies.” “Okay, maybe they don’t have all born babies.” I said, “Oh they have all born babies.” He says, “Why am I getting more ROP?” I said, “I don’t know, you talk to them, you find out what is their protocol and what are your protocols?”
And then they had a chat with each other, a nice professional chat, and they found out what to do. I go to the hospital, they have no ROP. I’m not getting any ROP to train my students for both the centers. So ROP can be reduced, it cannot be eliminated, but definitely it can be reduced and the amount of lasers we do can definitely be reduced by taking care of the systemic factors which I have discussed today.
The discharge card must have a very clear information about when to go, that it is important, and whom they have to meet, and when they have to meet. And when they come back to the pediatrician or the pediatric unit or they come back to the community, then we must checklist that the ROP screen was done, where is the report, have you got for eye check up, why have you not gone, please go.
There must, of course, be enough posters in your OPD and waiting area. Where there are breastfeeding posters, there are immunization posters, vaccination posters, we must have posters which inform the parents that the eye check up has to be done and how critical it is. And as I said, the ownership of vision, of course, should be by a team and this team has to be led by pediatricians. And of course the pediatric ophthalmologists are always there to participate in this program.
So let’s go. I hope all of us can do what Samarth in Lucknow has done. Put these big posters on his car. I didn’t get this idea, I’m an ROP lady for the last 20 years, and I didn’t get this idea. So he has put these big posters and whenever his car stops in the city, people know about ROP screening. So I’m sure that many of you will have many more brilliant ideas to spread the awareness. And make sure that every parent comes to know that if I have a premature baby, just like they know that my baby needs to put in drops or they need vaccination, they must know they must have this information that my baby needs an eye check up.
And this is thanks to all these new ROP teams, that is neonatologists, ophthalmologists, nurses, where they’re giving the right to sight. This is my son who was 28 weeks, 1300 grams. So they grow into amazing human beings. They do so well, they are so bright and we don’t want to end up something like this. Of course if they end up in this, then we do have a program to rehabilitate them, put them through proper training and they also do quite well. But that is not what we want. Every child has his right to sight, they’re not born blind, they’re not born with a disease. So we can, by proper treatment and care, we can help them to see this bright world and their smile will bring smiles to us. Thank you.
[Adio] Thank you so much.
[Subhadra] So before I close, Adio, if we have time.
[Adio] Thank you very much.
[Subhadra] Just five minutes, I wanted to share a movie, or a small movie video one of my students have made about ROP during COVID times. Because we are facing this epidemic, so what should be the plan, how should we take care? Because in my city, now I’m seeing that from outside my city I’m getting babies who were not screened timely or not screened properly during these last two months. And they’re all landing into very serious problems. But in my city, we set up the program in March and we have screened almost 300 babies in these last two month and we’ve treated alot of them. Including from overseas, many have put protocols in place. So just those who are interested, this is a five minute movie, where we just.
[Narrator] This presentation is to discuss the screening criteria and follow up during COVID-19 pandemic. And also to know the necessary safety precautions while screening. The protocols are based on the Indian ROP society consensus statement. According to which there is no change in the timing of first screening. The first screening will be done at 20 or 30 days as followed before. But the flexibility can be taken into account only in follow up and frequency of visits in low risk babies who are more than 34 weeks, more than 1500 grams, and stable systemically.
In such babies, if the retina is immature, or the ROP is at a low risk, and if it is beyond zone two anterior, then we can screen such babies once in three to four weeks. If it is zone two posterior, low risk ROP, then screening has to be done once in two weeks. If it is zone one and zone two posterior with pre plus, then better to treat the baby with laser on the same day rather than waiting for next week. By this we are reducing the number of visits and delaying the frequency of follow up.
Type One ROP and zone one ROP with vascularized fovea, then laser treatment has to be done on the same done and the baby has to be called after two weeks. If it is APROP, which is not amenable to laser, are zone ROP APROP, then better to give anti-VEGF injection on the same day and call the baby after two weeks. The parents must be instructed to send the photo of the baby’s eyes to the treating doctor by email or by WhatsApp on day one and day seven, so that the doctor can see whether there is any linear mark or redness that can develop endophthalmitis.
Stage four A and stage four B babies have to be undergone surgery immediately and follow up can be done after four weeks, and the parents can send the photo one week one and week three to the treating doctor. Stage five babies can wait, or the treatment can defer up to four to six weeks. A letter must be given from the hospital site to the parents so that they can show to the police for urgent travel passage during the follow up visits.
The necessary safety precautions the doctor must follow are, the mother must place the baby in the cradle under the radiant warmer, and must move aside. Maintaining a safe distance from the doctor and the doctor steps in. And the doctor is equipped with cap, mask, a proper gown, which covers the entire forearms, gloves must be worse, a safety goggle must be worn, and also necessary safety of footwear and boots has to be worn. The doctor connects the monitor and examines the baby under the radiant warmer.
Specular endomentry is not really necessary, unless if you are in doubt. And if you are using a specular manipulator, then it has to be changed between babies. If there is any conjunctivitis then try to avoid screening during that visit. And if screening is really mandatory during the visit, then vitamin eye drops can be put pre and post screening. And the doctor has to maintain a safe distance from the baby to prevent any aerosol transmission.
And once the screening is done, the lens must be cleaned with salt water and the rim of the lens and the knob of the in direct ophthalmoscope must be cleaned with alcohol swab. Once the screening is done, the baby’s properly covered and is left in the cradle and the doctor moves aside and then the mother steps in to take the baby from the cradle. By this we are maintaining a proper social distancing between the doctor, the mother, and the nurse.
If you are performing a long procedure like laser Indirect ophthalmoscopy, then it is better to do it under an aerosol box so that it diffuses the aerosol transmission.
The points to retain from this presentation are, ROP care is an emergency situation and COVID-19 pandemic has created a high risk situation in these babies. Reducing the visits and early treatment in suitable cases is an efficient strategy. And strict adherence to safety precautions is mandatory to maintain the safety of the baby, the doctor, and the parents.
Thank you for your patient listening, have a nice day.
[Subhadra] So what I would say is that some of the questions which are related to the glasses and how the optometrist help with vision therapy, and what are the protocols, these we all published very nicely in Community Eye Journal, Southeast Asia Edition. It’s meant for nurses and community health workers and all the details are given in very simple language, without too much of references and a lot of good pictures. So I would suggest if somebody can access. I can send to you, Adio, if somebody then would like to. Or to me, we can share the whole journal, it’s just a few pages, and written for health workers in very simple languages, practical aspects, what to do and what not to do. That’s a whole talk in itself. So I cannot talk on that.
[Adio] No you can’t talk about that.
[Subhadra] It’s already available. Okay about the glasses and that thing. Now somebody said what is the low birth rate is a risk and why is it a risk? Actually the low birthweight if it is at term, maybe it is not at risk. Actual risk is the prematurity. As I said, many of our mothers don’t know their maturity or prematurity, or how many weeks. We use birth rate as a surrogate measure. That if it is a low birth rate baby, then possibly it is premature. And of course, the pediatricians will check other things which tell them it’s a premature baby like what is called a Ballard score, the line you go, the color, the tones, all those parameters are there. But we use birth weight because it’s the easiest available parameter.
But ideally, if you know the gestational agem the ROP will really follow the gestational age in postmenstrual age of the baby. So yes, low birth weight because it is associated with prematurity. But if the baby is full term, but it is an IUGR baby and the weight is less, they don’t get ROP. So it is really a disease of prematurity rather than low birth rate. But yes, we use, that’s why we say low birth rate and/or prematurity. So we should never say just the birth rate because as I mentioned in my lecture, even big babies will get ROP if they have hydrocephalus or born to diabetic mothers.
Retinal steroids. So there is a list of diseases or conditions which are available with the gynocologists, what are the conditions where steroid has to be given? These steroids don’t cause any harm, actually they are good for the baby because they lead to improvement in the lungs. Lung function. So there’s a protocol. Common diseases are like pregnancy-induced hypertension, mothers with frequent fetal loss, what we call as bad obstetric history. Mothers who have fibroids with pregnancy, mothers who had assisted fertilization. So there’s a list of diseases already mentioned, what we call as placenta previa, so what are the high risk pregnancies, then in those it can be given. And even now people have other data which show that even in the late preterms, that even that 34, 35 weekers can be given. And even if the mother didn’t receive it because they don’t come from antenatal check up, when they come with preterm labor, we should inject one of those immediately on the table before delivering the baby. Even that has a 50% protection.
So these antenatal steroids is quite good both for not only the eyes but for the other health parameters of the baby as I mentioned. I think it’s a very good strategy and I’m happy that the evidence shows it and it has been adopted by our country. And UNICEF is also promoting its use in many other countries.
Which antibiotic is safe? I don’t know if you’re asking about the topical or the systemic? For me, one thing we have to remember is that all the eye drops that we use in babies are actually adult dose drops. They’re not pediatric drops. So what the eye drops have been made antibiotic drops are for 60 kg man. So you can just imagine a 1kg baby is receiving a drug like Gentamicin or I know whatever, Moxifloxicin, is actually a dose for a 60kg man. So the baby may not complain but all these antibiotics and in other drops also, the moment we put in the baby’s eye, it is rapidly absorbed. And it’s almost like giving a 60 gram bolus dose to this baby.
So any drug that we put, we should not just take it lightly. Okay, there’s some redness we’ll put some tobramycin, we’ll put gentamicin, we’ll put moxifloxacin. No, only give it if there’s a real infection. Otherwise, a little watering, redness, we can just manage with sac massage, we don’t need to give too much antibiotics. Even if there’s little conjunctivitis, it will go away on its own. So we don’t have to load them with a lot of antibiotics.
Now, the choice of antibiotics, what I do that in case I need to give, I usually try to get an antibiotic like tobramycin, which we don’t give for systemic infections. Because these antibiotics what we give in the eye also cause drug resistance. And you know today drug resistance against antibiotics is a huge, huge global phenomenon. And we should not add to that problem. So we should give an antibiotic like maybe soframycin or tobramycin and sometimes chloramphenicol drops which are very mild. They cover a broad spectrum, they cover the serious infections. And they are not used for systemic infection like pneumonias or meningitis so the amount of resistance will be less than deal with systemic infections. So systemic antibiotics I am not talking about, that the pediatricians will know.
And is there some adjacent therapy to help suppress the VEGF? I’m not aware, we only know about the Anti-VEGF drugs and also it has been shown that some of the steroids, they have suppressing activity. There are now some studies, some data coming up that there may be other drugs like doxycycline or some antimetabolic protein drugs. So there is some work being done, including in our lab, and we’re looking at other molecules which are not VEGF. Because VEGF is one major part of the newest process but there are other things also. Currently it’s only the anti-VEGFs which have been shown too, the anti-VEGF injections which have been shown to take care of the VEGF.
Now in which conditions do you perform laser and anti-VEGF at the same time? For me, the main treatment is laser. I give anti-VEGF very rare. But in zone one disease and APROP, I’m giving more and more anti-VEGF. But I do a combined treatment if I think that the baby will not follow. The main thing with anti-VEGF is with Avastin there’s a 10% recurrent later and when it recurs, it recurs very bad. And this recurrence can happen anytime. Some two to three weeks, up to one year. So you have to follow up them every two weeks, three weeks, four weeks, up to one year of age. And they become very fat and big babies. And then we have to examine them under anesthesia.
If you are using ranibizumab, that is Accentrix or Lucentis, then the recurrence is almost 40% as per the random trial. Which means every third, fourth baby will need more treatment. So for me, if the parent is not able to come back, then I give the anti-VEGF and after four, five, six, seven days, I go head and do the laser in the periphery nicely. And then my frequency of follow up can be less and then they don’t need to come that much.
The other problem is that the recurrence of the laser is very early and it is easily seen by most of the doctors. But the recurrence after anti-VEGF is very different. I’m also still learning, I have missed the recurrences, they are very subtle, they are curled very tiny frons, they’re not easy to see. So it makes it now who will render each ROP study and the anti-VEGF study recommends that the recurrences must be looked for by fluorescein angiography. How many of us have fluorescein angiography for babies? So it also becomes very challenging, those who are doing anti-VEGF therapy.
I think those who want to do immunotherapy, they should know about the disease, they should have all the facilities, and I like to do combined therapy, especially if my patient is a little less educated or is not going to follow up. But yes, I’ve had doctors, children and other people who really understand what I’m telling them that you have to come for follow up, they come religiously, then I do only monotherapy.
Every time we do laser there will be more myopia. But it’s not that anti-VEGF I don’t get myopia, so never promise your patient that I’m giving you an injection and not doing laser and that they will get less glasses. They can still get -7, -8 and then they’ll be very disappointed. So yes, it has better structure and outcomes, especially in zone one disease. So in one disease I’m using more anti-VEGF. And I add laser if I think they are not going to come.
What is the meaning of popcorn lesions? I could have shown you on slide. I didn’t show it. Popcorn lesions happen when you know the new vessels that your tiny frons, then they start regressing. So there’s a little bit of vitreous condensation which happens in that area and they’re little raised from the surface, they look like popcorns. And they should not be continuous, they should not be red. They should not be supplied by dilated vessels. Then they’re benign, they’re a sign of regression. The opposite, if they’re red, they’re elevated, they’re continuous like a sausage or a big lesion, then they may still be active. And they may not cause fibrin disease, but they will cause a whole lot of drag or retraction of the retina. So the popcorn are basically small tiny elevations from the retina which are condensation of the ridges on the new vessels.
Somebody wants to know which is the best college for masters in optometry? I think that’s beyond the scope of this presentation. Anti-VEGF I already said. And thank you for the recommendation.
And yes, red and green laser. Yes the green laser is very good, it’s easier to use, it’s less painful. The outcome’s are the same, whether you use red or green and the advantage of green is that you can use it for all other diseases also. And rarely is it painful. There’s a critical chance that the green can cause cataract if the pupil is not dilating well. Usually that will happen in somebody who’s not very good at lasers and focuses the light on the lens rather than on the retina. But in good hands I think that it’s the same and studies have shown that we can use either of the two and green is very good.
I think Adio is recording this and she will put it somewhere up on the website. And then everybody can see the recordings so that is not a problem.
[Adio] I’m recording this.
[Subhadra] So we are doing lasers under topical anesthesia. The baby expand their lungs? Yes, for the aerosol I have already shown you what we are doing. Also when we are doing lasers, we can do laser in the incubator box itself. Or we can have a plastic, acrylic box made, what is called an aerosol box, and do the laser through that box. Or you can also use an oxygen mask and tape it to the baby and put an airway tube in that so that the baby’s mouth is covered. Or a plastic sheet under which the air goes and you are in your PPE and you don’t get the aerosols. So both things can be done and that’s what we’re doing for the aerosol.
Okay so they said babies in families show up prematurely? No, I didn’t say families show up prematurely. I said families do you have any eye diseases? A lot of eye diseases in childhood are genetic. Retinoblastoma, familiar retinopathy, congenital cataract. So these are all familiar disease and it’s very stupid and shameful if you know one baby already went blind and we were not able to counsel the parents and explain to them that their second baby will also get this problem. So that is what I said.
So whenever a baby is born, we should triage them into three categories. One is term baby with no family history, one is term baby with a family history, and third is a premature baby. So term babies with no family history, their screening with torchlight and red glow on the day of birth. And then in follow up visits maybe every six months or something. And then warn the parents if they see some white or squint, they’re to return. And for those who have a family history, we should know what type of disease is there. If there’s a family history of retinitis pigmentosa, we’re not going to screen at birth. You can screen after when they are one year, two years of age because there’s no treatment for that.
But if it’s for GR, we have to tell you we’re at 34 weeks that is various family history of all these disease or detachment at birth, the next time we’ll get it. And there we deliver at 34 weeks, and examine and do the laser, within 24 hours of birth, and we can save this child. A lot of diseases and I’m just saying that if there’s a family history we should know what is the disease, when we have to screen, and we should counsel the parents. I didn’t say families have a history of prematurity. That is much, much less common.
So we are agreeing, all this ROP very nice. So I don’t have lasers, so some of you don’t have laser. I should refer him, what can wait?
Usually the ROP is divided into two parts. One is the low risk and one is the high risk. So low risk is one where the pupil is dilating nicely, the vessels are not dilated tortuous and the media is clear, and there is no new vessels and no hemorrhage, then you can follow. But if any of these is not there, there’s a new vessel, or there’s hemorrhage, or there’s dilation tortuous, or the pupil is not dilating, then these should be treated within 72 hours. We must not wait for the wait game to happen, it will be too late.
How steroids work? Our work has shown that there’s a lot of inflammation, we have done some vitreous studies in ROP and they’re shown that there’s a lot of inflammation. And the steroids also help but this is what I think they’re asking about the steroids for the lung maturity. Yes, the steroids help to improve the maturity of the lungs and I already said that the lungs have a direct connection to ROP. so if the lungs are mature, then you will get less serious ROP.
How do you get the parent to buy the idea for quick reference. So transport of the baby is not easy. I think that is a thing that we need to work with the pediatrician who is going to come, how they’re going to be doing? In our country, it usually was a big problem, but now with the government program, it’s called the (speaking in Hindi) There is transport arranged both for pregnant women and for the babies to go to various places if they are suffering from any birth defects. So if there are any identified birth defects, birth diseases.
Initially, when they identified these diseases of newborn, there was no eye disease in that. There were 14 diseases or some 20 diseases, including alkaptonuria, which I’ve never seen and thyroid disease and things like that. But there was no eye disease in that newborn screening program. And then I wrote to the head of that in the national government, two or three times I wrote to him, where is your vision? That’s all I wrote, I said, “Congratulations for the newborn screening program launched in India, but where is your vision?” But then he got it and now three diseases have been put in that program: congenital cataract, ROP, and screened and delayed development that is a visual impairment and mystagma, so that covers most of our disorders.
Of course we are hoping they will pick up. I think we have to work with the government, we have to work with the authorities and see how we can work with transporting these babies. It’s a challenge, it’s not easy, but I think that if we think of these as opportunities we will find some way out. Before it was here we did it, it took some time. In Bangladesh, they have a very good program. Other countries also, I think most people, as I said, are trying under the sustainable development goals to have better care for the newborns, our children should have better lives. We have to keep on pushing, we have to keep on asking, demanding, it will come.
By just thinking, oh my god, it’s so difficult, how it won’t happen, my government doesn’t work, it’s not going to change. We have to drive the change. As Mahatma Gandhi said, “Be the change that you wish to see in this world.”
[Adio] Yes, thank you very much, Subhadra.
[Subhadra] If you did anti-VEGF? I usually do laser. Okay.
[Adio] Yeah, (laughs) we can go on and on, the questions are so many and I’m sure if you listen to the lecture again, you’re going to get the answers to so many of these questions. We’re really happy, Dr. Subhadra, for joining us. It’s been a very stimulating time as usual. And I know that everybody, all around the world, are grateful for this, have had a very stimulating time. Thank you so much. I’m sure if we call on you again, for another topic, I’m sure you’ll be able to come? Right, Subhadra? Thank you very much.
[Subhadra] Yes! I’m thankful for the Nigerian Society and to Cybersight, thank you. And it was wonderful and I’m only a phone call or an email away from anybody around the world, whatever you need you can just message to me. Bye bye!
[Adio] Thank you very much! Thank you, bye bye, thank you so much!
[Subhadra] Thank you.
[Adio] And for the rest of our guests who are registered, thank you very much. We’re going to have this presentation sent to you, don’t worry about that. We’ll have that in the past and we get to have that in the future. Our next presentation is in September and you’re also invited. We’ll be sending out the adverts very shortly. Dr. Niranjan will be speaking to us, he’s based in Liberia and we’re going to have a very interesting topic to have to discuss with you in the next one.
Until next time, this is the Nigerian Pediatric Ophthalmologists and Strabismus Society saying thank you for joining us, until the next program. Thank you very much, okay, bye.