Lecture: An Eye on Vitamin A

DR SRINIVAS: Hello, everyone. So glad to have you join me today. So today we’ll be talking about an eye on vitamin A. My name is Dr. Sowmya Srinivas. I practice at Dartmouth Hitchcock Medical Center in Lebanon, New Hampshire. I have no disclosures for today’s talk. So vitamin A is a retinoid. It’s a fat soluble retinoid. That is influencing all of our tissues in our body through its effects on gene transcription. So whether you’re deficient in vitamin A or whether you have a toxic amount of vitamin A, it can have a lot of widespread effects, which we will learn about today. So this was a quote that captures what vitamin A does in the body. So vitamin A or retinol is arguably the most multifunctional vitamin in the human body, as it is essential from embryogenesis to adulthood. So vitamin A is a building block chromophore for rhodopsin, and transcription factors — transactions are proteins involved in the process of converting or transcribing your DNA into RNA. And transcription factor include a wide number of proteins. But these include RNA polymerase, and they initiate and regulate the transcription of genes. So we’ll begin with our first polling question today. Which is: Which of the following are physiologic roles of vitamin A? And you all got it correctly. So the answer — the vast majority of you said all of the above. Which is definitely true. So the physiologic roles of vitamin A include vision. It’s involved in epithelium, red blood cells, immunity, and also reproduction. So therefore all of the above is true. And here is what happens when you have… This is a chart showing you what happens when you are vitamin A deficient. So chronic dietary deficiency leads to tissue and plasma depletion, and that results in an alteration in genetic and also metabolic function in your body. And so this leads to systemic side effects. So it includes metaplasia, impaired immunity, morbidity, anemia, and poor growth. And that can lead to some of the ocular manifestations, which include keratomalacia, corneal ulceration, and night blindness. Though of course, as you can see on the left hand side of the pyramid here, you can see that the mortality risk increases, as you go up this pyramid. So here’s our next polling question. Which is: Which of the following is a spectrum of ocular diseases that can be caused by vitamin A deficiency? And you are correct again. So 71% of you said xerophthalmia, which is the correct answer. So the ocular complications of vitamin A deficiency is caused by deficiencies in vitamin A, which is dry eye. You can have corneal ulceration, corneal melting, which is keratomalacia, there can be night blindness, which is called nyctalopia, and retinopathy. So this spectrum of ocular diseases are called xerophthalmia. So as you recall, vitamin A is an antioxidant. And you need vitamin A for healthy functioning ocular surface. So recall that photoreceptor rhodopsin is required here. Which is a photopigment, and that is found in the rod cells of the retina. So recall that rhodopsin allows our eyes to see well at night. So night blindness, often the first sign of vitamin A deficiency — you’ll have patients complaining of night blindness with vitamin A deficiency. So really important to remember that nyctalopia or night blindness is one of the symptoms. So ocular complications of vitamin A deficiency. So here for normal histology, you have your typical mucous membranes, which are supposed to be non-keratinized. So think about your cornea and your conjunctiva. So the conjunctiva is a non-keratinized squamous and columnar epithelial, with mucin secreting goblet cells. Your cornea is also non-keratinized, but it’s stratified squamous epithelium. What happens when a patient has vitamin A deficiency is there is mucosal keratinization. So this results in ocular surface, GI, and respiratory epithelium concerns. And so that brings us to polling question three. What is your diagnosis of the pictures down below on your right hand side? And you are correct again. So the vast majority of you said Bitot’s spots, which is the correct answer here. So Bitot’s spots, if you look at the pictures there, they’re foamy, they’re appearing on the nasal and temporal conjunctiva. And they have been linked to vitamin A deficiency. And so here’s another picture on your left hand side of Bitot’s spots. Another complication for vitamin A deficiency is scarring of the cornea. So the middle picture shows that there is poor wetting on the tear film that causes vitamin A deficiency. And the picture on the right shows the concept we were just talking about, which is keratinization of the ocular surface. So remember that the cornea and the conjunctiva have to be non-keratinized. So the histology says that non-keratinized surfaces are normal. But when we have keratinization, as a result of vitamin A deficiency, you’ll have a patient like the example in the picture on your right hand side. So we talked about what can happen with vitamin A deficiency. But when you have too much of vitamin A, so vitamin A excess, that is certainly not a good thing either. And how can that happen? So one of the reasons vitamin A excess can happen is by diet. So if you’re consuming highly concentrated animal sources, such as bear, seal mouse liver, the vitamin A excess is likely to happen. Vitamin A excess is very unlikely if you have a plant-based diet. It’s exceedingly rare to have a vitamin A excess. Someone can also have a vitamin A excess if they’re abusing supplements. Vitamin A supplementation. Or certain retinoid medications can also cause vitamin A excess. So remember that either deficiency or excess can have effects in the body. And so what can our toxicity or vitamin A excess do? It can lead to birth defects. It can cause bleeding. It can cause shortness of breath. Cirrhosis. It can lead to increased pressure in the brain. And smokers who consume alcohol and beta carotene may be at increased risk for lung cancer or heart disease. So again, these are effects that may happen when there is an excess of vitamin A in the body. That brings us to the next poll question. Which is: What are the sources of vitamin A? So how can you get vitamin A? In your diet? All right. You’re all correct. Both of the above. So you can get vitamin A via plant and animal sources. Which we’ll review next. So plant includes beta carotene. So that is a provitamin. And animal sources. Retinyl palmitate, dairy, eggs, liver. So the picture on your right hand side shows some sources of vitamin A. Carrots certainly you’ve heard about for vitamin A. And a whole host of our fruit and vegetables, and also meat, dairy, eggs, liver, and so forth are sources of vitamin A. And so why does vitamin A deficiency happen? So in the United States, it’s typically because of malnutrition. So not getting the adequate doses of vitamin A that our body needs. Malabsorption. Which can typically happen after bariatric surgery. Or just a poor vitamin metabolism. And in the developing world, vitamin A deficiency is actually the leading cause of childhood blindness. Because of the examples we saw earlier. So that brings us into some of the cases we’ll talk about with vitamin A deficiency. So the first case here was a 68-year-old cachectic, which means really weak, Caucasian male. He had chronic illnesses, including AML, and also history of graft versus host disease. His ocular history included herpes simplex virus with central corneal ulcers, which were worse in his right eye. So we’ll go over his case next. His vision on the initial exam was 20/150 in the right eye and 20/25 in the left eye. And his entrance testing — so his pupils, confrontation fields, and extraocular movements were unremarkable. His IOP was 4 millimeters of mercury in the right eye and 5 millimeters of mercury in the left eye, and his anterior segment exam was unremarkable except for the significant changes that we’ll see in the next slide. So some of these significant changes include lagophthalmos, which was worse in his left eye, compared to the right eye. He had 1+ injection on the conjunctiva, which was worse in the right eye. And the cornea of the right eye showed these dense sort of central punctate epithelial keratitis, and there was also inferior central epithelial defect and a faint infiltrate. So he only had about 30% of the stroma remaining. In his left eye, there was infracentral epithelial defect, with punctate stain. So the picture on the screen is a picture of his right eye, with that dense keratitis, and also that epithelial defect, which you can see in the picture below. And corneal sensation was performed. So he essentially had no sensation in his cornea, on the right eye. A little bit — 1/4 sensation in his left eye. So there was no AC reaction, and there was no corneal perforation. And his dilated fundus exam was unremarkable. And so here you can see a baseline photograph of how this patient presented. With the epithelial defect. And so when we examined this patient, we thought of a few different differential diagnoses for this patient. The first on our list was severe dry eye. The second one was nutritional keratopathy. And recall that he had a history of rheumatoid arthritis. So because of that, we had to consider autoimmune melt, we had to consider HSV keratitis, either a bacterial or a fungal infection on his cornea. And so we ordered vitamin A levels. And so the reference for vitamin A is supposed to be — normal is between 32.5 to 78. And this patient’s initial vitamin A level was 16. So you can imagine that it’s extremely low. Making him vitamin A deficient. And because of this, based on our differentials and what we got for vitamin A, we thought that the changes on his cornea or keratopathy was thought to be because of vitamin A deficiency, given his medical and ocular history. So recall that he had no sensation on the cornea in his right eye. So we diagnosed this as neurotrophic keratopathy. And he had that central corneal ulcer, and also that thinning you saw in the picture, due to the vitamin A deficiency. And so the next steps for treating and managing this patient were: Corneal cultures were taken. And we had placed a bandage contact lens and replaced it daily when we saw him for follow-up. And we also did a lateral tarsorrhaphy in the right eye. Vigamox was prescribed for him. Every two hours in the right eye. Alternated with artificial tears every two hours in both eyes were also prescribed. And this patient showed continued improvement in the right eye, with healing of the epithelium. And certainly improvement in the vision. So based on this, what other treatment would you advise for this patient? So in addition to the Vigamox and tarsorrhaphy, what else would you recommend for this patient? And so that is absolutely right. So a good majority of you said vitamin A supplements. Which is exactly what this patient was recommended as the next step. So this was certainly beneficial in the patient’s recovery process. And upon giving him vitamin A supplements, recall that his baseline vitamin A level was 16. And it actually improved to 36 with these supplements. So he certainly continued this nutritional support, per his dietitian’s recommendations. And here is a follow-up image. So the keratopathy, as you recall in this case, was due to this severe vitamin A deficiency. And the picture here shows a remarkable improvement. As vitamin A supplementation and other measures were used to treat this patient. So there is a marked improvement in his cornea. As seen in the picture here. And just a before and after picture here, comparing the patient’s initial follow-up, initial exam, versus follow-up exam. So on to case number two. This is a 47-year-old Caucasian female with chronic kidney disease. And she was treated with dialysis for her CKD. And she also had a short bowel and gut syndrome. And also a history of nutritional deficiency. She lived in Nevada, but had been visiting the area due to her son, who was ill. And she was the primary driver, and reported that she was unable to drive safely, because of the significant decline in her vision. And her past ocular history included dry eye, for which she was on Restasis, but she actually reported that Restasis was pretty much unresponsive to her blurry vision and all of her dry eye symptoms. So in other words, the Restasis that she had been prescribed was not really helping with any of her symptoms. And so vision on the baseline exam without glasses was 20/30 in the right eye and 20/100 in the left eye. Her pupils, extraocular muscles, confrontation fields, were all normal. And her eye pressures were 18 in both eyes. And her ocular findings included anterior segment which was unremarkable, except for significant conj and corneal findings, as we’ll talk about below. So the conjunctiva had keratinization in both eyes. So in the left eye worse than the right eye. And then the cornea also showed mild punctate epithelial keratitis, with that central cloudy sort of dystrophy. And in the left eye, she had severe punctate epithelial keratitis. And it was a swirling pattern with a central cloudy dystrophy. Which I’ll show you in a picture coming up next. And there was no guttata in either eye. And dilated fundus examination was unremarkable in both eyes. So we also ordered vitamin A levels for this patient. Because we thought she could be vitamin A deficient, due to her medical and eye history. And certainly it did come back as 6.4. The reference, the normal, is between 32 to 78. So she was pretty severely vitamin A deficient. And we couldn’t get the follow-up vitamin A, as she moved back to Nevada. But I do have her baseline and follow-up photos. For this patient. And a few other things we did for this patient was: We put her on punctal plugs. And also referred her to nephrology, gastroenterology, and also nutritional services. And she was started on vitamin A supplements. So adults — for adults, vitamin A are 200,000 units, 60,000 mcg. So she was on it once daily for two days, and then repeat with a single dose after two weeks. And this is per the World Health Organization recommendations, which was prescribed for her in this case. And so this patient was to follow up in New Hampshire. She prolonged her stay. But we did refer her to a primary care doctor in Nevada. Who she had a follow-up with a month after her return to Nevada. And based on the one follow-up exam that we had, her symptoms had improved significantly. So recall that the vision in the left eye was 20/100. And with vitamin A supplementation and punctal plugs and the other measures, her vision markedly improved to 20/30 in that left eye. And so the punctate epithelial keratitis in the cornea had also improved, and this corresponds to the improvement in her vision. In both of her eyes. And so the first set of photos here are her visit at baseline. So these are just her initial visit. And as you can see, it may be a little tough, depending on lighting. But a lot of our dryness going on, on the cornea, a lot of SPK. And here’s her follow-up visit, which look a lot better, given her vitamin A supplementation. And other measures, including plugs and drops used for dry eye. And then our final case for vitamin A deficiency is a 42-year-old. He is a Caucasian male. Obese — excuse me. Female. Deaf, obese. History of alcohol abuse. And a severe multisystem disease, including nutritional deficiency, multiple sclerosis, anemia, sepsis, and liver failure. So the chief complaint for this patient was: Her eyes became very inflamed. Suddenly, within a few days. And so this patient was actually seen as an inpatient. And so we have the slit lamp findings here, with the corneal epithelial defect. With a corneal perforation in this case. With an iris plug. She had a very shallow, but a formed anterior chamber. Her Seidel was negative. And we could see that on her corneal stroma, thinning was pretty evident in her right eye. In her left eye, she had intact, loose epithelium with an area of severe thinning, which was likely a Descemetocele. In this eye, the Seidel was also negative, but with a deeper anterior chamber. We have a clear view of the posterior pole and no pathology was observed. There was no choroidal pathology, vasculitis, retinitis, or choroiditis appreciated in her eyes. So we decided to glue both of her eyes, given the corneal perforation and the rapidly progressive thinning over the course of a very short duration. And so she had glued bilateral staph aureus corneal ulcers, which was actually due to vitamin A deficiency. And we also got some cultures. So bilateral MSSA corneal ulcer. In the right eye, her cornea was perforated. And in the left eye, her cornea showed severe thinning. And because of this, the cornea was glued in both eyes. The right eye glue was pretty stable. And the AC was formed. But unfortunately in her left eye, which was pretty thin, the cornea actually ended up perforating sort of around the glue. On the following day. So then we thought her rapid bilateral corneal ulcer may be because of her severe nutritional deficiency. Particularly vitamin A. So we ended up ordering the vitamin A level for this patient. And initially, we thought the rapid corneal ulcer and melting, the keratomalacia, which is common, as we discussed, in vitamin A, was unclear, but likely multifactorial. So recall that this patient was actually obese, but despite her obesity, she may have had micronutrient deficiencies. So vitamin C was also low. Zinc was low. Vitamin D — and she also had mucositis. And there was also a presence of lagophthalmos. So the ulcer was present in the region of her lagophthalmos. And she had also been infected with MSSA, but there was no current active infection. And so we got some repeat corneal cultures. Which were negative in the left eye. But it came back positive for mixed GP organisms in her right eye. And the treatment for this patient was subconjunctival vancomycin. Twice in that eye. Since that culture was obtained. And she remained on Vigamox every three hours. And fortunately there was no progression to endophthalmitis for this patient. And here is a figure, with — not the perforation, but just severe thinning in her left eye, which is seen in the picture here. So again, recall that xerophthalmia is a spectrum of ocular diseases that can be caused by vitamin A deficiency. The signs include dry eye, corneal ulceration, melting or keratomalacia, which we saw in our last case, night blindness, nyctalopia, and also retinopathy. And so the next question for you is: We learned about some of the causes or ocular signs of vitamin A deficiency. But do you think… Here’s our poll question six — does vitamin A affect myopic progression? All right. So a few different responses here. Yes, no, maybe. I don’t know. And that question was actually studied in this paper, which we’ll go over next. All right. So could there be other associations of vitamin A deficiency? So, in other words, someone had vitamin A deficiency — could it lead to the progression of myopia? And think about sort of what we do for myopia. So could optical correction, certainly, sun protection, laser correction, vitamins, exercises, and all of these things were looked at. And so this study, which actually came out in 2020, they actually looked at dietary vitamin A associated with myopia from adolescence to young adulthood. And the reason why they looked at this was because, as you may know, there’s a huge myopia epidemic around the world. So as you know, progression of myopia can cause things like choroidal neovascularization, retinal detachment, especially with the rapid progression that we’re seeing in a lot of our children nowadays. So this was published in Translational Vision Science and Technology. In a recent Australian study. And it actually found no evidence that young adults with low vitamin A are likely to become myopic by age 20. So even though it’s not a linear relationship, there may be sort of a threshold for optimal vitamin A intake, and axial elongation. This evidence certainly — they looked at this, because of the myopic… The myopia epidemic locally. So they were looking into whether vitamin A prevents myopic progression or helps slow it down. But unfortunately it doesn’t appear to stem myopia progression in youth. And so again, the question was: Is vitamin A beneficial for preventing myopic progression? And so based on that study, they concluded that vitamin A is certainly beneficial for the eyes, like we just saw. But just not for preventing myopia. So this study showed that it can certainly help with other things. But you cannot prevent myopia with vitamin A. And certainly in cases of certain types of keratopathy, in susceptible patients, patients who have certain types of diseases, are weak, AML, which we saw, it’s important to assess vitamin A levels. Just because, as we saw in the three cases, vitamin A supplementation really also helped improve ocular signs and symptoms. So it’s really important to keep that as one of your differential diagnoses, when you’re looking at what may be contributing to the patient’s ocular signs and symptoms. So if you see someone with significant dry eye, that’s showing no improvement, like we saw in our second case, she was on a lot of dry eye therapy, Restasis, none of which was helping. I wouldn’t say get vitamin A in all your patients with dry eye, but certainly consider their systemic history as well, just to see if this would be one of the things to consider, with regards to treating your patient. And so conclusion: Ocular signs of dry eye or xerosis is due to vitamin A deficiency. And recall that xerophthalmia is a spectrum of ocular diseases that can be caused by vitamin A deficiency. So recall it includes dry eye, corneal ulceration, corneal melting, keratomalacia, night blindness, nyctalopia, and also retinopathy. But certainly keep in mind as far as myopic progression, vitamin A can certainly help in these ocular manifestations, but just not to slow down the progression of myopia. So that concludes my talk. I really appreciate you all attending and joining in. And I’m happy to answer any questions you may have. Thank you. >> Thank you, Dr. Srinivas. There are six questions so far, if you want to start going through those.

DR SRINIVAS: Sure. So how long is the vitamin A supplementation — what is the dose of vitamin A? So we just followed World Health Organization recommendations for prescribing vitamin A. As far as their duration of vitamin A… It really depends on what their levels are. So I would recommend just getting a follow-up vitamin A level on the patients. And certainly if it’s back to the normal levels, then you can certainly cut back on the dosage. But also keep in mind the conditions that the patient is diagnosed with. Sometimes they may have to be on vitamin A supplementation long-term. But also certainly keeping in mind that we don’t want to overdo it. Because we don’t want to cause vitamin A toxicity either. So that was with regards to dosing. So how long do you expect… Again, it really depends on the patient and what they have, as far as their underlying reason for the vitamin A deficiency. And as far as the interval testing, again, it’s a case by case basis. Looking at their systemic history as well, and certainly working with the patient’s nutritionist and pretty much their whole team, just to decide interval and repeating vitamin A testing, as far as when do we expect the vitamin levels to increase after supplementation. So treatment protocol for vitamin A deficiency — again, considering supplements, for sure. Measuring the levels of vitamin A. Again, based on World Health Organization recommendations, and making sure that we’re monitoring that closely with their whole team of doctors, just because it’s important. As an eye specialist, we have to work with our team, to see how long the patient is going to be on vitamin A. And the proper dose and what-not. So I would say work with the team of doctors to kind of give that guidance, as far as how long a patient needs to be on it. So vitamin A — maybe high levels are contraindicated in dry AMD. You have to be careful about smokers, history of smoking, and excessive vitamin A. So certainly some of the dry AMD medications have a dose of vitamin A. But I don’t think vitamin A is contraindicated in dry AMD. I don’t think… I think you would need a vitamin A oral supplement, versus a topical supplement. So as far as treating your patient holistically, you would certainly recommend drops. And plugs. Things like Restasis, other medications, cyclosporine for dry eye, but I don’t know about a topical vitamin A treatment that would resolve the issue. Because it is an underlying vitamin A deficiency. So you may need oral medications in patients with vitamin A deficiency. So I don’t know of any difference in oral versus parenteral prescriptions. Certainly for these three patients, we considered the oral supplementation. But again, it may depend on each case to see if it can be given in other ways, as far as supplementing with vitamin A. So what do we have to monitor in patients on vitamin A supplementation? Certainly getting their vitamin A levels is important. But also treating their ocular signs and symptoms. So again, if there is an infection, antibiotics, or if it’s just severe dry eye, like we saw in one of the cases, maximizing their dry eye treatment would be what is to be monitored on patients who will have been supplemented with vitamin A. So making sure that their ocular signs and symptoms are improving as well. So why was IOP so low in case one? Certainly I don’t think it’s related to the vitamin A deficiency. But certainly that is something that struck us as well. As far as why the IOP was pretty low in case one. So medical consultations with patients with vitamin A deficiency… Again, working with their team of doctors, because you certainly need a nutritionist on board, you need the patient’s primary care doctor, depending on whether they have kidney disease, nephrology, so really working with their team of doctors is advised, as far as medical consultations, for any patient with vitamin A deficiency. As far as how long we should supplement with vitamin A, again, it depends on each case. So working with the team of doctors and making sure that you’re obtaining vitamin A levels, for the recommendations to make sure that they’re not deficient in vitamin A. So certainly, if it comes to the normal levels, working with them to see if you can reduce the supplementation or there’s an underlying medical condition for which they have to be on vitamin A supplementation, working with their team to see how long we should be supplementing the patient with vitamin A. So that’s a good question, about xerophthalmia and fundus. So the cases I presented today didn’t actually have any retinopathy or issues going on in the back surface of the eye. But certainly that’s something to keep a watch for. Because vitamin A deficiency cannot only affect the anterior segment, but also certainly the posterior segment. So that’s a good question. I don’t have an example. Because these patients — fundus looks normal. So I don’t have a picture of the fundus for these patients. So that’s a good question as well, as far as how common is retinopathy due to vitamin A. So again, the cases we saw mostly involved the keratopathy and anterior segment. But certainly with vitamin A deficiency, it is common. And we essentially have to do a good dilated fundus exam. Just to see if the patient is affected both anterior and posterior segments, or just posterior segment, versus anterior segment only. Does vitamin A deficiency cause retinal displacement? Not that I know of. Just retinopathy. But not retinal displacement. How frequently fundus examination should be done? So fundus exam should be done certainly based on the initial exam, because you want to make sure that there are no posterior manifestations of vitamin A deficiency. And certainly depending on other concerns, maybe repeating a dilated fundus exam, based on, again, each case. Would you recommend routine vitamin A supplementation for a patient with ulcerative keratitis, where vitamin A levels are not readily available? Unlikely, because you certainly do not want to have an excess of vitamin A either. So vitamin A supplementation provides certainly very high doses of vitamin A. So I’m not sure if I would just give routine vitamin A supplementation, if you cannot test their levels of vitamin A. As far as vitamin A slowing down the progression of retinitis pigmentosa, again, I’m not sure… As far as the supplement that we need to slow down the progression… But it can certainly… You would work with your retina specialist and also their primary care team to see if it can be given for retinitis pigmentosa. Vitamin A’s role in the improvement of eyesight. You know, certainly if they’re vitamin A deficient and have dry eye or other concerns with vitamin A, vitamin A can reduce vision. Because the keratopathy it causes. So it can certainly improve eyesight. Especially if the etiology of the patient is a vitamin A deficiency. So whether the patient had low IOP from vitamin A deficiency? Unlikely. That’s not one of the known causes of vitamin A deficiency. So I don’t know… I think it may have been something else. But I don’t think the vitamin A deficiency caused the low IOP in that patient. So does vitamin A improve eyesight as a whole? And dry eye? Certainly the vitamin A… Their ocular surface is treated — if they’re vitamin A deficient, providing supplementation can certainly help improve eyesight. And also help improve their signs and symptoms of dry eye. So which group of pregnant mothers should get vitamin A supplementation? So certainly vitamin A is important, as you saw in embryogenesis. But as far as excess, vitamin A supplements… So that can also cause birth defects. I would really be cautious about pregnant mothers getting vitamin A. Unless, of course, they’re deficient. You can certainly supplement them with vitamin A. But if their levels are normal, I wouldn’t recommend any vitamin A supplements. Because recall that even higher levels of vitamin A can cause birth defects and other problems. As far as the link between measles and vitamin A deficiency? I am not too sure about that one. I don’t know if there’s a link between measles and vitamin A deficiency. When will you stop using vitamin A? Again, depends on each case. So if their levels are back up to normal, you would consult with a nutritionist and other members of the medical team to see if you would give just a lower dose. Or if it’s okay just to stop the vitamin A supplementation. So just to summarize: What is the safe dose of vitamin A to take on, on a daily basis? So again, I don’t know if patients who don’t have a deficiency need to take extra vitamin A on a daily basis. So certainly checking the levels of vitamin A, if you suspect a deficiency, can help. But I don’t recommend just taking supplements on a routine basis, if there’s not a deficiency in vitamin A. So I believe we answered that question. How long do you give the supplementation. Again, working with their team of doctors and nutritionists, and certainly measuring their levels, they should be evaluated in terms of how long to give the vitamin A. Any difference between vitamin A derivatives? Again, recall that there are plant and animal sources for vitamin A. So with animal sources, you’re much more likely to get toxicity in vitamin A, versus with the plant — compared with the plant-based diet. So we can get moxifloxacin at the half price of Vigamox. So again, it depends as far as… Ocular surface, what you’re treating them for. So they’re both good medications. But it depends on what you see on their corneas, as far as whether to use moxifloxacin or Vigamox. Again, how long do you need to supplement vitamin A before switching to dietary? All depends on their vitamin A levels. It also depends on their underlying systemic health. So if their underlying systemic health determines that they would be chronically deficient in vitamin A, you would probably need to supplement, before switching to… Instead of a dietary vitamin A supplement. So again, it depends on each case for that. So not sure… Why did we suspect the vitamin A deficiency in this patient? I’m not sure which case you’re talking about. But in all three cases, the patients had underlying systemic health issues. They were pretty weak and thin. AML and chronic kidney disease and other conditions. Nutritional deficiencies, which is why we suspected a vitamin A deficiency. In actually all of the three cases. Oral supplementation — enough if the patient has small intestine removed? Again, I would recommend working with the patient’s medical team to determine if oral supplementation is enough. Or if they would need other measures just to keep their vitamin A levels in check. What is the role of vitamin A eye ointment for dryness? So again, for routine dry eye and blepharitis patients, I would not recommend vitamin A supplementation. But certainly if I’m concerned about… If they have underlying chronic systemic issues, that would alert me to the reason for dryness and blepharitis, because of a vitamin A deficiency, I would certainly get vitamin A levels. But I wouldn’t give it to all of my dry eye patients. And if a child has severe malnutrition with vitamin A deficiency, what is the dose and how many days? So again, working with their medical team certainly helps. It depends on how deficient they are. And what their systemic health includes. To see the dosage and how many days they’re going to be on vitamin A. What objective measures do you use? To evaluate positive vitamin A… You know, again, vitamin A level. Getting a lab. A vitamin A level would be the best objective measure to see if they have supplementation — is improving or whether they have a supplementation failure. So I thank you all again for attending. And thank you, Orbis, for giving me the opportunity to speak today.