 Next we have Chris Baer. He's here from the University of U.S.A. and he's going to talk about the optical manifestations of Zika virus. Well, good morning. Like Renee said, my name is Chris Baer. I'm one of the fourth year medical students here at the University of Utah. I'm really excited to be able to talk with you this morning about a topic that I think is very interesting and also very timely. We're going to spend the next few minutes discussing the ocular manifestations of Zika virus and the purpose of this talk is really two-fold. First, we're going to spend a few minutes just talking about some basic background information about Zika virus. I think as health professionals it's important that we have a baseline working knowledge about this condition because if you haven't gotten questions about Zika already, chances are you're going to get them in the future. Unfortunately, Zika virus is not going away anytime soon and it's likely going to become an even bigger issue as people travel down to Brazil for the Olympics coming up here. So we're going to spend a few minutes just talking about some background information there. Next, and we're going to spend the majority of our time is discussing the ocular manifestations of Zika virus and that's where we'll spend the majority of our time here. So, a little bit of background. Zika is a member of the Flavivirus family which also includes pathogens such as dengue fever, West Nile virus and chikungunya. It's transmitted primarily by the 80s mosquito and you can see that bug here and this is a map of its presence here in the United States. You can see that it doesn't have a really large presence here in Utah but throughout the rest of the southern United States it's got a pretty wide area that it covers. While mosquito transmission is the most prevalent form of transmission it can also be transmitted importantly from mother to fetus and utero and it can also be transmitted sexually and that includes both from men and from women. This slide is just to show kind of the timeline of what we know about Zika virus. The first case was reported in 1952 and then we had a period of almost 60 years where it was really pretty quiet. We didn't hear much about Zika and then in 2007 we had our first outbreak. In 2013 we had a second outbreak and now in 2015 we have an outbreak here in Brazil that we all know about and I've put this up here just to show that there's something different about this strain of Zika virus. Why would we have a period of relative quiet for the past 60 years and then within the past 10 years we've had three major outbreaks here. There's a lot of interesting theories about why that is and it's a little bit beyond the scope of what we're going to talk about today but it's something to keep in the back of your mind. What's different about this particular strain of Zika virus? When people present with symptoms of Zika virus, most of the time there won't actually be any symptoms. 80% of people with Zika will be asymptomatic and when they do present with symptoms, most of the time they're going to be very nonspecific symptoms, specifically from an ophthalmology standpoint. The most common symptom that we see is a nonpareil and conjunctivitis. It tends to be self-limited. Now the symptom in infants is beginning to most press lately, is microcephaly and in Brazil, since the start of the sound break, their rates of microcephaly have actually increased over 20 fulums. So it's a big deal and that's why it's been getting a lot of press here. To diagnose Zika virus, the test that was used for a long time was a PCR test and now we also have the ability to do ELISA testing with IgM antibodies. So that's a real quick kind of background on just some basics about Zika virus. Now we're going to get to the point that we want to talk about is the ocular manifestation of Zika virus and we've had a couple outbreaks like we said in 2007 and 2013 and the only ocular manifestations that we really saw in those outbreaks was that nonpareil and self-limited conjunctivitis. But over the last about six months, there's been a lot of new information that's come out about new ocular findings in Zika virus and so I want to take you through and kind of run you through the timeline of the research that's been done over the past six months to show you kind of the evolution of our knowledge of these ocular findings as we go along. So in January of this year, a group led by Dr. Ventura published the very first paper about ocular findings in infants and so this is a small case series, three infants with microcephaly who were born to women with presumed Zika virus infection. Now remember that term presumed Zika virus infection, we're going to come back to it in a minute. What they found in this study was that all the infants had cerebral calcifications which you'll see is a recurring theme in infants who were affected with Zika virus. All of them had unilateral macular pigment modeling and loss of their foveal reflex and one infant in particular had pretty severe macular neuroretinal atrophy which you can see on this image right here. Now limitations of this study, obviously it's a very small sample size, three patients and this phrase presumed Zika virus infection is something I want to just highlight for a moment. This is a weakness of a lot of these early studies that we're going to talk about. At this time the only way to diagnose Zika virus was through that PCR test and that PCR test was really only useful during the acute phase of symptoms so during the first week or so of women who had symptoms. Now obviously these women who had symptoms during their pregnancy and now we're looking at them after delivery, it wouldn't make a lot of sense to test them at this time and so what the Ministry of Health in Brazil decided was to diagnose a woman with Zika virus in pregnancy they had to meet a couple of different clinical criteria. One, they had to have symptoms of Zika virus during pregnancy which these women had. Number two, they had to have other viral causes, other congenital infections ruled out so that includes things like toxoplasmosis, HIV, rubella and a few others and so that's a limitation of some of these earlier studies that we're basing our determinations on clinical findings rather than through serology. In February Dr. Ventura's group again published a slightly larger case series of this time 10 infants with microcephaly and all of these infants had ocular pathology. In this study 70% of these mothers had Zika-like symptoms during pregnancy and again they met that clinical criteria with a negative serology for some of these other congenital infections. Now this is a fairly busy table just kind of delineating the ocular manifestations that they saw there. I've broken it down for us here a little bit easier to see so there were 17 total affected eyes and they broke them down into two basic big findings. There were optic nerve abnormalities that they saw and in this top picture you can see a really nice example of optic nerve hypoplasia with a nice double ring sign right there as well as they also noticed optic nerve pallor and an increase in the cup to disc ratio. They also found several macular abnormalities. Again we talked about loss of the foveal reflex, pigment modeling and then coriorentinal atrophy and this bottom picture really shows I think a nice example of that pigment modeling found in one of these infant's eyes. That same month a separate group independently published a study that was very similar and had very similar results. This is a slightly larger study, 29 microcephalic infants, 10 of whom had ocular findings and interestingly the same percentage, about 70% of mothers had symptoms of Zika virus during their pregnancy. This is a table again of the findings and again we see very similar results. So pigment modeling, coriorentinal atrophy and optic nerve abnormalities are by far the most common abnormalities we see in these affected infants. And again, here are some pictures that really just kind of highlight some of the findings that we see here in this top picture. We have an enlarged cup to disc ratio bilaterally along with some pigment modeling and a coriorentinal atrophy there on the left and then on the bottom picture we see again coriorentinal scarring there as well as optic nerve abnormalities in these infants. Now in May Dr. Ventura's group published what I think is a very important study. This is a study that was the first time that serology was able to be used to definitively prove that Zika virus was in these infants. So what they did is they had 40 infants with microcephaly, 22 of these infants had ocular pathology. Now during the course of their testing this IgM ELISA testing became available and so they were able to test 24 of the 40 infants with this IgM ELISA testing and very importantly all of them. So 100% of these infants tested positive for Zika virus which I think is an important clue that Zika virus was present and the way that we did it before with symptomatology actually bore out the results here in serology that all of them were positive. Now this study looked at risk factors for developing ocular pathology in Zika virus infection. I want to highlight just a couple things. So first they found that the size of the baby's head so head circumference was a significant factor so those infants with smaller head circumferences had a significantly increased risk for developing ocular pathology. Now interestingly I thought axial length really wasn't a significant factor and maturity of the baby so whether they were born preterm, post-term or on time didn't have a significant impact either. Now while timing of delivery wasn't important timing of symptoms was and they found that women who had symptoms in the first trimester were statistically significantly at an increased risk for having a baby born with ocular pathology. And so this answered a couple important questions here. Number one, by confirming diagnosis with serology and number two, delineating the timing of symptoms that was important. Now there was still one I think big question that remains to be unanswered here and that's this. If you remember back in all these studies all of the infants that we've looked at were microcephalic and microcephaly, independent of anything else is associated with ocular pathology not dissimilar to what we've seen here before. And so the question becomes do these infants have these ocular findings because of Zika virus infection or are these ocular findings due to microcephaly that's induced secondary to Zika virus infection? It's a subtle distinction but I think it's an important one. And so just last month, Dr. Ventura's group again published this case report of a normal cephalic infant who had this core retinal lesion right here that we've seen I think in previous slides and this infant tested positive for Zika virus by RLISA testing. And so this is again one case report. It's not anything conclusive but it does provide some bit of evidence that infants who are normal cephalic can in fact present with these lesions due to Zika virus and maybe suggest that Zika virus itself is responsible for these lesions and not microcephaly that's secondarily induced. So I want to end with this particular case report here. This was published just very recently and I think this highlights an important point. Now this patient here presented with symptoms of Zika virus that we're concerning and he tested positive for Zika virus by both PCR and IgM. Now we said before that in all the case reports and all the literature that we have on Zika virus, we've had these two outbreaks in 2007 and 2013, the only findings that we saw in Zika virus were conjunctivitis. But this patient presented here positive for Zika virus and ended up developing uveitis and an anterior chamber pericentesis was done and aqueous humor tested positive for Zika virus. It may not project very well here but this picture here is trying to show that there's KP's present as well as inflammatory cells present in the anterior chamber kind of highlighting that picture of uveitis. This patient's visual acuity worsened slightly. He was treated with Ciprodex and ended up recovering very well according to the case report he's doing quite nicely. But I think this highlights an important point. This strain of Zika virus that we're dealing with right now is presumably different than what we've seen in the past. And so we're going to see symptoms that are different than what we've seen in the past. And so the chances that we see a case of Zika virus is admittedly very low but it's not out of the realm of possibility. And so if someone comes in with concerning symptoms, a suspicious travel history, Zika should be in the back of our mind and should remain on our differential for two important reasons. One, it helps us to treat the patient the best way possible. But number two, because we know that Zika virus is a sexually transmitted virus as well, if we identify these patients who are at risk, we can hopefully prevent pregnancies that are affected by a congenital infection as well. And so there's a lot of questions still remaining to be answered and I think the research is still evolving. You can see this is all over the past six months but it's kind of been exciting to see how things have evolved and how things have progressed and how much our knowledge has gained over just the past six months. So there's a lot to cover here in a short time. I really appreciate your attention and I'm happy to take any questions that you all may have.