 Charles Calvo in his presentation. Good morning. My name is Charles Calvo. Thank you for having me here. I wanted to share with you this morning an interesting case that I had the opportunity of encountering while working with a retina specialist in Reno, Nevada. And my presentation is titled The Reactivation of a Latent B virus, presenting us bilateral uveitis, vasculitis, and necrotizing herpetic retinitis. So the patient, he was a 41-year-old gentleman who presented with a decreased division and pain in his left eye. That began three weeks earlier. His past medical history was significant for being one of only 23 known survivors of a B virus infection. And this infection is a zoonotic infection that he contracted from a macaw monkey bite in 1981. He was 18 years old and he was working in a Charles River animal laboratory in the southeast. And he was bit by a macaw and he developed meningitis and encephalitis in which he subsequently recovered without any other neurological deficits. So I want to talk about the B virus just to get everyone up to speed on this rare virus. So it's an alpha herpes virus family and it's endemic among macaw monkeys. And unfortunately, it has a particularly high prevalence in the laboratory populations of these animals. So this virus is analogous to the herpes simplex virus 1 and 2 in humans. So in the macaw, it causes stomatitis, conjunctivitis, and genital lesions. But in humans, it's a devastating infection. The B virus and the herpes simplex virus also share morphologic and immunologic characteristics. There's some cross-reactivity of antibodies and a bit of history. It's called B virus because there was a physician named Dr. William Brevner who was studying poliomyelitis with Albert Saban. And he was bit. He ended up dying from that infection. And Albert Saban isolated the virus from his body and named it the herpes B virus after him. So this infection is quite devastating. It results in ascending cephalomyelitis that has a mortality rate of 80% in untreated individuals. And these individuals can present with fever, weakness, conjunctivitis, diplopia, nystagmus, and cranial nerve palsies. And that will present within five to 21 days from the exposure. And most of these patients will perish within six weeks of that infection. So fortunately though, this is a very rare infection. There have only been 50 identified cases since 1959. But 27 of them have resulted in death. And the transmission has been through macabites as we said with the patient I'm presenting. Scratches from the animal exposure to the monkey tissues or fluid. And there's actually been one human to human case where a husband had vesicles of B virus infection on his hand. His wife then applied hydrocortisone cream on the vesicles and then she applied it to herself for contact dermatitis and she ended up coming down with the infection as well. So we were able to do rental photography in this patient. And this is his left eye upon presentation, the visual acuity. His right eye was 2015, 2016 his left eye. And there you can see that there's pallor of the optic disc as well as diffuse vitritus present. Late phase fluorescein angiography was performed and you see there's hyper fluorescence of the optic disc as well as some leakage of the fluorescein along the inferior vascular trunk. In the temporal periphery of the left eye we noted that there was a coriorentinal scar that was present. And so from this this was the evidence that we had that the primary infection in 1981 did involve the left eye at least because there was a previous scar there. Again the left eye you see there's a retinal lesion, a retinal lesion nasally, well vitritus. And here's the right eye at the time of presentation, the visual acuity in that right eye was 2015 and the right eye was uninvolved at this time. So because of the findings on the examination and the imaging as well as his very significant past medical history, the patient was admitted to the hospital in a hospital in Reno, Nevada under infectious disease consultation and the patient began IV Gantt-Cyclovir. As well as the IV therapy he began several rounds of intravitural Gantt-Cyclovir injections. So we contacted the National B-Virus Center which is the headquarters of the study of this virus and it's in Atlanta, Georgia. And fortunately the B-Virus National B-Virus Center was already very well familiar with this patient. They had been monitoring the patient since his initial infection in 1981 and they had been following his serology about every year since that time. So we were able to have a lot of great information about this patient. So they recommended that vitreous samples be taken from the left eye as well as serum samples and so we sent it to Atlanta, Georgia for PCR and for serology. So the results of the PCR confirmed the presence of B-Virus so we came to the diagnosis that there was B-Virus infection. We did a serial vitreous samples that showed that there was decreasing viral load upon the Gantt-Cyclovir therapy. The serology as it was earlier was positive for IgG to the various B-Virus glycoproteins. And from this information and our discussions with the B-Virus Center to our knowledge this case was the first documented case of B-Virus latency and reactivation in a human. So this is an antibody profile graph that we were able to make and this shows data from 1991 to 2009. And the relationships between the different antibodies to the various glycoproteins B through G2, it's not well understood at this point the relationship between an active or chronic infection and how that relates to the serology. But from what the virologists know so far is that the GM and the G2 best correlate with an active infection. And so you can see right here there's a very sharp, very sharp spike and the red line corresponds with that sharp light blue line there. And that reflects this reactivation in the left eye. But what I'd like you to note is you see there's other spikes over the years that this patient has had but he's never had clinical manifestations of the infection until this time. So it's really poorly understood but we think that there's a lot of cross-reactivity between herpes simplex and B-Virus that gives these confusing antibody profiles. So the patient's left eye was starting to resolve and unfortunately the right eye became symptomatic. The patient had began having decreased vision in the right eye as well as pain. And this was during the time that he was now receiving just PO, Gantt-Cyclovir therapy. So you see that his visual acuity of 2015 quickly became 2030. And you see numerous white retinal lesions nasally in this patient. This early phase, forcing angiography one week after the right eye reactivation. You see the arterial and venous filling as well as a hemorrhage present just outside of the macula. Late phase angiography at the same time you see the hyperfluorescence of the optic disc and dilated and sheathed vessels present. So I wanted to show this profile to you again so if you see the initial spike right there of the GM and the G2 glycoprotein, you see a small real sharp spike right after it and that correlates with the reactivation in the right eye. So as I said, during the time of the right eye activation, he was already on antiviral therapy for the left eye. And so we put the patient back on IV Gantt-Cyclovir, intravitural injections of the Gantt-Cyclovir, and then also received a few rounds of Foscarinet. The right eye became much worse than the left eye was. The patient's vision proceeded to become about 20, 200. Vitriol traction was noted on exam in the right eye. And so the arenas specialist decided to give the patient prophylactic laser demarcation to prevent impending detachment. And so the progression of the infection was worse in the right eye as well. You could see that there was some iatrogenic inflammation, trauma from the laser. So the right eye was 2200, went about 20 or 400 at that time. Fortunately though, the patient did have a fairly good recovery. The right eye did develop a cataract that was removed. But vision in the left eye returned to 2020. But vision in the right eye was only able to return to 2050 after this infection. So I want to share with you just some of the recommendations from the National B-Virus Center and the CDC on B-Virus infection. And it depends on if it's just prophylaxis or if you're actually treating the infection, if there's a CNS symptoms present or not. So with our patient with the symptoms in the eye, we began with, again, cyclovir. So there's different modalities of antiviral therapy. So just in summary, this case demonstrates that B-Virus is capable of latency and reactivation in human hosts. And this reactivation can present only with ocular disease. And the 80% mortality rate in the untreated individuals has now become about almost 80% survival in people that are treated promptly with antiviral therapy. So there may be more of these patients presenting. And so in conclusion, if you have a patient that has exposure to primates, maybe works in a biology lab or something and they present with an ophthalmic complaint, B-Virus is something that should be on the differential. Any questions? Well, how similar this is to the acute retinal necrosis? I believe that it is very similar in appearance. You saw that there were some like inclusions in the retinal lesions. And it progressed from the periphery as you saw and it was moving more towards the middle of the fundus. So I believe that there is similarities of it. If the PCR was very helpful in distinguishing if this was a herpetic, necrotizing herpetic infection from simplex versus B-Virus. So that's how we were able to come to that conclusion. But as far as the famacyclovir, yeah, I know that in the literature it is shown that that has been used. But I think that these recommendations in part are in place because a lot of the bioavailability of the different antivirals compared to another, like that's why acyclovir is viewed as an alternative compared to main state of therapy. Just how frequent the patient needs to have it, the side effect profile and the bioavailability of those different antivirals. No, they were not an implant, they were just injections. Any other questions? Alright, thank you.