 All right. We're going to get started. The first presenter is Maressa LaRochelle, and she's going to be presenting on CMB Retinitis in Myanmar. Good morning. I'll be talking about my recent trip to Myanmar that I went on with Dr. Vaitali to work with HIV patients with CMB Retinitis. So we're in the world as Myanmar. It's a country in Southeast Asia also known as Burma that borders Thailand to the South. This is just a reminder that although there's different ocular pathology we can see in HIV, such as HIV retinopathy, progressive outer retinal necrosis, that CMB Retinitis is really the leading cause of irreversible blindness in patients with AIDS. And if caught early these patients can do quite well. The small photo is a picture taken of active CMB Retinitis with a little blood and retinal whitening, and then the larger photo is 15 years later of the same patient with just a little bit of RPE granularity in that area, but a 2020 eye. In contrast to a patient that was diagnosed too late and had 360 circumferential full thickness retinal necrosis, and despite eventual gans cycle of your implant, barrier laser, silicone oil, sclerobuccal, patients still lost all vision. So what's the situation with AIDS in Myanmar? This is a picture of David Haydn. He was the leader of our trip. He's a uveitis specialist in San Francisco, and he's been going to Myanmar for 10 years. His first trip with him was his 11th trip, specifically to work with the HIV positive population and CMB Retinitis. And back in 2006, you can see the statistics, there were a lot of patients with HIV that were dying without treatment. And we'll get to what task shifting means, but when he originally went, he had the intention of evaluating and treating CMB Retinitis patients himself. And he was paired with a young primary care doctor that took care of HIV patients there with Doctors Without Borders. Her name was Nini Tun, and he was assigned with her to sort of get assistance in clinic in her HIV patients. Well, the first night he was there, she took home his equipment, and it was an indirect ophthalmoscope, a 28-diaper lens, and some dilating drops. And she came back the next day and said, David, I can do it. I can see the retina. And she had dilated her sister and practiced looking and literally learned to see the retina the first day. So she said, let me look with you at the patients you see this week in my clinic. And sure enough, by the end of the week, she was diagnosing CMB Retinitis. And so it gave him the idea, it doesn't need to be ophthalmologist. This is a resource poor country. Doesn't need to be ophthalmologists that are treating CMB Retinitis. Why not train the HIV doctors that provide all the comprehensive care to these patients in indirect ophthalmoscopy and intravagal injection of GANS-like levier. So that's what he started doing about 10 years ago. And so that's what we mean by task shifting, is taking this, what's here, very subspecialized area of ophthalmology and bringing it to the primary care level where they have the resources. So back to why it's important. We know that CMB Retinitis is linked to a higher mortality in AIDS patients. A paper published in 2014 by Dr. Haydn and Dr. Toon with their experience in Myanmar shows that of the 94 patients they evaluated with CMB Retinitis, 28% of these died on an average of three months later. An additional 17% were lost to follow up, most likely because they died. So this number is actually a low estimate of the mortality associated with CMB Retinitis. And these patients aren't dying because they have an infection in their eye. They have a high mortality because they have CMB in their gut, in their lungs, in their CNS. And there's no way to diagnose it in those areas of the body. They don't have whole blood PCR of CMB like we do here. It's much harder to get a biopsy of the gut or the lung compared to looking in the back of the eye. So if no one's looking in the back of the eye and seeing it, they're not getting any treatment for their systemic CMB disease. Like we mentioned, there is a lack of diagnostic capacity, both in laboratory testing and also in availability of ophthalmologists that are doing the fundus exams. So we brought it to sort of the primary care level. And with the idea of training the AIDS clinicians, which there are really primary care physicians straight out of medical residency that just take care of a very high volume of HIV patients and become very good at HIV medicine. And by screening the eye, we increased the diagnosis of CMB, retinitis and disease tenfold. And so Dr. Haydn published in 2014 his successful results of training these HIV doctors in the last several years. And in real life experience, this is a doctor that was trained in 2008 in one of his workshops. And then one year later, he had done 1,000 exams, 500 intraocular injections of gancyclovir, and was treating between two and five cases of CMB retinitis per week. And CMB retinitis has been sort of ignored in the public health spectrum globally for several reasons. Despite being one of the opportunistic infections, and all five of the patients with HIV described in the 1981 CDC report of the beginning of the AIDS epidemic, the WHO guidelines failed to mention CMB retinitis in their Vision 2020 programs and things like that. So CMB retinitis is not on the list of most common causes of preventable blindness. So it gets ignored. Another part of that is cost. So oral valgancyclovir is not listed as one of the essential medicines on the WHO guidelines either, which brings us to the cost. So oral valgancyclovir or systemic valgancyclovir, IV is slightly cheaper but very similar to oral, requires induction phase, which costs over $2,000, followed by daily maintenance for at least three months, with a total cost of over $9,000 US, which is impossible in these countries, in comparison to intravitriolgancyclovir, which is available and costs 57 cents per injection. So that's why training these HIV docs to do intravitriolgancyclovir was feasible from a cost standpoint, even if they're doing them weekly for several months. So talking about our workshop, we went to a government hospital for the first time this year in Yangon, and we trained these eight primary care physicians. Two of them were from that government hospital, and the other six were from NGOs. And the last word along that line is the region they're from in Myanmar. So Kachin State, Dawey, Pago, they're flying in from all over the country to this workshop and then going back to their respective places to practice it. So it's a four-day workshop. I mentioned who we train. We like young, motivated physicians, usually one to three years out of their medical training that are seeing a high volume of HIV patients in their daily clinic. And they're sent for preparation, the curriculum and lectures a month in advance to start preparing. And they each have exclusive use of a battery-operated portable indirect alfamoscope as pictured and a 28-diameter lens and a homemade model of an eye to practice on for the week. In the mornings, we do lectures starting with just basic anatomy, basics on indirect, how to use the model eye, and then progressing as the week goes on into lectures on CMB retinitis and other AIDS-related retinal diagnoses. And then the fourth morning is a written examination that Dr. Videotally and I facilitated. And then each afternoon is where the magic happens. So we have about five to 10 patients with HIV, either with known CMB retinitis or very high risk for CMB retinitis, and we train these doctors bedside, ideally one-on-one, but there's more of them than us. So we sort of rotate through the beds, training them how to look at the eye and then doing drawings, comparing notes. And then I said plus or minus training on intravitural injection technique. And I'll go a little bit into that later. So there's a picture of learning indirect ophthalmoscopy and lining up the light with your thumb. And this is the model eye that Dr. Haydn actually creates. There's a YouTube video on how to make this and there's a little cut out of newspaper in the back of it with words so you can see how everything's flipped upside down and reversed. And this is when they were training on intravitural injections, holding the Q-tip at the angle that the needle should be before they do it with an actual needle. So this is the patients, summary of the patients we saw when we were there in the training part of the workshop. We saw 32 patients and 15 of them had CMB retinitis, four of them were active, and eight out of the 32 patients also had tuberculosis of the coroid, most of them asymptomatic. And then a sort of a smatter of HIV retinopathy, toxo, and interestingly three patients with cryptococcal meningitis. This is Dr. D'Italia and I and some of our students and a patient. And at the end of the course, this is a table of the responses from the trainees. We ask them how confident they are at the end of the course in identifying structures of the eye and most say moderately confident to highly confident as far as identifying these parts of the eye after only four days. And how confident are they in diagnosing the retinal diseases of active CMB, inactive CMB, cotton wool spots, and tuberculosis. And you can see the great majority are moderately confident to highly confident in these skills. I think this is the most important question we ask, is are they ready to start putting this into practice at the end of the week? Would they go on to their own clinic and start evaluating patients? And all eight said yes. This brings us back to the intervitural injections. So oral valgans like Avere is very expensive. And in 2013, the makers of this medicine teamed up with medicine's patent pool to reduce the cost by 90% to help prevent blindness and HIV positive patients. And they made this reduced cost available for 138 countries, including Myanmar. So now the systemic treatment was available, but like we mentioned, there's no diagnostic capacity of when do these patients need CMB treatment if no one's looking in the back of the eye. So the Monday that we were there in that workshop was the first day that the government hospital in Myanmar was ever used oral valgans like Avere on a patient's because we were there and we looked in the eye and we said this patient needs it. And so despite having access to it for several years, it was the first time they had the diagnostic capacity to put it into action. So that was actually really exciting. So we didn't train the doctors this year in intervitural injection, partly because oral valgans like Avere was available, and partly because we were at a government hospital and there's some political stuff going on about whether the government says it's okay that a non-optimologist is doing intervitural injections. So we didn't want to anger anyone in the hospital management and so we didn't train them this year. This is a picture actually pulled off of Facebook of some of the trainees at the end of their workshop. They were very proud of their certificates we gave them. They were like hashtag, I can see the retina, so we're excited. This is a separate project that's going on there. So there is a retina specialist in Yangon that has agreed to do barrier laser on inactive CMB retinitis patients that we pull together in order to prevent retinal detachment. He's been doing it for several years of the patients we send him. So when we were there, we evaluated 13 of these patients that had had barrier laser. And you can see by the vision that a lot of these patients are sort of end stage CMB retinitis. We evaluated two eyes that did have retinal detachment, but it was not an eye that had received the barrier laser prophylaxis. So our hypothesis is that doing the barrier laser prevents retinal detachment in some of these patients. So we have about 50 patients total and we're putting together the data to hopefully publish it as a means of preventing retinal detachment in resource poor settings. And so sometimes you go looking for one thing and find another. We did see a lot of CMB retinitis. But we also, as mentioned, saw eight patients with coroidal tuberculosis. And these patients often have no eye complaints. You just look in the back of the eye and you see these smooth, hypopigmented, deep coroidal lesions that are round and usually in the posterior pole. And we saw quite a bit of these. But this isn't something new. The text from 1892 reminds us of the importance of looking at the eye grounds for coroidal tubercles. And I'm just going to finish with an interesting case of a 35-year-old man we saw that was being treated with HIV. By the way, the HIV patients present their CD4 counts in like the teens or single digits like uniformly across the board. And 90% of them have tuberculosis with it. So this patient had been treated for TB and was HIV positive and complained about severe headaches. The month prior had an LT who was diagnosed with Cryptococcal meningitis. And the classic eye-finding Cryptococcal meningitis is fluorid papillodema. But this patient had no eye complaints, 20-20 vision. But we were interested in seeing the back of the eyes of these patients. So we looked and found these creamy, placoid, corioretinal lesions in the posterior pole of both eyes. And this is a very rarely described manifestation of ocular Cryptococcal. There's several, like, a handful of case reports in the literature, but that's about it. So a pretty interesting case. Thank you to all the support. And that's the beautiful pagoda in Yangon. Any questions? So, Marissa, the fabulous presentation and you bring up the big issue that's so often common in these situations, and that is that the perfect is the enemy to the good. And that often the perfect is the enemy to the good. And often countries for political reasons would hold off on a solution that maybe is 90, 95% effective because they want the perfect. Or in particular the politics of those that have trained saying, no, no, no, I have to do it even though there is not a chance that they can take care of the burden. And so it's a common problem that goes along, but very innovative. One question for you is that if you treat just with intraocular, obviously one of the issues you raised is that when you diagnose this, an HIV that is likely a systemic disease, and obviously if you do just an intraocular treatment, you're not going to be treating a systemic compound. So it would seem to me that that would be the problem if we were just doing intraocular injections. Am I missing something? No, that's exactly right. It does not prevent spread or involvement of the fellow eye when you're treating an intraocular with just one eye and you're not treating a systemic disease that's related to the high mortality. So it's in an unperfect solution and that's a little bit of the alphabet dilemma with it. But it's better than nothing. Again, that's right. You're going to maintain vision and I'm glad they brought it. I bet you a burden, even at 90% discount, there's still a thousand bucks for a lot of these developing worlds that's still a major burden. So many of you may not know for sure, but we're really excited and Marissa's joining the faculty here as of July and she's going to be a tremendous addition and we really appreciate her incredible work and thank you very much for this great effort here in Myanmar. Very good. How many of you have done so? You've used a lot of numbers. The government? So they're each from individual NGOs that were listed there and now it's been 10 years of doing this. Their NGOs are providing them for each individual doctor. From the beginning, David Heighten brought it up. Heighten brought it up. Heighten brought it up. Heighten brought it up. Heighten brought it up. Heighten brought it up. Heighten brought it up. Heighten brought it up. Heighten brought it up. Heighten brought it up. Heighten brought it up. At the beginning, David Heighten brought one and donated it and he brought it himself and then SAVA Foundation was sort of the overlying charity from San Francisco that was covering things that weren't covered from other NGOs locally. So they sort of provided some of the indirects as well.