 So, and thank you for that presentation, it was really good, really good to learn from, so. Our next presenter is Martin, he's actually a student here at, oh, okay, so Michael's going to go next. So, leaving order. So, Michael Ellis is going to present next to us. He is visiting us, he's working with Dr. Linney, he's visiting from University of Kansas School of Medicine, and he's going to be talking about conjunctival intraepithelial neoplasia. Thanks, Michael. Alright, so as Dr. Stagg mentioned, my name is Michael Ellis, I appreciate the opportunity to present today, and I'll be presenting on the topic of conjunctival intraepithelial neoplasia. So, just to give some background before we go into a case, it's the most common conjunctival malignancy in the United States, and it's common referred under the umbrella term, ocular surface squamous neoplasia in the literature. When you think about it, think back to your pathology, you think back to the full thickness epithelial involvement without penetration into the basement membrane, and subsequently the substantia propria, and that would be conjunctival intraepithelial neoplasia. So, common symptoms that patients present with redness, foreign body sensation, and even mild irritation, but up to 30% of patients can actually be asymptomatic. So, the case that I was involved with, with Dr. Lin, she was consulted by an outside plastic surgeon for a 35-year-old female with a precancerous lesion on the conjunctiva, confirmed to be conjunctival intraepithelial neoplasia through biopsy. From the patient's history, the patient was born blind, had juvenile cataracts, aniridia, nystagmus, and several anterior segment abnormalities. Now, at the time of the chart review, a genetic syndrome had not been identified, but through literature review, it is possible that this could be a PAC-6 mutation, which PAC-6 has been implicated in ocular development, and that will come into play as I discuss risk factors, and then also a prior oral CT had showed optic nerve coloboma, shallow orbits, and some proptosis, but no other masses. So, what are some other diagnostic options besides your biopsy? So, biopsy is the gold standard, but it also puts the patient at sometimes an unnecessary risk if you're wrong. And so, cytology is a relatively non-invasive method that's been described since the 50s. So, impression cytology can be useful by the use of cellulose acetate filter paper or by or poor membrane device, and there's been a published correlation rate with histology of 77 to 80%. There's also something called the Barrow's method of doing the impression cytology, and that can have a sensitivity up to 95%. Other diagnostic options that are available include high-resolution anterior segment ultrasound, microscopy, and OCT. So, risk factors. So, one of the most common risk factors would be exposure to ultraviolet B-light. HPV has been implicated, AIDS. A genetic predisposition deserved herma pigmentosa, and kind of playing into that failure delay in DNA repair. So, that PAC-6 mutation that I suspect has been implicated with other DNA mutations. And so, perhaps there is a component in our patient of that. So, chronic irritation, heavy smoking, and exposure to petroleum products have also been implicated. So, an exam. Our patient is no light perception on the right, unfortunately, and only light perception on the left eye. We're unable to examine the pupils. And some nystagmus has been noted with the extractomuscles, which is also a feature of the PAC-6 mutation. On an external exam, she had lagathomos in both eyes and telecampus. So, most notably on her slit-lamp exam, she had 2-plus injection inferior with a regular papillomonous-elevated lesion inferior extending temporally, approximately 15 millimeters horizontally going down into the fornix. The lesion also encroached upon the cornea, approximately 2 millimeters, with associated neovascularization. And you can also note the associated congenital abnormalities, such as the coloboma and the juvenile cataract. So, this is a picture in the public domain of conjunctival and trapezoidal neoplasia. I wanted to show a picture of something that had been diagnosed before treatment. I have a picture of our patient and subsequent slides. So, can anybody comment on differential diagnosis of, if you see something like this in the clinic, what you're likely to think? That's great. Thank you. So, here's just a list of some of the things that I came up with as well. So, Dr. Swan just gave us a great summary of some of the things to be thinking about. When you think about papilloma, conjunctival and trapezoidal neoplasia, the invasive squamous cell carcinoma, the conjunctiva, pretty difficult to differentiate those two just by looking at it, would probably require biopsy or prescient cytology to get the correct diagnosis. But here's a list of some other ones. And you mentioned lymphoma, and then also I read that coposi-sarcoma could be something that could be considered in this case as well. Here's just, here's a picture of a teridium and a nevus, which has also been noted to be in the differential, and then episcleritis. So, what do we do for our patients? So, the patient treatment, we recommend a top go-in-referring on one million units per milliliter four times daily for at least three months. So, because our patient had lag of almost in that irritation, we also recommend continuing the artificial tears four times a day. And the patient had been previously put on Neomycin polymixin, and we recommend that she continue that. So, I'd just like to discuss a few of the treatment options. This is kind of a landmark study by Taven and others in 1997, which pointed out a 33% recurrence rate with just excision alone, even if the margins were cleared, a 56% recurrence rate for incompletely excised lesions. So, the most common position for these lesions to develop is on the limbus, specifically in the nasal portion of the eye. And so, they house the corneal stem cells, and that can lead to stem cell deficiency. Also, cryotherapy and brachytherapy have been reported in the literature, but have been associated with negative side effects such as symblephron, iridus, corneal edema, ectropion, contractival, telengic tasia, sclerol, ulceration, among others. So, the other, as you look through the literature, they really, most papers lump together contractival, intripetheal, neoplasia with the dysplasia and squamous cell carcinoma under that umbrella term, ocular surface squamous, neoplasia. So, there has been no head-to-head studies comparing mitomycin C5 flora urusil and recombinant interferon, but a review article in 2013 by Nanji and others found that the comparison through the literature interferon alpha 2B has been found to have the least side effects while maintaining comparable rates of resolution and recurrence, with the only downside of price. So, when I looked up the price of this drug, it's about $800 for 3.2 milliliters. So, another, just another study illustrating the effectiveness of topical interferon. There was an association of people living in areas like the coast with higher UV levels that resulted in slower clinical resolution rates. And an association was found between the size of the lesion at that third month and treatment duration. So, other things that have been tried, topical babycesimab, there's been a couple of different studies looking at that, but no level one, level two evidence. So, I've just listed a couple case series up here. So, a study by Oskine and others looked at 10 eyes using 25 milligrams per milliliter, babycesimab for a mean of 7.8 weeks. And most notably, all patients ended up going, undergoing subsequent excisional biopsy, cryotherapy, and amnion membrane transplantation. But no recurrences were noted for six months after surgery and no significant local or systemic side effects were noted. As well as another study, a June 2015 publication by Oskine and others found a mean reduction in tumor area of 43% in one month and 68% in two months with also no systemic or visual side effects. So, there's also been reports of injecting babycesimab and that has shown some efficacy as well, but it also puts our patients at risk of side effects from the injection. And there's also been studies looking at sub-conjunctival ranibizimab, but has only been effective with multiple injections. So, just some patient follow-up. She's improved on the topical interferon for the two months, but she still has significant conjunctivocalases and it may require excision within the next few months. Her eye is becoming more red according to the family in association with that lag off the almost, noted on exam. So, here's a picture from the clinic on the day that I saw the patient and if you can make it out, like you can see in the inferior and limble areas that there is that lesion there extending superior temporally. So, follow-up, she remains on the interferon drops four times daily, and she had just finished the neomycin polymixin ointment, so we decided to restart maxisural ointment at night, artificial tears five times daily, and return to clinic in one month to reevaluate the need for surgery. There are my references, and thank you, Dr. Lin, for your help. I can't comment on why the plastic surgeon specifically started the antibiotics, but the patient does have lag off the almost and had the redness and irritation, and so I suspect that's why. Yeah, the literature that I read suggested that it is indeed effective. However, 100% of patients do have the side effects of my algaes and fevers, and they're rather unfavorable, so that's why they recommended more of, like, the topical.