 Thanks Kevin. Can everyone hear me all right? Okay. So first of all, I'm going to present a case that I saw a two-year-old with Lukakoria. So first of all, about where I'm from, last year in Fargo, we had the privilege of hosting ESPN College Game Day. That was this nice September fall day. There's North Dakota and it's glory. So if you're thinking of visiting, come earlier than rather than later. Yeah. Yeah. So without further ado, let's get to why I'm talking. So first of all, the patient we saw was a two-year-old male for giving him a name. We'll go with AJ. That was not his initials. First of all, his chief complaint why we saw him. He had a normal pupae reflex. His father noted that for about two weeks prior to coming into seeing the pediatrician, he noticed kind of a whitish glint in the pupae reflex while camping. So of note, past medical history for this two-year-old boy, he had a normal birth history. He was a full-term boy with no complications at birth. He was on normal weights. Family history was negative for vision loss of young age, vision loss for glaucoma or any other causes. And he did not have a past ocular history or nor was he on any medications or have any pertinent or any allergies of no. So Dr. Hoffman saw our patient, AJ, at the request of pediatrician. So on exam, the visual acuity on covering of the right eye, the child was quite temperamental and did not like their occlusion. On exam of the pupils, no APD was noted. Extraocular motility was full bilaterally. The red reflex was diminished on the left compared to the right. The alignment was orthophoric. The anterior segment exam was within normal limits. And the dilated fundus exam on the right eye, there was a normal posterior pole. And left, there were just noted to be vitreous opacities and a large raised white lesion in the periphery superiorly, and possibly nasally. So at this point, first of all, what would you think may be going on in this patient? And from a broader perspective, what are some of the things you should be thinking about in a patient who presents with local cordia med students, residents attending, jump on it. We've got a few out there, so don't be shy. Good. Thinking more broadly beyond what may seem likely to be presenting in this case, any other causes you might want to that may be confused with retinoblastoma. So the next slide have lists. We talked about retinoblastoma, Coates disease, cataract, other things could be ROP. That would seem to be less likely in our patient. As you have normal birth weight, full term, child fever, ocular toxicoriasis, PHPV, and even a coloboma. So that's by no means an exhaustive list. But as we get going, it will be quite obvious what we're going on. So Dr. Ramasubramanian performed an exam under anesthesia after having the patient referred to her from Dr. Hoffman. IOP was 14 in the right eye, 12 in the left, retinoscopy, plus one right eye. Plano in the left, anterior segment, again, was within normal limits bilaterally. Of note, there was no cataract, iris atrophy, or neovascularization of the iris. Funnest exam, I was within normal limits. And per Dr. Subramanian, there was a large nasal retinoblastoma measuring 14 by 14 by 9 millimeters with surrounding subretinal fluid and extensive vitreous seeds. And a left eye ultrasound was performed as well, showing a large nasal retina tumor with multiple vitreous seeds with a maximal thickness of 8.5 millimeters. So here's the red cam imaging. Does anyone want to kind of jump in and take a stab at what you see? And as you were saying, you can kind of see some of the spots here. It's easier from my vantage point, but in the lower left, you can see probably between the 12 and one o'clock position about a little more than halfway up the fundus. You can see kind of white spots. And that was what Dr. Subramanian was calling the vitreous seeding. So if you haven't seen that. Okay, so Dr. Subramanian is assessment and plan. First of all, she said it was consistent with the unilateral lateral retinoblastoma of the group E classification of the ICRB. They're 5, A, B, C, D, and E, with E being the most severe and having the worst prognosis. So for a plan, treatment options were discussed with the parents of the child and E nucleation was decided upon. It was also discussed that there would be a future need for systemic chemotherapy if high risk features were present, path, histopathologically. And I'll get to that in just a second here. And follow up to be, to include MRI twice yearly until five years of age to rule out intracranial tumor. And genetic testing and family screening were also going to be performed. Of note, there was a nine month old sibling who was going to be tested and to follow up with oncology regularly as well. So here's a couple, two slides of the tumor that I saw with Dr. Mamos on pathology readouts where I actually became involved with the case. So on the left, you can see the tumor part of it. You can see the vitreous seeding that initially started out as an exophitic mass and then becoming an endophitic mass. And you can see how it's bulging prominently anteriorly and consistent with what we saw in the rec-cam imaging. And you can also see down here, these kind of, excuse me, you can see these purple, within the optic nerve you can see these, these basophilic cells which are invading, so the tumor has invaded the optic nerve, but on closer, on a higher magnification you can see that the tumor again has invaded the nerve, but it is pre-laminar, it has not invaded the laminar crevosa, so that would be a better prognostic factor. So as part of the histology and ruling out if a tumor is high risk and would need systemic chemotherapy, you look at the anterior chamber and from the image on the left you can see a small spot that's basophilic and on the right you can see that image magnified with a few cells there. But per Dr. Mamos the tumor was moderately well differentiated, retinoblastoma with flexionary, Wittner-Steiner-Rosetz, seemed to be exophitic initially and had become endophitic, so of note for the high risk state to see if there was a need for systemic chemotherapy, no coronal invasion was noted, the trabecular mesh work was free of tumor, there was pre-laminar invasion of the optic nerve, however the distal nerve beyond the laminar crevosa was free of tumor and it was thought that the anterior chamber cells were probably a spillover and not necessarily a true infiltration, they were only seen on one slice of one slide and so the decision was made not to give adjuvant chemotherapy. So in going through the case I was curious about some of the treatment options, what had been discussed with Dr. Hoffman and Dr. Subramanian and parents, enucleation was the decided treatment, also other treatment included systemic chemotherapy, also known as chemo-reduction, typically with the vincristin and topocytin and carboplatin agents, this is typically has much more, many more systemic side effects and so other modalities are being investigated on but chemo-reduction still is, it's probably the most well studied and most used modality, external beam radiation is more used in the past, this one is associated with radiation exposure and secondary to that, potential tumors as well even within the orbit, for a retinoblastoma that wouldn't be as advanced, typically like an ICRB class grade A, you'd think about more focal local therapies, cryotherapy, laser therapy, thermotherapy, plaque reo therapy and of the last two I'll talk a little bit more about the inter arterial chemotherapy, it's a newer modality, it involves the injection of chemo-therapeutic agents directly into the optic nerve via cannulation of the femoral artery up into the ophthalmic artery and that's typically using melphalan, it was developed in the past by the 1950s and more recently Dr. Abramson in New York has been studying this as well as a group at Will's Eye and inter vitro chemotherapy can be used as well, so here's just an image, kind of a radiologic image showing the cannulation of the ophthalmic artery on the left, you can see the catheter tip just approaching the ophthalmic artery and on the right you can see the tip and then the perfusion of the orbit in the eye, so previously before, the study of the intravitual melphalan by the Shields Group in Philadelphia, they did a study using the inter arterial chemotherapy on 16 eyes, there was a subset of patients who had both solid tumor and either sub retinal seeds or vitreous seeds and so I wanted to look into that being that our patient had these vitreous seeds and so despite IAC treatment there were two patients of the nine that had the vitreous seeds that either had partial response or recurrence and so this is kind of a follow up study to that saying well is intravitual melphalan can't be used as a further treatment, so in this study 11 eyes of 11 patients with either viable persistent or recurrent vitreous seeds after initial treatment with either IV chemotherapy or chemo reduction or the IAC were given intravitual melphalan at the dosage of 20 to 30 micrograms with concurrent triple freeze cryotherapy to limit the prevention of meds or even cryoidal expansion of the tumor with the therapy and they found complete seed resolution after a mean of two injections, the range between one to six injections and by a mean of nine months with a range of six to 16 months followed complete vitreous seed regression with no recurrence was seen in all 11 cases and global salvagers noted to be 100 percent. So the six patients that were followed for nine months or longer from first injection no recurrence was observed, in the study they noted that there were no major complications of vitreous hemorrhage, infection, retinal hemorrhage or retinal detachment and however they did note some minor complications including focal RP modeling near the injection site in two eyes and non-axial posterior lens opacity. Other studies have reported more serious side effects but based on the study of the small sample size that was reported. So that concludes my case presentation on a two year old patient with retinoblastoma treated with a nucleation. Questions, thoughts, discussion? Thank you.