 We're going to go ahead and get started with Grand Rounds today, it's eight o'clock, my name is Russell Swann, I'm moderating today. So we have two medical students that we'll be presenting today. The first one is Tyson Olson. Tyson's visiting us from the University of Rochester. Now he's no stranger here. He grew up in South Jordan, went to undergrad at BYU, and today he'll be presenting on orbital-facial neurofibromatosis and vision loss. Who worked with Dr. Dries for the first two weeks and now he's working with Dr. Tye? Thanks. First of all, I'd like to thank everyone for being here and for allowing me to speak at Grand Rounds. And like Russell said, I'll be talking today about orbital-facial neurofibromatosis and specifically the causes of vision loss in this disease. And so I'm going to start out with a case of a patient who was co-managed by both Dr. Patel and Dr. Dries. He was referred from pediatric genetics for neurofibromatosis type 1 as well as some upper left eyelid swelling. And at that time he was a six-month-old boy. His mother reported that since birth he had had excessive tearing, redness, and rubbing of his left eye. He was born at 36 weeks via cesarean section. Other than neurofibromatosis type 1, he had no other medical problems and he had no previous surgeries. His mother did have neurofibromatosis type 1 and his social history, he lived at home with his mother and his father. On examination, his pupils were equal and reactive and he didn't have any afferent pupillary defect. And his visual acuity, he was able to fix with his right eye so it was noticed that his left eye was able to fix but was doing less so than his right eye. He had full ductions and versions, his cornea lens, optic nerve and fundus were unremarkable. And on external exam he had left proptosis, left upper lid ptosis and his corneal reflex lid margin distance on the left was 0.5 millimeters compared to 3 millimeters on the right with the soft tissue mass over the medial aspect of his brow and his forehead area. And on cycloplegic refraction, his right eye had a plus 1 sphere and he had 2.75 diopters of astigmatism on the left eye. You can see here this was when he presented, when he was 6 months old. You can see his brow hair is raised and he has the ptosis on the left and it's kind of taking an S shape which is characteristic of this disease as the neurofibroma is often affect the lateral aspect of the upper lid. You can see some facial fullness here as well as well as some down turning of the lateral part of his lips here on the left side as well. And MRI did reveal an extensive plexiform neurofibroma that had orbital and cavernous sinus as well as skull base and facial involvement as well as some component of sphenoid wing dysplasia and there was no features of optic pathway gliomas at that time. A visual evoked potential was performed that showed poor wavelengths on the left eye and his clinical course was the following. He was given glasses to correct his astigmatic anisomatropia. At 9 months he underwent left external levator resection and left anterior orbitotomy and reduction of the orbital tumor. And 6 months post-op you can see here his visual evoked potential significantly improved on the left eye. He did continue to have progressive myopia and astigmatic anisomatropia with his lateral fraction coming in at negative 5.50 plus 3 at 85. And at age 3 he had to undergo another surgery to debulk the neurofibroma further. And this is a picture of him after his first surgery. So you can see some improvement, well some progression of his ptosis laterally taking on more of an S-shape but still keeping away from the visual axis. So neurofibromatosis type 1 is an autosomal dominant disorder characterized by a mutation in the NF1 gene on chromosome 17 and it has an incidence of about 1 in 2600 to 1 in 3000 individuals with about 50% of those cases being de novo mutations which actually increase with increasing paternal age. The pathogenesis is the following. You have RAS here which is active in many signaling pathways in the cellular growth and proliferation cycle including MAP kinase pathway as well as mTOR. And in order to inactivate RAS neurofibroma activates a GTPase which dephosphorylates RAS leading to inactivation of RAS. And so without NF1 you get continued activation of RAS leading to unchecked growth and proliferation of cells especially in neural tissues. Diagnostic criteria is a clinical criteria to diagnose neurofibromatosis. You need two or more of the following which include six or more cafeolet spots, two or more neurofibromas or one plexiform neurofibroma as well as freckling and axillary or inguinal regions, optic gliomas, and two iris hamartomas or a first degree relative with NF1 or bony lesions such as sphenoid dysplasia. The ocular manifestations include least nodules which are hamartomas of the iris pigment epithelium as well as optic pathway gliomas which are present in about 15 to 20% of patients. These are usually asymptomatic and histologically benign although when symptomatic they can cause painless visual loss, proptosis, extrabismus and nystagmus. The visual loss depends on where these tumors are growing in the optic pathway anywhere from causing scatomas to heminoxias. Orbital facial neurofibromatosis has actually been kind of thought as a separate entity or a unique variant of NF1 and estimates say that it occurs in 1 to 22% of patients with NF1. It's characterized by neurofibromas that cause progressive disfiguring tumors of the orbit of the face. Interestingly, it's most commonly unilateral. Neurofibromas tend to favor the upper eyelid, brow and temporal region and they have a higher growth rate than neurofibromas elsewhere in the body and undergo aggressive growth especially early in childhood that tends to improve with age. These tumors cause significant functional and cosmetic effects as well. Some of the sequelae of orbital facial neurofibromatosis in the eyes are globe enlargement especially if the tumor involves the orbit. This leads to myopia which can lead to posterior staphylomas or myopic macular changes. Patients with orbital facial neurofibromatosis are also at risk for glaucoma. They get bony changes of the skull and orbit like sphenoid bone dysplasia like our patient had as well as S-shaped ptosis, proptosis and especially pulsatile proptosis if they do have dysplasia of the sphenoid bone and occasionally strabismus as well. This top strip of patients are three separate patients and you can just see the difference in severity of orbital facial neurofibromatosis from slight ptosis here to more significant S-shaped ptosis causing occlusion of the visual axis to involvement of the entire left face causing significant cosmetic and functional disability in this patient. This patient here is shown here 18 months and 24 months. You can see the rapid progression of his ptosis in that six month period. Interestingly here, you see that he's kind of taken on a left face turn in order to keep his visual axis clear on the left eye. This is an MRI showing sphenoid bone dysplasia here on the CT scan with an orbital tumor as well as a cavernous sinus tumor with proptosis and globe enlargement. The recent study looked at 55 patients with orbital facial neurofibromatosis to determine the cause of visual loss in these patients and out of these 55 patients 39 of them or 71% had significant visual loss on the affected side less than 20 over 60 had a mean visual acuity of 20 over 400 on that side. The most common cause for visual loss in this group of patients was amblyopia either from refractive air or from deprivation from the ptosis. Other causes included glaucoma, optic pathway gliomas, optic atrophy, retinal detachments as well as astigmatism. You can see from this study that these patients really do have significant visual loss on the side and early intervention is necessary to prevent visual loss in these patients. So in summary, orbital facial neurofibromatosis is a rapidly progressive disease that causes significant morbidity and mortality both functionally and cosmetically. A multidisciplinary approach is necessary to treat these patients including a pediatric ophthalmologist surgeon. Children less than 5 require frequent examinations both to monitor progression of tumor size changes in refractive air as well as screen for glaucoma. The visual loss in this disease is usually multifactorial with amblyopia due to refractive air and deprivation being the most common. And although glasses are difficult to wear due to the facial tumors it is necessary to make every attempt possible to provide adequate optical correction in these patients in order to prevent amblyopia. And also despite the rapid growth and recurrence of the tumors in young children early brow tosis repair may be necessary to keep the pupillary axis clear and prevent deprivational amblyopia as well. These are my references. And I'd like to thank Dr. Dries for allowing me to work in his clinic over the last few weeks as well as Dr. Patel for allowing me to use the pictures of the patient in this case. And as well as Alicia Doxin for making my rotation here at Moran possible. And thank all of you for allowing me to speak today as well. So one thing to remember in taking care of a fair number of these in my career is that because of the autosomal nature specifically Thanks. Thank you.