APPLICATION SUMMARY This is a K08 Mentored Clinician Scientist Research Career Development Award application for Bryce Chiang, MD PhD. Upon completion of ophthalmology residency, Dr. Chiang will be hired as an Assistant Professor of Ophthalmology at the Byers Eye Institute at Stanford. The purpose of this application is to provide Dr. Chiang with the needed training, mentorship, and support to become an investigator with expertise in ocular drug delivery, specifically to the optic nerve head. A clinical glaucoma fellowship will be completed during the 25% clinical time through the timeline of the K08 award. Dr. Chiang has assembled a mentorship team consisting of Dr. Jeffrey Goldberg, an expert on optic nerve neuro-protection and neuro- regeneration; and Dr. Mark Prausntiz, an expert in ocular drug delivery. In addition, he has identified key collaborators including Dr. Uday Kompella, an expert in ocular drug delivery; Dr. Joyce Liao, an expert in optic nerve diseases and animal models; Dr. Jonathan Lin, an ocular pathologist; Dr. Vinit Mahajan, a vitreoretinal surgeon. Optic neuropathy is a class of devastating vision threatening diseases that affect the optic nerve. There are no methods to selectively deliver therapeutics to the optic nerve head, and targeted delivery could improve outcomes due to physiologic spatiotemporal cues and/or selective targeting of injured tissue. The proposed technique is to access the optic nerve head by a SupraChoroidal-to-Optic-NErve (SCONE) injection. The central hypothesis is that the SCONE injection technique can be used to selectively target optic nerve head, and that therapies delivered with this method will be more efficacious compared with intravitreal or intraorbital optic nerve injections. The hypothesis of Aim 1 is that SCONE injection can be further optimized, and the technique will not impact the optic nerve head tissue functionally or structurally. The hypothesis of Aim 2 is that SCONE injection will be more localized to optic nerve head than intravitreal or intraorbital optic nerve injections. The hypothesis of Aim 3 is that Ciliary NeuroTrophic Factor (CNTF) delivered to the optic nerve head–either as free protein, or in a sustained release polymer, or transducing local cells with AAV–will bring greater neuroprotection and regeneration than intravitreal or intraorbital injections after optic nerve injury. The research may lead to improved delivery techniques to the optic nerve head, and will form the basis of an R01 application before the end of the K award.