Background: Glaucoma is a chronic ocular disease of both dogs and humans that results in blindness and ocular discomfort. Most commonly, end-stage glaucomatous eyes in dogs are enucleated to provide comfort. This intervention requires significant financial investment, general anesthesia, and has a psychological impact on some owners. Retrobulbar neurolytic injections are used in humans to provide immediate and long-acting pain relief, while simultaneously preserving the globe. Objectives: To determine the safety and efficacy of retrobulbar neurolytic ethanol injection in canine eyes with end-stage glaucoma. Animals: 16 client-owned dogs (19 eyes) diagnosed with end-stage glaucoma. Methods: All eyes underwent an ophthalmic examination, including Schirmer Tear Testing (STT), intraocular pressure (IOP) measurement, corneal touch threshold (CTT), anterior and posterior segment examination, and fluorescein staining. Subjects were sedated and administered a retrobulbar block with bupivacaine, followed by retrobulbar injection of ethanol or saline solution. At specified time points after the procedure, clients assessed their pet's comfort and side effects of the injections via survey. Subjects returned for enucleation. Owner perceived comfort after the enucleation was assessed at identical post-procedure time points and compared to that achieved with retrobulbar ethanol injection or control solution. Overall client satisfaction with each procedure, as well as the effects of retrobulbar ethanol injection on STT, IOP, CTT, and histological changes in retrobulbar tissues were investigated. Results: Retrobulbar neurolytic ethanol injections did not signficiantly improve owner perceived comfort compared to control group treatment or provide more comfort than enucleation. Retrobulbar ethanol injections did not signficantly lower IOP, but did significantly elevate CTT. There was a trend towards lower STT in eyes receiving retrobulbar ethanol injections. Retrobulbar ethanol injections were safe, well tolerated, and no differences in client satisfaction with particpation in the study were noted in either injection group. Histologically, globes in the treatment group displayed significantly greater inflammation and fibrosis; retrobublar tissue samples were not significantly different between control and treatment groups with regard to inflammation or fibrosis. Conclusions and Clinical Importance: Retrobulbar neurolytic ethanol injections were not determined to be an effective globe-sparing alternative treatment to provide analgesia for end-stage canine glaucoma. Enucleation remains an effective way to provide comfort to dogs with elevated IOP. / Master of Science / The glaucomas represent a diverse group of blinding and painful diseases associated with elevated intraocular pressure (IOP). Despite advances in the medical and surgical treatment of glaucoma, the long-term prognosis in dogs remains dismal for IOP control, comfort, and globe retention. Blindness and pain are common long-term outcomes, necessitating surgical salvage procedures aimed at restoring patient comfort, including enucleation (eye removal), intrascleral prosthesis, or intravitreal chemical cyclodestruction. The most commonly performed, effective, and predictable of these options is enucleation, but this requires general anesthesia, a considerable financial investment, risks post-surgical complications, and has a negative psychological impact on some owners. Retrobulbar neurolytic injections with absolute ethanol have been performed in humans with blind, painful eyes since the early 1900s. Immediate and long lasting pain relief can be achieved from 2 weeks to 2 years after a single injection. The purpose of this study is to determine the safety and efficacy of retrobulbar ethanol injections as a globe-sparing therapeutic option for end-stage glaucoma in dogs. Nineteen dogs presenting to the VTH ophthalmology service with end-stage glaucoma were enrolled in a prospective, randomized, double-masked clinical trial. Subjects were sedated and administered a retrobulbar injection of ethanol (n=9) or control saline solution (n=10). At specified time points after the procedure, clients assessed their pet’s comfort and side effects of the injections via survey. Three weeks later, subjects returned for enucleation and the level of comfort after the enucleation was assessed at identical post-procedure time points and compared to that achieved with retrobulbar ethanol injection or control solution. Retrobulbar neurolytic ethanol injections did not significantly improve comfort compared to control group sham treatment or provide more comfort than enucleation. Retrobulbar ethanol injections did not significantly lower IOP, but did significantly elevate corneal touch threshold in treated patients. There was a trend towards lower tear production in eyes receiving retrobulbar ethanol injections. Retrobulbar ethanol injections were safe, well tolerated, and no differences in client satisfaction with participation in the study were noted in either injection group. Further investigation is warranted to determine the optimal volume of retrobulbar ethanol to provide analgesia for patients with end-stage glaucoma as well as to determine the duration of clinical effect of these injections.