Introduction to Special Issue on Ocular Pathology and Drug Development.

Dysfunction of the visual system remains a leading cause of human disability worldwide. Preclinical studies are a key component of efforts to develop drugs and devices to ameliorate visual impairment. Although new opportunities for the delivery of targeted ocular therapeutics have been created, clinical success has been confounded by unique challenges of drug development for the eye. This Special Issue brings together a broad range of articles that augment our current understanding of the visual system and highlight methods for assessing ocular toxicity and some of the current challenges in ocular drug development. Topics addressed include the anatomy, developmental anatomy, and/or immunobiology of the visual system and associated lymphoid tissues; animal models; methods for assessing ocular toxicity; spontaneous background and procedure-related microscopic findings and common artifacts in histologic sections of ocular tissues; and novel ocular drug delivery systems.

Ketamine/Xylazine Anesthesia-Related Corneal Lesions in Rats With Surgically Implanted Venous Catheters Utilized in Nonclinical Intravenous Studies.

Nonclinical rodent studies with repeat slow intravenous dosing, such as safety assessments of anticancer therapeutics, often require the use of animals with surgically implanted catheters. Catheterization is a relatively short surgical procedure but requires use of anesthesia. Ketamine/xylazine injectable anesthesia is typically used because it has advantages over inhalation anesthesia including ease of administration, safety and predictability of effects, and relatively low cost. However, ketamine/xylazine anesthesia in rodents can also be associated with the development of undesirable corneal lesions of uncertain mechanism such as mineralization of Bowman's membrane or stroma, erosion/ulceration, inflammation, fibroplasia, and neovascularization. Such findings have the potential to confound study interpretation in programs for which the cornea is a potential target tissue. This case report describes the occurrence of ketamine/xylazine-related corneal lesions observed in surgically catheterized rats in a 16-day toxicity study for an oncology compound.