Assessment of Outer Retinal Remodeling in the Hibernating 13-Lined Ground Squirrel.

Purpose: We examined outer retinal remodeling of the euthermic and torpid cone-dominant 13-lined ground squirrel (13-LGS) retina using optical coherence tomography (OCT) imaging and histology. Methods: Retinas and corneas of living 13-LGSs were imaged during euthermic and torpid physiological states using OCT. Retinal layer thickness was measured at the visual streak from registered and averaged vertical B-scans. Following OCT, some retinas were collected immediately for postmortem histologic comparison using light microscopy, immunofluorescence, or transmission electron microscopy. Results: Compared to OCT images from euthermic retinae, OCT images of torpid retinae revealed significantly thicker inner and outer nuclear layers, as well as increases in the distances between outer retinal reflectivity bands 1 and 2, and bands 3 and 4. A significant decrease in the distance between bands 2 and 3 also was seen, alongside significant thinning of the choriocapillaris and choroid. OCT image quality was reduced in torpid eyes, partly due to significant thickening of the corneal stroma during this state. Conclusions: The torpid retina of the hibernating 13-LGS undergoes structural changes that can be detected by OCT imaging. Comparisons between in vivo OCT and ex vivo histomorphometry may offer insight to the origin of hyperreflective OCT bands within the outer retina of the cone-dominant 13-LGS.

Optical coherence tomography for assessment of microbicide safety in a small animal model.

Sensitive imaging techniques for small animals are needed to assess drug toxicity in preclinical studies. Optical coherence tomography (OCT) provides a noninvasive tool for high-resolution, depth-resolved visualization of drug-induced changes in tissue morphology. In a mouse model, we utilize OCT to assess vaginal tissue integrity following the application of topical microbicides (drugs used to prevent infection). Mice are challenged with herpes simplex virus-2 (HSV-2) to determine the correlation of tissue damage as quantified by OCT to increased susceptibility. The microbicide benzalkonium chloride (BZK) (0.02, 0.2, or 2%) or phosphate buffered saline control is administered intravaginally. In vivo OCT imaging and collection of tissue samples are performed after treatment. A quantitative OCT scoring system is applied to assess epithelial damage, and the results are compared with those of histology. A separate group of mice are treated similarly then challenged with HSV-2. Epithelial morphology quantified noninvasively by OCT and histology are dose-dependent (p<0.0001). The OCT scoring system detected a significant increase in epithelial damage with increasing BZK concentration (p<0.0001). These results paralleled an increase in HSV-2 susceptibility (p<0.005). OCT can be used as a noninvasive tool to assess topical drug toxicity in a small animal model with potential to predict increased susceptibility to vaginal infection.

Application of optical coherence tomography for monitoring changes in cervicovaginal epithelial morphology in macaques: potential for assessment of microbicide safety.

OBJECTIVES: Safety is a primary concern in the development of topical microbicides. Optical coherence tomography (OCT), a high-resolution, in-depth cross-sectional imaging modality, was utilized in conjunction with colposcopy to assess induced cervicovaginal epithelial changes that may predict product safety. STUDY DESIGN: OCT and colposcopic images of macaque vaginal and cervical tissues were obtained in excised tissue and in vivo under various conditions, including mechanical injury and nonoxynol-9 treatment. RESULTS: A scoring system was developed to categorize and quantify the OCT images based on morphologic features that indicate the presence or absence of an intact epithelial layer and inflammation. Using 3 categories (normal, mild to moderately abnormal, and severely abnormal), differences between healthy and injured tissue were apparent on OCT images. Normal images (category 1) had a bilayered structure representative of the epithelium and submucosa. Mild to moderately abnormal images (category 2) had areas of normal and abnormal epithelium. Severely abnormal images (category 3) had complete loss of the epithelium and/or inflammation, with loss of the bilayered structure on OCT. CONCLUSIONS: OCT is a noninvasive imaging modality complementary to colposcopy. It distinguished between normal and abnormal (or injured) tissue and thus holds promise for safety evaluations of candidate microbicides and other vaginal products.