Correlation of Optical Coherence Tomography and Retinal Histology in Normal and Pro23His Retinal Degeneration Pig

Abstract

PurposeWe correlate optical coherence tomography (OCT) retinal layer thickness measurements with histology in wild-type and retinal degenerative pigs.MethodsOCT scans were obtained using the Bioptigen Envisu R2200. In normal pigs, three eyes were imaged in vivo, and three eyes were imaged after enucleation. In the Pro23His retinal degeneration pigs (P23H), one eye was imaged in vivo and four eyes were imaged after enucleation. All eyes were fixed in 4% paraformaldehyde and processed for histology. Corresponding retinal locations on OCT and histology were identified using anatomic landmarks (optic nerve, retinal vessels, visual streak). Individual retinal layer thicknesses were measured by two independent, masked graders, and intraclass correlation coefficients were used to determine agreement. OCT and histologic retinal thickness measurements were averaged and compared.ResultsOCT and histologic measurements correlated highly in normal and diseased eyes (R2 = 0.91 and 0.92, respectively), and scans performed in vivo and ex vivo did not differ significantly. Despite good overall correlation, certain individual retinal layers (e.g., retinal nerve fiber layer [NFL], inner [INL] and outer [ONL] nuclear layers) appeared thicker on OCT compared to histology, while other layers (e.g., retinal pigment epithelium) appeared thinner. No statistically significant difference was found between OCT and histology for any retinal layer thickness measurement.ConclusionsRetinal layer thickness measurements correlate well with histology in pig eyes, but differences in individual retinal layers may be seen.Translational RelevanceOCT may be used in pigs to measure retinal thicknesses with good overall correlation to histologic measurements.

Noninvasive Imaging and Correlative Histology of Cone Photoreceptor Structure in the Pig Retina

“…Our results demonstrate their potential for sequential assessment of normal and TgP23H pig retinal structure in vivo. OCT images of the pig retina have been previously published by several groups,20,21,55,56 and our observations and interpretation of the outer retinal hyperreflective bands differ. These previous studies typically identify three hyperreflective outer retinal bands, whereas our images clearly show that five bands exist in the WT pig.…”

“…In contrast to our approach, one study removed the anterior segment of the eye prior to OCT imaging 20. The image resolution in a second study was insufficient to distinguish either sets of doublets,21 and it is noted that some of their OCTs occurred ex vivo. Indeed, when we attempted to image the retina both pre- and immediately post euthanasia, resolution declined as we also could not resolve the doublets (data not shown).…”

“…This widespread use as a preclinical model makes noninvasive ocular imaging increasingly important in order to observe disease progression16 and therapeutic safety and efficacy in vivo 17–19. While optical coherence tomography (OCT)20,21 and scanning light ophthalmoscopy (SLO) are valuable tools that have been applied to study the gross anatomy of the pig retina, the use of pigs in gene and cell therapy creates a pressing need for cellular resolution, noninvasive imaging.…”

Long distance retrograde degeneration of the retino-geniculo-cortical pathway in homonymous hemianopia

“…To assess changes in retinal thickness over time, we performed spectral-domain optical coherence tomography (OCT) (Cirrus HD-OCT model, Carl Zeiss Meditec, Dublin, CA, USA). Because age-related OCT thinning is relatively modest, at 1 µm of GCC or 2 µm of RNFL every decade [24, 25], the changes we measure over time likely reflected changes corresponding to the homonymous visual field defect. We performed the Macular Cube 512 x 128 and the Optic Disc 200 x 200 scans per manufacturer’s instructions.…”

“…Advances in optical coherence tomography (OCT) means that we now have a reliable in vivo method of measuring long-distance, retrograde degeneration of the visual pathway in humans at point-of-care locations such as the eye clinic [22, 23]. Commercial spectral-domain OCT machines provide resolution of 3-5 microns, which allow for quantification of individual retinal layers comparable to that of retinal histology [24, 25]. Advances in OCT segmentation means we can routinely segment the thickness of the layer containing retinal ganglion cells (ganglion cell layer or GCC) and the thickness of the layer containing unmyelinated retinal ganglion cell axons (retinal nerve fiber layer or RNFL).…”