Histopathology and Image Validation of Outer Retinal Tubulations in Age-Related Macular Degeneration
Advisory Committee Chair
Christine A Curcio
Advisory Committee Members
Scott W Ballinger
Cynthia Owsley
Lawrence C Sincich
Yuhua Zhang
Document Type
Dissertation
Date of Award
2016
Degree Name by School
Doctor of Philosophy (PhD) School of Optometry
Abstract
High-resolution imaging of the retina using spectral domain optical coherence tomography (SD-OCT) and adaptive optics scanning laser ophthalmoscopy (AOSLO) is revealing new information about photoreceptor degeneration in age-related macular degeneration (AMD) and other diseases impacting rod and cone photoreceptors. By SD-OCT, the hyperreflective outer retinal bands are visible due to the precise vertical compartmentalization and horizontal alignment of outer retinal cells and tissues (Müller cells, photoreceptors, RPE, and Bruch’s membrane). Validating these bands with normal eyes is difficult because the outer retina is very delicate making accurate histology requiring attached retina and vertically aligned photoreceptors challenging. Conversely, the bands are prominently perturbed in outer retinal tubulation (ORT). Histology is available to help interpret these perturbations. By SD-OCT, ORT, a neurodegeneration found in advanced AMD and some inherited retinal diseases, is identified as a hyperreflective border with a hyporeflective lumen located in the outer nuclear layer. By histology, ORT is a formation of degenerating cones pointing into a lumen encircled by the external limiting membrane (ELM), formed with Müller cells. This dissertation explores (1) the ultrastructure of inner segment (IS) mitochondria in degenerating cones in and outside ORT, including a clinicopathologic correlation between SD-OCT and histology of ORT demonstrating mitochondria as the organelle present in shrinking cone IS, and contributing along with the ELM to the hyperreflective ORT band, (2) ORT morphology in SD-OCT volumes and a human donor flatmount, including quantification of surviving cones in ORT and intensity of the hyperreflective ORT band, and (3) if degenerating cones in ORT have waveguide properties. Using SD-OCT of B-scan and en face images and histology of eyes with AMD, ORT was found to vary in complexity and shape. ORT quantifications of reflectivity features and surviving cones suggest distortion of cone mosaic in AMD. AOSLO imaging of ORT in subjects with AMD, revealed lack of ORT cone reflectivity, loss of waveguiding properties, and abnormal directionality. Whereas, SD-OCT imaging revealed reflective ORT cones that may depend partly on mitochondria as light scatterers within degenerating cone IS. These data support the Ellipsoid Zone nomenclature, and improves the interpretation of ophthalmic imaging of retinal diseases.
Recommended Citation
Litts, Katie M., "Histopathology and Image Validation of Outer Retinal Tubulations in Age-Related Macular Degeneration" (2016). All ETDs from UAB. 2307.
https://digitalcommons.library.uab.edu/etd-collection/2307
