Outer Retinal Tubulation (ORT) in Age-Related Macular Degeneration (AMD): Optical Coherence Tomographic (OCT) Findings Correlate with Histology

Abstract

 

Purpose

 

To correlate OCT and histologic findings of ORT secondary to advanced AMD in living patients and post-mortem specimens.

 

Methods

 

High-resolution OCT raster scans of 43 eyes (33 patients) manifesting ORT secondary to advanced AMD were correlated with histologic studies of post-mortem specimens. High-resolution sections through the fovea and superior perifovea of donor eyes preserved ≤4 hours of death (12 atrophic AMD and 40 neovascular AMD) were examined by light microscopy.

 

Results

 

ORT seen on OCT correlated with the histologic finding of tubular structures comprised largely of cones lacking outer segments and, in some cases, lacking inner segments, leaving a luminal border delimited by the external limiting membrane (ELM). ORT was observed in both open and closed configurations that were typically easily distinguished from cysts and photoreceptor islands on both OCT and histologically. Histology showed that the hyper-reflective luminal material seen on OCT represents retinal pigment epithelium (RPE) and non-RPE cells trapped within the ORT structure. ORT histologic findings correlated with OCT findings in regard to composition, location, shape, and different stages in ORT formation, for ORT with luminal cross-sectional diameter ≥ 31 µm on OCT.

 

Conclusions

 

Histologic correlation gives a better understanding of ORT formation and composition. ORT is comprised primarily of cone and Müller cells. The defining feature of ORT on OCT is a hyper-reflective line that appears to represent the ellipsoid zone, as the outer segments and inner segment / outer segment junction are infrequently observed in these structures. The occurrence of ORT bordered solely by ELM without inner segment ellipsoids (“ELM-only-ORT”) challenges OCT interpretation in the differentiation of ORT from cysts.

 

 

Figure 1 shows cross-sections through a large, ovoid outer retinal tubulation (ORT) in an AMD eye. Top image (histologic cross section) illustrates cones lining the ORT lumen, with inner segments pointing into the lumen and some preserved outer segments. Blue line below the cone nuclei represents the external limiting membrane (ELM). Bottom image (Spectralis OCT cross section) shows hyper-reflective material attached to the upper part of the hyper-reflective border (ellipsoid line), as well as intra-luminal free floating hyper-reflective material.

 

Keywords: 550 imaging/image analysis: clinical • 688 retina • 412 age-related macular degeneration