Outer Retinal Tubulation in Advanced Age-Related Macular Degeneration

Abstract

Purpose To compare optical coherence tomography (OCT) and histology of outer retinal tubulation (ORT) secondary to advanced age-related macular degeneration (AMD) in patients and in post-mortem specimens, with particular attention to the basis of the hyper-reflective border of ORT. Method A private referral practice (imaging) and an academic research laboratory (histology) collaborated on two retrospective case series. High-resolution OCT raster scans of 43 eyes (34 patients) manifesting ORT secondary to advanced AMD were compared to high-resolution histological sections through the fovea and superior perifovea of donor eyes (13 atrophic AMD and 40 neovascular AMD) preserved ≤4 hours after death. Results ORT seen on OCT corresponded to histologic findings of tubular structures comprised largely of cones lacking outer segments (OS) and lacking inner segments (IS). Four phases of cone degeneration were histologically distinguishable in ORT lumenal walls, nascent, mature, degenerate, and end-stage (IS and OS; IS only; no IS; no photoreceptors and only Müller cells forming external limiting membrane, ELM, respectively). Mitochondria, which are normally long and bundled within IS ellipsoids, were small and scattered within shrunken IS and cell bodies of surviving cones. A lumenal border was delimited by an ELM. ORT observed in closed and open configurations were distinguishable from cysts and photoreceptor islands on both OCT and histology. Hyper-reflective lumenal material seen on OCT represents trapped retinal pigment epithelium (RPE) and non-RPE cells. Conclusions The defining OCT features of ORT are location in the outer nuclear layer (ONL), a hyper-reflective band differentiating it from cysts, and RPE that is either dysmorphic or absent. ORT histologic and OCT findings corresponded in regard to composition, location, shape, and stages of formation. The reflectivity of ORT lumenal walls on OCT apparently does not require an OS or an IS/OS junction, indicating an independent reflectivity source, possibly mitochondria, in the IS.

Optical Coherence Tomography Angiography in Choroideremia

“…14 The RPE loss exceeded the EZ loss in nearly all eyes, and ORTs consistently extended beyond the margins of preserved RPE. In more advanced cases, as measured by ERG response, ORTs were more numerous and longer.…”

“…In the en face perspective, the ORT is characterized by an outer hyporeflective band that originates with photoreceptor cell nuclei, adjacent to a hyperreflective line that likely originates with the external limiting membrane and inwardly migrating inner segment mitochondria. 14 …”

Exploring Photoreceptor Reflectivity Through Multimodal Imaging of Outer Retinal Tubulation in Advanced Age-Related Macular Degeneration

“…The relative contributions of scattering and waveguiding in photoreceptors can be tested with outer retinal tubulation (ORT), a neurodegeneration and gliosis commonly found in macula of advanced AMD 22–26 and some inherited retinal diseases. 22,27–29 ORT contains degenerating long- and middle-wavelength-sensitive cones 30 pointing into a lumen encircled by the ELM, which is formed with Müller cells.…”

“…22,27–29 ORT contains degenerating long- and middle-wavelength-sensitive cones 30 pointing into a lumen encircled by the ELM, which is formed with Müller cells. 26,31 ORT cones degenerate by OS loss, IS shrinkage, and mitochondrial fission and migration within the IS, leaving an ELM circle lacking photoreceptors at the end-stage. 26,32 On SD-OCT B-scan, ORT is identified as a hyperreflective circular or ovoid profile with a hyporeflective lumen, located in the outer nuclear layer.…”

Prevalence of outer retinal tubulation in eyes with choroidal neovascularization

“…Recent clinicopathological findings showed that the ORT reflective border represents the mitochondria within degenerated inner segments (IS) translocated internally to the external limiting membrane (ELM), without the presence of outer segments [15, 16]. …”