Purpose: To compare optical coherence tomography (OCT) and histology of outer retinal tubulation (ORT) secondary to advanced age-related macular degeneration in patients and in postmortem specimens, with particular attention to the basis of the hyperreflective 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 age-related macular degeneration were compared to high-resolution histologic sections through the fovea and superior perifovea of donor eyes (13 atrophic age-related macular degeneration and 40 neovascular age-related macular degeneration) preserved ≤4 hours after death.
Results: Outer retinal tubulation seen on OCT correlated with histologic findings of tubular structures consisted largely of cones lacking outer segments and lacking inner segments. Four phases of cone degeneration were histologically distinguishable in ORT lumenal walls, nascent, mature, degenerate, and end stage (inner segments and outer segments, inner segments only, no inner segments, and no photoreceptors and only Müller cells forming external limiting membrane, respectively). Mitochondria, which are normally long and bundled within inner segment ellipsoids, were small and scattered within shrunken inner segments and cell bodies of surviving cones. A lumenal border was delimited by an external limiting membrane. Outer retinal tubulation observed in closed and open configurations was distinguishable from cysts and photoreceptor islands on both OCT and histology. Hyperreflective lumenal material seen on OCT represents trapped retinal pigment epithelium and nonretinal pigment epithelium cells.
Conclusion: The defining OCT features of ORT are location in the outer nuclear layer, a hyperreflective band differentiating it from cysts, and retinal pigment epithelium that is either dysmorphic or absent. Histologic and OCT findings of outer retinal tubulation corresponded in regard to composition, location, shape, and stages of formation. The reflectivity of ORT lumenal walls on OCT apparently does not require an outer segment or an inner/outer segment junction, indicating an independent reflectivity source, possibly mitochondria, in the inner segments.