Volumetric and En Face Hyper-Reflective Henle Fiber Layer in Age-Related Macular Degeneration

To analyze Henle fiber layer (HFL) hyper-reflectivity in age-related macular degeneration (AMD) with en face optical coherence tomography (OCT).

A total of 279 eyes affected by AMD were imaged with either an Optovue Avanti or Optovue Solix device. Imaging was conducted within a 3 × 3-mm area centered on the foveal avascular zone. Hyper-reflective HFL (hr-HFL) regions were segmented by binarizing en face OCT images generated by projecting a slab 45 to 65 µm below the inner nuclear layer and outer plexiform layer boundary. Pathological changes, including drusen, subretinal fluid, pigment epithelial detachments (PEDs), macular neovascularization (MNV), and geographic atrophy (GA) were semi-automatically segmented. We investigated the association of these features with the hr-HFL by measuring the overlap ratios, defined as the proportion of hr-HFL area overlapping with the pathological regions after projection onto the same plane.

Hyper-reflective HFL regions were distinguished by distinct patterns in AMD eyes. It consistently colocalized with drusen, subretinal fluid, PEDs, MNV, and GA. Quantitatively, hr-HFL area was significantly larger in AMD eyes compared to healthy controls (P < 0.001) but did not differ across AMD severity stages. The hr-HFL area correlated with the size of pathologic features (r = 0.64-0.93; all P < 0.001), suggesting that the hr-HFL marks outer retinal abnormalities in AMD.

Hyper-reflective HFL regions are a robust marker of outer retinal pathology in AMD. Structural changes such as drusen, fluid, and atrophy likely alter HFL orientation, leading to hyper-reflectivity. Although not specific to any single pathology, the hr-HFL reliably reflects the presence of AMD-related pathological changes.