Cumulative Loss of Inner Retinal Neurons in Healthy and Glaucoma Subjects

Purpose: Considerable ganglion cell (GC) loss occurs over the normal human lifespan and even more in ocular diseases such as glaucoma. Current clinical methods, however, lack sufficient resolution and sensitivity to directly detect GC loss. Here, we used adaptive optics optical coherence tomography (AO-OCT) to overcome these limitations, enabling longitudinal tracking of individual GC somas and direct measurement of their loss in healthy and glaucomatous eyes. Methods: Six healthy subjects and two patients with glaucoma were imaged at multiple retinal locations using AO-OCT. Healthy subjects were imaged annually for up to 3 years (4 total timepoints); patients with glaucoma were reimaged 2 to 3 years after baseline. Individual ganglion cell layer (GCL) somas were identified and tracked across sessions and soma densities were quantified. A flicker-based image comparison approach enabled sensitive detection of soma loss from which cumulative loss was determined by subject and location. Results: The GCL soma mosaic was highly stable, with 23,586 somas tracked in healthy subjects. Soma densities agreed with histologic values, including near the fovea, and correlated strongly with GCL thickness (R2 = 0.96). The mean soma loss rate in healthy subjects was -0.10%/year (95% confidence interval [CI] = -0.09 to -0.11%/year), with no significant differences across subjects or locations. By contrast, one glaucoma patient showed a loss rate within an arcuate defect over 100× greater (-31.6%/year; corresponding GCL thinning rate of -13%/year), whereas the other demonstrated a near-normal rate (-0.26%/year). Conclusions: In vivo measurement of individual GC soma loss is now feasible and provides a sensitive tool for longitudinal evaluation of GC health.