Researchers have demonstrated that adaptive optics optical coherence tomography (AO-OCT) can directly track the loss of individual retinal ganglion cell (GC) somas in living human eyes, offering a potentially more sensitive way to monitor glaucoma progression than conventional structural or functional testing.
The study, published in Investigative Ophthalmology & Visual Science, followed six healthy participants and two patients with glaucoma over several years. Using AO-OCT, the investigators repeatedly imaged the same retinal locations and tracked individual ganglion cell layer (GCL) somas over time. Healthy participants were followed annually for up to three years, while the two glaucoma patients were reimaged approximately two years after baseline.
Current clinical approaches generally infer GC loss indirectly through measurements such as retinal nerve fiber layer or GCL thickness, or through visual field sensitivity. These methods can be limited by inter-individual variability and by the very slow rate of age-related ganglion cell loss. By contrast, AO-OCT provides sufficient resolution to visualize individual GCL somas directly, potentially allowing clinicians to detect cellular changes before they become apparent on conventional testing.
Across the six healthy subjects, the researchers tracked 23,586 somas. The GCL mosaic proved highly stable, with approximately 99.7% of somas remaining unchanged during the three-year period. Nevertheless, the technique was sensitive enough to detect rare losses, producing an average soma loss rate of 0.10% per year. No significant differences in loss rate were observed between participants or retinal locations.
The findings in the two glaucoma patients highlighted the potential clinical value of this cellular-level approach. One patient demonstrated a relatively modest soma loss rate of 0.26% per year within an arcuate defect, with no detectable accompanying GCL thinning. The other glaucoma patient, however, showed a 31.6% annual soma loss rate, more than 100 times the mean rate observed in healthy subjects. In this eye, AO-OCT measured GCL thinning of approximately 13% per year at the same location, consistent with rapid focal disease progression.
The Indiana University researchers also found a strong relationship between GC soma density and GCL thickness in healthy eyes. However, this association appeared to weaken in more advanced glaucomatous damage, suggesting that layer thickness may become a less reliable surrogate for actual neuronal density as disease progresses.
The study remains preliminary. Its small cohort, limited number of retinal locations, and labor-intensive image analysis prevent the findings from providing population-level estimates or immediate clinical applicability. The authors also noted that further automation will be necessary before the technique can be scaled for routine practice.
However, the ability to directly observe individual ganglion cells disappearing over time represents an advance. According to the authors, AO-OCT could ultimately provide a powerful tool for longitudinal monitoring of glaucoma suspects and for assessing whether new therapies are successfully protecting retinal neurons.
