Toward Organelle Motility as a Functional Biomarker of Retinal Pigment Epithelium Health

Purpose: The purpose of this study was to quantify characteristics of retinal pigment epithelium (RPE) organelle motility in human subjects across the temporal (T) macula. Methods: In 11 healthy volunteers (HVs), we used high-speed adaptive optics-optical coherence tomography (AO-OCT) to image RPE cells from the fovea to 12°T. Organelle motility was calculated in the apical, middle, and basal layers as the time constant (τ) of the exponentially decaying speckle decorrelation function normalized to the photoreceptor layer. We imaged 7 HVs on 3 different days at the fovea and 7.5°T to characterize motility repeatability. We imaged 4 HVs on 2 systems with 830 nm and 1060 nm source wavelengths at 7.5°T to explore motility wavelength dependence. Results: Across the temporal macula, τ decreased from 15.3 (±2.4) to 10.9 (±2.7) seconds (-0.33 seconds/degrees) for the apical RPE, decreased from 9.4 (±1.8) to 8.5 (±1.9) seconds (-0.11 seconds/degrees) for the middle RPE, and was nearly constant (-0.05 seconds/degrees) at 6.7 (±1.0) seconds for the basal RPE at 1060 nm. Motility repeatability was moderate (coefficient of variance [CV] = 10.7% for all subjects and locations). At all RPE layers, τ measured shorter at 830 nm (apical = 6.8 ± 2.2, middle = 4.8 ± 1.0, and basal = 3.8 ± 0.7 seconds) compared with 1060 nm (apical = 10.4 ± 2.8, middle = 6.5 ± 1.6, and basal = 5.0 ± 1.1 seconds, P < 0.005). Conclusions: RPE organelle motility varies across the macula and cell depth. Our normative dataset will aid future studies of RPE-related retinal pathology. Translational Relevance: AO-OCT measured organelle motility is a potential functional biomarker of RPE cell health and ocular disease pathophysiology.