Two-Photon Vision in Age-Related Macular Degeneration: A Translational Study

Abstract

The recently introduced term “two-photon vision” relates to the visual perception resulting from a simultaneous absorption of two photons by photoreceptors. In this study, we determined two-photon retinal sensitivity in age-related macular degeneration (AMD) and compared it that in normal aging. Microperimetry was performed with visible (white) light and infrared (IR) light, which was perceived as green in the two-photon stimulation. In total, 45 subjects were included with one (better) eye studied. Furthermore, best-corrected visual acuity (VA) and ocular straylight were assessed. AMD resulted in decreased median (interquartile range) logMAR VA, i.e., 0.15 (0.05; 0.24), which in normal eyes was −0.02 (−0.06; 0.02). The two groups showed comparable straylight levels. Sensitivity to IR light was significantly lower in the AMD group (p < 0.001): 8.3 (7.4, 9.3) dB than in controls 10.7 (9.7, 11.2) dB. AMD also significantly affected visible light sensitivity (p < 0.001): 14.0 (11.0; 15.5) dB vs. 18.0 (16.3; 18.9) dB. Notably, the two-photon approach yielded a lower data spread. In conclusion, AMD considerably impairs retinal sensitivity measured in the single- and two-photon realm. However, two-photon-vision microperimetry may improve the testing accuracy and offer an additional diagnostic parameter (beyond VA measurements) for retinal function assessment.

Keywords: AMD; microperimetry; normal aging; retinal sensitivity; two-photon vision.

Figure 1

Optical coherence tomography images of a representative control (upper panel) and disease (lower panel) case. The solid red line indicates the automatic retinal layer segmentation, which defines the retinal thickness.

Figure 2

The distribution of retinal loci for sensitivity testing.

Figure 3

Grid point distribution superimposed over a macular thickness map with radial sector borders corresponding to 1 mm, 3 mm, and 6 mm ETDRS.

Figure 4

Two-group comparison for visible (left panel) and infrared light (right panel) sensitivity assessment. The box width indicates the interquartile range. The whiskers denote the fifth and 95th percentiles; the open squares refer to the mean value; and solid lines indicate the median level; points are individual data. **** p < 0.001.

Figure 5

Retinal sensitivity to visible (left panel) and infrared light (right panel) as a function of age. The median value over 44 points assessed in each AMD (red) and control (black) subject was taken. Error bars = interquartile range.

Figure 6

Retinal sensitivity maps of control (left panels) and AMD (right panels) participants compared using visible-light (Vis) microperimetry (upper panels) and two-photon mediated infrared light (IR) stimulation (lower panels). A triangular approach was applied to interpolate the area (colored gradient) between 44 measured loci (solid points). Control subjects’ results were marked in black; red marking indicates AMD patients. Error bars = interquartile range.

Figure 7

Box plots of the sensitivity results obtained along radially distributed retinal loci with a 1°, 2°, 4°, and 6° radius from the fovea. Note that the box width indicates the interquartile range. The whiskers denote the fifth and 95th percentiles; the outliers are marked as filled circles. The open squares refer to the mean value and solid lines indicate the median level. **** p < 0.001.

Figure 8

The relationship between the central subfield thickness of AMD (squares) and control (diamonds) subjects and retinal sensitivity measured using single- and two-photon approaches. The vertical line shows the median (reference) level found in the control group. The retinal thicknesses above and below the reference are marked in gray and blue, respectively.