Rod sensitivity, cone sensitivity, and photoreceptor layer thickness in retinal degenerative diseases

Abstract

Purpose: To evaluate the effects of selective rod and/or cone loss on frequency-domain optical coherence tomography (fdOCT) measures of photoreceptor structure in patients with retinal degenerative diseases.

Methods: Six patients with cone dystrophy (CD) and eight patients with retinitis pigmentosa (RP) were recruited from the Southwest Eye Registry on the basis of diagnosis and ERG findings. fdOCT horizontal line scans were segmented to obtain the thicknesses of the outer segments plus RPE (OS+) and the outer nuclear layer (ONL). The normalized product ONL*OS was obtained after dividing by mean ONL*OS values of 23 normal individuals. Visual field sensitivity profiles were obtained with a modified retinal perimeter, from the horizontal midline with short- and long-wave stimuli under dark- and light-adapted conditions.

Results: Patients with CD and normal rod-mediated sensitivity, but decreased cone-mediated sensitivity, showed normal ONL*OS outside the fovea. The total receptor layer was thinned in the fovea, consistent with loss in cone nuclei and Henle's fiber layer. Patients with RP and sensitivity in the dark that was mediated by cones showed ONL*OS thickness that was linearly related to cone sensitivity. ONL*OS thickness was linearly related to rod sensitivity in regions with greater loss of cone than rod sensitivity.

Conclusions: Both rods and cones can support an intact IS/OS junction and normal photoreceptor thickness measures. The product of ONL and OS thicknesses is proportional to the sensitivity mediated by the less abnormal type of photoreceptor.

Figures

Figure 1.

Segmented fdOCT scans from horizontal midline. Light green: BM/choroid; yellow: IS/OS; blue: INL/OPL. (A) Normal individual. (B) Patient 3718 with CD. (C) Enlarged image of normal macula. (D) Enlarged image of macula in patient3718. Green arrows: the point at which the IS/OS line became irregular; red arrows: the point at which the IS/OS line disappeared.

Figure 2.

Normalized fdOCT parameters plotted against linear TD values for the patient with CD shown in Figure 1. Dark dashed curve: normalized fdOCT values; vertical error bars indicate the 95% confidence intervals for normal fdOCT parameters. The gaps in the curves depicting the OS, ONL, and OS*ONL reflect the extent of the loss in the IS/OS junction line in the underlying OCT image (see Fig 1). Dark gray bars: TD(G-W), the linear decrease in rod sensitivity from normal. The length of the bar is 11°, consistent with the diameter of the test target. Light gray bars: TD(HFA), the linear decrease in cone sensitivity. Bar lengths are 0.86°, consistent with the diameter of the spot size 3 test target.

Figure 3.

Linear relationships between TDG-W (■), TDHFA (□) and normalized ONL*OS in the macula of CD patient 3718 (arrows) and all other patients with CD. The smooth curve is the prediction of a simple linear model, where normalized ONL*OS = 100.1TD.

Figure 4.

Top: sensitivity along the horizontal meridian after 45 minutes of dark adaptation. Sensitivity to the short-wave stimulus was higher than sensitivity to the long-wave stimulus at all locations, with an average difference of 18 dB outside the fovea. Vertical bars indicate 95% confidence interval for rod thresholds. Bottom: sensitivity along the horizontal meridian after 10 minutes of light adaptation (34 cd/m2). Sensitivity to the short-wave stimulus was slightly lower than sensitivity to the long-wave stimulus. Vertical bars indicate 95% confidence intervals for cone thresholds.

Figure 5.

fdOCT and MP-1 perimetry in patient 9754 with CD. (A) Dark-adapted fundus perimetric sensitivity was higher for blue than for red at all locations, indicating rod mediation of thresholds. (B) TDdark and TDlight (the difference in decibels between the patient values and mean normal values) are superimposed on a fundus photograph. For comparison, the fdOCT scan is aligned with the perimetric sensitivities. An enlargement is shown of the region indicated by the box. (C) Normalized ONL*OS thickness (dashed curve, left axis), along with rod-mediated TDdark (filled blue circles, right axis), cone-mediated TDlight (open red circles) and deviations from Humphrey perimetry (TDHFA, light gray bars). Photoreceptor layer thickness is within normal limits outside the fovea, as is TDdark (but not TDlight). (D) Normalized ONL*OS thickness was consistent with a linear relationship to TDdark.

Figure 6.

FdOCT and MP-1 perimetry in patient 5303 with RP. (A) Dark-adapted fundus perimetric sensitivity was similar for blue and red stimuli, consistent with cone mediation of all thresholds. (B) TDdark and TDlight are superimposed on a fundus photograph. For comparison, the fdOCT scan is aligned with the perimetric sensitivities. An enlargement is shown of the region indicated by the box. (C) Normalized ONL*OS thickness (dashed curve, left axis) is shown, along with linear TDdark (filled blue circles, right axis), linear TDlight (open red circles, right axis), and linear deviations from Humphrey perimetry (TDHFA, light gray bars, right axis). (D) A simple linear model predicts the relationship between ONL*OS thickness and TDlight.

Figure 7.

FdOCT and MP-1 perimetry in patient 9900 with RP. (A) Dark-adapted fundus perimetric sensitivity was higher for blue and than for red stimuli in the temporal retina, consistent with rod mediation of thresholds. (B) The horizontal fdOCT scan is shown along with TDdark and TDlight. An enlargement is shown of the region indicated by the box. (C) Normalized ONL*OS thickness is shown along with TDdark (filled blue circles), TDlight (open red circles) and TDHFA (light gray bars). Foveal thickness corresponds to a peak in TDlight, whereas relative ONL*OS thickness in the temporal retina corresponds to relatively normal values of TDdark. (D) The simple linear model for ONL*OS thickness (smooth curve) provides a better approximation to TDdark than to TDlight.

Figure 8.

Relationship between TD and normalized ONL*OS in RP. Top: four of the eight patients with RP had at least some locations in the central retina where sensitivity was mediated by rods. The simple linear model (solid curve) predicts the relationship between ONL*OS thickness and TDdark. Bottom: all eight patients with RP had at least some locations where sensitivity was mediated by cones. The simple linear model predicts the relationship between ONL*OS and TDlight.