Cone Spacing Correlates With Retinal Thickness and Microperimetry in Patients With Inherited Retinal Degenerations

Abstract

Purpose: To determine whether high-resolution retinal imaging measures of macular structure correlate with visual function over 36 months in retinal degeneration (RD) patients and normal subjects.

Methods: Twenty-six eyes of 16 RD patients and 16 eyes of 8 normal subjects were studied at baseline; 15 eyes (14 RD) and 11 eyes (6 normal) were studied 36 months later. Adaptive Optics Scanning Laser Ophthalmoscopy (AOSLO) was used to identify regions of interest (ROIs) with unambiguous cones at baseline to measure cone spacing. AOSLO images were aligned with spectral-domain optical coherence tomography (SD-OCT) and fundus-guided microperimetry results to correlate structure and function at the ROIs. SD-OCT images were segmented to measure inner segment (IS) and outer segment (OS) thickness. Correlations between cone spacing, IS and OS thickness and sensitivity were assessed using Spearman correlation coefficient ρ with bootstrap analyses clustered by person.

Results: Cone spacing (ρ = 0.57, P < 0.001) and macular sensitivity (ρ = 0.19, P = 0.14) were significantly correlated with eccentricity in patients. Controlling for eccentricity, cone spacing Z-scores were inversely correlated with IS (ρ = -0.29, P = 0.002) and OS thickness (ρ = -0.39, P < 0.001) in RD patients only, and with sensitivity in normal subjects (ρ = -0.22, P < 0.001) and RD patients (ρ = -0.38, P < 0.001). After 36 months, cone spacing increased (P < 0.001) and macular sensitivity decreased (P = 0.007) compared to baseline in RD patients.

Conclusions: Cone spacing increased and macular sensitivity declined significantly in RD patients over 36 months. High resolution images of cone structure correlated with retinal sensitivity, and may be appropriate outcome measures for clinical trials in RD.

Figure 1

Adaptive optics scanning laser ophthalmoscopy (AOSLO) image, spectral domain-optical coherence tomography (SD-OCT) horizontal and vertical scans, and fundus-guided microperimetry map superimposed in patient 30015 OD. (A) Macular sensitivity values in color-coded circles are shaded from green (normal) to red (stimulus not seen) based on the sensitivity measured at each location; color scale bar at top of panel; scale bar: 300 μm. (B) Magnified view of (A); regions of interest (ROIs) are outlined in white boxes; small white pixels indicate the patient's preferred retinal locus of fixation; scale bar: 300 μm. (C) Magnified view of ROI N1. Red crosses indicate positions of cones used to assess cone spacing; scale bar: 10 μm.

Figure 2

Cone spacing measures correlated with eccentricity as measured by distance from the fovea. The small black filled circles represent a normal data set composed of 27 controls. The dashed curved lines represent the 95% CI of this normal dataset, and the solid black line represents the mean. Normal subjects: blue; patients with RD: orange; circles: baseline measures; triangles: 36-month follow-up measures.

Figure 3

Outer retinal layer thickness correlated with cone spacing measures. (A) Inner segment (IS) thickness was significantly correlated with cone spacing in normal subjects and patients. (B) Outer segment (OS) thickness was significantly correlated with cone spacing in normal subjects and patients. (C) IS thickness was correlated with cone spacing Z-scores in patients but not normal subjects. (D) OS thickness was correlated with cone spacing Z-scores in patients but not normal subjects. Normal subjects: blue; patients with RD: orange; circles: baseline measures; triangles: 36-month follow-up measures. The gray bands on graphs C and D indicate the ±2 Z-score limits of normal subjects.

Figure 4

Correlation between outer retinal structure and macular function, measured as retinal sensitivity. (A) Retinal sensitivity was correlated with inner segment (IS) thickness in normal eyes but not patients. (B) Retinal sensitivity was correlated with outer segment (OS) thickness in normal eyes but not patients. (C) Retinal sensitivity was significantly correlated with cone spacing Z-scores in normal and patient eyes. Normal subjects: blue; patients with RD: orange; circles: baseline measures; triangles: 36-month follow-up measures; dB: decibels; the gray band in panel C indicates the ±2 Z-score limits of normal subjects.