Relationship between foveal cone structure and clinical measures of visual function in patients with inherited retinal degenerations

Abstract

Purpose: To study the relationship between cone spacing and density and clinical measures of visual function near the fovea.

Methods: High-resolution images of the photoreceptor mosaic were obtained with adaptive optics scanning laser ophthalmoscopy from 26 patients with inherited retinal degenerations. Cone spacing measures were made close to or at the foveal center (mean [SD] eccentricity, 0.02 [0.03] degree; maximum eccentricity, 0.13 degree) and were converted to Z-scores, fraction of cones, and percentage-of-cones-below-average compared with normal values for each location (based on 37 age-similar visually normal eyes). Z-scores and percentage of cones below average were compared with best-corrected visual acuity (VA) and foveal sensitivity.

Results: Visual acuity was significantly correlated with cone spacing (Spearman rank correlation ρ = -0.60, P = 0.003) and was preserved (≥ 80 letters), despite cone density measures that were 52% below normal. Foveal sensitivity showed significant correlation with cone spacing (ρ = -0.47, P = 0.017) and remained normal (≥ 35 decibels), despite density measures that were approximately 52% to 62% below normal.

Conclusions: Cone density was reduced by up to 62% below normal at or near the fovea in eyes with VA and sensitivity that remained within normal limits. Despite a significant correlation with foveal cone spacing, VA and sensitivity are insensitive indicators of the integrity of the foveal cone mosaic. Direct, objective measures of cone structure may be more sensitive indicators of disease severity than VA or foveal sensitivity in eyes with inherited retinal degenerations.

Trial registration: ClinicalTrials.gov NCT00254605.

Keywords: adaptive optics; cone sensitivity; cone structure; fovea; visual acuity.

Figures

Figure 1.

Adaptive optics scanning laser ophthalmoscopy images (0.5° × 0.5°) of foveal cone mosaics in six subjects' eyes, centered around the PRL of fixation (white crosshairs). Patients are arranged by increasing percentage of cones below average from left to right and top to bottom. Red crosshairs indicate cone selections used to calculate cone spacing Z-scores and percentage of cones below average, with blue diamonds indicating the average location of cone selections. Green lines and orange lines indicate 1 SD of fixation from the average PRL location in the horizontal and vertical directions, respectively. White scale bar: 0.25°.

Figure 2.

Top: Visual acuity measured as ETDRS letter scores correlates with cone spacing Z-scores. Vertically shaded grey region indicates the range of normal Z-scores (±2 SD); horizontally shaded region indicates the normal range of VA (100–85 letters). Center: Visual acuity plotted against percentage of cones below average. Vertically shaded grey region indicates percentage cone values corresponding to the normal range of Z-scores; horizontally shaded grey region indicates the normal range of VA. Red line indicates cone percentage after which ETDRS scores fall below 85 letters (20/20 acuity), which was determined by fitting the data to a locally weighted scatter plot smoothing (LOWESS) curve; red shaded region indicates 95% CIs. Bottom: Percentage of cones below average with threshold value and 95% CI for EDTRS scores below 80 letters (20/25 acuity).

Figure 3.

Top: Foveal sensitivity in logarithmic (decibel, left column) and linear (1/Lambert, right column) scales correlates with cone spacing Z-scores. Vertical grey regions indicate the normal range of Z-scores (±2 SD), and horizontal grey regions indicate the normal range of sensitivity. Bottom: Foveal sensitivity is plotted against percentage of cones below average. Red vertical lines indicate cone percentage after which foveal sensitivity became abnormal (<35 dB or <3162.28 1/Lambert), which was determined by fitting the data to a locally weighted scatter plot smoothing (LOWESS) curve; red shaded regions indicate 95% CIs.