Correlation of outer nuclear layer thickness with cone density values in patients with retinitis pigmentosa and healthy subjects

Abstract

Purpose: We studied the correlation between outer nuclear layer (ONL) thickness and cone density in normal eyes and eyes with retinitis pigmentosa (RP).

Methods: Spectral-domain optical coherence tomography (SD-OCT) scans were acquired using a displaced pupil entry position of the scanning beam to distinguish Henle's fiber layer from the ONL in 20 normal eyes (10 subjects) and 12 eyes with RP (7 patients). Cone photoreceptors were imaged using adaptive optics scanning laser ophthalmoscopy. The ONL thickness and cone density were measured at 0.5° intervals along the horizontal meridian through the fovea nasally and temporally. The ONL thickness and cone density were correlated using Spearman's rank correlation coefficient r.

Results: Cone densities averaged over the central 6° were lower in eyes with RP than normal, but showed high variability in both groups. The ONL thickness and cone density were significantly correlated when all retinal eccentricities were combined (r = 0.74); the correlation for regions within 0.5° to 1.5° eccentricity was stronger (r = 0.67) than between 1.5° and 3.0° eccentricity (r = 0.23). Although cone densities were lower between 0.5° and 1.5° in eyes with RP, ONL thickness measures at identical retinal locations were similar in the two groups (P = 0.31), and interindividual variation was high for ONL and cone density measures. Although ONL thickness and retinal eccentricity were important predictors of cone density, eccentricity was over 3 times more important.

Conclusions: The ONL thickness and cone density were correlated in normal eyes and eyes with RP, but both were strongly correlated with retinal eccentricity, precluding estimation of cone density from ONL thickness. (ClinicalTrials.gov number, NCT00254605.).

Keywords: adaptive optics scanning laser ophthalmoscopy; cone density; optical coherence tomography; outer nuclear layer thickness; retinitis pigmentosa.

Copyright 2015 The Association for Research in Vision and Ophthalmology, Inc.

Figures

Figure 1

The SD-OCT images acquired using conventional and directional (D-OCT) acquisition techniques. (A) Infrared fundus image with a horizontal SD-OCT B-scan through the fovea in a normal subject acquired through the center of the fovea. (B) Horizontal SD-OCT B-scan through the fovea in the same subject using D-OCT in which the incident light enters at the temporal edge of the pupil, while (C) shows D-OCT from the same subject with incident light displaced to the nasal edge of the pupil. With a variation of the incident light the HFL can be revealed as a hyper- (*) or hyporeflective (x) region adjacent to the OPL. The white cartoon inset shows the pupil entry position of the scanning laser beam.

Figure 2

The D-OCT image of a normal subject illustrates the method of retinal layer segmentation using the multipoint selection tool of ImageJ. The ONL thickness was defined as the distance between the inner edge of the ELM (4) to the outer edge of the HFL (3). 1, ILM; 2, the transition between the OPL and the HFL; 3, the transition between the HFL and the ONL; 4, ELM; 5, the outer edge of the RPE.

Figure 3

The AOSLO montage aligned with the B-scan SD-OCT image and the near-infrared fundus image. The capital letters N (nasal) and T (temporal) show the selected retinal regions along the central horizontal meridian with the respective locations on the SD-OCT B-scan. The inset in gray shows a representative cone mosaic at location T2 in this normal eye.

Figure 4

Tukey box plot of the average cone densities in normal eyes and eyes with RP at each single retinal location. The band inside the box is the median. The bottom and top of the box represent the first and third quartile, the whiskers are within 1.5 interquartile range (IQR) of the lower and upper quartile. Any data not included between the whiskers is an outlier and is plotted with a small circle. (A) Shows nasal retinal locations, and (B) temporal retinal locations.

Figure 5

Correlation between cone density and ONL thickness for all subjects ([A], Spearman's rank correlation coefficient [r] = 0.74; 95% CI, 0.67–0.82), normal subjects ([B], r = 0.74; 95% CI, 0.67–0.82), patients ([C], r = 0.70; 95% CI, 0.48–0.88) as well as for regions between 0.5° and 1.5° eccentricity ([D], r = 0.67; 95% CI, 0.55–0.81), and regions between 1.5° and 3° eccentricity ([E], r = 0.23; 95% CI, −0.06–0.48), only.