Detailed analyses of microstructure of photoreceptor layer at different severities of occult macular dystrophy by ultrahigh-resolution SD-OCT

Abstract

Purpose: To analyze the microstructures of the photoreceptor layer in detail in eyes with occult macular dystrophy (OMD, Miyake's disease) by ultrahigh-resolution spectral-domain optical coherence tomography (UHR-SD-OCT).

Observations: Twenty-eight normal subjects and 5 patients with OMD of different severities were studied. Cross-sectional images through the fovea were recorded with a UHR-SD-OCT system with a depth resolution of <2.0 μm. In patients with OMD, the UHR-SD-OCT images revealed abnormal photoreceptor microstructures which were not detected in the conventional SD-OCT images. The UHR-SD-OCT images showed that the interdigitation zone (IZ) was not present and the outer segments were hyperreflective with hyperreflective dots (HRDs) aligned like string of pearls during the earlier stages. There was a disruption of the ellipsoid zone (EZ) which appeared as clusters of larger HRDs, and these HRDs became less apparent with increasing time. The outer segments became hyporeflective and rod IZ became apparent with longer duration of the disease process.

Conclusions and importance: The UHR-SD-OCT images show detailed characteristics of the photoreceptor microstructures of different severities during the progression of OMD. These detailed observations will help in understanding the mechanisms involved in the retinal pathology and should provide important information for their treatments.

Keywords: Ellipsoid zone; Interdigitation zone; Occult macular dystrophy; Optical coherence tomography; Photoreceptors; Ultrahigh-resolution OCT.

Fig. 1

Ultrahigh-resolution SD-OCT (UHR-SD-OCT) image of a normal eye. A. Horizontal B-scan image across the fovea of a 41-year-old woman taken by a UHR-SDR-OCT device. B. Expanded image of the yellow rectangle in A. Locations of both the cone and rod interdigitation zone (IZ) are shown by red and blue dotted lines, respectively. C. Longitudinal reflectivity profiles (LRP) in the regions indicated by the yellow arrows on the flattened OCT image. Rod IZ is seen as a distinct hyperreflective peak between the cone IZ and RPE/Bruch's membrane in Temp. 2 but not in Temp.1. D. Vertical B-scan image across the fovea of the same subject in A, taken by UHR-SDR-OCT. E. Expanded image of the yellow rectangle in D. Locations of both the cone and rod IZs are shown by red and blue dotted lines, respectively. F. The LRP in the regions indicated by the yellow arrows on the flattened OCT image. The rod IZ is seen as a distinct hyperreflective peak between the cone IZ and RPE/Bruch's membrane in Inf.1, but not in Inf.2. ELM = external limiting membrane; EZ = ellipsoid zone of photoreceptor; IZ = interdigitation zone of photoreceptor; RPE = retinal pigment epithelium. Temp. = temporal; Inf. = inferior. . (For interpretation of the references to colour in this figure legend, the reader is referred to the Web version of this article.)

Fig. 2

Small dot-like regions with hyperreflectivity in the outer segments between the EZ and cone IZ in normal eyes. A. Vertical B-scan image across the fovea of a 31-year-old man with normal eyes taken by UHR-SDR-OCT. B. Expanded image of the yellow rectangles in A. C. Vertical B-scan image across the fovea of a 40-year-old woman with normal eyes taken by UHR-SDR-OCT. D. Expanded image of the yellow rectangles in C. Small dot-like regions with hyperreflectivity are observed between the EZ and cone IZ (Fig. 2B and D, black and yellow arrows). They are independent of the highly reflective EZ and cone IZ. EZ = ellipsoid zone of photoreceptors; C-IZ = cone interdigitation zone of photoreceptors; R-IZ = rod interdigitation zone of photoreceptors; RPE = retinal pigment epithelium; Inf. = inferior. . (For interpretation of the references to colour in this figure legend, the reader is referred to the Web version of this article.)

Fig. 3

B-scan images of five eyes in five cases with OMD listed according to the severity of visual acuity and photoreceptor atrophy from mild to severe. A. Horizontal B-scan image of the left eye of a 53-year-old woman whose decimal best-corrected visual acuity (BCVA) was 20/25. In the expanded image, the EZ is blurred and the cone IZ is disrupted at the fovea (white arrowhead). Both the EZ and cone IZ are normal only at the parafovea (yellow arrows). In the more peripheral region, the EZ appears slightly disrupted with clusters of hyperreflective dots (HRDs) (yellow arrowhead) and the cone IZ is not present. There are HRDs in the outer segment consecutively aligned in a line that appear like string of pearls (yellow asterisk). The expanded image (2x) of the string of pearls is shown below. B. Vertical B-scan image of the right eye of a 36-year-old man whose BCVA was 20/50. In the expanded image, the arch-shaped region of blurred EZ at the fovea is expanded laterally more than in Case A (white arrowhead), and HRDs are observed in the location of the outer segments (right-most yellow arrowhead). The EZ and cone IZ are normally observed in the peri-macular region (yellow arrows), but in the macular region, the EZ appears disrupted with cluster of HRDs (left-most three yellow arrowheads) and the cone IZ is not visible. C. Vertical B-scan image of the left eye of a 39-year-old man whose BCVA was 20/63. In the expanded image, the arch-shaped region of blurred EZ at the fovea is expanded laterally more than that in Case B, and the normal appearing ELM passes through it (white arrowhead). The cone IZ is not present in the entire macular region and the EZ appears disrupted with clusters of HRDs (yellow arrowheads). The outer segments appear like string of pearls (yellow asterisk). The expanded image (2x) of the string of pearls is shown below. D. Vertical B-scan image of the left eye of a 22-year-old woman whose BCVA was 20/125. In the expanded image, there is arch-shaped region of blurred EZ at the fovea, and the normal appearing ELM passes through it (white arrowhead). The cone IZ is not present in the entire macular region and the EZ appears disrupted with clusters of HRDs (yellow arrowheads). The outer segments appear more hyporeflective than in Cases A to C and the string-of-pearl-like structures are not present. E. Vertical B-scan image of the right eye of a 51-year-old woman whose BCVA was 20/200. In the expanded image, there is arch-shaped region of blurred EZ at the fovea (white arrowhead). The cone IZ is not observed in the entire macular region and the EZ appears blurred and hyporeflective with smaller number of HRDs than in Cases A to D (yellow arrowhead). The outer segments appear more hyporeflective than in cases A to C, and the rod IZ is clearly observed above the RPE (yellow arrow). F. Vertical B-scan images of the same eye as in C taken by a conventional SD-OCT. EZ = ellipsoid zone of photoreceptor; IZ = interdigitation zone of photoreceptor; OS = outer segment; RPE = retinal pigment epithelium.. (For interpretation of the references to colour in this figure legend, the reader is referred to the Web version of this article.)

Fig. 4

Longitudinal reflectivity profiles (LRPs) of a normal eye in Fig. 1, and Cases with OMD shown in Fig. 3B and E. A. Longitudinal reflectivity profiles (LRP) of a normal eye in Fig. 1 in the regions indicated by yellow arrows on the flattened OCT image. The EZ and Cone IZ have high and sharp peaks both in the locations of Inf. 1 and 2. B. LRPs of the case with OMD in Fig. 3B. The peak of the EZ appears high and sharp in Inf. 1, but lower and broader in Inf. 2. The peak of the Cone IZ does not appear in Inf. 2. C. LRPs of more advanced case with OMD in Fig. 3E. The peak of EZ appears lower and broader both in Inf. 1 and 2. The peak of Cone IZ does not appear either in Inf. 1 or 2. ELM = external limiting membrane; EZ = ellipsoid zone of photoreceptor; IZ = interdigitation zone of photoreceptor; RPE = retinal pigment epithelium. Temp. = temporal; Inf. = inferior. . (For interpretation of the references to colour in this figure legend, the reader is referred to the Web version of this article.)