MULTIMODAL IMAGING OF DISEASE-ASSOCIATED PIGMENTARY CHANGES IN RETINITIS PIGMENTOSA

Abstract

Purpose: Using multiple imaging modalities, we evaluated the changes in photoreceptor cells and retinal pigment epithelium (RPE) that are associated with bone spicule-shaped melanin pigmentation in retinitis pigmentosa.

Methods: In a cohort of 60 patients with retinitis pigmentosa, short-wavelength autofluorescence, near-infrared autofluorescence (NIR-AF), NIR reflectance, spectral domain optical coherence tomography, and color fundus images were studied.

Results: Central AF rings were visible in both short-wavelength autofluorescence and NIR-AF images. Bone spicule pigmentation was nonreflective in NIR reflectance, hypoautofluorescent with short-wavelength autofluorescence and NIR-AF imaging, and presented as intraretinal hyperreflective foci in spectral domain optical coherence tomography images. In areas beyond the AF ring outer border, the photoreceptor ellipsoid zone band was absent in spectral domain optical coherence tomography and the visibility of choroidal vessels in short-wavelength autofluorescence, NIR-AF, and NIR reflectance images was indicative of reduced RPE pigmentation. Choroidal visibility was most pronounced in the zone approaching peripheral areas of bone spicule pigmentation; here RPE/Bruch membrane thinning became apparent in spectral domain optical coherence tomography.

Conclusion: These findings are consistent with a process by which RPE cells vacate their monolayer and migrate into inner retina in response to photoreceptor cell degeneration. The remaining RPE spread undergo thinning and consequently become less pigmented. An explanation for the absence of NIR-AF melanin signal in relation to bone spicule pigmentation is not forthcoming.

Figure 1

Bone spicule-like intraretinal pigment aggregation in retinitis pigmentosa (RP) (P17). Color montage (A), short-wavelength fundus autofluorescence (SW-AF) (B) and near-infrared fundus autofluorescence (NIR-AF) (C) images. Bone spicule pigmentary changes (arrow heads) visible in color fundus photography are not autofluorescent in SW-AF and NIR-AF images.

Figure 2

Multi-modal fundus imaging and corresponding SD-OCT of bone-spicule pigment migration of RP patients (P57, P58 and P43). Near-infrared reflectance (NIR-R) (A,G), spectral domain optical coherent tomography (SD-OCT) (B, D, H), color fundus photography (C), short-wavelength fundus autofluorescence (SW-AF) (E) and near-infrared fundus autofluorescence (NIR-AF) (F). The horizontal axis and extent of SD-OCT scans is indicated by white lines with single arrows in the fundus images. The intraretinal hyperreflective cellular deposits (arrow heads) generate a shadow-effect in the SD-OCT and corresponding darkness in the SW-AF image. NIR-AF intensity is diminished with increased eccentricity.

Figure 3

Representative short-wavelength fundus autofluorescence (SW-AF), near-infrared fundus autofluorescence (NIR-AF), near-infrared reflectance (NIR-R) and color fundus images obtained from RP patients. The dotted lines indicate the outer border of the AF ring. Note the appearance of the AF ring in various modalities. Interior to the ring, there is brightness in the NIR-AF image and relative darkness in the SW-AF image. The zone of reduced melanin in the RPE monolayer (yellow arrows) permits choroidal vessel visibility.

Figure 4

Horizontal SD-OCT scans (A-H) and corresponding near-infrared fundus autofluorescence (NIR-AF) in P57, P23, P19, P48 and P22. The red lines (horizontal in the SD-OCT images and vertical (horizontal) in the fundus images) mark the zone where the ellipsoid zone (EZ) and RPE/Bruch’s bands are intact. The blue lines demarcate the zones where the EZ band is absent. The horizontal lines in A-H are placed below the reflectivity bands attributable to RPE/Bruch’s membrane in the SD-OCT images. Within the zones indicated by the blue lines, reduced pigmentation is apparent in color fundus, NIR-R and NIR-AF images. The latter aberration is more pronounced in the zones peripheral to the blue lines.

Figure 5

Scheme illustrating changes in the RPE and photoreceptor cells deduced by correlating information obtained by multi-modal imaging of RP patients. Bone spicule pigment in the fundus periphery (black) is populated by translocated RPE cells. The AF ring (1) is visible in both SW-AF and NIR-AF images and the outer border of the ring in NIR-AF and SW-AF images exhibits good correspondence. Outside the ring, changes (e.g. visibility of choroidal vessel) in the NIR-R, NIR-AF and SW-AF images are indicative of reduced RPE pigmentation in the original RPE monolayer (2). Reduced melanin pigmentation in the cells progresses (3) with distance from the AF ring (1). The photoreceptor ellipsoid zone (EZ) visible in SD-OCT images, terminates at the outer border of the AF ring thus creating a zone of EZ absence (5). With greater eccentricity (6) SD-OCT imaging reveals RPE displacement and progressive retinal delamination.