A 45-year-old asymptomatic woman was found to have retinal features consistent with basal laminar drusen on clinical examination. Blood pressure, urine dipstick, and renal function were all normal. Visual acuity without correction was 6/5 bilaterally. Fundus fluorescein angiography revealed multiple hyper-fluorescent soft and hard drusen scattered throughout the fundus (more numerous and extensive than seen ophthalmoscopically), with a greater concentration temporal to the macula (). Macular thickness and retinal nerve fiber layer thickness measured on the Cirrus HD-OCT (Carl Zeiss Meditec, Dublin, CA) was within the system’s normal limits. High-resolution images of the macula were obtained using a Bioptigen SD-OCT (Bioptigen, Durham, NC) equipped with a 878-nm (186-nm bandwidth) light source.11
A high-density 6 × 6-mm volume scan (1,000 A-scans/B-scan, 150 B-scans) from the patient’s left eye revealed a small, discrete drusen at 1.75° temporal to the fovea. At this location, images of the cone photoreceptor mosaic were obtained using a high-speed adaptive optics fundus camera.10,12,13
Individual frames were registered and averaged to increase the signal-to-noise ratio for the final image, as previously described.14
illustrates the co-registered fundus fluorescein angiography and adaptive optics images over the drusen, along with the corresponding SD-OCT image, performed using i2k Align Retina software (DualAlign, LLC, Clifton Park, NY) and Adobe Photoshop (Adobe Systems Inc., San Jose, CA).
Figure 1 Fundus fluorescein angiography montage of the patient’s left eye. Individual images were montaged using i2k Align Retina software (DualAlign, LLC, Clifton Park, NY). The white box indicates the area of the cone mosaic displayed in and (more ...)
Figure 2 Multimodal imaging of the retina. (A) Fundus fluorescein angiography and (B) adaptive optics images of the same patch of retina. (C) High-resolution spectral domain optical coherence tomography (SD-OCT) images using a broadband illumination with the Bioptigen (more ...)
Individual cones were identified using automated software,15
and cone density was subsequently analyzed using previously described methods.14
Although the contrast of the cone mosaic appears reduced over the drusen, cone density at this location (39,133 cones/mm2
) was not significantly decreased compared with previously published normative data from our group (mean ± 2 standard deviation [SD] = 41,974 ± 6,972 cones/mm2
We used a previously described Voronoi analysis16
to examine mosaic regularity (), comparing the geometry of the cones within 50 μm of the drusen and cones within 50-μm wide annular rings moving away from the drusen (ie, cones between 50 and 100 μm, between 100 and 150 μm, and so on). For the cones within 50 μm of the drusen, 45% had 6-sided Voronoi domains. For each of the other 50-μm annular rings, between 32% and 53% of the cones had 6-sided Voronoi domains (mean = 46%). In addition, the mean number of sides to the Voronoi domains for the cones within each 50-μm annular ring compared with that of the cones within 50 μm of the drusen was not significantly different (P
= .9959, Kruskal–Wallis analysis of variance). Thus, we concluded that the mosaic immediately overlying the drusen is regularly arranged, consistent with no significant cone loss.
Figure 3 Analysis of mosaic regularity analysis. Shown are the Voronoi boundaries associated with each cone identified using the automated program of Li and Roorda.15 Green color indicates Voronoi domains with 6 sides, reflecting hexagonal/triangular packing of (more ...)
Longitudinal reflectivity profile analysis of the SD-OCT images () revealed that the inner-segment layer (distance between the external limiting membrane and IS/OS layer) was of normal thickness both directly above the druse and immediately adjacent to it, compared with 167 previously published normals.10
The outer-segment layer (distance between IS/OS and retinal pigment epithelium layers) was normal (30 μm) immediately adjacent to the druse, but significantly thinner (18.2 μm, normal mean ± 2 SD is 32 ± 1.11 μm) directly above the druse. Although outer-segment shortening has been reported using fundus reflectometry techniques,17
the apparent thinning of the outer segment we observed on SD-OCT could be due to a shortening of the outer segment or to a splaying of the outer segment that is secondary to the volume occupied by the druse itself.
Figure 4 Disruption of the inner segment/outer segment (IS/OS) layers. On the left is a segment of the spectral domain optical coherence tomography (SD-OCT) image centered on the 65-μm wide druse. Longitudinal reflectivity profiles have been plotted for (more ...)