Retinal Pigment Epithelium Degeneration Associated With Subretinal Drusenoid Deposits in Age-Related Macular Degeneration

Abstract

Purpose: To test whether increased light transmission (hypertransmission) through subretinal drusenoid deposits (SDD) into the choroid in age-related macular degeneration (AMD) represented retinal pigment epithelium (RPE) degeneration.

Design: Cross-sectional study.

Methods: Nineteen eyes of 12 patients with early- to intermediate-stage AMD and 18 eyes of 12 normal subjects were evaluated with color fundus photography, optical coherence tomography (OCT), and high-resolution adaptive optics scanning laser ophthalmoscopy (AOSLO) at baseline and 24 months later. SDD were classified using an OCT-based 3-stage grading system. Hypertransmission beneath SDD into the choroid was examined in OCT. SDD microstructure was assessed with AOSLO. To characterize the hypertransmission-associated chorioretinal degeneration, choroidal thickness and photoreceptor length were measured in OCT at 1 mm and 2 mm superior, inferior, temporal, and nasal to the foveal center.

Results: OCT disclosed hypertransmission beneath stage 3 SDD in 8 eyes. These lesions showed a distinctive regressing structure in AOSLO, compared with stage 3 lesions without hypertransmission. The phenomenon persisted at follow-up, and new hypertransmission developed as SDD advanced. In eyes with hypertransmission, choroids were thinner than those of normal eyes at all sites (by 44%-56%, P ≤ .0028) and those of eyes with SDD but without hypertransmission at superior and temporal sites (by 31%-46%, P ≤ .039). Photoreceptors were significantly shorter than those in normal eyes (by 6%-26%, P ≤ .0379).

Conclusions: Hypertransmission into the choroid, accompanied with SDD regression and thinning of choroid and photoreceptor layers, indicates RPE degeneration associated with advanced stages in the SDD life cycle.

Figure 1

Subretinal drusenoid deposits (SDD) with and without hypertransmission revealed by multimodal imaging. Rows 1 and 2, an 84-year-old woman with intermediate stage age-related macular degeneration (AMD) (Age-Related Eye Disease Study (AREDS) grade 7, best corrected visual acuity (BCVA) 20/20) (subject 1, AMD-022). Rows 3 and 4, a 73-year-old man with intermediate stage AMD (AREDS grade 6, BCVA 20/25 (subject 2, AMD-041). In en face imaging, SDD appear as interlacing of yellow-white dots (color fundus photography, rows 1 and 3), a pattern of hyporeflective or hyper-reflective spots (infrared (IR) reflectance, middle panels of rows 1 and 3), a pattern of small hypo-autofluorescent areas against a background of mild hyper-autofluorescence (right panels of rows 1 and 3). In spectral domain optical coherence tomography (SD-OCT), SDD are hyper-reflective mounds internal to the RPE (color arrows, rows 2 and 4). SD-OCT scans were taken along the green lines in the IR images. (Row 2, left) SD-OCT revealed distinctive hypertransmission stripes (indicated by yellow arrowheads) in the choroid/sclera directly beneath 5 stage-3 SDD (yellow arrows). Meanwhile, (right, row 2) hypertransmission stripes (red arrowheads) also appeared underneath regressed SDD (red arrows) as examined in en face imaging. These hypertransmission stripes were not seen beneath the SDD (arrows in white, green and magenta in the IR image in row 3 and the SD-OCT in row 4) seen in subject 2.

Figure 2

Three light transmission patterns associated with subretinal drusenoid deposits (SDD) revealed by spectral domain optical coherence tomography (SD-OCT) and adaptive optics scanning laser ophthalmoscopy (AOSLO). The subject was an 85-year-old woman (AMD-022) with intermediate stage AMD (Age-Related Eye Disease Study grade 7, best corrected visual acuity 20/20). (Top row) High-resolution AOSLO retinal image montage is overlaid on color fundus photograph. The fundus appearance of SDD lesions with 3 light penetration patterns revealed by SD-OCT (bottom row) is shown in the magnified yellow box. SDD with patterns 1 (green arrowhead) and 2 (yellow arrowhead) appear as dot-like yellow-white lesions in color fundus photography, whereas the area with regressed SDD in pattern 3 (aqua arrowhead) presents a pigmentary change. (Middle row) In AOSLO, pattern 1 lesion (4 green arrowheads) shows a hyporeflective annulus surrounded the reflective core of the SDD. Pattern 2 lesion (4 yellow arrowheads) shows a dark split inside the hyperreflective core of the lesion. Pattern 3 lesion (4 aqua arrowheads) is a regressed SDD, showing dispersed lesion material and reflective spots without legible cone mosaic. Green arrow lines in the AOSLO images indicate the levels of SD-OCT B-scans shown in the top row. (Bottom row) SD-OCT revealed 3 light penetration patterns. Pattern 1 (left), there is no stripe of hypertransmission beneath the SDD (pointed by the green arrowhead). Pattern 2 (middle), the imaging light transmits through the SDD and forms a distinct hypertransmission stripe underneath the SDD (pointed by the yellow arrowhead) through the RPE into the choroid (Ch). The ellipsoid zone (EZ) of the photoreceptors has been broken by the lesion, but the retinal pigment epithelium (RPE) band is still visible. Pattern 3 (right), a hypertransmission stripe is underneath a regressed SDD (pointed by the aqua arrowhead), with a disrupted EZ and a fuzzy RPE band.

Figure 3

Progression of subretinal drusenoid deposit (SDD) with hypertransmission, seen with adaptive optics scanning laser ophthalmoscopy (AOSLO) and multiple spectral domain optical coherence tomography (SD-OCT) scans, at baseline and 24 months follow-up. The subject was a 73-year-old man (AMD-041) with intermediate AMD (Age-Related Eye Disease Study grade 6 at baseline, best corrected visual acuity 20/25). (Rows 1 and 2) AOSLO images of the same retinal areas taken at baseline and 24-month follow-up. Color arrowheads indicate 4 exemplary stage 3 SDD at baseline and their progression. By AOSLO stage 3 SDD has a hyporeflective annulus signifying non-visualized photoreceptors and a central reflective core signifying the lesion material. (Rows 3–6) Paired B-scans from the SD-OCT volumes taken at baseline and follow-up, as indicated by the green lines with arrowheads on the AOSLO images. The spacing between adjacent B-scans is 30 µm. Over 24 months, one regressing bi-lobed SDD (aqua arrowheads) has completely disappeared at the follow-up (Rows 1 and 3), associated with clearance of lesion material from the subretinal space and persistence of associated hypertransmission (Panel pairs B1–F1 to B5–F5, showing pattern 2 described in Figure 2). Another small regressing lesion (magenta, Rows 1 and 2) diminished in size and exhibited hypertransmission over time (panel pairs B5–F5 to B8–F8), exemplifying a Pattern 2 lesion progressing to Pattern 3. A large SDD (yellow arrowheads) without discernable hypertransmission at baseline shrank (Rows 1 and 2) and developed hypertransmission (panel pairs B5–F5 to B8–F8) at follow-up, demonstrating a Pattern 1 lesion progressing to Pattern 2. An adjacent small SDD (green arrowheads) associated with hypertransmission at baseline expanded at follow-up (Row 1), with hypertransmission persisting over the follow-up period. A version of these images without labelling is presented in Supplemental Figure 1.