Retro Mode Imaging for Detection and Quantification of Sub-RPE Drusen and Subretinal Drusenoid Deposits in Age-Related Macular Degeneration

Abstract

Background: Drusen and drusenoid deposits are a hallmark of age-related macular degeneration (AMD). Nowadays, a multimodal retinal imaging approach enables the detection of these deposits. However, quantitative data on subretinal drusenoid deposits (SDDs) are still missing. Here, we compare the capability of en-face drusen and SDD area detection in eyes with non-exudative AMD using conventional imaging modalities versus Retro mode imaging. We also quantitatively assess the topographic distribution of drusen and SDDs. Methods: In total, 120 eyes of 90 subjects (mean age ± standard deviation = 74.6 ± 8.6 years) were included. Coherent en-face drusen and SDD areas were measured via near-infrared reflectance, green (G-) and blue (B-) fundus autofluorescence (AF), and Retro mode imaging. Drusen phenotypes were classified by correlating en-face drusen areas using structural high-resolution spectral domain optical coherence tomography. The topographic distribution of drusen was analyzed according to a modified ETDRS (Early Treatment of Diabetic Retinopathy Study) grid. Intraclass correlation coefficient (ICC) analysis was applied to determine the inter-reader agreement in the SDD en-face area assessment. Results: The largest coherent en-face drusen area was found using Retro mode imaging with a mean area of 105.2 ± 45.9 mm² (deviated left mode (DL)) and 105.4 ± 45.5 mm² (deviated right mode (DR)). The smallest en-face drusen areas were determined by GAF (50.9 ± 42.6 mm²) and BAF imaging (49.1 ± 42.9 mm²) (p < 0.001). The inter-reader agreement for SDD en-face areas ranged from 0.93 (DR) to 0.70 (BAF). The topographic analysis revealed the highest number of SDDs in the superior peripheral retina, whereas sub-retinal pigment epithelium drusen were mostly found in the perifoveal retina. Retro mode imaging further enabled the detection of the earliest SDD stages. Conclusions: Retro mode imaging allows for a detailed detection of drusen phenotypes. While hundreds/thousands of SDDs can be present in one eye, the impact of SDD number or volume on AMD progression still needs to be evaluated. However, this new imaging modality can add important knowledge on drusen development and the pathophysiology of AMD.

Keywords: age-related macular degeneration; drusen; imaging; retro mode; subretinal drusenoid deposits.

Figure 1

Representative patient examples of study inclusion. Multimodal retinal imaging example of two included study patients with presence of sub-RPE drusen in intermediate AMD ((A), male patient, 65 years) and SDDs in non-exudative atrophic ((B), female patient, 79 years) AMD. Abbreviations: near-infrared (NIR), blue light fundus autofluorescence (BAF), Retro mode imaging (Retro).

Figure 2

SDD en-face area detection by readers. Example of SDD en-face areas manually outlined by two independent readers (A,B). NIR: near-infrared; BAF: blue fundus autofluorescence; GAF: green fundus autofluorescence; DR: Retro mode imaging deviated right; DL: deviated left.

Figure 3

Quantification of en-face drusen area in multimodal imaging. Multimodal retinal imaging example of en-face drusen quantification in two representative female patients with predominant presence of sub-RPE drusen (patient (A), 74 years) and SDDs (patient (B), 77 years) with intermediate AMD. En-face area values are given in mm² per imaging modality and patient. Notice the significantly greater en-face areas detected by Retro (DR) and Retro (DL) imaging in both cases. NIR: near-infrared; BAF: blue fundus autofluorescence; GAF: green fundus autofluorescence; DR: deviated right Retro mode imaging: DL: deviated left Retro mode imaging; multicolor corresponds to High-Res OCT B-scan. The position of the High-Res OCT B-scan is highlighted by the green line on the multicolor image. In the High-Res OCT B-scan, the presence of SDDs (black arrows) and sub-RPE drusen (black stars) are highlighted.

Figure 4

Multimodal retinal imaging example of sub-RPE drusen and SDD quantification using modified ETRDS grid. Multimodal retinal imaging example of drusen number quantification in two representative female patients aged 70 (case 1) and 77 (case 2) with intermediate AMD. Visible lesions were located in Retro mode as well as in OCT imaging and categorized into drusen phenotypes according to their typical structural alterations as seen in OCT imaging. Overlaying a modified ETDRS grid (details presented in Supplementary Figure S1) allowed the topographic analysis of SDDs (yellow dots) and sub-RPE drusen (slight white rings).

Figure 5

Topographical distribution of sub-RPE drusen and SDD according to modified ETDRS grid. This figure shows a graphical illustration of the topographical distribution of all drusen, as well as different drusen phenotypes in Retro mode imaging within the study subcohort according to a modified ETDRS grid. The results are presented as mean number of drusen per ETDRS subfield. Unit: number of lesions/mm².

Figure 6

Retro mode detects early SDD stages. Two representative study eyes presenting with early SDD stages detectable with Retro mode and high-resolution SD-OCT imaging (High-Res OCT). Consider the Retro mode image (A) with the red encircling the original size of the displayed area (*) as well as the enlarged red-encircled (#) area of interest shown in image (B). The exact location of the corresponding OCT scan is shown as a white-dashed line in the enlarged red rectangle (#). As SDDs were detectable in both patient examples, Retro mode imaging is capable of detecting even slight subretinal alterations representing the early stages of SDD (white arrows) [7].