AMD Subretinal Drusenoid Deposits

This 70YO male was referred for age-related macular degeneration (AMD). He was visually asymptomatic, and vision was 20/25 OD and 20/50 OS.

Optos color RG imaging shows extensive, mostly small drusen centered outside the fovea. These lesions are well visualized on the green channel but disappear on the red channel. Triton swept-source OCT shows these ‘drusen’ to represent subretinal drusenoid deposits (SDD), with numerous hyperreflective deposits scattered above the RPE. En face imaging through the outer retina most dramatically shows these SDD.

Learning Points:
SDD are polymorphous, light-gray, interconnected accumulations located above the RPE and are thus best visualized with blue or green illumination, as in our patient. SDD are now considered the third clinical feature for progression to late AMD (Agron et al, Ophthalmology 2022;129:1107-1119), in addition to large drusen and pigment abnormalities as defined in the Beckman classification (Ferris et al, Ophthalmology 2013;120:844-851).

They are present in about one-quarter of older adults with healthy maculas and in more than half of those with early-to-intermediate dry AMD. Clinically, they are often mistaken for conventional drusen and consist of lipid-rich material similar yet distinct from that found in soft drusen.

SDD are localized to rods, unlike typical soft drusen, which are more central and cone-based. As with drusen, SDD are dynamic and can grow, shrink, resolve, or even recur. There is an increased risk for delayed dark adaptation, macular atrophy, and types 2 and 3 MNV. In fact, type 2 neovascularization in the setting of AMD occurs almost solely in eyes with SDD.

This 70YO female was referred for asymptomatic age-related macular degeneration. Vision was 20/30 OD and 20/25 OS.

Triton color imaging of both eyes shows symmetrical ribbon subretinal drusenoid deposits. On swept-source OCT, these lesions appear as hyperreflective material mostly between the RPE and ellipsoid zone (EZ).

Learning Points:
Subretinal drusenoid deposits (SDD) are polymorphous light-gray interconnected accumulations located above the RPE. They are present in about one-quarter of older adults with healthy maculas and in more than half of those with early-to-intermediate dry AMD. They can appear as an array of dots, interconnected reticular bands (as in our patient), or confluent lesions (Suzuki and Spaide, AJO 2014;157:1005-1012). The dot variant is associated with macular neovascularization (MNV) and the confluent variant with macular atrophy (Zhou et al, Ophthalmology 2016;123:1530-1540).

Clinically, they are often mistaken for conventional drusen and consist of similar yet distinct lipid-rich material found in soft drusen. They are localized to rods, unlike typical soft drusen, which are more central and cone-based. As with drusen, SDD are dynamic and can grow, shrink, resolve, or even recur.

Since they are located above the RPE, they are best visualized with blue or green illumination. On OCT, they appear in 3 stages (Zweifel et al, Ophthalmology 2010;117:303-312) growing upwards from the RPE towards the external limiting membrane: stage 1, diffuse deposition of granular hyperreflective material between the RPE and the EZ, stage 2 material alters the EZ contour, and stage 3 conical appearance breaking through the EZ. Rod function seems to be preferentially affected, and there is an associated increased risk of delayed dark adaptation, macular atrophy and types 2 and 3 MNV. In fact, type 2 neovascularization in the setting of AMD occurs almost solely in eyes with subretinal drusenoid deposits.

In addition to large drusen and pigmentary abnormalities, SDD is the 3rd risk factor for progression to late AMD (Agron et al, Ophthalmology 2022;129:1107-1119). For a recent review, see Wu et al, Progress Retinal Eye Research 2022;88;101017.

This 77YO female presented with vision of 20/20 OD and 20/30 OS and extensive bilateral subretinal drusenoid deposits.

Swept-source OCT shows numerous hyperreflective deposits in the outer retina located just above the RPE. En face OCT dramatically shows the extent of the dot-like drusenoid material.

Learning Points:

Subretinal drusenoid deposits (SDD) are polymorphous light-gray interconnected accumulations located above the RPE. They are present in about one-quarter of older adults with healthy maculas and in more than half of those with early- to intermediate-stage dry AMD. They can appear as an array of dots (as in our patient), interconnected reticular bands, or confluent lesions (Suzuki and Spaide, AJO 2014;157:1005-1012). The dot variant is associated with macular neovascularization (MNV) and the confluent variant with macular atrophy (Zhou et al, Ophthalmology 2016;123:1530-1540).

Clinically, they are often mistaken for conventional drusen and consist of a similar yet distinct lipid-rich material to that found in soft drusen. They are localized to rods, unlike typical soft drusen, which are more central and cone-based. As with drusen, SDDs are dynamic and can grow, shrink, resolve, or even recur.

Since they are located above the RPE, they are best visualized with blue or green illumination. On OCT, they appear in 3 stages (Zweifel et al, Ophthalmology 2010;117:303-312), growing upwards from the RPE towards the ELM (external limiting membrane): stage 1, diffuse deposition of granular hyperreflective material between the RPE and the EZ (ellipsoid zone), stage 2, material alters the EZ contour, and stage 3, conical appearance breaking through the EZ.

Rod function seems to be preferentially affected, and there is an associated increased risk of delayed dark adaptation, macular atrophy, and types 2 and 3 MNV. In fact, type 2 neovascularization in the setting of AMD occurs almost solely in eyes with subretinal drusenoid deposits.

This 86YO female has dry AMD and has subretinal drusenoid deposits (SDD) located above the RPE layer.

Since they are located above the RPE, they are best visualized with blue or green illumination. Notice how the SDD are easily visible on the Optos green channel but disappear in the red channel. Typical drusen (not pictured) would be best seen in the red channel.

The OCT images of a similar (but different patient) illustrate various stages of SDD with outer retinal atrophy.

Learning Points:
Subretinal drusenoid deposits (SDD) are polymorphous light-gray interconnected hypoautofluorescent accumulations located above the RPE. They are present in about one quarter of older adults with healthy maculas and in more than half of those with early to intermediate dry AMD.

Clinically they are often mistaken for conventional drusen and consist of the same lipid-rich membranous debris found in soft drusen. As with drusen, SDD are dynamic and can grow, shrink, resolve, or even recur.

SDDs can appear on OCT as they appear in 3 stages (Zweifel et al, Ophthalmology 2010; 117:303-312) growing upwards from the RPE towards the ELM:

Stage 1- diffusegranular hyperreflective material between the RPE and EZ
Stage 2- material alters the EZ contour
Stage 3- conical, breaking through the EZ

Rod function seems to be preferentially affected, and there is an associated increased risk of delayed dark adaptation, macular pattern dystrophy-like subretinal vitelliform deposits (image 9), geographic atrophy and types 2 and 3 macular neovascularization.

In fact, type 2 neovascularization in the setting of AMD occurs almost solely in eyes with subretinal drusenoid deposits.