This document discusses different types of drusen and their characterization using multimodal imaging. It introduces soft drusen, cuticular drusen, and subretinal drusenoid deposits. Each type has distinct features on color photography, infrared imaging, autofluorescence, and optical coherence tomography. The document also discusses how drusen type relates to choroidal thickness and risk of developing different forms of neovascularization or geographic atrophy. A new classification system is proposed that better accounts for drusen subtypes and progression pathways in age-related macular degeneration.

1. DRUSEN CHARACTERIZATION
WITH
MULTIMODAL IMAGING

2. Introduction:
• Drusen are focal deposits of extracellular debris located between the basal
lamina of the retinal pigment epithelium (RPE) and the inner collagenous layer of
Bruch membrane
• Composed of lipid, carbohydrate, protein, zinc
• Types based on histology-complete ophthalmological examination including color
photography, fundus autofluorescence, near-infrared reflectance imaging,
spectral domain OCT (SD-OCT), and fluorescein angiography
• soft drusen,
• cuticular drusen,
• subretinal drusenoid debris

3. • SOFT DRUSEN –
• sub RPE
• linear membranous deposits
• CUTICULAR DRUSEN –
• densely packed, small, yellow-white nodular drusen that hyperfluoresce
during fluorescein angiography (‘‘starry-sky’’ fundus)
• first termed as basal laminar drusen by Gass
• subsequently renamed as cuticular drusen
• SUBRETINAL DRUSENOID DEBRIS –
• originally termed ‘‘reticular pseudo-drusen,’’
• aggregations containing typical drusen associated molecules but located in
the subretinal rather than the sub-RPE space

4. • Soft drusen are formed by mounds of deposit
under the retinal pigment epithelium. Soft
drusen generally range in size from more than
63 micron diameter. There may be some
attenuation of the retinal pigment epithelium
over the apex of the druse.
• Cuticular drusen are 50 mm to 75 mm in
diameter and jut up through the thickness of
the overlying retinal pigment epithelium.
• Subretinal drusenoid deposits show a range of
sizes larger than that of soft drusen; they can
be confluent and consequently be quite large
but also can have refractile elements that
emulate the appearance of cuticular drusen

5. Soft drusen Cuticular drusen Subretinal
drusenoid debris
Fundus photograph Yellow white
63-1000 micron
Centre lighter
than edge
Uniform,round,
punctate
50-75 micron
More pale yellow
FFA Minimal
hyperfluroscent in
later stage
Multiple pin point
hyperfluroscent
No to minimal
hyperfluroscence
Autofluroscence Hyperautofluroscent
(edge more)
hypoautofluroscent hypoautofluroscent
Infrared imaging Subtle variation hypo hypo
Histology Basal linear deposit RPE,blunted
triangles
Above RPE, conical
flattened, short
photoreceptor

6. • Color photograph.
• Infrared reflectance decreased
brightness in the region of the
soft drusen.
• Autofluroscence- There is a
subtle increase in
autofluorescence at the outer
edges of several drusen.
• OCT- showing the deposition of
material under the retinal
pigment epithelium.

7. • Numerous small drusen in the color photograph
• Near-infrared images.
• The autofluorescence image shows innumerable small hypoautofluorescent dots. These may
represent the numerical summation of both thinning of the overlying retinal pigment epithelium
and focal areas of retinal pigment epithelium degeneration
• OCT-closely packed blunted triangles, the bases of which sit on Bruch membrane with apices
toward the retina

8. Subretinal drusenoid deposits
• Color photograph -numerous
pinpoint drusen-like structures that
superficially resemble cuticular
drusen.
• Near-infrared scan- dark spots
corresponding to the small
drusenoid deposits .
• The autofluorescence image -
hypoautofluorescent spots
• OCT - conical deposits above the
retinal pigment epithelium.

9. • The RPE absorbs and attenuates blue light.
• SDD are on top of the RPE and therefore do not have any blue light attenuation.
Soft and cuticular drusen are under the retinal pigment epithelium, which attenuates blue
light in their reflective spectral profiles.
• Local thickness changes in the overlying retinal pigment epithelium are more acute for
cuticular drusen than for soft drusen. Retinal pigment epithelium thickness at the apex
of a cuticular druse is less than at the druse edge  less pigment to block the
excitation light used in fluorescein angiography and may account for the pinpoint
hyperfluorescence seen with these drusen

10. • Both cuticular and soft drusen appear yellow because of the removal
of shorter wavelength light by a double pass through the RPE.
• SDD are located on the RPE, are not subjected to short-wavelength
attenuation and therefore are more prominent when viewed with blue
light

11. DISEASE EXPRESSION IN
NONEXUDATIVE
AGE-RELATED MACULAR
DEGENERATION VARIES WITH
CHOROIDAL THICKNESS

12. • Accumulations of medium drusen (63–125 micron) or the appearance of a single
large drusen (>125 micron) constituted the threshold to diagnose AMD in the
Age-Related Eye Disease Study (AREDS)
• Pseudodrusen are extracellular accumulations of material located internal to the
RPE, under the retina, thus are called subretinal drusenoid deposits or SDD,
associated with thin choroid

13. • Disease expression of nonexudative AMD seemed to vary with choroidal
thickness
• Subretinal drusenoid deposits were more likely to be found in eyes diagnosed
with AMD if the choroid was thinner.
• Eyes with normal choroidal thickness were more likely to have conventional, soft
drusen
• SDD can be considered part of the AMD spectrum
• In AMD, choroidal thickness seems to have an important association with disease
expression.

14. PACHYDRUSEN
• Some patients may develop CNV after CSCR
• Associated with pachychoroid
• These patients showed the risk of ARMD
• Distinctive form of drusen that occur in eyes with what may be a thick choroid
that can be differentiated from the drusen typically seen in AMD.
• Drusen are generally larger than 125 micron, their appearance, grouping, and
pattern of distribution are different than typical soft drusen.

15. • A- Soft drusen often aggregate in the central macula, with a poorly defined ovoid outer
contour, focal hyperpigmentation. The larger choroidal vessels can often be faintly seen.
• B- pachychoroid-associated drusen can have a round or ovoid shape, they typically have more
complex outer contour. The choroid seems featureless and has a redder hue than does thinner
choroids.
• C- red hue, variation in the amount of pigmentation at the level of the RPE. The drusen may have
an undercut, eroded outer contour. There can be projections jutting from the central accumulations
of material.

16. Pachychoroid-associated drusen.
A. An isolated large drusen (arrow) near a choroidal nevus (open arrow), fundal red hue
B. The subfoveal choroidal thickness 594 mm.
C. Scattered pachychoroid-associated drusen. The drusen manifest unusual shapes and do not
have the grouping of typical soft drusen .
D. The subfoveal choroidal thickness is 352 mm

17. Subretinal drusenoid deposits (pseudodrusen).
A. widely scattered SDD that do not involve the
central macula. The underlying larger choroidal
vessels are easily seen and can have a yellowish hue.
B. The subfoveal choroidal thickness was 121 mm.
The SDD are seen as subretinal accumulations of
drusenoid material
Soft drusen
A. Close aggregation of round-to-ovoid deposits that
become confluent in the temporal juxtafoveal region.
There is focal hyperpigmentation over this area.
B. The subfoveal choroidal thickness was 162 mm. There
are homogenous accumulations under the subRPE

18. PACHYDRUSEN
• Scattered drusen with irregular outer
contours. There is widely varying
pigmentation throughout the posterior pole
• Autofluorescence image showing focal areas
of hypoautofluorescence and some small
areas of hyperautofluorescence indicative of
the RPE abnormalities.
• Indocyanine green angiography shows
multifocal hyperfluorescent areas of
choroidal vascular hyperpermeability.
• The subfoveal choroidal thickness is 377 mm.
There are drusenoid accumulations visible
under the RPE.

19. • Subretinal drusenoid deposits(pesudodrusen) are associated with GA
and with Type 2 and Type 3 CNV.
• Pachychoroid drusen shows an association with Type 1 CNV and
polypoidal choroidal vasculopathy
SDD(PSEUDODRUSEN) TYPE2 AND TYPE 3 CNVM
PACHYDRUSEN TYPE 1 CNVM,PCV

20. IMPROVING THE AGE-RELATED
MACULAR DEGENERATION
CONSTRUCT
NEW CLASSIFICATION SYSTEM

21. • Previous models did not encompass subretinal drusenoid deposits (pseudo-
drusen), subtypes of neovascularization, and polypoidal choroidal vasculopathy.
• In addition, Type 3 neovascularization starts in the retina and may not
necessarily involve the choroid.
• Soft drusen preferentially are found in areas of high cone density.
• Subretinal drusenoid deposits are preferentially found in regions with a high rods
density

22. • New aspect includes specific lipoprotein extracellular accumulations, namely
drusen and subretinal drusenoid deposits, as early AMD (corelatable with
choroidal thickness)
• Late AMD includes macular neovascularization or atrophy
• Type of extracellular deposit is predictive of the future course of the patient

23. • The proposed classification has predictive capabilities.
• Eyes with SDD can go on to atrophy, particularly associated with confluent SDD
• Whereas macular neovascularization, typically Type 3 macular neovascularization,
can develop associated with the dot form of SDD.

24. • Pachydrusen are associated with thick choroids , which in turn are associated
with progression to Type 1 macular neovascularization or PCV.
• Soft drusen can go to GA through regression or to Type 1 macular
neovascularization.
• A more typical path is to form focal hyperpigmentation, and in addition to GA,
Type 1, Type 2, and Type 3 macular neovascularization can develop