B DOCTOR YOSEF KHAN.

In AMD many changes may occur that may have impact on the appearance of fundus images. Main confounders in AMD are drusen, pigment alterations, choroidal neovascularization as well as sub- and intraretinal fluids.

S

OFT

D

RUSEN

Soft indistinct drusen may appear relatively uniform on color fundus photographs. However, other imaging modalities may discover a variety of optical properties within different drusen.

C

OLOR FUNDUS PHOTOGRAPHY

(A)

On color fundus photos, soft drusen have a whitish to yellowish appearance with poorly defined borders. Between drusen, brown pigment clumping may occur. It is hard to decide whether fluids are present or not.

N

EAR

I

NFRARED

R

EFLECTANCE

(B)

On NIR, large drusen appear as dark ring-shaped structures with relatively normal internal reflectance. The darkening may account for discrete subretinal fluid and photoreceptor disorder leading to increased scatter of near-infrared light. Pigment clumps lead to very strong signals on NIR.

F

UNDUS

A

UTOFLUORESCENCE EXCITED AT

488

NM

(C)

Most large drusen show a slightly increased signal and some smaller drusen have considerably increased FAF488. At the fovea, there are also areas of increased FAF488 not co- located with drusen, suggesting alteration of the FAF488 signal by photoreceptor loss. The pigment clumps do not appear to influence FAF488 results.

F

UNDUS

A

UTOFLUORESCENCE EXCITED AT

787

NM

(D)

Slight FAF787 signal decreases suggest masking of RPE autofluorescence by drusen, which largely do not appear to incorporate active fluorophores at that wavelength. Only a few small drusen fluoresce weak in the near infrared. A strong signal is co-located with the pigment clumps, possibly caused by the incorporated melanin.

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B

ASAL LAMINAR DRUSEN

Typically basal laminar drusen are not limited to the macular area but are also distributed peripheral to the vascular arcades. They are much smaller than soft drusen and may be relatively inconspicuous on funduscopy.

F

LUORESCEIN

A

NGIOGRAPHY

After injection of fluorescein, basal laminar drusen become visible as multifocal dot-like staining (hydrophilic behavior). This results in a typical “stars-in-the-sky” appearance. However, larger, confluent drusen complexes may also be hydrophobic and can cause local blockage phenomena.

N

EAR

I

NFRARED

R

EFLECTANCE

Most of the basal laminar drusen show unchanged (small drusen) of slightly decreased NIR (large drusen). However when drusen confluence, NIR may be dramatically increased and a strong signal can be observed. This points to changes of the biochemical drusen structure by time.

F

UNDUS

A

UTOFLUORESCENCE EXCITED AT

488

NM

Small drusen appear as hypo-autofluorescent dots surrounded by generally increased, speckled background fluorescence, while large drusen result in irregularly decreased FAF488. This particular pattern of FAF488 may be caused through blockage of RPE autofluorescence by drusen and intermittent lipofuscin accumulation.

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G

EOGRAPHIC ATROPHY

Geographic atrophy is the end-stage of dry age-related macular degenerations. It is characterized by a progressive atrophy of the RPE and the overlying outer retina. The simultaneous presence of drusen and atrophy is characteristic and discriminates the imaging appearance of this type of age-related macular degeneration from inherited atrophic macular diseases like in central areolar choroidea dystrophy or in Stargardt disease.

C

OLOR FUNDUS PHOTOGRAPHY

A large region of RPE atrophy releases direct view on the choroidal vessels. Around the atrophy numerous soft drusen of various size are visible. A tiny retinal remnant at the center allows visual acuity of 20/25 despite a large scotoma.

N

EAR

I

NFRARED

R

EFLECTANCE

The NIR signal is significantly increased at the atrophic area by strong reflections from the sclera. The central, preserved retina appears darker than the surrounding atrophy. Some drusen show increased reflectivity possibly due to some calcification.

F

UNDUS

A

UTOFLUORESCENCE EXCITED AT

488

NM

The atrophy appears dark as a result of absence of fundus fluorophores at that wavelength. At the undestroyed fovea a spot of increased autofluorescence is visible, pointing to photoreceptor elongation and lipofuscin accumulation. The central atrophy is surrounded by a thin, hyper-fluorescent halo (junctional zone).

F

UNDUS

A

UTOFLUORESCENCE EXCITED AT

787

NM

At the atrophic area, the choroidal background fluorescence is readily visible. Two spots of hypo-fluorescence may be caused by blockage phenomena through calcified drusen. The junctional zone is fairly quiet and shows occasional fluorescence increase. This image is supportive to discriminate the part of FAF787 caused by RPE and that attributable to the choroid.

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C

HOROIDAL

N

EOVASCULARIZATION

The occurrence of fibrovascular membranes is a complication in many cases of age-related macular degeneration but may also take place in other diseases like high myopia, uveitis, macular dystrophies, etc. New vessels may appear beneath the RPE (type 1, mainly “occult” on fluorescein angiography) or subretinal (type 2, mostly “classic” on fluorescein angiography). A large number of cases are mixed-type. The neovascular membrane consists of blood vessels and fibrous tissue and leads to sub- and intraretinal fluid accumulation, fibrin exudation and pigment clumping. Therefore, complex optical interactions may be expected.

F

LUORESCEIN ANGIOGRAPHY

(A)

Active dye leakage is a major characteristic in fluorescein angiography. This classic case has partially dried and shows reduced leakage. Around the neovascular membrane some staining is visible.

N

EAR

I

NFRARED

R

EFLECTANCE

(B)

The fibrovascular membrane appears as a bright ring with a dark halo, suggesting a blood-rich core and surrounding strongly reflecting substances like fibrin and melanin. This reflects former histological studies showing pigment clumps and fibrinous exudates around a fibrovascular center. There is a poorly defined decrease if NIR parallels the leakage zone on FFA.

F

UNDUS

A

UTOFLUORESCENCE EXCITED AT

488

NM

(C)

At the choroidal neovascularization, FAF488 is markedly reduced. This is often associated with local RPE and photoreceptor loss and thus with a poor visual prognosis. A large hyperfluorescent nimbus exceeds the leakage zone, suggesting photoreceptor loss but preserved RPE owing to former serous retinal detachment.

F

UNDUS

A

UTOFLUORESCENCE EXCITED AT

787

NM

(D)

In FAF787 a strong ring-like signal is co-located with the bright corona on NIR. Even though there is scarcely any filter leakage at this wavelength, pseudofluorescence is a possible reason for this signal increase. A halo of slightly increased FAF787 co-located with that on FAF488 suggests changes to the RPE melanin due to former subretinal fluid accumulation.

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