Ординатура / Офтальмология / Английские материалы / Optical Coherence Tomography in Age-Related Macular Degeneration_Coscas_2009

The presence of reticular drusen (especially visible in blue light) adjacent to the temporal arcades is an additional risk factor for wet AMD. They are hardly seen on TD-OCT sections of perimacular zones.

These reticular drusen are much more clearly visible on SD-OCT and enlarged views, which show a thickening band and undulations of the RPE but with no alteration of the outer nuclear layer (Figure 6).

Drusen and Outer Retinal Layers

Moreover, one of the major advantages of SD-OCT is to visualize reactions in the outer retinal layers when present.

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As drusen increase in size, they raise the RPE band, IS/ OS interface, and external limiting membrane, which then can appear irregular, thinned, and disrupted. The outer nuclear layer can also be modified, thinned, and invaded by a homogeneous or jagged moderately reflective zone (Figure 6).

These alterations reflect damage to inner and outer segments and photoreceptors as a whole over the largest drusen. They therefore constitute valuable signs of the impact of drusen and possible photoreceptor damage

Analysis of drusen is based not only on anteroposterior scans, but also on 3D scans. Future clinical trials of drusen volume measurements will allow even more reliable quantitative assessment of their course (Figure 7).

Natural History

Atrophy

Drusen usually progress towards atrophy as the material regresses and is replaced by a zone of atrophy of the RPE (Figure 8). Atrophy can be seen on monochromatic images and especially on red-free images.

On fluorescein angiography, RPE atrophy causes hyperfluorescence due to a window defect with late and progressive staining, while atrophy is hypo-fluorescent on ICG angiography.

The OCT examination easily confirms the diagnosis of RPE atrophy by showing thinning of the RPE band associated with thinning or even loss of the outer retinal layers.

These areas of atrophy replace perifoveal drusen and then gradually spread to the center of the macula causing loss of vision (Figure 9).

Drusenoid PED

Soft drusen usually increase in size and become confluent, resulting in the appearance of a drusenoid PED (Figure 10). Biomicroscopic findings are already suggestive with a wavy, irregular elevation and pigment migration, which can be star-shaped or web-shaped.

On fluorescein angiography, hypo-fluorescence due to pigment migration and xanthophyll pigment contrast with the zone of progressive hyper-fluorescence corresponding to the drusenoid PED.

However, on SLO-ICG angiography, drusenoid PEDs and the surrounding soft drusen remain hypo-fluorescent even in late images.

On OCT, the RPE band is elevated with gently sloping or sometimes wavy edges. The underlying drusenoid material is usually moderately hyper-reflective and Bruch’s membrane becomes visible.

Pigment migrations induce zones of fairly intense hyperreflectivity that alter and sometimes disrupt the IS/OS interface and external limiting membrane. They can also extend into the retina, causing localized disorganization (Figure 11).

Neovascular Complications

Drusen may evolve spontaneously to choroidal neovascularization, which can be characterized by fluorescein leakage. The presence or absence of leakage on fluorescein angiography and the presence of subretinal or intraretinal fluid on OCT are the most reliable diagnostic signs.

OCT can also demonstrate slight intraretinal fluid, even at a subclinical stage. This would suggest the presence of choroidal neovascularization. OCT should therefore be considered in all patients with soft, confluent drusen or a drusenoid PED who present with functional changes such as metamorphopsias or vision loss

CNV can lead to the formation of a vascularized PED, precisely detectable on OCT, as illustrated by the following example (clinical case No. 1, page 184, Figures 12, 13, and 14).

Clinical Signs

A 75-year-old patient followed for decompensation of occult CNV in his first eye, presented with the absence of any symptoms, signs of ARM on routine examination of the fellow eye. This eye had fairly numerous, tightly packed mostly hard drusen of various sizes. The largest drusen are slightly autofluorescent. VA RE: 20/32 - VA LE: 20/20.

Angiography shows rapid and early staining of numerous hard drusen, sometimes in clusters or even confluent and sero-granular. Soft drusen are not stained at

8this stage. There is no fluorescein leakage.

SLO-ICG shows the presence of a small number of dark, hypo-fluorescent perifoveal soft drusen.

At this stage, these lesions therefore correspond to mixed, predominantly hard drusen without complications (Figure 12a-d).

Six Months Later

The patient reported moderate symptoms with minimal metamorphopsias and moderate loss of visual acuity in the left eye (20/32).

Biomicroscopic examination revealed a recently developed, moderately dense macular hemorrhage measuring 1/2 disc diameter with a relatively flat, eccentric SRF which was clearly visible on autofluorescence.

On angiography, an irregular hyper-fluorescent area with pinpoint leakage occupied the nasal half of the fovea, with diffuse fluorescein leakage. This lesion was lined by hemorrhage. SLO-ICG showed a dark PED, which was seen as hyper-fluorescence of an occult choroidal neovascularization.

Suggested Diagnosis:

Recent occult CNV with hemorrhage detected dur-

ing routine follow-up of mixed drusen (Figure 13a,

b, and c).

Autofluorescence a

SLO-ICG c

Autofluorescence a

During Follow-Up

Stratus* horizontal section: almost normal appearance (Figure 14a).

At the level of the RPE band: several irregularities and limited elevations of the RPE with no posterior shadowing and with poorly reflective material, suggesting small soft drusen. No hard drusen are visible.

Posterior to the RPE: no alteration.

Anterior to the RPE: retinal layers have a normal appearance. Note the slight asymmetry of the hypo-reflective zone corresponding to Henle fibers.

Six Months Later

Stratus* horizontal section: appearance highly suggestive of CNV (Figure 14b).

At the level of the RPE band: moderate but regular elevation of the hyper-reflective band of the RPE.

Posterior to the RPE: the PED cavity is slightly reflective allowing visualization of Bruch’s membrane.

Anterior to the RPE: diffuse increase of retinal thickness and presence of subfoveal hyper-reflective material, which probably corresponds to retinal hemorrhage.

Diagnosis

The OCT examination demonstrated a limited PED

(corresponding to the hypo-fluorescent area visible

on SLO-ICG angiography).

The PED appears to be relatively flat but is characterized by the visibility of Bruch’s membrane, which has become distinct from the RPE.

A small amount of intraretinal fluid can be seen ante-

rior to the RPE with increased retinal thickness, which is especially visible in the nasal sector.

In the central zone, the hypo-reflective band of the outer nuclear layer is thinned and partially displaced by a hyper-reflective zone, probably corresponding to

retinal hemorrhage.

These signs are suggestive of a small zone of subfo-

veal classic CNV.

Fluorescein angiography confirms the presence of

CNV by showing more marked localized hyper-fluo- rescence in this zone with fluorescein leakage.

On ICG angiography, the PED is localized and clearly visible. The sub-RPE fluid accumulation is due to leakage from occult CNV. A small area of classic CNV is also detected (but too small to show the features of a characteristic network).

This “minimally classic” CNV shows signs of recent decompensation, confirmed by hemorrhage, fluorescein leakage, the dark PED on ICG angiography, elevation of the RPE band on OCT, and moderate loss of visual acuity.

Anti-VEGF intravitreal injection is indicated, which

has to be followed regularly by VA and imaging.

The proposed treatment of monthly intravitreous injections of anti-VEGF (Lucentis*) was monitored each month by visual acuity, OCT, and fluorescein and ICG angiography with follow-up of one year.

Visual acuity initially declined with recurrence of symptoms during the second month then rapidly improved to become stable at 20/25 by the third month (ie, after the second injection).

A third injection of anti-VEGF was administered to

8maintain the result.

OCT

▬The thickness of the neurosensory retina decreased by the first month, but a prominent SRF, (which was confirmed with angiography) was observed after the first injection.

However, symptoms and loss of visual acuity were observed only at the third month.

The presence of a fine layer of subretinal fluid, which increased despite improvement of visual acuity, prompted continuation of treatment (Figure 15a-d).

▬At the fourth month, the situation was greatly improved with resolution of leakage and minimal persistence of a flat, partially organized PED.

▬However, one month later, recurrence of a marked SRF with signs of photoreceptor damage, justified another IVT injection (Figure 15e and f).

▬Subsequent follow-up OCT examinations showed a stable appearance with persistence of a small SRF but with no symptoms.

Despite partial normalization of the outer layers, SDOCT and the enlarged images showed signs of damage to outer segments, which had become abnormally visible and irregular at the edge of the SRF (Figure 15g and h).

The lesion appeared to have paradoxically increased in size after the first injection, extending superiorly and inferiorly.

It then stabilized with almost no change of irregular hyper-fluorescence. No signs of hemorrhage were visible, and the surface area of the lesion did not increase.

ICG Angiography

The neovascular network remained barely visible for the first 6 months. The dark PED can be seen but with poor delineation and poor contrast.

However, at the last 2 follow-up examinations, the neovascular network became more clearly visible and welldefined without an increase in size and appeared to be poorly perfused.

Conclusion

This case of drusen with a recent hemorrhagic com-

plication of minimally classic CNV illustrates rapid

subjective and objective improvement during the third month, after the second injection. Visual acuity

became 20/25 and remained stable on two successive examinations, therefore justifying temporary suspen-

sion of IVT injections.

However, a small recurrence was observed 2 months later that resolved immediately after the 4th injec-

tion. The situation then remained stable until the 12th month with no further treatment.

This improvement contrasts with the persistent SRF

observed on OCT, possibly due to fluid accumulation,

with signs of damage to outer segments, before

complete resorption.

These discordant findings indicated monthly followup.

The various types of drusen remain the best markers of early changes in age-related maculopathy.

The clinical presentation of drusen is variable and they are also considerably, but gradually modified during the course of the disease.

Drusen have often been used to analyze the various stages of ARM in order to create a severity index, which would allow ophthalmologists to predict progression to true macular degeneration, either atrophic or especially neovascular.

Biomicroscopic examinations and counting of drusen on color fundus photographs are widely used as they are inexpensive and easy to perform.

However, drusen are more readily visible and much more numerous on red-free photographs and especially fluorescein angiography.

SLO-ICG angiography allows simple and precise visualization of soft drusen, their confluence, and their progression towards drusenoid PED.

OCT is an added advancement, which demonstrates elevation of the RPE band, visibility of Bruch’s membrane, and the homogeneous or heterogeneous appearance of drusen deposits.

Spectral-Domain OCT has provided even greater advancement, as it can be used to analyze alterations of the external limiting membrane, IS/OS interface, and the outer nuclear layer, to detect signs of photoreceptor damage.

SD-OCT 3D volume reconstruction allows calculation of drusen volume, which would be useful for statistical studies.

Drusen volume is an inexpensive and quantifiable prognostic indicator that can be used to accurately monitor the response to treatment.

SD-OCT analysis of drusen, combined with fluorescein and ICG angiography, is useful for early diagnosis of complications and to differentiate from other diagnoses, which also cause RPE atrophy or lipofuscin deposits.