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

Clinical Signs

An 83-year-old monocular woman due to longstanding AMD presented with recent, progressive decline of visual acuity in the right eye with metamorphopsias, which interfered with reading.

VA RE: 20/63 - VA LE: 20/200.

Biomicroscopic Examination

Vast, heterogeneous, grayish lesion of the posterior pole, 3 DD in diameter, located subfoveally but extending as far as the optic disc without hemorrhage.

Autofluorescence

An elongated, interpapillomacular, heterogeneous, hypofluorescent area with an irregular crown of hyper-fluores- cence (Figure 6a, b, and c).

11 Fluorescein Angiography (Figure 6d)

Early and intense hyper-fluorescence of the entire welldefined and well-delineated interpapillomacular lesion

with a network of radial neovascularization and a peripheral anastomotic arcade. These encroached onto the fovea and caused intense fluorescein leakage.

SLO-ICG Angiography (Figure 16e)

The neovascular membrane rapidly filled and was drained by several large vessels in the region between the optic nerve and macula. The network was composed of thin but dense vessels, which occupied all of the foveal region.

Suggested Diagnosis:

Large subfoveal classic CNV extending to the optic

disc. It arose in the region between the optic disc and

the macula with no detectable occult CNV associated

with it.

Horizontal section

The RPE was clearly visible and appeared to be thickened in the foveal region and as far as the optic disc, with a hyper-reflective band just anterior to and almost fused with the RPE.

Anterior to the RPE, a small amount of intraretinal fluid with increased retinal thickness, displacement of the central retina, and loss of the foveal depression (Figure 7a).

Vertical section

The hyper-reflective band anterior to the RPE was more clearly visualized in the foveal region with a moderate increase of retinal thickness and diffuse intraretinal fluid.

The hyper-reflective classic CNV displaced the neurosensory retina anteriorly with slight attenuation of the foveal depression (Figure 7b).

Monthly intravitreous injections of anti-VEGF therapy were continued for 1 year with follow-up by visual acuity, OCT, fluorescein angiography, and SLO-ICG angiography. The response to treatment was initially satisfactory but was followed by gradual deterioration of visual function over the last months of follow-up.

Visual acuity initially improved to 20/40 after the first 3 injections, then gradually decreased to 20/80.

TD-OCT

On the first follow-up examination

Regression of intraretinal fluid and reduction of retinal thickness (206 μm), but the pre-RPE hyper-reflective band became more clearly visible and denser (false white color) (Figure 8a).

At the third month

11 The appearance was similar, but the increased thickness of the hyper-reflective zone justified a third intravitreous injection, which was followed by functional improvement (Figure 8b).

SD-OCT

At the ninth month

The SD-OCT signs showed partial improvement, especially in the foveal region. However, despite quarterly maintenance IVT injections, examination of layers demonstrated the presence of a fine hyper-reflective band just

At this Stage

This case of large, isolated classic CNV was demon-

strated on OCT as hyper-reflective material, which dis-

placed the neurosensory retina anteriorly, with slight attenuation of the foveal depression.

These signs were suggestive of a well-delineated,

large, subfoveal classic CNV membrane extending as far as the optic disc and without any associated occult neovascularization.

The response to treatment was immediately favorable

with regression of the small amount of intraretinal fluid and fluorescein leakage (but without major alteration of the outer retinal layers).

anterior to the RPE, suggestive of fibrosis of the neovascular membrane.

The IS/OS interface was visible and thickened with alteration of the nuclear layer in the central region (Figure 8c). Most importantly, signs of complete atrophy of the outer retinal layers were observed with loss of the outer nuclear layer in the region between the optic disc and the macula.

On the last examination

One year after onset of the disorders, atrophy of the outer retinal layers in the region between the optic disc and the macula was confirmed.

The external limiting membrane and IS/OS interface were visible in the foveal zone and a fine hyper-reflective band was still present anterior to the RPE (Figure 8d).

Fluorescein Angiography

The neovascular membrane and fluorescein leakage regressed and then completely resolved by the third month. However, atrophy of the RPE gradually spread to involve the entire macular region as far as the optic disc.

This atrophy was confirmed on autofluorescence by extension of hypo-fluorescent spots throughout this region (Figure 8a-d).

ICG Angiography

Rapid regression of the membrane, which became undetectable by the second month (Figure 8a-d).

A minor recurrence justified a 3rd injection followed by maintenance therapy every 3 months.

After one year of follow-up, 3 months after the last treatment, improvement was maintained. However, persistence of a fine hyper-reflective band just ante-

rior to the RPE, (suggestive of fibrosis) with thickening of the IS/OS interface and alteration of the nuclear layer was demonstrated by SD-OCT.

Stabilization of the lesion with useful VA justified suspension of IVT injections but with prolonged and close follow-up.

a

Æ IVT 1

b

Æ IVT 3

c

Æ Abstention

b

External Limiting Membrane

▬Fluorescein angiography provides major, easy to interpret, and a recognized source of information for the diagnosis of classic choroidal neovascularization.

These other imaging modalities can also help identify those cases with a good prognosis (“good responders”) and those more difficult cases requiring more complex treatments.

It demonstrates the neovascular membrane, its afferent and efferent branches, its anastomotic arcade, and the characteristic fluorescein leakage (when at least one early frame and one late frame are available).

Fluorescein angiography has therefore become the “gold standard” for the diagnosis and localization of classic choroidal neovascularization.

▬Time-Domain OCT has rapidly acquired an important role, as it is easy to perform and allows almost intuitive interpretation of the main findings.

Classic CNV is usually visualized as a spindle-shaped hyper-reflective subretinal band anterior to and in contact with the RPE (Figure 9).

This band is accompanied by an exudative reaction, easily identified as a subretinal optically empty zone associated with diffuse intraretinal fluid and cysts that can become large.

Variations of intraretinal fluid can be easily compared by following retinal thickness (central or in various sectors in the macular region).

TD-OCT has therefore become a first-line test to evaluate response to treatment.

▬However, TD-OCT findings must be confirmed by angiograph–not only in unclear and difficult cases– but also for decision making.

This is particularly helpful when deciding whether to continue intravitreous injections, the intervals between injections, and when treatment should be stopped.

Other imaging modalities also provide complementary data that are useful to establish a precise diagnosis, and to more accurately follow the natural history or the response to treatment.

▬SLO-ICG angiography therefore appears to be essential to determine whether classic CNV is isolated or associated with occult CNV, either at presentation or subsequently.

ICG angiography is also important to identify polypoidal formations and its accompanying abnormal choroidal vascular membrane.

Another use of ICG angiography is in the detection of chorioretinal anastomosis within a hot spot and with intense leakage.

▬The more recently available SD-OCT imaging provides more information for the demonstration of classic choroidal neovascularization.

SD-OCT confirms the typical features of CNV such as:

▬The absence of a PED,

▬The pre-RPE site of classic CNV, and

▬Intraretinal leakage.

SD-OCT also allows visualization of the outer retinal layers and can therefore detect alterations of photoreceptors (inner segments/outer segments) and the outer nuclear layer (Figure 10).

These structures are profoundly altered by proliferation of classic CNV, but their presence or reappearance are excellent markers of a favorable outcome.

Complete resolution of hyper-reflective classic CNV or, on the contrary, persistence of more or less intense subretinal fibrosis are usually well-correlated with visual acuity.

▬SD-OCT, when correlated with the various imaging modalities, is particularly useful in classic choroidal neovascularization to:

–Confirm whether classic CNV is isolated or associated with occult CNV,

–Monitor the response to treatment, and

–Determine the frequency and duration of IVT injections.

Definitions

Atrophic form or “Dry AMD” is defined by areas of RPE atrophy, often resulting from regression of confluent soft drusen.

These areas of atrophy, usually perifoveal, gradually spread to become confluent, forming a partial, then complete ring, and finally involving the center of the macula.

At this stage, the visual symptoms, initially moderate and related to a paracentral scotoma, suddenly deteriorate with marked loss of visual acuity because the fovea is no longer spared.

The primary RPE lesion is associated with alteration, then obliteration of the underlying choriocapillaris, and death of photoreceptors in the zones of RPE atrophy.

These areas of atrophy generally present with clearly demarcated, irregularly shaped margins (“geographic atrophy”). They are frequently highlighted by a hyperpigmented border in the junctional zone. Accumulation of lipofuscin in this area results in accentuated autofluorescence.

Histologically, RPE atrophy is accompanied by a loss of the outer nuclear layer, and the outer plexiform layer becomes in direct contact with basal laminar deposits

Complications

Atrophy therefore constitutes one of the major complications of age-related maculopathy (ARM or precursor stage) which progresses to age-related macular degeneration.

Dry AMD is characterized by the absence of an exudative reaction.

However, choroidal neovascularization can occur at any time during the course, usually on the foveal margin of an area of atrophy.

Deterioration of visual impairment therefore may not only be directly correlated with extension of atrophy but also to CNV proliferation.

This justifies a complete imaging assessment whenever a patient with already diagnosed dry AMD experiences a deterioration of visual acuity.

There are several possible causes of atrophy.

▬Geographic atrophy is the most common form. This term refers to all types of RPE atrophy, which extend and progressively coalesce and cause degeneration of overlying photoreceptors.

These lesions are well-delineated and sometimes present with irregular “geographical” contours.

Atrophic areas, derived from degeneration of drusen, are initially isolated and perifoveal. They then gradually enlarge to form areas measuring 1/4 to 1/2 DD with retinal pigment migrations.

Areas of atrophy slowly become organized all around the fovea, initially with central sparing. Slow involvement of the central fovea follows, which results in severe loss of visual acuity. These lesions are often bilateral and symmetrical but not necessarily simultaneous.

▬RPE tears can lead to the formation of an atrophic area in the zone exposed by retraction of the retinal pigment epithelium.

▬Loss of vitelliform material, replaced by a zone of macular atrophy, is another way dry AMD may develop. There is sometimes residual vitelliform material around the edges associated with this type of atrophy.

Frequency

The frequency of dry AMD is much higher than suggested by the first studies, which were conducted in tertiary care centers.

General population studies tend to show that dry AMD is just as frequent as wet AMD.

Indocyanine Green Angiography

The screen formed by the normal RPE is attenuated in infrared light. However, loss of RPE allows visualization of the rare, but persistently perfused choroidal vessels that may cross beneath these areas.

In the late phases, RPE atrophy is characterized by slight hypo-fluorescence (Figures 1f and g).

The course of dry AMD may be complicated by choroidal neovascularization, particularly at the foveal margins. CNV is clearly visible on SLO-ICG angiography.

Contribution of OCT

OCT constitutes an easy-to-use imaging modality for follow-up and detection of complications of dry AMD that must subsequently be confirmed by angiography.

Time-Domain OCT

This is easily demonstrated on multiple TD-OCT sections. This shadowing usually masks the thinning and/or loss of the RPE.

▬The second diagnostic sign is thinning of the neurosensory retina over zones of atrophy, which is particularly serious when it involves the central zone.

Thinning of the central retina correlates well with loss of central visual acuity.

On closer examination, loss of the hypo-reflective layer corresponding to the outer nuclear layer can be seen.

▬The third important feature is the absence of exudative signs.

Any increase in retinal thickness at the edge of a zone of atrophy must raise the suspicion of a neovascular complication.

Spectral-Domain OCT

The signs described above are easily demonstrated on SDOCT. In addition, the following attributes can be seen:

▬Thinning and loss of the RPE are clearly visualized, but maintenance of the straight line representing Bruch’s membrane is an important sign.

▬The external limiting membrane and IS/OS interface are severely altered and/or no longer visible and become disrupted early.

▬In the most severe forms, the outer nuclear layer is no longer visible in the zones of atrophy.

▬The outer plexiform layer comes directly in contact with Bruch’s membrane. This accounts for thinning of the neurosensory retina, while the inner retinal layers may remain relatively unchanged.

Prognosis

RPE atrophy is irreversible and causes death of almost all photoreceptors in the atrophic area, resulting in a corresponding scotoma.

Due to the current absence of effective treatment, dry AMD has a poor prognosis despite the hopes raised by a recent clinical trial (AREDS study), which demonstrated the benefits of antioxidants, vitamin A, and vitamin C supplements.

The intense back-shadowing in zones of atrophy, extending well into the choroid, is the defining sign of atrophy.

Future research includes ongoing studies on micro-nutri- tion and as well as RPE transplantation procedures.