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

Since Donald Gass’s pioneering work in 1967, which demonstrated the role of choroidal neovascularization (CNV) in wet (exudative) AMD, visible (classic) CNV well-demarcated and well-defined on fluorescein angiography, has become the most characteristic form of AMD.

Initial Definitions

Classic CNV has a typical clinical course, presenting with rapid and severe symptoms. It is defined by its characteristic angiographic signs: a clearly visible neovascular membrane causing early and intense fluorescein leakage (Figure 1).

The rapid progression of choroidal neovascularization, initially extrafoveolar or juxtafoveolar, towards the center of the fovea, constitutes a major threat to vision. Classic choroidal neovascularization therefore was considered a therapeutic emergency at a time when only laser photocoagulation could halt its progression and preserve useful vision.

Fluorescein angiography combined with indocyanine green angiography allowed not only early diagnosis but also exact localization of the neovascularization, which lead to the distinction between classic choroidal neovascularization and occult choroidal neovascularization. The latter form is poorly-delineated and poorly visible on fluorescein angiography.

Current Classification

From pathological correlations, Donald Gass proposed an even better classification based on anatomical location:

▬Type 1: Neovascularization arising between Bruch’s membrane and the RPE.

▬Type 2: Neovascularization arising between the RPE and the neurosensory retina (after penetrating

through the RPE).

As indicated in the 2008 Annual Report of the French ophthalmological Society (G. Soubrane), it is now unanimously agreed that:

▬Classic choroidal neovascularization arises and proliferates anterior to the RPE (pre-RPE choroidal neovascularization).

Examination of early lesions and their natural history has demonstrated that:

▬Isolated classic pre-RPE CNV rapidly leads to severe and acute complications that dominate the clinical picture.

▬In a different context, initially isolated occult subepithelial CNV can be progressively complicated by the proliferation of classic choroidal neovascularization, either small (minimally classic), or large (predominantly classic).

Only systematic use of SLO-ICG angiography is able to demonstrate or exclude the presence of initially poorly-de- fined occult CNV associated with classic CNV (Figure 1). A combination of these two types of CNV (classic and occult) is the form most frequently observed in clinical practice.

Frequency

Isolated classic choroidal neovascularization appears to be relatively rare and has been estimated (in several publications) to represent between 10% and 15% of newly diagnosed cases.

However, isolated classic choroidal neovascularization is important clinically due to its rapid course and the need for rapid angiographic assessment.

Immediate treatment is essential due to the rapid and severe threat to central vision, caused by exudative reactions, hemorrhages, and later fibrous proliferations.

These complications cause irreversible damage to photoreceptors and vision.

Contribution of OCT

contrast, are extremely suggestive and characteristic, OCT is able to provide additional information:

▬By evaluating the presence of an exudative (and/or hemorrhagic) reaction by means of indirect signs, such as intraretinal fluid, even initially limited.

▬By demonstrating the presence of the hyper-reflec- tive, subretinal complex anterior to the RPE, typical of classic CNV.

▬By demonstrating in many opportunities, the presence of a PED, indicating the concomitant presence of poorly-defined occult CNV that may be missed on fluorescein angiography.

Comparison of fluorescein angiography and SLO-ICG angiography findings with OCT images validates interpretation of the direct and indirect signs observed on OCT, confirms the diagnosis of classic CNV, and helps to guide treatment.

Imaging Modalities

TD-OCT visualizes indirect signs and direct signs.

11

Indirect signs:

Indirect signs are related to abnormal leakage with subretinal and intraretinal fluid accumulation.

The serous detachment of the neurosensory retina is usually moderate, essentially visible at the edge of the hyperreflective zone. It may sometimes be more extensive.

Accentuation of vascular leakage results in intraretinal fluid either diffuse with increased retinal thickness, or collected in the cystoid spaces of inner retinal layers (Figure 1).

During the progression of disease, cysts can become numerous, larger, spread to multiple layers, or travel towards the center of the fovea.

Intraretinal fluid and the presence of a hyper-reflective complex and their associated inflammatory reaction induce progressive loss of the foveal depression, which is sometimes replaced by a marked elevation.

A zone of posterior shadowing is another fairly specific indirect sign of hyper-reflective classic CNV that limits passage of light towards the posterior pole.

Finally, OCT demonstrates irregularities or thickening of the RPE band and sometimes even localized disruption, suggesting protrusion of neovascularization.

Direct signs:

The essential direct sign indicating the presence of classic CNV is a fairly intense zone of hyper-reflectivity anterior to the RPE (Figure 1).

This hyper-reflective complex is usually spindle-shaped, sometimes distinct from the RPE or, on the contrary, adherent and even fused with the RPE. It is outlined by a zone of posterior shadowing. The exact nature of this poorly-demarcated hyper-reflective zone is difficult to determine on TD-OCT.

SD-OCT

Indirect signs of intraretinal fluid and direct signs of hy- per-reflectivity are also seen, but even more information can be learned from analysis of the retinal layers and their abnormalities.

The RPE (although attenuated by shadowing due to the neovascular lesion) remains clearly visible and is not detached from Bruch’s membrane.

Analysis of serial (raster) sections often reveals one or several disruptions in the RPE allowing passage of classic

CNV.

Anterior to the RPE, a SRF is almost always present (often with shifting fluid), and its internal and external margins are often highlighted by bright hyper-reflective spots

The neovascular membrane is visualized by a zone of hyper-reflectivity, whose contours appear to be continuous with a thickened and hyper-reflective IS/OS interface

The external limiting membrane is displaced and often disrupted over the neovascularization.

The hyper-reflective zone corresponding to classic CNV comprises a denser zone (with scattered bright hyper-re- flective spots) that invades or displaces the outer nuclear layer. As a consequence, the outer nuclear layer becomes poorly visualized.

Diffuse intraretinal fluid and cysts induce major changes of the middle and inner retinal layers. The hyper-reflec- tive lesion and intraretinal fluid induce loss of the foveal depression and a marked increase in central retinal thickness.

Vitreomacular adhesions often persist.

Clinical Signs

A 68-year-old woman with known AMD for three years presented urgently for metamorphopsias and recent rapid loss of vision in the right eye. She was monocular with long-standing poor vision in the left eye.

VA RE: 20/100 - VA LE: 20/400.

Biomicroscopic examination: hemorrhagic, central foveal macular lesion measuring about 1 DD, surrounded by numerous hard drusen.

Autofluorescence: the central hemorrhage was located over the xanthophyll pigment with a large circular halo of hyper-fluorescence (Figure 2a and b).

Fluorescein Angiography (Figure 2c and d)

Deep retinal hemorrhage with irregular margins in the center of the macula, crossed by several retinal vessels.

11 The hemorrhage was surrounded by a crown of numerous, miliary, hard drusen with a few soft drusen.

Well-demarcated hyper-fluorescence was observed in the center and gradually increased with fluorescein leakage and pooling in cystoid spaces.

SLO-ICG Angiography (Figure 2e and f)

Early phase: Despite the hemorrhage, the neovascular membrane was rapidly perfused with several radial branches and a peripheral arcade.

Late phase: The membrane became clearly visible on ICG angiography but was partially masked in the thicker zones of the hemorrhage.

This lesion was isolated with no other choroidal abnormalities and no occult neovascularization.

Suggested Diagnosis:

Small classic CNV membrane (1 DD) partially masked by hemorrhage. SLO-ICG angiography confirmed no associated occult neovascularization.

Horizontal section

Multiple, minor irregularities of the RPE were observed but without signs of separation from Bruch’s membrane. The RPE was partially masked by shadowing due to a pre-RPE hyper-reflective lesion, but remained visible with a possible disruption (arrow).

Anterior to the RPE, the outer nuclear layer, external limiting membrane, and IS/OS interface were well-visualized on either side of the central lesion with a small SRF.

The IS/OS interface was gradually thickened in the central zone and appeared to delineate a large hyper-reflec- tive complex anterior to the RPE. This caused posterior shadowing.

The outer nuclear layer remained visible, but was partially invaded by a more reflective, dense zone related to hemorrhage. The inner retinal layers remained well-organized but with a large central cyst.

Vertical section

The RPE (partially masked by shadowing) and the small SRF were well-visualized, together with the vast pre-RPE hyper-reflective complex, which corresponded to classic CNV. The dense zone masking the outer nuclear layer probably corresponded to retinal hemorrhage anterior to the CNV.

The zone corresponding to the autofluorescent halo consisted of small hyper-reflective zones in the outer retinal layers, suggesting the presence of lipofuscin deposits.

Monthly intravitreous injections of anti-VEGF (Ranibizumab*) were continued for 6 months with follow-up by visual acuity, OCT, fluorescein angiography, and ICG angiography.

Immediately satisfactory results were obtained with rapid stabilization.

Visual acuity was markedly improved by the first examination, increasing to 20/40 and then stabilizing at 20/32 with resolution of metamorphopsias.

SD-OCT

By the first follow-up examination

Intraretinal fluid decreased considerably with resolution of cysts and a marked decrease in retinal thickness

(429 μm).

11

The hyper-reflective lesion remained unchanged, but the outer retinal layers were more clearly visible: the IS/OS interface remained thickened and the external limiting membrane was visible with several bright hyper-reflective spots.

The dense zone of hemorrhage was markedly decreased and the outer nuclear layer regained a regular appearance (Figure 3a).

At this Stage

This case of isolated classic CNV associated with mac-

ular hemorrhage immediately showed a favorable response to treatment.

Pre-treatment SD-OCT demonstrated a pre-RPE hy- per-reflective complex with leakage and disorganiza-

tion of the outer retinal layers.

Intraretinal fluid resolved rapidly with improvement

of visual acuity, a normal appearance to the outer reti-

nal layers, and resolution of inflammatory signs.

No marked relapse was observed during 6 months

of follow-up, but a 3rd injection was helpful.

After the second injection

Improvement continued with resolution of intraretinal fluid and bright hyper-reflective spots. Outer retinal layers were almost normal.

At the third month

Recurrence of a small SRF and several bright hyperreflective spots, justifying a third injection.

At the sixth month

No signs of leakage were present and the outer retinal layers were clearly visible and well-organized. However, the fovea remained elevated by the well-delineated, dense, pre-RPE hyper-reflective complex, suggestive of progressive fibrosis of classic CNV.

Fluorescein Angiography

The neovascular membrane rapidly decreased in size and became retracted with no fluorescein leakage. Only a limited zone of late staining with a small peripheral residual hemorrhage was still visible (Figure 3a-d).

ICG Angiography

Rapid regression of the membrane was seen and it was no longer visible after the second month (Figure 3a-d).

Even still, the pre-RPE hyper-reflective complex per-

sisted, suggesting progressive fibrosis

It was denser than at the beginning but was welltolerated with no major reactive signs.

Treatment was suspended in view of the rapid stabili-

zation of the lesion with satisfactory visual acuity.

The persistence of fibrosis anterior to the RPE justified

continuing observation.

A close and prolonged observation remained neces-

sary, particularly due to the fact of the irreversible loss

of vision in the fellow eye.

FA

c

Æ IVT 3