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

▬This PED, which may be serous and optically empty, is associated with choroidal neovascularization, has variable prominence, and is sometimes domeshaped.

Size

The size of this serous space depends on the degree of exudation and the type of neovascularization.

▬PED (or its serous component) may be associated with varying densities of fibrovascular proliferation, which is moderately reflective and heterogeneous on OCT, and corresponds to a fibrovascular

PED

8▬ The PED can also be serosanguinous or even hemorrhagic. Blood blocks the light, giving this type of PED an opaque appearance with marked posterior shadowing.

The term vascularized PED is often used to describe its origin from abnormal exudation of choroidal neovascularization, or to describe its variable composition, from a predominantly serous space to the fibrovascular form with predominant fibrosis.

Various Clinical Appearances of PED

Different clinical appearances of PEDs (which may simply correspond to successive stages) can be distinguished on OCT:

▬Either an apparently optically empty cavity almost entirely filled with serous fluid, or

▬A moderately reflective cavity suggesting the presence of fibrovascular tissue or fibrotic scar tissue (which may be very marked).

▬Wavy PED comprising several more or less flattened spaces, observed in advanced and organizing forms.

Spectral-Domain OCT (SD-OCT) allows more detailed analysis by demonstrating:

▬Hyper-reflectivity due to superficial or deep retinal hemorrhage, or hemorrhage underneath the RPE, or mixed hemorrhage (often associated with retinal tears),

▬Hyper-reflectivity due to other causes (deposits, pigment, fibrosis, etc.), and

▬The outer retinal layers separately

SD-OCT allows increasingly detailed analysis of the outer retinal layers

It can demonstrate alterations in the outer nuclear layer external limiting membrane, and IS/OS interface

These landmarks, delineating the outer segments and inner segments, are used to detect signs of photoreceptor cell damage.

These alterations are related to the presence and progression of neovascularization. These same areas can subsequently become fibrous scarring with possible atrophy of these outer retinal layers.

The presence of reactive signs, such as bright hyperreflective spots and dense zones, appears to be particularly informative.

These reactive lesions are sometimes reversible, suggesting that they may correspond to a concurrent and adjacent inflammatory response.

Imaging Modalities

TD-OCT clearly distinguishes the various features of PED:

▬Minimal PED: in the early forms,

▬Rounded and bullous, optically empty PED serous space associated with occult CNV that appears to be situated in a notch, or

Histological Correlations

Recently published studies on Ultrahigh-Resolution OCT (UHR-OCT) suggest the possibility in the near future, of almost histological detection of photoreceptor cell damage.

Modern OCT therefore plays a major role in not only diagnosing and following AMD but also helps to improve our understanding of the pathogenesis of the disease.

A series of clinical cases illustrate the contribution OCT in the detection of occult choroidal neovascularization of AMD and compare OCT findings with angiographic and clinical findings to confirm the clinical impression and guide treatment.

Clinical cases have been selected to illustrate increasing degrees of disease severity, emphasize the importance of early diagnosis, assess the diameter of the neovascular lesion, and to highlight the importance of regular follow-up to monitor for the presence of complications.

This case series cannot represent all of the many different manifestations of AMD observed in clinical practice.

Follow-up of these various cases illustrate the unpredictable nature of treatment response. Some eyes responded very favorably, others are associated with recurrences and sometimes disappointing results.

The goal was to try to predict the course of the disease and define the optimal treatment strategy in terms of the duration and frequency of injections. The final prognosis remains difficult to predict.

This series of cases illustrates the clinical spectrum of occult choroidal neovascularization.

The various imaging modalities are compared to determine their respective roles during follow-up (natural history or response to treatment).

Whenever possible, all imaging modalities are presented: color and monochromatic fundus photography, fluorescein and SLO-ICG angiography, and the various modalities of OCT (Time-Domain or SpectralDomain).

Features Common to all Imaging Modalities

RPE detachments, a feature visible by other modalities, is confirmed by OCT.

All forms of occult choroidal neovascularization are characterized on OCT by separation of the RPE from the line that probably represents Bruch’s membrane.

This pigment epithelium detachment (PED) is initially minimal and then gradually becomes more extensive. It is related to the presence of CNV and exudation induced by the abnormal permeability of these vessels.

The presence of a PED appears to be one of the simplest diagnostic signs for the presence of occult CNV.

The best results are obtained when the lesions are diagnosed at an early stage (small lesions, little or no hemorrhage, minimal or no fibrosis).

Recurrences are more frequent and the end result is more disappointing with the presence of fibrosis.

The presence of dense hyper-reflectivity anterior to the RPE appears to be the most severe sign.

However, an unexpected improvement may be observed either at the beginning of treatment or when a recurrence is treated immediately.

Recurrences can occur even after a long period of stabilization, suggesting that, although current treatments constitute a remarkable progress, they are unable to control all factors responsible for choroidal neovascularization.

The improvements provided by SD-OCT allow unprecedented analysis of the outer retinal layers, particularly the photoreceptors and the structures surrounding them.

Clinical and Biomicroscopic Signs

A 72-year-old woman treated for wet AMD in her left eye reported no symptoms in her right eye.

Both eyes were regularly examined.

VA RE: 20/20 – VA LE: 20/40.

Clinical examination revealed a few, medium-sized soft drusen, predominantly perifoveal with no SRF or hemor-

8rhage.

Autofluorescence Image

No alteration in the foveal area (of xanthophyll pigment). Presence of a minimal hyper-fluorescence in the temporal macular area with no signs of SRF (Figure 2).

Angiography (Figure 2)

Fluorescein angiography: progressive, irregular, poorlydelineated, temporal macular hyper-fluorescence over 1 disc diameter with several sites of fluorescein leakage and pinpoints. There is also central masking by xanthophyll pigment, which represents a false image of foveal sparing.

ICG angiography: multiple irregular hyper-fluorescence zones within the dark background of the PED occupying the subfoveal macula. This lesion was suggestive of a barely visible neovascular network. Presence of a poorlydelineated plaque in the late phase.

Suggested Angiographic Diagnosis:

Area of occult CNV in a very small PED without hemorrhage (dormant), with no signs of decompensation and no symptoms.

OCT showed a minimal, regular, thin PED.

However, separation of the RPE from Bruch’s membrane (BM) that became clearly visible, confirmed the presence of a PED with a homogeneous, moderately reflective cavity and minimal shadowing.

The exudative reaction was very minor, causing only a slight increase in retinal thickness, but no SRF or cysts (Figure 3).

The outer nuclear layer was also thinned over the juxtafoveal PED, which extended as far as the center of the fovea.

The other retinal layers were not altered.

The foveal depression remained unchanged and preserved its normal profile (Figure 3).

Diagnosis

In this clinical case, whereby ophthalmological examination was performed in the context of follow-up of the fellow eye, imaging demonstrated an early stage of asymptomatic and uncomplicated CNV.

Fluorescein angiography demonstrated a limited area of irregular hyper-fluorescence with pinpoints, suggesting occult CNV with false image of foveal sparing due to xanthophyll pigment.

SLO-ICG angiography confirmed the presence of subfoveal CNV measuring 1.5 DD. It was characterized by

clearly visible hyper-fluorescence which contrasted with the dark and hypo-fluorescent PED.

The diagnosis was therefore confirmed: recent, isolated occult choroidal neovascularization or vascu-

larized PED without signs of decompensation and asymptomatic.

There was no indication for treatment at this stage (particularly at the time of the initial diagnosis, when

PDT was the only available treatment modality).

The patient was reassessed every six months.

Follow-up of the natural history of this lesion was obtained in the context of observation of the fellow eye over a period of 30-months by evaluation of visual acuity and imaging by OCT, fluorescein angiography, and ICG angiography.

The natural history was initially reassuring with relatively minor and slowly progressive changes and maintenance of almost normal visual acuity, perceived as comfortable

8by the patient.

The decision to treat this fellow eye was taken after a decline in visual acuity (5/10) experienced at the 30th month, especially as imaging confirmed the deterioration.

On OCT, the initially minimal PED gradually spread over a larger area and became thicker with a more irregular and wavy appearance.

The RPE did not appear to be thickened or fragmented, and the cavity remained moderately reflective.

On the other hand, the moderate intraretinal fluid persisted and then increased with alteration of the outer nuclear layer (Figure 4a).

Conclusion

This lesion consisted of occult CNV detected during systematic examination of the fellow eye. There was

an absence of any symptoms, which had remained

dormant and stable for more than two years.

The diagnosis was confirmed by the various imaging modalities, despite the absence of symptoms.

A wait-and-see approach, requested by the patient, appeared justified in view of the excellent quality of vision and the limited treatment available at that time.

OCT showed diffuse intraretinal fluid that appeared to slightly dissociate the various retinal layers, even affecting the inner plexiform layer with a layer of subretinal fluid (Figure 4b).

At the fifth examination, this serous SRF had become larger, involving almost all of the foveal region. This major change associated with the loss of visual acuity led to the decision to initiate treatment.

On the first fluorescein angiography examination, the hyper-fluorescent zone appeared to remain unchanged and was only visible in the temporal macular zone.

However, at the fourth and especially the fifth examination, it occupied 2/3 of the foveal area but always with slow and late fluorescein leakage from occult choroidal neovascularization (Figure 4c).

On ICG angiography, the image of occult CNV contrasting with the dark PED changed very little, but each examination confirmed that the lesion was subfoveal and occupied all of the fovea.

At the last examination, the lesions had clearly worsened on all three imaging modalities in parallel with loss of visual acuity (Figure 4d).

However, clinical observation subsequently demonstrated deterioration allowing rapid introduction of intravitreous anti-VEGF therapy.

The immediate result, with improvement of visual acuity and resolution of symptoms, reassured the patient to such a degree that she wanted to stop injections after the first session.

The persistence of several abnormalities on the various imaging modalities justified maintenance of regular observation, at least every three months (or more frequently, if new symptoms developed).

Clinical Signs

A 72-year-old woman experienced loss of visual acuity in the left eye to 20/50 about three weeks prior to presentation, associated with worrisome metamorphopsias.

Vision in the other eye was normal at this stage.

VA RE: 20/20 - VA LE: 20/50.

Biomicroscopic examination showed a few soft drusen and a small SRF about 1 DD, without hemorrhage or

8exudate.

Fluorescein angiography: Progressive, heterogeneous and poorly-delineated temporal macular hyper-fluores- cence measuring about 1 DD with diffuse and pinpoint leakage. Central masking by xanthophyll pigment.

SLO-ICG angiography: Irregular subfoveal area of hyperfluorescence within the dark PED, suggesting occult CNV (Figure 5).

Suggested Angiographic Diagnosis:

Occult CNV within a small PED.

OCT confirmed the diagnosis suggested by angiography by showing diffuse intraretinal fluid with increased retinal thickness.

A serous retinal detachment was also clearly visible on OCT but with no disorganization of retinal layers.

The RPE was slightly irregular and thinned with a rounded, regular but fairly prominent PED displacing the retina and SRF surrounding the PED (Figure 5).

The diagnosis of occult choroidal neovascularization with PED and SRF was confirmed, consistent with the patient’s loss of visual acuity (4/10) experienced for several weeks. Photodynamic therapy, the only available treatment at

that time, was initiated immediately. The response to treatment was immediately favorable with resolution of the SRF and improvement of VA, despite persistence of the unchanged PED. Subsequent follow-up at the 6th month, one year, and two years showed remarkable stabilization of the lesion and VA at 20/32-20/40.

There was little change in the angiographic signs, but the lesion also did not deteriorate (Figure 6a, b, and c).

On OCT, the PED was flat but hypo-reflective with no signs of fibrosis. The neurosensory retina had a normal architecture with good visibility of the IS/OS interface and no SRF (Figure 6d).

PED

a

ICG

b

ICG

ICG

PED

d

ICG