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

Clinical and Biomicroscopic Signs

A 72-year-old woman presented with slowly declining visual acuity and metamorphopsias mainly in the left eye, experienced for several months prior to examination.

VA LE: 20/80 – VA RE 20/40.

Biomicroscopic examination revealed several, mediumsized perifoveal drusen associated with a central SRF

8measuring 2 DD.

Autofluorescence images showed the presence of a regular, circular halo with no alteration of xanthophyll pigment.

Fluorescein and SLO-ICG Angiography

Fluorescein angiography: irregular, progressive 2 DD hy- per-fluorescence with leakage and pinpoints. This zone comprised a clearly-delineated area of marked hyperfluorescence with fluorescein leakage.

ICG angiography: the small area of classic CNV was rapidly stained and surrounded by a dark border (Figure 14). Occult CNV was observed later, forming a poorly-defined subfoveal neovascular network within the dark PED.

Suggested Angiographic Diagnosis:

Occult CNV associated with a small area of classic CNV

(minimally classic).

At the RPE Level

Several undulations and elevations were observed within the RPE, delineating multiple pockets of relatively flat, irregular, and wavy PED.

The RPE was irregular with thinner and thicker zones delineating the vascularized PED.

The PED cavity was hypo-reflective allowing visualization of Bruch’s membrane.

A moderately reflective (green) band was visible posterior to the RPE, with an optically empty zone situated even more posteriorly.

Anterior to the RPE

The neurosensory retina was thickened with diffuse intraretinal fluid and loss of the foveal depression.

A small SRF was visible between the pockets of the PED and especially around the PED (clearly visible on the vertical section).

In particular, a zone of subfoveal hyper-reflectivity was contiguous with the RPE, caused disorganization of the outer layers, and represented classic CNV.

Treatment consisted of verteporfin photodynamic therapy (PDT), the standard treatment at that time, followed by IVT injections of anti-VEGF for a recurrence.

These treatments initially provided a functional improvement, followed by stabilization of visual acuity, except during the recurrence.

Clinical Features

Autofluorescence photographs showed extension of the lesion with early changes in the central zone (Figure 16).

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TD-OCT examinations demonstrated changes of the zone of hyper-reflectivity corresponding to classic CNV during this follow-up (Figure 17a-d).

The overall appearance on OCT sections appeared to fairly accurately reflect the progression, resolution, and then recurrence of classic CNV and intraretinal fluid, although the subretinal component was only slightly detectable.

▬A marked improvement was observed by the second PDT session, but the hyper-reflective zone of classic CNV was still visible.

▬One year later, after 3 PDT sessions, the hyper-reflec- tive classic CNV had resolved but a minimal SRF still remained.

▬Two years later, although the lesions appeared to be stable, the patient developed a recurrence marked by return and marked extension of a preretinal zone of hyper-reflectivity with leakage, extensive SRF and increased retinal thickness.

Complementary PDT and IVT injections of anti-VEGF (a single session) were therefore performed.

▬After 3 years of follow-up, marked improvement with stabilization, reapplication, and preservation of normal retinal thickness.

On fluorescein angiography, the improvement mainly involved the classic CNV component, which initially resolved and then recurred. Treatment appeared to have little effect on the zone of occult CNV, which remained stable with no signs of deterioration (Figure 17c).

On ICG angiography, the CNV appeared to become atrophied and limited to large draining vessels. The outline of PDT was clearly visible.

Clinical Signs

A 60-year-old man presented with visual discomfort in the right eye with a few micropsias and deformed images, with normal visual acuity and no symptoms in the left eye.

VA RE: 20/32 - VA LE: 20/20.

Biomicroscopic Examination and

Fluorescein and ICG Angiography

Progressive hyper-fluorescence and pinpoints in the inferior and temporal region with slow fluorescein leakage. A localized inferior nasal lesion with much more intense fluorescein leakage was visualized in this zone (Figure 18 arrow).

Autofluorescence

Biomicroscopic examination demonstrated numerous soft drusen of various sizes, sometimes clustered or con-

8fluent forming a superior and temporal crown.

All of the inferior macular region was raised and blurred with a grayish inferior nasal zone but without hemorrhage and/or lipid exudates (Figure 18).

Autofluorescence photographs did not show any abnormal hyper-fluorescence but the presence of an oval-shaped zone of hypo-fluorescence corresponding to the raised zone.

SLO-ICG angiography showed a vast hypo-fluorescent oval-shaped subfoveal PED, well-delineated on the late phases. A small hyper-fluorescent zone was clearly visualized within the PED, suggesting occult CNV that had become visible (Figure 18 arrow).

Suggested Angiographic Diagnosis:

Recent decompensation of a vascularized PED with jux-

tafoveal choroidal neovascularization, corresponding

to minimally classic CNV.

Horizontal section

At the RPE level, presence of a relatively small PED, mainly temporal but extending as far as the fovea. This PED was relatively flat with good visibility of Bruch’s membrane. The PED cavity was hypo-reflective and almost optically empty.

Anterior to the RPE, the neurosensory retina was only slightly modified with good preservation of retinal structure and minimal intraretinal fluid. CNV were barely visible on this section.

Oblique section

The PED was not visible on this section, which demonstrated hyper-reflectivity related to the presence of juxtafoveal classic CNV anterior to the RPE with adjacent retinal thickening (Figure 19).

The foveal depression was only slightly modified, confirming the recent onset of the lesion explaining the good visual acuity.

Diagnosis

Stratus* TD-OCT demonstrated a relatively flat pigment epithelium detachment. The PED cavity was almost optically empty. An adjacent hyper-reflective lesion, anterior to the RPE, associated with a limited exudative reaction and moderate retinal thickening was also demonstrated with no disorganization of retinal layers.

This combination of signs was suggestive of occult choroidal neovascularization with recent appearance of a small area of juxtafoveal classic choroidal neovascularization, often called minimally classic

Fluorescein angiography was suggestive of this lesion,

occurring at a relatively young age and accompanied by numerous drusen.

SLO-ICG angiography confirmed these findings and clearly confirmed the diagnosis.

This lesion was recent with moderate symptoms. A

diagnosis of drusenoid PED could be considered, but the presence of an exudative reaction confirmed the diagnosis and justified immediate anti-VEGF therapy to prevent progression.

The response to treatment by monthly intravitreal antiVEGF injections (Lucentis*) was monitored by visual acuity, OCT, FA, and ICG angiography.

Satisfactory results were rapidly obtained with subjective improvement of symptoms and restoration of normal VA by the second month, leading the patient to request suspension of treatment for 1 month.

However, a third injection to consolidate the results was performed after the fourth follow-up visit.

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Since this time, the patient has been followed by VA, which has remained satisfactory despite two recurrences, rapidly resolving after intravitreal injections.

On TD-OCT, the moderate intraretinal fluid resolved rapidly, but returned at each recurrence.

▬On the first follow-up examination, the PED remained unchanged, but retinal thickening had clearly decreased (but persisted over the classic CNV) with localized alteration of the outer nuclear layer (Figure 19a).

▬On the second follow-up examination (1 month after the first IVT injection), the serous retinal detachment had collapsed and was no longer visible (Figure 19b).

The zone corresponding to rapid and intense fluorescein leakage was less hyper-reflective and almost undetectable on conventional Time-Domain OCT and remained unchanged on the second and third examinations.

Conclusion

This case of occult CNV associated with active juxtafoveal and subfoveal classic CNV was examined at a very early stage. The clinical course in response to

treatment was favorable with recovery and maintenance of normal visual acuity.

This emphasizes the value of early diagnosis to allow treatment as early as possible.

Visual acuity was restored even more rapidly than all of the imaging signs, which nevertheless resolved in parallel.

Spectral-Domain OCT (Spectralis*) demonstrated a relatively flat residual hypo-reflective lesion anterior to the RPE with no exudative reaction. The neurosensory retina had regained an almost normal organization with a homogeneous, symmetrical foveal depression.

Detailed image analysis showed a very flat PED outlined by Bruch’s membrane. The external limiting membrane was continuous with a normal appearance. Several alterations of the IS/OS interface and outer nuclear layer are visible with a few bright hyper-reflective spots (Figure 19c).

Several recurrences with SRF and loss of VA were treated with further injections (Figure 19d). The patient has now been followed for one year with injections at each episode (5 injections).

At the last examination, the lesions appeared to have considerably regressed with good stabilization. Outer retinal layers, well visualized by Spectralis*, showed few alterations with persistence of slight fibrosis underneath the RPE (Figure 19e).

On fluorescein angiography, by the first follow-up examination, the fluorescein leakage suggestive of classic CNV remained visible but had decreased in size and intensity, with late staining and without completely disappearing. The PED was virtually no longer visible.

On ICG angiography, the zone corresponding to CNV had become hypo-fluorescent, even at late phases, and smaller. The hypo-fluorescent image of the PED faded and regressed by the 2nd examination.

Despite persistence of minor alterations on both

types of angiography and minimal PED on OCT, the normal appearance of the external limiting membrane and IS/OS interface indicated a good visual

prognosis (Figure 19e).

Regular follow-up during the second year, at least every 3 months (or more frequently in the case of symptoms) remained essential.

The place of maintenance therapy has not yet been clearly defined and must be considered case-by-case during follow-up.

Spectralis* SD-OCT illustrates the ability to detect minimal but clinically significant changes.

At the initial stage, with minimal symptoms and almost normal visual acuity, SD-OCT demonstrates the initial PED from Bruch’s membrane as well as any early changes of photoreceptors (Figure 20a).

The course of the lesions and the results of treatment can be followed, not only in terms of the usual criteria of

8intraretinal fluid and retinal thickness, but also in terms of the first alterations of the retinal layers and probably

inflammatory reactive signs (bright hyper-reflective spots and intraretinal denser zones).

These various structures are visible on standard sections of the posterior pole, but are particularly well-visualized on enlarged images despite slightly accentuated noise.

In this Patient,

The first recurrence was marked by a small subfoveal SRF associated with thickening and irregularity of the RPE, especially marked in the central zone.

Photoreceptor outer segments presented a jagged and irregular appearance, suggesting possible photoreceptor damage in the zone where they are separated from the RPE.

The IS/OS interface was much thicker and hyper-re- flective but remained intact, like the external limiting membrane.

The outer nuclear layer was also slightly modified, thinned, and more reflective than in normal zones. Several bright hyper-reflective spots were also observed adjacent to the lesion and on the edges of the SRF.

All these changes were moderate, as the recurrence

was only very recent (Figure 21).

▬During the second recurrence, all these signs were accentuated: vascularized PED, accumulation of

These lines are generally more clearly visible on a black (or white) background than on color images (Figure 20a-d).

On the first examination and during follow-up, the first step therefore consists of looking for Bruch’s membrane separated from the RPE, suggesting a PED and the presence of occult CNV.

The course of the PED is studied by analyzing the RPE and the more or less prominent dome-shaped or wavy pigment epithelium detachment, and the extent of the exudative reaction or fibrosis.

Analysis of the inner and outer segments and the IS/OS interface and external limiting membrane that delineate them, is just as important as evaluation of subretinal and intraretinal fluid.

bright hyper-reflective spots and dense zones. However, the absence of disorganization of retinal

layers indicated a good prognosis (Figure 22).

▬At the last examination, after a stable period lasting 6 months, the prognosis was fairly easily established on the basis of:

▬Classical criteria (absence of intraretinal fluid and normal thickness),

▬As well as additional SD-OCT criteria:

▬persistence of a few rare bright hyper-reflective spots,

▬IS/OS interface, external limiting membrane, and outer nuclear layer continuous and clearly visible.

Note the moderate localized alteration at the site of

classic CNV (Figure 23).

During obligatory long-term observation, these criteria can be easily compared by using an eye-tracking system.