Ординатура / Офтальмология / Учебные материалы / Uveitis Text and Imaging Text and Imaging Text and Imaging 2009
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Figure 75A: ICGA diagnostic information—MEWDS. Faint fundus findings with severe visual field defect (Figure 75B) that was diagnosed as optic neuritis
Figure 75B: ICGA diagnostic information—MEWDS. Severe visual field defects that led to the erroneous diagnosis of optic neuritis
ICGA TO MONITOR DISEASE EVOLUTION AND RESPONSE TO THERAPY
Most of the ICG angiographic signs regress after the introduction of inflammation suppressive therapy, except chorioretinal atrophy that will remain hypofluorescent because of the loss of the choriocapillaris. Another situation where hypofluorescence does not mean active disease is choroidal stromal scarring as can be seen in Vogt-Koyanagi-Harada disease. In the latter situation stromal fibrosis is hypothesized not allowing the ICG molecule to diffuse in those areas that remain dark throughout the angiographic phases and that do not respond to treatment any more.16 After the onset of therapy many of the angiographic signs such as choroidal
Figure 75C: MEWDS. FA showing hyperfluorescent disc and late faint mottled retinal hyperfluorescence
Figure 75D: MEWDS. Only ICGA showed lesons clearly sugestive of MEWDS showing coalescent hypofluorescent areas and peripapillar hypofluorescence (originally published and reprinted from Ocular Immunology and Inflammation 2000;8:275-83)
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Figure 76: Differential inflammatory involvement (and evolution) of retina and choroid in birdshot chorioretinopathy measured by FA and ICGA. At presentation the inflammation is mainly present in the choroid and moderate in the retina. After inflammation suppressive therapy, retinal inflammation (yellow line) is barely under control, whereas ICGA (green line) shows that HDDs rapidly disappear, leaving depigmented areas that progressively appear over time (pink arrow).
inflammatory vasculopathy or stromal partial thickness foci, hypofluorescent in the intermediate angiographic phase and isofluorescent in the late phase, disappear often very quickly, within days after the start of treatment. Similarly, full-thickness inflammatory foci, hypofluorescent up to the late angiographic phase, may disappear or become partial thickness inflammatory foci (hypofluorescent until intermediate phase and isofluorescent in the late phase) depending on when the follow-up angiography is performed after introduction of therapy. The quick response of choroidal ICGA signs to therapy is probably explained by the rich vascularisation of the choroidal space, giving optimal access to systemic corticosteroid/immunosuppressive therapy. We were able to show by sequential follow-up of a group of birdshot patients put under corticosteroid/immunosuppressive therapy, that ICGA signs responded very well and quickly to therapy while mean retinal involvement measured by FA could merely be prevented from progressing (Figure 76). Appearance of depigmented fundus lesions was not prevented by treatment and may represent resolution without scarring of the choroidal stromal foci seen early by ICGA that have eliminated choroidal pigment.
In VKH disease, ICGA allowed to monitor choroidal involvement especially by following HDDs
(Figures 44A to D) and showed that in most cases smoldering choroidal disease is going on unless sufficiently dosed inflammation suppressive treatment is applied for a sufficiently prolonged period of time. Subclinical choroidal disease can reappear during tapering, after initial high dose corticosteroid therapy or is never completely suppressed because of insufficinet therapy and is most probably responsible for the sunset glow fundus very often developing at a later stage of disease.76 Detection and monitoring of choriocapillaris inflammation is most of the time possible only by ICGA as shown by the case of multifocal choroiditis presented in Figures 29A to C.
ICG angiography, thus appears as a very sensitive modality to show and follow the evolution of choroidal lesions, both at the level of the choriocapillaris and at the stromal level that is able to show subclinical recurrence in diseases with primary or preponderant choroidal involvement. As is the case for FA in Behçet’s disease and other monitoring modalities in uveitis, ICGA should not be neglected for the appropriate follow-up of patients with choroiditis.
CONCLUSION
Indocyanine green angiography is a young investigational modality being performed for routine
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clinical purposes only since the early nineties of last century when the availability of reliable equipment made it possible. Unfortunately ICGA was understood with difficulty for two reasons. Firstly, clinicians used to perform FA, did not understand the difference of mechanisms generating hyperfluorescence and hypofluorescence on ICGA and kept on interpreting ICGAs using the FA principles of window effect and masking effect, which do mostly not apply in ICGA.
Secondly, experimental studies preceding the era of routine clinical use of ICGA, mainly interested in imaging large choroidal vessels generated the erroneous notion that the ICG molecule did not leak into the choroidal stroma and postponed the understanding of ICGA. For inflammatory diseases ICGA has been codified and standardised since several years.16
In contrast to other new investigational modalities such as OCT that represent an improved visualisation of lesions that are already accessible with other means such as fundoscopy or FA, ICGA shows additonal lesions, mainly in the choroid, that are usually not accessible or demonstrated by other means. The choroid is responsible for posterior inflammation in an equal if not higher proportion of cases when compared to the superficial structures as the retina. Therefore, in cases where choroidal involvement is suspected, ICGA is as important if not more imporant than FA and dual ICGA and FA angiography is highly recommended in such cases.
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B.Anterior Segment ICG Angiography
Carl P Herbort
INTRODUCTION
Indocyanine green angiography (ICGA) may also be used to analyse conjunctival, episcleral and scleral vasculature of the anterior bulbus. This is possible because of the macromolecular behaviour of the ICG molecule. As fluorescein has a small molecular weight, it leaks easily and, more importantly, it is washed out very quickly and therefore is not useful to investigate conjunctival, episcleral or scleral vessels. ICGA, for the anterior bulbar sclera and overlying tissues, was used to determine conjunctival and episcleral vacular patterns after trabeculectomy and after pterygium surgery.1,2 In inflammation it was first reported in 2000 to be useful in differentiating episclertitis from sceritis.3 In a review article on ICGA in inflammation the use of anterior bulbus ICGA was put forward especially in the investigation of scleritis.4
PRINCIPLES OF INDOCYANINE GREEN ANGIOGRAPHY (ICGA) FOR THE ANTERIOR SEGMENT AND ANGIOGRAPHIC TECHNIQUE
PRINCIPLES
The molecular weight difference between indocyanine green (775 daltons) and fluorescein (354 daltons) molecules does not account for the specific behaviour obtained with ICG as compared to fluorescein. Beside the different wavelength at which ICG fluoresces, the crucial difference between these two fluorescing molecules comes from their binding affinity to proteins.5-8 The ICG molecule is nearly completely protein bound and predominantly so to large sized proteins,9 whereas up to 20% of the fluorescein molecules are not protein bound and therefore easily extrude from vessels, impregnate tissues but are also very quickly washed out again.
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ANGIOGRAPHY SYSTEMS
The same two angiographic systems, as exposed in the previous chapter, are used to perform indocyanine green angiography of the anterior bulbus.10 The first system using a conventional fundus camera linked to a digitisation system of images is probably more easy to use for this anterior application. The system using a scanning laser ophthalmoscope (SLO) which produces a confocal video-angiography allowing to precisely
focalize on a given plane is more difficult to use for this purpose as a special device has to be added.11 The same standard protocol as for dual fluorescein and indocyanine green angiography is followed which can be extended to a “triple” anterior ICG, posterior ICG and posterior fluorescein angiography.4,12 It is indeed often indicated to perform such a triple angiography as intraocular pathology may be associated to eye wall pathology such as in scleritis (Figures 1A-C).
Figure 1A: Anterior bulbus ICGA
Figure 1B: Fundus ICGA showing swollen vorticose veins as well as sparse hypofluorescent dark dots
Figure 1C: Fluorescein angiography showing mottled irregular fluorescence in the inferior temporal quadrand as well as hyperfluorescent disc
Figures 1A-C: Anterior scleritis confirmed by anterior bulbar ICGA
Seventeen year old girl presenting with left bulbar injection having a history of orbital pain waking up the patient in the morning. Injection is present in the temporal inferior quadrant of the left bulbus over a nodular elevation (Figure 1A; left picture). At 3 mintes after ICG injection, hypefluorescent and leaking vessels are seen n this area (Figure 1A; middle picture) At 12 minutes after ICG injectionsdiffuse staining of the area is seen (Figure 1A; right picture).
Triple angiography was performed showing intraocular inflammatory signs. Fundus ICGA shows swollen vorticose veins and hypofluorescent dark dots indicating also posterior scleritis and spill-over inflammation into the choroid (Figure 1B). Fundus fluorescein angiography shows hyperfluorescent disc and irregular mottled fluorescein patterns (Figure 1C)
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Figure 2: Same patient as figure 1. Anterior bulbus ICGA frames of different bulbus areas photographed by asking patient to change gaze direction
ANGIOGRAPHIC PROTOCOLE
1.In practice, early ICGA posterior pole frames are taken up to about 2 minutes to determine whether there is a choroidal perfusion delay that can also be shown by fluorescein angiography or whether there are early hyperfluorescent choroidal stromal vessels as can be seen in VKH disease or severe scleritis.
2.From 2 to 5 minutes, early external pictures are taken in in the different directions of gaze to give imaging access to most of the anterior bulbar surface (Figure 2).
3.Intermediate phase posterior segment frames are then taken from 7-12 minutes (posterior pole and 8 panoramic pictures) Most of the relevant information on choroidal involvement is coming from the later, intermediate or late phase frames that show the physiologic egressing process of the indocyanine green macromolecular complex from the choriocapillaris into the choroidal stroma. The presence of space occupying choroidal inflammatory lesions such as granulomas that will appear hypofluorescent against the fluorescing background because ICG cannot diffuse into that area. Hypofluorescent dots represent overflowing inflammation from the sclera (Figure 1B). In this angiographic phase a frequent sign seen in case of scleritis is congestion of vorticose veins, probably because the venous egress from the eyeball is made difficult by the inflamed and swollen sclera.
4.A second round of external frames can then be performed at about 12 to 15 minutes.
5.The following step is to perform fluorescein angiography going up to 10 minutes.
6.The physiologic choroidal background fluorescence is analysed again at a second time point (late phase, 28-33 minutes) with pictures of the posterior pole as well as 8 panoramic pictures to visualize the fundus on 360 degrees.
7.Repeat anterior frames can then again be obtained (±35 minutes).
ANGIOGRAPHIC INTERPRETATION AND SEMIOLOGY (THE ICGA SIGNS IN ANTERIOR SEGMENT BULBAR DISEASE)
Main signs to look for in anterior bulbar ICGA are hyperfluorescent scleral vessels already seen at 3 minutes and much better identified at 15 minutes giving way to diffuse hyperfluorescence at 30-35 minutes) (Figures 3A and B). If such a sequence of images is seen, the diagnosis of scleritis can be made or comfortably confirmed. Anterior bulbar ICGA is not of diagnostic utility, as mostly the diagnosis is already made when ICGA is decided. Sometimes it is helpful to distinguish episcleritis from scleritis.13 However the presence of hyperfluorescent subconjunctival vessels that leak do not absoltely exclude episceritis.
Associated signs can be seen on fundus ICGA, such as hypofluorescent areas irregular in distribution and size, indicating spill-over scleral inflammtion into the choroid. Sometimes there are even fluorscein angiographic signs to be seen such as irregularity of fluorescence. On fundus ICGA frames congestion of vorticose veins associated with anterior bulbar hyperfluorescence has to be searched, a typical ICGA sign in scleritis.
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Figure 3A:
Figure 3B: Anterior bulbus 360 degrees pictures. By asking the patient to change gaze directions all 360 degrees of anterior bulbar sclera is seen. Note that only infero-temporal quadrant shows diffuse hyperfluorescence (top right frame)
Figures 3A and B: Patient with necrotizing scleritis due to Wegener’s granulomatosis. Inflamed vessels are seen in the bulbus colour photograph in the temporo-inferior quadrant (Figure 3A, far right): Leaking scleral vessels ar seen in the intermediate phase (12-15 minutes) (Figure 3A, second from right picture). Diffuse hyperfluorescence is seen in the same area at the late angiographic phase (± 30 min.) (Figure 3A, third picture from right). After introduction of combined corticosteroid and immunosuppressive therapy, leakage of scleral vessels compleely disappeared (Figure 3A, far left picture)
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Figure 4A: Scleritis confirmed by anterior bulbar ICGA (left frame) with resolution after treatment (right frame)
Figure 4B: Fundus ICGA of case with anterior scleritis, showing faint hyperfluorescent dark dots
Figures 4A and B: Forty-three year old lady referred for episcleritis. She presented a red temporal nodular hyperhemic zone and complained of pain waking the patient up in the early morning. Anterior bulbar ICGA showed areas of leakage well visible on late frames (Figure 4A, right picture). After 5 days of systemic non steroidal antiinflammatory drug therapy combined with topical 1.0% prednisolone drops 8 times daily the leaking bulbar area completely disappeared (Figure 4A, left picture): Fundus ICGA showed also hypofluorescent dark dots showing that there is a slight intraocular involvement (spill-over inflammation into the choroid) (Figure 4B)
CLINICAL USE OF ANTERIOR BULBAR ICGA
The main use of anerior bulbar ICGA is to monitor therapeutic effect in order to identify subcliical persistance of vasculitis of scleral and/or episcleral vessels. This is very important in order to adapt therapy as zero tolerance of inflammation should be the aim in these potentially blinding diseases (Figures 4A and B).
The advantage is that external or anterior bulbar ICGA can be performed during the same angiographic procedure performed for fundus angiographic imaging (Figures 4A and B).
KEY POINTS
•External or anterior bulbar ICGA can be performed together with dual fluorescein / ICG angiography
•It is indicated when scleritis is suspected, where it can be useful to differentiate episcleritis from scleritis
•Its diagnostic use for scleritis is modest, its most useful contribution being more in disease monitoring and evolution of disease in response to therapy
REFERENCES
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