Ординатура / Офтальмология / Учебные материалы / Uveitis Text and Imaging Text and Imaging Text and Imaging 2009

Figure 29: FFA R/E in a patient with retinal vasculitis showing leakage from retinal vessels in the posterior pole during dye transit with areas of capillary non-perfusion temporally

phase with their abnormal branching patterns and progressive increase in leakage during late phases19 (Figure 32).

Neovascularisation may be associated with capillary non-perfusion identified by fluorescein angiography. It is believed that blood vessel growth

Figure 30: FFA L/E showing extensive retinal capillary nonperfusion in the macular area

is caused by angiogenic factors released from the ischaemic retina. Peripheral laser photocoagulation to areas of retinal ischaemia is indicated. In contrast, some eyes with retinal vasculitis and neovascularisation do not show retinal vascular occlusion, and FFA

Figure 32: FFA L/E showing leakage from new vessels on the optic disc during late phase

reveals diffuse capillary leakage. This type of neovascularisation might develop from stimuli derived from inflammatory cells or mediators. In such cases, neovascularisation typically is located at or near the optic disc and is seen to involute with anti-inflam- matory therapy alone20 (Figures 33A-D).

If left untreated, neovascularisation may result in vitreous haemorrhage or tractional retinal detachment.

OTHER RETINAL VASCULAR CHANGES

FFA may assist in the evaluation of retinal vascular macroaneurysms, which are a characteristic feature of ocular sarcoidosis and idiopathic retinal vasculitis aneurysms and neuroretinitis (IRVAN) syndrome (Figures 34A to C).

OPTIC DISC

Optic disc oedema due to papillitis is the most common optic disc change, usually accompanying severe intermediate uveitis or posterior uveitis (Figures 35A- F).

It is clinically characterised by vascular congestion and hyperaemia, absence of the cup, and blurring of the margins. FFA demonstrates optic disc leakage and staining in late phase, with or without blurring of optic disc margins and papillary vasculature.

FFA is useful in diagnosing subclinical papillitis by showing hyperfluorescence and in monitoring the

course of disease and response to treatment. It may also assist in the evaluation of other forms of optic nerve involvement associated with uveitis, including neuroretinitis, optic disc infiltration, anterior ischaemic optic neuropathy, and papilloedema.

RETINAL PIGMENT EPITHELIUM

In the normal situation, the retinal pigment epithelium (RPE) is a monolayer of cells connected by tight

junctions that prevent escape of most molecules, including fluorescein and proteins, from the choriocapillaris into the subretinal space, which is maintained in a state of relative deturgescence (outer retinal-blood barrier). In addition, the RPE acts as an optical filter of irregular density to partly obscure the fluorescence emitted from the choroid in the visible spectrum of light. FFA is therefore the method of choice to investigate RPE alterations associated with uveitis.

ANATOMIC RPE CHANGES

A relative decrease or abscence of pigment in the RPE, when associated with minimal or no alteration in the underlying choriocapillaris, will cause early hyperfluorescence by “window defect” because of the greater amount of inciting blue light reaching the choroid and the greater visibility of the choroidal fluorescence.

Accumulation of melanin or other material within or beneath the RPE will cause choroidal hypofluorescence by blockage effect.

Inactive (or healed) inflammatory chorioretinal lesions appear as well-defined chorioretinal atrophic areas associated with more or less pigmentation due to RPE hyperplasia. On fluorescein angiography, hyperpigmentation causes hypofluorescence by blockage effect. RPE atrophy causes early hyperfluorescence by “window defect” if the underlying choriocapillaris is preserved or minimally involved by atrophy (Figure 13). If atrophy is more extensive with loss of choriocapillaris, there is hypofluorescence associated with visibility of large choroidal vessels and late hyperfluorescence due to scleral staining. The scleral staining is explained by the diffusion of the small fluorescein molecule from adjacent areas with an intact choriocapillaris. On the reverse, the same atrophic area appearing as hyperfluorescent in the late FFA phase will appear hypofluorescent on ICG angiography as the large macromolecular ICG-protein complex is too bulky to diffuse and stain atrophic areas.

RPE CHANGES ASSOCIATED WITH EXUDATIVE RETINAL DETACHMENT

FFA allows optimal characterisation of RPE signs associated with exudative retinal detachment such as that occurring in Vogt-Koyanagi-Harada disease.

It shows multiple hyperfluorescent pinpoints at the level of RPE representing the sites of fluid passage with deposition of the dye at the level of the RPE. This is followed by pooling of dye in areas of exudative retinal detachment (Figures 36A to D).

The same phenomenon occurs and the same hyperfluorescent pinpoints are seen on ICG angiography with accumulation of the ICG dye at each point where liquid is leaking through the RPE. Similar

fluorescein angiographic patterns can be observed in sympathetic ophthalmia and posterior scleritis.

In the convalescent stage of the disease that has caused serous retinal detachment (for instance Vogt- Koyanagi-Harada disease) the damage to the RPE such as loss of cells or clumping of pigment coming from damaged RPE cells is very well identified by FFA which shows an irregular pepper and salt coarse aspect of the RPE in all areas that have suffered from fluid accumulation. The limits to which the fluid extended is very well demarcated by FFA showing sharp margins between damaged RPE areas and the normal regular aspect of background choroidal fluorescence of non-involved areas.

CHOROID

CHORIOCAPILLARIS NON-PERFUSION

Although FFA is not an ideal investigation for the choroid, some information can nevertheless be gained on choriocapillaris perfusion within the first minute of angiography. There may be early choroidal hypofluorescent areas indicating choriocapillaris perfusion delay or non-perfusion in several choroiditis entities, including Vogt-Koyanagi-Harada disease (Figures 37A to C) and inflammatory choriocapillaropathies, such as serpiginous choroiditis (Figures 38A to C), acute posterior multifocal placoid pigment epitheliopathy (APMPPE) (Figures 39A to F), and multiple evanescent white dot syndrome (MEWDS).

In serpiginous choroiditis, the active borders show early hypofluorescence with progressive diffuse staining in late frames.

Other conditions sharing similar pathophysiologic mechanisms (choriocapillaris non-perfusion) and showing a similar kind of picture include APMPPE, and multifocal choroiditis and in the differential diagnosis of such lesions are choroidal tuberculosis and syphilis that can produce secondary choriocapillaris perfusion disturbance.

Figure 39 illustrating a case of APMPPE, the nonperfusion of the choriocapillaris is well apparent on the early frames (middle picture top row). On the late frame there is leakage and staining and sometimes even pooling due to increased permeability of inner retinal vessels. The dye comes indeed from inner

retinal vessels that respond to outer retinal ischaemia due to choriocapillaris non-perfusion. Toxoplasmic retinochoroiditis too may show choriocapillaris nonperfusion in active stage (Figures 40A to C).

FFA is also useful in documenting response to a therapy in these lesions (Figures 41A to F).

In contrast to ICG angiography, FFA is incapable of giving information on the choriocapillaris beyond the early phases of angiography. It cannot determine

whether the capillary nonperfusion seen in the first seconds or the first minute of FFA is only due to perfusion delay or to choriocapillaris non-perfusion and does not give good imaging access to the rest of choroid.

CHOROIDAL FOLDS

Choroidal folds are commonly observed in Vogt- Koyanagi-Harada disease and posterior scleritis.

Clinically, they are seen as alternate dark and yellow bands, which often involve the posterior pole. These folds may have a horizontal, vertical, or oblique orientation. On FFA alternate dark and light bands are seen corresponding to choroidal folds.The crest of the fold and the trough respectively appears as hyperfluorescent and hypofluorescent (Figures 42A to C).

These characteristic changes in background choroidal fluorescence may be explained by histopathologic changes occurring in the choroid and the overlying RPE which is stretched and more permeable to light on the crest, the reverse being the case in troughs.

FFA is useful in detecting subclinical choroidal folds and in differentiating folds of the choroid from folds in the retina, which do not alter background choroidal fluorescence.

CHOROIDAL NEOVASCULARISATION

Choroidal neovascularisation (CNV) may complicate any pathologic process that disturbs the pigment epithelium and Bruchs’ membrane. It may occur in the course of numerous uveitic entities, including multifocal choroiditis, presumed ocular histoplasmosis syndrome, serpiginous choroiditis, Vogt-Koyanagi-

Harada disease, sarcoidosis, tuberculosis, and toxoplasmosis (Figures 43A to C). In early stages of CNV, biomicroscopic clues include the presence of subretinal or intraretinal lipid exudates or haemorrhage, often in association with pigment epithelial or localised neurosensory detachment. Occasionally, a choroidal neovascular membranes itself may be visible as a dirty greyish area on colour pictures surrounded by a pigmented changes.

Choroidal neovascular membranes (CNVM) can be of two types as has been described for age related macular degeneration namely classic and occult. In classic CNV, the new vessel fill early during angiography, tend to be well-defined and almost always show progressive leakage throughout the study. The hyperfluorescence seen with occult CNV, by contrast tends to be poorly defined and less pronounced.

Differentiation of a macular scar from active choroidal neovascularisation is important. On FFA chorioretinal scars demonstrate hyperfluorescence beginning first in the periphery, adjacent to normal

choroid, with later spread to the centre of the scar (staining without leakage). In neovascularisation, hyperfluorescence begins in the area of CNV and then spreads more peripherally. The later phase shows hyperfluorescence of the entire lesion.

FFA may help differentiate CNV from active inflammatory lesion.

DRAWBACKS

Fluorescein angiography is a good modality for documenting and diagnosing uveitis condition. But it has few drawbacks in particular in cases of uveitis.

1.Poor mydriasis: For a good quality fundus photograph and angiogram good pupillary dilation is a prerequisite. This is of major concern in cases of uveitis due to presence of posterior synechiae.

2.Ocular media: Media should be good to get good quality picture. Patients with uveitis frequently have complicated cataract, vitreous opacity, inflammation, and posterior capsular opacity in pseudophakic patient making good angiography

difficult and in some cases impossible. Especially in pseudophakic eye there is a problem of reflection from the intraocular lens surfaces.

3.Fluorescein angiography has limited role in defining the disease of the choroid.

4.Some patients have severe allergy to the dye used and fluorescein angiography is not useful in this group of patient.

5.In some of the systemic disease like decreased cardiac out put, etc. there is poor concentration of dye reaching the retinal vessels and does not produce a good quality scan.

6.As a cannula is to be placed in a vein it may be difficult to perform FFA in children.

KEY POINTS

1.Fluorescein is a safe injectable dye but variable degree of adverse reaction can occur, from mild nausea to death.

2.Different ocular tissues have variable response to fluorescein. Retinal pigment epithelium and retinal vessel endothelium are impermeable while choriocapillaris are freely permeable resulting in initial choroidal flush.

3.Abnormal angiogram results in hypofluorescence and hyperfluorescence in various phases of angiogram. Therefore it is important to study all the phases of angiogram for correct interpretation of angiogram.

4.Some of important conditions that are better visualised on FFA include cystoid macular oedema, vasculitis and neovascularisation.

5.It is useful in diagnosing various uveitic entities and monitoring therapeutic response.

6.Fluorescein angiography is a useful investigation differentiating between active and inactive choroidal lesion.

REFERENCES

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Carl P Herbort

INTRODUCTION AND HISTORICAL BACKGROUND

INTRODUCTION

For many years angiographic investigation of posterior uveitis was limited to fluorescein angiography (FA), a technique that is useful for the analysis of the superficial structures of the fundus including the optic disc, the retina and the retinal pigment epithelium (RPE). Because fluorescence emitted by the fluorescein sodium molecule (FNa) is within the visible light spectrum and is stopped by the screen constituted by the retinal pigment epithelium (RPE), FA is unable to give information on the choroid with the exception of the choriocapillaris during the first 50-60 seconds when fluorescence is massive.

Since the early nineties of last century, technical advances have made it possible to use indocyanine green angiography (ICGA) in every day practice to show choroidal vascular structures and inflammatory lesions thanks to the infrared fluorescence of the indocyanine green (ICG) molecule that is visible through the RPE.

The choroid is the site of origin of posterior intraocular inflammations at least as often if not more often than the retina. Unlike the retina where lesions are accessible to fundoscopy or fluorescein angiography at an early stage of disease and can be analysed in a very sensitive fashion by FA, exploration of the choroid was very limited and gross so far. Only choroidal foci of sufficient importance causing yellow-white

discolouration of the fundus red reflex were detected through the screen of the RPE by fundoscopy. Fine alterations caused by choroiditis or the early stages of disease were however not accessible to imaging unless they produced alterations on the adjacent structures such as the overlying RPE and/or retina.

Therefore, appraisal of inflammatory fundus lesions due to choroiditis was mainly descriptive based on fundoscopy, with little information on early inflammatory lesions, their site of origin or the potential sequence of inflammatory events.1

Since the availability of indocyanine green angiography, more detailed investigation of the choroid was made possible, giving information on early and/or subclinical disease, on the structures involved by the inflammatory process leading to a more appropriate classification of posterior uveitis based on the mechanisms of choroidal inflammation. Some of these mechanisms have been verified histopathologically while others are still presumed and need manifest proofs.

HISTORICAL BACKGROUND

Indocyanine green (ICG) has been used in other medical fields well before it was introduced in ophthalmology. Since 1957 this natural dye has been used to measure cardiac output. In ophthalmology, ICG has been used for angiography since 1973.2 Thanks to the macromolecular character of the ICG molecule (see below) this dye is remaining intravascularly in the large choroidal vessels. It is this property that allowed early authors and articles on ICG