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

Because of reduced clarity in the vitreous, it may be difficult to obtain a second fluorescein study directly after the first. Thus good repeat angiogram may be possible only after a week’s interval.

ABNORMAL PATTERNS (TABLE 1)

Abnormal patterns that are seen on FFA are hyperfluorescence and hypofluorescence.

Hyperfluorescence

Hyperfluorescence can be because of dye leakage, increased transmission or abnormal vessels. Leakage of dye can result in pooling of dye either in retina or in subretinal space. The potential spaces present within the retina have a different anatomic configuration than fluid spaces present under the retina and the two show a different fluorescein pattern. Intraretinal fluid spaces in the macular area show petalloid pattern characteristics of cystoid maculopathy (Figure 10).

Pooling of the dye can occur in subretinal space (exudative sensory detachment) or under retinal pigment epithelium (pigment epithelial detachment) (Figures 11A to D).

Increased transmission results in hyperfluorescence (window effect or window defect). When pigment epithelial cells are atrophic or less in number, more fluorescence from the underlying choriocapillaris will be visible (Figures 12 and 13). Increased transmission occurs in atrophic pigment epithelium, after inflam-

Figure 11A: FFA right eye showing pooling of the dye in subretinal space in late phase

Figure 11B: Fundus photograph left eye showing a well defined blister like lesion suggestive of pigment epithelium detachment (arrow)

Figure 10: FFA left eye showing leakage from vessels, posterior pole leakage and cystoid macular oedema

Figure 11C: Fluorescein angiogram in the early phase shows a hyperfluorescence area corresponding to the lesion in Figure 11B (arrow)

Figure 11D: FFA in the late phase shows increase in the intensity of hyperfluorescence compared to Figure 11C but there is no leakage of dye, a feature characteristic of pigment epithelium detachment (arrow)

Figure 13: FFA same eye (Figure 12) showing transmission hyperfluorescence corresponding to RPE atrophy

Figure 12: Fundus photograph of patient with uveitis showing dull foveal reflex with possible RPE atrophy

mation, photocoagulation scar, choroidal folds (peak of fold).

Abnormal vessel formation is another cause for hyperfluorescence. These vessels can be retinal or subretinal. Vessels start hyperfluorescence in the early phases of angiography. Abnormal vessels in retina can be because of vascular tortusities, dilatation and shunts, neovascularisation, aneurysms, telangiectasis and vasculitis. Neovascularisation, tortusity and dilatation can also be seen over the disc. Subretinal abnormal vessel occur in choroidal neovascular membrane, chorioretinal anastomosis, etc.

Hypofluorescence

Hypofluorescence results because of blockage of light from normal fluorescencing structures or lack of adequate circulation in an area of retina or choroid.

Blockage of dye can result from preretinal lesions (opacities of the vitreous and refractive media, preretinal gliosis and fibrosis, preretinal haemorrhages), intraretinal lesions (haemorrhages, pigment, hard exudates) and subretinal lesions (haemorrhages, pigment, inflammation, fluid, hard exudates). Hypofluorescence resulting from blocked fluorescence need to be differentiated from areas of capillary nonperfusion due to ischaemia (Figures 14 to 16A-B).

The blocked fluorescence will remain the same through all the phases of angiography.

Hypofluorescence can be due to vascular filling defects. Retinal vascular defects occur in central retinal artery occlusion, branch retinal artery occlusion, central retinal vein occlusion, branch retinal vein occlusion or lesion in capillary bed as seen after photocoagulation, capillary non-perfusion areas as in Eales’ and other vasculitis condition.

The choroid can normally show hypofluorescence in early phases. An irregular “geographic” pattern is common, dark hypofluorescent areas fill slowly during a period of three or four seconds; presumably these patches are seen in early phases because of incomplete filling of dye in certain ciliary vessels. This is a normal

Figure 14: Fundus photograph upper temporal quadrant left eye showing vasculitis with exudates and retinal haemorrhages

Figure 15: Corresponding FFA to Figure 14 upper temporal quadrant left eye showing blocked fluorescence corresponding to the retinal haemorrhages whereas periphery shows areas of capillary nonperfusion (arrows)

pattern of choroidal filling (Figures 17A-D). Occlusion of choroidal vessels can be seen in choroiditis lesions which appear as hypofluorescent in early phases to become hyperfluorescent in late phases.

FLUORESCEIN ANGIOGRAPHY IN UVEITIS

FFA is a very important tool in the evaluation and management of posterior segment inflammation. It can be of value in diagnosing specific uveitic entities, evaluating the activity of inflammatory lesions, evaluating retinal vascular involvement, detecting

Figure 16A: Fundus photograph right eye showing subretinal bleeding with peripapillary choroidal neovascular membrane associated with fibrosis

Figure 16B: Late phase angiogram showing blocked fluorescence in the area of subretinal haemorrhage and hyperfluorescence of the choroidal neovascular membrane

macular complications, and assessing the optic disc involvement.

FFA gives useful information principally on the superficial structures of the fundus (retina, retinal vessels, and optic disc), on the retinal pigment epithelium, on the choriocapillaris in the early phase, as well as immediately subretinal disease process such as subretinal neovascular membranes.

RETINA

FFA is especially useful to study inflammatory diseases of the retina. As the free unbound fluorescein molecule is very small it will leak out even from minimally inflamed retinal vessels including capilla-

ries. This procedure thus has a high sensitivity to demonstrate inflammation in these superficial structures. This is not at all the case for indocyanine green angiography where more than 98% of the dye forms a macromolecular complex with proteins and is therefore not sensitive for retinal inflammation.

ACTIVITY OF FOCAL INFLAMMATION

FFA allows better characterisation of the amount of inflammatory activity of toxoplasmic retinochoroiditis than clinical examination (Figures 18A-C). It demonstrates early hypofluorescence of the focus of retinochoroiditis. Dye leakage occurs later, expanding from the margin of the lesion. Similarly, FFA can be marginally helpful in evaluating other focal or

multifocal chorioretinitis because FFA is especially useful to evaluate the retinal component of inflammation but provides poor information on choroidal involvement, in contrast to the ICG angiography.

RETINAL VASCULITIS

Retinal vasculitis can occur in many inflammatory diseases, including sarcoidosis, Behçet’s disease, Birdshot chorioretinopathy, systemic lupus erythematosis, syphilis, tuberculosis, toxoplasmosis, acute retinal necrosis syndrome, frosted angiitis, and Eales’ disease.

Retinal vasculitis is observed on fundus examination as focal or diffuse vascular sheathing; FFA shows staining of the vessel wall or dye leakage. Retinal

Figures 18A-C: (A) Toxoplasmic retinochoroiditis associated with serous retinal detachment (arrows), (B and C) Early hypofluorescence and late hyperfluorescence with staining and pooling of dye in subretinal space

vasculitis can be classified as phlebitis (or periphlebitis), arteritis, and capillaritis (capillary inflammation) (Figures 19A-D).

FFA allows much better characterisation of retinal vasculitis and its complications than clinical examination and is particularly useful in the diagnosis and evaluation of the subclinical retinal capillary involvement (Figures 20A and B). Medical treatment is best adjusted on the basis of FFA signs rather than solely on clinical findings. One disease where FFA is the method of choice for follow-up is Behcet’s uveitis.

Retinal vessel and capillary staining or leakage can be classified as focal, multifocal, or diffuse, with involvement of the periphery and/or posterior pole in one or more quadrants. Diffuse leakage from retinal capillaries is found in birdshot chorioretinopathy where it produces diffuse oedema and impregnation of the retina. The amount of leakage from capillaries in birdshot chorioretinopathy is sometimes so profuse that during the early angiographic phase the major retinal veins are never really marked by the dye, which was interpreted as a perfusion delay by Gass.11 When looking at the arteriovenous circulation by ICG angiography the transit time is absolutely normal and veins are clearly marked in a normal time span at 18-20” because the ICG dye is not extruding from retinal vessels. Therefore this can be called a pseudoperfusion delay with failure of sufficiently marking large veins due to lack of fluorescein dye in the early angiographic phase (Figures 21A and B).

Especially in the later phase of angiography, FFA shows also leakage from larger veins such as in birdshot chorioretinopathy or Behçet’s uveitis, causing staining of the perivascular space (Figure 22). Leakage from arteries can be seen in Behçet’s uveitis.

Leakage of dye from the retinal capillaries in the posterior pole can occur with or without involvement of the macular area.

CYSTOID MACULAR OEDEMA

Cystoid macular oedema (CME) is the most common cause of visual loss in patients with uveitis. It can be detected by slit-lamp biomicroscopic ophthalmoscopy, but fluorescein angiography and optical coherence tomography (OCT) are mandatory in detecting and follow-up macular oedema, assessing its pattern, its amount and the associated retinal changes.

Leakage of dye from retinal capillaries in the macula causes CME, the evaluation of which is best done by FFA especially when the dynamic aspect of fluid accumulation is investigated.

FFA feature of CME includes telangiectasis of the parafoveal capillaries, with progressive leakage and accumulation of dye in the cystic spaces surrounding the fovea. Characteristically, there is accompanying hyperfluorescence of the optic disc. The characteristic “petalloid” pattern of parafoveal hyperfluorescence is

Figure 22: FFA of a patient with Birdshot chorioretinopathy showing leakage from larger veins

presumably related to the unique anatomy of the parafoveal retina. The inner layers of the retina are absent in the area surrounding the fovea, and the remaining Müller cells, bipolar cells and photoreceptor cell processes are oriented more horizontally in the plane of the retina and spread out radially around the foveal centre. Excess fluid, accumulating within the inner nuclear or outer plexiform layer of the parafoveal retina, whether in swollen and degenerating Müller cells or as extra cellular fluid collects in the radially drawn spaces.12 This results in the typical chrysanthemum ”flower petal” pattern seen on FFA.

CME has been angiographically graded into the following grades by Miyake:13

Grade 0° : no sign of fluorescein leakage (Figure 23) Grade I° : slight fluorescein leakage into cystic spaces but not enough to enclose the entire fovea

centralis (Figure 24)

Grade II° : complete circular accumulation of the fluorescein in the cystic space but its diameter is smaller than 2 mm (Figure 25)

Grade III° : the circular accumulation of fluorescein is larger than 2.0 mm in diameter (Figure 26).

In 1984; Yannuzzi proposed a slightly different classification as follows:14

Grade 0: no perifoveal hyperfluorescence

Grade 1: incomplete perifoveal hyperfluorescence Grade 2: mild 360 degree hyperfluorescence Grade 3: moderate hyperfluorescent area being

approximately 1 disc diameter across Grade 4: severe 360 degree hyperfluorescence with

the hyperfluorescent area being approximately 1.5 disc diameter across.

Figure 23: FFA of left eye showing no sign of fluorescein leakage in the foveal area

Figure 24: FFA of left eye showing complete circular accumulation of the fluorescein in cystic spaces but its diameter is less than 2 mm

The area of leakage of the dye seen with FFA appears not to correlate well with visual acuity.15

Although FFA is required in the evaluation of uveitic cystoid macular oedema, it should be complemented with OCT to accurately quantify retinal thickening and detect associated serous retinal detachment or vitreomacular traction.

RETINAL VASCULAR OCCLUSION

Retinal periphlebitis or arteritis may be severe enough to induce branch retinal vein occlusion or branch retinal artery occlusion, with or without subsequent

Figure 25: FFA of right eye showing slight fluorescein leakage into cystic spaces but not sufficient enough to enclose the entire fovea centralis

Figure 26: FFA of right eye showing that circular accumulation of fluorescein is greater than 2.0 mm in diameter

decrease in vision. Such occlusive events may manifest with clinical features, but FFA is particularly useful in confirming the diagnosis, determining the site of occlusion, and evaluating the potential subsequent capillary hyperpermeability or obliteration. FFA may also be useful in the evaluation of cenral retinal vein or artery occlusion, a less common complication of retinal vasculitis16 (Figures 27A-E).

Retinal capillary closure, also called retinal capillary nonperfusion or retinal ischaemia, is a common

complication of many uveitic entities associated with retinal vasculitis including tuberculosis, sarcoidosis, Behçet’s disease, Eales disease, and idiopathic vasculitis.16-19

Retinal ischaemia can only be suspected clinically, and FFA is required to establish the definitive diagnosis. FFA reveals the presence of areas of capillary dropout and leakage of dye from dilated telangiectatic vessels at the border of the perfused and non-perfused areas. FFA also allows assessing the extent and location of areas of capillary nonperfusion. Retinal ischaemia commonly involves the periphery and retinal neovascularisation may develop in case of extensive peripheral capillary nonperfusion (Figures 28 and 29).

When retinal capillary non-perfusion affects the macula, it causes enlargement of the foveal avascular zone (Figure 30). FFA is absolutely essential for diagnosing macular ischaemia, particularly in patients whose visual acuity fails to improve despite appropriate medical treatment and macular ischaemia is suspected. An entity where this complication can be found classically is Behçet’s uveitis.

After successful inflammation suppressive therapy, FFA will show decreased or absent leakage from vessels (Figures 31A to F).

Figure 28: FFA of right eye during dye transit showing areas of capillary non-perfusion in the superior periphery of the retina

RETINAL NEOVASCULARISATION

Retinal or optic disc neovascularisation occurs in 10-15% of patients of retinal vasculitis. It can be detected both clinically and angiographically, but the latter is a better modality to identify new vessels that are not visible clinically. The newly formed vessels become distinctly outlined during the arteriovenous