Fluorescein and indocyanine green angiography for uveitis

Abstract

In recent years enormous progress has been achieved in investigational procedures for uveitis. Imaging is one such example with the advent of new methods such as indocyanine green angiography, ultrasound biomicroscopy and optical coherence tomography to cite only the most important. This tremendous increase in precision and accuracy in the assessment of the level and degree of inflammation and its monitoring comes in parallel with the development of extremely potent and efficacious therapies. In view of these developments, our whole attitude in the appraisal and investigation of the uveitis patient has to be adapted and correctly reoriented integrating the recent developments and this is no different for ocular angiography.

Keywords: Fluorescein; Indocyanine Green Angiography; Uveitis.

Figure 1

Complementary information from fluorescein fundus angiography and from indocyanine green angiography FFA draws its advantages from the small size of the fluorescein molecule (picture top left) and gives information on all superficial structures of the fundus including preretinal and intraretinal hemorrhages, optic disc, retinal vessels, neovessels, retina, macula, sub retinal space, RPE and chorioretinal atrophy, choriocapillaris and choroidal neovessels. ICGA draws its advantage from the infrared fluorescence of the ICG molecule and from its macromolecular behavior. ICG extrudes from the largely fenestrated choriocapillaris (picture top right) and impregnates and is stuck in the choroidal stroma, so low lighting inflammatory foci seen in dark because diffusion of ICG is impaired CMO - cystoid macular oedema; CNV - choroidal neovessels; NVD - neovessels disc; NVE - neovessels elsewhere; RPE - retinal pigment epithelium

Figure 2

Schematic diagram of fluorescein angiographic signs in uveitis

Figure 3

Case of anterior scleritis (top left) with vasculitis shown by anterior ICGA (top middle) with no apparent clinical posterior involvement seen on fundus examination (top right). FFA clearly shows hyperfluorescent hot disc indicating posterior involvement (bottom left) which was confirmed by ICGA showing diffuse choroidal hyperfluorescence confirming the presence of posterior scleritis (bottom right)

Figure 4

FFA signs: Retinal vasculitis; (a) Birdshot retinochoroidopathy; (b) Severe vasculitis in Behçet's uveitis; (c) Vasculitis in intermediate uveitis related to multiple sclerosis; (d) Disc neovessels and retinal neovessels in intermediate uveitis of the pars planitis type

Figure 5

Retinal non perfusion in a case of Behçet's uveitis in temporal inferior area

Figure 6

Birdshot chorioretinopathy. Birdshot is an inflammatory disease where the choroid and retina are primary independent targets of the inflammatory process. Retinal involvement can show profuse capillary leakage causing massive exudation into the retina at the origin of a pseudo-delay of arteriovenous circulation as large veins are still not opacified at 45 seconds (bottom right frame). The ICG frame (top left) shows that arteriovenous transit is already complete at 19 seconds

Figure 7

FFA signs: Macular ischemia and macular oedema; (a and b) FFA (7a) of macula showing central hypofluorescence (enlargement of avascular zone) indicating macular ischemia; change in tissue density well shown on a C-scan OCT (7c, right picture. Delineation of ischemia is clearly shown on SLO fundus picture (7b, bottom left); (c and d) Cystoid macular oedema well shown on FFA (7c) but not seen on spectral OCT (7d)

Figure 8

FFA signs: Intraretinal pooling, exudative retinal detachment and atrophy; (a) FFA shows choriocapillaris non perfusion (top) in a patient diagnosed as APMPPE; gradually there is intraretinal and sub retinal pooling (5a, two bottom pictures) due to extrusion of fluorescein coming from the inner retinal capillaries in response to outer retinal ischemia due to choricapillaris non perfusion; (b) FFA exudative retinal detachment with hyperfluorescent pinpoints where choroidal leakage is occurring in a case of VKH disease; (c) Same fundus frame on ICGA showing hyperfluorescence of ERD as well as hyperfluorescent pinpoints-; (d) FFA shows papillitis and mottled RPE with well defined limits between diseased and healthy RPE (high water marks) in a case of VKH. Left picture is an ICG frame of the same area showing numerous persisting HDDs indicating active disease; (e) Chorioretinal atrophy, late hyperfluorescent on FFA and hypo fluorescent on ICGA

Figure 9

FFA (ICGA) signs: Inflammatory chorioretinal neovascularization. 8a. FFA shows leaking and staining in area adjacent to toxoplasmic scar, before intravitreal Avastin(R) (left picture) and after (right picture); 8b. Same lesion before (L) and after (R) seen by ICGA. 6c. Same lesion seen by OCT, before (top picture) and after Avastin (two bottom OCTs)

Figure 10

ICG angiographic principles The ICG molecule (775 daltons) (9a) is 98% protein bound forming a large macromolecular ICG-protein complex (> 58'000 daltons) (9b) that extrudes freely through the large fenestrations of the choriocapillaris (9c) progressively impregnating the choroidal stroma (9d).This physiological fluorescence is impaired by two mechanisms producing hypofluorescent ICGA lesions: (1) choriocapillaris non perfusion (9e) occurring in inflammatory choriocapillaropathies and (2) mass effect due to space occupying lesions such as inflammatory foci here shown as the full-thickness stromal granuloma on (9f) explaining the hypofluorescence seen on ICGA

Figure 11

(b) Schematic interpretation of indocyanine green angiography hypofluorescence; (2b) Schematic interpretation of indocyanine green angiography hypofluorescence

Figure 11a

(a) Schematic interpretation of indocyanine green angiography hypofluorescence

Figure 12

ICGA signs of choriocapillaris non perfusion Areas of patchy or geographic ICGA hypo fluorescent areas of variable sizes present in the early, intermediate and late angiographic phases, in a case of APMPPE, corresponding to confluent plaques of deep fundal discoloration. They often leave atrophic areas as seen in serpiginous choroiditis in the convalescent phase

Figure 13

Stromal inflammatory foci/granulomas in Vogt-Koyanagi-Harada disease Typical even regularly distributed hypofluorescent evenly sized dark dots indicating numerous choroidal granulomas

Figure 14

Choroidal stromal vasculitis in Vogt-Koyanagi-Harada disease. Hypo fluorescent dark dots surrounded by indistinct fuzzy choroidal vessels (top frames) showing normalization after only 3 days of pulse intravenous corticosteroid injections (bottom frames)

Figure 15

Choriocapillaris non perfusion in a case of APMPPE/AMIC Choriocapillaris non perfusion is shown by patchy geographic areas of hypofluorescence in the intermediate phase of angiography (top right picture) and in the late angiographic phase (bottom left picture) that resolve almost completely in the convalescent stage of disease 2 months later (bottom right picture). The late fluorescein frame on the top left shows hyperfluorescence, corresponding to the ICG areas of choriocapillaris non perfusion that can only be explained by leakage from the capillaries of the inner retina in response to ischemic signals from the outer retina

Figure 16

Diffuse perilesional choroidal hyperfluorescence in subclinically progressing serpiginous choroiditis. ICGA (right quartet of pictures) shows many more involved areas than shown by fluorescein angiography (left quartet of pictures) and shows hyperfluorescence around progressing lesions

Figure 17

Choroiditis in Sarcoidosis (15a) Unevenly sized randomly distributed lesions; (15b) well seen in the intermediate ICG angiographic phase (15a, middle and left frames) and disappearing in the late phase (right frame), indicating that these presumed granuloma are of partial thickness not filling the stroma from sclera to choriocapillaris. The lesions are hardly visible on fluorescein angiography

Figure 18

Multifocal choroiditis (the iceberg effect or constellation). Fundus pictures show minimal signs limited to faint depigmentation (16a, black arrows) and FFA shows absolutely no abnormalities (16b), whereas ICGA shows extensive choriocapillaris involvement with large geographic areas of non perfusion (16c and 16 d) which we now know to be a risk factor for CNV, which the patient developed one year later as seen on FFA (16e) and fundus images (bottom right)

Figure 19

ICGA guided treatment of VKH disease. 17.1. VKH at presentation: Numerous hypofluorescent dark dots indicating granulomatous foci in the choroid as well as fuzzy choroidal vessels indicating choroidal vasculitis. Following intravenous pulse steroid therapy followed by high dose oral steroids HDDs disappear completely and choroidal vessels regain a normal pattern (17.2) Upon tapering there is recrudescenc of subclinical choroidal disease (17.3.), that prompts reincrease of oral steroid therapy and introduction of azathioprine. After slow tapering of steroid therapy first followed by tapering of azathioprine over 2 years the patient remains recurrence free.(17.4)

Figure 20

The essential role of ICGA for early diagnosis of birdshot retinochoroiditis. Patient in his mid-forties presenting with blurred vision OS due to the presence of vitritis (top right). FFA shows retinal vasculitis OS of large veins and small vessels (bottom middle). The right eye seems not affected (top left). However, ICGA shows numerous hypofluorescent dark dots on the left (bottom right) but also on the right (bottom left), typical for birdshot retinochoroidopathy