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

Figure 28: Acute idiopathic blind spot enlargement (AIBSE).

Extensive nonor hypoperfusion of the choriocapillaris explains the enlarged blind spot in the AIBSE form of MEWDS (Courtesy Alessandro Mantovani, Como, Italy)

presenting subclinical disease.39,40 The numerous reports on associated blind spot enlargement in many of the diseases presently regrouped in the category of primary inflammatory choriocapillaropathies is an indication for a common physiopathogenic mecha- nism.41-44 Furthermore, the reports including ICGA investigation in their work, show that visual field alterations are related to peripapillary hypofluorescence indicating choriocapillaris non perfusion as the physiopathogenic process at the origin of blind spot enlargement (Figure 28).

KEY POINTS: ANGIOGRAPHIC SIGNS MULTIPLE EVANESCENT WHITE DOT SYNDROME (MEWDS) AND ACUTE IDIOPATHIC BLIND SPOT ENLARGEMENT (AIBSE)

•Fundus findings: discrete discolourations in midperiphery and granular aspect of macula

•ICGA: hypofluorescent dots (choriocapillaris non perfusion) and peripapillary hypofluorescence in acute phase resolving in 4-8 weeks

•FA: hypofluorescence (early), discretely hyperfluorescent foci (late) or absent FA findings ± cystoid macular oedema; disc hyperfluorescence.

•AIBSE: entity described before the ICGA era behaving as MEWDS without fundus signs that have probably resolved or are subclinical.

Acute Posterior Multifocal Placoid Pigment Epitheliopathy (APMPPE) or Acute Multifocal Ischaemic Choriocapillaropathy (AMIC)

Acute posterior multifocal placoid pigment epitheliopathy (APMPPE) was first described by Donald Gass in 1988 as a primary disease of the retinal

pigment epithelium.45 The erroneous attribution of the disease site to the RPE is understandable as the choriocapillaris could hardly be explored at that time. Fluorescein angiography yields information on the choriocapillaris only up to the first 60 seconds after injection. Because the follow-up FAs showed RPE changes the primary impact was thought to be at this location. Deutman and colleagues, however, based on the choriocapillaris non perfusion seen on early FA frames, clearly indicated that it was the choriocapillaris rather than the pigment epithelium that was primarily involved and he suggested to rename the disease acute multifocal ischaemic choroidopathy (AMIC).27,30

ICGA signs in APMPPE/AMIC are characterised by unevenly sized geographic hypofluorescent areas randomly scattered and confluent in the posterior pole present in the early and intermediate phase of angiography but very distinctly visible in the late ICG angiographic phase (Figure 25A). In contrast to MEWDS where the choriocapillaris hypofluorescent areas are smaller, more diffuse, more even but less intense, involvement is more focal in APMPPE but hypofluorescence is more intense probably indicating complete choriocapillaris non perfusion.26 On followup angiograms these signs resolve almost completely with the exception of a few areas of persisting hypofluorescence due to chorioretinal atrophy.16 Because the pattern of hypofluorescence is so characteristic, most authors that published ICGA studies on APMPPE concluded that lesions were due to primary choriocapillaris vascular disease,46,47 choroidal vascular occlusion16 or hypoperfusion,26 confirming what some authors had already suspected on the base of fluorescein angiography showing choriocapillaris perfusion delay.27,30 ICGA brought the additional information not available from fluorescein angiography, indicating that the choriocapillaris perfusion delay seen on fluorescein angiography corresponds indeed not only to perfusion delay but to choriocapillaris non perfusion.

Analysed in parallel with ICGA, FA signs support the primary involvement of the choriocapillaris and its consequences on the retina. In the acute phase there is early choriocapillaris hypofluorescence indicating perfusion delay (non perfusion). In the late angiographic phase there is usually pronounced hyperfluorescence corresponding to the areas of perfusion delay seen on FA and to the hypofluorescent areas seen on

Figure 29A: Multifocal choroiditis—FA and ICGA. FA pictures (right frames) performed at ptation (top) after one month of systemic corticosteroid therapy (middle) and 4 months of corticosteroid therapy (bottom) show pre-existing chorioretinal scars but no evolution over time. ICGA pictures (left frames) show a cluster of confluent hypofluorescent areas more extensive than what is seen on FA, including old scarred lesions and new choriocapillaris lesions in a patient complaining of photopsias. Only ICGA shows regression of lesions after 1 month (middle) and 4 months (bottom) of systemic corticosteroid therapy not at all visible on FA (originally published and reprinted from: Ocular Immunology and Inflammation 2000;8:275-83)

ICGA reflecting choriocapillaris non perfusion (Figure 25B). This leakage leading to late hyperfluorescence cannot come from the choroid as we now know that the ICGA hypofluorescent areas correspond to choriocapillaris non perfusion. If it were coming from the choroid we would see hyperfluorescent pinpoints as in exudative VKH retinal detachments signaling the sites of leakage of liquid through the RPE-Bruch’s membrane complex. Moreover if leakage and staining were coming from the choroid it would be expected that the placoid lesions would stain from their periphery inward which is not the case. Therefore, it makes

Figure 29B: Multifocal choroiditis–computerised Octopus™ visual fields. Restoration of visual field defects occur in parallel to resolution of hypofluorescent ICGA areas (originally published and reprinted from: Ocular Immunology and Inflammation 2000;8:275-83)

Figure 29C: Multifocal choroiditis – Fundus aspect.

Fundus view of angiographic case shown in Figure 29A

sense to attribute the leakage leading to the late FA hyperfluorescence to the vessels of the inner retina that respond to ischaemic signals from the outer retina which depends on the choriocapillaris for oxygen and nutrients. Retinal oedema corresponds to the yellow plaques seen on fundus examination (Figure 25C). In the convalescent phase most FA signs regress except for the mixture of window and masking effects corresponding to cicatrised lesions of the RPE that will persist and are not relevant for the evolution of the disease. Healing of the choriocapillaris can only be shown by ICGA and recovery and functional prognosis can only be evaluated using ICGA.16,18,33

SUMMARY: ANGIOGRAPHIC SIGNS IN APMPPE/AMIC

•Yellowish deep bilateral discolouration at posterior pole (with serous exudative retinal detachments in hyperacute cases)

Multifocal choroiditis (MFC) is a more heterogeneous entity than the previously described MEWDS and APMPPE. When seen by the clinician most of the cases already show chorioretinal scars, as if preceding silent episodes occur before the disease becomes symptomatic at the time of a recurrence. The cases described as presumed ocular histoplasmosis syndrome (POHS) in patients with a negative hypersensibility skin test to Histoplasma capsulatum and coming from non endemic areas for histoplasmosis should probably be assimilated to multifocal choroiditis.48 The characteristics of all the subtypes of multifocal choroiditis are

(1) the numerous small randomly distributed chorioretinal scars, (2) the recurrent behaviour of the disease as well as (3) the propensity to develop secondary neovascular membranes which is much more frequent than in all other primary inflammatory choriocapillaropathies PICCPs.49

The first set of ICGA signs identifies old scarred chorioretinal lesions and consists of hypofluorescent areas persisting up to the late angiographic phase, distributed at random in the fundus, corresponding to hyperfluorescence on the late fluorescein angiographic phase, typical for chorioretinal atrophy from scars of previous inflammatory episodes seen on fundus examination.50 The second set of ICGA signs can be seen in addition to the previously described signs when choroiditis recurs or can be seen in their absence when it is the first episode of multifocal choroiditis. The signs consist of hypofluorescent areas, almost non visible on fluorescein angiography and not visible on fundus examination, representing areas of new inflammatory involvement corresponding to scotomas on visual field testing (Figures 29A and B). As in MEWDS, some cases may present peripapillary hypofluorescence translating functionally into an enlarged blind spot18,50,51 (Figure 30). The latter signs respond to systemic corticosteroids and can regress completely if therapy is started early. The only

Figure 30A: Multifocal choroiditis. Case with associated extensive peripapillar ICGA hypofluorescence

Figure 30B: Multifocal choroiditis—negative FA. No FA lesons can be seen in the case of MFC with extensive ICGA lesions shown in Figure 30A

modality to monitor the evolution or resolution of these active lesions is ICGA (Figure 29A).

Fluorescein angiography shows mainly signs of chorioretinal scarring associating window defects to masking effects where there is pigment clumping. In the active phase FA may show faint late hyperfluorescence in areas of ICGA hypofluorescent dark areas corresponding to new lesions. The use of FA is however of little use to assess and follow active disease, as FA angiographic signs are often absent or faint in new areas of inflammatory involvement that are, however, clearly shown by ICGA18,33,50,51 (Figure 29A). Visual field defects corresponding to new lesions resolve in parallel to resolution of ICGA hypofluorescent areas (Figure 29B).

KEY POINTS: ICGA AND FA SIGNS IN

MULTIFOCAL CHOROIDITIS

•Recurrent mostly bilateral chorioretinal inflammatory diseases with small faintly apparent yellowish active foci and older chorioretinal scars

•ICGA: (1) hypofluorescent areas (early, int. and late): scars and (2) active foci (the latter only detectable by ICG)

•FA: early hypo and late hyperfluorescence (scars); active foci rarely seen by FA

•Subretinal inflammatory neovascularisation frequent (up to 30%) identified by dual FA/ICGA

Figure 31. Serpiginous choroiditis. Fundus lesions.

Typical creeping lesions going out from the disc

Serpiginous Choroiditis

Serpiginous choroiditis is a progressive recurrent primary inflammatory choriocapillaropathy that leads to non reversible destruction of the chorioretina52-54 (Figure 31). It affects more elderly patients in addition to the young healthy adult age group traditionally affected by the other PICCPs. In India, however, patients are of the same young adult age group as all other PICCPs and the etiology is tuberculous in origin, infectious or immune mediated, until proven otherwise.55,56

Indocyanine green angiography of old lesions shows mainly hypofluorescent areas up to the late angiographic phase indicating chorioretinal scarring and atrophy57 (Figure 32A). ICGA shows the extenson of lesions more clearly than fluorescein angiography (Figure 32B). In areas of active disease progression, ICGA shows hypofluorescent areas that go beyond the lesions apparent on fundoscopy and/or fluorescein angiography18 (Figure 32A). Another ICGA sign that can give information on the activity of the process is a diffuse perilesional hyperfluorescence that is not always seen on FA16 (Figure 33). Recently OCT has given some elements on the progression of the lesional process in the transitional zone betweeen scarred retinal and still functional retina, showing hyperreflectivity at the RPE-choriocapillaris level together with oedema in the overlying retina (Figure 34). Furthermore, ICGA is the best diagnostic procedure to distinguish neovascular membranes from reactivating disease in PICCPs, showing early hyperfluore-

Figure 32A: Serpiginous choroiditis. ICGA. Snake like creeping atrophic lesions appearing hypofluorescent due to atrophy. In atrophic areas only large choroidal vessels are still seen. The adjacent areas show slight hyperfluorescence probably indicating disease activity

Figure 32B: Serpiginous choroiditis. FA. The same atrophic areas seen by ICGA are hypofluorescent in the early phase of angiography and hyperfluorescent in the late phase. In this case FA also shows some areas of bright fluorescence at the edge of atrophic lesions indicating disease activity

scence in neovascular membranes instead of the hypofluorescence characteristic for new serpiginous lesions.16 In contrast to ICGA, fluorescein angiography of the active progressing edges can show hypofluorescence in the early phase followed by progressive late staining, a pattern compatible with outer retina

Figure 33: Serpiginous choroiditis. Perilesional hyperfluorescence. Close-up on transition areas especially OD showing ICGA hyperfluorescence compatible with disease activity

Figure 34: Serpiginous choroiditis. Optical coherence tomography (OCT). The cut goes through preserved retina showing thickening and oedema and hyper-reflectivity at the choriocapillaris-RPE interface and then through atrophic chorioretina shown by calipers

ischaemia. Older lesions appear as window defects associated with blockage caused by pigment loss alternating with pigment clumping, a typical pattern for chorioretinal atrophy and scars.54

KEY POINTS: ANGIOGRAPHIC SIGNS

IN SERPIGINOUS CHOROIDITIS

•Fundus findings: acute stage: geographic white-grey to yellow peripapillary lesions +/- serous detachments; chronic stage: atrophic pigmented scars

•ICGA: acute: geographic hypofluorescence (= choriocapillaris non-perfusion) surrounded by choroidal hyperfluorescence. Chronic: hypofluorescence (= atrophy)

•FA: acute: early hypofluorescence and late impregnation; chronic: early hypofluorescence and late hyperfluorescence (window effect) ( = atrophy)

Rare Entities and Unclassifiable Entities

Acute zonal occult outer retinopathy (AZOOR) and acute annular outer retinopathy (AAOR)

Gass described a syndrome characterised by photopsias, acute bilateral loss of outer retinal function, minimal initial fundus changes and an abnormal ERG, which he called acute zonal occult outer retinopathy (AZOOR).58-61 To date there is limited or no informa-

Figure 35: Acute macular neuroretinopathy (AMN). Typical dark brown discolouration of macula. No ICGA was done in this case

tion on ICGA signs in AZOOR but choriocapillaris disease can be anticipated. Fluorescein angiography is normal at the onset when fundoscopy shows no alterations and then with chronicity, alterations of the RPE become manifest and are objectively shown by fluorescein angiography62 (see Chapter 22H). Possibly or even most probably AZOOR represents the spectrum of PICCPs where choriocapillaris non perfusion associated with all these diseases is much more important and unusually widespread.

Acute macular neuroretinopathy (AMN)

Acute macular neuroretinopathy (AMN) is a rare chorioretinopathy affecting young adults mono or bilaterally, producing disturbing symptoms of photopsia and often occurring after a flu-like illness like many of the other PICCPs.63 Fundus changes are characterised by large macular orange-brown plaques (Figure 35). Fluorescein angiography shows early choroidal hypofluorescence or can be unremarkable. The visual field can show a central scotoma. AMN has been described in association with MEWDS in the same patient placing the disease into the category of PICCPs.64 The whole picture of this entity perfectly corresponds to and is characteristic of PICCPs. Choriocapillaris perfusion pathology was reported on the base of electrophysiology and infrared images by one group65 and these choriocapillaris perfusion problems were linked to ICGA hypofluorescence in another group.66 We recently saw a patient examined in the early phase showing the typical fundus colour changes

Figure 36: Indocyanine green angiography in AMN. Similar case as shown in Figure 35. ICG hypofluorescence is present in the macular area. (Courtesy Alessandro Mantovani, Como, Italy)

associated with ICGA hypofluorescence of the whole macular area indicating choriocapillaris pathology and linking the disease to the PICCPs (Figure 36). A French group, however, recently reported a case compatible with AMN where no ICG findings were recorded.67

Intermediary and unclassifiable forms of PICCPs

In some cases there is a hybrid presentation associating characteristics of different PICCPs, having the morphology of one disease and the evolution of another, such as APMPPE with a disease course characterised with recurrences behaving like serpiginous choroiditis called by some authors AMPPiginous choroiditis and later described as relentless placoid chorioretinitis31,32 (Figure 37). Indocyanine green angiographic findings present all the characteristics of choriocapillaris non perfusion and remains the common denominator of this spectrum of intermediary or unclassifiable forms of PICCPs.18

Sometimes a well-known label cannot be applied to the clinical and ICG angiographic findings in given patients. In these cases the important thing is to recognise the ICG angiographic signs pointing towards choriocapillaris disease (choriocapillaris non perfusion). Once the frame of the pathology, i.e. disease of the choriocapillaris, has been recognised, patients should be closely followed clinically and by ICG angiography. In case of improvement, treatment can be held back. In case of deleterious evolution corticosteroid with or

Figure 37: Ampiginous choriocapillaritis. A case of APMPPE taking the aspect and the evolutionary pattern of serpiginous choroiditis

without immunosuppressives have to be introduced. It is also dangerous to attribute patients to a given entity and not take into account the functional evolution in deciding the therapeutical attitude. We have seen the dramatic situation of a patient showing typical choriocapillaritis with choriocapillaris non perfusion that could, however, not be attributed to a known entity. Unfortunatelly the label of APMPPE was applied and consequently therapeutic abstention was decided resulting in chorioretinal macular atrophy in the first eye (Figure 38A). Several weeks later the other eye was involved and still no treatment was given because of the APMPPE label given to the patient’s condition and chorioretinal macular atrophy occurred in the other eye (Figure 38B). When corticosteroid therapy was given hypofluorescent choriocapillaris non perfusion lesions regressed but there was no significant functional improvement (Figure 38C).

Figure 38A: Choriocapillaritis not classifiable into a known entity. Involvement of first left eye showing choriocapillaris non perfusion, while right eye still looks normal

ICGA SIGNS IN STROMAL CHOROIDITIS

In addition to exploration of the choriocapillaris, indocyanine green angiography allows also to explore and investigate stromal choroidal inflammatory disease and detect lesions even at an early and/or subclinical stage of evolution not accessible so far to investigational tests.23

Two lesional processes will generate ICGA signs in stromalchoroiditis.Thisisononehandtheinflammatory focus, mostly granulomatous, causing hypofluorescence because the ICG dye is prevented from diffusing into these areas (Figures 12C and 13C). Depending on the extent of infiltration of the granuloma, full-thickness or partial thickness, the ICGA image (hypofluorescence, HDDs)willbeinfluenced(Figures12and13).Thesecond concomittant, associated mechanism is inflammation of the surrounding choroidal stromal vessels causing abnormal leakage from larger vessels that adds to the

Figure 38B: Unclassifiable choriocapillaritis. Numerous hypofluorescent areas due to choriocapillaris non perfusion in second right eye 3 months after involvement of first left eye

Figure 38C: Unclassifiable choriocapillaritis. Regression of some of the lesions in the secondly affecred right eye after systemic corticosteroid therapy

Figure 38D: Bilateral chorioretinal atrophy due to an unclassifiable choriocapillaritis (originally published and reproduced from Uveitis and Immunological Disorders. Edited by Pleyer U, Mondino B (Eds). Berlin, Heidelberg, New York: Springer; 2004)

physiological ICG exudation from the fenestrated choriocapillaris and is at the origin of increased diffuse fluorescence around the hypofluorescent inflammatory foci (Figure 39A). In contrast to primary inflammatory choriocapillaropathies,ICGAsemiologicsignsofstromal choroiditis, the HDDs and the diffuse hyperfluorescence surrounding the dark dots have been explained histopathologically. Histopathology has been available since some time for Vogt-Koyanagi-Harada disease, sympathetic ophthalmia and sarcoidosis and recently granulomas and choroidal stromal vasculitis have been

Figure 39A: Fuzzy indistinct vessels and late diffuse choroidal hyperfluorescence

Figure 39B: Late difuse choroidal hyperfluorescence

found in an autopsy case of birdshot chorioretinopathy showing more or less dense granulomas of variable size as well as vasculitis of large stromal vessels21,22 (Figures 13C and 14).

There are two main specific ICGA signs that can be seen in diverse proportions according to the type of disease:

1.Even, regularly distributed ICGA hypofluorescent dark dots (HDD) in case of birdshot chorioretinopathy, Vogt-Koyanagi-Harada disease and sympathetic ophthalmia or diversely sized hypofluorescent areas in case of sarcoidosis or tuberculosis present in the early and intermediate phase, either remaining hypofluorescent in the late phase (full thickness inflammatory foci) or becoming isofluorescent in the late phase in case of partial thickness inflammatory foci. The mechanism causing these HDDs should not be called a masking or blocking effect but a “mass

effect” as there is no screen hiding the ICG fluorescence but absence of fluorescence is produced by inflammatory foci occupying the choroidal space not allowing ICG to diffuse16 (Figures 12 and 13).

2.Around the inflammatory lesions appearing as hypofluorescent dark dots (HDDs), the larger choroidal vessels lose their normal aspect and appear fuzzy, indicating choroidal vasculitis that allows pathologic extrusion of the ICG-complex from the larger usually impermeable vessels that adds to the physiologic ICG impregnation of the stroma coming from the choriocapillaris. This is at the origin of late diffuse choroidal hyperfluorescence16 (Figures 9, and 39B)

More rare signs to look for are:

1.In homogeneous filling of choriocapillaris due to perfusion delay in the very early phase of ICGA.

2.Microfocal bright hyperfluorescent pinpoints since post-early phase in case of inflammatory serous retinal detachment such as in Voght-Koyanagi- Harada disease corresponding to the hyperfluorescent pinpoints seen in the same location on fluorescein angiography.

3.Microfocal hyperfluorescent pinpoints appearing in the late phase in the affected areas that can be seen in all granulomatous entities such as sarcoidosis, syphilis or tuberculosis.

4.Disc hyperfluorescence in the late phase in case of very severe inflammation.

5.Secondary inflammatory choriocapillaropathy in case of severe stromal inflammation in the form of irregularly shaped confluent geographic areas of hypofluorescence.

Primary Stromal Choroiditis

Primary obligatory stromal choroiditis comprises several conditions where the inflammatory process is selectively targeting choroidal stromal structures. In Vogt-Koyanagi-Harada disease the target is a melanine associated protein in stromal melanocytes and a similar process is probably occurring in sympathetic ophthalmia. The regular pattern and the even distribution of choroidal lesions in birdshot chorioretinopathy and the histological lesions shown in a recent histopathological report also strongly suggests targeted stromal inflammatory involvement, most probably also at

the level of stromal melanocytes in this condition also.21,22 Because the inflammatory process is taking its origin within the choroidal stroma, ICGA is especially suited to investigate and follow-up these entities as it can show subtle lesions and sub-clinical and early changes not shown by any other means.

Vogt-Koyanagi-Harada Disease

Vogt-Koyanagi-Harada (VKH) disease is a bilateral, granulomatous panuveitis due to an autoimmune process that in the eye is directed against proteins associated with stromal melanocytes that can cause secondarily exudative retinal detachments. Systemic manifestations such as meningeal signs and cutaneous signs (poliosis, alopecia, vitiligo) and dysacusis can be associated usually occurring at subsequent time.68-71 Histopathologic evaluation reveals thickening of the choroid with stromal cellular inflammation constituted by macrophages, lymphocytes and epithelioid cells containing melanin, which is the histopathologic lesion at the origin of the ICGA sign of hypofluorescent dark dots (HDDs)72-73 (Figure 12C). The lesional process in this disease defines VKH as a strictly primary choroidal stromal inflammatory disease and involvement of the adjacent structures is only secondary to choroidal disease. VKH is, therefore, the typical example of a primary stromal choroiditis as is the case for sympathetic ophthalmia and birdshot chorioretinopathy (see below). To understand both ICGA and FA angiographic signs it is useful to recall the classical fundus signs including optic disc hyperhemia and swelling, multifocal exudative serous retinal detachments in the acute phase of the disease or in active recurrences (Figure 40A), followed in the late stage by depigmentation at the level of the choroid (sunset glow fundus), and pigment clumps (Figure 40B). Peripheral yellowwhite small round chorioretinal atrophic lesions may correspond to scars of Dalen-Fuchs nodules (Figure 40B). With chronic evolution, diffuse retinal pigment epithelium alterations classically appear as “salt-and- pepper” on fundus and FA images and the limits of the acute exudative retinal detachment can be seen as a line of pigment depositis called “high-water mark” or high-water line.72,73 This is due to retinal pigment epithelial changes produced by the serous retinal detachments and is very well shown by fluorescein angiography (Figure 41).

Figure 40A: Serous retinal detachments in VKH disease.

Numerous and confluent serous retinal detachments around the disc and along the arcades

Figure 40B: FA of serous retinal detachments in VKH. The numerous retinal serous detachments with their hyperfluorescent leaking dots are more clearly put in evidence by FA

Figure 40C: Ocular coherence tomography (OCT) of serous retinal detachments. (Courtesy Prof. Manabu Mochizuki, Tokyo) The serous retinal detachment can take voluminous dimensions. It should be remembered that this is a secondary manifestation of the primary choroidal inflammation and is a good parameter to follow in the early treatment period. It gives, however, no information on the choroidal inflammation itself

Figure 40D: Peripheral yellow scars typical of VKH disease

Figure 41: RPE changes after reattachment of the serous retinal detachment on FA. Alternation of hyperfluorescence (window defect) due to disappearance of RPE cells and hypofluorescence (masking effect) due to clumping of pigment. Well visible limit of serous detachment (high-water marks) in the periphery of the dryed detachment area. Note also disc hyperfluorescence

ICGA signs in acute VKH disease

Looking at ICGA signs in a chronologic fashion from the start of the angiography to the late phases at least 7 characteristic signs can be identified. At the very early angiographic phase choriocapillaris perfusion inhomogeneity with delay in some sectors appearing as dark hypofluorescent geographic areas can be seen in most cases (Figure 42). Very early also, choroidal hyperfluorescent and leaking vessels are seen indicating choroidal vasculitis or choroidal inflammatory vasculopathy (Figure 43). One of the main characteristc features seen on ICG angiography in an acute inflammatory episode of the disease is the presence of disseminated, evenly sized, regularly distributed HDDs appearing 3-6 minutes after dye injection (Figure 44A) and well visible in the

Figure 42: Inhomogeneity of choriocapllaris filling in VKH

Figure 43: Early hyperfluorescent leaking choroidal vessels.

Numerous hyperfluorescent vessels indicate choroidal vasculitis

intermediate phase (8-12 minutes) (Figures 44B, 44C-left frames). A proportion of these hypofluorescent dots remain hypofluorescent in the late angiographic phase, others become isofluorescent indicating partial thickness choroidal infiltration (Figure 44C, right 4 frames). After the start of highdose inflammation suppressive therapy the proportion of HDDs remaining hypofluorescent until the late phase of angiography is decreasing and at the end of a successful treatment all HDD have disappeared (Figure 44D). In association with HDD, in the intermediate phase there are diffuse fuzzy choroidal leaking vessels indicating a much more diffuse choroidal vasculitis than the early hyperfluorescent vessels seen in the early phase (Figure 45). The corollary to intermediate phase fuzzy vessels is diffuse choroidal hyperfluorescence in the late phase (Figure 46). In very acute disease the disc that is usually hypofluorescent can become hyperfluorescent indicating