An update of multimodal imaging in white dot syndrome

Abstract

The white dot syndromes are a group of phenotypically similar disorders characterized by multiple lesions at the level of the outer retina, retinal pigment epithelium, and choroid. Common white dot syndromes whose imaging modalities have been described in this article are multiple evanescent white dot syndrome, acute posterior multifocal placoid pigment epitheliopathy, acute zonal occult outer retinopathy, multifocal choroiditis and panuveitis, punctate inner choroidopathy, serpiginous choroiditis, and birdshot chorioretinopathy. The various imaging modalities help us to better understand the pathophysiology of the various entities and help in diagnosing, monitoring, and prognosticating them. Optical coherence tomography angiography (OCTA) is a comparatively newer tool that helps us to visualize lesions in the choroid that correlate with indocyanine green angiography (ICGA) findings. Even though it is of limited value and cannot replace ICGA, it had gained considerable interest among ophthalmologists. Similarly, the noninvasive nature of modalities such as fundus autofluorescence and OCT makes them appealing and preferable over invasive techniques such as fundus fluorescein angiography and ICGA.

Introduction

The white dot syndromes are a group of phenotypically similar disorders characterized by multiple lesions at the level of the outer retina, retinal pigment epithelium (RPE), and choroid. The etiology is not completely understood. However, the advent of advanced imaging modalities has shed light on the pathophysiology of the various entities and helps in diagnosing, monitoring, and prognosticating them. Common white dot syndromes are multiple evanescent white dot syndrome (MEWDS), acute posterior multifocal placoid pigment epitheliopathy (APMPPE), acute zonal occult outer retinopathy (AZOOR), multifocal choroiditis and panuveitis (MFCP), punctate inner choroidopathy (PIC), serpiginous choroiditis (SC), and birdshot chorioretinopathy (BSC). Here, we have attempted to concisely put forward the findings and their significance in various imaging modalities in the various mentioned common disorders that fall under the umbrella of the white dot syndrome. The imaging findings in each entity are summarized in Table 1.

Table 1.

Overview of imaging findings of the various white dot syndrome entities

	Fundus image	FAF	FFA	ICGA	OCT
MEWDS	Active several yellowish-white lesions at the level of RPE or deep retina maximally concentrated at the posterior pole. Foveal granularity Resolution - no pigmentation/atrophy Later staged - rarely CNVM	Acute: Indistinct hyperAF lesions Subacute: Become less numerous, small hyperAF dots surrounded by a hypoAF halo	Early hypofluorescent areas Later stage wreath-like early hyperfluorescence	Corresponding hypocyanescent areas Later stage: May become isocyanescent or even hypercyanescent in the intermediate-late phase	Active: Diffuse-disrupted ellipsoid zone at the lesion site, round hyperreflective foci in the outer nuclear layer, focal interruptions of RPE Resolution-recovery with intact layers
APMPPE	Active-subretinal yellowish-white creamy placoid lesions are seen predominantly at the posterior pole with minimal inflammatory reaction Resolution - leaves behind chorioretinal atrophic patches and pigmentation at the level of RPE	Acute - corresponding areas of hypoAF Resolving - mixed hyper and hypoAF pattern Resolution - homogenous hypoAF	Active - early hypofluorescence, and late staining Inactive: Window defects	Active: Hypocyanescent patches which remain hypocyanescent throughout Inactive: Isocyanescence or persistent well-defined hypocyanescence with visibility of the deeper choroidal vasculature	Active: Disruption of the EZ and outer retinal layers, hyperreflectivity of the outer retinal layers Resolving/resolution: Hyperreflectivity fades and there is RPE atrophy or partial restoration of the lost retinal layers
AZOOR	Active: Orange demarcating line between the involved and uninvolved retina Later stage: Cystoid macular edema, multifocal chorioretinal scars, perivenous exudation, narrowed retinal vessels, and RPE atrophy	Trizonal pattern in seen where speckled hyperAF indications the active lesion and hypoAF lesions are seen in old lesions (refer to text)	Not very specific	Not very specific	Active lesion: Multifocal hyperreflective material in the subretinal space Resolved lesions: Loss of outer retinal layers
MFCP, PIC	Active: Yellow-orange, round or oval, sometimes elevated Resolution: Punched out atrophic scars Chronic: CNVM, more commonly in PIC	Active: Round areas of minimal hyperAF or spot of hypoAF with hyperAF margin Resolved: hypoAF	MFCP - early hypofluorescence with late staining and leakage PIC - early mild hyperfluorescence with leakage in the late frames Old lesions: Window defects	Active: Hypocyanescent areas which remain so throughout Resolved: Hypocyanescence with visibility of the deeper choroidal vasculature	Active: conical focal chorioretinal elevations breaking through the RPE and BM, the tip of which may be ruptured leading to infiltrates in the outer retina. Focal choroidal hyperreflectivity present below the lesions. Disruption of ellipsoid zone and outer retinal layer Resolved: Disruption of ellipsoid zone and outer retinal layer
SC	Active: Well-defined grayish-white or grayish-yellow discoloration at the deeper retinal layers Resolved: Chorioretinal atrophy or scarring	Active: HyperAF lesions or hyperAF margins of hypoAF lesions Resolving: hyperAF and hypoAF mix Resolved/old - hypoAF	Active: Early hypofluorescence with late staining Resolved: Window defects	Active: Hypocyanescent areas which remain so throughout Resolved: Hypocyanescence with visibility of the deeper choroidal vasculature	Active: Uniform outer retinal hyperreflectivity Resolved: Granular outer retinal hyperreflectivity, atrophy of the layers. Thinned out retina
BSC	Active: Multiple white-creamy choroidal ovoid rice-shaped lesions appear like a birdshot from a shotgun, usually in peripapillary area Later stage: Peripapillary atrophy	Active: HyperAF lesions Resolving: hyperAF and hypoAF mix Resolved/old - hypoAF	Active: Silent or mildly hypofluorescent lesions, become more hyperfluorescent in the late phase Resolved: Window defects	Active: Hypocyanescent dark dots, that may or may not correspond with clinically visible lesions, are seen during the intermediate phase which either remains so in the late phase or becomes isocyanescent Resolves completely or hypocyanescence with visibility of the deeper choroidal vasculature	Increased retinal nerve fiber layer thickness, disruption at EZ Resolved: EZ disruption, choroidal thinning

MEWDS: Multiple evanescent white dot syndrome, APMPPE: Acute posterior multifocal placoid pigment epitheliopathy, AZOOR: Acute zonal occult outer retinopathy, MFCP: Multifocal choroiditis and panuveitis, PIC: Punctate inner choroidopathy, SC: Serpiginous choroiditis, BSC: Birdshot chorioretinopathy, FAF: Fundus autofluorescence, FFA: Fundus fluorescein angiography, ICGA: Indocyanine green angiography, OCT: Optical coherence tomography, RPE: Retinal pigment epithelium, CNVM: Choroidal neovascular membrane, EZ: Ellipsoid zone, hyperAF: Hyperautofluorescent, hypoAF: Hypoautofluorescent

Multiple Evanescent white Dot Syndrome

MEWDS was first described in 1984. They occur typically in young myopic women, usually following an episode of viral illness. They are thought to be at the benign end of the choriocapillaris spectrum with inflammation affecting the end capillaries. This leads to multiple circumscribed areas of choroidal hypoperfusion with corresponding photoreceptor damage. Depending on the area affected, visual loss can be minor or severe. This disease usually self-resolves without treatment within 8–10 weeks.[1,2]

Fundus photo

Several yellowish-white lesions with size ranging from 100 μ to more than 200 μ are seen at the level of RPE or deep retina. They may be located at the posterior pole, peripapillary area, and mid-peripheral retina, with maximum concentration being at the posterior pole. Foveal granularity, also known as Jampol dots, is present, and there may be mild optic disc inflammation.[1] At times the fundus may appears normal with the activity being picked up only on imaging [Figure 1a]. It is believed that lesions usually resolve without leaving behind any pigmentation or atrophy. The presence of pigmentation or atrophy usually indicates the presence of other inflammatory maculopathies.[1] Complications such as choroidal neovascular membrane (CNVM) are rare in MEWDS but have nevertheless been reported.[3]

Figure 1.

Multiple evanescent white dot syndrome: (a) Fundus photo with no significant findings, (b) Fundus fluorescein angiography (FFA) reveals wreath-like punctate hyperfluorescent lesions along with disc staining in the mid phase, (c) ICGA shows several hypocyanescent spots (black arrowheads). Acute posterior multifocal placoid pigment epitheliopathy: (d) Fundus photo of the right eye showing several creamy placoid lesions. FFA shows hypofluorescence (e) of lesions in early phase and hyperfluorescence (f) in late phase indicating that the lesions are active

Fundus autofluorescence

Indistinct hyperautofluorescent lesions corresponding to areas of indocyanine green angiography (ICGA) hypoperfusion are seen on blue fundus autofluorescence (BAF). This is due to RPE dysfunction secondary to the choriocapillaris at these sites. Subsequent loss of photoreceptor and RPE damage lead to hypoautofluorescent lesions. Foveal involvement is however not clear on BAF due to the masking effect of macular pigments such as lutein, zeaxanthin, and meso-zeaxanthin. The infrared wavelength of light in near-infrared fundus autofluorescence (NIR AF) is able to penetrate through these pigments and show hypoautofluorescent lesions even if BAF appears to be normal. Dotted hyperautofluorescence on BAF has been reported in the subacute phase which evolves to exhibit different patterns. They became less numerous few weeks after the initial presentation and then persisted for several months, they retracted centripetally becoming small hyperautofluorescent dots surrounded by a hypoautofluorescent halo, or they became hypoautofluorescent. In some cases, they even resolved leaving no trace abnormalities behind.[4]

Fluorescein angiography and indocyanine green angiography

Hypocyanescent areas due to hypoperfusion of the affected choriocapillaris are seen on ICGA. Corresponding to these areas, fundus fluorescein angiography (FFA) may show two patterns. There may be early hypofluorescent areas due to a transient block of fluorescence by the inflammation located at the level of the outer retina secondary to choriocapillaris. However, damaged RPE cells will lead to wreath-like early hyperfluorescence due to window defect [Figure 1b].

Lesions on ICGA may stay hypocyanescent throughout [Figure 1c] or may become isocyanescent or even hypercyanescent in the intermediate-late phase.

Disc hyperfluorescence is also seen and vasculitis has also been reported.[2]

Optical coherence tomography

SD-OCT usually shows a diffuse disrupted ellipsoid zone at the lesion site which becomes focal during the recovery period and ultimately recovers and becomes continuous during the late recovery period. Punctate or round hyperreflective foci in the outer nuclear layer may also be seen which disappear in the recovery phase.[5] RPE may be intact, or there may be focal interruptions which recover later. There may be signal hypertransmission through the choroid and sclera with an overlying intact RPE which disappears at recovery. Transient subretinal deposits representing debris consisting of damaged photoreceptor fragments may also be seen. Region of foveal granularity has been reported to exhibit ellipsoid and interdigitation zone disruption, focal thickening of RPE with hyperreflective material, and vertical hyperreflective line through the outer nuclear layer.[6]

Optical coherence tomography angiography

Hypoperfusion at sites of choroidal inflammation leads to corresponding flow void areas in OCTA at the level of choriocapillaris. There is complete resolution of these areas with recovery of the disease. However, this is usually found in the more severe cases of MEWDS. In end capillaries, capillary dropouts are usually not detected making OCTA an inappropriate imaging option in MEWDS.[7]

Acute Posterior Multifocal Placoid Pigment Epitheliopathy

APMPPE is a rare inflammatory disorder where there is primary inflammation of the choriocapillaris with secondary involvement of RPE and photoreceptors. The inflammation occurs at the level of mid-sized vessels.[2] It was first described in 1968 by Gass. It occurs in young healthy adults and is often preceded by viral illness or vaccination. In general, it is a self-resolving condition and requires no treatment.[8]

Fundus photo

Subretinal yellowish-white creamy placoid lesions are seen predominantly at the posterior pole, not extending beyond the equator [Figure 1d]. There may be minimal associated inflammatory reaction. The lesions resolve over a few weeks leaving behind chorioretinal atrophic patches and pigmentation at the level of RPE. There may also be associated papillitis and/or retinal vasculitis.[8]

Fundus autofluorescence

Acute lesions show corresponding areas of hypoautofluorescence probably due to retinal cell edema. Sometimes, few of the lesions may not show any abnormality on fundus autofluorescence (FAF). As the disease evolves, disruption in the RPE layer, with an increase in pigmentation or thickness, leads to a mixed hyper- and hypoautofluorescent pattern. Subsequent photoreceptor cell death or RPE atrophy leads to a more homogenous hypoautofluorescence.[9]

Fundus fluorescein angiography and indocyanine green angiography

APMPPE has been recently classified as a primary choriocapillaris affecting mid-sized vessels. In the active phase on ICGA, the affected choriocapillaris are seen as hypocyanescent patches which remain hypocyanescent throughout all the phases of the angiogram. On the other hand, FFA of active lesions shows early hypofluorescence, probably due to choroidal hypoperfusion and RPE layer edema, and late staining [Figure 1e and f]. These findings lead to two schools of thought. One is that the inflammation is primarily at the choriocapillaris and the other is that the inflammation is primarily at the outer retina and RPE leading to masking effect that leads to the appearance of corresponding hypocyanescence on ICGA. Inactive lesions may be seen on ICGA as either isocyanescence due to restoration of normal circulation of the choriocapillaris or persistent well-defined hypocyanescence with visibility of the deeper choroidal vasculature.[2,10]

Optical coherence tomography

On OCT, corresponding to placoid lesions, disruption of the EZ and outer retinal layers is seen. There may also be hyperreflectivity of the outer retinal layers. As the disease resolves, the hyperreflectivity fades and there is RPE atrophy or partial restoration of the lost retinal layers. Other signs such as neurosensory detachment and bacillary layer detachment have also been reported in APMPPE. Enhanced depth imaging OCT shows us the progressive change in the choriocapillaris with active stage showing increased thickness and hyporeflectivity which may become normal or become thin and atrophic.[10]

Optical coherence tomography angiography

OCTA shows flow void areas corresponding to ICGA nonperfusion areas. Reperfusion may be seen with healing of the lesions. This finding finally supports the thought of inflammation primarily being at the level of choriocapillaris. It has been suggested that OCTA is able to clearly differentiate between choriocapillaris atrophy and hypoperfusion. The number, size, and location of lesions are predictive factors of visual prognosis.[11]

Acute Zonal Occult Outer Retinopathy

AZOOR was first described by Gass in 1993 and is characterized by rapid loss of one or more large zones of outer retinal function. It occurs predominantly in young to middle-aged women. There may be a preceding viral illness. No definite treatment has been proven and a trial of systemic steroids and/or immunosuppressive agents may be given. Spontaneous resolution has also been reported.[5]

Fundus photo

The fundus may be normal at the time of examination. A few weeks after onset, the patient may develop cystoid macular edema, multifocal chorioretinal scars, perivenous exudation, narrowed retinal vessels, and RPE atrophy and clumping resembling retinitis pigmentosa. The fovea is usually spared. There may be an orange demarcating line between the involved and uninvolved retina, which could be continuous, interrupted, or scalloped in appearance [Figure 2a and b].

Figure 2.

Acute zonal occult outer retinopathy. Fundus photo of the right (a) and left (b) eyes showing areas of retinal pigment epithelial alteration (blue arrows). FAF of the right (c) and left (d) eyes showing trizonal pattern (Zone 1: White star, Zone 2: Black star, Zone 3: Yellow star). OCT of the right (e) and left (f) eyes showing outer retinal loss and speckled hyperreflectivity (black arrows) with foveal thinning in the left eye (f)

Fundus autofluorescence

The demarcating line is seen more clearly on FAF as a hyperautofluorescent line. A characteristic trizonal pattern is seen in AZOOR [Figure 2c and d] normal autofluorescence is seen outside the demarcating line (zone 1), speckled hyperautofluorescence is seen within the AZOOR lesion (zone 2), and hypoautofluorescence is also seen which corresponds to RPE atrophy (zone 3). The speckled hyperautofluorescence is usually seen in subacute lesions.[12]

Fundus fluorescein angiography and indocyanine green angiography

ICGA may be normal or show hypocyanescence in areas of RPE atrophy.[13] FFA is not very specific and may reveal window defects, retinal vascular staining or leakage optic disc staining, and peripheral hyperfluorescent spots.[14]

Optical coherence tomography

OCT findings can be correlated to the trizonal pattern seen on FAF. Retinal layers are normal in zone 1. In zone 2, multifocal hyperreflective material is present in the subretinal space. Photoreceptor, RPE, and choroidal atrophy are seen in zone 3[12] [Figure 2e and f].

Optical coherence tomography angiography

OCTA shows the integrity of the choriocapillaris which can also be seen on ICGA.[5]

Other modalities such as visual fields and electroretinogram are useful in AZOOR.

Multifocal Choroiditis and Panuveitis and Punctate Inner Choroidopathy

MFCP was first described in 1984 by Dreyer and Gass while PIC was first described by Watzke, also in 1984. They occur typically in young adult myopic women. They are considered to be part of the same spectrum and are characterized by small, punctate lesions of the inner choroid and/or RPE. They are bilateral though the fellow eye may be affected several years after the first eye is affected.[15,16]

Fundus photo

The active lesions of MFCPU are yellow-orange, round or oval, sometimes elevated, and usually >250 μm in size. Punched-out atrophic scars may be seen in the later stage which involve loss of choroid and RPE in a circular fashion, typically with pigment clumping at the edge. The lesions are usually located at the mid-periphery and periphery of the fundus with or without posterior pole involvement [Figure 3g]. Anterior chamber and vitreous inflammation are present. Peripapillary atrophy, scarring, and curvilinear chorioretinal streaks called linear streaks or Schlaegel lines may be seen.[15]

Figure 3.

Punctate inner choroidopathy: (a) Fundus photo shows scarring choroidal neovascular membrane in the right eye with a few surrounding small yellowish-white lesions (blue arrows) which were more prominently appreciated on FAF as hypoautofluorescent spots (black arrows) surrounded by speckled hyperautofluorescence (yellow arrow) (b). Fundus fluorescein angiography (FFA) shows hyperfluorescence of lesions (white arrow) in the late phase (c) with corresponding hypocyanescence (green arrow) on Indocyanine green angiography (ICGA) (d). (e) OCT shows scarred CNVM with (f) OCT-A showing abnormal vascular network on the avascular slab. Multifocal choroiditis: (g) Fundus photo of the left eye showing multiple chorioretinal atrophic patches (blue arrow), (h) FAF showing several hypoautofluorescent areas (white arrows) indicating old lesions, (i) FFA in the late phase showing hyperfluorescent lesions (black arrows) with corresponding hypocyanescent areas (yellow arrows) on ICGA (j)

The active lesions of PIC are round-oval yellow-white or cream-colored (<150 μm in size) [Figure 3a] and may be associated with an overlying serous elevation. Lesions may resolve completely or leave behind atrophic scarring. The lesions are usually located at the posterior pole. There is low to absence of anterior chamber and vitreous inflammation. Choroidal neovascularization is more common [Figure 3e and f].[16]

Fundus autofluorescence

The FAF findings of MCP and PIC have been found to be similar. RPE elevations are noted as round areas of minimal hyperautofluorescence. However, if there is a breach in the RPE, FAF shows a corresponding spot of hypoautofluorescence with hyperautofluorescent margin [Figure 3b and h]. Atrophic spots are seen as hypoautofluorescence.[17,18]

Fundus fluorescein angiography and indocyanine green angiography

There is choriocapillaris with involvement of precapillary arterioles and ICGA reveals hypocyanescent areas which remain so throughout [Figure 3d and j].

On FFA, active lesions in MFCP generally demonstrate early hypofluorescence with late staining and leakage [Figure 3i] whereas lesions in PIC show early mild hyperfluorescence with leakage in the late frames [Figure 3c]. Atrophic scars demonstrate window defects.[15,16]

Optical coherence tomography

The OCT findings are characterized by conical focal chorioretinal elevations breaking through RPE and Bruch’s membrane the tip of which may later rupture leading to an outpouring of infiltrates into the outer retina. Focal choroidal hyperreflectivity is present below the lesions. Ellipsoid zone and outer retinal layer may also be disrupted. Vitreous cells may be seen. As the lesions heal, RPE may stabilize leading to a reduction in the hyperreflectivity. Hyperreflective infiltrates have been found in the choroidal layers.[17,18]

Optical coherence tomography angiography

OCTA shows flow void areas corresponding to lesions and also helps in assessing CNVM. An area of surrounding hyporeflectivity around the CNVM has been reported. The size of this hyporeflectivity increased with worsening activity in some patients.[11]

Serpiginous Choroiditis

SC is a primary choriocapillaris that usually affects the proximal larger vessels.[2] It leads to secondary extensive damage to RPE and photoreceptors and is usually irreversible. Visual impairment is significant if fovea is involved. It is a bilateral, asymmetric, and progressive condition and needs to be treated aggressively.[19]

Fundus photo

A creeping type of choroiditis is seen that begin in the peripapillary area and extend outwards in a geographical pattern. There is well defined greyish white or greyish yellow discolouration at the deeper retinal layers [Figure 4a and g]. New lesions usually arise from the margins of old ones. End result is extensive areas of chorioretinal atrophy or scarring. SC also has a macular variant where the macular region is predominantly involved.

Figure 4.

Multifocal serpiginous choroiditis: (a) Fundus photo shows several chorioretinal atrophic patches, (b) FAF shows hyperautofluorescence surrounding hypoautofluorescent lesion indicating activity (black arrow). Hypoautofluorescent margins of hyperautofluorescent or mixed hypo- and hypoautofluorescent lesions indicate resolving lesions (yellow arrow), (c) Fundus fluorescein angiography (FFA) shows hypofluorescent lesions with sharp hyperfluorescent margins in the mid phase and (d) Indocyanine green angiography (ICGA) shows corresponding hypocyanescent lesions, (e) OCT shows outer retinal layer defect with choroidal hyperreflectivity (blue arrow), (f) OCTA of choriocapillaris slab shows flow void areas corresponding to lesion. Serpiginous choroiditis: (g) Fundus photo showing a geographic pattern of choroidal lesions, FFA in early (h) and mid phase (i) showing early hypofluorescence and late staining with the presence of hyperfluorescent disc. ICGA in early (j) and mid phase (k) showing early hypocyanescence and later deeper choroidal vessels indicating healed atrophic areas (yellow arrows) and few areas that remained hypocyanescent indicating activity (white arrows) (l) OCT shows loss of outer retinal layers, vitreous cells are present. OCTA at superficial (m) and deep (n) layers showing flow void areas

Fundus autofluorescence

Deep retinal edema leads to hypoautofluorecent lesions due to masking effect at very early stage of the disease. There may be a hyperautofluorescent halo surrounding these lesions. This is probably due to thickening of normal adjacent RPE cells surrounding the edematous RPE patch. The hypoautofluorescence becomes increasingly hyperautofluorescent over the next few days along with increasing clinically visible pigmentation within the lesions. This in turn is surrounded by a sharp hypoautofluorescent border corresponding to depigmentation at the fundus examination [Figure 4b]. As the disease keeps resolving, central area shows speckled hyperautofluorescence. With complete inactivity, the lesions become predominantly hypoautofluorescent.[20]

Fundus fluorescein angiography and indocyanine green angiography

In active stage, ICGA shows large areas of hypocyanescence which remains so throughout [Figure 4d,i,k]. Corresponding to these, FFA shows hypofluorescence in early phase due to RPE edema and choriocapillaris non-perfusion. Late stage staining is seen due to seepage of dye from the surrounding healthy choriocapillaris [Figure 4c,h,j].[2]

Optical coherence tomography

Outer retinal hyperreflectivity is seen in both active and healed lesions [Figure 4l]. In active lesions, they are more uniform and is followed by atrophy of the layers. In healed lesions, outer layers become indistinguishable and hyperreflectivity is more granular and irregular [Figure 4e]. Subretinal fluid may be present. Retina in healed lesions appear to be thinned out. Choroidal hyperreflectivity has been described(waterfall effect). In active lesions, it is because of inflammatory cell inflammation in the choroid whereas in healed lesions it is due to increased light transmission due to overlying RPE atrophy.[19,21]

Optical coherence tomography angiography

Choriocapillaris lesions can be identified as flow void areas on OCT A [Figure 4 f,m,n] and the disease can be monitored by examining the size and area of the lesions.[10]

Birdshot Chorioretinopathy

BSC is a bilateral ocular inflammation where there is stromal choroiditis along with concomitant retinal vasculitis mostly involving large retinal veins. There is a strong association with HLA A29 allele.[22]

Fundus photo

Multiple white-creamy choroidal ovoid rice-shaped lesions appear like a birdshot from a shotgun [Figure 5a and b]. The lesions can be one-eighth to one-half optic disc diameter or larger and confluent. They are usually clustered in the peripapillary area. The lesions may develop hyperpigmentation. The lesions may coalesce around the optic disc leading to peripapillary atrophy.[22]

Figure 5.

Birdshot choroidoretinopathy. Fundus photo of right (a) and left (b) eye showing multiple ovoid depigmented areas(blue arrows) with peripapillary atrophy(blue dots). ICGA photo of right (c) and left (d) eye showing multiple hypocyanescent dark dots(black arrows) FFA of photo of right (e) and left (f) eye showing disc hyperfluorescence and vasculitis

Fundus autofluorescence

Hyperautofluorescence serves as a marker of earlier inflammatory changes. Hyperautofluorescent lesions are associated with shorter duration of the disease and may be due to stress responses in the RPE due to the underlying inflammation or due to fluorophores from infiltrating leukocytes. They gradually progress to granular or confluent hypoautofluorescence. The most common pattern reported on FAF was the presence of peripapillary confluent hypoautofluorescence. Confluency indicated a longer duration of the disease. Linear hypoautofluorescence streaks along retinal vessels may represent retinal vasculitis.[23]

Fundus fluorescein angiography and indocyanine green angiography

On ICGA, hypocyanescent dark dots (HDDs), that may or may not correspond with clinically visible lesions [Figure 5c and d], are seen during the intermediate phase which either remains so in the late phase or becomes isocyanescent. Fuzzy indistinct choroidal vessels are noted. BSC is a primary stromal choroiditis. The inflammatory foci are seen as HDD with seepage of dye in the surrounding.[2]

Delay in fluorescein circulation time has been reported. Cream-colored lesions were either silent or mildly hypoautofluorescent on FFA. Disc hyperfluorescence is seen in the active phase along with vasculitis of small retinal vessels appearing as small hyperfluorescent foci spread over the fundus [Figure 5e and f]. These foci do not correspond to the clinically visible lesions or ICGA lesions and progressively become more hyperfluorescent in the late phase suggesting retinal inflammation.[10]

Optical coherence tomography

Disruption at the EZ is noted. Active lesions may show increased retinal nerve fiber layer thickness. EDI-OCT can show various choroidal layer findings such as choroidal thinning, hyperreflective choroidal foci, choroidal hyperreflectivity, and the presence of suprachoroidal hyporeflective spaces. No association between the hyporeflective spaces and clinically visible lesions has been noted.[22] Perivascular thickness associated with retinal vasculitis has also been studied.[24]

Optical coherence tomography angiography

OCTA demonstrates multiple flow voids corresponding with HDD seen on ICGA. They are located adjacent to large vessels in the Haller layer suggesting that the acute inflammation originates in the Haller’s layer. The flow voids regress with treatment, but in chronic, untreated cases, full-thickness choroidal flow void persists.[25]

Conclusion

Multimodal imaging plays an important role in the management of uveitic entities. It has helped us to understand the pathophysiology of the diseases better. OCTA is a comparatively newer tool that helps us visualize lesions in the choroid that correlate with ICGA findings. Even though it is of limited value and cannot replace ICGA, it had gained considerable interest among ophthalmologists. Similarly, the noninvasive nature of modalities like FAF and OCT makes them appealing and preferable over invasive techniques such as FFA and ICGA.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.