Diagnostic Challenges in Inflammatory Choroidal Neovascularization

Abstract

Inflammation plays a key role in the induction of choroidal neovascularization (CNV). Inflammatory choroidal neovascularization (iCNV) is a severe but uncommon complication of both infectious and non-infectious uveitides. It is hypothesized that its pathogenesis is similar to that of wet age-related macular degeneration (AMD), and involves hypoxia as well as the release of vascular endothelial growth factor, stromal cell-derived factor 1-alpha, and other mediators. Inflammatory CNV develops when inflammation or infection directly involves the retinal pigment epithelium (RPE)-Bruch's membrane complex. Inflammation itself can compromise perfusion, generating a gradient of retinal-choroidal hypoxia that additionally promotes the formation of choroidal neovascularization in the course of uveitis. The development of choroidal neovascularization may be a complication, especially in conditions such as punctate inner choroidopathy, multifocal choroiditis, serpiginous choroiditis, and presumed ocular histoplasmosis syndrome. Although the majority of iCNV cases are well defined and appear as the "classic" type (type 2 lesion) on fluorescein angiography, the diagnosis of iCNV is challenging due to difficulties in differentiating between inflammatory choroiditis lesions and choroidal neovascularization. Modern multimodal imaging, particularly the recently introduced technology of optical coherence tomography (OCT) and OCT angiography (noninvasive and rapid imaging modalities), can reveal additional features that aid the diagnosis of iCNV. However, more studies are needed to establish their role in the diagnosis and evaluation of iCNV activity.

Keywords: fluorescein angiography; indocyanine green angiography; inflammatory choroidal neovascularization; multimodal imaging; near-infrared autofluorescence; optical coherence tomography; optical coherence tomography angiography; uveitis.

Figure 1

(a) Fundus autofluorescence image, showing hypoautofluorescence of inactive postinflammatory lesions (red arrows) and hyperautofluorescence of active inflammatory lesions (green asterix); irregular autofluorescence is present above the postinflammatory scar suspected for inflammatory choroidal neovascularization (yellow arrow); (b,c) fluorescein angiography images, showing early isofluorescence with late staining (d) of the lesions as a result of a retinal pigmented epithelium window defect; no evident features of inflammatory choroidal neovascularization are observed.

Figure 2

(a) Color picture of the fundus showing inactive inflammatory foci in the macula region with changes at the retinal pigmented epithelium level; (b,c) fluorescein angiography images demonstrate early isofluorescence with late staining (d) of the lesions as a result of a retinal pigmented epithelium window defect without features of inflammatory choroidal neovascularization (red arrows).

Figure 3

(a) Fundus autofluorescence image shows hypoautoflurescence of inactive postinflammatory lesion in macula (red arrow) with hyperautofluorescent area representing the active inflammatory focus at its lower margin (green arrow), at the upper border of the scar the area of irregular autofluorescence is present (yellow arrow); (b,c) early and middle frames of indocyanine green (ICG) angiograms reveal a visibility of the choroidal vessels in the area of the inactive postinflammatory focus and small hypocyanescent area at its lower border corresponding to active choroidal inflammation; (d) late ICG angiogram demonstrates homogeneous hypocyanescence of the postinflammatory lesion with evidence of late hypercyanescence at its upper margin (yellow circle). The patient was diagnosed with inflammatory choridal neovascularization.

Figure 4

(a,e) Color pictures of the fundus presenting well-defined and partially pigmented chorioretinal scars at the sites of previous chorioretinal inflammation in the macula of both eyes; (b,f) fundus autofluorescence demonstrate hypoautofluorescent foci that correlate with photoreceptor and retinal pigment epithelium damage; (c,d,g,h) early and late frames of indocyanine green angiograms revealed the presence of homogenous hypocyanescent foci related to retinal pigment epithelium damage due to postinflammatory scarring; no features of inflammatory choroidal neovascularization are observed.

Figure 5

(a) Color picture of the right eye diagnosed for punctate inner choroidopathy; (b) optical coherence tomography scan demonstrates hyperreflective material above the retinal pigment epithelium with the presence of subretinal and intraretinal fluid corresponding to an active inflammatory choroidal neovascularization with multiple vertical finger-like projections extending anteriorly into the outer retina—the “pitchfork sign” (yellow arrows).

Figure 6

(a) Color picture of the fundus shows macular subretinal fibrosis; (b) optical coherence tomography scan revealed hyperreflective material under the retinal pigment epithelium (yellow arrow), subretinal fluid is present (red arrow); (c–f) optical coherence tomography angiography (OCTA): the scan of the superficial capillary plexus is undisrupted (c); the scan of the deep capillary plexus shows a capillary impairment (d); the scans of outer retinal layer and choriocapillaris demonstrate pathological vessels presenting inflammatory choroidal neovascularization (iCNV) (yellow circles); (g) OCTA scan B presents the blood-flow in outer retinal layer (black arrows); (h) OCTA vessel density map is complementary and shows the presence of pathological vessels corresponding to iCNV (yellow circle).

Figure 7

(a,c) Color pictures of the right eye diagnosed for punctate inner choroidopathy; (b,d) optical coherence tomography scans demonstrate choroidal thickness (CT) changes under inflammatory choroidal neovascularization before and after the treatment—the “sponge sign”. Before treatment, CT corresponded to 257 µm and then decreased to 202 µm after intravitreal bevacizumab injection.

Figure 8

(a₁,a₂) Early and middle stages of indocyanine green angiography present hypocyanescent spots indicating active inflammatory lesions (red arrows); (a₃) late stage shows hypercyanescent plaque (green circle); (b–e) optical coherence tomography angiography (OCTA): the scan of the superficial apillary plexus is undisrupted (b); the scan of the deep capillary plexus shows a small area of capillary impairment below the macula (c); the scans of the outer retinal layer and choriocapillaris demonstrated pathological vessels presenting inflammatory choroidal neovascularization (green circles) (d,e); (f) OCTA B scan shows the presence of a trace of subretinal fluid (yellow arrow), blood flow in the outer retinal layers (green arrow), and intraretinal fluid (pink arrow), indicating the presence of active inflammatory choroidal neovascularization; (g) OCTA vessel density map presents a net of pathological vessels (yellow circle).

Figure 9

(a) Early frame of fluorescein angiography demonstrates the presence of isofluorescence of the inactive inflammatory lesion related to serpiginous choroidopathy; (b) Late frame of fluorescein angiography presents hyperfluorescent area of inactive postinflammatory lesion as a result of a “window defect” with irregular staining above it (yellow arrow); (c–f) Optical coherence tomography angiography demonstrated normal superficial and deep capillary plexi (c,d); the scans of outer retina and choriocapillary layers show the net of pathological vessels (e,f); (g) OCTA B scan shows the presence of subretinal mass with blood flow (black arrows); (h) OCTA vessel density map presents a net of pathological vessels (yellow circle); (i) Optical coherence tomography presents the hyperreflective subretinal lesion (yellow arrow) with subretinal fluid (red arow) and intraretinal fluid (blue arrow) showing the evidence of active inflammatory choroidal neovasularization.