RESIDUAL CHOROIDAL VESSELS IN ATROPHY CAN MASQUERADE AS CHOROIDAL NEOVASCULARIZATION ON OPTICAL COHERENCE TOMOGRAPHY ANGIOGRAPHY: Introducing a Clinical and Software Approach

Abstract

Purpose: To present a postprocessing approach in optical coherence tomography angiography (OCTA) to facilitate the visualization and interpretation of lesions in age-related macular degeneration with coexisting atrophy and choroidal neovascularization (CNV).

Methods: This retrospective study included 32 eyes of 26 patients with atrophy and treated CNV and 8 eyes with treatment-naive geographic atrophy. En face optical coherence tomography slabs highlighting atrophy were pseudocolored and merged with the corresponding OCTA. Cross-sectional optical coherence tomography and postprocessed OCTA were analyzed to identify CNV and normal choroidal vessels in relationship to the atrophy. We correlate the OCTA findings with those in a donor eye with treatment-naive geographic atrophy studied with transmission electronic microscopy.

Results: Medium-sized choroidal vessels were displaced anteriorly in areas of atrophy in all 40 eyes (100%), visualized in the choriocapillaris slab in all eyes, and in the outer retinal slab in 30 of 40 eyes (75.0%). Cross-sectional OCTA was used to confirm the presence of CNV. Postprocessing successfully highlighted the CNV and distinguished it from choroidal vessels in atrophy. Donor eye transmission electronic microscopy confirmed the anterior displacement of medium-sized choroidal vessels in geographic atrophy.

Conclusion: The anterior displacement of larger choroidal vessels in atrophy requires clinician vigilance to avoid misinterpreting these vessels as CNV on en face OCTA. Our proposed postprocessing approach offers a potential solution to facilitate the interpretation of en face OCTA in these cases. In the absence of other tools, clinicians are encouraged to rely on the location of flow relative to Bruch membrane on cross-sectional OCTA flow images.

Fig. 1

Post-Processing Algorithm for Highlighting Areas of Geographic Atrophy (GA) on OCT Angiography (OCTA). Treatment-naïve Eye with GA. A. OCTA of choriocapillaris and cross-sectional OCT with red segmentation boundary lines. The dotted line shows location of B-scans. Normal choroidal vessels are displaced anteriorly in the area of GA and seen in choriocapillaris slab. B. En face structural OCT slab of the choroid with cross-section below. Extra signal penetrating the choroid in GA appears bright on the en face image. C. Binary rendition of OCT slab of the choroid used to select the area of GA (white). Choroidal illumination is seen in area of GA on the cross-section. D. Pseudo-colored OCTA of choriocapillaris highlights GA boundaries. Blood vessels in GA are pseudo-colored on a spectrum from blue to yellow and vessels in areas with relatively intact retinal pigment epithelium vessels are magenta. Red flow overlay on cross-sectional OCTA demonstrates a choroidal vessel abutting Bruch’s membrane in GA (blue arrow). White arrow points to a choroidal vessel located more posteriorly outside GA..

Fig. 2

Anterior Displacement of Choroidal Vessels in Areas of Multi-Lobular Geographic Atrophy (GA). Treatment-naïve Eye with GA. A. Pseudo-colored OCT angiography (OCTA) of manually segmented slab at the anatomical choriocapillaris. Blue arrows indicate a large choroidal blood vessel displaced anteriorly, making it visible in choriocapillaris slab. Blue circle shows choroidal vessels with morphology suspicious for choroidal neovascularization (CNV). B. En face structural OCT with same segmentation as (A) clearly visualizes the large choroidal vessel (blue arrow). C. Cross-sectional OCT with red flow signal overlay. Red flow signal from large vessel (blue arrow) is entirely contained within the blood vessel structure on OCT in (D) (blue arrow), suggesting anterior displacement and not artifact. Location of red flow signal from possible CNV formation (circle) in (C) is below Bruch’s membrane and could represent CNV that has not infiltrated above Bruch’s membrane. It is also possible that these are residual (not neovascular) vessels that are part of the Sattler’s layer and have moved anteriorly into the area of atrophy.

Fig. 3

Transmission Electron Microscopy (TEM) of Inferior Choroid Outside the Area of Geographic Atrophy (GA). Treatment-Naïve Donor Eye with GA from 87-year-old Caucasian Male. In this area outside of GA, the retinal pigment epithelium and photoreceptors are present, but the photoreceptors appear disorganized. This blood vessel appears to be choriocapillaris because it lacks pericytes and the endothelial cells have very thin processes, as well as numerous fenestrations and tight junctions.

Fig. 4

Transmission Electron Microscopy (TEM) Demonstrating a Choroidal Venule Abutting Bruch’s Membrane in Geography Atrophy (GA). Same treatment-Naïve Donor Eye with GA shown in Figure 3. A. Low magnification TEM of area absent retinal pigment epithelium and photoreceptors, with several choriocapillaris lumens missing, thickening of Bruch’s membrane and a thin scar. The viable blood vessel (black box) is shown in B–D. B. Montage of higher magnification images reveals that the vessel is a venule, which closely abuts Bruch’s membrane in an area of GA. The venule lacks fenestrations and has pericyte processes surrounding the entire vessel. C. High magnification TEM from left box in (B) shows a pericyte on the venule in close proximity to Bruch’s membrane. D. High magnification TEM from right box in (B) highlights the proximity of the venule to Bruch’s membrane (~1–2 μm). The image also reveals degenerative cell processes between venule and Bruch’s membrane, which may represent remnants of choriocapillaris.

Fig. 5

Transmission Electron Microscopy (TEM) Example of Choroidal Blood Vessel Abutting Bruch’s Membrane in Geography Atrophy (GA). Same Treatment-Naïve Donor Eye with GA shown Figures 3 and 4. This large blood vessel located within the area of atrophy (absent retinal pigment epithelium cells and photoreceptors and has a thin scar), abuts Bruch’s membrane (top), lacks fenestrations, and is surrounded by pericyte processes (black arrow, top).

Fig. 6

Choroidal Vessels Displaced toward Bruch’s Membrane in a Treatment-Naïve Eye with Multi-lobular Geographic Atrophy (GA). A. OCT angiography (OCTA) of choriocapillaris and cross-sectional OCT with segmentation boundary lines. In the area of GA, choroidal vessels are located in the same plane as is the choriocapillaris in areas outside GA. B. OCTA of outer retina (with suppression of projection artifact) and cross-sectional OCT. En face outer retina image shows flow signal that could be misinterpreted as choroidal neovascularization. The outer segmentation boundary on cross-section (red line) is artifactually displaced deeper into the superficial choroid in areas of retinal pigment epithelium (RPE) loss (yellow arrow). C. En face structural OCT slab of the choroid used to select the area of RPE atrophy. White arrow on cross-section shows the more posterior location of choroidal vessels in areas with no RPE atrophy. D. Pseudo-colored OCTA of choriocapillaris and cross-sectional OCT with red flow overlay. Pseudo-coloring confirms that flow signal related to outer retinal flow abnormalities is due normal choroidal vessels displaced anteriorly in GA.

Fig. 7

Normal Choroidal Vessels Artifactually Appearing in the Outer Retinal Slab of a Treatment-Naïve Eye with Geographic Atrophy (GA). A. OCT angiography (OCTA) of choriocapillaris and cross-sectional OCT with segmentation boundary lines. B. OCTA of outer retina and cross-section. Segmentation error (outer segmentation boundary displaced posteriorly in GA) as well as the anterior displacement of normal choroidal vessels cause vessels to appear in outer retina slab. C. En face structural OCT slab of the choroid used to select area of GA. D. Pseudo-colored OCTA of choriocapillaris and cross-sectional OCT with red flow overlay. In this figure, we added an extra post-processing step where blood vessels appearing in the outer retinal slab are pseudo-colored green and overlaid onto the choriocapillaris. Vessels with morphology suspicious for choroidal neovascularization (CNV) are highlighted by the circle. Blue arrow on the cross-sectional OCTA confirms that these vessels are below Bruch’s membrane and therefore not CNV.

Fig. 8

Choroidal neovascularization (CNV) along the Border of Geographic Atrophy (GA). A. OCT angiography (OCTA) of choriocapillaris and cross-sectional OCT with segmentation boundary lines. Choroidal vessels in GA (top and left quadrants) complicate angiogram interpretation. B. OCTA of outer retina with cross-section. The outer retina slab highlights the large CNV membrane outside GA (center) with large caliber feeder vessels extending into the GA (top left quadrant). C. En face structural OCT slab of the choroid used to select retinal pigment epithelium (RPE) atrophy. White arrow on cross-section shows the more posterior location of major choroidal vessels in areas without RPE atrophy. D. Pseudo-colored OCTA of choriocapillaris and cross-sectional OCT with red flow overlay. Blood vessels appearing in the outer retina are pseudo-colored green. Cross-sectional OCTA shows flow signal related to the CNV (red arrow) located below the intact elevated RPE (Type 1 CNV).

Fig. 9

Choroidal Neovascularization (CNV) within the Area of Geographic Atrophy (GA). A. OCT angiography (OCTA) of choriocapillaris and cross-sectional OCT with segmentation boundary lines. The diffuse network choroidal vessels visible throughout the scan could either be normal choroidal vessels or CNV. B. En face OCTA of outer retina reveals flow signal suspicious for CNV. Cross-sectional OCT shows subretinal hyper-reflective material (SHRM) above the retinal pigment epithelium (RPE) also suggestive of CNV (red arrow). C. En face structural OCT slab of the choroid used to select area of RPE atrophy. D. Pseudo-colored OCTA of choriocapillaris and cross-sectional OCT with red flow overlay. Vessels in area of GA (entire scan) are pseudo-colored on a spectrum from blue to yellow. Vessels appearing in the outer retina are pseudo-colored green. This image illustrates that the CNV is entangled within the normal choroid. Cross-sectional OCTA reveals a subtle CNV lesion with red flow signal within the SHRM lesion (red arrow).