17.4 Optical Coherence Tomography Angiography (OCTA): Chorioretinal Plexuses & Biomarkers

Optical Coherence Tomography Angiography (OCTA): Chorioretinal Plexuses & Biomarkers

Clinical Core: Optical Coherence Tomography Angiography (OCTA) delivers non-invasive, depth-resolved, three-dimensional angiograms of retinal and choroidal microvascular networks. By isolating motion contrast from red blood cell flux across repeated B-scans, OCTA eliminates dye injection risks while resolving individual capillary plexuses—superficial, deep, and choriocapillaris—that overlap and blur on conventional fluorescein angiography.

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Physical Principles of OCT Angiography (OCTA)

Conventional dye-based angiography (FA and ICGA) captures two-dimensional, time-resolved planar images of dye transit, filling, and leakage. However, FA cannot differentiate the superficial capillary bed from the deep capillary bed because the fluorescein signal from multiple depths is integrated onto a single sensor plane. Furthermore, dye leakage and pooling obscure fine capillary details in macular edema and neovascularization.

Motion Contrast & Decorrelation Imaging

OCTA generates vascular contrast by using the patient's own circulating erythrocytes (red blood cells) as intrinsic contrast agents:

1. Sequential B-Scan Acquisition: The OCT scanner rapidly acquires multiple consecutive B-scans (typically 2 to 4 repeated B-scans) at the exact same transverse retinal coordinate within a brief time interval (e.g., 5 milliseconds).
2. Static vs. Dynamic Tissue:
   • Static Structural Tissues: Retinal layers without blood flow (e.g., nuclear layers, plexiform layers, sclera) exhibit consistent optical backscattering over time. Their backscattered light waves retain identical amplitude and phase.
   • Dynamic Intravascular Lumens: Erythrocytes moving through capillaries, arterioles, and venules constantly change position. Consequently, the backscattered light wave exhibits temporal fluctuations in amplitude, phase, or both.
3. Decorrelation Signal: Software algorithms calculate the pixel-by-pixel difference—the decorrelation—between sequential scans. Areas with high decorrelation are mapped as perfused blood vessels, while static tissues with near-zero decorrelation are rendered black.

The SSADA Algorithm & Complex Decorrelation

Bulk ocular motion (e.g., microsaccades, cardiac pulse, respiration) causes unwanted global phase shifts that can overwhelm capillary signals:

• Split-Spectrum Amplitude-Decorrelation Angiography (SSADA): Developed by Jia, Huang, and colleagues, SSADA splits the wide spectral bandwidth of the OCT signal into multiple smaller, overlapping spectral sub-bands. It calculates amplitude decorrelation within each individual sub-band and averages them. Because splitting the spectrum broadens the coherence length in the axial direction, SSADA dramatically reduces sensitivity to axial bulk motion noise without degrading transverse capillary resolution.
• Complex Decorrelation / Optical Microangiography (OMAG): Other platforms utilize both amplitude and phase information (complex decorrelation) or full-spectrum algorithms combined with hardware eye-trackers to maximize capillary sensitivity.

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Segmentation Slabs & Anatomical Vascular Networks

OCTA software automatically segments the volumetric retinal dataset into anatomically defined parallel slabs bounded by structural OCT interfaces. The standard clinical slabs include:

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|                     OCTA ANATOMICAL SEGMENTATION SLABS                            |
+-----------------------------------------------------------------------------------+
| 1. SUPERFICIAL RETINAL CAPILLARY PLEXUS (SCP)                                     |
|    Boundaries: Internal Limiting Membrane (ILM) to IPL / INL junction             |
|    Anatomy: Located in RNFL & GCL; centripetal linear capillaries; feed arterioles|
+-----------------------------------------------------------------------------------+
| 2. DEEP RETINAL CAPILLARY PLEXUS (DCP)                                            |
|    Boundaries: IPL / INL junction to OPL / ONL junction                           |
|    Anatomy: Located in INL & OPL; polygonal lobular meshwork; site of PAMM        |
+-----------------------------------------------------------------------------------+
| 3. AVASCULAR OUTER RETINA                                                         |
|    Boundaries: OPL / ONL junction to Bruch's Membrane                             |
|    Anatomy: Normally ZERO flow signal; flow confirms Type 2 CNV or Type 3 RAP     |
+-----------------------------------------------------------------------------------+
| 4. CHORIOCAPILLARIS SLAB                                                          |
|    Boundaries: 10 - 30 µm slab immediately below Bruch's Membrane                 |
|    Anatomy: Dense continuous capillary meshwork; flow voids indicate ischemia     |
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1. Superficial Retinal Capillary Plexus (SCP)

• Anatomical Localization: Extends from the ILM down to the boundary between the Inner Plexiform Layer (IPL) and Inner Nuclear Layer (INL).
• Vascular Architecture: Occupies the nerve fiber layer and ganglion cell layer. Composed of terminal arterioles, venules, and interconnected linear capillary networks arranged in a radiating, centripetal pattern around the foveal avascular zone. In the peripapillary region, this slab includes the radial peripapillary capillary (RPC) plexus, which runs parallel to nerve fiber bundles.

2. Deep Retinal Capillary Plexus (DCP)

• Anatomical Localization: Spans from the IPL/INL boundary down to the junction between the Outer Plexiform Layer (OPL) and Outer Nuclear Layer (ONL).
• Vascular Architecture: Localized primarily within the inner nuclear layer and outer plexiform layer. Characterized by a dense, polygonal, lobular capillary network arranged in converging star-like or vortex patterns around central draining venules. The DCP consists purely of capillaries, lacking muscularized arterioles.
• Vulnerability to Ischemia: Because of its distal position in retinal hemodynamics, the DCP is exceptionally susceptible to microvascular hypoperfusion. Ischemic infarction of the DCP results in Paracentral Acute Middle Maculopathy (PAMM), which manifests on structural OCT as a hyperreflective band at the level of the INL and on OCTA as profound deep capillary dropout.

3. Avascular Outer Retina

• Anatomical Localization: Sliced from the OPL/ONL boundary down to the outer surface of Bruch's membrane (encompassing the photoreceptor inner/outer segments and outer nuclear layer).
• Normal Physiology: In a healthy eye, this anatomical compartment contains no blood vessels; the normal decorrelation signal is zero (completely dark).
• Pathological Neovascularization: Any detectable decorrelation flow signal in this slab is pathognomonic for pathological neovascularization:
  • Type 2 Choroidal Neovascularization (Classic CNV): Neovascular vessels that have breached Bruch's membrane and the RPE, proliferating in the subretinal space.
  • Type 3 Neovascularization (Retinal Angiomatous Proliferation / RAP): Intraretinal telangiectatic neovascular tufts originating from the deep capillary plexus that dive downward into the avascular outer retina toward the RPE.

4. Choriocapillaris Slab

• Anatomical Localization: A thin 10 to 30 µm slab positioned immediately below the hyperreflective Bruch's membrane complex.
• Vascular Architecture: Appears as a dense, homogeneous, granular capillary sheet with microscopic intercapillary spaces.
• Clinical Biomarkers: Evaluated for flow voids (areas of signal dropout) reflecting choriocapillaris hypoperfusion or atrophy in geographic atrophy, diabetic choroidopathy, systemic hypertension, and inflammatory chorioretinopathies (e.g., APMPPE, MEWDS). This slab is also essential for delineating Type 1 (Occult) CNV, which proliferates within the sub-RPE space above Bruch's membrane.

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Quantitative OCTA Biomarkers

Automated software algorithms extract objective, reproducible metrics to track microvascular disease progression and response to anti-VEGF pharmacotherapy.

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OCTA Image Artifacts & Troubleshooting Strategies

Because OCTA relies on motion contrast and automated segmentation, images are highly prone to unique artifacts that can mimic pathology or conceal true lesions.

1. Bulk Motion Artifacts

• Cause: Patient microsaccades, tremor, breathing, or head shifts cause rapid global displacement of retinal tissue between consecutive B-scans.
• Appearance: Appears as bright white or dark black horizontal transverse stripes across the en-face angiogram, accompanied by horizontal vessel displacement or "shearing" defects.
• Troubleshooting: Ensure active eye-tracking is locked on the iris/retinal features; utilize orthogonal dual-volume acquisition (fast-X and fast-Y scans) which merges horizontal and vertical raster volumes to cancel motion vectors; instruct the patient to fixate firmly on the target.

2. Projection Artifacts

• Cause: Fluctuating shadows cast by moving erythrocytes in the superficial retinal capillary plexus pass through deeper hyperreflective structures—specifically the RPE and outer plexiform layer. The fluctuating shadow alters the backscattered light phase and amplitude, creating a false decorrelation signal in the deeper slabs.
• Appearance: Duplicated "ghost" copies of superficial large vessels and capillaries appear falsely projected onto the deep capillary plexus, avascular outer retina, and choriocapillaris slabs.
• Troubleshooting: Activate Projection-Resolved OCTA (PR-OCTA) software algorithms, which mathematically compare the decorrelation value of deeper pixels with the overlying superficial pixels and remove identical vessel patterns from the deeper slabs.

3. Segmentation Errors

• Cause: Distortions of normal retinal anatomy by pathology—such as cystoid macular edema (CME), large pigment epithelial detachments (PEDs), subretinal fluid, or severe vitreomacular traction—cause the automated algorithm to place slab boundary lines at the wrong anatomical depth.
• Appearance: Non-vascular tissue (e.g., fluid cysts) or out-of-plane vessels (e.g., superficial vessels captured in the deep slab) distort the angiogram, creating pseudo-flow voids or false vascular networks.
• Troubleshooting: The technologist must inspect the cross-sectional B-scans with color-coded segmentation lines; access the manual segmentation editor; and manually reposition the boundary lines to follow true anatomical layers.

4. Shadow / Signal Attenuation Artifacts

• Cause: Dense optical media—such as intraretinal hemorrhages, hard exudates, dense vitreous floaters (asteroid hyalosis), or dense cataracts—absorb and scatter OCT light, preventing light from reaching underlying vascular beds.
• Appearance: Appears as a well-circumscribed patch of complete flow absence (pseudo-non-perfusion) in the deep capillary plexus and choriocapillaris.
• Troubleshooting: Cross-reference the OCTA en-face angiogram with the corresponding structural OCT B-scan and reflectance image. If the area of absent flow matches a hyperreflective shadow-casting opacity, the defect is a shadow artifact rather than true vascular non-perfusion.