Choroidal Neovascularization (CNV) Workup

Updated: Dec 06, 2021
  • Author: Lihteh Wu, MD; Chief Editor: Andrew A Dahl, MD, FACS  more...
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Laboratory Studies

Laboratory studies may be indicated if certain underlying medical conditions, such as pseudoxanthoma elasticum (PXE), are present.


Imaging Studies

Fluorescein angiography

Fluorescein angiography (FA) is an essential tool in diagnosing and managing CNV. Several angiographic patterns have been described for CNV.

A lesion that hyperfluoresces in the early phases of the angiogram, maintains well-demarcated borders, and leaks late (obscuring its borders) is a classic CNV.

A lesion whose borders cannot be determined by FA is an occult CNV. Fibrovascular pigment epithelial detachment (PED) and late leakage of undetermined source (LLUS) represent patterns of occult CNV. A fibrovascular PED is a lesion that is elevated solidly and hyperfluoresces irregularly to different degrees. The lesion may be well demarcated or poorly demarcated. LLUS is seen during FA as an irregular, indistinct, late, sub-RPE leakage.

According to its location relative to the center of the fovea, CNV has been classified as extrafoveal (200-1500 µm), juxtafoveal (1-199 µm), and subfoveal.

Indocyanine green angiography

Indocyanine green (ICG) is a water-soluble tricarbocyanine dye that contains 5% sodium iodide; it rapidly binds almost completely to globulins after intravenous injection. ICG has a peak absorption and fluorescence in the near infrared range. This allows visualization of choroidal pathology through overlying serosanguineous fluid, pigment, or a thin layer of hemorrhage that usually blocks visualization during FA. Because ICG is bound tightly to the plasma proteins, less dye escapes from the choroidal circulation, allowing better definition of choroidal vasculature.

Three types of ICG patterns that are assumed to represent CNV may be imaged. A hot spot is a well-defined focal hyperfluorescent area that is less than one disc area in size. Hot spots usually fluoresce early. A plaque refers to a hyperfluorescent lesion that is larger than one disc area in size. A plaque usually does not fluoresce early, and its intensity diminishes late. Finally, some eyes harbor a combination of plaques and hot spots. In these eyes, the hot spots may be at the edge of the plaque, may overlie the plaque, or may be far from the plaque.

High-speed or dynamic ICG angiography uses a scanning laser ophthalmoscope that takes up to 32 frames per second. These images are recorded like a movie, and the flow in and out of the vessels can actually be seen. The main use of dynamic ICG angiography is in the identification of CNV feeder vessels that are located in the Sattler layer of the choroid.

Optical coherence tomography

CNV causes thickening and fragmentation of the highly reflective RPE-choriocapillaris band. If the CNV is well defined, it is seen as a fusiform thickening of the RPE-choriocapillaris band. In contrast, poorly defined CNV is seen as a diffuse area of choroidal hyperreflectivity that blends into the normal contour of the normal RPE band. A normal boundary between the choriocapillaris and the RPE cannot be defined.

A subretinal hemorrhage is seen as a layer of moderate reflectivity that elevates the neurosensory retina and causes optical shadowing, resulting in a lower reflectivity of the underlying RPE and choroid. Serous, hemorrhagic, or fibrovascular RPE detachments reveal focal RPE elevations with shadowing of the structures beneath the elevated areas. Serous detachments are characterized by complete shadowing of the underlying structures. A hemorrhagic RPE detachment shows a moderately reflective layer beneath the detached RPE. Fibrovascular RPE detachments demonstrate moderate reflectivity throughout the entire sub-RPE space under the elevation.

Detachments of the neurosensory retina appear as elevations of a moderately reflective band above the RPE band. RPE tears can be seen as thick elevated areas of high reflectivity. The underlying choroid is completely shadowed, whereas the adjacent choroid reveals a hyperreflective image because of the absence of RPE. Retinal edema or thickness can be measured objectively by defining the anterior and posterior borders of the retina.

Rogers and coworkers have proposed an optical coherence tomography (OCT) classification scheme of CNV following photodynamic therapy (PDT). [1]

Stage I occurs shortly after PDT and lasts for about a week. It is characterized by an inflammatory reaction that causes an increase in intraretinal fluid in a circular fashion that corresponds with the treatment spot.

Stage II represents the restoration of a near-normal foveal contour with diminished subretinal fluid occurring 1 week to 4 weeks after treatment.

Stage III represents reperfusion and involution of CNV. It typically occurs 4 weeks to 12 weeks after treatment and is subdivided into two categories based on the ratio of subretinal fibrosis to fluid present. Stage IIIa contains a greater subretinal fluid to fibrosis ratio, indicating active CNV. Lesions in Stage IIIb have more prominent fibrosis with minimal intraretinal fluid, indicating inactive CNV.

Further involution of CNV may lead to cystoid macular edema, signifying Stage IV.

In Stage V, CNV and the subretinal fluid resolve, leading to fibrosis and retinal thinning.

Despite the many advantages of OCT, FA remains the imaging modality of choice in the management of CNV. Currently, OCT cannot replace FA in the management of CNV.

With the advent of anti-VEGF therapy, OCT plays a major role in the management of CNV. Most clinicians use the presence of fluid on the OCT scan as an indication of CNV activity and the need for further treatment.

Optical coherence tomography angiography

Optical coherence tomography angiography (OCT-A) is a noninvasive imaging modality that visualizes the vascular anatomy of the fundus by detecting motion contrast between repeated OCT B-scans at the same site. Since the only moving objects in the fundus are the erythrocytes, the images produced represent a map of blood flow. OCT-A is depth resolved and permits differentiation of the different capillary plexuses.

OCT-A has several limitations, including a limited field of view, image artifacts, and inability to demonstrate leakage. Current en face OCT-A suffers from two major problems: flattening of the depth information within a given layer, causing loss of the vascular interrelationships within the layer, and the need for segmentation. In many eyes with pathologic changes, accurate segmentation is not possible because the layers cannot be readily identified. [23]

Since OCT-A does not require dye injection, it is much safer than fluorescein or indocyanine green angiography. Intravenous access is unnecessary, and there is no risk of anaphylaxis. With the current technology, the sensitivity of OCT-A for CNV detection varies from 50% to 100%. [24, 25]


Histologic Findings

New capillaries and fibroblasts originate from the choroid and grow through a defect in the Bruch membrane into the subretinal space (type 2 CNV) or the sub-RPE space (type 1 CNV). Reactive hyperplastic RPE is present at the advancing edge of CNV.

Specimens obtained from surgical excision of CNV reveal that the most common cellular components are vascular endothelium and RPE. These were present in more than 85% of samples. Fibrocytes and macrophages also have been identified in more than 50% of specimens. Extracellular components include collagen and fibrin. VEGF has been identified in the specimens obtained during submacular surgery.