Over the last decades, substantial developments in
retinal imaging offered a paradigmatic change in the
understanding of the pathophysiology of wet age-related
macular degeneration (AMD). We have reached a point of
sophistication that seemed unattainable a few years ago. A
myriad of imaging devices is now available at our discretion,
representing a unique opportunity to offer our patients
better clinical care. In order to reduce the risk of progressive
and enduring visual loss associated with wet AMD,
early identification and prompt initiation of treatment is
warranted. Since its introduction in 1961 by Novotny and
Alvis (1), fluorescein angiography (FA) became the gold
standard for the diagnosis and classification of choroidal
neovascularization (CNV). However, a major limitation
of traditional angiography resides in its inability to image
the entire retinal capillary system or to directly visualize
new vessels, resorting on indirect clues such as fluid
accumulation or leakage to recognize neovascularization (2).
Wide-field image acquisition, confocal scanning laser
ophthalmoscopy, adaptive optics and indocyanine
green angiography (ICGA) have broadened the use of
classic angiography. With complementary ICGA, better
visualization of the deep vessels can be obtained due to peak
excitation (805 nm) and emission (835 nm) in the nearinfrared
region. Nevertheless, ICGA is neither available nor
routinely performed in many institutions throughout the
world. Also, despite the ability to detect dynamic patterns
of dye transit and leakage, angiography systems (FA and
ICGA) remain expensive, time-consuming and invasive
procedures. Although generally safe, side effects like nausea;
vomiting or even severe allergic reactions may develop in a
minority of patients, thus limiting its repeated use (3).
The advent of optical coherence tomography (OCT)
revolutionized retinal imaging by providing a fast, simple,
and noninvasive method to assess retinal structure at a
microscopic level. Since its debut more than two decades
ago, profound improvements in the scanning speed,
resolution and image depth led to an explosive growth of
OCT in clinical practice, with a significant effect in clinical
decision making (4). Even though technical sophistication
improved the OCT diagnostic yield for wet AMD, there
are no agreed-on standards for diagnosing CNV based
strictly on cross-sectional OCT (5). Structural OCT cannot
detect blood flow, nor can it reliably distinguish vasculature
from fibrous and other surrounding tissue (6). Therefore,
structural OCT must ultimately be used in combination
with angiography systems to diagnose CNV accurately.
By conveying noninvasive, three-dimensional scans of
both the superficial and deep retinal capillary plexuses and
the choriocapillaris, OCT angiography (OCTA) brought a
new insight into the vascular abnormalities that accompany
neovascularization. OCTA detects endoluminal flow by
mapping erythrocyte movement over time and comparing
sequential OCT B-scans at a given cross-section, thus
allowing simultaneous visualization of structure and blood
flow (5). In addition to providing enhanced anatomic detail,
OCTA allows quantitative metrics of the CNV area and
generates data on vascular flow (2). Several studies have
demonstrated that OCTA can accurately identify type 1
and type 2 neovascularization (5-10), offering an unrivaled
morphological characterization of the CNV net (e.g., treelike,
glomerular, fragmented) that far exceeds FA, ICGA and OCT. In addition, the presence of a fibrovascular
capsule, afferent feeder trunk and peripheral anastomosis
within the CNV can be clearly assessed (10). Preliminary
findings from a recent study by de Carlo et al. (5) where 30
eyes with OCTA and same-day FA were evaluated, reported
a sensitivity of 50% (4/8) and a specificity of 91% (20/22)
for CNV detection with OCTA. In the future, we may
be able to correlate the morphological patterns of CNV
with disease course, prognosis, and response to treatment.
Furthermore, the non-invasive nature of the technique
allows comprehensive lesion monitoring after treatment
with anti-VEGF compounds. Quantitative measurements
of the CNV flow area and flow index reported by Huang
et al. (11) showed a rapid shutdown of flow over the initial
2 weeks after treatment with anti-VEGF, followed by
reappearance of the CNV channel by the fourth week
and fluid reaccumulation at 6 weeks. As demonstrated by
Lumbroso et al. (12) and Marques et al. (10), sequential
examinations can shadow morphological changes in
the neovascular network, closely tracking the timings
of vascular network remodeling in patients undergoing
treatment. Ultimately, this may allow the advent of tailored
and customized treatment regimens for wet AMD patients,
built upon the CNV net morphology at baseline and its
response to treatment.
OCTA may also be useful in the screening of eyes at risk
for CNV. Unilateral CNV is an established risk factor for
the development of neovascularization in the fellow eye.
Screening this population for early detection of CNV may
have both therapeutic and prognostic implications. A pilot
study by Palejwala et al. (13), showed that OCTA was able
to identify focus of CNV that were not identifiable on FA
and structural OCT. OCTA detects CNV by the presence
of an abnormal pattern of vascular flow above the Bruch
membrane, therefore being able to identify neovascular
lesions that do not leak on FA. Whether nonexudative CNV
is a predecessor of wet AMD or a distinct clinical entity is
yet to be determined, as well as if we should or should not
start anti-VEGF treatment in these cases.
In conclusion, this revolutionary imaging modality is
redefining our understanding of wet AMD by conveying
detailed, depth-resolved information on the retinal and
choroidal vascular networks, both at a structural and
functional level. The ability to accurately image CNV
noninvasively and to qualitatively and quantitatively appraise
its changes longitudinally, turn OCTA into an attractive
alternative to more invasive imaging modalities such as FA
and ICGA. However, attention should be drawn to first validate its accuracy and assess the reproducibility of its data
in high-powered studies. Also, further study is needed to
determine the clinical significance of nonexudative CNV,
including how often these lesions convert to wet CNV and
at what point, if any, anti-VEGF treatment is warranted.
We embark on this new era of retinal imaging with great
expectations in mind, hoping that OCTA can point out new
clinical coordinates to improve the everyday management
of exudative AMD. As new functionalities and technical
enhancements continue to ripen, only further improvement
is to be expected.
