It’s been almost 2 years since OCT angiography began arriving in retina clinics across the country. The reviews of early adopters are promising, but clear-eyed. Although OCTA boasts many diagnostic advantages over its intravenous-based counterpart, fluorescein angiography (FA), most physicians don’t see the technology sending fluorescein dye and its catheters to museum shelves any time soon.

“I view OCTA more as a complementary modality than as a replacement,” says Nadia K. Waheed, MD, MPH, associate professor of ophthalmology at Tufts University School of Medicine and director of the Boston Image Reading Center. “In some cases, it can provide you with enough information so you may not feel compelled to also perform FA. However, dye-based angiography, FA and indocyanine green (ICG), still remain the gold standard for many diseases. OCTA still cannot detect leakage, which is visible with FA.”

Daniel Esmaili, MD, a retina specialist with Retina Vitreous Associates in Los Angeles, also sees OCTA as a complement to FA for the foreseeable future.

“I’m finding that my FA utilization has skewed toward performing wide-field studies to evaluate the retinal periphery, as macular blood flow can be captured nicely with OCTA,” Dr. Esmaili says. “As OCTA technology advances, we might eventually see a time when it can be a true replacement for FA, but we aren’t there yet.”

STRENGTHS OF OCTA

By now, you well know that OCTA is a noninvasive imaging modality that provides three-dimensional images of the retina and choroidal microvasculature. In November 2015, Zeiss became the first company to receive U.S. FDA marketing clearance of its AngioPlex OCT angiography system. Optovue followed 5 months later, when its AngioVue imaging system received FDA clearance in February 2016. The systems remain the only two competing for U.S. market share, although a third is on the way (See “OCTA: Current and Coming Attractions,” page 14).

As it did then, the OCTA spotlight still tends to focus on the speed, ease, and beauty of the technology compared with FA. Unlike FA, which requires intravenous administration of contrast dye and can take up to 30 minutes to obtain two-dimensional images of superficial retinal vasculature, OCTA typically takes less than 1 minute, and results in vivid images of all levels of the retina and choroid. Indeed, it’s hard not to get caught up by the advanced technology.

“OCTA allows us to visualize retinal vasculature in vivo like never before,” says Dr. Waheed. “OCTA images are fascinating. With OCTA, we can visualize vasculature in three dimensions. It is truly technology of the future.”

The FDA, however, bases its approvals on a technology’s efficacy in identifying and diagnosing conditions and diseases. With OCTA, these conditions included neovascular age-related macular degeneration (nAMD), choroidal neovascularization (CNV), retinovascular changes from diabetic retinopathy, retinal vein and artery occlusions, and retinal neovascularization.

Almost 2 years later, retina specialists in daily practice are finding OCTA to be as good as, if not significantly better than FA in these applications.

“OCTA really shines in the assessment of retinal vascular diseases and choroidal neovascularization,” says Dr. Esmaili. “For retinal vascular diseases such as diabetic retinopathy and retinal vein occlusion, OCTA provides exquisite detail of capillary perfusion. For CNV, OCTA shows the neovascular complex in detail, and this helps with both diagnoses and evaluating treatment response.”

“FA as a test of macular disease is on life support,” says Jay S. Duker, professor and chairman of ophthalmology at the Tufts Medical Center and Tufts University School of Medicine and director of the New England Eye Center. “As more clinicians can access OCTA, and as the software improves, it will be hard to find a macular disease that requires FA studies.”

Jesse J. Jung, MD, with East Bay Retina Consultants in Oakland, CA, agrees, noting that initial non-neovascular and nAMD patients, in particular, benefit from OCTA because of the ease of identification of CNV. Dr. Jung also finds OCTA helpful in diagnosing cases of macular ischemia as a result of diabetes, retinal vein or artery occlusions, or sickle cell maculopathy.

“Correlating the severity of increased foveal avascular zones or dropout of the superficial or deep capillary plexuses is helpful to understanding if visual acuity is primarily limited by the macular ischemia,” he says. “The literature and my personal experiences have shown that the level of macular ischemia does correlate with visual acuity, but not exactly 1:1, and I find that the more severe the capillary dropout, the more likely that visual acuity will be affected. Furthermore, I can show the OCTA image and educate patients about the severity of their disease.”

OCT angiography also has an ability to reveal clinically occult vascular changes, says Dr. Waheed.

“In retinal vascular disease, often, there are vascular changes as seen on OCTA before clinically apparent disease,” she says. “This is true for some dry AMD patients, as well those who may have quiescent CNV prior to developing subretinal fluid. I don’t treat these patients, but I do follow them more frequently.” Dr. Waheed says she uses OCTA on almost every patient with wet AMD to diagnose and follow the progression of CNV, and to check for CNV in patients with central serous choroidopathy.

“In diabetic retinopathy, we can follow ischemic areas as seen by capillary dropout, and monitor for regression of pre-retinal neovascularization over time,” she adds.

OCTA: Current and Coming Attractions

Two competing OCT angiography (OCTA) systems are available for clinical patient care in the U.S., with a third on the way. The first two systems make use of spectral domain OCT (SD-OCT), while the third leverages the more recently developed swept-source OCT (SS-OCT). Unlike the superluminescent diode laser used in SD-OCTA systems, SS-OCTA uses a short-cavity laser that scans or ‘sweeps’ over the retina to acquire images.

“Swept-source OCTA has advantages over spectral-domain OCTA, but disadvantages as well,” says Jay S. Duker, professor and chairman of ophthalmology at the Tufts Medical Center and Tufts University School of Medicine and director of the New England Eye Center. “SS-OCT is faster and penetrates deeper. It has better retinal coverage. However, it has worse axial resolution and is much more expensive by a factor of two.”

Here’s an overview of all three systems.

AngioPlex

Marketed by Zeiss, AngioPlex became the first OCT angiography system to win FDA clearance in September 2015. AngioPlex employs a proprietary algorithm, Optical Microangiography Complex (OMAGC), which uses both amplitude and phase variance to acquire its images in one 3-second scan. Scan sizes come in 3 x 3 mm with 245-pixel resolution, and 6 x 6 mm and 8 x 8 mm with 350-pixel resolution. Zeiss AngioPlex features FastTrac eye tracking technology, which eliminates motion artifacts and enables tracking of OCTA scans at the same precise location from visit to visit. The system also features AngioPlex Metrix* analysis, which provides vascular quantification and vascular change analysis. Other features include 11 clinical presets, patient setting memory, color, movie mode, and fundus image overlay.

AngioPlex is either included, or available as an upgrade, on the Cirrus 5000 HD-OCT.

AngioVue

Marketed by Optovue, AngioVue received FDA marketing clearance in February 2016, but was introduced to markets outside the U.S. in September 2014. The technology employs a proprietary algorithm, SSADA, which is designed to increase the OCTA signal for optimal imaging at all retinal depths. The technology acquires images in 70,000 A-scans per second, or 3 seconds per OCTA scan. Scan sizes come in 3 x 3, 6 x 6, and 8 x 8 mm, with resolutions of 304 x 304 pixels. AngioVueHD is a higher density scan pattern (400 x 400 pixels) available in 4.5 x 4.5 mm for imaging of the optic disc, and 6 x 6 mm for macular imaging. A two-scan Montage feature combines two high-density 6 x 6-mm scans from the optic disc and the macula to produce a wide-field (10 x 6 mm) montage view. Other features include multi-mode, the automatic overlay of OCTA images onto a 12 x 9 mm OCT volume; colorization; and color movie mode. Projection artifacts are automatically removed by the system in the outer retinal zone to improve image quality.

AngioVue is available as a software upgrade for Optovue Avanti users; as a comprehensive system with anterior segment, retina, glaucoma, and OCTA technologies; and as an AngioVue Retina System, designed specifically for retina specialists with OCT and OCTA technologies.

SS OCT Angio

This forthcoming system from Topcon Medical Systems uses a 1050 nm laser light source that is inherently faster than commercial SD-OCT angiography scan speeds, explains Topcon Product Manager Thai Do. Do says the longer wavelength allows deeper penetration into tissue, resulting in less signal roll off and much clearer OCTA images, especially in deeper regions of the eye, such as the choriocapillaris.

“The longer wavelength is also invisible to the patient, so they can focus on the fixation and not the scanning line,” Do says, adding that the system employs a proprietary algorithm known as OCTARA (OCT-A by Ratio Analysis).

He declined to say when the company expects to introduce the product in the U.S.

“At the moment, I can’t share any release information. We have an aggressive schedule for release, but due to our regulatory rules, I don’t think I can share that information. It is currently sold everywhere else in the world. We are approaching 1,000 units sold globally,” he says.

When released, SS-OCT Angio is expected to be available on Topcon’s DRI OCT Triton, which features SMARTTrack technology that follows fixation movement, detects blinking, and compensates the scan. The DRI OCT Triton is a multimodal machine that combines, color fundus, auto-fluorescence, fluorescein angiograms, structural OCT (posterior and anterior), and OCT-A. The OCT-A scan patterns are 3 x 3, 4.5 x 4.5 mm, 6 x 6, and 9 x 9 mm. The 3-, 4.5-, and 6-mm scan sizes feature a 320 x 320 resolution, while the 9 x 9 is 512 x 512. Nine image mosaics are available that stitch images together to form a wide-field view.

“All the units in the market work pretty well, and the companies are constantly in competition to make their units better,” says Nadia K. Waheed, MD, MPH, associate professor of Ophthalmology at Tufts University School of Medicine and director of the Boston Image Reading Center.

“That is the great part of having multiple companies competing in this space,” Dr. Waheed says. “Lots of smart people get together and refine the technology so that if one company comes up with something that works really well, you can bet the other one will compete and try to come up with something even better.”

*Editor’s note: ZEISS PLEX Elite 9000 Swept-Source OCT was the first OCTA system utilizing a 1060 nm Swept Source to be cleared by the U.S. FDA for posterior ocular imaging in October 2016. That system, however, is available only for clinical research purposes.

WEAKNESSES OF OCTA

Despite its considerable strengths, OCTA has its clinical shortcomings. Indeed, specialists consulted for this article say FA retains its superiority in several important aspects.

“Because OCTA requires a relatively stable eye to obtain clear images, patients with poor fixation are difficult to image effectively,” says Dr. Waheed. “In addition, areas with large pigment epithelial detachments (PEDs) or intravitreal hemorrhage block OCT signal and decrease the quality of the angiography. FA or ICG demonstrate leakage of fluid without respect to PED or eye motion.”

Dr. Jung agrees, noting that OCTA’s image acquisition capability is “very efficient” in patients with clear media and good visual acuity that allows stable fixation.

“Unfortunately, with most of the patients who have significant pathology, poor media, or significant dry eye, I have more difficulty acquiring quality images that can be interpreted correctly,” he says. “Therefore, I have limited OCTA to certain disease processes and also don’t acquire them on patients whom I know have difficulty fixating or poor media.”

Dr. Jung also still uses FA and OCT B scans for certain macular conditions, such as identifying microaneurysms to laser in non-central diabetic macular edema, as well as follow-up treatments in CNV.

“The microaneurysms are seen easier with FA compared with OCTA, and OCT B-scans are more useful in deciding the management with anti-VEGF use for subsequent treatment follow-ups for CNV treatments,” he says. “The lack of objective data points (either vessel density or perfusion) that have been correlated with visual acuity and can be compared between visits makes OCTA less reliable and functional for subsequent visits at this time, but may improve in the future.”

OCTA, he and other physicians reiterated, also doesn’t show leakage and is less useful for identification of vasculitis. It’s for reasons like these that Dr. Jung and other physicians believe that OCTA and FA will continue to serve alongside each other for some time.

“I participated in a multicenter imaging study¹ that analyzed the sensitivity of OCTA in identifying Type 1 CNV,” Dr. Jung says, explaining that the study identified 85.7% of 105 eyes with type 1 neovascularization confirmed by FA and OCT B-scans could be detected with OCTA and structural OCT B-scans from the OCTA. The sensitivities of FA data alone and en face OCTA data alone for visualizing type 1 neovascularization were 66.7% for both, respectively. Significant factors that precluded visualization of neovascularization using en face OCTA was height of the PED, low signal strength, and treatment-naive disease.

“This shows that utilizing FA and OCTA/OCT B-scans together allow for an increased sensitivity/specificity in identifying pathology associated in neovascular AMD,” he says.

“Including the limitations mentioned earlier, OCTA won’t completely replace FA. FA will still be required to visualize leakage, and although widefield OCTA will allow for imaging of the vascular layers, likely out to the mid-periphery and vortex veins, ultra-wide field FA will still provide information about retinal capillary perfusion out to the ora.”

THE FUTURE LOOKS BRIGHT FOR OCTA

Nevertheless, advances in the technology will continue to improve OCT angiography (See “Keep Your Eyes Open: Expert Advice on OCTA,” page 13).

“The limitations with OCTA will continue to improve with [advances] in objective software analyses, swept-source technology, and wide-field OCTA imaging, and [OCTA] will eventually become more efficient and useful in clinical practice,” Dr. Jung says. “Continued use and development will improve our ability to care for our patients and we will likely find other uses for OCTA in retinal diseases.”

Dr. Esmaili agrees that OCTA is a significant advance and that its value will continue to increase as physicians gain more experience with the technology and the information it provides.

“If I were a new retinal specialist entering the workforce today, I would embrace OCTA with the understanding that this modality will eventually be as commonplace as OCT is today,” he says, drawing a comparison to OCT technology launched in the early 2000s, which he said took several years to become widely adopted because practitioners had to be convinced that OCT would change the way they cared for patients.

“Once this value was demonstrated, OCT became ubiquitous in retina practice,” he says.

“I predict we will follow a similar path with OCTA. As studies show the value of the technology, specialists will be motivated to adopt these systems in their practices.” NRP

REFERENCE

1. Inoue M, Jung JJ, Balaratnasingam C, et al. A comparison between between optical coherence tomography angiography and fluorescein angiography for the imaging of type 1 neovascularization. Invest Ophthalmol Vis Sci. 2016;57(9):OCT314-323.