OCT ANGIOGRAPHY

The Promise of OCT Angiography

Retina specialists share their thoughts about this evolving method for evaluating retinal vascular abnormalities

BY SUSAN WORLEY, CONTRIBUTING EDITOR

With new technologies and treatment models emerging at an unprecedented pace in the field of retina, the swell of enthusiasm that surrounds each new, potentially paradigm-changing clinical tool is becoming increasingly familiar. Accordingly, many experts, practices, and institutions are finding that they are more inclined to reserve judgment about the clinical utility of the latest phenomenon until they have gathered considerable evidence to support its use.

In the case of OCT angiography (OCTA), many newer retina specialists have been enthusiastically following pilot studies and related developments for several years, though largely from the sidelines.

“I have not had the opportunity to use this technology yet,” says Paul Hahn, MD, PhD, assistant professor of ophthalmology and vitreoretinal surgery at Duke University, “so my knowledge of it is still limited to what I’ve learned from reading about it and attending presentations. At Duke, our imaging experts are certainly excited about OCTA and have begun to evaluate it. They are currently in the process of comparing available platforms, but have not yet invested in the technology for routine clinical use.”

Vincent Hau, MD, PhD, a retina specialist at Kaiser Permanente, says his experience thus far with this new technology has, likewise, been limited to reading publications and attending presentations.

“Although there has been a real explosion of information about OCTA in the past year, this is still very new technology,” says Dr. Hau, “and the experts who have had the most experience with it are largely those who have used it in clinical research. Although the photos obtained are amazing, practices may still be in search of a compelling reason to invest in OCTA when they already have FA and SD-OCT. At Kaiser Permanente, OCT angiography is of particular interest to our retina specialists. As the technology evolves, we will continue to focus on how this novel imaging modality might facilitate medical decision making and improve patient outcomes.”

The number of new retina specialists who have gained hands-on experience with OCTA — including specialists such as Netan Choudhry, MD, director of vitreoretinal surgery at the Herzig Eye Institute in Toronto, now in his fifth year of practice — is still relatively small.

“I’m currently conducting research with OCTA that involves examining the response to anti-VEGF therapy in patients with diseases such as wet age-related macular degeneration,” says Dr. Choudhry. “OCTA is an exciting imaging modality that allows retinal physicians to examine the blood flow in the retina in a non-invasive way, but there are many questions still to be answered regarding this new technology. So far, our early observations have supported a role for OCTA in monitoring treatment response. We will soon see OCTA integrated into clinical trials with more advanced software in the months ahead.”

Most retinal specialists who have yet to use OCTA are continuing to follow the dialogue taking shape around its emergence, in the form of meeting presentations and recent thought-provoking journal articles, such as those in the special November 2015 issue of Retina. Such dialogue is helping to clearly delineate the advantages and drawbacks of this new technology, and, in turn, will likely help to guide its evolution.

Here, several experts with various backgrounds discuss the potential value of OCTA, particularly for monitoring patients with diabetes-related pathologies.

WHY THE EXCITEMENT OVER OCTA?

“Optical coherence tomography angiography is a new innovation in ocular imaging that has only recently become FDA approved in the United States,” says Jay S. Duker, MD, professor and chairman of ophthalmology at the Tufts Medical Center and Tufts University School of Medicine in Boston and director of the New England Eye Center.

Indeed, less than a year ago, in September 2015, Zeiss Medical Technology became the first company to receive FDA clearance for this technology, with the approval of AngioPlex OCT Angiography.

More recently, a second imaging platform became available when, in February 2016, Optovue announced the FDA clearance and immediate U.S. commercial availability of the AngioVue Imaging System (See sidebars for overviews of both platforms). Since early 2015, partly in anticipation of FDA approval, a string of publications emerged in rapid succession, describing the benefits of this new technology, and assessing its potential to replace or supplement approaches to clinical assessment and monitoring that represent current standards of care.

One recent publication, for example, reports the results of a prospective observational study that evaluated the use of OCTA for detecting early microvascular changes in the eyes of individuals with diabetes who did not have clinical retinopathy.¹ In the introduction to their report, the authors note that biomicroscopic fundus examination is currently the gold standard for screening patients for diabetic retinopathy (DR), and that while fluorescein angiography (FA) may be a more sensitive method of detecting DR, it is an “invasive, costly, and time-consuming” approach, and therefore, not practical for such screening in clinical practice.

Their study concludes that OCTA, a relatively fast, sensitive, and non-invasive technique, may be able to detect diabetic eyes at risk for developing retinopathy, and also may be useful for quick, non-invasive screening for diabetes in individuals who have not yet received a systemic diagnosis.

Notes Dr. Duker, one of the co-authors of the study: “Images obtained with OCTA, while similar to those obtained with fluorescein angiography, are based on blood flow data, are depth-encoded, and give a more detailed view of the microvasculature.”

OCTA does not require contrast dyes, such as those used to obtain images during FA or indocyanine green (ICG) angiography; instead, OCTA captures motion contrast, or changes in the OCT signal that are caused by the flow of blood through blood vessels in the retina. Also, OCTA images are not compromised by the leakage and staining that are used to detect vascular abnormalities with FA.

A range of different algorithms, which vary depending on the OCTA platform, are used to process multiple OCT scans and interpret the resulting three-dimensional images. OCT analytics, or methods for enhancing flow detection and limiting motion-related “noise,” are among the many features of this new technology that are expected to evolve considerably in the coming years.

Michael P. Kelly, FOPS, director of Duke Eye Imaging at the Duke University Eye Center, offers his own take on the future of OCTA. “Because OCTA is a completely new way of imaging and evaluating the retina, we are still in virgin territory, much like we were in the early days of fluorescein angiography, ICG angiography, or TD-OCT,” says Kelly.

Among the many changes Kelly anticipates in the relatively near future is a gradual increase in the size of the retinal area that can be captured.

“Currently, the field of view (FOV) is small, at only 3x3 mm; larger fields of 6x6 mm can be captured, but have half the resolution,” says Kelly. “Expect future versions of OCTA to offer larger FOVs, covering more retinal real estate, with higher resolution.”

ADVANTAGES AND DRAWBACKS OF OCTA

Because the detection and evaluation of retinal vascular abnormalities are such a critical and integral part of managing the eye care of patients with diabetes, many experts are predicting that OCTA’s greatest potential may lie in revolutionizing the monitoring, and perhaps even classification, of diabetes-related pathologies.

“With respect to diabetic retinopathy,” says Dr. Duker, “OCTA shows certain early features in unprecedented detail. Enlargement of the foveal avascular zone (FAZ), areas of capillary non-perfusion, and some microvascular abnormalities can be seen with much better clarity than with FA. On the other hand, certain microaneuryms are not visible on OCTA, probably due to limited blood flow. OCTA is also very efficient at diagnosing areas of retina and optic disc neovascularization.”

Although OCTA may eventually improve the visualization of diabetic macular edema (DME) as well, at present OCT remains the standard for monitoring patients with this disorder.

“The importance of OCTA with regard to DME is not clear at the present time,” says Dr. Duker. “DME can be diagnosed with traditional cross-sectional, structural OCT and its response to therapy can be followed in this manner as well. At present, there is no data to suggest that OCTA features may alter current diagnostic or therapeutic recommendations for DME.”

OCT also holds promise for improving the detection and monitoring of other disorders involving the pathologic growth or condition of blood vessels in the inner retina, outer retina, and choriocapillaris. Choroidal neovascularization (CNV) associated with AMD² and retinal vein occlusion³ are just two examples of pathologies for which OCTA images have been shown to provide information that is superior to that provided by conventional OCT. Although OCTA was designed for imaging the retina, recent publications also have suggested that it may be used for imaging corneal vascularization.

OCTA may offer images of vessels that are, in many respects, superior to those obtained with FA; however, most experts do not believe that OCTA will serve as a replacement for FA any time soon.⁴

“Among the drawbacks of OCTA images are their inability to detail leakage, and, at present, their limited ability to image the peripheral retina,” says Dr. Duker.

Due in part to the complexity of OCTA and the extra-ordinary amount of data processing it involves, image artifacts also are a common drawback and may interfere with accurate interpretation of images.⁵ Therefore, familiarity with OCTA and considerable training on the part of clinicians may be necessary to reduce the likelihood of misinterpreting images. In the foreseeable future, information provided by FA will continue to have value as well.

“We would all love to have a non-invasive modality to offer our patients — one without the risks associated with FA,” says Dr. Choudhry. “However, as we have seen with other imaging tests, each of our technologies provide a unique perspective on a single disease state and often work best when viewed together, in a multi-modality approach.”

READY FOR PRIME TIME?

Although commercial OCTA platforms are now available — and already have been adopted by some practices and academic organizations — whether the technology is immediately suitable for all clinical and research environments is still a matter of debate.

“OCTA requires a substantial upfront capital investment,” says Dr. Duker. “While newer OCT platforms manufactured in the past year or two may be upgradeable at a moderate additional cost, for many offices, brand new hardware will be required. Once the platform is acquired, however, the time-related cost of performing an OCTA is considerably less — it requires only 3 to 6 seconds per eye — and no injection of dye is needed.”

Dr. Choudhry, who has used OCTA primarily for research, anticipates that integration of the technology into clinical practice will be relatively straightforward; however, he says that technicians and photographers may encounter a learning curve in acquiring, generating, and displaying images. In general, readiness for OCTA will vary among practices based on their current level of technological sophistication.

“A great deal depends on whether practices have a system capable of an upgrade,” says Richard Rosen, MD, vice chairman and surgeon director of the New York Eye and Ear Infirmary of Mount Sinai. “If that is the case, OCTA can be added as just a software upgrade or software-plus-hardware upgrade. Otherwise, you would need to purchase one of two currently available systems: one that has comprehensive OCT and OCTA features or one that just provides OCT and OCTA features designed specifically for retina practices.”

Dr. Rosen notes that the long-term rewards of having OCTA are likely to be worth the up-front investment.

“Beyond the initial investment is the return on investment for your practice from the immediacy of enhanced accuracy,” he says. “By incorporating OCTA into my practice, I am able to survey the vascular status of my patients regularly, in addition to monitoring thickness change and structural evidence of edema. Prior to the availability of OCTA, many retinal specialists came to rely on serial OCT imaging for routine monitoring, adding vascular imaging with FA or ICG mostly only when the clinical picture was unclear. Because OCTA imaging is much less burdensome to the patients and to my practice workflow, it has become part of the standard diagnostic survey of a patient’s condition at each visit.

“OCTA imaging takes seconds and avoids the risk of potential side effects of contrast angiography. Because I don’t have to plan ahead like I do with FA or ICGA, I can follow patients more precisely and more frequently to see how their disease is progressing and determine the effectiveness of their treatment regimen. The comprehensive picture of the retina that OCTA provides allows me to respond in a more timely manner and avoid unpleasant surprises from late, unexpected findings.”

Amir H. Kashani, MD, PhD, of the USC Eye Institute, and assistant professor of clinical ophthalmology at the Keck School of Medicine, who has used OCTA in both research and clinical settings, also believes that the technology is ready for clinical use.

“I have been using OCTA in a research capacity for the last 2 years, and it has, in many cases, demonstrated pathology or clinically relevant findings that were otherwise not known or visible on other imaging modalities,” says Dr. Kashani, who has been using OCTA in his client for regular patient care as well since the FDA approval in 2015.

“While OCTA is a new technology,” adds Dr. Kashani, “I think it is already becoming a very powerful tool for assessment of retinal vascular diseases, such as diabetic retinopathy, retinal venous occlusions, and AMD. For example, in subjects with mild or no clinically detectable diabetic retinopathy, we have found abnormalities in the foveal capillaries using OCTA. In some cases, this is accompanied by subclinical edema, but in others it is not. Therefore, OCTA assessment of diabetic subjects is potentially the only way to detect subclinical microvascular changes in early diabetic retinopathy. Fluorescein angiography would not be indicated in these subjects because their disease is so mild, and they are often completely asymptomatic. In subjects with retinal venous occlusion, we are conducting studies that show significant differences between the unaffected eye and healthy controls. This suggests that OCTA of the contralateral eyes of subjects with RVO may play a role in detecting those at higher risk for recurrent or bilateral RVO. These are all preliminary studies, which we are submitting for publication, but the clear trend is that OCTA is a novel technology that can provide clinical information that is otherwise not attainable in a clinical setting.

“In short,” says Dr. Kashani, “I believe that OCTA will impact patient care in the next 10 years as significantly as OCT has impacted patient care in the past 10 years.” NRP

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