OCT angiography provides noninvasive close-up viewing of retinal vasculature

Over the past 20 years, OCT has developed rapidly as a noninvasive method of retinal imaging. OCT angiography, or OCTA, is the latest evolution of this technology, allowing extreme close-up imaging of the retinal vasculature for assessing retinal vascular diseases, and holds potential for guiding treatment decisions and monitoring patient responses to therapy.

According to Yuichiro Ogura, MD, PhD, professor and chair of ophthalmology at Nagoya City University, Japan, OCT angiography is the greatest breakthrough in ophthalmology in several years.

“Until now, we only had fluorescein angiography, and that was a 2-D image where you could not separate superficial and deep lesions. The big step forward of OCT angiography is that you can analyze the retina layer by layer,” he said.

Image: Ogura, Y

“We knew from animal studies or cadaver eyes that there was a difference between superficial capillary and deep capillary, but only now we are able to see it live in human eyes,” he said.M

This advancement comes with the additional bonus of being a dye-less technique.

“Fluorescein and ICG are effective dyes with a good safety profile but may cause allergies and shock in some patients,” Ogura said.

Direct analysis of blood flow

“This huge progress consists of having both functional and morphological assessment from a single dye-less examination,” Gabriel J. Coscas, MD, emeritus professor of ophthalmology at the University of Paris XII in Créteil, France, said. “The rapid and noninvasive nature of the OCTA allows for easier follow-up of morphological and functional changes in prolonged, repetitive and even monthly evaluations.”

For many years, in traditional OCT, subretinal or intraretinal fluid accumulation was a test of treatment efficacy to select the best schedule of intravitreal injections. Nevertheless, a large number of patients remained nonresponders or partial responders, despite multiple efforts.

“By directly analyzing activity criteria and blood flow in the CNV network before initial treatment and in the follow-up, OCTA can guide us more effectively in our treatment and re-treatment decisions,” Coscas said.

With OCTA, blood flow is imaged by motion contrast, Ogura said.

“What it does is take serial scans and separate the signal of what is moving and what is not moving. It subtracts the signal that is not moving, so you get only the scattering signal from moving particles, that is red blood cells in the retinal or choroidal vessels,” he said.

This evolution was made possible by the development of ultrafast swept-source OCT, scanning at a speed of 7,000 to 10,000 scans per second.

Capabilities of OCTA

SriniVas R. Sadda, MD, president and chief scientific officer of Doheny Eye Institute in Los Angeles, USA, is attracted to OCTA in part because of the ability to visualize the retinal microcirculation noninvasively without the use of dye, while at the same time reaping the benefits of OCT imaging.

“That network is so fine and so tightly packed that with a traditional fluorescein angiogram we could never see it. But now with OCTA, we are able to observe the network,” Sadda said.

This visualization also extends to the central part of the macula.

“With OCTA, you have a lot more confidence for assessing retinal capillary perfusion status, which can be very helpful in understanding various retinal vascular diseases, with diabetic retinopathy and retinal vein occlusions being the most common,” Sadda said.

OCTA is also being used to evaluate macular telangiectasia. “We are able to see the vascular anomalies in so much more detail,” he said.

Another advantage of OCTA’s superior contrast is the ability to glean more quantitative data. Whereas fluorescein angiography typically relies on subjective categories to define mild, moderate or severe loss of blood vessels, OCTA has the potential to use automatic computer algorithms to quantify the level of capillary loss, Sadda said.

“[Optovue] is starting to provide numerical retinal vascular data such as flow density analysis. We can expect that all companies in short order will add quantitative metrics. Once you have quantitative metrics, you can follow disease much more precisely and understand the relationship between these anatomic parameters and other visual function measures,” Sadda said.

Companies currently involved in this new development of OCTA are Carl Zeiss Meditec, Heidelberg Engineering, Optovue and Nidek. The Zeiss AngioPlex and Optovue AngioVue platforms are already available in some markets.

OCTA in AMD

At Retina 2015, Nadia K. Waheed, MD, MPH, an associate professor of ophthalmology at Tufts University School of Medicine in Boston, USA, presented on OCTA of wet age-related macular degeneration and diabetes.

“Using OCTA will most likely be paradigm-changing as far as treatment and development of treatment,” she said. “However, right now, a lot of people are skeptical about the clinical utility of OCTA because current treatment paradigms for diabetic retinopathy and wet macular degeneration almost exclusively use structural OCT to guide treatment and do not rely on any kind of angiographic information.”

But as more cases of wet AMD are investigated with OCTA, “we are seeing things that we have not seen before on fluorescein,” Waheed said. “One of the reasons for this is that OCTA provides beautiful depth resolution.”

Early studies using OCTA on wet AMD “have been really promising,” Waheed said. “Not only is OCTA able to reliably detect CNV in wet AMD, but it might also be used as treatment follow-up to guide us in the future about treatment decisions.”

Coscas was the lead author of an article in Retina that compared OCTA using Spectralis (Heidelberg) with traditional multimodal imaging in patients with exudative AMD for guiding treatment options. The prospective case series of 80 eyes described the use of very thin sections of CNV lesions.

While automatic segmentation might help in detection, manual segmentation will be more precise for CNV analysis, he said.

He suggested performing “transverse section analysis or horizontally aligned to the retinal pigment epithelium (RPE) profile or Bruch’s membrane (BM) profile, beginning above the RPE to identify pre-epithelial CNV, progressing in 30 µm layers between RPE and BM to image the entire subepithelial CNV network and finally toward the choroidal-scleral interface for feeder and draining vessels and for choroidal vessels and connections.”

Five criteria of activity or quiescence of CNV in exudative AMD were analyzed in the study.

“These criteria could be valuable during post-treatment follow-up for evaluating treatment efficacy,” Coscas said. “Coupled with the conventional OCT B-scan, which assesses fluid accumulation, OCTA may become the choice method to evaluate the activity or quiescence of the lesion and suggest the treatment decision.”

OCTA and diabetic eye disease

Likewise, OCTA “shows us in very fine detail and in very high resolution the vascular changes that are taking place in diabetes,” Waheed said. “Unlike fluorescein, which can only show us the superficial layer of blood vessels, OCTA can also show us changes in the deep retinal vessels. We are starting to visualize changes now on imaging that we traditionally were able to see only in pathologic specimens.”

In an article published in Retina, Waheed and colleagues demonstrated that OCTA may be able to detect early microvascular changes, such as foveal avascular zone (FAZ) changes and capillary nonperfusion, in eyes of diabetic individuals before the clinical signs of diabetic retinopathy (DR) appear.

Similar findings were also published in Retina by Ogura’s group using the AngioVue system.

“Diabetic eyes showed statistically significant FAZ enlargement compared with healthy eyes, regardless of the presence of retinopathy,” Ogura said.

“We also found that about 80% of microaneurysms are located in the deep capillary plexus layer and that inside the retinal edema, 91% of microaneurysms are in the deep layer. These results suggest that microaneurysms in the deep capillary plexus might be responsible for the formation of macular edema in DR,” he said.

According to Ogura, it is easy to explain why in diabetes there is more damage in the deep capillaries.

“You have the major retinal vessels on the surface of the retina, and they have connections with superficial capillaries and deep capillaries. Deep capillaries have to go deep and come back to the surface. This is a long way to go, and they can be damaged very easily with the disease,” he said.

Current limitations and future developments

Ogura is also studying OCTA use in AMD, myopic CNV and retinal vein occlusion. The use of a dye-less, noninvasive technique has the potential to revolutionize the management of all retinal diseases, he said.

“At present, there are some limitations. Right now the field of view is very narrow, 3 mm × 3 mm or 6 mm × 6 mm, and you cannot go to the periphery, but as technology progresses, over the next 5 years or so, I am expecting that it will replace fluorescein angiography. Currently, we need fluorescein angiography for the periphery,” he said.

“Given time, we have the ability to expand OCTA technology into widefield imaging by stitching together smaller pieces of images to obtain a wide field of view,” Waheed said. “It typically takes 3 to 4 seconds to secure an image, and the overall patient time in the room is probably closer to 10 minutes because you take multiple images.” This is still less time-consuming than fluorescein angiography, which normally takes 15 to 20 minutes.

“Fluorescein and ICG angiography are invasive methods and carry a small risk of adverse reactions. You cannot perform them every week or month, but with OCTA you don’t have such limitations and can perform it every time the patient comes,” Ogura said. “This is an invaluable advantage, the greatest evolution in the field of retina in several years. I am looking forward to the next developments of this technique.” – by Michela Cimberle and Bob Kronemyer

For more information:

Gabriel J. Coscas, MD, can be reached at Centre Hospitalier Intercommunal de Créteil, 40, Avenue de Verdun, 94010 Créteil, France; email: gabriel.coscas@gmail.com.

Yuichiro Ogura, MD, PhD, can be reached at Department of Ophthalmology and Visual Science, Nagoya City University Graduate School of Medical Sciences, Mizuho-ku, Nagoya 467-8601, Japan; email: ogura@med.nagoya-cu.ac.jp.

SriniVas R. Sadda, MD, can be reached at 1355 San Pablo St., Suite 100, Los Angeles, CA 90033; email: ssadda@doheny.org.

Nadia K. Waheed, MD, MPH, can be reached at Tufts Medical Center, 800 Washington St., Box 450, Boston, MA 02111, USA; email: nwaheed@tuftsmedicalcenter.org.

Disclosures: Coscas reports he is a consultant for Heidelberg Engineering. Ogura reports no relevant financial disclosures. Sadda reports he has served as a consultant and received research support from Optos and Carl Zeiss Meditec and has been a consultant for Topcon and Nidek. Waheed reports she has been a consultant for Iconic Therapeutics, a contract researcher for Carl Zeiss Meditec and a member of the speakers bureau for ThromboGenics.

 

 

What other pathologies, besides retinal diseases, could benefit from the use of OCT angiography?

OCTA may image abnormal vasculature in anterior segment and cornea

OCTA has the potential to become an important diagnostic tool in the world of ophthalmology. Its main advantages are its ability to rapidly capture cross-sectional and en face images of tissue layers of the eye and its associated vessels in a noninvasive manner.

Current OCTA systems are optimized for the retina and optic disc. Nonetheless, we adapted two systems for the anterior segment and cornea to evaluate corneal vascularization with promising results. We first described the technique in normal eyes and found good repeatability for image quality score and good interobserver agreement for vasculature measurements. Then we demonstrated that an anterior segment-optimized OCTA system has several potential clinical applications, such as preoperative evaluation of corneal vascularization before corneal transplantation, monitoring anti-VEGF treatment response in the anterior segment or even for the resolution of feeder vessels after fine-needle diathermy. We also recently compared OCTA adapted for anterior segment imaging to indocyanine green angiography in eyes with corneal vascularization. We found that the agreement between OCTA and ICGA scans was good in terms of measuring areas of corneal vascularization, which may suggest a role for OCTA in monitoring of changes in corneal vessels in future clinical trials.

Future studies with optimization of OCTA systems for the cornea could extend to ocular surface diseases or to the evaluation of limbal stem cell deficiency.

 

References:

Ang M, et al. Br J Ophthalmol. 2015;doi:10.1136/bjophthalmol-2015-307338.

Ang M, et al. Br J Ophthalmol. 2016;doi:10.1136/bjophthalmol-2015-307706.

Ang M, et al. Ophthalmology. 2015;doi:10.1016/j.ophtha.2015.05.017.

Marcus Ang, MD, is a consultant, Cornea and Refractive Service, Singapore National Eye Centre and assistant professor at Duke-NUS, Singapore. Disclosure: Ang reports no relevant financial disclosures.

Glaucoma may benefit from in vivo observation

Raised IOP is the most important modifiable risk factor for glaucoma and is directly influenced by episcleral venous pressure. Directly assessing episcleral venous pressure in animals via cannulation of episcleral veins or injections of radioactive tracers cannot be extrapolated to clinical studies, while indirect measurements of episcleral venous pressure using venomanometers are inconsistent.

Characterizing the episcleral venous system and aqueous outflow channels in vivo, safely and reliably with OCTA, is potentially useful as it may enhance the efficacy of microinvasive glaucoma surgeries by guiding placement toward high-outflow capacity collector channels. These ab interno microstents maintain patency of the outflow pathway via trabecular bypass and/or expansion of Schlemm’s canal, which should theoretically result in detectable changes to the episcleral venous system as well.

Additionally, one may potentially evaluate interventions such as Rho kinase inhibitors, latrunculin, pilocarpine or selective laser trabeculoplasty, which manipulate the trabecular meshwork cytoskeleton/resistance. Unfortunately, in our experience the main difficulties are in overcoming motion artifact and consistently imaging the same area again.

Meanwhile, recent OCTA studies of the optic nerve head have suggested the superficial disc vasculature and the deeper lamina cribrosa microvascular network are attenuated in glaucoma. Furthermore, the optic disc blood flow index has been shown to have very high sensitivity and specificity in differentiating glaucomatous eyes from normal eyes and is directly correlated to visual field changes. These findings show some promise toward a diagnostic component to OCTA, too.

 

Reference:

Jia Y, et al. Ophthalmology. 2014;doi:10.1016/j.ophtha.2014.01.021.

Shamira Perera, MD, is a senior consultant, Glaucoma Service, Singapore National Eye Centre, and adjunct associate professor at Duke-NUS Medical School, Singapore. Disclosure: Perera reports he is on the advisory board of Allergan and receives honoraria from Alcon, Allergan and Ellex.