ZEISS OCT Angiography eNewsletter Series
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What is OCT-A, and how does it differ from FA?
By Amir H. Kashani, MD PhD

Figure 1. This OCT angiogram shows the left eye of a 69- year-old patient with macular telangiectasia. The patient has classic findings of microvascular changes in the temporal macula that appear in all three layers of the OCT angiogram (color code: red: inner retina; green: mid retina; blue: outer retina). The top left panel shows the OCTA of the inner retina. Milder changes are noted in the mid-retinal layer (top right panel). In addition, retinal vessels are noted in the outer retina (bottom left panel), where there are usually no vessels.
What is OCT-A, and how does it differ from FA?
OCT-A stands for optical coherence tomography-angiography, which is a promising technology still under investigation. Currently, fluorescein angiography (FA) is the standard of care for evaluating numerous retinal diseases, but it requires the intravenous injection of a dye with subsequent photography to visualize the retinal vasculature. OCT-A, on the other hand, allows for the noninvasive imaging of the retinal vasculature.
Instead of using the optical scattering properties of tissue to provide 3-D images, which normal OCT does, OCT-A looks at the variation in the intensity and phase of the light caused by the flow of red blood cells. OCT-A differs from FA in that the OCT-A signal reflects off of red blood cells, rather than being emitted by fluorescein dye. Based on the properties of the light reflected from these blood cells, we can tell that blood cells are in motion and identify retinal vessels.
What are the primary advantages of OCT-A?
The primary clinical benefit of OCT-A is that the clinician can image both eyes as many times as desired without the need for intravenous dye injection. If the patient blinks, for example, retaking the picture requires only a few seconds. OCT-A can eliminate the complicated step (as well as the potential side effects) of injecting the patient with dye, and also the time-sensitive process of capturing a series of images during the circulation of the dye. Being able to conveniently image both eyes is a huge benefit compared to fluorescein, where the doctor has to choose the “most important” eye for imaging.
Also, the small-vessel resolution of OCT-A is in many cases superior to FA. In fact, it is very close to the resolution of histology in some ways.
how are you testing oct-a clinically?
Currently, my team and I are testing OCT-A on the ZEISS CIRRUS device in a number of investigator-initiated, IRB-approved research studies. We are applying this imaging technology to eyes that have diseases affecting the retinal vasculature, such as diabetic retinopathy, retinal vein occlusions, retinal arteriolar occlusions, etc. We are also starting to examine diseases that affect the choroidal vessels.
In many cases, I foresee OCT-A to be a viable alternative to fluorescein angiography, because it is faster, non-invasive, and has excellent spatial resolution.
Amir Kashani, MD PhD, is an Assistant Professor in the Department of Ophthalmology at the University of Southern California and the USC Eye Institute. He is a clinical investigator for the OCT-A technology on the CIRRUS OCT device. Dr. Kashani may be reached by email at ahkashan@usc.edu.

Clinical Use of the New CIRRUS HD-OCT
By Jean-Francois Korobelnik, MD

Figure 1. SD-OCTA Cirrus (Zeiss) of a patient with branch vein occlusion: non perfusion involving the border of the FAZ is visible.

Figure 2. SD-OCTA Cirrus (Zeiss) of a patient with diabetic retinopathy: non perfusion area with IRMA is visible, as the center of the macula looks normal.
WHAT DO YOU FEEL ARE THE CLINICAL BENEFITS OF USING THE CIRRUS OCT-HD WITH AngioPlex OCT-ANGIOGRAPHY?
My team and I have been using the CIRRUS prototype on an almost daily basis for the past few months to study eyes that we suspect of having macular or retinal pathology. High-definition OCT angiography (OCT-A) enables us to conduct an exploratory examination of what we think may be abnormal pathology in the posterior pole.
We find the CIRRUS OCT-A device most useful in cases of diabetic macular edema and retinal vein occlusion, where we can easily see if there is perfusion or non-perfusion involving the macula and/or the border of the macular zone. Non-perfusion that is very close to the fovea is invisible with ophthalmoscopy, but it is easily viewed with OCT-A on the CIRRUS device. The 3-D image is of such high quality that we often do not need to use fluorescein angiography. It helps us detect DME and RVOs more easily than we could previously.
HOW DO YOU ENVISION USING OCT-A IN YOUR DAILY PRACTICE?
We plan to use CIRRUS OCT-A as a tool for imaging the retina in addition to fundus photography and our usual OCT examination with Bscan and mapping. With OCT-A on the CIRRUS device, we can better evaluate whether a patient with macular vascular disease has a chance of visual improvement with injections, or if the prognosis is poor. For example, if a macula’s perfusion is poor, then we can expect the potential for visual recovery to be poor as well.
HOW EASY IS OCT-A IMAGE ACQUISITION WITH THE CIRRUS HD-OCT?
The image acquisition process is extremely quick and intuitive. The eye tracker works in concert with the high-speed processor to capture an image in less than 1 minute. My technicians and I have not had any problems acquiring an image with the OCT-A prototype; it is very simple.
Even if the eye’s fixation is poor, the eye tracker is so adept that we almost always get a good-quality image.
WHAT EXCITES YOU ABOUT OCT-A TECHNOLOGY?
My team and I are enjoying exploring the capabilities of this new technology, OCT-A, on the CIRRUS HD-OCT, and we are learning how the images correlate with other technologies. For example, we have captured some very nice images of the vascular network in eyes with wet AMD, and we are studying how these images correlate with B-scan images. We would like to determine whether there are signs of pathology visible on the OCT-A before they appear on B-scan or OCT mapping. Diabetic retinopathy and CNV in myopic eyes are also areas among others where OCT-A appears to be extremely helpful.
Jean-Francois Korobelnik, MD, practices in the Department of Ophthalmology, Centre Hospitalier Universitaire de Bordeaux, Hospital Pellegrin, Bordeaux, France. Professor Korobelnik states that he has no financial interest in this subject matter. He may be reached via e-mail: jean-francois.korobelnik@chu-bordeaux.fr.

AngioPlex May Help Detect Asymptomatic Choroidal Neovascularization in Dry AMD
By Philip J. Rosenfeld, MD, PhD
I have maintained a research relationship with ZEISS for well over 10 years, and thus I have been involved in the development of the spectral-domain CIRRUS HD-OCT (ZEISS) system, as well as the new angiography platform known as AngioPlex OCT-angiography (OCT-A). AngioPlex OCT-A represents the beginning of what will be a series of ZEISS innovations in OCT-A imaging. I consider this a breakthrough instrument, because the OCT-A technology, along with the innovative FastTrac motion correction feature, allows us to identify details of the macular microvasculature that we have never seen before.
WHAT ARE THE CLINICAL BENEFITS OF ANGIOPLEX?
Clinically, the AngioPlex is very accessible because it is easy to use, and it is an extension of the current CIRRUS platform. It allows us to obtain a higher number of A-scans in a B-scan line in less time, because it has a scanning rate of 68,000 A-scans per second. Thus, the instrument can offer unique scan patterns, such as a high-density 3x3-mm scan. The greater pixel density imparts a higher image quality for visualizing macular structures, as well as the microvasculature from the OCT angiographic B-scan and en face flow images.
OCT-A is a modification of traditional en face OCT imaging. In addition to looking at just structure, we can now view the flow of blood through the macular microvasculature. The AngioPlex OCT-A does this by repeating each B-scan four times in the exact same location. Because blood has high reflectivity, OCT-A can detect the motion of the erythrocytes through the vessels. The system finds the decorrelation signal between each sequential B-scan to determine the changes that have occurred between each scan, and these changes represent the movement of blood. By stacking the images together, we get an en face projection, and it looks like a normal angiographic image, but without the use of intravenous dyes. The AngioPlex OCT-A uses light alone to capture images that are complementary to traditional fluorescein angiographic images.
IS THE ANGIOPLEX EASY TO USE COMPARED TO CONVENTIONAL OCT AND ANGIOGRAPHY?
After undergoing prototype testing, the final AngioPlex OCT-A system is very user-friendly. The device’s image-capture function is fast and includes an advanced motion-tracking system to ensure that the four successive images are registered in the same location. The device’s scan area goes as high as 6x6 mm, a size that is the same as the current Cirrus HD-OCT, and encompasses most macular pathologies. Furthermore, the AngioPlex OCT-A allows us to segment these images into en face layers so that we can visualize the superficial, deep, and outer avascular layers of the retina, as well as the choriocapillaris and the choroidal circulations. With such precise imaging, we can localize pathology to specific layers, which is particularly useful for following disease progression.
In short, I believe the ZEISS AngioPlex is a breakthrough clinical tool that will help us understand and map the onset, progression, and recurrence of macular diseases. This device has significantly improved upon conventional OCT and is complementary to dye-based angiography. After using the Zeiss AngioPlex system, I feel confident that traditional dye-based angiography for most macular diseases will be unnecessary.
CLINICAL EXAMPLE
My staff and I recently used the AngioPlex to evaluate patients with dry age-related macular degeneration (AMD). These patients are not usual candidates for angiography using fluorescein or indocyanine green, because it is unnecessary in most cases, and the benefits of early disease detection cannot justify the potential risks and expense, since Medicare does not cover it for that indication. Historically, we have followed these patients by examining the fundus with biomicroscopy, fundus photography, autofluorescence, and traditional OCT. However, none of those techniques reliably identify when choroidal neovascularization (CNV) first appears. We have developed severity scales that are predictive for when dry AMD might convert to wet AMD, but we have only been able to detect CNV when vessels begin to leak or bleed. Usually, by the time we notice these changes on OCT, the patient is already reporting a change in his or her vision. Thus, before the use of the AngioPlex OCT-A, we could not detect the asymptomatic onset of CNV.
I wondered if we could use OCT-angiography to identify blood vessels that were quiescent. Could we identify neovascular complexes that were sitting under the retinal pigment epithelium before they started to leak or bleed? We could just look for CNV in asymptomatic patients, but the absence of evidence that CNV was present is not evidence of CNV absence. We did not know the sensitivity and specificity of the technique. Just because we could not detect the CNV, did not mean it was not present. We needed a positive control, and that control was indocyanine green angiography. So, we performed a study of patients who had received traditional angiography for wet AMD in one eye, and these patients also had dry AMD in their contralateral eye. Studies have shown that patients who develop wet AMD in one eye had a greater likelihood to developing wet AMD in their fellow eye within 5 years.1,2
Of the patients we were following with OCT-angiography, we identified 11 individuals who underwent dye-based traditional fluorescein and indocyanine green angiography for their wet AMD in one eye, and we could also search for quiescent CNV in their fellow eye with dry AMD. Of these 11 patients, three were diagnosed with plaques (the early sign of CNV on ICG angiography) in the eyes with dry AMD. In these eyes, the CNV was obvious when imaged with AngioPlex OCT-A, and we are now conducting a larger survey to answer the question of how commonly we see CNV in patients who are diagnosed with dry AMD.
DISCUSSION
If we can now see CNV even before blood vessels start leaking, then it begs the question, why are we even bothering with fluorescein and indocyanine green angiography? I no longer see a reason to use traditional dye-based angiographic imaging in my routine wet AMD cases. In my opinion, OCT-angiography is going to be a paradigm shift for retinal specialists, although admittedly, it has an uphill battle against the revenue afforded by traditional dye angiography. I do believe, however, that OCT angiography is the future of macular imaging. Because of the exceptional image quality this technology can achieve, I do not think we can justify the continued use of intravenous dyes for routine cases. OCT-angiography is safer, faster, cheaper, and more easily repeatable in a way that dye angiography is not, and OCT-A provides better images through cataracts. OCT-angiography should be the first-line imaging strategy for exudative diseases of the macula. Also, with a capture rate of 4 to 5 seconds, no dilation being necessary, and no bright flashing lights being used, OCT-angiography is clearly preferred by my patients.
Philip J. Rosenfeld, MD, PhD, is professor of ophthalmology at Bascom Palmer Eye Institute in Miami, Florida. He receives research funding from ZEISS, and ZEISS and the University of Miami share licensing agreements for certain algorithms. Dr. Rosenfeld may be reached at (305) 326-6148; prosenfeld@med.miami.edu.
References:
1. Davis MD, Gangnon RE, Lee LY, et al. The Age-Related Eye Disease Study severity scale for age-related macular degeneration: AREDS Report No. 17. Arch Ophthalmol. 2005;123(11):1484-1498.
2. Friberg TR, Bilonick RA, Brennen PM. Risk factors for conversion to neovascular age-related macular degeneration based on longitudinal morphologic and visual acuity data. Ophthalmology. 2012;119:1432-1437.
VOLUME 1
What is OCT-A, and how does it differ from FA?
OCT-A stands for optical coherence tomography-angiography, which is a promising technology still under investigation. Currently, fluorescein angiography (FA) is the standard of care for evaluating numerous optical diseases, but it requires the injection of a dye to image the retinal vasculature. OCT-A...
VOLUME 2
Clinical Use of the New CIRRUS HD-OCT
My team and I have been using the CIRRUS prototype on an almost daily basis for the past few months to study eyes that we suspect of having macular or retinal pathology. High-definition OCT angiography (OCT-A) enables us to conduct an exploratory examination of what we think may be abnormal pathology...
VOLUME 3
AngioPlex May Help Detect Asymptomatic Choroidal Neovascularization in Dry AMD
I have maintained a research relationship with ZEISS for well over 10 years, and thus I have been involved in the development of the spectral-domain CIRRUS HD-OCT (ZEISS) system, as well as the new angiography platform known as AngioPlex OCT-angiography (OCT-A). AngioPlex OCT-A represents the beginning...
