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.