Intricacies of Zeiss Angioplex OCTA system revealed

OCT Angiography (OCTA) is an extension of the ophthalmic applications of Optical Coherence Tomography (OCT) that has been the subject of research for more than a decade. Whereas OCT is used mostly for cross-sectioning imaging, OCTA is used in the en-face (frontal) mode, cross-section mode, and all steps in between.It offers high-resolution, 3D, layered (repeated B-scans computed and aligned pixel by pixel) imaging of the retinal vasculature – including microvasculature. The imaging is produced non-invasively over user-selectable areas ranging from 3 X 3 mm up to 8 X 8 mm.Previously, all of that has been accomplished in a single image capture of generally 1–2 minutes. However, with Zeiss’ AngioPlex Image Capture, that time has been reduced to as little as 3–5 seconds. Based on its CIRRUS HD-OCT, the AngioPlex syst uses a scan rate of 68,000 per second via its OCT microangiography-complex (OMAG) algorithm and FastTrac retinal tracking software.Dr Anna Tan, an Adjunct Assistant Professor from the Singapore National Eye Centre and the Singapore Eye Research Institute (see breakout box) expanded on the latest technological advancents in a series of Expert Sessions held in Sydney and Melbourne in late April.Tan explained that to image the blood vessels, the instruments ploy motion-contrast imaging that uses differences in back-scattered OCT signal intensity (amplitude) between aligned, sequential B-scans.{{quote-A:R-W:500-I:7-Q:“The technology has been ‘brewing in the background’ for over a decade. We were just waiting for the OCT syst hardware to run fast enough, and for the angiography algorithm to be efficient enough, to produce a high-quality angiogram in reasonable scan time.”-WHO:Professor David Huang, Co-developer of Ophthalmic OCT}}To enhance the image further, Zeiss technology utilises additional information taken from the phase shifts in the OCT signal. Patient movent is compensated for and, theoretically at least, the images show only erythrocytes within retinal blood vessels.Selection of the depth used for on-screen display is possible due to the layering used in the technology. In the AngioPlex interface, such manual segmentation is augmented by a pre-set menu of logical anatomical levels, represented as icons on the left of the screen.The depth is also displayed as a line or a plane in sectional and 3D diagrams, so that it is clear to the viewer what layer or data slab is being displayed. Such control is especially useful in differentiating retinal and choroidal issues, diabetic retinopathy, retinal occlusions, and micro-aneurysms.In branch retinal vein occlusions (BRVOs), the extent of the ‘absent’ or disrupted circulation is apparent immediately. Similarly, the extent of the foveal avascular zone (FAZ) in normal and abnormal cases can be measured at different depths – a feature especially useful in cases of macular oeda.The use of multi-segmentations allows the construction of a detailed, overall picture and may be required on occasions when incorrect segmentation implies that avascular/no blood flow areas exist. Unfortunately, different OCTA instruments, using different algorithms, produce different and/or incomplete results when comparisons are attpted. In longitudinal studies, the same instrument needs to be deployed if valid comparisons are to be made.Generally, the smaller the area scanned, the higher the resolution, making smaller details visible. It’s possible to provide the same level of fine detail over larger areas by creating a montage of multiple images, however, this involves more time and effort. Tan said the time required to montage was similar to that of a full fluorescein angiogram (FA).Artefacts, such as discontinuous blood vessels, can appear in generated images when signal strength is suboptimal. Confusion can also result from alteration to the RPE, which acts as a mirror when intact or as a light absorber when absent. However, small pigment epithelium detachments (PEDs) can appear as bright spots in en-face OCTA. OCTA can also detect quiescent choroidal neovascularisation (CNV) tangles.Although most of Tan’s current professional practice is Zeiss-based, she does have access to competing OCTA products and she noted that, compared with the Zeiss AngioPlex syst, some of the competing products have greater issues with scanning artefacts.Tan has been an OCT user almost from the time it became commercially available (2002 with the launch of Zeiss’ Stratus instrument) and an OCTA user from the beginning. OCTA is also one of her main research interests, especially tying fundal appearance and measurable functions to OCT and OCTA images.She has also found the technology particularly useful in polypoidal choroidal vasculopathy (PCV) – PEDs and exudative changes in the choroid that can lead to subretinal fibrosis.As PCV is more common in East Asian people Tan’s Singapore location means she is confronted with the condition relatively frequently. She estimated FA alone or OCTA alone could diagnose most conditions correctly in about 67% of cases, but the combination of FA and OCTA raises that figure to around 86%.Additional research is directed towards the use of OCTA, or a derivative of it, to pursue glaucomatous changes in the eye, especially in the context of peripapillary blood circulation.Software is also available for post-processing, examination of alternative views, image manipulation, and data analysis in a practitioner’s office away from the instrument. The ability to view and analyse results rotely can be especially important in a large clinic, as it allows the instrument to be used by others.Will it replace FA or ICGATan’s short answer was no. This is because FA and ICGA (indocyanine green angiography) offer a large field-of-view (FofV) limited only by the FofV of the fundus camera deployed, whereas OCTA offers a small FofV – especially if fine detail is required. Furthermore, vessel leakage cannot be imaged by OCTA currently because, unlike FA, no dye is used so extravascular blood/blood derivatives are ‘transparent’ to the syst.The absence of a dye injection time also means there is no way of establishing a chronology of leakage. However, Dr Philip Rosenfeld of the Bascom Palmer Eye Institute in Miami, quoted in a 2016 Review of Ophthalmology article on OCTA, stated that macula oeda, appearing as increased retinal thickness, was a reliable proxy for vessel leakage in all conditions except macular telangiectasia type II (MacTel II) and in that condition, normal OCT as well as OCTA will disclose the structural changes present.{{image3-a:r-w:400}}That aside, Rosenfeld still saw some disadvantages in the artefacts that can appear in OCTA scans, many of which anated from the intervening blood vessels. Those vessels are the targets for the image processing algorithms used by manufacturers and another reason superior computing power is required if screen outputs are to appear in a timely manner.Essentially, OCTA is not a stand-alone diagnostic tool in its current form. Using AMD as an example, Tan said she would normally use FA for the initial diagnosis and analysis of a patient’s retinal vasculature, and OCTA subsequently because of its convenience, rapidity, and the progression analysis it offers. Additionally, patients would probably welcome the use of regular OCTA instead of repeated FAs.Tan uses the 3-step (Types 1–3) classification that links OCT, FA, and ICGA information for each type to describe neovascularisation. Other parameters, such as blood velocity, are beyond the technology currently. According to Tan, ICGA is superior at imaging the choroid and deeper layers than FA.One discovery made possible through OCTA is that so-called ‘dry’ AMD appears to be a disease of the whole of the choroid. This is because OCTA shows that areas beyond the obvious are also affected, despite it being regarded as a localised case of decreased choroidal perfusion.Tan believes that OCTA interpretation is still imperfect and there is more to be gleaned even from current imaging. Her parting comment was to consider whether or not OCTA should become the new gold standard for imaging CNV.What is the history of OCTA?OCTA’s history is less clear and involved more researchers than OCT itself. In a late 2016 interview with OIS-TV, Professor David Huang, co-developer of ophthalmic OCT, said, “the technology has been ‘brewing in the background’ for over a decade. We were just waiting for the OCT syst hardware to run fast enough, and for the angiography algorithm to be efficient enough, to produce a high-quality angiogram in reasonable scan time.”Huang claims that the two dominant algorithms used in current OCTA devices originated at his university – Casey Eye Institute at Oregon Health and Science University in Portland. He revealed Dr Ruikang (Ricky) Wang developed OMAG, as used by Zeiss in 2011, and that he developed the split-spectrum amplitude decorrelation angiography (SSADA) algorithm in 2012, as used in the Optovue AngioVue.Huang also noted that the concept was under investigation for at least 10 years in Professor Yasuno’s lab in Japan and, like most, they had to wait for the hardware to operate fast enough to capture useful images.{{image4-a:l-w:400}}While Zeiss Meditec was the first company to release an OCT in the form of its the research-oriented time-domain OCT1 in 1995, the first to market an OCTA instrument was Optovue (AngioVue, 2014). Optovue were also the first to release a spectral-domain OCT (SD-OCT) device. However, there is some suggestion that its initial OCTA offering may have been rushed to market for competitive reasons, because some original software was revised almost immediately.OCTA is perhaps even more software/firmware intensive and dependent than OCT. Some companies have based their OCTA offerings on a separate hardware platform, meaning that practices can end up with two OCT-based instruments, an expensive undertaking.Zeiss has created a significant software layer for the latest version of its CIRRUS platform that also allows for changed metrics and analytics. However, because of computing power, speed, and storage requirents, only the CIRRUS 5000 HD-OCT is compatible with AngioPlex. In addition to Zeiss, OCTA offerings are available from Nidek, Optovue, Topcon and Heidelberg Engineering. .Associate professor I-Van HoAssociate Professor I-Van Ho, a noted Sydney-based medical retina and vitreoretinal surgeon, moderated the Sydney event and used a number of case histories and images to illustrate the utility of AngioPlex.His general approach was similar to Tan’s, insofar as he tried to match AngioPlex images and data with compatible information provided by other technologies to gain a better understanding of what is being investigated.Ho said the AngioPlex instrument’s printout alone should never be relied on in isolation and instead, he advised the audience to play with the data sets to gain a better understanding of each case.Regardless of its utility, Ho does not perform AngioPlex routinely on every patient. Typically, he ploys a 6 X 6 mm scan, does few montages, and uses wide-field fundus imaging regularly. Ho uses AngioPlex to show retinal areas with reduced perfusion rates to highlight micro-aneurysms and disclose capillary abnormalities.{{quote-A:R-W:500-I:6-Q:"The angioplex instrument’s printout alone should never be relied on in isolation."-WHO:I-van Ho, Medical Retina and Vitreoretinal Surgeon}}He also believes that the presence of fewer micro-aneurysms is a predictor of a better response to anti-VEGF therapy, a claim that some recently published studies support.If, for some reason, an FA cannot be performed or would be imprudent in light of the patient’s general health, OCTA is very helpful. In some retinal vein occlusion with persistent macular oeda cases, Ho said he would use AngioPlex to determine the area most affected and then use a laser to address local areas of non-perfusion.This reduces the amount of VEGF influencing the area’s vessels, possibly extending the time needed between anti-VEGF injections. In his PCV cases, he still regards ICGA as the gold standard for routine investigation.Ho said the presence of polyps resulted in a variable AngioPlex appearance corresponding to low and high blood flow areas, and the use of a cross-section in AngioPlex was better at revealing high and low flow areas near the RPE.He also finds AngioPlex effective for showing MacTel cases and useful in diabetic retinopathy. Provided the same instrument type is used, Ho finds repeatability very good but, as Tan noted earlier, the situation is poor once attpts at cross-platform comparisons are attpted.Ho lauded AngioPlex for its speed, ease of capture, and image presentation options. However, he noted that when trying to make rapid comparisons between sequential images, other image platforms performed differently and some were slow at rendering images on screen, making comparisons difficult, if not impossible.About the speaker Dr Anna TanAdjunct Assistant Professor of Duke-NUS Medical School, Dr Anna Tan, is a consultant medical retina specialist in the Medical Retina Department of the Singapore National Eye Centre (SNEC), a tertiary referral centre. Although schooled in Singapore, Dr Tan studied medicine at the Melbourne Medical School, University of Melbourne (UniMelb).She also completed an advanced Bachelor of Science degree hosted conjointly by UniMelb and Imperial College, London within the six years of her medical course. For that degree, she studied tissue engineering and cultured lung tissue cells on various materials.Upon graduation, she practised general surgery in Melbourne for two years. Through her career, Tan also developed an interest in humanitarian endeavours in the developing world, an interest she acts upon regularly to this day by visiting Myanmar, Cambodia, India, and the Philippines.{{image5-a:l-w:300}}Tan returned to Singapore with a personal interest in ophthalmology and accepted an offer of specialty training locally (Fellowship of the Acady of Medicine, Singapore) soon after her return. At that time, Singapore accepted only about 10% of applicants for ophthalmology specialty training. Singapore’s approach to specialty training is based on the UK model, comprising of six years rather than the four years ployed in most other jurisdictions, and she graduated in 2013.She then proceeded to obtain a Fellowship of the Royal College of Surgeons, Edinburgh and she spent the first year after completing her ophthalmology fellowship pursuing her evolving interest in medical retina and the die was cast.To further her interest in that subspecialty, Tan undertook multiple medical retina fellowships, including those offered by the SNEC – the University of Bonn’s Ophthalmology Department under Professor Frank Holz – and the Vitreous Retina Macula New York (VRMNY) under Drs Lawrence Yannuzzi and K Bailey Freund.However, on her way to Bonn, she spent some of her spare time at the Aravind Eye Hospital in Pondicherry, India, to learn the art of manual cataract surgery, also known as small incision cataract surgery. She also was fortunate enough to receive a scholarship funded by the Singapore Government to pursue overseas training in new and upcoming areas that would benefit health services in Singapore.The increasing dand for retinal services in Singapore, especially those related to AMD, is sufficiently large to support the pursuit of two branches of the subspecialties, surgical retina and medical retina. The latter was Tan’s choice because it allowed the use of a more diverse range of ophthalmological skills that more closely matched her own interests.Describing herself as a clinician-investigator with a conjoint appointment at the Singapore Eye Research Institute (SERI), Tan has published more than 30 peer-reviewed articles and contributed three book chapters on her subspecialty, which now involves a large amount of ocular imaging and related clinical research.Among her other achievents, she has been awarded four acadic grants including the Khoo Clinical Scholarship and the Acadic Clinical Program Grant for clinician-scientists/investigators.Tan’s other interests within her subspecialty include inherited retinal diseases, AMD, and the related areas of low vision and visual rehabilitation. For the latter, she is responsible for evolving multi-disciplinary teams at SNEC, which consists of optometrists, occupational therapists, social workers, and nurses.Notwithstanding the fact many in the audience either owned or had access to an OCTA instrument, there was little doubt that most wanted the latest information, if not the latest device, from this evolving product category.