Maintenance of normal vision depends on an efficient and regulated blood supply to the retina. Compromise of this, as for example with vascular occlusions, haemorrhages, aneurysms or neovascular response to ischaemia, results in vision loss. Diagnosis, assessment of extent of disease and monitoring of the impact of treatments all require accurate visualisation of the vasculature.
Though ophthalmoscopy in its various forms will reveal major surface structural changes (haemorrhages, vessel calibre variation, absence of perfusion or atrophy), deeper lesions and anomalies are not easily seen and, even for visible superficial change, there is little indication of disruption extent beyond a subjective interpretation of often indistinct images.
The mainstay of retinal vascular flow assessment has for many years been fluorescein angiography, along with the less often used technique of indocyanine green angiography for choroidal assessment. Both techniques require the intravenous injection of a coloured dye after which the fundus is photographed under the appropriate light input as the dye flows through the vascular bed. Areas of non-perfusion appear black, while leakage sites fluoresce increasingly as fluid exits a vessel (Figures 1a and 1b).
[CaptionComponent="1976"][CaptionComponent="1977"]Injection of the dyes presents some dangers. As a penniless pre-reg I remember taking part in a drug trial at an eye hospital. This included a fluorescein angiography assessment and, to take part, I had to complete an extensive consent order which warned of the very many possible adverse reactions that can occur. Nausea and vomiting were worrying enough, but when I read that fatality can occur as a result of anaphylactic shock I had second thoughts.
A second problem with the dye approach is that, as the fluid fills the anomalous vascular bed, the build-up of dye tends to obscure details of the image and blur the boundaries of any neovascularisation. Furthermore, the final images are two dimensional, so depth of lesion and involvement of different retinal layers is difficult to specify.
There is now a different approach. OCT angiography is a non-invasive technique allowing precise and defined visualisation of three-dimensional vascular structure (Figure 2).
[CaptionComponent="1978"]OCT angiography
Relax – I am not going through (yet again) the major advantages OCT assessment has offered to eye care practitioners. However, recent years have seen efforts to analyse the varying signals that result when the OCT is aimed at blood vessels as a result of red blood cell transit.
Initial interest was in Doppler OCT. This relies on the difference between signals from flow towards and away from the viewer along a path parallel to the incident light.
As such, most circulation (which happens oblique or perpendicular to the beam) is not analysed. More successful have been various techniques looking at the information contained in the speckle pattern – the scattered point response reflected from a multi-layered and irregular structure such as the vascular bed of the retina and of the choroid. Detail of the exact nature of the vessels is possible by analysing the different amplitudes of reflected light, phase differences of the reflection or a combination of both amplitude and phase variance.1 One of these techniques, which has proved very effective, is an amplitude-based method called split-spectrum amplitude-decorrelation angiography (Ssada).
Split-spectrum amplitude-decorrelation angiography
The Ssada algorithm detects changes in a vessel lumen as blood flows through it. As the lumen changes shape, so does the amplitude of a reflected signal. The change over repeated OCT scans allows a three-dimensional picture to be constructed of the vessel and the blood flow, along with a rejection of the ‘noise’. Instead of assessing amplitude across the full spectrum, Ssada uses four-fold amplitude splits that improve the signal to noise ratio and speed up the scanning process. More splits may enhance the image further. Importantly, Ssada can be used with currently available OCT machines.2
AngioVue
The US company Optovue have been at the forefront of OCT development for years. It pioneered spectral domain OCT, for example, which significantly improved the images from OCT and more recently used its high speed OCT system as the platform for using the Ssada algorithm. The result is the AngioVue, a familiar OCT with the ability to undertake non-invasive angiography quickly and safely along with all the other many OCT assessments now demanded by practitioners.
Though obviously of immediate interest to ophthalmology, the extra dimension offered by the AngioVue should be of interest to the primary eye care sector too. Haag-Streit UK, distributor of the AngioVue, recently loaned me the machine to try out (Figure 3).
[CaptionComponent="1979"]The AngioVue is based around the Optovue spectral domain OCT platform so the unit performs excellently as a high-end OCT. Figure 4 shows the high definition single scan of healthy retinas. Note the detail of the vitreous as well as the definition of the retinal layers.
[CaptionComponent="1980"][CaptionComponent="1981"]
Achieving these images was simplicity itself. RNFL assessment, 3D disc analysis (Figure 5) and retinal mapping are all present.
[CaptionComponent="1982"]Anterior capture is possible after adding the lens adapter (Figure 6) and pachymetry (including mapping – Figure 7) and angle assessment (Figure 8) are all easy to perform.
[CaptionComponent="1983"][CaptionComponent="1984"][CaptionComponent="1985"]
3D representation (primarily to instruct the patient – Figure 9), layer differentiation, parameter analysis and so on are all possible as one might hope. Selection of the angiography scan provides information about the vascular flow in less than three seconds.
[CaptionComponent="1986"]Angioflow and en face
When undertaking angiography, the patient is asked to maintain steady fixation while the retina or disc is focused on screen. After a couple of blinks to steady the tear film, two scans are taken; one vertically orientated and one horizontal. Artefacts (due to eye saccades) appear as thin white streaks on the image but Optovue (working with MIT) have developed motion correction technology (MCT), which removes these from the final composite image.
The vascular structure at four depths is then displayed – superficial retina, deep retina, outer retina and choriocapillaris (Figure 10 – note how for the healthy retina, there is no blood flow in the outer retina).
[CaptionComponent="1987"]Areas of non-perfusion would appear as dark (Figure 11) while choroidal neovascularisation encroaching into outer retina, as in early wet AMD, is clearly defined (Figure 12).
[CaptionComponent="1988"][CaptionComponent="1989"]Figure 10 also shows how en face images of the four depths may be displayed alongside flow information to help in analysing structural influences upon flow. Figure 13 shows colour representation of healthy retina and Figure 14 a colour assessment of blood flow at the optic disc.
[CaptionComponent="1990"][CaptionComponent="1991"]The AngioVue represents an important step forward in OCT assessment and one which I believe will further extend the range of health assessments possible in primary care. Look out for some case studies in Optician early next year.
References
1 J M Schmitt et al. Speckle in Optical Coherence Tomography. J Biomed Opt. 4(1), 95-105 (Jan 01, 1999)
2 Yali Jia et al. Quantitative optical coherence tomography angiography of vascular abnormalities in the living human eye. April 20 in the Proceedings of the National Academy of Sciences. www.pnas.org/content/112/18/E2395
Further information at www.haagstreituk.com