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 Table of Contents  
CURRENT OPHTHALMOLOGY
Year : 2021  |  Volume : 9  |  Issue : 1  |  Page : 18-23

Optical coherence tomography angiography: Unveiling the new entity in glaucoma diagnostics


Guru Nanak Eye Centre, New Delhi, India

Date of Submission15-Apr-2020
Date of Decision20-May-2020
Date of Acceptance07-Oct-2020
Date of Web Publication10-Apr-2021

Correspondence Address:
Jigyasa Sahu
A-24 Vrindavan Apartments, Sector-6, Plot-1, Dwarka, New Delhi - 110 075
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/jcor.jcor_43_20

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  Abstract 


Optical coherence tomography angiography (OCT-A) is an emerging technology in the field of glaucoma, probably due to its role in potentiating early diagnosis as well as evaluating subtle positive effects after therapy. Being a noninvasive modality, it is gaining wide popularity in ophthalmic diagnostics. Recent studies have shown a decrease of different blood flow indices like peripapillary and macular vessel and perfusion density in glaucoma patients when compared to the normal population. It has been shown to have acceptable repeatability and reproducibility. This article aims to discuss the pros and cons of imbibing OCT-A in the armamentarium of glaucoma diagnostics. Furthermore, limitations and fears of such a step have been discussed along with the scope for further research areas. Its relative newness, cost inefficiency, and lack of normative data pose diagnostic dilemmas to glaucoma specialists. On the other hand, the never extinguished inquisitiveness of studying blood flow in glaucoma has been sustained by growing research in this field.

Keywords: Glaucoma, optical coherence tomography angiography, optical microangiography, vessel density


How to cite this article:
Sahu J. Optical coherence tomography angiography: Unveiling the new entity in glaucoma diagnostics. J Clin Ophthalmol Res 2021;9:18-23

How to cite this URL:
Sahu J. Optical coherence tomography angiography: Unveiling the new entity in glaucoma diagnostics. J Clin Ophthalmol Res [serial online] 2021 [cited 2021 Jun 22];9:18-23. Available from: https://www.jcor.in/text.asp?2021/9/1/18/313475



Optical coherence tomography angiography (OCT-A) is a no-injection, dye-free method for visualizing ocular vasculature. Beginning from the first description of OCT-A in delineating retinal and choroidal vessels, it has come a long way to now being described for iris and anterior segment vasculature also.[1] It aims to contrast blood vessels from static tissue by assessing the change in the OCT signal caused by flowing blood cells. The importance of understanding the vascularity of the eye cannot be emphasized enough. Wide clinical applications of OCT-A have already been discussed by retina specialists, be it visualizing the capillary non-perfusion areas in diabetic retinopathy or localizing the abnormal vasculature in choroidal neovascular membrane or idiopathic polypoidal choroidal vasculopathy.

The vascular theory of glaucoma is not new. Findings such as optic disc hemorrhage, presence and enlargement of peripapillary atrophy, high prevalence of vasospastic phenomenon like migraine and raynauds and possible effect of nocturnal hypotension point to a role of vascular dysregulation in development and progression of glaucoma. Radial peripapillary capillaries are a fine vascular network in association with the optic nerve head (ONH) hypothesized to have a role in glaucoma. Time and again, modalities like Doppler, fundus fluorescein angiography , and laser speckle flowmetry have been used to revisit the role of vascular theory in glaucoma.

In this article, we will be discussing how this non-invasive technique has the potential to bring a paradigm shift in glaucoma diagnostics.


  Principle of Optical Coherence Tomography Angiography Top


OCT-A based on amplitude or intensity was initially described in 2005 when Barton and Stromski[2] adapted laser speckle analysis for time-domain OCT. In principle, OCT-A compares sequential B-scans acquired at the same location to detect change. As stationary structures would appear static in sequential B-scans, changes detected by OCT-A are largely attributed to erythrocyte movement in the perfused vasculatures. A number of algorithms, such as split-spectrum amplitude-decorrelation angiography (SSADA), OCT-A ratio analysis (OCTARA), and optical microangiography (OMAG) have been devised to compute blood flow measurements from the sequential B-scans.[3],[4]

Several OCT manufacturers now offer OCT devices, including algorithms enabling the practitioner to obtain regular OCT B-scans as well as volumetric angiographic images. So far, Angiovue OCT-A (Optovue Inc., Fremont, California) based on the SSADA algorithm, Zeiss AngioPlex (Cirrus HD-OCT 5000, Zeiss Meditec. Inc.) based on OMAG algorithm and Swept-Source OCT-A employed in a swept-source OCT DRI Triton (Topcon DRI OCT Triton Swept-source OCT, Topcon, Japan) using the OCTARA algorithm are commercially available. Prototypes of the Spectralis OCT2 module (Heidelberg Engineering, Germany) with a full spectrum amplitude decorrelation algorithm, and a prototype of AngioScan (RS-3000 Advance OCT, Nidek Co., Ltd., Japan) based on a complex decorrelation algorithm are currently being tested. Further, there are other OCT-A modules under development, such as the OCT-A system in the Copernicus Revo and REVO NX by OPTOPOL.[5]


  Technique of Obtaining Angiographic Image for Glaucoma Diagnostics Top


The OCT-A is essentially done similar to routine retinal OCT scans. Though various companies claim to obtain scans in an undilated pupil too, the best of scans are achieved with a semi/full dilated pupil. Vessel density is defined as the percentage area occupied by the large vessels and microvasculature in a particular region. There are three angiographic fields of view available in the Cirrus machine including 3 mm × 3 mm, 6 mm × 6 mm, 8 mm × 8 mm with the 6 mm × 6 mm scan being most widely used for both discs as well as macula. Conventionally selecting either of the three modes centers a square of the said dimensions over the macular region. Disc angiography is performed using 6 mm × 6 mm scan manually centering the target square over the disc [Figure 1]. Various OCT-A image artifacts can routinely impede the quality of the scan obtained. These include weak signals, motion artifacts and projection artifacts. A weak signal could arise due to media opacities like cataract, small pupil size, and beam defocus. Motion artifacts can be due to saccades or blinks, which may manifest as motion lines [Figure 2], vessel duplication, and breaks in vascular continuity. Projection artifacts, on the other hand, are shadows of superficial vasculature on deeper layers of the retina.[6]
Figure 1: Optical coherence tomography angiography image of peripapillary (surrounding disc) vasculature in a normal individual analysed quantitatively with grid in Angioplex (Cirrus HD-optical coherence tomography 5000, Zeiss Meditec. Inc.)

Click here to view
Figure 2: Motion artefacts compromising image quality and providing false low vessel density values. (a) angiographic image of a superficial layer in the peripapillary region showing reduced vessel density and capillary drop out zone (red arrow). (b) Structural image of superficial layer in peripapillary region showing black band due to motion artefact (red arrow)

Click here to view


Recently ONH angiography 4.5 mm × 4.5 mm has been incorporated in the latest software update of Cirrus HD-5000, which offers machine automated centration of the target square over the disc. The machine offers eye-tracking for reducing motion artifacts, but in practice due to longer scan times compared to OCT, OCT-A scan quality is frequently compromised due to motion. Furthermore, the low visual acuity and fixation difficulties in advanced glaucoma patients lead to further degradation of angiographic imaging. All these factors emphasize on the importance of checking fundus image quality as well as the signal strength before starting to interpret or quantify OCT-A images for glaucoma diagnosis.

Once a good quality angiographic image has been obtained, the next step is to select the correct segmentation boundaries [Figure 3]. For peripapillary vessel densities, usually the superficial layer is quantitatively analyzed by selecting the grid option. This option eliminates the need to transfer the image to external image software (imageJ, MATLAB, etc.) for calculation of vessel density. Inbuilt quantifiable parameters minimize the risk of loss of image quality during transfers. Some of the most commonly reported measurements in the literature include vessel density (percentage of detected vessel area over the imaged area), flow index (representing average decorrelation signal), and blood flux index (the mean flow intensity in the vessel area). It is noteworthy that these indices are surrogate measures and their validity for measurement of blood flow remains to be investigated. The segmentation slab also varies among different devices and this may be a reason for inconsistency in the results of different machines.
Figure 3: Segmentation slabs of Angioplex (Cirrus HD-optical coherence tomography 5000, Zeiss Meditec. Inc.)

Click here to view



  Optical coherence tomography angiography and Glaucoma Top


OCT-A gives us insights into its role in glaucoma diagnostics by both quantitative and qualitative ways.

In recent years there has been a sudden growing interest in finding correlation between various vascular parameters and glaucoma. Different companies have ventured into different segmentation patterns and different algorithms for the calculation of quantitative vascular data. For any new test to be incorporated into the diagnostic/prognostic algorithm the repeatability and reproducibility has to be ascertained. OCT-A has acceptable repeatability and reproducibility, with the coefficient of variation below 7% over a range of parameters, including those from the macula, the optic disc, and the peripapillary region, and for all 3 of the algorithms used (SSADA, OCTARA, and OMAG). Signal strength index values of the scans also positively correlated with the intra-visit repeatability of OCT-A measurements.[7],[8],[9],[10],[11],[12],[13],[14]

Literature review gives us a peek into how almost majority evidence talks about reduced optic nerve vascularity in patients of glaucoma. Furthermore, the diagnostic ability increased with increasing severity of glaucoma,[15],[16],[17] illustrating that increasing severity of glaucoma was correlated with more pronounced vascular and structural damage.

Liu et al. did one of the pioneer works on the role of OCT-A in glaucoma in 2012-2014, where they found low ONH perfusion and attenuation of the normally dense microvasculature in glaucoma eyes as compared to normal eyes. They also found a positive correlation between disc flow index and the visual field pattern standard deviation.[18] Liu et al. also found the qualitative and quantitative reduction of peripapillary vessel density and flow index in glaucoma eyes compared to normal eyes.[8] Wang et al. further supported the findings in 62 glaucoma eyes and also went on to find a direct correlation between retinal nerve fiber layer (RNFL), ganglion cell complex (GCC), and OCT-A vessel density.[17] Ichiyama et al. observed that the capillary dropout matched spatially to areas of RNFL defects[19] [Figure 4].
Figure 4: Angiography results supplementing optical coherence tomography retinal nerve fibre layer findings in a glaucoma patient. (a) Optical coherence tomography angiography image of peripapillary vasculature in a glaucoma patient showing reduced vessel density and capillary drop out area in inferior sector (red arrow) (b) Structural image showing wedge shaped darker area corresponding to area of decreased vessel density (c) retinal nerve fibre layer thickness map of the same patient showing an inferior notch in the disc (d) retinal nerve fibre layer deviation map showing inferior red areas (loss of nerve fibres) corresponding to angiographic vessel density loss in inferior sectors (black arrow)

Click here to view


Packed with such evidence, researchers were determined to find out if this diagnostic surprise could help us pre-diagnose glaucoma or provide us with a new method to know the type and severity of glaucoma. This gave rise to studies that showed vascular parameters of OCT-A had better discriminatory abilities than structural ones (like RNFL) for differentiating between pre-perimetric and perimetric glaucoma.[20],[21],[22] Along with peripapillary vasculature assessment, a role of macular vessel density was also explored. Both parameters were seen to decrease in glaucoma patients, with maximum correlation seen in infero-temporal and supero-temporal regions.[23],[24],[25],[26]

OCT-A has added to the diagnostic proficiency when combined with OCT RNFL.[27] An important finding in multiple studies was that peripapillary, optic disc, and macular OCT-A parameters showed a stronger functional association with visual fields compared to the functional association of nerve fiber layer with fields.[28],[29],[30],[31] This finding suggested that probably OCT-A parameters (vessel density, flow index, and blood flow index) could act as better visual function biomarkers in glaucoma eyes than the OCT parameters (RNFL and GCC). Vessel density measurements may also offer advantages in early diagnosis since vessel density asymmetry showed significantly higher area under curve (AUC) for differentiating suspicious discs from healthy ones compared with RNFL thickness asymmetry.[32]

Another major reason that reckons the need for OCT-A incorporation in glaucoma diagnostics is the floor effect that is encountered with OCT in advanced glaucoma. Rao et al. showed, in their study, that in later stages of glaucoma (visual field mean deviation between–20 and–30 decibels), the diagnostic ability of vessel density was better than that of the RNFL[33],[34] declaring OCT-A parameters in the peripapillary area to be better biomarkers in advanced glaucoma than OCT parameters, with a less pronounced floor effect in OCT-A than in OCT.

Another pathology where RNFL thickness measurements are supposedly not very accurate is myopia and atypical ONH morphology. In glaucoma with high myopia, the relationship of the visual field and peripapillary vessel density is significantly greater than the corresponding RNFL thickness by OCT. Perifoveal perfusion is also altered in myopia with torted discs.[35] Thus, in these cases, also OCT-A provides better diagnostic accuracy than OCT parameters.

Is the role of OCT-A in glaucoma limited to superficial layers? was the next question! Deeper retinal layer studies revealed that the association was not as strong as that of the superficial.[12],[36],[37],[38],[39] This could be explained by either no true relation or a masking effect due to projection artifacts casted by superficial layers on the deeper ones. Recently choroidal layers were also studied for possible linkage with glaucoma. It was observed that parapapillary microvascular deficit was seen in deeper choroidal layers in glaucoma patients. These patients also had a higher prevalence of lamina cribrosa defects, a lower vessel density, a lower visual field mean deviation, and lower RNFL and choroidal thicknesses.[40],[41]

Spectral domain OCT-A was also used to investigate the peripapillary microvasculature of glaucoma patients with and without lamina cribrosa defects.[42] The peripapillary region was found to have a lower vessel density in the group with lamina cribrosa defects. The regions of the microvascular impairment corresponded to the location of lamina cribrosa defects. These findings suggested a causal relationship between lamina cribrosa defects and microvascular abnormalities in the disc.

Another area of interest was whether one could differentiate between the subsets of glaucoma by angiography or if a specific subtype (say normal tension glaucoma [NTG]) was more relatable to a vascular phenomenon. OCT-A findings substantiated the presence of vascular deficit in NTG eyes too.[13],[43],[44] However, there is a paucity of studies comparing NTG and primary open-angle glaucoma (POAG), leading to unclear results.[13],[43] When angle-closure glaucoma was compared to POAG, it was seen that a uniform reduction of vessel density is found in angle-closure glaucoma while a regional reduction is usually found in POAG.[17],[45] This could probably be explained by the fact that repeated acute spike of intraocular pressure in angle-closure glaucoma eyes leads to a more generalized vascular compromise due to a mechanical effect, whereas in POAG, this was due to a sustained sectoral ischemic effect.

Limitations and future directions

A major limitation of OCT-A remains the motion artifacts which degrade image quality substantially and lead to confusion in intra and inter visit differences. Secondly, operator dependency cannot be disregarded as it can significantly influence quantification. Thirdly, there is a paucity of normative databases and knowledge of epidemiologic variability. Since OCT-A is a relatively new entity long-term studies are still underway. We still fail to understand whether vascular abnormalities detected by OCT-A are a cause or a consequence of optic nerve damage in glaucoma. This temporal association could empower us with a marker to detect the population at risk of developing glaucoma. It is important to note that vessel density may depend upon IOP changes, systemic perfusion status, vascular dysregulation, retinal oxygenation, and hypercapnia at the time of measurements.[46],[47],[48],[49] The literature is limited regarding its ability to detect the progression of glaucoma. Finally, the reversibility of vasculature after the intervention to lower IOP is another area which needs testament. Anterior segment angiography could play a role in determining bleb vascularity in operated trabeculectomies and neovascularization of the iris in case of chronic uveitis and neovascular glaucomas.


  Conclusion Top


To conclude, the fundamental understanding of OCT-A in glaucoma remains mysterious and difficult to a large extent even now. Its wow factor in glaucoma still needs to be elucidated. Nevertheless, OCT-A has definitely emerged as a reliable, objective technique with an acceptable repeatability and reproducibility.[50] OCT-A has an equivalent power to differentiate between normal and glaucoma eyes and when combined with OCT, is supplemental to the distinction. Studies have suggested its potential in categorizing differences between different types of glaucoma also. In addition, the ability to quantify angiographic information allows objective monitoring of treatment response. Given the encouraging results, we believe that in near future OCT-A may become a part of routine glaucoma diagnostics, apace with OCT and visual field testing!

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
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