The impact of intraocular pressure on optical coherence tomography angiography: A review of current evidence.

A scoping review of 45 peer-reviewed manuscripts involving intraocular pressure (IOP) change and concurrent optical coherence tomography angiography (OCTA) assessments was performed to aggregate knowledge, summarize major findings, and identify gaps in literature and methodology relating to the effect of IOP change on OCTA. Articles were identified through PubMed/Medline, Google Scholar, Cochrane, Web of Science, and article reference lists. A total of 838 results were identified, and 45 articles met the inclusion and exclusion criteria for detailed analysis. OCTA metrics including vessel density (VD), perfusion density, and flow density of the superficial capillary plexus and the radial peripapillary capillaries were analyzed in relation to relative temporal IOP changes. Overall, IOP changes were found to affect superficial vascular plexus (VD) measurements on OCTA, especially when IOP elevated above the physiologic normal range (10-21 mmHg). No significant association was found between diurnal IOP variation and OCTA metrics. Cataract surgery improved the whole-image signal strength and VD regardless of changes in IOP. Beta-blockers were associated with paradoxically reduced vessel density in normal tension glaucoma patients in two studies. Although glaucoma surgical intervention studies were inconsistent and limited by scan quality and low sample sizes, patients requiring glaucoma surgery exhibited attenuated postoperative superficial VD recovery despite significant IOP reductions with surgical intervention. In addition to ensuring near-perfect signal strength with minimal media opacities and controlling for high myopia, central corneal thickness, and the presence of retinopathy, clinicians should consider the statistically significant impact of IOP on OCTA metrics when interpreting results.

Reduced macular thickness and macular vessel density in early-treated adult patients with PKU.

PURPOSE: Macular structure is poorly evaluated in early-treated phenylketonuria (ETPKU). To evaluate potential changes, we aimed to examine retinas of PKU patients using optical coherence tomography (OCT) with additional OCT angiography (OCTA) and compare the results to healthy controls. METHODS: A total of 100 adults were recruited in this monocentric, case-control study: 50 patients with ETPKU (mean age: 30.66 ± 8.00 years) and 50 healthy controls (mean age: 30.45 ± 7.18 years). Macular thickness, vessel density and flow area of the right eye was assessed with spectral domain OCT angiography SD-OCT(A). Macular microstructural data between the ETPKU and control group was compared. In the ETPKU group, the relationship between visual functional parameters (best corrected visual acuity [VA], spherical equivalent [SE], contrast sensitivity [CS] and near stereoacuity) and microstructural alterations was examined. The dependency of OCT(A) values on serum phenylalanine (Phe) level was analysed. RESULTS: There was significant average parafoveal and perifoveal total retinal layer thinning in ETPKU patients compared to healthy controls (p < 0.016 and p < 0.001, respectively), while the foveal region remained unchanged in the ETPKU group. Whole macular and parafoveal superficial capillary plexus density was significantly decreased in ETPKU compared to controls (p < 0.001). There were no significant differences in the foveal avascular zone, nonflow area, macular superficial and deep capillary plexus between the groups. The temporal parafoveal inner retinal layer thickness was found to negatively correlate with individual Phe levels (r = -0.35, p = 0.042). There was no difference in vascular density and retinal thickness in the subgroup analysis of patients with good therapy adherence compared to patients on a relaxed diet. CONCLUSIONS: Durable elevation in Phe levels are only partially associated with macular retinal structural changes. However, therapy adherence might not influence these ophthalmological complications.

RTVue XR AngioVue Optical Coherence Tomography Angiography Software Upgrade Impacts on Retinal Thickness and Vessel Density Measurements.

Purpose: To determine the impact of an AngioVue software upgrade on total retinal thickness (RT) and inner retinal vessel density (VD) measurements derived from optical coherence tomography angiography (OCTA). Methods: Optovue OCTA images (3 × 3 mm) from 126 individuals (105 healthy eyes and 72 eyes with retinal disease) were acquired before an upgrade of the AngioVue software, which resulted in an inward shift of the outer boundary of the inner retinal vessels and improved Bruch's membrane segmentation. Total RT and inner retinal VD values were extracted before and after the software upgrade for comparison. Bias and limits of agreement (LA) were calculated. Results: The mean (SD) age of participants was 46 (17) years. Mean (LA) foveal RT increased by 3.0 (-11 to +17) and 3.7 (-11 to +18) µm (P < 0.001) and parafoveal RT increased by 9.7 (-3.8 to +23) and 6.4 (-2.5 to +15) µm (P < 0.001) in healthy and diseased retina, respectively. Mean (LA) foveal inner retinal VD decreased by 6.6 (2.5-11) and 7.7 (0.4-15) percentage units (P < 0.001) and parafoveal inner retinal VD decreased by 4.1 (1.2-7.0) and 4.7 (0.5-8.9) percentage units (P < 0.001) in healthy and diseased retina, respectively. Conclusions: The AngioVue software upgrade resulted in an unexpected increase in total RT and an expected reduction in inner retinal VD measurements in all regions due to altered segmentation. Translational Relevance: RT and VD measures derived from the newer AngioVue software version are not directly comparable to the reported normative data derived from the older software.

Vessel density and En-face segmentation of optical coherence tomography angiography to analyse corneal vascularisation in an animal model.

Background: Optical coherence tomography angiography (OCTA) is a novel non-invasive angiography technology that has recently been extensively studied for its utility in anterior segment imaging. In this study, we compared a split-spectrum amplitude decorrelation angiography (SSADA) OCTA and an Complex OCT signal difference angiography [corrected] (CODAA SD) [corrected] OCTA system to current angiographic technique, indocyanine green angiography (ICGA), to assess corneal vascularisation in an animal model. Methods: We imaged 16 rabbits, (one eye per animal) with corneal vascularisation using SSADA OCTA (AngioVue; Optovue Inc., USA), CODAA OCTA [corrected] (Angioscan; RS-3000 Nidek Co. Ltd., Japan) and ICGA in the same region of interest of the cornea at successive time-points. We then analysed all scanned images for vessel density measurements and used paired t-tests and Bland-Altman plots to examine for significant differences. The en-face segmentation images from each of the OCTA scans were also extracted and were matched at every 50 µm segmentation to be compared for vessel density at the respective depths. Results: Bland-Altman plots revealed a good agreement between all three imaging techniques (P > 0.05) for all vessel density measurements computed, and the ranges of 95% limit of agreement were acceptable from a clinical perspective. No significant difference was reported, with ICGA (µ = 16.52 ± 8.94%) being more comparable to the CODAA [corrected] OCTA (µ = 16.23 ± 9.51%; p = 0.50) than the SSADA OCTA (µ = 17.09 ± 7.34%; p = 0.33) system. Also, a good correlation value (r > 0.9) was obtained when comparing the vessel density measurements of the en-face segmentations between the OCTA systems. Conclusions: Comparable vessel density quantification between the two OCTA systems, and with ICGA was obtained. Segmentation analysis of the vasculature at different depths showed varied performance in the two OCTA systems relative to each other. The implications of the study may help to aid in the development of better OCTA algorithms for the anterior segment and its use in clinical translational research.

Intrasession Repeatability and Interocular Symmetry of Foveal Avascular Zone and Retinal Vessel Density in OCT Angiography.

PURPOSE: To measure intrasession repeatability and interocular symmetry of the foveal avascular zone area (FAZA) and superficial retinal vessel density (SRVD) using AngioVue Analytics optical coherence tomography angiography (OCTA). METHODS: Fifty healthy individuals were prospectively enrolled. OCTA scans (3 × 3 and 6 × 6 mm) were acquired twice in right and once in left eyes. FAZA (with and without rescaling) and SRVD for 18 regions (whole, fovea, parafovea, six parafoveal subregions, and nine square zones) were compared between two scans in right eyes (repeatability) and between both eyes (symmetry). Coefficients of repeatability (CRs) and limits of agreement (LAs) were calculated. RESULTS: Axial length-based image size rescaling had negligible impact on the intrasession CR of FAZA in both 3 × 3- and 6 × 6-mm images. The intrasession CRs for the foveal SRVD were 3.3% and 6.1% in the 3 × 3- and 6 × 6-mm OCTA images, respectively. Age and axial length did not influence test-retest variability of FAZA or SRVD. The interocular LAs in FAZA (0.039-0.059 mm2) was comparable to its CR. However, the interocular LAs in foveal SRVD were -4.5% to +3.8%, with 13% of the cohort showing an interocular difference greater than the CR. CONCLUSIONS: FAZA repeatability is not influenced by image size correction, and foveal SRVD is more variable in 6 × 6- than 3 × 3-mm OCTA images. Low image quality may contribute to interocular SRVD asymmetry. TRANSLATIONAL RELEVANCE: CRs and LAs can be used to set a threshold for true changes in FAZA and SRVD in longitudinal studies of healthy individuals.

Microvasculature dropout detected by the optical coherence tomography angiography in nonarteritic anterior ischemic optic neuropathy.

OBJECTIVE: To investigate microcirculation characteristics of peripapillary superficial retina and optic disc in eyes with nonarteritic anterior ischemic optic neuropathy (NAION) using optical coherence tomography angiography (OCTA). METHODS: Forty-one eyes of 30 NAION patients and 30 eyes of 30 normal subjects were evaluated with OCTA (AngioVue, Optovue). The whole vessel density, inside disc vessel density, peripapillary vessel density, and vessel densities based on the sectorial division in the nerve head mode peripapillary superficial retina and RPC mode optic disc were measured respectively. RESULTS: In the NAION group, vessel densities in both the peripapillary superficial retina and optic disc were significant reduced (P < 0.01), as compared with the control group. The whole vessel density of the optic disc in chronic NAION group were significantly lower than that in acute NAION group (P < 0.01). The whole and temporal vessel density of the peripapillary superficial retina was significantly correlated with log MAR VA (r = -0.381 and r = -0.337, both P < 0.05). Vessel densities in both the peripapillary superficial retina and optic disc were reduced (P < 0.05) in unilateral involved eyes, as compared to the unaffected fellow eyes, except for the inside disc (P = 0.270) and SN (P = 0.054) vessel density in the optic disc, while there was no difference in the fellow eyes compared to the normal eyes. CONCLUSION: In NAION patients, a dropout of microvasculature in peripapillary superficial retina and optic disc could be detected by OCTA directly. OCTA might become a useful tool for detection and monitoring of NAION. Lasers Surg. Med. 50:194-201, 2018. © 2017 Wiley Periodicals, Inc.

The application of optical coherence tomography angiography in retinal diseases.

Optical coherence tomography angiography (OCTA) is a new, noninvasive imaging technique that generates real-time volumetric data on chorioretinal vasculature and its flow pattern. With the advent of high-speed optical coherence tomography, established enface chorioretinal segmentation, and efficient algorithms, OCTA generates images that resemble an angiogram. The principle of OCTA involves determining the change in backscattering between consecutive B-scans and then attributing the differences to the flow of erythrocytes through retinal blood vessels. OCTA has shown promise in the evaluation of common ophthalmologic diseases such as diabetic retinopathy, age-related macular degeneration, and retinal vascular occlusions. It quantifies vascular compromise reflecting the severity of diabetic retinopathy. OCTA detects the presence of choroidal neovascularization in exudative age-related macular degeneration and maps loss of choriocapillaris in nonexudative age-related macular degeneration. We describe principles of OCTA and findings in common and some uncommon retinal pathologies. Finally, we summarize its potential future applications. Its current limitations include a relatively small field of view, inability to show leakage, and a tendency for image artifacts. Further larger studies will define OCTAs utility in clinical settings and establish if the technology may offer its utility in decreasing morbidity through early detection and guide therapeutic interventions in retinal diseases.

Deep Capillary Macular Perfusion Indices Obtained with OCT Angiography Correlate with Degree of Nonproliferative Diabetic Retinopathy.

PURPOSE: To evaluate the integrity of macular and temporomacular vasculature in nonproliferative diabetic retinopathy (NPDR) with noninvasive optical coherence tomography angiography (OCTA) and correlate perfusion indices with degree of NPDR. METHODS: In this prospective observational cross-sectional study, 102 eyes with newly diagnosed NPDR (mild NPDR, 36; moderate NPDR, 21; severe NPDR, 13; NPDR with diabetic macular edema [DME], 32) underwent OCTA. Sixty eyes of normal subjects served as control. Degree of NPDR (based on Early Treatment Diabetic Retinopathy Study criteria) was confirmed with fluorescein angiography. Automated OCTA/split-spectrum amplitude decorrelation angiography software generated perfusion indices (vessel density and flow index) from images of the retina. The perfusion index of superficial and deep retinal plexuses was obtained in both perifoveal (central 1-3 mm) and parafoveal (3-6 mm) areas. RESULTS: Deep plexus parafoveal vessel density was 25.23% (±6.1) in mild NPDR, 20.16% (±6.16) in moderate NPDR, 11.16% (±4.16) in severe NPDR, and 17.91% (±4.42) in NPDR + DME compared to normal subjects (36.93% [±8.1]; (p<0.01). Spearman correlation coefficient (rs) between vessel density and level of NPDR severity in the parafoveal region showed inverse correlation for both superficial (rs -0.87; p = 0.083) and deep (rs -0.96; p = 0.017) plexus. Similarly, when vessel density of the perifoveal region was compared with level of NPDR severity, inverse correlation was noted in both superficial (rs -0.85; p = 0.08) and deep (rs -0.98; p = 0.011) plexus. CONCLUSIONS: Optical coherence tomography angiography clearly delineated the retinal microcirculation and allowed quantification of vascular perfusion of each layer. As diabetic retinopathy progressed, a decrease in perfusion index is more pronounced in the deep retinal plexus and precedes changes in superficial plexus.

Optical coherence tomography angiography of macular telangiectasia type 1: Comparison with mild diabetic macular edema.

OBJECTIVE: The present study aimed to investigate the characteristics of macular telangiectasia type 1 (Mac tel type 1) using spectral-domain optical coherence tomography angiography (OCTA) and compare them with the characteristics of mild diabetic macular edema (DME), to provide a new objective method for quick clinical diagnosis and treatment. METHODS: A retrospective comparative analysis of 9 Mac tel type 1, 15 DME, and 15 normal eyes was performed using fluorescein angiography, spectral-domain optical coherence tomography, and OCTA. The morphological changes, retinal vessel density, and nonperfused areas were evaluated using split-spectrum amplitude-decorrelation angiography algorithm. RESULTS: OCTA revealed obvious saccular capillary telangiectasia and loss of parafoveal vascular density of Mac tel type 1. However, a number of line segment hyperreflective signals around the macula and more distinct nonperfusion in DME were observed. The quantitative foveal avascular zone mean area in Mac tel type 1 was larger than that in the normal eyes (0.40 ± 0.06 mm2 vs. 0.88 ± 0.19 mm2 , P < 0.001). However, the area in DME (1.52 ± 0.38 mm2 ) was larger than that in Mac tel type 1 (P < 0.001), and the foveal zone area in DME (1.127 ± 0.05 mm2 ) was also lager than it in Mac tel (P < 0.05). The vascular density of the superficial layer reduced in both Mac tel type 1 and DME (compared with normal eyes). The difference between Mac tel type 1 (49.56 ± 5.23)% and DME(44.58 ± 3.82)% was significant in the superficial capillary layer (P < 0.01). The vascular density of the retinal deep layer also reduced in both Mac tel type 1 and DME (compared with normal eyes). The difference between Mac tel type 1 (53.78 ± 7.36)% and DME (53.64 ± 4.96)% was no significant in this layer (P > 0.05). CONCLUSION: Morphological differences between Mac tel 1 and DME can be observed on OCTA. Superficial vascular density and non-perfusion area may serve as a quantitative method to identify them. Lasers Surg. Med. 49:225-232, 2017. © 2017 Wiley Periodicals, Inc.

Deep and superficial OCT angiography changes after macular peeling: idiopathic vs diabetic epiretinal membranes.

BACKGROUND: To assess changes in deep and superficial perifoveal capillary plexus after macular peeling in idiopathic and diabetic epiretinal membrane (iERM and dERM, respectively). METHODS: Cross-sectional comparative study. We included 40 eyes from 40 patients affected by iERM (20 eyes) and dERM (20 eyes), as well as 34 eyes from 17 healthy, age-matched patients. Patients received a complete ophthalmic evaluation including axial and en-face scanning spectral-domain analysis, optical coherence tomography angiography, and microperimetry. Split-spectrum amplitude-decorrelation angiography images were obtained to quantify the deep and superficial layers of perifoveal capillary-free zone (CFZ). The main outcome measures were: (i) differences at baseline between deep and superficial CFZ in iERM and dERM vs control, and (ii) changes in deep and superficial CFZ plexus after surgery in iERM vs dERM. RESULTS: The deep CFZ only significantly increased in dERM at the end of the follow-up period (6 months). No statistically significant differences were found between preoperative and postoperative superficial vascular plexus in iERM or dERM. At the end of the follow-up, statistically significant differences between preoperative and postoperative ganglion cell complex (GCC) average were found only in the iERM group. Best-corrected visual acuity significantly improved after surgery both in the iERM (P = 0.0053) and dERM (P < 0.0001) groups. After 6 months, macular sensitivity increased in the iERM group, but there was no statistically significant change in the dERM group. CONCLUSIONS: In dERM, the deep CFZ significantly increases after ILM peeling, whereas postoperative angiography changes were not significant in iERM. This could be because the impaired diabetic perifoveal capillary plexus are more sensitive to the iatrogenic damage to Müller cells, induced by peeling.

Optical Coherence Tomography Angiography in Retinal Diseases.

Optical coherence tomography angiography (OCTA) is a new, non-invasive imaging system that generates volumetric data of retinal and choroidal layers. It has the ability to show both structural and blood flow information. Split-spectrum amplitude-decorrelation angiography (SSADA) algorithm (a vital component of OCTA software) helps to decrease the signal to noise ratio of flow detection thus enhancing visualization of retinal vasculature using motion contrast. Published studies describe potential efficacy for OCTA in the evaluation of common ophthalmologic diseases such as diabetic retinopathy, age related macular degeneration (AMD), retinal vascular occlusions and sickle cell disease. OCTA provides a detailed view of the retinal vasculature, which allows accurate delineation of microvascular abnormalities in diabetic eyes and vascular occlusions. It helps quantify vascular compromise depending upon the severity of diabetic retinopathy. OCTA can also elucidate the presence of choroidal neovascularization (CNV) in wet AMD. In this paper, we review the knowledge, available in English language publications regarding OCTA, and compare it with the conventional angiographic standard, fluorescein angiography (FA). Finally, we summarize its potential applications to retinal vascular diseases. Its current limitations include a relatively small field of view, inability to show leakage, and tendency for image artifacts. Further larger studies will define OCTA's utility in clinical settings and establish if the technology may offer a non-invasive option of visualizing the retinal vasculature, enabling us to decrease morbidity through early detection and intervention in retinal diseases.

In vivo optical imaging of amblyopia: Digital subtraction autofluorescence and split-spectrum amplitude-decorrelation angiography.

BACKGROUND AND OBJECTIVES: Amblyopia is a visual impairment that is attributed to either abnormal binocular interactions or visual deprivation. The retina and choroids have been shown to be involved in the development of amblyopia. The purpose of this study was to investigate the retinal and choroidal microstructural abnormalities of amblyopia using digital subtraction autofluorescence and split-spectrum amplitude-decorrelation angiography (SSADA) approaches. METHODS: This prospective study included 44 eyes of 22 patients with unilateral amblyopia. All patients who received indirect ophthalmoscopy, combined depth imaging spectral domain optical coherence tomography (OCT), SSADA-OCT, and macular blue light (BL-) and near-infrared (NIR-) autofluorescences underwent pupil dilation. The subfoveal choroidal thickness (SFCT) was measured. BL- and NIR-autofluorescences were determined for all patients and used to generate subtraction images with ImageJ software. The superficial, deep layers of the retina, and inner choroid layer were required for SSADA-OCT. RESULTS: For the normal eyes, a regularly increasing signal was observed in the central macula based on the subtraction images. In contrast, a decreased signal for the central patch or a reduced peak was detected in 16 of 22 amblyopic eyes (72.7%). The mean SFCT of the amblyopic eyes was greater than that of the fellow normal eyes (399.25 ± 4.944 µm vs. 280.58 ± 6.491 µm, respectively, P < 0.05). SSADA-OCT revealed a normal choroidal capillary network in all fellow normal eyes. However, 18 of 22 amblyopic eyes (86.4%) exhibited a blurry choroidal capillary network, and 15 of 22 amblyopic eyes (68.2%) displayed a dark atrophic patch. CONCLUSIONS: This is the first report of amblyopia using SSADA-OCT and digital subtraction images of autofluorescence. The mechanistic relationship of a thicker choroid and choroidal capillary atrophy with amblyopia remains to be described. The digital subtraction image confirmed the changes in the microstructure of the amblyopic retina as a supplementary approach to detect the progression of amblyopia. Lasers Surg. Med. 48:660-667, 2016. © 2016 Wiley Periodicals, Inc.

Quantitative analysis of choroidal neovascularization by split spectrum amplitude decorrelation angiography OCT / 中华实验眼科杂志

Background Choroidal neovascularization (CNV) is a major cause of visual loss in many fundus diseases.Fundus angiography (FA) is essential for the diagnosis,location and treatment of CNV.However, FA is an invasive examination method.Split spectrum amplitude decorrelation angiography (SSADA) OCT can quickly and clearly provide vascular signals.However, whether SSADA-OCT is feasible in the evaluation of CNV remains unclear.Objective This study was to detect and quantify CNV using OCT angiography.Methods Thirteen patients with unilateral CNV were included in Beijing Tongren Eye Center from June 2014 to August 2014.All affected eyes of the subjects were scanned with a high-speed frequency domain OCT.The SSADA-OCT images were obtained by scanning of macula covered 6 mm×6 mm area.The CNV area and grey scale were computed from the en face OCT images of retinal layer and choroidal layer.This study followed the Helsinki Declaration and was approved by the Ethics Committee of Beijing Tongren Hospital,and written informed consent was obtain from each patient prior to any medical examination.Results SSADA-OCT angiogram revealed CNV area and location confirmed by fluorescein angiography,and the CNV blood flow information of internal limiting membrane,inner plexiform layer,retinal pigment epithelium,and choroid was exhibited by OCT angiography.All CNVs with different causes showed the well defined and hyperreflected signal in macular region.The average CNV area was (0.15 ±0.09)mm2 , and the average grey scale of CNV was 75.40±32.35 in the affected eyes,and that in the contralateral eyes was 26.99±22.87 in the 300 μm area,showing significant elevation in gray scale in the affected eyes compared with the contralateral eyes (t =6.946, P＜0.001).Conclusions OCT angiography is a noninvasive observation technique of retinal and choroidal blood flow.It can provide quantitative information and detailed images of CNV.