Adriano Carnevali

Optical coherence tomography angiography of myopic choroidal neovascularisation

Background/aims To describe the morphological features of choroidal neovascularisation (CNV) and to report the ability of optical coherence tomography angiography (OCT-A) to detect the presence of myopic CNV by means of this new technique. Methods Myopic CNV cases were individuated from a pool of patients with pathological myopia consecutively presenting between October 2015 and March 2016. OCT-A images were assessed for classification of morphological features, and to estimate sensitivity and specificity. Results Thirty-six eyes of 28 consecutive patients with myopic CNV were included. In 4 out of 36 eyes it was not possible to classify the CNV ‘shape’, ‘core’, ‘margin’ and ‘appearance’ because the vascular network was not clearly visualised due to the poor quality of the examination. CNV shape on OCT-A was rated as circular in 9 eyes and irregular in 23 eyes. CNV core was visible in 11 eyes. CNV margin was considered as well defined in 16 eyes and poorly defined in 16 eyes. CNV appearance showed an ‘interlacing’ aspect in 16 eyes and a ‘tangled’ aspect in the other 16 eyes. A total of 11 CNVs were defined as active, 9 of which (81.8%) were interlacing, while a total of 21 were inactive, 14 of which (66.7%) were tangled. OCT-A sensitivity turned out to be 90.48% and specificity was 93.75%. Conclusions We describe the OCT-A features of myopic CNV secondary to pathological myopia and demonstrate its high sensitivity and specificity for neovascular detection. Qualitative evaluation of OCT-A characteristics may allow one to recognise different patterns, possibly corresponding to different degrees of neovascular activity.

Choroid morphometric analysis in non-neovascular age-related macular degeneration by means of optical coherence tomography angiography

Aims To describe the vascular changes in patients affected by non-neovascular age-related macular degeneration (AMD), featuring reticular pseudodrusen (RPD), drusen, or both RPD and drusen by means of optical coherence tomography angiography (OCT-A). Methods Cross-sectional observational case series. Patients with non-neovascular AMD presenting at the Medical Retina Service of the Department of Ophthalmology, University Vita-Salute San Raffaele in Milan were recruited. Patients underwent best-corrected visual acuity, biomicroscopy, infrared reflectance, short-wavelength fundus autofluorescence and OCT-A (AngioPlex, CIRRUS HD-OCT 5000, Carl Zeiss Meditech, Dublin, USA). Main outcome was quantification of vessel density, stromal tissue, and vascular/stromal (V/S) ratio at the choriocapillaris (CC), the Sattler and Hallers and the whole choroid layers among different groups of patients with non-neovascular AMD by means of binarised OCT-A scans. Results 45 eyes of 34 patients were enrolled (15 eyes of 11 patients with RPD, group 1; 15 eyes of 11 patients with drusen, group 2; 15 eyes of 12 patients with mixed phenotype, group 3). The CC, the Sattler and Hallers and the whole choroid vessel density were reduced in all groups of patients (p=0.023, p=0.007 and p=0.011 in group 1, group 2 and group 3 for the CC; p=0.021, p=0.037 and p=0.043 in group 1, group 2 and group 3 for the Sattler and Hallers density; p=0.016, p=0.002 and p<0.001 in group 1, group 2 and group 3 for the choroidal density), with significantly lower V/S ratios compared with healthy controls. Conclusions Patients with non-neovascular AMD show significant choroidal vascular depletion and fibrotic replacement, suggesting a possible role in the pathogenesis and progression of the disease.

Reproducibility and reliability of optical coherence tomography angiography for foveal avascular zone evaluation and measurement in different settings

Purpose: Optical coherence tomography angiography (OCTA) allows delineating the foveal avascular zone (FAZ) easily and noninvasively. The present study aims to test reproducibility and reliability of FAZ evaluation by means of OCTA in different settings. Methods: Twenty-four eyes of 24 normal subjects were investigated using AngioVue OCTA Imaging System. A series of OCTA acquisitions were taken both in basal and in different experimental settings after vasoactive stimuli. Images were evaluated separately by two operators and FAZ area was measured both manually and using the built-in automated measurement tool. Results: No differences for FAZ area were found in the repetition of basal acquisitions, neither in manual nor in automated measurement (0.215 ± 0.06 vs. 0.216 ± 0.07, and 0.268 ± 0.05 vs. 0.264 ± 0.09, first vs. second basal measurement in square millimetres for manual and automated evaluation, P = 0.25 and P = 0.35, respectively). Interoperators correlation was optimal (r2 = 0.978 [95% CI 0.981–0.976]). No differences were found among the other settings, which included first basal and then repeated (second) in the morning, after flickering light stimulus, after a Bruce treadmill stress test, after 30 minutes dark adaptation, and basal in the evening, neither in automated nor in manual measurements. Automated measurements for nonflow areas provided significantly larger diameters than manual ones. Conclusion: AngioVue OCTA Imaging System produces highly reproducible FAZ images with a high interoperators concordance level. Optical coherence tomography angiography capability to detect FAZ area seems not to be influenced by any of the vasoactive stimuli considered in the current study. Nonflow areas seem to be larger when measured automatically than manually.

Optical Coherence Tomography Angiography of Diabetic Retinopathy

PURPOSE To describe the optical coherence tomography angiography (OCTA) features of diabetic retinopathy. METHODS Literature review and case series. RESULTS Four cases are presented. CONCLUSION OCTA is an effective method for evaluating retinal changes in diabetic retinopathy and represents a novel complement or alternative to fluorescein angiography. Although OCTA should currently be considered an investigational technique, in the near future, it may play key roles in the diagnosis and management of diabetic retinopathy.

CLINICAL SPECTRUM OF MACULAR-FOVEAL CAPILLARIES EVALUATED WITH OPTICAL COHERENCE TOMOGRAPHY ANGIOGRAPHY.

Purpose: To describe macular-foveal capillaries (MFC) by means of optical coherence tomography angiography and to identify the clinical spectrum of this angiographic feature. Methods: Patients with MFC presenting at the Medical Retina & Imaging Unit of the Department of Ophthalmology, University Vita-Salute San Raffaele in Milan were recruited. Patients underwent a complete ophthalmologic examination that included slit-lamp examination, fundus examination, measurement of best-corrected visual acuity, fundus autofluorescence, and spectral-domain optical coherence tomography (Spectralis HRA + OCT; Heidelberg Engineering, Heidelberg, Germany). Fluorescein angiography was performed in selected cases. Optical coherence tomography angiography was performed through Zeiss prototype (AngioPlex, CIRRUS HD-OCT models 5000; Carl Zeiss Meditec, Inc, Dublin, OH). Results: Twelve eyes of 10 consecutive white patients (5 men and 5 women; 50%) presenting MFC were included. Mean age was 66.2 ± 10.2 years (range, 53–79 years); mean best-corrected visual acuity was 0.1 ± 0.13 logarithm of the minimum angle of resolution (range, 0–0.4 logarithm of the minimum angle of resolution, corresponding to 20/20 to 20/50). Mean central macular thickness was 348 ± 57.6 &mgr;m. Two patients were affected by macular pucker, two by postsurgical macular edema, two by age-related macular degeneration, one by diabetic retinopathy, one by dome-shaped macula, one presented with chronic serous chorioretinopathy, and one with branch artery occlusion. Six eyes disclosed a complete absence of the foveal avascular zone, whereas the six other cases showed a partial foveal avascularity. No significant difference was found between complete and incomplete MFC with regards to best-corrected visual acuity (P = 0.272) and central macular thickness (P = 0.870). Conclusion: Cases of persistent MFC are heterogeneous in demographic characteristics, fundus appearance, and visual function. However, MFC, presenting either as complete absence of the foveal avascular zone or only partial foveal avascularity, may complicate different retinal abnormalities or represents a coincident finding.

Optical coherence tomography angiography: evolution or revolution?

Fluorescein angiography (FA) and indocyanine green angiography (ICGA) are gold standard diagnostic tools to study retinal vessels in clinical practice. Both FA and ICGA require intravenous dye injection, which can result in nausea and, rarely, anaphylaxis [1,2]. Leakage of dye in the later frames of the angiogram is used to identify any injuries like retinal vascular abnormalities or choroidal macular neovascularization (MNV). Optical coherence tomography angiography (OCT-A) is a new method for visualizing the retinal vasculature and choroidal vascular network. It is a dye-free, rapid, and threedimensional (3D) method. OCT-A is based on algorithms that convert multiple A-scans to OCT-A images. OCT angiograms are co-registered with OCT B-scans that are obtained concurrently, allowing for visualization of both retinal flow and structure in tandem. Images are based on the concept that in a static eye the only moving structure in the fundus of the eye is blood flowing through its vessels and contrast is generated based on the difference between moving cells in the vasculature and the static surrounding tissue. Technology for OCT-A is based on different types of algorithm such as split-spectrum amplitude-decorrelation angiography (SSADA), optical microangiography (OMAG) or fullspectrum amplitude-decorrelation angiography (FSADA-ADA). SSADA technology splits the OCT image into different spectral bands, increasing the number of usable image frames and it is developed to minimize scanning time. OMAG is a recently developed imaging technique that produces 3D images of dynamic blood perfusion within micro-circulatory tissue beds at an imaging depth up to 2.0 mm [3,4]. Finally, FSADA-ADA technology guarantees clear differentiation between blood flow and static tissue without sacrificing axial resolution (i.e. depth resolution) in OCT images. Although OCT-A is a promising tool, it is currently affected by image artifacts, which may be at risk of misinterpretation by the clinician. As described by Spaide et al. [5], artifacts consist either in visualization of unwanted or loss of necessary information. The most common artifacts belonging to the former category are: (i) projection artifacts, where both a vascular or avascular structure is erroneously visualized in the tissue below (i.e. superficial retinal vessels projection in deeper retinal layers, intraretinal pigment, or highest part of drusen resembling vascular structure); (ii) eye-motion artifacts, seen as horizontal white lines in conjunction with lateral displacement of the image. Regarding the latter category of artifacts, most common are: (i) media opacity, masquerading vessels below; (ii) intraor subretinal deposit (i.e. drusenoid or vitelliform materials, blood), which can create a focal defect underneath; (iii) blood flow too slow or fast to be detected (i.e. microaneurysm). Several algorithms have been developed in order to deal with artifacts (i.e. eye tracking, motion artifacts subtraction, projection removal); however, many other artifacts can arise in the post-processing phase, including defect in layer segmentation in pathologic eyes (i.e. degenerative myopia, wide pigment epithelial detachment, tissue atrophy) or, paradoxically, generated by the artifacts-correction algorithms themselves (i.e. vessel doubling, stretch artifacts). Although clinical applications of OCT-A embrace the entire spectrum of chorioretinal diseases, the most promising fields are those vessel-related, including age-related macular degeneration (AMD), MNV, diabetic retinopathy, retinal vascular occlusion, inflammatory diseases, macular telengectasia. With regard to AMD, OCT-A permits to study MNV, including type 1 (subretinal pigment epithelium), type 2 (subretinal), type 3 (intraretinal, also known as retinal angiomatous proliferation), and polypoidal choroidal vasculopathy [6]. OCT-A can also demonstrate quiescent non-exudative neovascularizations even in asymptomatic patients [7,8]. The individuation of MNV prior to their activation may be useful to identify a population at risk of developing symptomatic AMD [7,8]. Morphological changes of vascular network following antiangiogenic treatment have been elucidated by OCTA. Huang and colleagues [9] observed MNV shrinkage 2 weeks after treatment, followed by MNV resumption at 4 weeks and fluid recurrence at 6 weeks. Assessment of exudative AMD activity with OCT-A is extremely attractive and, in the future, OCT-A may guide the timing of treatment prior to fluid recurrence. Another interesting application of OCT-A is the study of MNV in chronic central serous chorioretinopathy (CSCR), which seems to be more frequent than previously thought. OCTA can individuate MNV in CSCR with high specificity, sensitivity, and perfect agreement with FA [10]. However, abnormal

Ultra-wide-field fluorescein angiography in diabetic retinopathy: A narrative review

Fluorescein angiography (FA) is a useful examination in patients suffering from diabetic retinopathy (DR). Traditional angiograms explore 30°-50° of the retina at once; however, visualization of peripheral retina is fundamental in order to assess nonperfused areas, vascular leakage, microvascular abnormalities, and neovascularizations. In order to expand the field of view, wide-field and ultra-wide-field imaging has been developed allowing to image up to 200° of retinal surface in one single shot. The aim of this narrative review was to provide an overview of the role of the most recent technique of ultra-wide-field fluorescein angiography in DR.

Optical coherence tomography angiography findings in laser maculopathy

Purpose Handheld laser pointer thermal injury affects primarily the retinal pigment epithelium (RPE). However, so far no study has reported on the possible effects of laser pointers in the deeper layers, beneath the RPE. Here, we describe the spectral-domain optical coherence tomography angiography findings in the choriocapillaris of a patient with laser maculopathy. Methods A 13-year-old boy presented to our department with decreased vision in the left eye 12 hours after having stared at the beam of a laser pointer. Results Structural optical coherence tomography (OCT) showed 2 focal hyperreflective columns at the fovea extending from the RPE, involving all outer retinal layers, and terminating at the outer plexiform layer. The patient also underwent OCT angiography (OCT-A), which in the choriocapillary segmentation revealed 2 hypointense lesions in correspondence of the focal hyperreflectivities detected on structural OCT. We hypothesize that the OCT-A findings could represent a rarefaction of the choriocapillaris. However, the choriocapillary OCT-A findings could also represent artifacts due to the overlaying hyperreflective lesions. Conclusions It is known that the RPE is primarily damaged by the laser injury. Our findings suggest that the thermal injury could involve also the choriocapillaris, and thus not limited to the RPE. Multimodal imaging in laser maculopathy including OCT-A may lead to a better comprehension of the pathogenesis of laser retinal damages.

Optical coherence tomography angiography in the evaluation of geographic atrophy area extension

Purpose To investigate the application of optical coherence tomography angiography (OCT-A) in evaluation of geographic atrophy (GA) secondary to age-related macular degeneration (AMD). Methods Patients with GA were prospectively enrolled and studied with blue fundus autofluorescence (FAF), en face structural OCT, and OCT-A. OCT-A images were acquired using a slab of whole choroid, whereas en face structural OCT images were obtained at the ellipsoid zone (EZ), at the choroidal (CH) level, and at the scleral (SC) level. Three readers independently measured the GA extension areas and evaluated the foveal sparing in each examination. Intraobserver/interobserver agreements and agreement between each couple of imaging techniques were assessed. Results A total of 47 eyes (26 patients, mean age 76 ± 7 years) with GA (mean area using FAF: 8.77 ± 5.00 mm2) were included. Intraobserver and interobserver agreement was excellent for all imaging techniques (intraclass correlation coefficient [ICC] > 0.985), even if en face EZ structural OCT revealed the poorest quality agreement limits. Considering the analysis between each couple of imaging techniques, ICC was excellent between OCT-A compared with FAF (ICC: 0.995), followed by en face structural OCT at CH level (ICC: 0.992), at SC level (ICC: 0.986), and at EZ level (ICC: 0.973). No differences were detected between multifocal and monofocal GA lesions. Considering the evaluation of foveal involvement, lower agreements were disclosed between FAF and all other imaging techniques. Conclusions OCT-A is a reliable technique for easily visualizing and quantifying GA with the advantages, compared to current imaging techniques, of offering together both structural and blood flow information regarding retinal and choroidal layers and excluding choroidal neovascularization.

Choroidal neovascularization and coincident perforating scleral vessels in pathologic myopia

Purpose To describe the coincidence of perforating scleral vessels and choroidal neovascularization (CNV) in pathologic myopia. Methods Medical records and multimodal imaging were reviewed from patients with CNV secondary to pathologic myopia who presented to the Medical Retina and Imaging Unit of San Raffaele Hospital in Milan between October 2015 and March 2016. Main outcomes were the prevalence of coincident perforating scleral vessels and overlying CNV and association between perforating scleral vessels and CNV position within the macula and neovascular activity. Results Forty-one eyes of 39 patients (6 male, 33 female, mean age 63.7 ± 14.1 years) with CNV secondary to pathologic myopia were included in the study. Scleral perforating vessels (average number of perforating vessels per eye 2.1 ± 1.0) were found in 29 out of 41 eyes (70.7%) at the site of CNV. There was no association between presence of perforating vessels and neovascular activity or CNV position. Conclusions Perforating scleral vessels are often coincident with myopic CNV. We hypothesize that scleral vessels located beneath myopic CNV can play a role in neovascular development.