OCT Angiography in Children

Michele Fortunato

OCT Angiography in Children

COORDINATOR: Angela Turtoro CONTRIBUTORS: Francesco Bandello, Enrico Borrelli, Gilda Cennamo, Francesco Gelormini, Luciano Gravina, Bruno Lumbroso, Arcangelo Menna, Feliciana Menna, Chiara Nardella, Alfredo Pece, Francesca Periti, Carmen Plaitano, Giuseppe Querques, Marco Rispoli, Riccardo Sacconi, Maria Cristina Savastano, Filippo Simona, Angela Turtoro

Translated by Domenica Modarelli Revised and edited by Leila Myftija

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2021 © Copyright 2019 ISBN 978-88-31256-10-0 978-88-31256-35-3

All the authors do not have any financial interests.

All rights reserved, especially the right of publication and circulation, as well as the right of translation.

No part of the work can be reproduced in any form, through photocopies, microfilm, CD-ROM or other electronic means, without the written consent of the publisher or the authors. Data, figures, opinions, and assertions contained herein are the sole responsibility of the authors and not of the publisher.

AUTHORS Francesco Bandello Ophthalmology Department, IRCCS San Raffaele Hospital, Milan

Enrico Borrelli Ophthalmology Department, IRCCS San Raffaele Hospital, Milan

Gilda Cennamo Federico II University, Naples

Luciano Gravina ASL (Local Public Health Unit) Caserta

Francesco Gelormini Ophthalmology Department, IRCCS San Raffaele Hospital, Milan

Michele Fortunato Bambino Gesù Hospital, Rome

Bruno Lumbroso Italian Macula Center, Rome

Arcangelo Menna Hospital of the Annunziata, Naples

Feliciana Menna FMH Ophthalmology and Ophthalmic Surgery, Locarno, Switzerland

Chiara Nardella Dermopatic Institute of the Immacolata, IRCCS, Rome

Alfredo Pece Melegnano Hospital, Milan

Francesca Periti IRCCS San Matteo Hospital, Pavia

Carmen Plaitano IRCCS San Matteo Hospital, Pavia

Giuseppe Querques Ophthalmology Department, IRCCS San Raffaele Hospital, Milan

Marco Rispoli Italian Macula Center, Rome

Riccardo Sacconi Ophthalmology Department, IRCCS San Raffaele Hospital, Milan

Maria Cristina Savastano Italian Macula Center, Rome

Filippo Simona FMH Ophthalmology and Ophthalmic Surgery, Locarno, Switzerland

Angela Turtoro Pugliese Hospital, Catanzaro

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TABLE OF CONTENTS PREFACE ...................................................................................................................................... 7 INTRODUCTION ..................................................................................................................... 11 Chapter 1 OCT Angiography: Importance of the new application and diagnostics .......................................................... 13 Chapter 2 Pediatric retinal and choroidal vascularization .................................................................. 19 1.0 INTRODUCTION ............................................................................................................ 19 2.0 ANATOMY OF THE MACULA .................................................................................... 19 3.0 MACULAR VASCULATURE ........................................................................................ 20 3.1 RETINAL VASCULAR SYSTEM ................................................................................... 20 3.2 CHOROIDAL VASCULAR SYSTEM ............................................................................ 20 4.0 PHYSIOLOGICAL VASCULAR CHANGES OF THE MACULA IN CHILDREN ANALYZED WITH OCT-A ............................................................................................ 21 5.0 CONCLUSIONS ............................................................................................................... 24 Chapter 3 OCT Angiography in children: comparison of vascular parameters between full-term and pre-term babies .................................................................................................................. 25 1.0 INTRODUCTION ............................................................................................................ 25 2.0 MATERIALS AND METHODS ..................................................................................... 25 3.0 RESULTS ........................................................................................................................... 28 4.0 DISCUSSION .................................................................................................................... 30 Chapter 4 Congenital anomalies of the optic nerve .............................................................................. 35 1.0 INTRODUCTION ............................................................................................................ 35 1.1 ANGIOGRAPHIC EXAMINATIONS .......................................................................... 39 1.2 SPECTRAL-DOMAIN OCT ........................................................................................... 40 1.3 OCT ANGIOGRAPHY .................................................................................................... 41 1.4 COMPARING OCT-A AND FAG ................................................................................. 43 2.0 OBJECTIVE OF THE STUDY ......................................................................................... 45 3.0 MATERIALS AND METHODS ..................................................................................... 45 4.0 RESULTS ........................................................................................................................... 46 5.0 DISCUSSION .................................................................................................................... 49 6.0 CONCLUSIONS............................................................................................................... 50 Chapter 5 OCT-A and Leber-Coats Disease ........................................................................................... 51 1.0 INTRODUCTION ............................................................................................................ 51

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2.0 ANGIOGRAPHIC EXAMINATIONS AND SPECTRAL-DOMAIN OCT .............. 53 3.0 OCT ANGIOGRAPHY .................................................................................................... 56 3.1 CLINICAL CASES ........................................................................................................... 56 Chapter 6 OCT-A and pediatric glaucoma .............................................................................................. 59 1.0 PEDIATRIC GLAUCOMA ............................................................................................. 59 2.0 OCT ANALYSIS ............................................................................................................... 60 3.0 OCT-A (OCT ANGIOGRAPHY) ANALYSIS .............................................................. 62 3.1. QUALITATIVE ANALYSIS USING OCT-A ............................................................... 62 3.2. QUANTITATIVE ANALYSIS USING OCT-A ............................................................ 66 3.2.1 QUANTITATIVE INDEXES AT A MACULAR LEVEL.......................................... 67 3.2.2 ANALYZING OPTIC NERVE-RELATED QUANTITATIVE INDEXES .............. 69 4.0 CLINICAL CASES ........................................................................................................... 72 5.0 CONCLUSIONS ............................................................................................................... 79 Chapter 7 Clinical cases .............................................................................................................................. 81 1.0 MACULAR CHOROIDAL NEOVASCULARIZATION IN PATIENT WITH DIAGNOSIS OF TUBEROUS SCLEROSIS.................................................................... 81 2.0 ANGIOID STREAKS COMPLICATED BY CHOROIDAL NEOVASCULARIZATION............................................................................................. 84 3.0 DISC NEOVASCULARIZATION IN PATIENT WITH PREVIOUS ROP DIAGNOSIS....................................................................................................................... 85 4.0 AREOLAR CHOROIDAL DYSTROPHY WITH PREMATURE ONSET ................. 86 5.0 OCT ANGIOGRAPHY FOR RPE AND RETINAL HAMARTOMA........................ 88 Bibliography .............................................................................................................................. 89

PREFACE

The introduction of OCT Angiography produced a substantial change in clinical ophthalmologic practices. The possibility of viewing retinal vessels without the use of a dye injection, being able to quantify recorded data, associating them individually to different capillary layers and, finally, without having to dilate a patient’s pupil, are great benefits that contributed to changing the role of OCT Angiography as an experimental method to an alternative and, often, valid replacement for retinal fluorescein angiography. The number of retinal fluorescein angiographies performed in our wards and clinics is constantly decreasing, to the advantage of this new technique.

The benefits of an OCT Angiography are important, especially when dealing with pediatric patients who do not tolerate pupil dilation and intravenous dye injections. It is, therefore, easy to imagine that the success of OCT Angiographies in the pediatric population is bound to further increase in the near future. My friend, Michele Fortunato, did a great job in writing this book, which collects the experiences of several specialists, the first in Italy, who took an interest in the use of this new diagnostic technique for pediatric patients. I am sure that other works in the same field will soon follow this contribution. I want to congratulate Dr. Fortunato on this initiative. I hope he reaches the success that his enthusiasm and expertise surely deserve.

Francesco Bandello

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Within the cultural panorama of diagnostic imaging, there was the need for a book regarding the use of OCT Angiography (OCT-A) in pathologies affecting children and young adults. After his recent book on OCTs in children, in this publication, Michele Fortunato describes a number of pathologies for which OCT-A was implemented.

Introduced in clinical practice in just the past three years, OCT Angiography has already started arousing curiosity and interest. The possibility of performing an angiography with a dye-free method has already changed the pathophysiology of many diseases in several adult pathologies, especially macular neovascular ones, allowing for a more precise differential diagnosis but, above all, allowing for a change in follow-up methods for patients treated with intravitreal injections. Old cultural ways in a context as new as the pediatric one, but one that is still unique and replete with expert testimonials, which aid in oftentimes difficult diagnoses, offering innovative insights. In describing this new technique, Michele – who has always been at the forefront in diagnosing and treating ophthalmic pediatric diseases – knows that this is just the beginning, but he still surprises us with something entirely new in an objective but also critical and proactive manner. OCT-As have opened up a new world. Higherperforming OCT-As, which are faster and more precise, with an extremely high definition and resolution, are already leading to a decrease in the use of fluorescein angiographies that, in the pediatric field, are more complex to implement. This publication is a great incentive, when it comes to interpreting pediatric pathologies, and offers a comprehensive overview that opens realms of discussions and debates.

Congratulations to Michele and to all the authors.

Alfredo Pece

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INTRODUCTION “Performing fluorescein angiographies in pediatric patients often requires narcosis.... I hope less aggressive diagnostic equipment in clinics will be developed for children one day.” This is how I ended an interview in 2004 with a popular international journal. I would like to thank all those exceptional experts who – coordinated with great results

by Doctor Angela Turtoro – contributed to this publication, which is a follow-up to the book, “OCT in età pediatrica” (OCT in Children), and one that the Italian ophthalmologic clinical panorama certainly needed.

Michele Fortunato

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Chapter 1

OCT Angiography: Importance of the new application and diagnostics Maria Cristina Savastano, MD1 - Marco Rispoli, MD1 Bruno Lumbroso, MD1 1

Italian Macula Center, Rome

The analysis of the retinal choroidal vascular flow has always aroused interest in the ophthalmologic clinical world. In the last few years, the analysis of the retinal choroidal vasculature without the intravenous injection of a contrast medium has allowed for the study of many pathologies in various patients. OCT Angiography is a method based on high-resolution imaging techniques that are able to assess the retinal choroidal flow within vessels.1 Technically, OCT Angiography is based on an amplitude-decorrelation analysis.

Introduced in 2005 by Barton et al.2, it can register decorrelation movements.

To better understand this method, consider that this system can register the difference between static and moving signals. The only moving signal originates from blood tissue which is, therefore, registered as a decorrelation signal.

Unlike fluorescein angiography, which is currently still considered the gold standard in retinal vascular imaging, OCT Angiography has reached an exponential application in clinical daily

practice. This development is connected to the rapid execution of the diagnostic examination, without any risk for the patient, allowing for it to be easily performed even on children.

Like any newly introduced method, OCT Angiography necessitates a new means for interpreting the images generated, with the aim of identifying the parameters required in reaching a correct diagnosis. An important concept is that OCT Angiography is three-dimensional and analyzes tissue, layer by layer, based on “en-face” or frontal images. This allows to obtain actual tomographies, which correspond to the retinalchoroidal vascular layer of interest. The first identified vascular planes were the superficial vascular plexus (SVP) and the deep vascular plexus (DVP).3 Figure 1 illustrates the comparison between vascular representation in fluorescein angiography (FAG) and OCT Angiography (OCT-A). What is most evident at first sight are the overlapping vascular planes, which can be observed with FAG. Instead, the superficial (SVP)

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Figure 1. Comparison between vascular representation in fluorescein angiography (FAG) and OCT Angiography (OCT-A). FAG represents various overlapping vascular plexuses; OCT Angiography allows for scanning the various superficial (SVP) and deep (DVP) vascular planes separately.

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and deep (DVP) vascular planes can be distinguished through OCT Angiography.

These are clearly represented separately and reveal different morphological features. The superficial vascular plexus, made up of large retinal vessels with a mean diameter of 120 μm, is situated in the group of ganglion cells and has a “spider web” structure. The deep vascular plexus, made up of vessels with a mean diameter of 60 μm, is situated in the

internal core layer and external plexiform layer. The morphological aspect of this layer resembles small fans with many small horizontal and vertical interconnections.

The superficial and deep vascular plexuses are interconnected between each other through a dense web of small vertical vessels that anastomose with each other (Figure 2).

Anatomically, the retinal vascular layers are clearly described by Campbel et. al.

Figure 2. Representation of several parallel scans that, distanced at 20 micron from the superficial capillary plexus (SCP) lead to the deep plexus (DCP). The blue circle in A highlights a detail of the retinal vessel. Following its development in B and C, note how this detail leads to the view of fan-shaped vascular fraying in D. This detail demonstrates how the plexuses are interconnected, as reported in the anatomical studies.

Anatomically, the retinal vascular layers are clearly described by Campbell et al.

Their study illustrates the representation of the vascular retina in the radial peripapillary plexus (RPCP), as well as the superficial (SVP), intermediate (IVP), and deep vascular plexus (DVP).4 OCT Angiography confirmed the presence of these layers through in vivo analysis, although an analysis of the intermediate plexus finds limited application from a clinical viewpoint. Therefore, only the superficial and deep vascular plexuses are taken into consideration.

The OCT Angiography study allows to not only identify the retinal vascular plexuses, but also the choriocapillaris and choroidal ones. Moreover, it allows to analyze the avascular area situated in correspondence of the outer core plexus.

OCT Angiography is able to analyze the vascular flows within a precise range of 0.5 mm/sec and 2 mm/sec.1 This implies that the system is not able to identify flows that are too slow or too fast, therefore, they appear as areas without any flow. This happens for large choroid vessels that appear dark, since their flow

is greater than the flow established (Figure 3).

The importance of studying retinal vascular layers on different planes through OCT Angiography allows to identify anomalies in only several areas, which are often the starting point for an early diagnosis, as occurs with diabetic retinopathy. In fact, microcirculation in the early stages of diabetic retinopathy may primarily only affect the deep vascular plexus, leaving the superficial one intact. Moreover, identifying every plane, in turn, allows to precisely locate the position of the pathological process, as in the case of a neovascular membrane with flows that can be above or below the RPE. This precise distribution allows for a differential diagnosis: Type 1 neovascularization below the RPE, Type 2 neovascularization above the RPE. Another important aspect of the analysis performed through OCT Angiography is the morphology that can be identified without the indirect effect that derives from the use of a dye, as in FAG. A typical example could be the diffusion of the dye in the event of a defect in permeability. This effect – that, at a first

Figure 3. OCT Angiography allows to clearly identify the superficial vascular and the deep vascular plexuses. The avascular layer in a physiological condition does not have irregular flows. The choriocapillaris layer is clearly visible and presents a dense and regular capillary network without vascular flow in correspondence with the large choroidal vessels.

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Figure 4. Clinical case of diffuse retinal epitheliopathy caused by chronic central serous retinopathy. In the B-scan (A), there is evidence of a pachychoroid with choroidal vessels that present an increase in diameter. An intraretinal edema affects both the inner and outer core layer, and the separation of the neuroepithelium is also visible in the foveal area. A thin flat separation of the RPE can be seen in the foveal area. Autofluorescence (B) shows signs of the involvement of the large retina with gravitational epitheliopathy phenomena. The Fluorescein angiography (C) shows large areas of hyperfluorescence where spread and impregnation phenomena are not well distinguished. The OCT Angiography analysis (D) shows one area with irregular flow (detail included in the red area), which represents a neovascular membrane.

Figure 5. Example of an artifact of segmentation and its correction. The OCT-A image on the left shows an irregular flow in the superior extra-foveal area (red arrow). On the bottom left, corresponding to the visible segmentation on the B-scan, an automatic segmentation defect (blue arrow) is visible. This segmentation artifact produces a flow deriving from the choriocapillaris layer and not from the avascular one. A manual correction (central image - blue arrow) produces a real image without any artifact (on the right - red arrow).

approach in an OCT Angiography assessment might even seem counterproductive – is interesting when determining the actual morphological aspect of CNV, as well as the peripapillary neovessels of a diabetic retinopathy or the presence of irregular flows in the acute or chronic stage of Central Serous Chorioretinopathy, and so on5 (Figure 4).

Currently, many studies using OCT Angiography are being assessed in an attempt to identify special morphological markers designed to precociously diagnose or detect specific pathologies.

Although OCT Angiography has many advantages, there are also some disadvantages to be considered. The images obtained must be interpreted after the automatic segmentation of the device is carefully assessed. The presence of any possible artifacts that can lead to an incorrect diagnosis should always be taken into consideration6 (Figure 5).

Artifacts deriving from segmentation are not the only errors that may occur.

To this regard, the fact that the learning curve is not always that short should be

taken into consideration. Currently, scans of the posterior pole, and the area right beyond the arcades, can be performed, even if wide-angle assessment methods are being studied.

In the event of inflammatory retinalchoroidal pathologies, a vascular analysis does not always allow for a correct interpretation of the clinical picture. As for structural OCTs, a good transparency of the diopter media and a minimal fixation ability by the patient are required. In conclusion, we can say that the introduction of OCT Angiography has, by now, become part of daily clinical practice. The study of different pathologies through OCT Angiography is unveiling new information that will probably generate new interpretations and diagnoses in the future. As for any new method implemented, the data collected must be studied and interpreted, in order to reach a correct diagnosis.

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