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Fig. 26.16 Tubercular choroidal granuloma: hypouorescence seen corresponding to the lesion in mid-phase ICGA
A. Kulkarni et al.
(e) Serpiginous choroidopathy: On ICGA, the
26.4 Conclusions
active edges of the lesion appear hypouo­rescent [39]. Late hyperuorescence is a marker of choroidal hyperpermeability and may indicate a more rapid progression of the illness. The boundaries of the healed lesions are clearly dened and appear hypouores­cent. The pigmentation of the lesion edges often appears dark on ICGA due to blocked uorescence. At the same time, the atrophy
Dye-based angiography can give detailed infor­mation about the shape, extent, and vascularity of most retinochoroidal pathologies effectively and affordably. It is invaluable in establishing diagnosis, prognosticating, and managing sev­eral diseases, making it one of the most com­monly used tools in an ophthalmologist’s
armamentarium. of the RPE and choriocapillaris enables the visualization of the underlying large- and medium-sized choroidal arteries [7].
Funding Hyderabad Eye Research Foundation,
Hyderabad, India.
(f) Choroidal granulomas: Choroidal granulomas
can be seen in both primary and secondary stromal choroiditis like Vogt-Koyanagi­Harada disease and tubercular and sarcoid uveitis. Choroidal granulomas displace cho-
Disclosure TYYL: Consultant: Allergan, Bayer, Boeh-
ringer Ingelheim, Iveric Bio, Novartis, Oculis, Roche;
Speaker: Alcon, Bayer, Chendu Kanghong Biotech,
Novartis, Roche.
roidal vessels and block ICG dye from lling the area of the choroidal stroma occupied by
References
the choroidal granulomas (Fig. 26.16). As a result, during the early and middle phases of ICGA, they present as hypouorescent round lesions. The granulomas gradually get sur­rounded by the dye in the late phases, making them less prominent [7]. After therapy, these gradually shrink and eventually disappear, which can be better identied and monitored by ICGA [40].
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22. Yannuzzi LA, Flower RW, Slakter JS. Indocyanine green angiography. Mosby Incorporated; 1997.
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Paediatric Wide-Field Retinal
Imaging
27
SouravPal
27.1 Introduction
The use of wide-eld imaging on paediatric sub­jects is primarily targeted at but is not restricted to the detection of retinopathy of prematurity (ROP). Early detection of the disease at stage-1, which appears as a thin demarcation line on the retina between the vascular and avascular region, can largely reduce the risk of severe vision loss. Therefore, for nding signatures of ROP at its early stage, imaging of the extreme peripheral regions around the ora serrata becomes far more important than imaging the central part of the retina.
27.2 History andStages ofROP
The disease was more apparent with the invention of incubators in the early 1940s. ROP was rst reported in 1942 and identied as a cause of excess oxygen concentration inside incubators. In 1949, Owens and Owens [1] described the early stages of ROP and its progression. With the advancement of incubators and the increased number of premature survivals, cases of vision loss due to ROP signicantly increased by the 1950s. The rst attempt to deal with this problem
S. Pal (*) Forus Health Pvt. Ltd., Bengaluru, India e-mail: sourav@forushealth.com
universally was made by Reese etal. [2] by clas­sifying the disease in 1953. More than 30years went by, and many such attempts were made [3
6] before a group of 23 ophthalmologists from 11
different counties collaborated to propose the International Classication of Retinopathy of Prematurity (ICROP) in 1984 [7] to dene proto­cols for ROP studies. The third edition, published in 2021, is currently used for ROP screening [8]. In all practical cases, the state of vascularization is investigated, classied, and recorded in multiple circular zones with the optic disc at the centre.
The central zone or Zone-I is the circular area around the optic disc with a radius twice the dis­tance between the optic disc and macula (d). (Fig.27.1). Zone-I boundary makes an angle of approximately 45° at the centre of the eyeball [9] (Fig. 27.2). This slightly varies for premature babies with postmenstrual age (PMA) due to rapid changes in the eyeball size [9].
Zone-II is the annular region concentric to Zone-I and adjacent to it with an extension till nasal ora serrata. The boundary of Zone-II closely matches the equator [10] (Fig.27.2), at least on the nasal side. The Zone-II boundary makes an angle between 180°and200° at the centre of the eyeball. Additionally, ICROP denes a narrow annular zone inside Zone-II. This is named Posterior Zone-II, adjacent to Zone-I, and has a thickness twice the diameter of the optic disc. In ICROP, this is marked as an area prone to more severe disease than ROP.
© The Author(s), under exclusive license to Springer Nature Singapore Pte Ltd. 2024 T. Das, P. Satgunam (eds.), Ophthalmic Diagnostics, https://doi.org/10.1007/978-981-97-0138-4_27
347
348
Fig. 27.1 Schematic representation of three zones and other features of the left (LE) and right (RE) eyes
Optical Inc., Mentor, USA), a portable non-con­tact digital fundus camera with an FoV of 45°. In a study, Prakalapakorn et al. [12] could image only Zone-I and little beyond that. Results show the possibility of detecting pre-plus or plus dis­eases [13], characterized by dilated and tortuous arterioles near the posterior pole. But it failed to capture signatures of an early stage of ROP.Hence, a wide-eld imaging system, which gives exibil­ity to the user and allows imaging up to the ora serrata with no or little tilt in the device, remained the rst preference over the years.
S. Pal
Fig. 27.2 Different zones and FoV at the centre of the eye
Zone-III is the crescent-shaped retinal area on the temporal side of Zone-II.By Toslak etal. [10] and Atkinson [11], the far extent of Zone-III makes an angle of 230° at the centre of the eyeball.
Therefore, it is evident that a conventional fun­dus camera system with a eld of view (FoV) between 40°and50° can image up to Zone-I nor­mally. An odd tilt in the device is needed to cover Zone-III and image ora serrata. A similar attempt was made with the Pictor imaging system (Volk
27.3 Wide-Angle Imaging Technology
A binocular indirect ophthalmoscope (BIO) is the gold standard for ROP screening. But it necessi­tates an experienced ophthalmologist. Screening using BIO is generally time- consuming. Thus, ROP screening with BIO is less practical for devel­oping countries with poor patient-to-physician ratios; therefore, there is a need for wide-angle digital cameras. The wide- angle camera facilitates photo-document a larger area of the retina in a lesser time for future reference. Additionally, a minimally trained technician with a wide-angle
ab
27 Paediatric Wide-Field Retinal Imaging
349
camera can participate in an ROP screening pro­gramme. Telemedicine- based ROP screening is effective too [1416]. It overcomes the barrier of poor patient-to- physician ratio and reaches out to larger populations to ensure timely screening and treatment wherever necessary. Wide-angle imag­ing system with digital image recorder is an insep­arable part of the programmes.
Fig. 27.3 System architecture adopted by RetCam, PanoCam, and Icon
27.3.1 Currently Available Wide­Angle Cameras
RetCam by Natus Medical Inc. (Middleton, USA), previously known as Clarity Medical System Inc., is the rst paediatric retinal camera with FoV from 30 to 130° through changeable front attachments. Many other manufacturers, like Forus Health Pvt. Ltd. (Bangalore, India), Phoenix (Pleasanton, USA), and Visunex Medical Systems (Fremont, USA) subsequently intro­duced wide-eld imaging devices, named 3nethra neo, Icon and PanoCam, respectively. Devices like RetCam, PanoCam and Icon build on a trol­ley, as shown in Fig. 27.3. Probe consists of imaging and illumination optics along with an imaging sensor. All of them has integrated dis­play and computing system. Control unit gener­ally holds light sources and other control circuits that establish a communication between software and imaging system. All of them uses a foot­pedal to control light intensity and focus on the retina as and when needed. PanoCam probe has the distinctive quality of operating wirelessly. Conversely, 3nethra neo has a compact control unit that holds the probe, which contains light source, illumination, and imaging optics. It gets connected to and uses a laptop/PC as display and computing system. Figure 27.4 shows an upgraded version of 3nethra neo, which facili­tates uorescein imaging is named as 3nethra neo-HD FA.
Table 27.1 presents various models offered by the above four manufacturers and their compari­son. Despite diversied features, many similari­ties in basic structure exist. All systems use white
Fig. 27.4 3nethra neo-HD FA by Forus Health Pvt. Ltd.; (a) probe and its control unit, (b) imaging unit/probe
350
Table 27.1 Presents various models offered by the above four manufacturers and their comparison
Device Manufacturer FoV Imagesize Portability FA RetCam shuttle Natus Medical 130° VGA Heavy No RetCam 3 130° 2 MP Heavy Ye s RetCam envision 130° 1.5 MP Heavy Yes 3nethra neo Forus Health 120° 4 MP Compact No 3nethra neo-HD FA 150° 20 MP Compact Ye s Panocam LT Visunex Medical Systems 130° 8 MP Heavy – Panocam Pro 130° 13 MP Heavy – Icon Phoenix 100° Heavy
MP megapixel; VGA video graphics array
S. Pal
ring-shaped light to illuminate the retina, operate in contact with the cornea, and obtain true colour images.
27.4 Technology
We describe the technology using a camera sys­tem made in India. But basically, the technology is similar across currently available cameras.
27.4.1 Optical Design ofImaging System
Most of the wide-angle fundus cameras in paedi­atric imaging works in contact with the cornea to avoid an increase in lens diameter abnormally. Generally, a meniscus lens is selected as the con­tact lens. The radius of the contact surface is gen­erally selected between 6 and 7mm to match it with the corneal curvature of the baby. Optical components that follow contact lens act like a relay system; these generally form an intermedi­ate real image of the retina before carrying it for­ward and shaping it appropriately for the selected sensor. The imaging system of the 3nethra neo­ HD FA (Forus Health, Bangalore, India) is sche­matically shown in Fig.27.5. Imaging systems of wide-angle cameras have strategically similar designs but differ in how they distribute the opti­cal power.
There are two groups of relay lenses. Relay lens Group-1 forms an intermediate
image and guides rays towards the aperture of the
system. The 3nethra neo-HD FA uses a trans­pupillary illumination scheme. The aperture is placed at a plane conjugate to the pupil of the eye so that the entrance pupil of the imaging system coincides with the pupil for reex-free imaging (see Sect. 27.4.3.1).
Relay lens Group-2 determines the nal image size suitable for the camera/sensor in use. Another job of it is balancing residual aberration from the previous group of lenses. The 3nethra neo-HD FA uses a tunable focus lens to make the neces­sary correction aligned with the changes in the refractive power of the eye. An electronically controlled tunable focus lens enables a smooth, vibration-free operation. Without such lenses, a physical movement of Group-2 lenses is needed for focus. Although contact and Group-1 lenses decide the FoV, Group-2 lenses play an important role in image formation without vignetting.
27.4.2 Understanding ofField
ofView
Understanding and expressing the FoV correctly is critical when working with wide-angle fundus cameras. Historically, the FoV is dened as the angle subtended by the front optics of any imag­ing system at the pupil of the eye (Fig.27.6a). This is usually named as external angle, θex [11]. An oversimplied expression, θin = θex/1.33 for calculation of internal angle θin is sometimes use­ful but not accurate in all practical cases. A ray of light from the retina follows a multifold path through the vitreous humour, crystalline lens, and
xe
=+
()
()
n/
27 Paediatric Wide-Field Retinal Imaging
Fig. 27.5 Schematic of 3nethra neo-HD FA imaging system
351
Fig. 27.6 Illustration of external angle, internal angle, and eye angle
aqueous humour, having refractive indices of
27.4.3 Illumination System ofWide-
1.33, 1.42, and 1.33, respectively, before exiting the eye. Finding the nodal point of the eye and mapping the external angles in relation to it is, therefore, benecial for greater precision. The eye angle ,θe, is the angle subtended by the retinal area being imaged at the centre of the eyeball. Modern-day wide-angle cameras use θe to spec-
Fundamentally, there are two types of illumina­tion systems: (1) trans-pupillary—uses a clear window of the pupil of the eye to throw light onto the retina, and (2) trans-scleral—utilizes sections of the sclera to deliver light to the retina.
ify the FoV of the system.
Figure 27.6b schematically presents θex and θe,
27.4.3.1 Trans-pupillary Illumination
in reference to the nodal point of the eye N, which is very close to the posterior surface of the crys­talline lens [17]. With these factors considered, Yao etal. [18] arrived at the following relation­ship between the two angles.
1
2051 2
ee
sin.si
x
As per the above expression, an external angle of 50° is equivalent to an eye angle of 74.89°, which closely matches the result presented by Atkinson [11]. As per Atkinson and Mazo,
θe=1.48θex, which is also effective in many prac-
tical cases.
A trans-pupillary illumination system is the most widely used illumination scheme for retinal imaging [19] (Table27.1). It complies with the Gullstrand principle [2022], which states that the lighting and imaging channels must be sepa­rated near the pupil, from the corneal surface to the crystalline lens, for glare-free retinal imaging. In general, the illumination beam enters through an annular zone near the margin of the pupil, and the light scattered back from the retina is col­lected through the central part of the pupil (Fig. 27.7) [19, 22]. Fig. 27.7(b) shows the
Angle Cameras
System
352
S. Pal
a
Fig. 27.7 A schematic of trans-pupillary illumination that follows the Gullstrand principle. (a) The illumination beam enters through an annular zone near the margin of
arrangement in the 3nethra neo-HD FA. A smaller diameter of the ring illumination system leaves little space for the imaging beam, which can severely affect the optical resolution and light throughput. Given that a larger ring diameter will require a larger pupil for better imaging, a judi­cial selection of ring diameter is very important. To make the system suitable for a wider age group, it must be designed considering the rapid structural changes in the eye, and hence the nature of light reex, from premature to infants.
RetCam uses a bundle of optical bre arranged in the shape of a ring to generate a ring light. The other end of the bre bundle is fused and is used as a light collector from a halogen source. In con­trast, 3nethra neo or 3nethra neo-HD FA uses a waveguide structure made of acrylic material to shape desired ring light. It uses an array of LEDs arranged on an annular PCB (printed circuit board) as a light source, placed near the base of the waveguide structure. Light gets coupled into the waveguide, bounces back from the walls due to total internal reection, and propagates towards the circular output end of it.
27.4.3.2 Trans-scleral Illumination
Trans-scleral illumination is an alternative to the trans-pupillary illumination scheme that utilizes the pupillary area fully for imaging [10, 2328]. The history of trans-scleral illumination can be traced back to the early 1970s when Pomerantzeff et al. [29, 30] imaged the retina by delivering
b
the pupil; the light scattered back from the retina is col­lected through the central part of the pupil. (b) The tip of the imaging probe in 3nethra neo-HD FA
light through the palpebral region of the sclera. Named, Equator-plus, it had an extended FoV to capture the retina from anterior to the equator, nearly 148°.
In 2002 Panoret–1000, a trans-scleral illumi­nation-based system, was introduced. It could obtain images of the optic disc and ora serrata together in a single frame. But the clinical deploy­ment of this device was not successful. Unlike the Equator-plus camera that delivers light through the eyelid, the illumination system of Panoret–1000 requires scleral contact increasing the risk of contamination, inammation, and abrasion to the sclera and cornea. Currently, Panoret–1000 is commercially not available.
Pars-plana (a Latin phrase for Flat area) is a at portion of sclera 3–4mm posterior to the lim­bus with a width of ~4mm. Pars-plana region has a comparatively lower density of muscle, blood vessels, pigmentation, and consequently more transparent than other parts of the sclera. Therefore, scleral illumination through the pars­plana region is of utmost interest to recent inves­tigators. Figure 27.8 schematically represents a trans-pars-scleral illumination scheme, where generally, a bre-optics illumination probe is placed over the sclera on the pars-plana region to produce a diffuse illumination over the retina. Thus, the entire pupil area is available for imag­ing without any possibility of crosstalk with the illumination beam. The transitive pars-plana area reduces the risk of any physical hazard by
27 Paediatric Wide-Field Retinal Imaging
353
enabling suitable light levels on the retina with little input energy.
The primary benet of trans-scleral lighting is the ability to use the entire pupil area for imag­ing. This allows for some degree of wide-angle imaging even without pupil dilation. Additionally, it gives freedom to the designer to plan optical systems with higher resolution. Wide-angle cam­eras of Table27.1, having a eld of view around 130° offer an optical resolution ranging between 20 and 35lp/mm at the centre of the eld.
The biggest disadvantage of trans-scleral illu­mination is its usability and, in some cases, asso­ciated safety issues. This type of illumination
Fig. 27.8 Schematic representation of trans-pars-planar illumination scheme
system is not tightly coupled with the imaging system. Two independent movements by two hands are needed to capture an image. Despite many advantages, trans-scleral illumination probably is not very popular till it becomes more user-friendly.
27.4.4 Fluorescein Angiography
Most state-of-the-art wide-angle fundus cameras can perform fundus uorescein angiography (FA). FA is a tool for investigating vascular changes not evident in a colour fundus image. The development of digital imaging in the late twentieth century made FA easier and more prac­tical, and it has become an indispensable part of ROP treatment [31]. Currently, FA is invariably performed before laser photocoagulation to map the retinal vascularization more precisely.
In FA, retinal images are captured with the time of acquisition offset from the injection of Sodium uorescein (NaFl) dye. NaFl absorbs energy in the blue and emits it in the green region of the visible spectrum [32]. A typical absorption and emission spectrum of the NaFl is shown in Fig.27.9. It has peak absorption at 495nm, which is pH dependent and slightly shifts towards the left when injected into blood [33]. NaFl emits light in the approximate range of 515–600 nm, with a peak at 540nm.
The source is typically selected with a peak around 480nm. A typical spectrum of the source
a
Fig. 27.9 Spectrum associated with uorescein angiography (a) absorption and emission spectrum of sodium uores- cein; (b) spectrum of illumination and imaging beam after going through optical lters
b