Heidelberg Spectralis Ultra-Widefield Fundus Fluorescein Angiography in Infants TIMOTHY H.M. FUNG, IMRAN H. YUSUF, KANMIN XUE, LEWIS M. SMITH, AND CHETAN K. PATEL
PURPOSE:
To describe the intraoperative use of the Heidelberg Spectralis for ultra-widefield fundus fluorescein angiography in infants. DESIGN: Retrospective observational case series. METHODS: A modified Heidelberg Spectralis was used to perform ultra-widefield fundus fluorescein angiography in infants undergoing an examination under general anesthesia for a range of retinal vasculopathies. Peripheral angiographic findings, angiographic image acquisition time, and any complications were reviewed. RESULTS: A total of 22 eyes of 11 infants underwent intraoperative ultra-widefield fundus fluorescein angiography using the modified Heidelberg Spectralis. Ultrawidefield fundus fluorescein angiography was successfully performed in all infants and permitted capture of the posterior pole as well as the peripheral retina in a single shot centered on the macula. Peripheral retinal pathologies captured include neovascularization, capillary nonperfusion, and skip areas from previous laser treatment. Capturing of angiographic images took a mean time of 7.09 minutes. Image artifact from condensation of the ultra-widefield lens was noted during imaging of 1 infant. CONCLUSIONS: The modified Heidelberg Spectralis is an effective and reliable imaging tool for performing ultra-widefield fundus fluorescein angiography in infants. It is capable of capturing wide-angle images of high quality. The technique has advantages as an alternative to RetCam fluorescein angiography in infants undergoing an examination under general anesthesia. (Am J Ophthalmol 2015;159:78–84. Ó 2015 by Elsevier Inc. All rights reserved.)
T
HE IMPORTANCE OF FUNDUS FLUORESCEIN ANGIOG-
raphy (FA) of the peripheral retina in infants with retinal vasculopathies such as retinopathy of prematurity (ROP), familial exudative vitreoretinopathy (FEVR), and incontinentia pigmenti is well recognized for the diagnosis of neovascularization, capillary nonperfusion, and leakage. Infants are incapable of keeping their eyes open and steady for a long time, which is why Accepted for publication Sep 18, 2014. From Oxford Eye Hospital (T.H.M.F., I.H.Y., K.X., L.M.S., C.K.P.) and University of Oxford (T.H.M.F., C.K.P.), Oxford, United Kingdom. Inquiries to Mr Chetan K Patel, Oxford Eye Hospital, Headley Way, Headington, Oxford, OX3 9DU, United Kingdom; e-mail: ckpatel@ btinternet.com
78
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2015 BY
conventional outpatient angiography is underused. Our group has shown that the Optos system (Optos PLC, Dunfermline, Scotland, UK) is fast enough to permit ultra-widefield fundus FA in outpatients in premature and term infants aged up to 6 months with or without oral sedation using the ‘‘flying baby’’ position.1–3 Beyond 6 months of age, infants are generally too heavy to hold still for such a technique to be effective. Fluorescein angioscopy under general anesthesia using a binocular indirect ophthalmoscope is an option, but it is not ideal as there is no permanent objective record generated for review.4 RetCam (Clarity Medical System, Pleasanton, California, USA) is currently the only widely available imaging modality used to perform FA on a supine infant under general anesthesia. Peripheral sweeps and montage techniques are often necessary when information about the retinal periphery is required. These techniques are labor intensive, require highly skilled photographers, and do not permit the simultaneous capture of the posterior pole and periphery in a single frame, limiting the evaluation and comparison of the phases of the angiogram across different parts of the fundus. The Heidelberg Spectralis ultra-widefield fundus FA imaging system (Heidelberg Engineering, Heidelberg, Germany) is said to capture a wider field of view of the fundus in a single photograph without ocular surface contact. This imaging modality has been used to evaluate an adult patient with Von Hippel-Lindau syndrome.5 The Heidelberg Spectralis has been used previously in infants for spectral-domain optical coherence tomography (OCT).6 Since November 2012, we have been using the Heidelberg Spectralis ultra-widefield fundus FA imaging modality intraoperatively as part of our routine clinical care and management of infants with retinal vasculopathies. The purpose of this report is to describe the findings of an audit that retrospectively reviewed all infants who underwent intraoperative ultra-widefield fundus FA with the Heidelberg Spectralis in a National Health Service tertiary center setting. The technique adopted for performing intraoperative ultra-widefield fundus FA and the utility, angiographic findings, and complications of ultra-widefield fundus FA were reviewed in our group of infants. In addition, the fundal field of view obtained with the Heidelberg Spectralis ultra-widefield lens was compared with the RetCam 130-degree lens using a schematic infant model eye.
ELSEVIER INC. ALL
RIGHTS RESERVED.
0002-9394/$36.00 http://dx.doi.org/10.1016/j.ajo.2014.09.030
FIGURE 1. Modified Heidelberg Spectralis imaging system used to image supine infants in the operating room.
PATIENTS AND METHODS INSTITUTIONAL BOARD APPROVAL AT THE OXFORD EYE
Hospital was granted and logged permitting an audit that retrospectively reviewed all case records of infants who underwent an examination under general anesthesia with intraoperative ultra-widefield fundus FA with the Heidelberg Spectralis for routine clinical care over an 18-month period (November 1, 2012 to April 30, 2014). The review of infants was carried out in accordance with the Data Protection Act and the Declaration of Helsinki. Informed written parental consent for the angiography procedure had been obtained for all infants. The ultra-widefield fluorescein angiographic imaging modality for the Heidelberg Spectralis was purchased by our hospital using charitable funds following a costneutral loan for 2 weeks in 2012. Ultra-widefield fundus FA was performed with 10% fluorescein administered intravenously as a bolus at a dose of 0.1 mL/kg, followed by a 5 mL 0.9% saline flush. Mydriasis was obtained with 0.5% cyclopentolate and 2.5% phenylephrine. A Liebermann pediatric speculum (Duckworth & Kent, Hertfordshire, UK) was used to retract the eyelids. Infants were imaged with the Heidelberg Spectralis imaging system, consisting of a scanning laser ophthalmoscope (SLO) camera head connected, through a flexible fiberoptic cable, to a moveable cart housing the retinal viewing screen and the touch panel. To image infants in a supine position, the imaging system was modified by disassembling the SLO camera head from its mount by removing the Allen screw that secures it at the bottom of the arc guide. The SLO camera head was then mounted onto a multi-positional bracket at the end of a customized adjustable arm (Base Design Limited, Great Dunmow, Essex, UK) and secured tightly by a bolt (Figure 1). Adjustable wheel handles on the bracket allowed 4 degrees of freedom of movement to enable adjustment and optimization of alignment of the SLO camera head to the infant’s eyes. VOL. 159, NO. 1
All images were obtained in the operating room with the photographer at the head of the bed. During image acquisition, the SLO camera head was stabilized by resting the hand on the adjustable arm to keep movement of the arm and the camera head to a minimum. An assistant operated the computer software while the photographer obtained the images. To obtain images of the highest quality, the high-resolution acquisition modality in the fluorescein angiography mode was used. Regular corneal hydration with a balanced salt solution was necessary to improve the clarity of images and to preserve the integrity of the corneal surface. Imaging of the retina up to the ora serrata was made possible by rotating the globe with a toothed forceps and indenting the sclera with a squint hook. The images obtained appeared upright on the retinal viewing screen as the computer software automatically corrected the orientation of the SLO camera head at the time of imaging. For each infant, the data reviewed included age, sex, gestational age, age at imaging, birth weight, diagnosis, treatment, and any complications that occurred. All retinal images were reviewed on the Heidelberg Eye Explorer software. The duration of the imaging process was defined as the difference in time between the first and last image captured, which is automatically recorded. Peripheral angiographic findings and the presence of any artifacts were evaluated from the images.
RESULTS OVER AN 18-MONTH PERIOD, A TOTAL OF 22 EYES OF
11 infants underwent intraoperative noncontact ultrawidefield fundus FA using the modified Heidelberg Spectralis. Of the 11 infants, 6 were male and 5 were female. Eight patients were premature infants diagnosed with ROP with a mean gestational age of 24.75 weeks (range 23–26 weeks) and a mean birth weight of 744.38 g (range 650–870 g). Mean postnatal age at imaging was 47.38 weeks (range 33–91 weeks). Three patients were term infants with diagnoses of incontinentia pigmenti and FEVR with a mean age of 7 months (range 3–12 months). Tables 1 and 2 summarize the demographics, diagnoses, angiographic findings, and the utility of ultra-widefield fundus FA in our group of infants. Ultra-widefield fundus FA was successfully carried out in all infants and permitted capture of the posterior pole as well as the peripheral retina in a single shot centered on the macula (Figure 2). All infants had infrared reflectance images obtained with the ultra-widefield lens prior to the acquisition of ultra-widefield fluorescein angiographic images (Figure 3). A range of peripheral retinal pathologies was captured, including neovascularization, capillary nonperfusion (Figure 4), skip areas from previous laser treatment
NONCONTACT FUNDUS ANGIOGRAPHY IN INFANTS USING SPECTRALIS
79
TABLE 1. Summary of the Demographics, Peripheral Angiographic Findings, and Utility of Heidelberg Spectralis Ultra-widefield Fundus Fluorescein Angiography in Premature Infants With Retinopathy of Prematurity Gestational Age
Birth Weight
Postnatal Age
(Weeks)
(g)
(Weeks)
1
26
870
44
2
26
665
3 4
24 24
5 6
Infant
Utility of Ultra-widefield Fluorescein Sex
Diagnosis
Peripheral Angiographic Findings
Male
ROP
41
Male
ROP
575 790
33 41
Female Male
ROP ROP
23 25
650 850
91 49
Male Male
ROP ROP
7
24
785
36
Male
ROP
8
26
770
44
Female
ROP
Peripheral leakage and nonperfusion Peripheral leakage and nonperfusion Peripheral leakage Peripheral leakage and nonperfusion Peripheral nonperfusion Peripheral nonperfusion, laser skip areas Resolution of peripheral leakage Peripheral leakage
Angiography
Targeted laser treatment Targeted laser treatment Diagnosis Targeted laser treatment Targeted laser treatment Targeted laser treatment Assessment of previous treatment Targeted laser treatment
ROP ¼ retinopathy of prematurity.
TABLE 2. Summary of the Demographics, Angiographic Findings, and Utility of Heidelberg Spectralis Ultra-widefield Fundus Fluorescein Angiography in Term Infants With Familial Exudative Vitreoretinopathy and Incontinentia Pigmenti Infant
1 2 3
Age (Months)
Sex
Diagnosis
3 12 6
Female Female Female
Familial exudative vitreoretinopathy Incontinentia pigmenti Incontinentia pigmenti
Peripheral Angiographic Findings
Utility of Ultra-widefield Fluorescein Angiography
Peripheral leakage Normal Peripheral ischemia
Targeted laser treatment Documentation Targeted laser treatment
FIGURE 2. Heidelberg Spectralis ultra-widefield fluorescein angiogram of the right (Left image) and left (Right image) eyes of a 33-week postnatal age infant, highlighting type 1 retinopathy of prematurity and preretinal hemorrhage in the left eye. Normal retinal vascular development is seen in the right eye. These images demonstrate the ability of the Heidelberg Spectralis ultra-widefield fluorescein angiographic imaging system to capture the posterior pole and the periphery in a single shot centered on the macula.
(Figure 5), and areas of peripheral retinal ischemia (Figure 6). No systemic complications were encountered during or after the general anesthesia or from the 80
ultra-widefield fundus FA imaging process. In the images of 1 infant, an area of artifact arose from condensation that had developed across the ultra-widefield lens during
AMERICAN JOURNAL OF OPHTHALMOLOGY
JANUARY 2015
FIGURE 3. Heidelberg Spectralis ultra-widefield infrared image (Left image) demonstrating resolution of plus disease in a 36-week postnatal age infant post bevacizumab treatment for stage 3 retinopathy of prematurity in zone 1. Ultra-widefield fluorescein angiogram (Right image) of the same infant shows regression of active neovascularization post bevacizumab treatment.
FIGURE 4. Heidelberg Spectralis ultra-widefield fluorescein angiogram of the right (Left image) and left (Right image) eyes of a 41-week postnatal age infant with previously treated stage 3 retinopathy of prematurity in zone 2 with plus disease. Fluorescein angiography demonstrated peripheral vascular leakage (Left image and Right image: black arrowhead), capillary nonperfusion (Left image and Right image: white arrow), and laser skip areas (Right image: white arrowhead).
the imaging process (Figure 7). Eliminating the condensation with an air current across the ocular-device interface removed the artifact and restored the image clarity. There was no motion artifact on any of the images obtained, as the adjustable arm was stabilized and the infant’s eyes were akinetic with an eyelid speculum in place. Capturing of angiographic images took a mean time of 7.09 minutes.
DISCUSSION WE HAVE REVIEWED THE INTRAOPERATIVE USE OF A MODI-
fied Heidelberg Spectralis unit for performing noncontact ultra-widefield fundus FA in infants. The technique was VOL. 159, NO. 1
safe with no untoward complications. However, it is important to bear in mind the potential risk of local and systemic complications of using intravenous sodium fluorescein, which range from mild nausea, itch, and skin rash to the more severe reaction of anaphylactic shock.7 The high-resolution ultra-widefield angiographic images obtained were able to detect peripheral retinal pathology and guide targeted laser photocoagulation to areas of retinal ischemia. We found that corneal hydration with 0.9% saline was essential for good images. Condensation of the ultra-widefield lens can occur because of the close working distance between the imaging device and the eye, but it is easily dealt with by creating an air current near the eye when the artifact is noted on the monitor.
NONCONTACT FUNDUS ANGIOGRAPHY IN INFANTS USING SPECTRALIS
81
FIGURE 5. Heidelberg Spectralis ultra-widefield fluorescein angiogram of the right eye of a 49-week postnatal age infant with previously treated stage 3 retinopathy of prematurity in zone 1. Ultra-widefield fluorescein angiogram reveals persistent plus disease with a laser skip area temporally (white arrow).
FIGURE 6. Heidelberg Spectralis ultra-widefield fluorescein angiogram of the left eye of a 3-month-old infant born term with incontinentia pigmenti. Ultra-widefield fluorescein angiogram shows an area of peripheral retinal ischemia superotemporally (white arrow).
Ultra-widefield fundus FA has been shown to be useful in the cooperative pediatric patient population in the outpatient setting to evaluate peripheral retinal pathology.8,9 82
FIGURE 7. Heidelberg Spectralis ultra-widefield fluorescein angiogram demonstrating a shadow artifact in the retinal image inferotemporally as a result of condensation of the ultrawidefield lens. This artifact can arise owing to the close working distance of the ultra-widefield lens and the eye of an infant. Producing an air current across the ocular-device interface will eliminate this artifact.
When angiography is required under general anesthesia in uncooperative infants, ultra-widefield fundus FA with the Heidelberg Spectralis has several potential advantages over RetCam FA. First, there is no contact with the ocular surface and, as such, compression artifact will not occur. Second, confocal optics of SLO imaging devices produces images of superior quality at lower retinal irradiances that allow a greater sensitivity for detecting vascular leakage and areas of capillary nonperfusion.10,11 Third, the ability to capture the posterior pole and periphery of the retina in a 1-shot image obviates photomontages, avoiding their potential limitations, which include skipped areas and local variations in magnification and contrast. The Heidelberg Spectralis has supplementary imaging modalities to FA that can be used intraoperatively with the ultra-widefield lens. These include infrared reflectance imaging and indocyanine green angiography. Spectral-domain OCT, multicolor fundus imaging, and autofluorescence are other imaging modalities that can be used intraoperatively with the Heidelberg Spectralis, but these modalities can only be operated with the standard 30-degree lens. The RetCam, in contrast, has only a fundus color imaging modality in addition to FA. Disadvantages of using the Heidelberg Spectralis include the presence of central artifact in the infrared reflectance images and the large size of the wide-angle lens, which one might find difficult to use in a deep-set eye.
AMERICAN JOURNAL OF OPHTHALMOLOGY
JANUARY 2015
FIGURE 8. Schematic drawing of the infant model eye (Left image) that has a 10-degree incremental grid lasered onto its internal posterior surface (Right image). This model eye was used to quantify the difference in the fundal field of view of the Heidelberg Spectralis ultra-widefield lens and the RetCam 130-degree lens.
FIGURE 9. (Left image) Single-shot field of view of an infrared reflectance image obtained from the Heidelberg Spectralis ultrawidefield lens. (Right image) Single-shot field of view of a color image obtained from the RetCam 130-degree lens. These images were obtained from imaging the grid on the posterior surface of the infant schematic model eye. The total area visualized in each image was determined using the pixel measurement function of the Adobe Photoshop CC software. The Heidelberg Spectralis ultrawidefield lens imaged a greater area than the RetCam 130-degree lens (436 700 pixels vs 203 400 pixels).
When our department was procuring a fluorescein angiographic imaging device for infants, one of the important factors was the fundal field of view, which was said to be larger for the Heidelberg Spectralis ultra-widefield lens compared with the RetCam 130-degree lens. To quantify this, we compared the field of view of the Heidelberg Spectralis ultra-widefield lens with the RetCam 130-degree lens using an infant model eye, which was constructed based on Gullstrand’s model of the human eye (Figure 8, Left image).12 A grid with 10degree inclinations in multiple meridians was lasered onto the posterior surface of the model eye (Figure 8, Right image). Infrared reflectance images of the grid were taken with the Heidelberg Spectralis ultra-widefield lens and color images VOL. 159, NO. 1
were taken with the RetCam 130-degree lens (Figure 9). All images were captured through a 7 mm artificial pupil. The images were exported as Joint Photographic Experts Group files and analyzed using Adobe photo editing software (Photoshop CC; Adobe Systems, San Jose, California, USA). Using the software a free-style line was made, demarcating the most peripheral area of visible grid in each image. This area was then highlighted, and its pixels were quantified using the pixel measurement function of the Adobe Photoshop CC software. The total area visualized was compared between the 2 imaging modalities. Each measurement was performed for 5 independent images and averaged. Statistical analysis was performed using statistical software (SPSS 19.0 for
NONCONTACT FUNDUS ANGIOGRAPHY IN INFANTS USING SPECTRALIS
83
Windows; SPSS Inc, Chicago, Illinois, USA). Comparison between imaging modalities were performed using the unpaired Student t test and P values
PURPOSE:
To describe the intraoperative use of the Heidelberg Spectralis for ultra-widefield fundus fluorescein angiography in infants. DESIGN: Retrospective observational case series. METHODS: A modified Heidelberg Spectralis was used to perform ultra-widefield fundus fluorescein angiography in infants undergoing an examination under general anesthesia for a range of retinal vasculopathies. Peripheral angiographic findings, angiographic image acquisition time, and any complications were reviewed. RESULTS: A total of 22 eyes of 11 infants underwent intraoperative ultra-widefield fundus fluorescein angiography using the modified Heidelberg Spectralis. Ultrawidefield fundus fluorescein angiography was successfully performed in all infants and permitted capture of the posterior pole as well as the peripheral retina in a single shot centered on the macula. Peripheral retinal pathologies captured include neovascularization, capillary nonperfusion, and skip areas from previous laser treatment. Capturing of angiographic images took a mean time of 7.09 minutes. Image artifact from condensation of the ultra-widefield lens was noted during imaging of 1 infant. CONCLUSIONS: The modified Heidelberg Spectralis is an effective and reliable imaging tool for performing ultra-widefield fundus fluorescein angiography in infants. It is capable of capturing wide-angle images of high quality. The technique has advantages as an alternative to RetCam fluorescein angiography in infants undergoing an examination under general anesthesia. (Am J Ophthalmol 2015;159:78–84. Ó 2015 by Elsevier Inc. All rights reserved.)
T
HE IMPORTANCE OF FUNDUS FLUORESCEIN ANGIOG-
raphy (FA) of the peripheral retina in infants with retinal vasculopathies such as retinopathy of prematurity (ROP), familial exudative vitreoretinopathy (FEVR), and incontinentia pigmenti is well recognized for the diagnosis of neovascularization, capillary nonperfusion, and leakage. Infants are incapable of keeping their eyes open and steady for a long time, which is why Accepted for publication Sep 18, 2014. From Oxford Eye Hospital (T.H.M.F., I.H.Y., K.X., L.M.S., C.K.P.) and University of Oxford (T.H.M.F., C.K.P.), Oxford, United Kingdom. Inquiries to Mr Chetan K Patel, Oxford Eye Hospital, Headley Way, Headington, Oxford, OX3 9DU, United Kingdom; e-mail: ckpatel@ btinternet.com
78
Ó
2015 BY
conventional outpatient angiography is underused. Our group has shown that the Optos system (Optos PLC, Dunfermline, Scotland, UK) is fast enough to permit ultra-widefield fundus FA in outpatients in premature and term infants aged up to 6 months with or without oral sedation using the ‘‘flying baby’’ position.1–3 Beyond 6 months of age, infants are generally too heavy to hold still for such a technique to be effective. Fluorescein angioscopy under general anesthesia using a binocular indirect ophthalmoscope is an option, but it is not ideal as there is no permanent objective record generated for review.4 RetCam (Clarity Medical System, Pleasanton, California, USA) is currently the only widely available imaging modality used to perform FA on a supine infant under general anesthesia. Peripheral sweeps and montage techniques are often necessary when information about the retinal periphery is required. These techniques are labor intensive, require highly skilled photographers, and do not permit the simultaneous capture of the posterior pole and periphery in a single frame, limiting the evaluation and comparison of the phases of the angiogram across different parts of the fundus. The Heidelberg Spectralis ultra-widefield fundus FA imaging system (Heidelberg Engineering, Heidelberg, Germany) is said to capture a wider field of view of the fundus in a single photograph without ocular surface contact. This imaging modality has been used to evaluate an adult patient with Von Hippel-Lindau syndrome.5 The Heidelberg Spectralis has been used previously in infants for spectral-domain optical coherence tomography (OCT).6 Since November 2012, we have been using the Heidelberg Spectralis ultra-widefield fundus FA imaging modality intraoperatively as part of our routine clinical care and management of infants with retinal vasculopathies. The purpose of this report is to describe the findings of an audit that retrospectively reviewed all infants who underwent intraoperative ultra-widefield fundus FA with the Heidelberg Spectralis in a National Health Service tertiary center setting. The technique adopted for performing intraoperative ultra-widefield fundus FA and the utility, angiographic findings, and complications of ultra-widefield fundus FA were reviewed in our group of infants. In addition, the fundal field of view obtained with the Heidelberg Spectralis ultra-widefield lens was compared with the RetCam 130-degree lens using a schematic infant model eye.
ELSEVIER INC. ALL
RIGHTS RESERVED.
0002-9394/$36.00 http://dx.doi.org/10.1016/j.ajo.2014.09.030
FIGURE 1. Modified Heidelberg Spectralis imaging system used to image supine infants in the operating room.
PATIENTS AND METHODS INSTITUTIONAL BOARD APPROVAL AT THE OXFORD EYE
Hospital was granted and logged permitting an audit that retrospectively reviewed all case records of infants who underwent an examination under general anesthesia with intraoperative ultra-widefield fundus FA with the Heidelberg Spectralis for routine clinical care over an 18-month period (November 1, 2012 to April 30, 2014). The review of infants was carried out in accordance with the Data Protection Act and the Declaration of Helsinki. Informed written parental consent for the angiography procedure had been obtained for all infants. The ultra-widefield fluorescein angiographic imaging modality for the Heidelberg Spectralis was purchased by our hospital using charitable funds following a costneutral loan for 2 weeks in 2012. Ultra-widefield fundus FA was performed with 10% fluorescein administered intravenously as a bolus at a dose of 0.1 mL/kg, followed by a 5 mL 0.9% saline flush. Mydriasis was obtained with 0.5% cyclopentolate and 2.5% phenylephrine. A Liebermann pediatric speculum (Duckworth & Kent, Hertfordshire, UK) was used to retract the eyelids. Infants were imaged with the Heidelberg Spectralis imaging system, consisting of a scanning laser ophthalmoscope (SLO) camera head connected, through a flexible fiberoptic cable, to a moveable cart housing the retinal viewing screen and the touch panel. To image infants in a supine position, the imaging system was modified by disassembling the SLO camera head from its mount by removing the Allen screw that secures it at the bottom of the arc guide. The SLO camera head was then mounted onto a multi-positional bracket at the end of a customized adjustable arm (Base Design Limited, Great Dunmow, Essex, UK) and secured tightly by a bolt (Figure 1). Adjustable wheel handles on the bracket allowed 4 degrees of freedom of movement to enable adjustment and optimization of alignment of the SLO camera head to the infant’s eyes. VOL. 159, NO. 1
All images were obtained in the operating room with the photographer at the head of the bed. During image acquisition, the SLO camera head was stabilized by resting the hand on the adjustable arm to keep movement of the arm and the camera head to a minimum. An assistant operated the computer software while the photographer obtained the images. To obtain images of the highest quality, the high-resolution acquisition modality in the fluorescein angiography mode was used. Regular corneal hydration with a balanced salt solution was necessary to improve the clarity of images and to preserve the integrity of the corneal surface. Imaging of the retina up to the ora serrata was made possible by rotating the globe with a toothed forceps and indenting the sclera with a squint hook. The images obtained appeared upright on the retinal viewing screen as the computer software automatically corrected the orientation of the SLO camera head at the time of imaging. For each infant, the data reviewed included age, sex, gestational age, age at imaging, birth weight, diagnosis, treatment, and any complications that occurred. All retinal images were reviewed on the Heidelberg Eye Explorer software. The duration of the imaging process was defined as the difference in time between the first and last image captured, which is automatically recorded. Peripheral angiographic findings and the presence of any artifacts were evaluated from the images.
RESULTS OVER AN 18-MONTH PERIOD, A TOTAL OF 22 EYES OF
11 infants underwent intraoperative noncontact ultrawidefield fundus FA using the modified Heidelberg Spectralis. Of the 11 infants, 6 were male and 5 were female. Eight patients were premature infants diagnosed with ROP with a mean gestational age of 24.75 weeks (range 23–26 weeks) and a mean birth weight of 744.38 g (range 650–870 g). Mean postnatal age at imaging was 47.38 weeks (range 33–91 weeks). Three patients were term infants with diagnoses of incontinentia pigmenti and FEVR with a mean age of 7 months (range 3–12 months). Tables 1 and 2 summarize the demographics, diagnoses, angiographic findings, and the utility of ultra-widefield fundus FA in our group of infants. Ultra-widefield fundus FA was successfully carried out in all infants and permitted capture of the posterior pole as well as the peripheral retina in a single shot centered on the macula (Figure 2). All infants had infrared reflectance images obtained with the ultra-widefield lens prior to the acquisition of ultra-widefield fluorescein angiographic images (Figure 3). A range of peripheral retinal pathologies was captured, including neovascularization, capillary nonperfusion (Figure 4), skip areas from previous laser treatment
NONCONTACT FUNDUS ANGIOGRAPHY IN INFANTS USING SPECTRALIS
79
TABLE 1. Summary of the Demographics, Peripheral Angiographic Findings, and Utility of Heidelberg Spectralis Ultra-widefield Fundus Fluorescein Angiography in Premature Infants With Retinopathy of Prematurity Gestational Age
Birth Weight
Postnatal Age
(Weeks)
(g)
(Weeks)
1
26
870
44
2
26
665
3 4
24 24
5 6
Infant
Utility of Ultra-widefield Fluorescein Sex
Diagnosis
Peripheral Angiographic Findings
Male
ROP
41
Male
ROP
575 790
33 41
Female Male
ROP ROP
23 25
650 850
91 49
Male Male
ROP ROP
7
24
785
36
Male
ROP
8
26
770
44
Female
ROP
Peripheral leakage and nonperfusion Peripheral leakage and nonperfusion Peripheral leakage Peripheral leakage and nonperfusion Peripheral nonperfusion Peripheral nonperfusion, laser skip areas Resolution of peripheral leakage Peripheral leakage
Angiography
Targeted laser treatment Targeted laser treatment Diagnosis Targeted laser treatment Targeted laser treatment Targeted laser treatment Assessment of previous treatment Targeted laser treatment
ROP ¼ retinopathy of prematurity.
TABLE 2. Summary of the Demographics, Angiographic Findings, and Utility of Heidelberg Spectralis Ultra-widefield Fundus Fluorescein Angiography in Term Infants With Familial Exudative Vitreoretinopathy and Incontinentia Pigmenti Infant
1 2 3
Age (Months)
Sex
Diagnosis
3 12 6
Female Female Female
Familial exudative vitreoretinopathy Incontinentia pigmenti Incontinentia pigmenti
Peripheral Angiographic Findings
Utility of Ultra-widefield Fluorescein Angiography
Peripheral leakage Normal Peripheral ischemia
Targeted laser treatment Documentation Targeted laser treatment
FIGURE 2. Heidelberg Spectralis ultra-widefield fluorescein angiogram of the right (Left image) and left (Right image) eyes of a 33-week postnatal age infant, highlighting type 1 retinopathy of prematurity and preretinal hemorrhage in the left eye. Normal retinal vascular development is seen in the right eye. These images demonstrate the ability of the Heidelberg Spectralis ultra-widefield fluorescein angiographic imaging system to capture the posterior pole and the periphery in a single shot centered on the macula.
(Figure 5), and areas of peripheral retinal ischemia (Figure 6). No systemic complications were encountered during or after the general anesthesia or from the 80
ultra-widefield fundus FA imaging process. In the images of 1 infant, an area of artifact arose from condensation that had developed across the ultra-widefield lens during
AMERICAN JOURNAL OF OPHTHALMOLOGY
JANUARY 2015
FIGURE 3. Heidelberg Spectralis ultra-widefield infrared image (Left image) demonstrating resolution of plus disease in a 36-week postnatal age infant post bevacizumab treatment for stage 3 retinopathy of prematurity in zone 1. Ultra-widefield fluorescein angiogram (Right image) of the same infant shows regression of active neovascularization post bevacizumab treatment.
FIGURE 4. Heidelberg Spectralis ultra-widefield fluorescein angiogram of the right (Left image) and left (Right image) eyes of a 41-week postnatal age infant with previously treated stage 3 retinopathy of prematurity in zone 2 with plus disease. Fluorescein angiography demonstrated peripheral vascular leakage (Left image and Right image: black arrowhead), capillary nonperfusion (Left image and Right image: white arrow), and laser skip areas (Right image: white arrowhead).
the imaging process (Figure 7). Eliminating the condensation with an air current across the ocular-device interface removed the artifact and restored the image clarity. There was no motion artifact on any of the images obtained, as the adjustable arm was stabilized and the infant’s eyes were akinetic with an eyelid speculum in place. Capturing of angiographic images took a mean time of 7.09 minutes.
DISCUSSION WE HAVE REVIEWED THE INTRAOPERATIVE USE OF A MODI-
fied Heidelberg Spectralis unit for performing noncontact ultra-widefield fundus FA in infants. The technique was VOL. 159, NO. 1
safe with no untoward complications. However, it is important to bear in mind the potential risk of local and systemic complications of using intravenous sodium fluorescein, which range from mild nausea, itch, and skin rash to the more severe reaction of anaphylactic shock.7 The high-resolution ultra-widefield angiographic images obtained were able to detect peripheral retinal pathology and guide targeted laser photocoagulation to areas of retinal ischemia. We found that corneal hydration with 0.9% saline was essential for good images. Condensation of the ultra-widefield lens can occur because of the close working distance between the imaging device and the eye, but it is easily dealt with by creating an air current near the eye when the artifact is noted on the monitor.
NONCONTACT FUNDUS ANGIOGRAPHY IN INFANTS USING SPECTRALIS
81
FIGURE 5. Heidelberg Spectralis ultra-widefield fluorescein angiogram of the right eye of a 49-week postnatal age infant with previously treated stage 3 retinopathy of prematurity in zone 1. Ultra-widefield fluorescein angiogram reveals persistent plus disease with a laser skip area temporally (white arrow).
FIGURE 6. Heidelberg Spectralis ultra-widefield fluorescein angiogram of the left eye of a 3-month-old infant born term with incontinentia pigmenti. Ultra-widefield fluorescein angiogram shows an area of peripheral retinal ischemia superotemporally (white arrow).
Ultra-widefield fundus FA has been shown to be useful in the cooperative pediatric patient population in the outpatient setting to evaluate peripheral retinal pathology.8,9 82
FIGURE 7. Heidelberg Spectralis ultra-widefield fluorescein angiogram demonstrating a shadow artifact in the retinal image inferotemporally as a result of condensation of the ultrawidefield lens. This artifact can arise owing to the close working distance of the ultra-widefield lens and the eye of an infant. Producing an air current across the ocular-device interface will eliminate this artifact.
When angiography is required under general anesthesia in uncooperative infants, ultra-widefield fundus FA with the Heidelberg Spectralis has several potential advantages over RetCam FA. First, there is no contact with the ocular surface and, as such, compression artifact will not occur. Second, confocal optics of SLO imaging devices produces images of superior quality at lower retinal irradiances that allow a greater sensitivity for detecting vascular leakage and areas of capillary nonperfusion.10,11 Third, the ability to capture the posterior pole and periphery of the retina in a 1-shot image obviates photomontages, avoiding their potential limitations, which include skipped areas and local variations in magnification and contrast. The Heidelberg Spectralis has supplementary imaging modalities to FA that can be used intraoperatively with the ultra-widefield lens. These include infrared reflectance imaging and indocyanine green angiography. Spectral-domain OCT, multicolor fundus imaging, and autofluorescence are other imaging modalities that can be used intraoperatively with the Heidelberg Spectralis, but these modalities can only be operated with the standard 30-degree lens. The RetCam, in contrast, has only a fundus color imaging modality in addition to FA. Disadvantages of using the Heidelberg Spectralis include the presence of central artifact in the infrared reflectance images and the large size of the wide-angle lens, which one might find difficult to use in a deep-set eye.
AMERICAN JOURNAL OF OPHTHALMOLOGY
JANUARY 2015
FIGURE 8. Schematic drawing of the infant model eye (Left image) that has a 10-degree incremental grid lasered onto its internal posterior surface (Right image). This model eye was used to quantify the difference in the fundal field of view of the Heidelberg Spectralis ultra-widefield lens and the RetCam 130-degree lens.
FIGURE 9. (Left image) Single-shot field of view of an infrared reflectance image obtained from the Heidelberg Spectralis ultrawidefield lens. (Right image) Single-shot field of view of a color image obtained from the RetCam 130-degree lens. These images were obtained from imaging the grid on the posterior surface of the infant schematic model eye. The total area visualized in each image was determined using the pixel measurement function of the Adobe Photoshop CC software. The Heidelberg Spectralis ultrawidefield lens imaged a greater area than the RetCam 130-degree lens (436 700 pixels vs 203 400 pixels).
When our department was procuring a fluorescein angiographic imaging device for infants, one of the important factors was the fundal field of view, which was said to be larger for the Heidelberg Spectralis ultra-widefield lens compared with the RetCam 130-degree lens. To quantify this, we compared the field of view of the Heidelberg Spectralis ultra-widefield lens with the RetCam 130-degree lens using an infant model eye, which was constructed based on Gullstrand’s model of the human eye (Figure 8, Left image).12 A grid with 10degree inclinations in multiple meridians was lasered onto the posterior surface of the model eye (Figure 8, Right image). Infrared reflectance images of the grid were taken with the Heidelberg Spectralis ultra-widefield lens and color images VOL. 159, NO. 1
were taken with the RetCam 130-degree lens (Figure 9). All images were captured through a 7 mm artificial pupil. The images were exported as Joint Photographic Experts Group files and analyzed using Adobe photo editing software (Photoshop CC; Adobe Systems, San Jose, California, USA). Using the software a free-style line was made, demarcating the most peripheral area of visible grid in each image. This area was then highlighted, and its pixels were quantified using the pixel measurement function of the Adobe Photoshop CC software. The total area visualized was compared between the 2 imaging modalities. Each measurement was performed for 5 independent images and averaged. Statistical analysis was performed using statistical software (SPSS 19.0 for
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Windows; SPSS Inc, Chicago, Illinois, USA). Comparison between imaging modalities were performed using the unpaired Student t test and P values
