The spectrum of pediatric retinal disorders encompasses a wide range of uncommon diseases that differ from retinal diseases in adults.1 Childhood diseases include retinopathy of prematurity, inherited retinal dystrophies, trauma, tumors, congenital malformations, and uveitis. In evaluating these diseases, fluorescein angiography can be a useful diagnosis and management tool.
Historically, it has been difficult to obtain high quality fluorescein angiography of children in the office. Therefore, fundus photography in young children is typically performed with the RetCam (Clarity Medical System, Pleasanton, CA).2,3 This is a contact lens system with a 120-degree field of view. Although infants can be examined with “swaddling,” older children often require examination under anesthesia.
Ultra wide field technology uses a scanning laser ophthalmoscope (Optos PLC, Dumfermline, Scotland, UK) and is a non-contact method that captures up to 200 degrees of visible fundus. According to the manufacturer’s web site, the camera was originally designed to screen children for peripheral retinal abnormalities without the need for dilation.
The purpose of this study was to report the use of UWFFA in pediatric retinal diseases. We hypothesized that the quality and field of view of the images obtained with the use of UWFFA will provide meaningful information relevant for evaluation of pediatric patients, including documentation, diagnosis, and management of retinal vascular diseases.
Patients and Methods
With Institutional Review Board approval, a retrospective chart review was done at the Jules Stein Eye Institute. An ultra wide field imaging database was searched for patients who had undergone UWFFA (Optos PLC) at age 12 years or younger. Fluorescein angiography was performed with 5% fluorescein dye dosed by weight and injected into the subject’s arm. A standardized protocol originally designed for adult patients was used, and included a 25-gauge butterfly needle.
Charts were reviewed and data were collected, including age, gender, visual acuity, dilation, diagnosis, and patient course. UWFFA was reviewed to assess its value in (1) documentation, (2) diagnosis, and (3) patient treatment. Images were reviewed with Vantage V2 Software (Optos PLC) and manipulated with standard digital enhancement techniques such as zoom, contrast, and gamma adjustment.
All images were evaluated for the presence of angiographic phases (choroidal, arterial, venous, recirculation). The best images from each phase were chosen for field of view and artifact analysis. Quadrants (superior, nasal, inferior, temporal) were considered visible if fundus beyond the equator could be evaluated in the image. Artifacts that obscured a complete quadrant were considered significant and were recorded.
Over a 5-year period, 3,104 patients had imaging performed with ultra wide field technology. Sixty-four patients were younger than 12 years, and 18 of these patients had UWFFA. Two patients were excluded from this study due to missing charts. Sixteen patients were included in the study. The mean age was 9.3 years (range: 5 to 12 years). Twelve patients (75%) were male. Both eyes were imaged in 15 patients in the venous and late phase. One eye could not be imaged due to phthisis bulbi, secondary to a complete retinal detachment caused by stage 5 retinopathy of prematurity. All eyes were dilated at the time of UWFFA. Visual acuity in the study eye ranged from 20/15 to light perception.
The results of the angiographic phase evaluation are shown in Table 1. In one of 16 patients (6.25%), choroidal filling phase was captured. Seven of 16 patients (43.8%) had arterial phase captured. All 16 patients (100%) had images taken from the venous and recirculation phases. A total of 40 images were chosen for field of view and artifact analysis. The mean number of quadrants per phase ranged from 2.9 to 4.0.
Table 1: Angiographic Phase, No. (%) of Patients and Mean No. of Visible Quadrants in That Phase
Artifacts, when present, occurred due to inadequate eye opening leading to peripheral obstructions that decreased the field of view (Table 2). Twelve of 40 images (30%) had eyelashes obscuring the inferior fundus (Figure 1A). Six of 40 images (15%) had blinking motion artifact obscuring the nasal fundus. Three of 40 images (7.5%) had eyelid blocking the superior and inferior fundus (Figure 1B). Anterior media opacities, either a corneal scar or cataract, limited the angiographic evaluation in two of 40 images (5%) (Figure 1C). In 1 of 40 images (2.5%), the nose significantly obscured the temporal quadrant. Visible iris, which indicates that the patient was positioned too far away from the camera, was seen in one of 40 images (2.5%) (Figure 1D).
Table 2: Artifacts, No. (%) of Images Affected, and Fundus Quandrant(s) That Were Blocked
Figure 1. (A) Eyelash artifact in the inferonasal quadrant in patient 2. (B) Eyelid artifact with a normal angiogram in patient 8. (C) Anterior corneal scar with angiogram showing peripheral laser scars and non-perfusion in Coat’s disease and (D) iris and eyelid artifact with a normal angiogram in the fellow eye in patient 7.
A 9-year-old girl with juvenile rheumatoid arthritis presented with visual acuity of 20/50 in the right eye and 20/20 in the left eye and an unremarkable clinical examination (patient 1). UWFFA showed peripheral vascular leakage in both eyes, which was helpful in diagnosing uveitis because the patient had no other signs of intraocular inflammation. The patient was treated by a pediatric rheumatologist for systemic control of disease.
Two patients presented with decreased vision due to pars planitis. The first patient (patient 2) was an 8-year-old boy with visual acuity of 20/80 in the right eye and 20/60 in the left eye due to macular edema. UWFFA showed bilateral vascular leakage in the macula and a marked fern pattern of leakage in the periphery, which was useful in diagnosing vasculitis (Figure 2A). The patient was treated with oral steroids.
Figure 2. (A) Angiogram of pars planitis with cystoid macular edema (inset) and late peripheral vascular leakage in patient 2. Note the superior eyelash artifact in the inferior fundus. (B) Angiogram of treated pars planitis showing mild peripheral vascular leakage in patient 3. Note the inverted nose artifact in the temporal fundus and the shadow artifact from the dexamethasone intravitreal implant (arrow). (C) Normal angiogram of a child (patient 6) with arthropathy confirming no retinal vasculitis. (D) Angiogram of retinopathy of prematurity showing macular dragging, peripheral neovascularization (arrow), and peripheral non-perfusion in patient 9.
The other patient with pars planitis was a 12-year-old girl (patient 3). Her visual acuity was 20/15 in the right eye and 20/40 in the left eye due to cystoid macular edema. UWFFA confirmed cystoid macular edema in the left eye and mild bilateral vascular leakage in the far periphery. Optical coherence tomography also showed cystoid macular edema. The patient was treated with off-label use of 0.7 mg dexamethasone intravitreal implant (Ozurdex; Allergan, Irvine, CA) with resolution of macular edema. Visual acuity 6 months after steroid implantation was 20/20 (Figure 2B).
A 5-year-old boy was referred for headache, joint pain, and ocular inflammation in his right eye (patient 4). Visual acuity was 20/40 in the right eye, with 3+ anterior chamber cell. UWFFA revealed peripheral vascular hyperfluorescence in the right eye. Diagnosis of juvenile sarcoidosis and possible Blau syndrome was made with the help of UWFFA. The patient was treated with topical steroids and atropine.
An 8-year-old girl presented with visual acuity of light perception and signs of panuveitis and retinal detachment in her right eye (patient 5). Systemic work-up was negative. UWFFA showed peripheral capillary non-perfusion with late peripheral vascular leakage. A vitrectomy was performed to repair the retinal detachment. It was unclear whether the detachment was serous or rhegmatogenous.
A 12-year-old boy with a history of anti-nuclear antibody–negative arthropathy was referred for an eye examination to rule out uveitis (patient 6). Medical history included a metabolic storage disease that had led to cardiomegaly, heart transplantation, and chronic immunosuppression. Eye examination was normal and UWFFA was useful in confirming the lack of retinal vasculitis (Figure 2C).
Retinal Vascular Diseases
A 7-year-old boy was diagnosed as having Coat’s disease (patient 7). He presented with visual acuity of counting fingers in his left eye due to chronic cystoid macular edema. UWFFA confirmed macular leakage, peripheral telangiectasia, and laser scars (Figure 1C). Targeted retinal photocoagulation was performed based on peripheral non-perfusion detected with UWFFA.
A 6-year-old boy was diagnosed as having Coat’s disease and had been operated on with resulting visual acuity of no light perception (patient 8). UWFFA was obtained to assess the good eye, which was confirmed to be normal with UWFFA. The family was offered reassurance (Figure 1B).
An 11-year-old girl was monocular due to retinopathy of prematurity (patient 9). Visual acuity in her better seeing eye was 20/250 due to macular dragging. UWFFA highlighted an anatomically abnormal macula and revealed temporal neovascularization (Figure 2D). The patient was treated with targeted laser photocoagulation to areas of peripheral non-perfusion with resolution of neovascularization.
Hereditary Retinal Dystrophies
A 5-year-old boy with X-linked retinoschisis had cystoid spaces in his macula on optical coherence tomography (patient 10). The right eye had superior, peripheral retinal schisis with 20/60 visual acuity due to cystoid macular edema changes. The left eye had been successfully operated on for a retinal detachment with 20/60 visual acuity postoperatively. UWFFA showed stippling in the macula and late leakage in the periphery, consistent with retinoschisis (Figure 3A). The patient was treated with observation.
Figure 3. (A) Angiogram of X-linked retinoschisis with macular stippling (inset) and peripheral hyperfluorescence at the edge of the schisis cavity in patient 10. (B) Angiogram of Stargardt disease with macular atrophy (inset), a silent choroid, and staining of flecks in the posterior pole in patient 11. (C) Color fundus photograph of an eye after trauma with silicone oil and proliferative vitreoretinopathy in patient 11. Note the nose and iris artifact in the temporal fundus. (D) Angiogram highlighting the extent of scarring and severity of injury in patient 12.
A 10-year-old boy had bilateral macular dystrophy and 20/200 visual acuity in both eyes due to retinal pigment epithelium atrophy (patient 11). Electroretinogram and electrooculogram had been normal. UWFFA revealed macular atrophy, a silent choroid, and staining of flecks, which confirmed the diagnosis of Stargardt disease (Figure 3B). The family was counseled for the genetic significance of an inherited retinal dystrophy and the patient was observed.
A 12-year-old boy presented with macular changes in both eyes and visual acuity of 20/20 in the right eye and 20/50 in the left eye due to retinal pigment epithelium atrophy (patient 12). The electroretinogram was normal and the electrooculogram was severely abnormal. He was diagnosed as having Best’s disease. UWFFA had late leakage in the macula of the left eye consistent with staining with a normal periphery. The family was counseled for the genetic significance of a dominantly inherited retinal dystrophy and the patient was observed.
An 11-year-old boy had been operated on elsewhere for intraocular foreign body removal (patient 13). He presented with aphakia and an anterior chamber intraocular lens was placed at our institution. UWFFA was performed, which showed staining of retinal scars without evidence of choroidal neovascularization. Final visual acuity was 20/40 due to corneal aberrations.
A 12-year-old boy had been operated on elsewhere for intraocular foreign body removal and retinal detachment associated with trauma (patient 14). He presented with counting fingers visual acuity, glaucoma, band keratopathy, and silicone oil in the eye. UWFFA was performed, which highlighted extensive proliferative vitreoretinopathy in all four quadrants and the severity of the injury (Figures 3C–3D). No further intervention was recommended and the family was given monocular precautions.
A 6-year-old boy presented with 20/25 visual acuity and a pigmented macular lesion (patient 15). UWFFA showed late staining of the lesion located in the equatorial region of the temporal quadrant that was consistent with an inactive toxoplasmosis scar. Serum IgG titer was positive for toxoplasmosis antibody. The patient was observed.
A 12-year-old girl presented with 20/100 visual acuity in her left eye and a pigmented, elevated lesion superior to the optic nerve (Figure 4A) (patient 16). The lesion was dark with discrete borders on green-free photography (Figure 4B). UWFFA showed early blockage and late punctate leakage (Figure 4C). Ultrasonography demonstrated a highly reflective lesion and the initial diagnosis was choroidal hemangioma. Despite treatment with four sessions of photodynamic therapy, which decreased vascular leakage (Figure 4D), the lesion continued to grow in size. The patient was diagnosed as having choroidal melanoma and treated with I-125 plaque brachytherapy, which resulted in lesion regression.
Figure 4. Patient 16. (A) Color fundus photograph of a pigmented, elevated lesion superior to the optic nerve. (B) Green-free photograph. (C) Angiography before treatment showing punctate areas of leakage. (D) Angiography after photodynamic therapy showing decreased leakage.
Diagnosis categories included uveitis, hereditary retinal dystrophy, retinal vascular disease, trauma, infection, and tumor (Table 3). Six patients (75%) had both macular and peripheral angiography findings. Five patients (31.3%) had peripheral angiography findings only. Two patients (12.5%) had macular findings only. Two patients (12.5%) had normal angiographic findings in the study eye. UWFFA was useful for documentation in all patients, from whom data relevant for diagnosis were obtained in 11 of 16 cases (69%) and affected management decision in 10 of 16 cases (63%).
Table 3: Summary of Patient Demographics, Angiographic Findings, Utility of UWFFA and Diagnosis
This series describes a spectrum of pediatric retinal diseases encompassing uveitis, hereditary retinal dystrophies, childhood retinal vascular diseases, trauma, infection, and tumors that were imaged with ultra wide field imaging. Ultra wide field color fundus photography has been shown to be superior to traditional fundus photography in its ability to image through media opacities and easier patient positioning.4 A patient satisfaction survey found that 75% of patients preferred ultra wide field photography to traditional fundus photography based on speed and patient comfort.5
UWFFA has been useful in studying adult retinal vascular diseases, tumors, and uveitis.6–12 Unique advantages of UWFFA include the ability to capture a large area of retina in a simultaneous angiographic phase and visualize peripheral perfusion abnormalities not otherwise detectable. In vein occlusions, peripheral non-perfusion on UWFFA has been related in macular edema and pathological neovascularization.8,9
In the current study, we reported angiographic phases, peripheral artifacts, and the significance of perfusion abnormalities using ultra wide field imaging in a cohort of pediatric patients. Angiograms were systematically evaluated to see whether all four angiographic phases were captured. Only one patient, age 12 years, had four phases imaged, although photographers were not specifically given instructions to image the choroidal phase. Seven of 16 patients (43.8%) had the arterial phase captured. All patients had late phases successfully taken. We hypothesize that this is due to the time it takes to console the child after fluorescein injection and to reposition the head.
If early phases are of interest, it may be better to place an intravenous line to allow time for the child to calm down before injecting fluorescein. In children, intravenous access can usually be obtained in either the back of the hand, antecubital space, or great saphenous vein at the ankle. Based on our experience, we recommend establishing direct communication with the photographer, especially if early phases or a specific region is needed.
There are known artifacts such as eyelashes that decrease the field of view and appear in the opposite quadrant. Artifacts were systematically reviewed in this study. The most common artifact was superior eyelash artifact, present in 12 of 40 images (30%), which appeared in the inferior part of the image. Overall, the mean number of peripheral quadrants visualized was high, ranging from 2.9 to 4.0. There were fewer artifacts seen in the later phases, consistent with the hypothesis that children are more cooperative during the later phases.
Several methods have been employed to decrease eyelash artifacts, such as placement of a speculum or taping eyelashes back with butterfly stitches (Steri-Strip; Nexcare, St. Paul, MN). However, these maneuvers are not well tolerated in children and often dry out the corneal surface, thus negating their advantages. Instead, the patient can be instructed to look up while pulling the inferior eyelid down to image the superior fundus and avoid eyelash artifact. When looking down to image the inferior fundus, a cotton swab can be used to gently hold the superior eyelid back.
Abnormal peripheral angiographic findings were observed in 12 of 16 patients (75%). These included vasculitis, telangiectasia, and neovascularization. Some of these lesions may have been appreciated on clinical examination, but exact characterization was challenging or impossible without angiography. Presumably these findings would not have been detected or would have been difficult to detect with conventional angiography. It should be noted that even with a cooperative patient and a high quality image such as in Figure 2C, there are still artifacts related to the limitations of an azimunthal projection.7 In other words, the more peripheral areas of retina are distorted because the images are flat depictions of a round surface.
This study was limited due to its retrospective nature. The angiograms were taken by different photographers with a standardized protocol created for adults. We recommend creating a specific protocol for fluorescein angiography in children to maximize the quality of UWFFA. This includes considering placement of an intravenous line when early angiographic phases are of specific interest. It is also recommended that the entire procedure be explained to the child and family beforehand.
This series of patients highlights uncommon retinal vascular diseases seen by pediatric retinal specialists and the utility of UWFFA in documentation, diagnosis, and treatment of these patients. Future studies could consider comparing UWFFA with traditional angiography in children and comparing UWFFA in children to adults.
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- Prasad PS, Oliver SC, Coffee RE, et al. Ultra wide-field angiographic characteristics of branch retinal and hemicentral retinal vein occlusion. Ophthalmology. 2010;117:780–784. doi:10.1016/j.ophtha.2009.09.019 [CrossRef]
- Oliver SC, Schwartz SD. Peripheral vessel leakage (PVL): a new angiographic finding in diabetic retinopathy identified with ultra wide-field fluorescein angiography. Semin Ophthalmol. 2010;25:27–33. doi:10.3109/08820538.2010.481239 [CrossRef]
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Angiographic Phase, No. (%) of Patients and Mean No. of Visible Quadrants in That Phase
|Angiographic Phase||Patients (n = 16)||Quadrants Visible (mean)|
|Arterial||7 (43.8 %)||2.9|
Artifacts, No. (%) of Images Affected, and Fundus Quandrant(s) That Were Blocked
|Artifact||Images (n = 40)||Quadrant(s) Blocked|
|Blinking motion||6 (15%)||Nasal|
|Eyelid blocking||3 (7.5%)||Superior, inferior|
|Anterior media opacity||2 (5.0%)||All|
Summary of Patient Demographics, Angiographic Findings, Utility of UWFFA and Diagnosis
|Pt||Age (y)||Gender||Angiographic Findings||Utility of UWFFA||Specific Diagnosis||Diagnosis Category (%)|
|1||9||F||Peripheral leakage||X||X||X||JRA||Uveitis (37.5%)|
|2||8||M||CME and peripheral leakage||X||X||X||Pars planitis||Uveitis (37.5%)|
|3||12||F||Peripheral leakage||X||X||X||Uveitis (37.5%)|
|4||5||M||Peripheral leakage||X||X||X||Juvenile sarcoidosis||Uveitis (37.5%)|
|5||8||F||Non-perfusion with late peripheral leakage||X||X||X||Panuveitis||Uveitis (37.5%)|
|7||7||M||CME and peripheral telangiectasia||X||X||Coat’s disease||Retinal vascular (18.8%)|
|8||6||M||Normal||X||X||Coat’s disease (fellow eye)||Retinal vascular (18.8%)|
|9||11||F||Peripheral neovascularization||X||X||ROP||Retinal vascular (18.8%)|
|10||5||M||CME and peripheral leakage||X||X||X||XLRS||Hereditary retinal dystrophy (18.8%)|
|11||10||M||Silent choroid with flecks||X||X||Stargardt’s disease||Hereditary retinal dystrophy (18.8%)|
|12||12||M||RPE atrophy||X||X||X||Best’s disease||Hereditary retinal dystrophy (18.8%)|
|13||11||M||Staining of scars||X||Retinal detachment||Trauma (12.5%)|
|14||12||M||Staining of scars||X||IOFB||Trauma (12.5%)|
|15||6||M||Staining of scars||X||Toxoplasmosis scar||Infectious (6.3%)|
|16||12||F||Leakage around tumor||X||X||X||Choroidal melanoma||Tumor (6.3%)|