Journal of Pediatric Ophthalmology and Strabismus

Short Subjects 

Equivalence of Oral Fluorescein Angiography to Intravenous Fluorescein Angiography in Evaluating Pediatric Optic Nerve Pathology

Hilliary E. Inger, MD; Catherine O. Jordan, MD; Fatoumata Yanoga, MD; David L. Rogers, MD

Abstract

Differentiating true optic nerve edema from pseudo-optic nerve edema is a diagnostic dilemma faced by pediatric ophthalmologists. This case series suggests that oral fluorescein angiography is equivalent to intravenous fluorescein angiography in making this distinction. [J Pediatr Ophthalmol Strabismus. 2019;56:e68–e72.]

Abstract

Differentiating true optic nerve edema from pseudo-optic nerve edema is a diagnostic dilemma faced by pediatric ophthalmologists. This case series suggests that oral fluorescein angiography is equivalent to intravenous fluorescein angiography in making this distinction. [J Pediatr Ophthalmol Strabismus. 2019;56:e68–e72.]

Introduction

Optic disc drusen occur in approximately 0.4% of children and their appearance on clinical examination can mimic that of true optic nerve swelling.1 A variety of testing modalities are available to help differentiate optic disc drusen from cases of true optic nerve swelling, and a recent study suggested that intravenous fluorescein angiography (IVFA) was the most accurate diagnostic method to make this distinction in children.1,2 However, IVFA is limited in pediatrics by its need for venipuncture. As an alternative to IVFA, oral fluorescein angiography (OFA) has been used to document both retinal and optic nerve pathology.3–7 We present a case series supporting the equivalence of OFA to IVFA in distinguishing pediatric pseudo-optic nerve edema from true optic nerve edema. This study was approved by the Institutional Review Board at Nationwide Children's Hospital in Columbus, Ohio.

Case 1

An 11-year-old girl presented for optic nerve evaluation in the setting of worsening headaches. An ophthalmologic examination was significant for 360 degrees of optic nerve elevation without vessel obscuration in both eyes. Fundus autofluorescence showed positive autofluorescence at both optic nerve heads (Figure 1). IVFA was completed, showing increasing circumferential hyperfluorescence at the disc margin in both eyes, and a more central hyperfluorescent nodule on the nerve in the left eye. All areas of hyperfluorescence maintained sharp margins, consistent with staining. A diagnosis of pseudo-optic nerve edema secondary to optic disc drusen was made. At the follow-up visit 10 days later, OFA showed a similar staining pattern at each optic nerve.

Optic nerve imaging of case 1. A1–A3 (right eye), B1–B3 (left eye): oral fluorescein angiography images at 20, 30, and 60 minutes after dye consumption. Increasing circumferential and nodular hyperfluorescence, but margins of hyperfluorescence remain sharp. C1 (right eye), C2 (left eye): color photographs showing 360 degrees of optic nerve head elevation without vessel obscuration. D1 (right eye), D2 (left eye): positive autofluorescence of each optic nerve head. E1–E3 (right eye), F1–F3 (left eye): intravenous fluorescein angiography images at < 1, 2 to 3, and > 5 minutes after dye injection. Increasing circumferential (both eyes) and nodular (left eye) hyperfluorescence, but margins of fluorescence remain sharp.

Figure 1.

Optic nerve imaging of case 1. A1–A3 (right eye), B1–B3 (left eye): oral fluorescein angiography images at 20, 30, and 60 minutes after dye consumption. Increasing circumferential and nodular hyperfluorescence, but margins of hyperfluorescence remain sharp. C1 (right eye), C2 (left eye): color photographs showing 360 degrees of optic nerve head elevation without vessel obscuration. D1 (right eye), D2 (left eye): positive autofluorescence of each optic nerve head. E1–E3 (right eye), F1–F3 (left eye): intravenous fluorescein angiography images at < 1, 2 to 3, and > 5 minutes after dye injection. Increasing circumferential (both eyes) and nodular (left eye) hyperfluorescence, but margins of fluorescence remain sharp.

Case 2

A 14-year-old boy was referred for evaluation after an outside examiner had concern for bilateral optic nerve edema. Ophthalmologic examination revealed 360 degrees of optic nerve elevation without vessel obscuration in both eyes. Fundus autofluorescence was normal in both eyes (Figure 2). IVFA showed circumferential hyperfluorescence at the disc margin in the right eye. The left eye demonstrated similar circumferential hyperfluorescence and a central nodular pattern of hyperfluorescence. These findings were consistent with staining, because the hyperfluorescence maintained sharp borders throughout the study. At a follow-up visit 7 days later, OFA showed findings similar to that of the IVFA.

Optic nerve imaging of case 2. A1–A3 (right eye), B1–B3 (left eye): oral fluorescein angiography images at 20, 30, and 60 minutes after dye consumption. Mild circumferential hyperfluorescence of the optic nerve in both eyes, with a nodular component on the left side. The margins of hyperfluorescence remain sharp, consistent with staining. C1 (right eye), C2 (left eye): color photographs showing 360 degrees of optic nerve head elevation without vessel obscuration. D1 (right eye), D2 (left eye): negative autofluorescence of each optic nerve head. E1–E3 (right eye), F1–F3 (left eye): intravenous fluorescein angiography images at < 1, 2 to 3, and > 5 minutes after dye injection. Circumferential disc margin hyperfluorescence in both eyes (left > right) with an associated nodular pattern in the left eye. Margins of hyperfluorescence remain sharp.

Figure 2.

Optic nerve imaging of case 2. A1–A3 (right eye), B1–B3 (left eye): oral fluorescein angiography images at 20, 30, and 60 minutes after dye consumption. Mild circumferential hyperfluorescence of the optic nerve in both eyes, with a nodular component on the left side. The margins of hyperfluorescence remain sharp, consistent with staining. C1 (right eye), C2 (left eye): color photographs showing 360 degrees of optic nerve head elevation without vessel obscuration. D1 (right eye), D2 (left eye): negative autofluorescence of each optic nerve head. E1–E3 (right eye), F1–F3 (left eye): intravenous fluorescein angiography images at < 1, 2 to 3, and > 5 minutes after dye injection. Circumferential disc margin hyperfluorescence in both eyes (left > right) with an associated nodular pattern in the left eye. Margins of hyperfluorescence remain sharp.

Case 3

A 6-year-old boy presented to the emergency department with headaches and decreased vision. Ophthalmologic examination was significant for decreased visual acuity (20/125 in the right eye and hand motions in the left eye) and 360 degrees of optic nerve elevation without vessel obscuration in both eyes. OFA showed increasing hyperfluorescence of the optic nerve with indistinct margins in both eyes consistent with leakage and true optic nerve edema (Figure 3). The following day (> 24 hours later), IVFA was performed and showed similar findings in both eyes. The patient was found to have a lumbar puncture opening pressure of 35 cm H2O and enhancement of both optic nerves on intracranial imaging concerning for optic neuritis.

Optic nerve imaging of case 3. A1–A3 (right eye), B1–B3 (left eye): oral fluorescein angiography images at 20, 30, and 60 minutes after dye consumption. Increasing circumferential hyper-fluorescence with indistinct margins. C1 (right eye), C2 (left eye): color photographs showing 360 degrees of optic nerve head elevation without vessel obscuration. D1 (right eye), D2 (left eye): negative autofluorescence of each optic nerve head. E1–E3 (right eye), F1–F3 (left eye): intravenous fluorescein angiography images at 2 to 5 minutes on the right and 1 to 6 minutes on the left after dye injection. Diffuse hyperfluorescence at the optic nerve head with indistinct margins. Earlier phase photographs were unable to be obtained because the correct camera filter was inadvertently turned off at the beginning of the study.

Figure 3.

Optic nerve imaging of case 3. A1–A3 (right eye), B1–B3 (left eye): oral fluorescein angiography images at 20, 30, and 60 minutes after dye consumption. Increasing circumferential hyper-fluorescence with indistinct margins. C1 (right eye), C2 (left eye): color photographs showing 360 degrees of optic nerve head elevation without vessel obscuration. D1 (right eye), D2 (left eye): negative autofluorescence of each optic nerve head. E1–E3 (right eye), F1–F3 (left eye): intravenous fluorescein angiography images at 2 to 5 minutes on the right and 1 to 6 minutes on the left after dye injection. Diffuse hyperfluorescence at the optic nerve head with indistinct margins. Earlier phase photographs were unable to be obtained because the correct camera filter was inadvertently turned off at the beginning of the study.

Case 4

A 15-year-old girl presented for evaluation in the setting of headaches and double vision. Ophthalmologic examination showed bilateral abducens nerve palsies and 360 degrees of optic nerve elevation with large vessel obscuration at the disc margin in both eyes. A lumbar puncture was performed, revealing an opening pressure of greater than 55 cm H2O and intracranial imaging was without structural lesion. This confirmed a diagnosis of idiopathic intracranial hypertension. IVFA at the time of presentation revealed increasing hyperfluorescence with indistinct margins at each optic nerve head consistent with leakage (Figure 4). Three days later, OFA showed persistent leakage at both optic nerve heads, similar to what was seen on the IVFA.

Optic nerve imaging of case 4. A1–A3 (right eye), B1–B3 (left eye): oral fluorescein angiography images at 20, 30, and 60 minutes after dye consumption. Increasing hyperfluorescence with indistinct margins. C1 (right eye), C2 (left eye): color photographs showing 360 degrees of optic nerve head elevation with some large vessel obscuration at the disc margin in both eyes. Cotton wool spots are also present on each nerve. D1 (right eye), D2 (left eye): negative autofluorescence of each optic nerve head. E1–E3 (right eye), F1–F3 (left eye): intravenous fluorescein angiography images at < 1, 3, and > 5 minutes after dye injection. Increasing hyperfluorescence at the nerve head in both eyes with indistinct margins.

Figure 4.

Optic nerve imaging of case 4. A1–A3 (right eye), B1–B3 (left eye): oral fluorescein angiography images at 20, 30, and 60 minutes after dye consumption. Increasing hyperfluorescence with indistinct margins. C1 (right eye), C2 (left eye): color photographs showing 360 degrees of optic nerve head elevation with some large vessel obscuration at the disc margin in both eyes. Cotton wool spots are also present on each nerve. D1 (right eye), D2 (left eye): negative autofluorescence of each optic nerve head. E1–E3 (right eye), F1–F3 (left eye): intravenous fluorescein angiography images at < 1, 3, and > 5 minutes after dye injection. Increasing hyperfluorescence at the nerve head in both eyes with indistinct margins.

Discussion

Optic disc drusen are acellular deposits of unknown etiology that, when present, can mimic the appearance of papilledema and other causes of true optic nerve swelling.1 Optic disc drusen are the most common cause of pediatric pseudo-optic nerve edema, and as a result, making this distinction is a challenge faced by pediatric ophthalmologists.1,2

In a recent pediatric study, there were no cases of papilledema misinterpreted for pseudo-optic nerve edema when using IVFA as a diagnostic modality.2 As a result, the authors suggested that IVFA was the best imaging technique to correctly differentiate pediatric optic disc drusen from true swelling.2 However, performing IVFA requires peripheral intravenous access through which the fluorescein dye is administered, which can limit its utility in pediatrics.1 Additionally, although nausea and vomiting comprise the most common side effects of IVFA, there is a risk of more severe, and even life-threatening, adverse reactions.8,9 Administration of fluorescein orally has been thought to reduce the risk of both serious and minor reactions and, because it avoids the need for intravenous access, is a more appealing option for use in children.7

OFA has been used in select cases to obtain images to evaluate for the presence or absence of macular edema in aphakic children and to identify areas of retinal nonperfusion in children with incontinentia pigmenti and retinopathy of prematurity.3,4,6 However, the sensitivity of OFA to detect papilledema and other causes of optic nerve swelling has not been extensively studied. In 1987, Ghose and Nayak5 described their experience with using oral fluorescein to characterize the optic nerves of normal children, children with clinically suspected pseudo-optic nerve edema, and children with early papilledema. However, since these publications, the utility of OFA to differentiate pseudo-optic nerve edema from true optic nerve swelling has not been examined.

We presented the IVFA and OFA findings of two cases of pseudo-optic nerve edema secondary to optic disc drusen and two cases of true optic nerve swelling. In cases of pseudo-optic nerve edema, the hyperfluorescence noted at the optic nerve maintained sharp borders in both the OFA and IVFA studies. This was consistent with staining, which is expected given the diagnosis of optic disc drusen. However, in our cases of true optic nerve swelling, the hyperfluorescence increased in intensity and size, and demonstrated increasingly indistinct borders in both the OFA and IVFA studies. This pattern of hyperfluorescence is consistent with leakage, which is characteristic of true optic nerve edema.

When evaluating an optic nerve for possible swelling, it is important to remember that it is possible for optic disc drusen and true edema to coexist.10 Although patients may have enhanced depth imaging optical coherence tomography, B-scan, or fundus autofluorescence testing consistent with optic disc drusen, it is imperative to ensure that they do not have superimposed swelling. The role of fluorescein angiography in this setting is invaluable and can provide the practitioner with critical information to help guide patient care.

In this set of patients, we had the opportunity to perform both the IVFA and OFA studies. This was not done to clarify a diagnostic question, but instead to demonstrate the equivalence of the OFA to the IVFA in diagnosing pediatric optic nerve pathology. The findings of this study suggest that OFA may be of great benefit in differentiating cases of pediatric pseudo-optic nerve edema from causes of true optic nerve swelling, but a larger scale study confirming its efficacy is needed.

References

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Authors

From the Department of Ophthalmology, Nationwide Children's Hospital; Columbus, Ohio (HEI, COJ, DLR); and the Department of Ophthalmology, The Ohio State University, Columbus, Ohio (FY).

The authors have no financial or proprietary interest in the materials presented herein.

Correspondence: Hilliary E. Inger, MD, Department of Ophthalmology, Nationwide Children's Hospital, 555 S. 18th St., Suite 4-C, Columbus, OH 43205. E-mail: Hilliary.inger2@nationwidechildrens.org

Received: June 07, 2019
Accepted: August 19, 2019
Posted Online: December 09, 2019

10.3928/01913913-20191016-02

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