Papilledema is an urgent ophthalmologic finding, as it indicates increased intracranial pressure, which may be caused by serious neurologic conditions like a brain tumor or meningitis. However, in children, pseudopapilledema is more common than true papilledema. Pseudopapilledema occurs when the optic nerves appear elevated due to anatomical factors, such as optic disc drusen (the most common cause of pseudopapilledema). When drusen are buried within the optic disc, as frequently occurs in children, they simulate true papilledema. If pseudopapilledema is misdiagnosed as papilledema, children may undergo an invasive and unnecessary workup including neuroimaging with sedation and lumbar puncture. Moreover, if papilledema is initially misdiagnosed as pseudopapilledema, children may experience delays in proper diagnosis and management of life-threatening disorders.

Several ancillary ophthalmic imaging techniques, including ultrasonography, fluorescein angiography, optical coherence tomography (OCT), autofluorescence, fundus photography, and multicolor confocal scanning laser ophthalmoscopy (cSLO), have been used to differentiate pseudopapilledema (particularly in the context of optic disc drusen) and papilledema in adults. However, many of these imaging techniques are less useful in children, due to unique characteristics of pediatric optic disc drusen. For example, optic disc drusen in children are less likely to be calcified and more likely to be buried, so they may not be detected by techniques that rely on calcification (such as ultrasonography), and they may not demonstrate autofluorescence due to obscuration by overlying tissue.

Optimal Differentiation of Pediatric Papilledema from Pseudopapilledema

Because of the serious implications of misdiagnosing pediatric papilledema and pseudopapilledema, I and other members of the American Academy of Ophthalmology (AAO) Ophthalmic Technology Assessment Committee Pediatric Ophthalmology/Strabismus Panel sought to identify the optimal method to differentiate the two diagnoses. We performed a systematic review of the literature and reported the accuracy of ultrasonography, fluorescein angiography, OCT, autofluorescence, fundus photography, and multicolor cSLO in differentiating papilledema and pseudopapilledema in children, when compared with the gold standard of clinical diagnosis. Each article included in the review received a level of evidence grading by the panel’s methodologist.

The assessment included six articles, which were all graded as level III evidence (Table). Ultrasonography, which is commonly used in adults to identify optic disc drusen, was found to be suboptimal in differentiating pediatric pseudopapilledema from papilledema. Positive percent agreement with clinical diagnosis ranged from 33% to 95% (95% confidence interval [CI], 2% to 100%), and negative percent agreement ranged from 58% to 100% (95% CI 43 to 100%). We found that fluorescein angiography—a combination of two OCT protocols incorporating retinal nerve fiber layer thickness and Bruch’s membrane opening width—and multifocal cSLO had the highest positive percent agreement (ranging from 92% to 100%; 95% CI, 69% to 100%) and negative percent agreement (ranging from 92% to 100%; 95% CI, 70% to 100%) with clinical diagnosis.

However, we caution that none of the imaging modalities demonstrated sufficient accuracy for differentiation of pediatric papilledema and pseudopapilledema when used in isolation, especially considering the overall lack of data; only one study each evaluated fluorescein angiography and multicolor cSLO. We recommend that imaging modalities be used as an adjunct to complete ophthalmic history and examination when deciding whether children should undergo further workup for increased intracranial pressure.

Looking Ahead

Future research recommendations include larger studies with rigorous adherence to diagnostic criteria for papilledema, in addition to masked graders and multi-institutional collaboration, to generate higher-quality levels of evidence. Furthermore, we propose standardization of optic nerve OCT scan acquisition and interpretation in children with pseudopapilledema, similar to the recent guidelines for adults published by the Optic Disc Drusen Studies Consortium. Finally, we suggest that future studies explore the use of newer OCT algorithms, such as three-dimensional analysis, as these novel techniques may improve the ability of imaging technologies to assist in this difficult diagnostic dilemma.