Papilledema can be one of the most alarming clinical findings to encounter during a comprehensive eye examination. As primary eyecare providers, it is crucial to differentiate true papilledema from pseudopapilledema. Pseudopapilledema is generally not an urgent finding and is managed very differently than papilledema.
Differentiating papilledema from pseudopapilledema can seem initially daunting; however, this article will provide the necessary clinical pearls for distinguishing and managing both conditions appropriately.
Papilledema: An overview
Papilledema is a disease where there is swelling of the optic nerve (a form of optic disc edema), specifically due to the elevation of intracranial pressure (ICP).1 ICP is the pressure exerted by the blood, cerebrospinal fluid (CSF), and other fluids inside the skull on the brain tissue.1
An increase in the volume of blood and CSF within the intracranial space can result in high ICP and can be observed in the following circumstances:1,2
- Space-occupying lesion: Brain tumor or brain hemorrhage
- Increase in blood volume: Venous sinus thrombosis
- Increase in CSF: Obstructive hydrocephalus
- Idiopathic intracranial hypertension
The optic nerve’s meningeal layers are continuous with the brain’s meningeal layers, making intracranial CSF also continuous with the CSF surrounding the optic nerve. This allows for situations of elevated ICP to be exerted directly onto the optic nerve.
The elevated ICP disrupts the normal pressure gradient across the optic nerve, and whether this is from mechanical compression or ischemia to the optic nerve axons, it causes retrograde axoplasmic flow across the optic nerve resulting in papilledema.1,2
Figure 1: Papilledema from idiopathic intracranial hypertension in a 36-year-old Hispanic female patient.
Figure 1: Courtesy of Kevin Cornwell, OD.
Signs and symptoms of papilledema
With papilledema, the following are the most common signs and symptoms:1,7
- Commonly occurs bilaterally and rarely unilaterally
- Elevated optic nerve head, blurred disc margins, dilated veins, disc hemorrhages and/or exudates, and peripapillary retinal folds known as Paton’s lines
- Lack of spontaneous venous pulsations at the optic disc is a sign of elevated ICP due to the ICP equaling or exceeding the intraocular pressure (IOP), causing the spontaneous venous pulsations to cease
- Enlarged blind spot on a visual field assessment during the acute stage
- Transient vision loss
- Horizontal binocular diplopia (CN 6 palsy)
- Pulsatile tinnitus
- Headaches
- Nausea and vomiting may present with acute rises in ICP
The largest study of IIH, The Idiopathic Intracranial Hypertension Treatment Trial (IIHTT), revealed the most common symptoms that participants presented with were headache, transient vision loss, pulsatile tinnitus, and dizziness. In addition, weight gain and obesity were risk factors for IIH. Demographics in the IIHTT showed patients were commonly female, had an average age of 29, and had a body mass index (BMI) of 39.9kg/mm2.8
Taking a deeper look at pseudopapilledema
Pseudopapilledema is caused by abnormalities, largely physiologic, that surround the optic nerve and obscure the nerve margins. These abnormalities can cause an elevated appearance to the optic nerve without edema and swelling of the retinal nerve fiber layers.3,4,5,6
There are several different causes of pseudopapilledema:
- Small optic nerves: Hyperopic eyes have shorter axial lengths and can appear to have an elevation of the optic nerve head.3
- Burgmeister papillae: An incompletely regressed hyaloid artery that can obscure the optic nerve and its margins.3
- Myelinated nerve fibers: Oligodendrocytes can migrate past the lamina cribrosa and obscure the margins of the optic nerve.3
- Optic disc drusen (ODD): Calcium, hyaline, and other protein deposits located anterior to the lamina cribrosa that can progress from deep to superficial retinal nerve fiber layers, resulting in an increase in elevation of the optic nerve head over time.4,5
- Vitreopapillary traction (VPT): The posterior hyaloid of the vitreous remains attached to the anterior optic nerve head and can exert traction; this can cause the appearance of optic nerve elevation.6
Signs and symptoms of pseudopapilledema
Depending on the etiology, pseudopapilledema can present with an appearance of an elevated optic nerve head, blurred disc margins, and visual field defects; however, patients are commonly asymptomatic.
In cases of ODD, the drusen may be superficial and easily visible on examination as refractile bodies or yellow drusen.9 Common patterns of field defects in ODD include enlarged blind spots and peripheral defects.9 Visual function loss correlates with the amount of drusen in the optic nerve head and is more severe within patients with superficial drusen, drusen larger than 500μm, or coalescent drusen.9
Rarely, patients with ODD may notice transient vision loss, which can be attributed to ischemia from the vascular compression by the drusen. This circumstance can lead to non-arteritic ischemic optic neuropathy (NAION).9,10
Differential diagnosis: Papilledema vs. pseudopapilledema
During a comprehensive eye exam, it is imperative to take a thorough case history that includes asking about a patient’s symptoms, if any, and current medications in detail, as some medications have been linked to IIH, such as estrogen, oral contraceptives, isotretinoin, vitamin A derivatives, and tetracyclines.8
When assessing the optic nerve head in both eyes, an initial observation of an elevated optic nerve head and blurred disc margins needs to be further examined in order to distinguish between true optic disc edema and pseudopapilledema. Blurred and bumpy optic disc margins can occur when ODD is deep in the optic nerve and obscured by the overlying retinal nerve fiber layer where direct visualization is not possible.
In optic nerves with buried drusen, there should not be any ambiguous blood vessels, nor should there be any vascular changes such as hemorrhages or exudates which commonly occur with optic disc edema.9,10 When disc edema is observed in the clinic, the patient may present with poor visual acuities and transient visual obscurations, among several other symptoms.
Ancillary testing to distinguish between optic disc edema and ODD include:
- Intravenous fluorescein angiography (IVFA): IVFA is the gold standard test for the diagnosis of true optic disc edema or papilledema, which will show leakage from the optic nerve if disc edema is present, and pseudopapilledema will only show late staining of the nerve.11
- Fundus autofluorescence (FAF): FAF will highlight more superficial drusen within the optic nerve which hyper-autofluoresce.11
- B-scan ultrasonography: B-scan ultrasonography can detect drusen as a hyperechoic signal at the nerve head that creates an acoustic shadow and a deep artifact.12
- Optical coherence tomography (OCT): OCT can be used to document the peripapillary retinal nerve fiber layer thickness, and for visualization of the deep structures of the optic nerve that include buried drusen.11,13 Drusen appear as hyporeflective masses with hyperreflective borders on OCT.11,13 It is important to note that OCT is not considered reliable in distinguishing true disc edema from pseudopapilledema.11,13
Imaging and referral for optic disc edema
Once optic disc edema is diagnosed, other causes such as intraocular inflammation, central retinal vein occlusion, compressive optic neuropathy, optic neuritis, and ischemic optic neuropathy need to be ruled out before papilledema can be diagnosed.2
The initial workup of optic disc edema should include blood work that encompasses a complete blood count, blood sugar, angiotensin-converting enzyme, erythrocyte sedimentation rate, and a syphilis serology that may help look for signs of infectious, metabolic, and inflammatory diseases.2,11
When there is a concern for true papilledema, optometrists should not hesitate to immediately refer the patient to the nearest hospital emergency room for diagnostic testing (e.g., magnetic resonance imaging [MRI] and lumbar puncture). Having access to an on-call general ophthalmologist at a hospital or a neuro-ophthalmologist can also be helpful.
Hypercoagulation can also be tested for patients suspected of cerebral venous sinus thrombosis.14 Contrast-enhanced magnetic resonance imaging of brain and orbits as well as magnetic resonance venography are done to respectively search for mass or venous sinus thrombosis.14
Once neuroimaging demonstrates no risk of herniation, a lumbar puncture is performed to document ICP by measuring the opening pressure.1,2 Cerebrospinal fluid studies to analyze protein, glucose, cell count and differential, and cultures are also diagnostic in ruling out neoplastic, infectious, and inflammatory causes.1,2,11
Medical and surgical treatment options for papilledema and pseudopapilledema
The treatment for papilledema is aimed at addressing the cause of the raised ICP. In cases of a brain mass being present, surgical treatment may be indicated.2 Venous sinus thrombosis starts with prevention management that includes anticoagulation medications.14
IIH is diagnosed in patients with appropriate workup and documented high ICP where no structural or other localizing causes are present. These patient’s symptoms are typically managed with acetazolamide, modifying hormonal contraceptives, and weight loss.8
Surgical measures such as optic nerve sheath fenestration are considered when vision is thought to be severely threatened.2,8 Ventriculoperitoneal and lumboperitoneal shunts are other surgical procedures that can reduce ICP by draining the CSF.2,8
The prognosis for papilledema is related to the chronicity of the disease. A constant elevation of ICP can lead to irreversible damage of the nerve fiber layer which can cause visual field defects to worsen over time, including eventual central visual acuity loss.2,8
The prognosis of ODD is generally very good.9,10,11 With time, Individuals with drusen can develop visual field defects that are usually mild, in the periphery, and very slowly progressive.10,11 There are no recognized treatment options for ODD; however, off-label use of ocular hypotensive drops have been used for management of ODD in severe cases. Complications of ODD should receive treatment as they occur as there are no preventative measures available at this time.
Figure 2: Optic disc drusen OU in a 34-year-old Caucasian female patient, treated off-label with latanoprost QHS OU.
Figure 2: Courtesy of Kevin Cornwell, OD.
Patients with ODD are at a higher risk of experiencing NAION, and these patients have an increased risk of developing NAION in the other eye.15 Individuals with ODD are also at risk of central retinal artery occlusions and central retinal vein occlusions due to the potential compression of the surrounding arteries, veins, and retinal ganglion cell axons by the ODD.16,17
In VPT, a posterior vitreous detachment can cause the traction on the optic nerve head to automatically settle and resolve. If the patient is severely symptomatic, a pars plana vitrectomy could be a possible treatment.6
In conclusion
In differentiating papilledema from pseudopapilledema, a timely workup needs to be a priority, as this is critical in managing these cases promptly and successfully.
Appropriate referrals to specialists should be made where proper analysis of the optic nerves and adjunctive tests are performed for additional guidance. This allows for precise and effective communication between co-managing and referring healthcare providers that optimize patient care and safety.
