Mistaking congenital anomalies for acquired disease

Congenital anomalies comprise a spectrum of disorders of varying severity. When severe, such anomalies are readily appreciated at birth or in early infancy. Examples of neuro-ophthalmic anomalies that present early in life include congenital esotropia, ptosis and severe bilateral optic nerve hypoplasia. Milder forms may not be detected until adulthood and may come to medical attention in several ways. In some cases, patients are asymptomatic, and their congenital anomaly is detected only when the visual system is evaluated for another purpose. Examples of this include persistent myelinated nerve fiber layer, pigmented lesions of the optic disc and partial forms of optic nerve hypoplasia. In other cases, the patient does have symptoms that could be due to a condition that resembles a congenital anomaly. An example of this scenario is the patient who seeks medical attention because of headaches and is found to have pseudopapilledema. In still others, an abnormality that has been present since birth only becomes symptomatic in adult life. For example, many forms of ocular misalignment can be kept in check by binocular fusion, only to decompensate in midlife for a variety of reasons. The Chiari malformation, while clearly a congenital malformation, often remains asymptomatic throughout childhood but causes progressive neurologic deficits in adulthood. Similarly, aqueductal stenosis may decompensate after years of stability.

Recognition of the congenital nature of an abnormality is important because unnecessary testing

and treatment can then be avoided. In most cases there are sufficient clinical clues to help make this determination.

Headaches and elevated discs

Case: A 15-year-old high-school student consulted her family physician because of headaches. She had had an occasional “sick headache” since age eight but these had become more frequent over the past year. Her headaches were accompanied by nausea and photosensitivity and were usually relieved by sleep. She was unaware of any factors that precipitated her headaches. She was otherwise healthy and her growth and development had been normal. She denied pulsatile tinnitus, transient obscurations of vision and diplopia. Her general examination was normal, but fundus examination revealed bilateral optic disc elevation. This finding prompted a brain MRI that was normal. A lumbar puncture was recommended but, at her mother’s request, she was sent first for neuro-ophthalmic consultation.

Visual acuity was 20/20 in each eye with normal color vision, pupillary responses and ocular motility. Visual field testing was normal by Goldmann perimetry. Fundus examination showed moderate elevation of both optic discs without opacification of the nerve fiber layer or venous engorgement (Figure 3.1). Based on the optic disc appearance, pseudopapilledema due to buried drusen was suspected.

Is there a way to confirm the presence of drusen in this patient?

Drusen can be demonstrated with orbital ultrasonography, CT scan or by demonstrating autofluorescence. In this case, an orbital ultrasound (B-scan) was performed, which showed hyper-reflectivity within the disc substance of each eye, confirming a diagnosis of drusen (Figure 3.2). This patient’s headaches were thought to be migrainous and were managed accordingly.

Discussion: Optic disc drusen are a common congenital anomaly, found in up to 2% of normal individuals. Drusen are inherited as an autosomal dominant trait but with irregular penetrance. Earlier theories held that individuals with drusen are born with a tendency to form small concretions within the optic disc, which may cause damage to optic nerve fibers either by direct compression or by interfering with blood supply. Current thinking, however, suggests that the initial step in the process of drusen formation involves leakage of axoplasmic material from neurons. Over time, this substance

Figure 3.2 Orbital B-scan ultrasonogram shows hyper-reflectivity within the disc substance consistent with drusen (arrow).

tends to collect calcium, iron, mucopolysaccharides and other material (Figure 3.3). The reason for this axonal leakage is unclear, perhaps related to an anomaly of the lamina cribrosa rather than a metabolic defect of axoplasmic transport. Whatever the exact mechanism, we now view disc drusen as a form of chronic optic neuropathy that is very slowly progressive over a lifetime.

Figure 3.3 Cross section through the optic disc in an eye with buried drusen. Intrapapillary drusen appear as concretions within the substance of the prelaminar nerve head (arrows).

Disc drusen are bilateral in 75% of cases. The severity of drusen, both in terms of disc appearance and optic nerve function, is extremely variable. Visual field abnormalities are common, found in up to 87% of affected eyes. However, visual acuity is rarely reduced because the defects usually involve the arcuate or radial nerve fiber bundles rather than the papillomacular bundle. Occasionally, drusen are associated with vascular events involving the optic disc and retinal circulations, most notably anterior ischemic optic neuropathy and spontaneous hemorrhages into the nerve head. Such secondary complications can cause acute loss of vision that involves the central field and thus reduces visual acuity. Although drusen can produce slowly progressive visual loss over a lifetime, such deficits are not usually disabling. In most cases, the chief significance of drusen (and other forms of congenital disc elevation) is not that it is a serious condition, but rather that it looks like something serious, namely papilledema.

In young children, drusen are more likely to be buried, whereas in adults they are often visible on the disc surface (Figure 3.4). An effective technique for appreciating surface drusen is to use the smallest light of the direct ophthalmoscope to illuminate one part of the disc while observing another area. In this manner, light reflects off the side of small refractile bodies making them more apparent. Eyes

Figure 3.4 Disc photograph showing prominent drusen on the disc surface.

Table 3.1 Ophthalmoscopic features in papilledema vs. pseudopapilledema

with buried drusen pose more of a diagnostic challenge, the specific task usually being the distinction between pseudopapilledema and papilledema (i.e. disc edema due to increased intracranial pressure). There are several ophthalmoscopic observations that are helpful for distinguishing between congenital and acquired disc elevation (see Table 3.1 – and Figures 3.5, 3.6 and 3.7). The most

Figure 3.6 Papilledema. Despite well-developed disc swelling, there is preservation of a sharp disc margin, illustrating the limitation of using this feature to distinguish congenital from acquired disc elevation.

sensitive and specific indicator of acquired disc edema is opacification of the nerve fiber layer. This opacification is best understood by recalling the pathophysiology of papilledema; namely obstruction or slowing of axoplasmic transport

Figure 3.7 Optic disc drusen with anomalous branching of the retinal vasculature and prominent peri-papillary pigment changes, features that commonly accompany drusen.

with resultant swelling of axons. Because the nerve fiber layer is between the examiner’s eye and the patient’s retinal blood vessels, such opacification is best appreciated by noting obscuration of these vessels (Figure 3.5A). The presence of “blurred

disc margins” is not a particularly useful sign (Figure 3.6).

Examination of the retinal vessels can provide additional clues. In true papilledema, the capillaries on the disc surface are usually hyperemic and the retinal veins become tortuous, distended and nonpulsatile (Figure 3.5B). In addition, the branching pattern of the retinal vasculature is often anomalous in eyes with drusen (Figure 3.7). The absence of spontaneous pulsations is not a helpful differential finding since pulsations are visible in just 60% of the normal population; however their presence speaks strongly against increased ICP. Observing the size of the physiologic cup is also helpful. In most eyes with pseudopapilledema the cup is absent; in fact, the center of the disc is often the most elevated area. In contrast, filling in of the physiologic cup is a late event in the evolution of papilledema. In most cases, by the time the cup is obliterated, the nature of the disc elevation is no longer in question (Figure 3.5).

Disc hemorrhages may occur in either condition but the pattern of hemorrhage is informative. In papilledema, hemorrhages are typically within the nerve fiber layer (sometimes termed “flame” or “splinter” hemorrhages, Figure 3.8A) whereas in pseudopapilledema they are usually deep, are located just at the edge of the disc and have a crescentic shape (Figure 3.8B). Repeated hemorrhages of this sort lead to pigment alterations in the peri-papillary area, a common finding in eyes with drusen (Figure 3.7). In occasional cases, development of a subretinal neovascular net causes repeated hemorrhage and leakage into the surrounding retina.

Drusen can usually be suspected from the ophthalmoscopic appearance. Their presence can sometimes be confirmed on a non-contrast orbital CT, although with less sensitivity than ultrasound (Figure 3.9A). Drusen are not visible on MRI. In the hands of an experienced examiner, ultrasonography is the preferred investigative tool. Finding

hyper-reflective signal within the substance of the optic disc confirms a diagnosis of buried drusen, whereas the presence of a widened nerve sheath is indirect evidence for increased intracranial pressure. Fundus photography also can be helpful: with the cobalt filter used for fluorescein angiography but without injection of dye, surface drusen may be revealed by their autofluorescence (Figure 3.9B). Fluorescein angiography can also furnish useful information: absence of leakage in the late phases of the study effectively rules out acquired disc edema.

In most cases, a diagnosis of pseudopapilledema can be established based on the history and examination findings, with particular emphasis on ophthalmoscopic findings. In some cases, the addition of ancillary testing, as described above, can be confirmatory. It is rarely necessary to proceed with a lumbar puncture to exclude causes of acquired disc edema. The diagnosis of congenitally anomalous discs should not be considered a diagnosis of exclusion.

Diagnosis: Buried drusen (pseudopapilledema)

Tip: Pseudopapilledema can usually be distinguished from acquired disc edema based on ophthalmoscopic appearance.

Inferior altitudinal visual field defects

Case: This 24-year-old receptionist was found to have an abnormal visual field on a routine screening test. The patient was unaware of the defect and had no visual or neurologic symptoms although she did acknowledge that she had always been considered clumsy and tended to trip over things. She was otherwise healthy. Family history was negative for neurologic or eye disease except for diabetic retinopathy in her mother. A more complete eye examination demonstrated visual acuity of 20/20 in each eye with normal color vision, pupillary responses and intraocular pressures. Goldmann perimetry confirmed an inferior altitudinal defect in each eye (Figure 3.10). The optic discs