AION rarely occurs in children with optic disc drusen.406,440 Rare cases of AION may complicate cranial vault reconstruction. Lee et al338 described a 5-year-old boy who developed bilateral blindness following cranial vault reconstruction for nonsyndromic sagittal synostosis. Prone positioning, intraoperative blood loss, controlled hypotension during surgery, and eyelid edema may have contributed to this blindness. However, his visual acuity gradually recovered to 3/200 in the right eye and 20/20 in the left eye.

Ischemic optic neuropathy may produce sudden blindness in children on continuous peritoneal dialysis.325 Patients generally present with light perception and bilateral mydriasis, unreactive to bright light. Retinal examination discloses bilateral disc swelling, edema, and hemorrhages. Blood pressure is generally low, and dehydration may or may not be present. Hypovolemia is suspected to be the cause. Partial improvement of vision may occur over several months. Kim et al304 described a 2-year-old child with end-stage renal disease on continuous peritoneal dialysis who lost vision bilaterally and had unreactive pupils bilaterally secondary to AION. He was dehydrated and received intravenous fluid on admission, as well as methylprednisolone and levodopa. On day 3, his pupils again became reactive to light, and his vision improved. A combination of acute and chronic ischemia may also cause AION in patients with autosomal recessive polycystic kidney disease who are not on dialysis. One of these patients had massive blood loss secondary to esophageal varices from associated portal venous hypertension.91

Posterior ischemic optic neuropathy (PION) following spine surgery has been reported in both adults and children.69,305 Most patients initially have normal-appearing discs without swelling, with gradual development of optic atrophy.69 Although younger patients have a better prognosis for visual recovery, some patients fail to recover.305 Special features of complex spinal surgery that may predispose to PION include long operating times, substantial intraoperative blood loss, deliberate hypotensive anesthesia, prone positioning and, possibly, direct pressure on the globe from a badly positioned headrest.305

Autoimmune Optic Neuropathy

Autoimmune optic neuropathy was first described by Dutton et al.137 His three patients were defined by a recurrent corti- costeroid-dependent optic neuropathy.180 Elevated antinuclear antibodies without defined collagen-vascular disease were the early markers for this disorder. Kupersmith’s subsequent series319 included anticardiolipin antibody in their evaluation and found four of six patients to be positive for the disorder. Bielory et al48 found that 82% of their patients with autoimmune optic neuropathy were positive for the IgM idiotype. Skin biopsy usually demonstrated abnormalities on

light microscopy, immunofluorescence, or both.48 It is unclear whether anticardiolipin antibodies represent a marker for the condition or whether they are immunogenic. Most patients do not demonstrate the classic triad of thrombocytopenia, vasoocclusion, and recurrent miscarriage, and rarely develop a defined collagen disease.

Frohman et al180 described autoimmune optic neuropathy in a 4-year-old girl who experienced four episodes of bilateral optic neuritis with mild concurrent weakness, ataxia, or dizziness. Autoimmune optic neuropathy was diagnosed because of the presence of anticardiolipin antibody and an abnormal skin biopsy with thrombin and immunoreactant deposition. Although autoimmune optic neuropathy in adults is usually treated with immunosuppression, she was treated with corticosteroids, gammaglobulin (because of the risk of long-term immunosuppression in a child), and aspirin, which diminished the intensity of her attacks.

Optic disc swelling can accompany the autoimmune polyendocrinopathy syndrome, type 1 (also known as autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy [APECED] syndrome).84 This rare immune disorder causes progressive endocrine tissue destruction, cell-mediated immunity deficiency, and ectodermal dystrophies. Clinical manifestations usually appear in childhood and consist of hypoparathyroidism, oral candidiasis, and adrenocortical insufficiency, chronic malabsorption, and diarrhea. Ocular complications include dry eye, iridocyclitis, cataract, retinitis pigmentosa, optic disc swelling, and optic atrophy.377 Antibodies against the retina and optic nerve have been found in one patient with autoimmune polyendocrinopathy syndrome.586

Pseudopapilledema

Anomalous elevation of the optic disc is a primary diagnostic consideration in the child referred for papilledema.252 Buried drusen in the optic disc is the most common form of pseudopapilledema in childhood and must be distinguished from other causes of pseudopapilledema, such as hyperopia, myelinated nerve fibers, epipapillary glial tissue, and hyaloid traction on the disc.484

Optic Disc Drusen

The word drusen, of Germanic derivation, originally meant tumor, swelling, or tumescence.357 According to Lorentzen,357 the word was used in the mining industry approximately 500 years ago to indicate a crystal-filled space in a rock. Other terms such as hyaline bodies and colloid bodies are occasionally used to describe drusen of the optic disc.174

The fact that drusen may closely simulate early or chronic papilledema, that they are associated with visual field defects, and that they occasionally show solitary hemorrhages often serve to complicate the diagnostic picture and impart a sense of urgency to the diagnosis.479 If buried drusen go unrecognized, the elevated optic discs may precipitate inappropriate diagnostic studies.467

The conceptual problem that persists in understanding the evolution of disc drusen comes from viewing drusen as the cause rather than the effect of an underlying configurational anomaly of the disc. This tendency carries over into our analysis of associated complications (e.g., the lack of correspondence between visual field abnormalities with the position of visible drusen on the disc has puzzled many). It is helpful to recognize at the outset that the time course of the evolution of optic disc drusen and the histopathological findings suggest that disc drusen actually result from axonal degeneration rather than encroaching upon adjacent axons to cause their degeneration. Disc drusen signify a chronic, low-grade optic neuropathy measured over decades.

Epidemiology

Lorentzen356 examined 3,200 routine cases from an ophthalmological practice in Denmark and found that 11 had drusen of the optic disc (for a prevalence of 0.34%). This prevalence increased by a factor of 10 in family members of patients with disc drusen.357 Friedman et al176 examined 737 cadavers and found disc drusen in 15. The drusen were often minute and situated deep within the optic nerve tissue. Francois,168 and later Lorentzen, concluded that familial drusen are transmitted as an autosomal dominant trait. Subsequent studies

have confirmed the familial nature of this anomaly.254,356,517 Disc drusen are rare in blacks.254,366,467 The early notion that disc drusen are associated with hyperopia has not been substantiated.254,398,467 In one large study,467 visible disc drusen were bilateral in about two-thirds of cases, whereas pseudopapilledema associated with buried drusen was bilateral in 86% of cases. Although Erkkila147 found a high prevalence of clumsiness, learning disabilities, and neurological problems in her Finnish population of children with drusen, subsequent studies have failed to substantiate these findings.

Ophthalmoscopic Appearance in Children

In our experience, most childhood cases present initially with pseudopapilledema secondary to buried drusen (Fig. 3.20). In this setting, the disc appears elevated, and its margins are blurred or obscured.174 The elevated disc may have a gray or a yellow-white discoloration. Disc drusen tend to become more ophthalmoscopically conspicuous with age.381 In older children, there is often a scalloped contour to the disc margins, due to the presence of partially buried drusen protruding from the edge of the disc into the peripapillary retina.174

Buried drusen are most visible at the margin of the disc, where they impart an irregular lumpy-bumpy contour to the line of demarcation between the elevated disc and the retina (Fig. 3.21). Exposed drusen are more frequently found on the nasal side of the optic disc. Surface drusen appear as yellowish, globular, hemitranslucent formations on the optic disc, often accumulated in larger or smaller conglomerations357 (Fig. 3.2). They may occur singularly, in grape-like clusters, or as fused conglomerations, varying in size from small dots to several vein widths in diameter.174 With direct illumination,

Fig. 3.22  (a) Buried disc drusen with superior and inferior juxtapapillary subretinal neovascular membranes. (b) Fluorescein angiogram demonstrates typical patchy hyperfluorescence of disc drusen,

along with late peripapillary staining corresponding to juxtapapillary subretinal neovascular membranes. Courtesy of Stephen C. Pollock, M.D.

the central portion of each druse shines uniformly, while the border may appear as a glistening ring. With indirect illumination of the druse from light focused on the peripapillary retina, the druse shines uniformly, except for a brighter, semicircular marginal zone on the side opposite the spot of light (known as inverse shading).

In addition to the small size of the optic disc and the absence of a central physiological cup, the disc vasculature is anomalous (Fig. 3.21). The major retinal vessels are increased in number and often tortuous (Fig. 3.21). They tend to branch early and sometimes trifurcate or quadrificate. The prevalence of cilioretinal arteries is also increased, with estimates ranging

from 24.1%400 to 43%.147 Mustonen398 found peripapillary atrophy or pigment epithelial derangement in 29.7% of eyes (Fig. 3.22). Retinal venous loops or anomalous retinociliary shunt vessels are occasionally seen.

Distinguishing Buried Disc Drusen from Papilledema

The distinction between pseudopapilledema associated with buried drusen and papilledema (or other forms of optic disc edema) is sometimes difficult, but there are several clinical signs that serve to distinguish these two conditions (Table 3.12).252

The late phases may be characterized by some minimal blurring of the drusen that may either fade or maintain fluorescence (staining). Unlike in papilledema, however, there is no visible leakage along the major vessels.480,517 Venous anomalies (venous stasis, venous convolutions, and retinociliary venous communications) and staining of the peripapillary vein walls are occasionally seen.278

Neuroimaging

The distinction between papilledema and pseudopapilledema has been aided by CT scanning and ultrasonography, which readily demonstrate calcification within the elevated optic disc.37,179 It is not uncommon to see a child referred for possible papilledema arrive for consultation with their “negative” CT scan in hand, only to find undetected calcification of the optic discs on review of the scan (Fig. 3.23). One large study322 found that drusen of the optic disc are more reliably diagnosed using B-scan echography than CT scanning or B-scan echography. OCT has demonstrated that many cases of papilledema have peripapillary subretinal fluid and submacular fluid that is not clinically evident.251

Histopathology

Optic disc drusen are situated anterior to the lamina cribrosa; they occur nowhere else in the brain. They consist of homogenous,

Fig. 3.23  “Normal” CT scan showing posterior scleral calcification corresponding to optic disc drusen. Courtesy of Stephen C. Pollock, M.D.