Optic Disc Drusen in Children

Abstract

Optic disc drusen occur in 0.4% of children and consist of acellular intracellular and extracellular deposits that often become calcified over time. They are typically buried early in life and generally become superficial, and therefore visible, later in childhood, at the average age of 12 years. Their main clinical significance lies in the ability of optic disc drusen, particularly when buried, to simulate true optic disc edema. Misdiagnosing drusen as true disc edema may lead to an invasive and unnecessary workup for elevated intracranial pressure. Ancillary testing, including ultrasonography, fluorescein angiography, fundus autofluorescence, and optical coherence tomography, may aid in the correct diagnosis of optic disc drusen. Complications of optic disc drusen in children include visual field defects, hemorrhages, choroidal neovascular membrane, non-arteritic anterior ischemic optic neuropathy, and retinal vascular occlusions. Treatment options for these complications include ocular hypotensive agents for visual field defects and intravitreal anti-vascular endothelial growth factor (anti-VEGF) agents for choroidal neovascular membranes. In most cases, however, children with optic disc drusen can be managed by observation with serial examinations and visual field testing, once true optic disc edema has been excluded.

1. Introduction

Optic disc drusen are acellular calcified deposits located both intracellularly and extracellularly first described by Muller in 1858.¹³⁰ The main clinical significance of optic disc drusen in children is that they can simulate true optic disc edema (Figure 1).^{52; 81; 127; 189; 213} Misdiagnosing drusen as true disc edema may lead to an extensive, invasive and unnecessary work-up for elevated intracranial pressure, including neuroimaging and lumbar puncture.¹¹⁵ Optic disc drusen are typically buried in the optic disc early in life and become more superficial later.^{7; 57; 79; 196} In children, therefore, drusen are more likely to be buried and may be more difficult to detect.⁴⁵

Figure 1.

Comparison of optic disc in children with optic disc drusen and papilledema. A) Optic disc photos of a 10 year old boy with bilateral buried optic disc drusen. The disc margins are blurred, but there are no hemorrhages, exudates, or vessel obscuration. B) Optic disc photos of a 5 year old girl with mild papilledema due to increased intracranial pressure secondary to the use of exogenous growth hormone. Disc margins are blurred with mild obscuration of vessels, but no hemorrhages or exudates.

1.A. Pathogenesis

The pathogenesis of optic disc drusen is unknown. The three classical theories on the formation of optic disc drusen postulate that they are caused by a disturbance in axonal metabolism with slowed axoplasmic flow;^{197; 204} congenitally dysplastic discs with a propensity for drusen formation;^{139; 174} or a small scleral canal that physically compresses the optic nerve, causing ganglion cell death, with extrusion and calcification of mitochondria.¹³² The latter theory has been called into question by a study that showed that the scleral canal in patients with optic disc drusen was not smaller than controls when measured by optical coherence tomography (OCT).⁵¹

1.B. Demographics

The prevalence of optic disc drusen in children is about 0.4%.⁴³ In adults, studies have found a prevalence of 0.5 to 2.4%.^{7; 56} The lower prevalence of optic disc drusen reported in children is likely due to the difficulty in detecting buried drusen. In children and adults, optic disc drusen are more common in females and Caucasians and are bilateral in over two-thirds of cases.^{7; 19; 97; 171; 203}

1.C. Inheritance

Optic disc drusen are frequently familial. Family members of patients with optic disc drusen have up to ten times the risk of harboring optic disc drusen compared to the general population, and they have an increased risk of optic disc dysplasia and anomalous retinal vasculature.^{4; 118} Optic disc drusen can also be inherited as part of a genetic syndrome with other ocular or systemic manifestations.

2. Association of optic disc drusen with other ocular or systemic disorders

Optic disc drusen have been reported in association with many ocular (Table 1) and systemic (Table 2) disorders; however, there are only a few disorders in which optic disc drusen have been demonstrated to occur more frequently than in the general population.

Table 1.

Ocular disorders reported in association with optic disc drusen

Acquired myelinated nerve fibers40; 83

Adams-Oliver syndrome107

Aneurysm of the ophthalmic artery35

Astrocytic hamartoma165

Best’s vitelliform macular dystrophy15

β-thalassemia10

Birdshot chorioretinopathy and Cacchi-Ricci syndrome198

Combined hamartoma of the retina and retinal pigment epithelium28

Congenital night blindness205

Familial macular dystrophy96

Glaucoma169; 176

Gyrate atrophy66; 207

Idiopathic intracranial hypertension67; 94; 100; 102; 166; 171; 172

Idiopathic parafoveal telangiectasia133

Joubert syndrome199

Morning glory disc anomaly164

Ocular tumoral calcinosis59

Optic nerve tumors21; 111

Peripapillary central serous retinopathy128

Pigmented paravenous retinochoroidal atrophy (PPRCA)216

Pseudoxanthoma elasticum and angioid streaks33; 46; 89; 116; 122; 157; 191

Retinitis pigmentosa8; 34; 41; 71; 106; 126; 130; 147; 149; 155; 161; 167; 192; 209

Severe Early Childhood Onset Retinal Dystrophy (SECORD)210

Tilted optic disc65

Tubulointerstitial nephritis and uveitis (TINU) syndrome26

VACTERL association124

Table 2.

Systemic disorders reported in association with optic disc drusen

Alport syndrome54

Alstrom syndrome188

Cystic fibrosis72

Delayed language development and dyslexia119; 180

Down syndrome91

Headaches and seizures disorders45; 180

Intracranial tumor13; 14; 27; 120; 136; 139; 160; 171

Klippel-Trenaunay syndrome21

Mental retardation180

Noonan syndrome113

Primary megalencephaly80

Psychomotor retardation171

Schizophrenia171

Sturge Weber syndrome202

Teeth and jaw anomalies53

Trisomy 15q214

Tuberous sclerosis206

2.A. Retinitis pigmentosa

The association of retinitis pigmentosa (RP) with optic disc drusen has been known since the first case of optic disc drusen was published by Muller in 1858.¹³⁰ The frequency of optic disc drusen in children with retinitis pigmentosa is not known. The largest study of optic disc drusen in patients with RP included both adults and children and found that 9.2% of patients with RP had optic disc drusen. The frequency of optic disc drusen in children was not reported separately, however, and because fundus photography was used, the authors may not have identified buried non-calcified drusen in children.⁷¹ Optic disc drusen are hypothesized to develop in eyes with retinitis pigmentosa as a result of retinal ganglion cell axonal degeneration.^{106; 126; 161} Degenerating axons extrude mitochondria, which become calcified and form drusen.²⁰⁴ Optic disc drusen have been associated with subtypes of retinitis pigmentosa including Usher syndrome and the syndrome of nanophthalmos-retinitis pigmentosa-foveoschisis-optic disc drusen.^{34; 41; 192} Genetic analysis has shown that a mutation in the Membrane-type Frizzled-related protein (MFRP) gene is responsible for some cases of the latter syndrome.^{8; 34; 147; 167; 209} More recently, a mutation in the crumbs homolog 1 (CRB1) gene has been reported in a family with nanophthalmos-retinitis pigmentosa-foveoschisis-optic disc drusen syndrome who did not harbor a mutation in MFRP.¹⁵⁵

2.B. Pseudoxanthoma elasticum and angioid streaks

Optic disc drusen have likewise been reported in association with pseudoxanthoma elasticum (PXE) and angioid streaks.^{46; 116; 122; 157; 191} Reports of the incidence of optic disc drusen in pseudoxanthoma elasticum and angioid streaks are as high as 25%;^{122; 157; 191} however, the frequency of this association in children is not known. Many of the studies of optic disc drusen in PXE and angioid streaks did not include children and, in those that did, the findings in children were not separately reported. The cause of optic disc drusen in these disorders is postulated to be elastin mineralization in the lamina cribrosa from deposition of polyanions in the abnormal elastin fibrils. Calcium is believed to bind to these polyanions, resulting in the formation of macromolecules that disrupt axonal transport and lead to the formation of drusen.^{33; 89; 122} The gene responsible for the combination of optic disc drusen, angioid streaks, and pseudoxanthoma elasticum has yet to be elucidated.⁹⁰

2.C. Alagille syndrome

Alagille syndrome has similarly been shown to be associated with optic disc drusen.^{42; 98; 150} This disorder is a form of familial intrahepatic cholestasis, with neonatal jaundice and paucity of intrahepatic bile ducts. Many ocular findings have been reported in association with Alagille syndrome, including posterior embryotoxon, pigmentary retinopathy, and optic disc drusen.¹⁵⁰ Ultrasonographic evidence of optic disc drusen is found in at least one eye in 90% of children with Alagille syndrome and both eyes in 50%.¹⁵⁰ The pathogenesis of optic disc drusen in Alagille syndrome is unclear. Eyes in Alagille syndrome have shorter than expected axial lengths, which could contribute to a small scleral canal with resultant axonal disruption and formation of optic disc drusen.¹⁵⁰ Alagille syndrome is also associated with metabolic abnormalities that cause deposition of lipofuscin in the retinal pigment epithelium and Bruch membrane.⁸⁷ These deposits may also disrupt axonal transport and contribute to drusen formation.¹⁵⁰

3. Clinical findings

3.A. Symptoms

Patients with optic disc drusen are frequently asymptomatic, and optic disc drusen are often discovered incidentally on ophthalmologic examination. In children, ophthalmologic examination is prompted by a systemic symptom such as headache, vomiting, or seizure in 48% of patients. The remainder undergo examination for unrelated ocular issues such as strabismus, or as a part of routine screening.⁴⁵ Children are less likely than adults to report symptoms attributable to optic disc drusen, such as transient visual obscurations¹⁸² and visual field defects (Figure 2).^{36; 119; 152}

Figure 2.

Characteristic visual field defects in a patient with bilateral optic disc drusen. The left eye has a small inferonasal scotoma, and the right eye has a predominantly nasal inferior arcuate defect.

3.B. Visual field defects

Visual field defects are more common in superficial compared to buried drusen, and therefore visual field defects tend to increase in frequency with increasing age.^{138; 185} Erkkila found visual field defects in 10 of 89 eyes (11%) of children with optic disc drusen.⁴⁵ The average age of patients in this study was 9.8 years. In a study of older children with optic disc drusen (mean age of 10.2 years at presentation, followed for an average of 44 months), Hoover et al found visual field defects in 18 of 35 eyes (51%).⁷⁹ The authors reported that the average age at which visual field defects were detected was 14 years, while the mean age at which drusen became superficial and visible was 12.1 years.⁷⁹

Noval et al studied 15 children with visual field defects from buried or superficial optic disc drusen and found that the most common visual field defect was a nasal inferior arcuate scotoma (32%), followed by unspecified nasal defect (21%), constricted visual field (21%), and enlarged blind spot (18%).¹⁵² Visual field constriction occurred in 50% of eyes with superficial drusen, compared to 17% of eyes with buried drusen.

Longitudinal studies of visual field defects in optic disc drusen suggest that progression is generally slow.^{109; 190} Shelton et al examined 23 eyes of 16 patients over a mean of 9.7 years and found the average change in mean deviation (MD) on Humphrey visual field (HVF) to be −0.78 dB, with the majority of eyes showing no clinically significant decrease in MD.¹⁹⁰ Lee and Zimmerman followed 32 patients with optic disc drusen over 36 months and reported that the annual rate of visual field loss on Goldmann visual field (GVF) testing was 1.6%.¹⁰⁹

3.C. Examination findings

Central visual acuity is typically unaffected by optic disc drusen.^{45; 119; 152} Patients may have an afferent pupillary defect if drusen are unilateral or asymmetric.³⁶ The optic disc usually appears elevated, and there may be superficial or deep hemorrhages.^{45; 77; 119} The drusen are typically located nasally and cause a lumpy bumpy appearance if superficial. Buried drusen are difficult to appreciate on slit lamp examination, but may sometimes be seen adjacent to vessels or the disc margin with oblique illumination.^{36; 45; 171} Additionally, the retinal vasculature of eyes with optic disc drusen is frequently anomalous.⁴⁹ In children, optic disc drusen are associated with a cilioretinal artery in 43% of eyes, optociliary shunt vessels in 4%, and more vascular tortuosity and early branching of vessels compared to control eyes.^{44; 45}

3.D. Distinguishing from true optic disc edema by funduscopy

When optic disc drusen are suspected, it is imperative to rule out true optic disc edema, which is distinguished from drusen on examination by obscuration of peripapillary vessels, hyperemia, hemorrhages, cotton wool spots, Paton lines, and exudates around the optic disc.^{36; 77} In many cases, however, it may be difficult to distinguish between optic disc drusen and true mild disc edema based on clinical examination alone, particularly when drusen are buried (Figure 1). In these cases, ancillary testing can be helpful.

4. Diagnostic testing

Various ancillary tests, including B-scan ultrasonography,^{55; 105; 151; 168} fundus autofluorescence,^{95; 140; 145} orbital computed tomography (CT) scan,^{12; 131; 162} fluorescein angiography (FA),^{24; 159; 177} scanning laser ophthalmoscopy,^{75; 103; 187} electrophysiology,^{17; 18; 23; 142; 186} and more recently optical coherence tomography (OCT),^{31; 88; 112; 125; 215} have been used to identify optic disc drusen. These tests may be less useful in children who typically have buried drusen that are more difficult to detect.

4.A. B-scan ultrasonography

B-scan ultrasonography is considered the gold standard imaging modality to detect optic disc drusen.^{7; 55; 105; 151} Drusen characteristically appear hyperechoic with posterior shadowing on ultrasonography (Figure 3). The B scan is able to scan the entire area of the optic disc using sweeping movements of the ultrasound probe. In a study of children and adults comparing B-scan ultrasonography, preinjection control photography for detection of autofluorescence, and orbital CT scan, B-scan ultrasonography detected significantly more cases of optic disc drusen,¹⁰⁵ but identified only 39 of 82 cases (48%) of suspected buried optic disc drusen. This is likely because the undetected drusen were not calcified.⁶ Because optic disc drusen in children are more frequently non-calcified and buried,^{57; 79; 196} the sensitivity of ultrasound for diagnosis of drusen in children may be lower than in adults, and ultrasonography may become positive over time as drusen become calcified.¹⁵⁶ Petrushkin et al described five children who had optic disc drusen not seen on B-scan ultrasonography at presentation whose drusen later became detectable by ultrasonography at a mean age of 8.8 years.¹⁵⁶

Figure 3.

Appearance of calcified optic disc drusen on ultrasonography. The calcified drusen produce a hyperechoic signal at the optic disc with posterior shadowing.

4.B. Fundus autofluorescence

Optic disc drusen display autofluorescence and can therefore be detected on preinjection control photography (Figure 4B) and scanning laser ophthalmoscopy.^{39; 95; 105; 140; 145} Autofluorescence, however, does not reliably detect buried drusen, possibly because of attenuation from overlying tissue.^{105; 140} Kurz-Levin et al found that autofluorescence detected over 96% of superficial drusen but only 27% of buried drusen in a study including both adults and children.¹⁰⁵ In contrast, in a study of 24 children with optic disc drusen, Gili et al reported that autofluorescence was able to detect drusen in 94% of cases.⁶³ The presence of drusen, however, was established by B-scan ultrasonography, which does not reliably detect non-calcified drusen. Therefore, the usefulness of autofluorescence in identifying optic disc drusen in children, who are more likely to harbor non-calcified buried drusen, has not been conclusively determined.

Figure 4.

Fundus photography, autofluorescence, and fluorescein angiography in a 12 year old girl with optic disc drusen. A) Color fundus photography demonstrates blurred disc margins and superficial gliosis. B) Preinjection control photography shows hyperautofluorescence of optic disc drusen bilaterally. C) Late phase fluorescein angiography demonstrates nodular staining of the optic discs with no leakage.

4.C. Orbital computed tomography (CT)

Orbital CT has also been used to image optic disc drusen.^{12; 82; 105; 131; 162; 217} Like B-scan ultrasonography, CT detects calcification of drusen. It is limited by the 1.5 mm thickness of slices, which may miss drusen, and has been shown to be inferior to ultrasonography.¹⁰⁵ Given the concerns regarding excess radiation in children, and the low sensitivity of CT scans for detecting optic disc drusen, we do not recommend ordering CT scans in children for this purpose.

4.D. Fluorescein angiography (FA)

Fluorescein angiographic characteristics of eyes in children with optic disc drusen include optic disc staining¹⁵⁹ and delayed filling of the peripapillary choriocapillaris in 43% of cases.^{44; 45} Fluorescein angiography may be used to distinguish between optic disc drusen and true optic disc edema.^{24; 140; 159; 177} Pineles and Arnold found that true disc edema was characterized by early or late disc leakage, while optic disc drusen displayed staining without leakage.¹⁵⁹ Superficial optic disc drusen demonstrated early and late nodular disc staining in 90% of cases, while buried drusen showed early nodular staining in 25% and late nodular staining in 29% (Figure 4C).¹⁵⁹ Their study included both children and adults, with a mean age of 36 years. The above results suggest that fluorescein angiography in children may not reliably detect nodular staining by buried drusen, but may be helpful to rule out true disc edema.

In younger children, intravenous fluorescein angiography (IVFA) may not be possible because of intolerance of venipuncture. In such cases, oral fluorescein angiography (oral FA) may be considered.^{60; 144} The role of oral FA for distinguishing between pseudopapilledema and true optic disc edema in children is unclear. Young patients who cannot tolerate venipuncture may also be unable to cooperate with image capture during oral FA.¹⁴⁴ Moreover, the sensitivity of oral FA may be less than IVFA for detection of optic disc edema. Ghose and Nayak performed oral FA in 30 eyes with suspected papilledema and 16 eyes with pseudopapilledema in children aged 1 month to 10 years.⁶⁰ The optic disc in eyes with suspected pseudopapilledema showed similar findings to normal children, with fluorescence of the optic disc at 30 minutes that nearly disappeared by 60 minutes post-injection. Of 30 eyes with suspected papilledema, only 12 (40%) showed positive findings on oral FA, defined as focal or diffuse late disc hyperfluorescence at 60 minutes.

4.E. Optical coherence tomography (OCT)

A relatively new modality for imaging optic disc drusen is optical coherence tomography (OCT).^{5; 31; 50; 76; 88; 93; 104; 112; 114; 135; 195; 211; 215} On OCT, optic disc drusen can be seen as a focal hyperreflective mass posterior to the outer plexiform and outer nuclear layers, with absence of the inner and outer segment photoreceptor junction (Figure 5);¹¹² however, Kulkarni et al found standard spectral-domain OCT (SD-OCT) to be unreliable at distinguishing between buried optic disc drusen and true optic disc edema in children and young adults.¹⁰⁴ They noted that, in several cases of mild disc edema, OCT showed nonspecific hyperreflective areas underneath the optic nerve that were confused with drusen.

Figure 5.

Optical coherence tomography of optic disc demonstrating drusen. The drusen appear as hyperreflective masses posterior to the outer plexiform and outer nuclear layers, with loss of the inner and outer segment photoreceptor junction.

4.F. Retinal nerve fiber layer (RNFL) analysis

Investigators have also used OCT, as well as scanning laser ophthalmoscopy and fundus photography, to examine the retinal nerve fiber layer (RNFL) in patients with optic disc drusen.^{16; 32; 48; 62; 74; 88; 92; 103; 141; 153; 154; 158; 170; 201} In a study of OCT RNFL in children with optic disc drusen, Noval et al found the RNFL thickness to be higher than controls in eyes with partially or completely buried drusen and lower than controls in eyes with superficial drusen.¹⁵² The RNFL defect is typically nasal, with sparing of the temporal RNFL.⁶² A new OCT parameter, macular ganglion cell-inner plexiform layer (GCIPL) thickness, may show thinning earlier than the RNFL in buried optic disc drusen in both children and adults.^{25; 163} Some authors have sought to use OCT RNFL thickness to distinguish between optic disc drusen and true disc edema, in which RNFL thickness may be higher, especially nasally;^{11; 88; 181} however, the degree of RNFL thickening in true disc edema may depend on the severity of edema, and thickness may not differ significantly between mild optic disc edema and pseudopapilledema.⁹²

4.G. Enhanced-depth imaging OCT (EDI-OCT) and swept-source OCT (SS-OCT)

Enhanced-depth imaging OCT (EDI-OCT) and swept-source OCT (SS-OCT), which image more posteriorly than standard SD-OCT, have shown promise in detecting optic disc drusen.^{125; 183; 194} Merchant et al examined 32 eyes with clinically definite optic disc drusen and 25 eyes with suspected optic disc drusen in children and adults.¹²⁵ They found that B-scan ultrasonography, SD-OCT, and EDI-OCT all detected every case of clinically definite optic disc drusen; however, in 25 eyes with suspected buried optic disc drusen, EDI-OCT detected 17 cases, while SD-OCT and B-scan ultrasonography were positive in 14 and 7 eyes, respectively. EDI-OCT was significantly better than B-scan ultrasonography at identifying buried drusen.

4.H. Electrophysiology

Electrophysiological testing has also been performed in both adults and children with optic disc drusen, and abnormalities are thought to be related to the degree of nerve fiber layer damage.⁷ Scholl et al performed pattern electroretinogram (pERG) testing on 24 eyes with optic disc drusen and reported P50 amplitude reduction in 17% of eyes and reduction or absence of the N95 component in 79% of eyes.¹⁸⁶ Multiple investigators have studied visual evoked responses in eyes with optic disc drusen, and the results have been mixed, with P100 latency prolongation reported in 0 to 83% of eyes.^{17; 18; 23; 121; 142; 186; 208} Given the variability in these electrophysiological changes, as well as the difficulty of performing these tests in young children, they are not routinely ordered for diagnosis of optic disc drusen in children.

5. Complications

Although optic disc drusen are typically considered benign, they may be associated with various ocular complications in children.

5.A. Visual field defects

As discussed previously, visual field defects occur in up to 51% of children and become more common with increasing age.^{79; 138} The average age at which visual field defects are detected in children with optic disc drusen is 14 years.⁷⁹ Visual field loss in patients with optic disc drusen may have a vascular etiology, as visual field defects correlate with lower systolic flow velocities in the central retinal artery in both adults and children with optic disc drusen.¹

5.B. Hemorrhagic complications

Optic disc drusen are also associated with several hemorrhagic and vascular complications.^{73; 77; 110; 134; 173; 178; 179; 212} Peripapillary subretinal, retinal, and vitreous hemorrhages occur at a frequency of 2 to 13%.^{20; 49; 110} Sanders et al divided the hemorrhagic complications associated with optic disc drusen into three categories: small, superficial hemorrhages limited to the optic disc; large hemorrhages on the optic disc extending in the vitreous; and deep peripapillary hemorrhages extending from the optic disc under the surrounding retina.¹⁷⁸ In their series of seven patients with hemorrhagic complications of optic disc drusen, Sanders et al included three children. One of these children had a disc hemorrhage leading to vitreous hemorrhage, whereas the other two had subretinal hemorrhage simulating choroidal malignant melanoma that resulted in enucleation in one case.¹⁷⁸

5.C. Choroidal neovascular membrane (CNVM)

Choroidal neovascular membrane formation is a complication of optic disc drusen that is thought to occur more frequently in children (Figure 6).^{3; 7; 22; 137; 184} Mustonen found two cases of choroidal neovascular membranes, both in children, in a series of 200 adults and children with optic disc drusen.¹³⁷ The neovascular membrane is typically located in the peripapillary region and is frequently associated with good visual acuity without treatment.⁷³ In some cases it can extend into the macula and fovea, causing vision loss via submacular fluid and/or hemorrhage.^{9; 99; 178; 184}

Figure 6.

Regressed juxtapapillary choroidal neovascular membrane secondary to optic disc drusen, with subretinal fibrosis and pigment mottling (Courtesy of Anthony C. Arnold, MD).

5.D. Non-arteritic anterior ischemic optic neuropathy (NAION)

Non-arteritic anterior ischemic optic neuropathy (NAION) is the most common ischemic complication of optic disc drusen and has been postulated to be the most frequent cause of visual loss in this disorder.¹¹⁹ Compared to patients with classic NAION, patients who have optic disc drusen and develop NAION are typically younger (late teens to early twenties) without systemic risk factors.^{64; 148; 171} Patients with systemic risk factors may develop NAION at an unusually young age or have bilateral involvement. Nanji et al reported a case of NAION in a 12-year-old boy with optic disc drusen and cited travel to high altitude and dehydration from emesis as possible contributory factors.¹⁴³ Choi et al described a 19-year-old male with bilateral optic disc drusen who developed bilateral NAION with visual field constriction.³¹ Systemic risk factors for NAION included a history of systemic hypotension and smoking, as well as dehydration while backpacking at an altitude of over 11,000 feet at the time of the ischemic events.

5.E. Retinal vascular occlusions

Case reports have also been published of central and branch retinal artery occlusion and central retinal vein occlusion in association with optic disc drusen.^{30; 47; 58; 61; 68; 78; 108} These retinal vascular occlusions occur at a younger age than is typical for these disorders in patients without optic disc drusen; the youngest reported patient developed a branch retinal artery occlusion at the age of 11 years.⁶¹ In most cases, patients with optic disc drusen who developed a retinal vascular occlusion at a young age also had another systemic risk factor, such as migraine, contraceptive use, systemic hypertension, atrioseptal defect, or travel to altitude.⁷

6. Treatment

6.A. Visual field defects

If true optic disc edema has been ruled out, patients with asymptomatic optic disc drusen may be observed with serial visual field testing. Because visual field defects occur in up to 51% of children with optic disc drusen,^{79; 119} regular visual field testing is important and should be performed as soon as children can do so reliably. In cases with progressive visual field defects, topical ocular hypotensive therapy may be initiated, although there have been no studies to evaluate the effectiveness of this therapy in children or adults.^{7; 70} The usual precautions when using ocular hypotensives in children apply. α-agonists should be used with caution in young children because of the risk of central nervous system depression, and β-blockers should be avoided in patients with respiratory disorders such as asthma. Surgical treatment of visual field defects due to optic disc drusen with optic nerve sheath fenestration or radial optic neurotomy is controversial and not considered standard of care, but success has been reported by a few authors.^{85; 86; 129; 146}

6.B. Choroidal neovascular membranes

Optic disc drusen complicated by choroidal neovascular membranes can potentially be observed if they are asymptomatic and do not involve the macula. Successful treatment of optic disc drusen with CNVM has been reported with surgery,^{123; 200} laser photocoagulation,³⁸ photodynamic therapy,^{29; 193} and more recently intravitreal anti-vascular endothelial growth factor (anti-VEGF) agents.^{2; 9; 37; 69; 84; 99; 175} Both bevacizumab and ranibizumab have been used successfully in children with CNVM secondary to optic disc drusen as young as five years of age.^{9; 99} Although some clinicians use anti-VEGF agents to treat infants with retinopathy of prematurity, concerns still exist regarding the safety of these drugs, particularly bevacizumab, in the pediatric population.⁹⁹ The long-term systemic effects on developing organs have yet to be determined, and they should be used with caution in children.

6.C. Non-arteritic anterior ischemic optic neuropathy (NAION) and retinal vascular occlusions

Ischemic complications of optic disc drusen in children, including NAION and retinal vascular occlusions, should be managed as in the absence of drusen. In children with retinal vascular occlusions, consideration should be given to initiating a work-up for a secondary cause, such as hypercoagulability or atrioseptal defect, as these vascular occlusions are rare in children with optic disc drusen in the absence of a systemic risk factor.^{7; 47}

7. Conclusions

Optic disc drusen in children are typically bilateral and are more likely to be buried than in adults. Thus, they may be difficult to distinguish from true optic disc edema, which mandates exploration for secondary causes of increased intracranial pressure, such as a mass lesion of the brain or pseudotumor cerebri syndrome. Ancillary testing, especially ultrasonography, fluorescein angiography, fundus autofluorescence, and optical coherence tomography, may be helpful in distinguishing between optic disc drusen and true disc edema, although these tests may be less sensitive for detecting buried drusen in children. It is important to consider optic disc drusen in the differential for papilledema, as 50 to 55% of children initially diagnosed with papilledema have optic disc drusen as their final diagnosis.^{101; 117} If optic disc drusen are correctly diagnosed initially, patients may avoid unnecessary further work-up and expense. Leon et al reported that in children ultimately diagnosed with optic disc drusen, when an ultrasound was ordered as the initial test, the cost of evaluation was $305, compared to $1,173 when neuroimaging was ordered first.¹¹⁵ The presence of optic disc drusen, however, does not exclude true disc edema, and optic disc drusen occur simultaneously with true disc edema in some children.^{67; 100; 172} Therefore, in patients with signs or symptoms suspicious for another disorder, further evaluation may be necessary even if optic disc drusen are detected.

Complications of optic disc drusen include visual field defects in up to 51% of children, and less commonly hemorrhages, choroidal neovascular membrane, non-arteritic anterior ischemic optic neuropathy, and retinal vascular occlusions. Consideration may be given to initiating ocular hypotensive therapy in patients with progressive visual field defects secondary to optic disc drusen, although α-agonists and β-blockers should be used with caution in children. Choroidal neovascular membranes complicated by submacular hemorrhage and/or fluid with decreased visual acuity may be treated with intravitreal anti-VEGF agents. Both bevacizumab and ranibizumab have been successfully used in children, although the long-term systemic effects of these drugs in the pediatric population have yet to be elucidated. In most cases, children with optic disc drusen can be managed by observation with serial examinations and visual field testing, once true optic disc edema has been excluded.

Methods of literature search

A search of the MEDLINE database was conducted during December 2015 using the following key words: optic disc and drusen and child; optic disc and drusen and children; optic disc and drusen and pediatric; optic disk and drusen and child; optic disk and drusen and children; optic disk and drusen and pediatric; optic nerve and drusen and child; optic nerve and drusen and children; and optic nerve and drusen and pediatric. The search covered all published literature through December 2015. The bibliographies of key articles were also hand-searched to identify further references. References spanned the period from 1858 to December 2015. All articles judged to be of clinical importance were included. The review was limited to peer-reviewed papers published in English. Abstracts of articles in other languages were included if the abstracts were published in English. Search results were collected and abstracts screened to remove any articles not relevant to the topic. The total number of references for this review is 217.