Ординатура / Офтальмология / Английские материалы / Imaging of Orbital and Visual Pathway Pathology_Muller-Forell_2005

Optic Pathway Pathology in Children

Pollack IF, Mulvihill JJ (1997) Neurofibromatosis 1 and 2. Brain Pathol 7:823–836

Russell-Eggitt I, Harris CM, Kriss A (1998) Delayed visual maturation. An update. Dev Med Child Neurol 40:130–136 Sener RN (1996) Septo-optic dysplasia associated with cere-

bral cortical dysplasia (cortico-septo-optic dysplasia). J Neuroradiol 23:245–247

Shuper A, Horev G, Kornreich L, Michowiz S, Weitz R, Zaizov R, Cohen IJ (1997) Visual pathway glioma. An erratic tumour with therapeutic dilemmas. Arch Dis Child 76:259–263

Sorkin JA, Davis PC, Meacham LR, Parks JS, Drack AV, Lambert SR (1996) Optic nerve hypoplasia: absence of posterior pituitary bright signal on magnetic resonance imaging correlates with diabetes insipidus. Am J Ophthalmol 122:717–723

Sperl W, Felber S, Skladal D, Wermuth B (1997) Metabolic stroke in carbamyl phosphate synthetase deficiency. Neuropediatrics 28: 229–234

Steinlin M, Martin E, Schenker K, Boltshauser E (1992) Myelination of the optic radiation in Leber congenital amaurosis. Brain Dev 14:212–215

Steinlin M, Schmid M, Landau K, Boltshauser E (1997) Fol- low-up in children with Joubert syndrome. Neuropediatrics 28:204–211

145

Tselis AC, Lisak RP (1995) Acute disseminated encephalomyelitis and isolated central nervous system demyelinative syndromes. Curr Opin Neurol 8:227–229

Upadhyaya M, Cooper DN (1998) Neurofibromatosis type 1: from genotype to phenotype. Bios Scientific, Oxford

Van der Knaap MS, Valk J (1995) Magnetic resonance of myelin, myelination, and myelin disorders, 2nd edn. Springer, Berlin Heidelberg New York, pp 1–21, 31–49

Waugh MC, Chong WK, Sonksen P (1998) Neuroimaging in children with congenital disorders of the peripheral visual system. Dev Med Child Neurol 40:812–819

Wilichowski E, Pouwels PJW, Frahm J, Hanefeld F (1999) Quantitative proton magnetic resonance spectroscopy of cerebral metabolic disturbances in patients with MELAS. Neuropediatrics 30:256–263

Wingerchuk DM, Hogancamp WF, O’Brien PC, Weinshenker BG (1999) The clinical course of neuromyelitis optica (Devic’s syndrome). Neurology 53:1107–1114

Yakovlev PI, Lecours AR (1967) The myelogenic cycles of regional maturation of the brain. In: Minkowski A (ed) Regional development of the brain in early life. Blackwell, Oxford, pp 3–70

Yoneda M, Maeda M, Kimura H, Fujii A, Katayama K, Kuriyama M (1999) Vasogenic edema on MELAS: a serial study with diffusion-weighted MR imaging. Neurology 53:2182–2184

6Orbital Pathology

W. Müller-Forell and S. Pitz

CONTENTS

6.1Globe 147

6.1.1Congenital Lesions 148

6.1.2Tumors 150

6.1.3Inflammatory Disorders 166

6.1.4Miscellaneous Lesions 169

6.2Conal/Intraconal Area 179

6.2.1Solid Tumors 179

6.2.2Vascular Lesions 183

6.2.3Inflammatory Lesions 205

6.2.4Miscellaneous

(Amyloidoma, Metastasis, Varia) 221

6.3Extraconal Area 226

6.3.1Tumors 226

6.3.2Tumor-like Lesions 248

6.3.3Inflammatory Lesions 253

6.3.4Lacrimal Gland 265

6.3.5Traumatic Lesions 282

6.3.6Miscellaneous 287

6.4Optic Nerve 298

6.4.1Tumors 298

6.4.2Inflammatory Lesion 318

6.4.3Traumatic Lesions 323 References 329

an orbital manifestation of a systemic condition, like lymphoma or hyperthyroidism. Another important diagnostic factor is the age of the patient: infections, trauma, and various malignant tumors (e.g., rhabdomyosarcoma or neuroblastoma) constitute the most frequent orbital diseases in children, while Graves’ disease represents the leading disease in middle life, and the greatest number of neoplasms are observed in the group of elderly patients (Rootman 1988).

The ophthalmologic examination should consist of an assessment of visual acuity, inspection, testing of motility, exophthalmometry, slit lamp findings as well as an evaluation of pupillary function, refraction anomalies, pathologic changes of the fundus, and visual field deficits. The relevant information should be routinely communicated before beginning the neuroradiological examination.

6.1 Globe

The orbit may be affected by more than 107 different clinical pathologies with a confusing number of symptoms (Rootman 1988). While only a small number of these diseases require diagnostic imaging, the evaluation of clinical signs and symptoms plays a crucial role in determining the appropriate neuroradiological investigation. Inflammatory disease may present with a history of acute progression, generally associated with pain, and a subacute course may lead to the diagnosis of, e.g., Graves disease, while benign tumors are characterized by chronic, painless progression. Concomitant internal diseases, on the other hand, may lead to the initial diagnosis of

PD W. Müller-Forell, MD

Institute of Neuroradiology, Medical School University of Mainz, Langenbeckstrasse 1, 55101 Mainz, Germany

S. Pitz, MD

Department of Ophthalmology, Medical School University of Mainz, Langenbeckstrasse 1, 55101 Mainz, Germany

The majority of diseases of the globe are assessed by ophthalmologic methods, with the ultrasound technique being ideally suited in an ophthalmologic setting. However, in some cases patient-related factors may exert a negative effect on the outcome of the investigation, and magnetic resonance imaging (MRI) may be indicated in children or noncooperative patients. MRI is the method of choice, in particular when leukokoria might prevent the funduscopic evaluation of a process.Yet,even under normal conditions, the high anatomical resolution provided by the most advanced MRI technology does not allow differentiation of the three primary layers of the globe: the sclera, uvea, and retina. Nevertheless, due to the fact that some ocular diseases are accompanied by detachment and/or effusion, the different primarily potential spaces may be visualized.

Symptoms indicating the presence of an intraocular pathology are closely related to the time of manifestation of the disease: Congenital lesions may

present with obvious asymmetry of the eyes, e.g. an apparently microphthalmic eye (see Sect. 5.2.2). Binocular disease with severely impaired visual function may lead to nystagmus. Leukokoria (syn. cat’s eye) is a hallmark of intraocular pathology: normally both fundi reflect light (visible as an annoying phenomenon in some photographs). An intraocular cause of the change in color has to be ruled out if the light reflex in one eye appears grayish or white (instead of red, caused by the blood-filled uvea just below the transparent retina). In addition to the congenital cataract, the most common causes of leukokoria are (in order of incidence) retinoblastoma (>50%, see Sect. 6.1.2.1), a persistent hyperplastic primary vitreous (see Sect. 6.1.1.3), Coats disease (see Sect. 6.1.1.4), followed by retinopathy of the premature (ROP), unilateral congenital cataract, and intraocular inflammation (Toxocara) (Howard and Ellsworth 1965; Mafee 1996). In these cases, leukokoria is frequently accompanied by strabismus. The direction of the eye deviation serves as a diagnostic indicator in strabismus: while nonorganic strabismus in childhood commonly occurs as a convergent squint, organically induced strabismus primarily presents as an exodeviation (divergent squint) (Elston 1997; Hunter and Ellis 1999). The accurate identification of the cause of leukokoria is essential to ensure prompt identification and appropriate treatment,particularly in the case of retinoblastoma, a highly malignant primary retinal cancer (Mafee 1996).

sectioning of the affected orbit) to varying degrees of microphthalmos. In pure anophthalmos, the extraocular muscles may be well developed. In microphthalmos, the eye is small but present, sometimes accompanied by a colobomatous cyst with a primarily inferior location as evidence of the absent closure of the embryonic optic fissure (with the defect extending to the retina, choroid, and sclera). This cyst may be the cause of rapidly increasing swelling, mimicking neoplasia. A variety of bony and soft-tissue deformities is characteristic in all cases of anophthalmos and in most cases of microphthalmos.The mechanism by which the presence of the globe induces growth of the surrounding orbit, facial and adnexal structures is not yet understood, and descriptions of the growth-inducing characteristics have been based on clinical and experimental observations (Casper et al. 1993).

One role of imaging under the described conditions is to rule out associated intracranial abnormalities (see Sect. 5.2.2), the other is to evaluate the orbital content and to identify the presence of extraocular muscles in patients who may undergo surgery for microphthalmos. However, when anophthalmos is suspected, the presence of cryptophthalmos (the eye is covered with a layer of skin), a combined cyst, or retinoblastoma must be ruled out (De Potter et al. 1995). Another important differential diagnostic measure is the exclusion of orbital cephalocele, in order to avoid the choice of an inappropriate surgical approach to the cystic orbital lesion.

6.1.1

Congenital Lesions

6.1.1.1

Anophthalmos, Microphthalmos, Orbital Cysts

Congenital anophthalmos represents a rare condition and is characterized by bilateral absence of the globe, due to a developmental defect with growth failure of the primary optic vesicle out of the cerebral vesicle in early embryonic development (De Potter et al. 1995). Microphthalmos is characterized by an unilateral incidence and may be observed as either an isolated disorder or (in about 10%) in association with other craniofacial anomalies (De Potter 1995; Mafee 1996) (see Sect. 5.2.2).

In clinical practice, the term anophthalmos is applied in cases where no eye is visible on inspection. However, there is a broad spectrum of abnormalities extending from the absence of any ocular structure (which can be definitively assessed only by histologic

6.1.1.2

Optic Nerve Coloboma/Staphyloma

Although there is no actual need for diagnostic imaging in optic nerve coloboma, it may represent an incidental finding in systemic disorders (e.g., Joubert or Warburg syndrome). The characteristic features of optic nerve coloboma should be known because it serves as an important differential diagnostic criterion identifiable as a congenital or acquired notch, gap, hole, or fissure in which tissue or a portion of tissue is lacking (Hopper et al. 1992; Mafee 1996). In clinical ophthalmology, two forms of optic nerve coloboma can be differentiated: (a) isolated from the optic nerve and (b) retinochoroidal coloboma. Congenital coloboma represents an anomaly of the optic head, occurring during organogenesis of the eye (Taylor and Hoyt 1997; Cassier et al. 1986). Coloboma may affect the optic nerve, ranging from small “optic pits” to large optic nerve colobomas comprising the entire disc diameter, the so-called

morning-glory papilla, and may involve the retina, the choroid/iris, as well as the lids. The vast majority of these colobomatous tissue defects are typically located in the inferior uveal quadrant, as in this location the closure of the embryonic eye cup is defective (Taylor and Hoyt 1997). The characteristic ophthalmoscopic findings of complete coloboma of the optic nerve disc, a morning glory papilla, include an enlarged, excavated disc with a central core of white tissue,surrounded by an elevated annulus of light and variable pigmented subretinal tissue (Mafee 1996). CT and MRI show a posterior global defect with optic disc excavation (Fig. 6.27a–c). Any cystic retroglobal structure associated with microphthalmos should be suspected as being a colobomatous cyst (Mafee 1996) (see 6.1.1.1). In contrast to coloboma, staphyloma is rarely a congenital condition, and most cases are observed in conjunction with severe myopia as an ectasia of the posterior globe (Fig. 6.1). This condition is caused by an attenuated sclera, due to changes in the composition of proteoglycans in the interfibrillar substance of the ectatic sclera (Gardner et al. 1984; Cassier et al. 1986). Other rare etiologies of staphyloma include postoperative thinning of the sclera following repeated surgery.

6.1.1.3

Persistent Hyperplastic Primary Vitreous

Persistent hyperplastic primary vitreous (PHPV) is a congenital anomaly resulting from the abnormal persistence of the fetal fibrovascular primitive

stroma (hyaloid system) of the eye (Manschot 1958; Castillo et al. 1997). This congenital, primarily unilateral anomaly may be present at birth and is the most common lesion closely resembling a retinoblastoma. PHPV can, however, be differentiated on the basis of the history and an ocular examination. Leukokoria may be identified in a microphthalmic eye at birth or during the first weeks of life,and on examination of the anterior segment, the ciliary processes are shown to be drawn into a contracting, retrolental, loose fibrovascular mass attached to a cataractous lens, representing the remnants of the fetal hyaloid artery that should have regressed by the 8th month of gestation (Reese 1955; De Potter et al. 1995).

As both conditions may lack calcification, CT is not always able to differentiate PHPV from retinoblastoma, and MRI is therefore the method of choice in the differential diagnosis (Mafee et al. 1987a; De Potter et al. 1995). The fibrovascular retrolental mass appears hypointense in T1-weighted and T2weighted images, while the vitreous body appears hyperintense with both modalities. The detached gliotic retinal tissue may have a funnel-like appearance as it arises from the optic disc and extends to the retrolental mass, presenting hypointense with hyperintense subretinal fluid on T1-weighted and T2weighted images (Fig. 6.2). It may demonstrate none or moderate enhancement after i.v. gadolinium administration. In the presence of hemorrhage into the subretinal space, a gravitational fluid-fluid level may be seen (De Potter et al. 1995; Kueker and

Ramaekers 1999).

6.1.1.4

Coats’ Disease

Coats’ disease is a unilateral idiopathic retinal vascular disorder in which teleangiectasia and aneurysmatic retinal vessels cause progressive intraretinal exudation and possibly exudative retinal detachment (Coats 1908; Egerer 1974; Silodor et al. 1988; De Potter et al. 1995; Mafee 1996). Although mostly young males aged 6–8 years old are affected, the condition is occasionally encountered in adults. Even though present at birth, the vascular anomaly of Coats’ disease does not generally become symptomatic until retinal detachment occurs, which finally leads to central vision loss (Sherman et al. 1983) and to the development of painful neovascular glaucoma, necessitating enucleation of the affected eye (Silodor et al. 1988). The ophthalmoscopic findings vary in accordance with the stage of progression. At the early stages of the disease, the diagnosis is reliably established by ophthalmoscopy, and CT or MRI findings provide little additional information. Therapy with photocoagulation, cryotherapy, or both of these methods reduces or even eliminates dilated and saccular aneurysms,exudates,and retinal detachment (Egerer et al. 1974; De Potter et al. 1995). At more advanced stages, complete secondary exudative retinal detachment with accumulation of cholesterol particles in the subretinal space may develop (De Potter et al. 1995). Diagnostic imaging is helpful at this stage and used in differentiating advanced Coats’ disease from exophytic retinoblastoma to prevent

enucleation for suspected retinoblastoma (Chang et al. 1984; Silodor et al. 1988).

Although CT can confirm calcification in retinoblastoma, MRI is superior to CT in differentiating Coats’ disease from retinoblastoma (De Potter et al. 1995; Mafee et al. 1989; Mafee 1996). The most significant finding in T1-weighted, PD, and T2-weighted images is the identification of homogeneous hyperintensity of the subretinal fluid caused by the high protein content in comparison with the vitreous body of the opposite eye (Fig. 6.3). While the detached V-shaped retina, identified by a low signal on both T1and T2-weighted images,may show enhancement after i.v. gadolinium, the subretinal fluid does not (Mafee 1996; De Potter et al. 1995). In contrast, MRI is able to highlight the retinoblastoma as an inhomogeneous, moderately hyperintense mass on T1-weighted and PD sequences (but with hypointense areas on T2-weighted images), allowing differentiation from the associated retinal detachment with exudation (Fig. 6.4). After i.v. contrast administration, the tumor mass shows moderate to marked enhancement in retinoblastoma, in contrast to the subretinal fluid in Coats’ disease (Mafee et al. 1989; De Potter et al. 1995).

6.1.2 Tumors

Tumors of the globe may arise from different layers, the most common ones being the choroid and the retina. Retinoblastoma in children and malignant

melanoma in adult patients represent the most significant diagnoses.

6.1.2.1 Retinoblastoma

Retinoblastoma is the most common, highly malignant intraocular tumor in childhood (see also Sect. 5.2.4).Over 90% of all diagnoses of retinoblastoma are

made in children younger than 5 years of age, with an equal sex distribution (Abramson 1982). Four types of retinoblastoma have been recognized:

1.Non-heritable retinoblastoma presumably caused by postzygotic retinoblast mutation,

2.Retinoblastoma inherited as an autosomal dominant trait,

3.Retinoblastoma associated with the deletion of band 14 of the long arm of chromosome 13 and

4.Bilateral retinoblastoma and pinealoma (trilateral retinoblastoma) (Jakobiec et al. 1977; Abramson et al. 1981; Bader et al. 1982; Mafee 1996).

As the prognosis depends on the stage of tumor growth, an early and thorough ophthalmological and neuroradiological diagnosis is not only a challenge for the attending physicians, but mandatory for the treatment of the young patients. A retinoblastoma is the prototype of a hereditary tumor and occurs in 1:20,000 of all newborns. About 50% of all cases, presenting as multifocal bilateral tumors, are hereditary (Knudson 1978). The latter form of retinoblastoma is inherited as an autosomal dominant trait due to a mutation in both alleles of the RB1-gene at chromosome 13q14 (Cavanee et al. 1986; Bachmann et al. 1998). While the first of these mutations is a germ-cell mutation, the second occurs locally in diverse primitive retinal progenitor cells (either nuclear layer or photoreceptor cells) (Kyritsis et al.1984),which serves to explain the bilateral and multifocal occurrence (Abramson 1982; Hopper et al. 1992; Bachmann et al. 1998). However,

15% of children presenting with a unilateral retinoblastoma harbor a germinal mutation. The remaining cases of retinoblastoma are sporadic, due to a mutation in both alleles of the RB-gene in one single primitive retinal cell (Zhu et al. 1992; Lohmann et al. 1997). They are unilateral and monofocal and occur in older children.

The small ovoid or round tumor cells comprise scant cytoplasm and relatively large nuclei and may be composed of poorly to well differentiated tumor cells, the latter forming Flexner–Wintersteiner rosettes. Due to rapid growth, retinoblastoma may display extensive necrosis or foci of calcification (Popoff and Ellsworth 1971; Tso 1980).

Retinoma as a nonmalignant manifestation of RB1 mutation (Gallie et al. 1982) develops when the second mutation occurs in a nearly developed retinal cell with reduced potential to acquire mutations, resulting in a benign disordered growth of the retina.

The most common clinical sign of retinoblastoma, found in 60% of the patients, is leukokoria (Fig. 6.5) followed by strabismus (20%). Other clinical signs

like pain caused by secondary glaucoma (Abramson 1982) are considerably rarer. Three different growth patterns are discerned:

1.An endophytic pattern with anterior tumor growth from the retina into the vitreous cavity with vitreous seeds, simulating endophthalmitis.

2.The exophytic pattern: the tumor grows into the subretinal space, producing a secondary retinal detachment and thus simulating Coats’ disease (Haik et al. 1985; De Potter et al. 1995).

3.In diffuse retinoblastoma, the tumor grows along the retina, appearing as a placoid mass, simulating inflammatory or hemorrhagic conditions. This rare form presents diagnostic difficulties because of its lack of calcification and its frequent occurrence outside the typical age group (Haik et al. 1985).

Although ophthalmoscopy allows confirmation of retinoblastomas as small as 0.02 mm, imaging techniques should be used in the diagnosis of these tumors. In addition to ultrasonography, CT and MRI are valuable tools in the assessment of tumor extension in the medial, inferior, and lateral aspects of the globe, extraocular extension, intracranial metastasis, and/or a second tumor. Calcification is frequently present in retinoblastoma (>90%),since DNA released from necrotic retinoblastoma tumor cells has a propensity to form a DNA-calcium complex (Mafee 1996). These calcifications may be small or large, single or multiple, punctuate or finely speckled (Char et al. 1984; Mafee and Peyman 1987; Casper et al. 1993). In children younger than 3 years old, intraocular calcification is highly suggestive of retinoblastoma, because only microphthalmos and colobomatous cysts also exhibit calcification. As mentioned above, the diffuse form of retinoblastoma may have no calcification (Mafee and Peyman 1987; Char et al. 1984), and the diagnosis may be difficult. A retinal astrocytoma (ocular hamartoma) may – sometimes prior to any other clinical signs of tuberous sclerosis – likewise present with intraocular calcification (Mafee and Peyman 1987) (Fig. 6.7).

Although the specificity of MRI in detecting calcifications is inferior to CT, it represents the most important imaging method in the pretherapeutic differential diagnosis of retinoblastoma. This is due to its high sensitivity in highlighting pathologic changes in the ocular anatomy, enabling the simultaneous assessment of possible intracerebral infiltration caused by perineural growth along the optic nerve. Retinoblastomas appear slightly hyperintense compared to normal vitreous matter on T1-weighted

and proton-weighted images (Fig. 6.4), while on T2weighted images, they are seen as areas of low signal intensity (Mafee 1996) (Fig. 6.6). Especially fat-sup- pressed sequences after injection of paramagnetic gadolinium further increase the high sensitivity of MRI due to the fact that retinoblastomas exhibit moderate to marked enhancement (Figs. 6.4–6.6). In case of infiltration of the choroid, no enhancement is seen in this particular region (De Potter et al. 1996; Flanders et al. 1996). MRI technology allows the detection of tumors as small as 2–3 mm, if the patients undergo a thorough examination in all three directions (Figs. 6.4, 6.6). Although retinoblastoma is a bulbar tumor, we consider the use of a surface coil obsolete in the diagnosis of this pathology when performed as a single examination. Despite its excellent sensitivity and high resolution, the limited field of vision (FOV) of the simple surface coil renders the indispensable examination of the optic nerve,chiasm, contralateral globe, and/or cerebrum impossible, in contrast to phase array surface coils (see Chap. 1).

The most common differential diagnoses of retinoblastoma are lesions also presenting with leuko-koria, e.g.,PHPV lesions (Fig.6.2) (see Sect.6.1.1.3) and Coats’ disease (see Sect. 6.1.1.4) (Fig. 6.3). Less frequently observed are retinal detachment,endophthalmitis,toxocariasis, late stages of ROP (retinopathy of the premature), choroidal hemangioma (Fig. 6.16), ciliary body medulloepithelioma, retinal hamartoma, or drusen of the optic nerve head. Drusen of the optic head consists of a primarily autosomal-dominant preliminary mucoprotein matrix deposit with blurred papilla, but only subclinical visual field deficits (Fig. 6.8), a differential diagnosis to papilledema in idiopathic cerebral hypertension (see also Sect. 6.4.1.3.3), and demonstrates calcification of the optic head (Mafee et al. 1995; De Potter et al. 1996). Other rare differential diagnoses of leukokoria are morning glory anomaly or retinal detachment (Mafee 1996; Yan et al. 1998), while choroidal astrocytomas are seen in the course of a tuberous sclerosis (Fig. 6.7). Although case reports exist about rare infections with optic nerve involvement in cysticercosis, intraocular echinococcosis (Fig. 6.9), with a presentation closely resembling leukokoria, is rather unusual (Chandra et al. 2000).

6.1.2.2

Malignant Uveal Melanoma

Malignant melanoma of the ciliary body and the choroid is the most common primary intraocular malignant disease in adults. The incidence of the disease increases with age and ranges from 5.2 to 7.5