Ординатура / Офтальмология / Английские материалы / Essentials in Ophthalmology Pediatric Ophthalmology Neuro-Ophthalmology Genetics_Lorenz, Borruat_2008

gins of up to a number of centimetres were used to ensure that the entire tumour was treated. Not unexpectedly the reports of treatment-associated morbidity are frequent [25, 30].

Due to the tendency to use Kaplan Meier curves to express survival following treatment, readers are presented with a gloomy if not dismal picture from most reports [28, 30]. This is fuelled by the misapprehension that tumourrelated mortality is the inverse of actuarial survival. Most papers do not quote the actual mortality rates and even less frequently the mortality rates directly attributable to the initial tumour. Often death is due to other disease or to second tumours (occasionally induced by radiotherapy). In those papers where it is possible to discern this information, tumour-related deaths are very infrequent. Tow et al. [62] reported that 2/47 (4%) patients died as a direct result of their tumours during a follow-up period of 10–28 years. Khafaga et al. [28] reported 5/50 deaths with a follow-up of 2.4–16.5 years, but only 2 (4%) of these were attributable to the OPGs. Tow et al. [62] do not present their data with Kaplan Meier curves. Khafaga et al. [28] do represent their data in this way and at 10 years the survival is 75%. As the median follow-up was 7 years we know the cohort size has shrunk considerably at 10 years. Thus the five deaths will have a far greater effect on the much reduced cohort size at 10 years, accounting for the 75% survival if the cohort size had reduced to 20 patients.

A further difficulty is the selection bias in papers looking at treatment of this condition. By comparing the distribution of the location of tumours in each of the papers we see that posterior tumours are heavily represented in most. This is in stark contrast to Tow et al. [62]. Thus, as Tow et al. [62] and others have shown that posteriorly located tumours have higher intrinsic morbidity and mortality (in the absence of treatment), it is not surprising that overall morbidity and mortality is higher in papers in which this group is over-represented, irrespective of the treatment utilized. The converse is also true: as minimally progressive tumours are under-represented, morbidity and mortality measures will be skewed in an adverse direction irrespective of the treatment modality.

Summary for the Clinician

■Bias in the literature produces an unnecessarily gloomy picture of the prognosis for these tumours.

■Tumour-related mortality is likely to be in the region of 4%.

5.3.1.1 Paediatric

The Consensus Statement from the NF1 optic pathway glioma task force [34] offers clear guidelines for the assessment, surveillance and management of patients with and without OPGs. The recently reported Australian experience [60] supports the stance taken by this task force but emphasizes the need for continued vigilance as many patients developed later progression of their OPG. The management of other patients depends on the site of the tumour.

Also, although it was thought to occur infrequently, the very real possibility of spontaneous regression [51] in these tumours may not only have an influence on our management choice but also needs to be taken in to account when considering the response to treatment described in the literature. If Parsa et al. [51] are correct in their assertion that spontaneous tumour regression happens with a high frequency, response to any of these treatment modalities needs to be reassessed. Currently it is not possible to correctly ascertain whether tumour regression is spontaneous or the direct result of therapy.

Summary for the Clinician

■Spontaneous regression may have occurred in patients who have had “successful treatment” for their tumours.

5.3.1.1.1 Optic Nerve

Miller [44] sets out a very pragmatic approach to tumours confined to the orbital optic nerve. If one were to consider survival alone, then sur-

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gical removal of these tumours appears to offer good results. Unfortunately there is universal visual morbidity associated with this approach. If surgery is reserved for patients with progressive visual dysfunction, gross cosmetic disfigurement or MRI evidence of extension of the tumour towards the chiasm, then the visual function and survival are maximized [62]. There are insufficient data on the management of tumours in this location with radiotherapy or chemotherapy to make meaningful suggestions about these treatment modalities, due to the under-representation of anterior tumours in treatment papers. This would suggest that large numbers of these patients have been followed-up (or not diagnosed) without referral to a treatment centre over the years. What can be said is that observation, surgical excision and radiotherapy all have equally high survival for tumours restricted to the optic nerve [28, 30, 62].

5.3.1.1.2 Optic Chiasm

In the literature there is greatest experience with radiotherapy for tumours in this location [10, 14, 20, 21, 25, 28, 30, 62]. In a large number of cases radiotherapy has been used in combination with partial resection as complete resection is not an option in these patients. More posterior tumours (e.g., OCHG versus OCG) are more likely to require surgical debulking. Some authors have advocated early intervention with radiotherapy as in a few cases improved visual function has been demonstrated [14]. Others have adopted a wait and see approach [62] and have demonstrated maintenance of good visual function in the least affected eye for decades.

What is clear from the literature is that delivery of radiotherapy has improved dramatically over the last two decades and novel delivery systems have decreased the morbidity (and potentially mortality) associated with radiotherapy [10, 14]. MRI, three-dimensional planning and conformal stereotactic delivery have shrunk the high isodose curves to within a few millimetres of the tumour volume without evidence of marginal recurrence. Conventional external beam radiotherapy was also associated with large exit

beams exposing adjacent and sometimes distant structures to high doses of photons. Proton delivery systems now offer the possibility of no exit beam and therefore highly targeted treatment [20].

Summary for the Clinician

■Anterior tumours – surgery if progressive visual loss, gross cosmetic disfiguration or MRI evidence of extension towards the chiasm.

■Chiasmal tumours – radiotherapy (or chemotherapy) if progressing. Use 3D conformal or proton beam. Posterior tumours may require surgical debulking.

5.3.1.2 Adult

OPG presenting as an adult poses a significant management dilemma. If the patient is middleaged or older then biopsy of the lesion is essential. Biopsy-proven OPG in this age group is universally fatal, usually within months. Radiotherapy may increase survival, but the effect is marginal at best and does not improve visual function [13]. The confusion with orbital inflammatory processes at initial presentation, both symptomatically and on imaging, has been highlighted by most authors [8, 41]. This serves as a reminder that typical optic neuritis should only be diagnosed in younger individuals. Although the median age of patients with this malignant subtype is 56 the range of ages in the literature is from 22 to 79 years [13]. Thus patients presenting in their third decade pose a particular diagnostic dilemma. Compare Fig. 5.1b (a 24-year-old man with NF1 and a benign OCG) with Fig. 5.4 (a 72-year-old woman with a bi- opsy-proven malignant glioma). If stigmata of NF1 are present biopsy is probably avoidable. In all other cases biopsy will be required to (1) accurately assess the non-inflammatory nature of the mass and (2) to determine the degree of differentiation and growth potential.

Summary for the Clinician

■Biopsy is required in the absence of stigmata of NF1.

■If the diagnosis is confirmed on biopsy the prognosis is very poor.

5.3.2 Meningiomas

A clear understanding of the natural history of these tumours has long evaded the ophthalmic literature. Data on long-term follow-up of individuals in the absence of surgical intervention have only become available in the last two decades [15, 17, 27, 54, 55, 63]. Prior to this enthusiasm for complete surgical clearance, despite the impossibility of achieving it, was the norm [66]. This resulted in temporary control of the tumour but had immediate and disastrous consequences for vision. This type of intervention also made clear the folly of opening the dural sheath to either decompress the nerve or to attempt partial removal. This approach led to widespread recurrence within adjacent structures, in an unconstrained fashion [66]. The poor visual outcome from this approach has again been recently documented [54].

It is now clear that if a patient presents with good vision they are likely to maintain this for years [16, 54, 63]. It is also clear that earlier con-

cerns about intracranial spread, propensity to affect the opposite optic nerve or chiasm, or other intracranial vital structures were misplaced [17, 44]. Even when these tumours invade the middle cranial fossa they behave in a benign fashion. Al-Mefty [2] points out that they will have an intervening layer of arachnoid between them and other vital structures preventing their envelopment, in effect behaving like type III anterior clinoidal meningiomas.

Hormonal and chemotherapeutic manipulation of ONSM have both been reported with poor long-term effects [13, 28]. Many different approaches to the therapeutic delivery of radiation therapy have now been reported. Numerous editorials have indicated the change in approach to treatment that has occurred in the last decade [40, 42, 43]. In an attempt to control the dose of radiotherapy delivered to the opposite optic nerve as well as other adjacent vital structures, stereotactic fractionated radiotherapy [1, 5, 37, 52] or three-dimensional conformal radiotherapy [31, 47, 49] have been employed. Both techniques produce good control of the tumour and limit the deleterious effect of radiation on adjacent and distant structures. In addition a sizable number of patients demonstrate either stability or improvement in their vision (acuity and field) for years after treatment. The only remaining question is at what stage in the disease process to administer radiation therapy [45]. As imaging is now able to detect tumours at an earlier stage and patients are often presenting with excellent visual function, therapeutic intervention is probably best reserved until a demonstrable progressive decline in vision has occurred. At this stage early intervention with conformal or stereotactic radiotherapy offers the best available disease control at present [45].

Fig. 5.4.  Coronal view of a malignant optic chiasm glioma in a 72-year-old patient

Summary for the Clinician

■Observe unilateral tumours even in the presence of intracranial extension.

■Offer 3D conformal or stereotactic radiotherapy if there is progressive visual loss.

First two decades Either

Common – type 1 Occasional

Kinking of orbital nerve; fusiform enlargement; hyperintense on T2; whole nerve enhances

5.4 Conclusions

Our ability to detect even small tumours affecting the optic pathway has improved tremendously since the introduction of MRI. Although it is still not perfect (intracanalicular meningiomas). Clinical and imaging characteristics are summarized in Table 5.1. Clear guidelines now exist for diagnosing and monitoring patients with both optic pathway gliomas and optic nerve sheath meningiomas. Timing of therapeutic intervention is still a subject of some debate and only long-term well-constructed treatment trials following patients for decades will determine if intervention is more costly in terms of collateral damage than the disease process itself. Whereas preservation of life was the aim of therapy in the pre-MRI era, a clear understanding of the indolent nature of most of these tumours and developments in the field of radiation therapy have led us to a point where preservation of vision is now the primary aim of treatment.

References

1.Andrews DW, Faroozan R, Yang BP et al (2002) Fractionated stereotactic radiotherapy for the treatment of optic nerve sheath meningiomas: preliminary observations of 33 optic nerves in 30 patients with historical comparison to observation with or without prior surgery. Neurosurgery 51:890–904

2.Al-Mefty O (1990) Clinoidal meningiomas. J Neurosurg 73:840–849

in Neurofibromatosis type 1. Curr Opin Neurol 17:101–105

4.Backhouse O, Simmons I, Frank A et al (1998) Optic nerve breast metastasis mimicking meningioma. Aust NZ J Ophthalmol 26:247–249

5.Becker G, Jeremic B, Pitz S et al (2002) Stereotactic fractionated radiation in patients with optic nerve sheath meningioma. Int J Radiat Oncol Biol Phys 54:1422–1429

6.Bosch MM, Wichmann WW, Bolthauser E et al (2006) Optic nerve sheath meningiomas in patients with neurofibromatosis type 2. Arch Ophthalmol 124:379–385

7.Brazier DJ, Sanders MD (1996) Disappearance of optociliary shunt vessels after optic nerve sheath decompression. Br J Ophthalmol 80:186–187

8.Brodovsky S, ten Hove MW, Pinkerton RMH et al (1997) An enhancing optic nerve lesion: malignant glioma of adulthood. Can J Ophthalmol 32:409–413

9.Brodsky MC, Hoyt WF, Barnwell SL et al (1988) Intrachiasmatic craniopharyngoima: a rare cause of chiasmal thickening. J Neurosurg 68:300–302

10.Combs SE, Schulz-Ertner D, Moschos D et al

(2004) Fractionated stereotactic radiotherapy of optic pathway gliomas: tolerance and longterm outcome. Int J Radiat Oncol Biol Phys 62:814–819

11.Cooling RJ, Wright JE (1979) Arachnoid hyperplasia in optic nerve glioma: confusion with orbital meningioma. Br J Ophthalmol 63:596–599

12.Cunliffe IS, Moffat DA, Hardy DG et al (1992) Bilateral optic nerve sheath meningiomas in a patient with neurofibromatosis type 2. Br J Ophthalmol 76:310–312

13.Dario A, Iadini A, Cerati M et al (1999) Malignant optic glioma of adulthood. Case report and review of the literature. Acta Neurol Scand 100:350–353

14.Debus J, Kocagöncü O, Höss A et al (1999) Fractionated stereotactic radiotherapy (FSRT) for optic glioma. Int J Radiat Oncol Biol Phys 44:243–248

15.Dutton JJ (1992) Optic nerve sheath meningiomas. Surv Ophthalmol 37:167–183

16.Dutton JJ (1994) Gliomas of the anterior visual pathway. Surv Ophthalmol 38:427–452

17.Egan RA, Lessell S (2002) A contribution to the natural history of optic nerve sheath meningiomas. Arch Ophthalmol 120:1505–1508

18.Frisen L, HoytWF, Tengroth BM (1973) Optociliary veins, disc pallor and visual loss: a triad of signs indicating spheno-orbital meningioma. Acta Ophthalmol 57:241–249

19.Fuller JJ, Mason JO, White MF et al (2003) Retinochoroidal collateral veins protect against anterior segment neovascularization after central retinal vein occlusion. Arch Ophthalmol 121:332–336

20.Fuss M, Hug EB, Schaefer RA et al (1999) Proton radiation therapy (PRT) for pediatric optic pathway gliomas: comparison with 3D planned conventional photons and a standard photon technique. Int J Radiat Oncol Biol Phys 45:1117–1126

21.Grill J, Laithier V, Rodriguez D et al (2000) When do children with optic pathway gliomas need treatment: an oncological perspective in 106 patients treated in a single centre. Eur J Paediatr 159:692–696

22.Hollenhorst RW Jr., Hollenhorst RW Sr., MacCarty CS (1977) Visual prognosis of optic nerve sheath meningiomas producing shunt vessels on the optic disk: the Hoyt-Spencer syndrome. Trans Am Ophthalmol Soc 75:141–163

23.Irvine AR, Shorb SR, Morris BW (1977) Optociliary veins. Trans Am Acad Ophthalmol Otolaryngol 83:541–546

24.Jackson A, Patankar T, Laitt RD (2003) Intracanalicular optic nerve meningioma: a serious diagnostic pitfall. Am J Neuroradiol 24:1167–1170

25.Jenkin D, Angyalfi S, Becker L et al (1993) Optic glioma in children: surveillance, resection or irradiation? Int J Radiat Oncol Biol Phys 25:215–225

26.Jennings JW, Rojiani AM, Brem SS et al (2002) Necrotizing neurosarcoidosis masquerading as a left optic nerve meningioma: case report. Am J Neuroradiol 23:660–662

27.Kennerdell JS, Maroon JC Malton M et al (1988) The management of optic nerve sheath meningiomas. Am J Ophthalmol 106:450–457

28.Khafaga Y, Hassounah M, Kandil A et al (2003) Optic gliomas: a retrospective analysis of 50 cases. Int J Radiat Oncol Biol Phys 56:807–812

29.Kornreich L, Blaser S, Schwarz M et al (2001) Optic pathway glioma: correlation of imaging findings to the presence of neurofibromatosis. AJNR Am J Neuroradiol 22:1963–1969

30.Kovalic JJ, Grigsby PW, Shepard MJ et al (1990) Radiation therapy for gliomas of the optic nerve and chiasm. Int J Radiat Oncol Biol Phys 18:927–932

31.Lee AG, Woo SY, Miller NR et al (1996) Improvement in visual function in an eye with a presumed optic nerve sheath meningioma after treatment with three-dimensional conformal radiation therapy. J Neuroophthalmol 16:247–251

32.Liauw L, Vielvoye GJ, de Keizer RJW et al (1996) Optic nerve glioma mimicking an optic nerve meningioma. Clin Neurol Neurosurg 98:258–261

33.Lindblom B, Truwit CL, Hoyt WF (1992) Optic nerve sheath meningioma: definition of intraorbital, intracanalicular and intracranial components with magnetic resonance imaging. Ophthalmology 99:560–566

34.Listernick R, Louis DN, Packer RJ et al (1997) Optic pathway gliomas in children with neurofibromatosis 1: consensus statement from the NF1 optic pathway glioma taskforce. Ann Neurol 41:143–149

35.Listernick R, Ferner RE, Piersall L et al (2004) Late-onset optic pathway tumors in children with neurofibromatosis 1. Neurology 63:1944–1946

36.Liu GT, Brodsky MC, Phillips PC et al (2004) Optic radiation involvement in optic pathway gliomas in neurofibromatosis. Am J Ophthalmol 137:407–414

37.Liu JK, Forman S, Hershewe GL et al (2002) Optic nerve sheath meningiomas: visual improvement after stereotactic radiotherapy. Neurosurgery 50:950–957

38.Mashayekhi A, Sheilds JA Sheilds CL (2004) Involution of retinochoroidal shunt vessel after radiotherapy of optic nerve sheath meningioma. Eur J Ophthalmol 14:61–64

39.Massry GG, Morgan CF, Chung SM (1997) Evidence of optic pathway gliomas after previously negative neuroimaging. Ophthalmology 104:930–935

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5

Optic Nerve Tumours

40.Matthews TD, Anderson IRC (2002) Meningiomas: the anterior visual pathway. Curr Med Lit Ophthalmol 12(4):77–83

41.Millar WS, Tartaglino LM, Sergott RC et al (1995) MR of malignant glioma of adulthood. AJNR Am J Neuroradiol 16:1673–1676

42.Miller NR (2002) The evolving management of optic nerve sheath meningiomas. Br J Ophthalmol 86:1198

43.Miller NR (2002) Radiation for optic nerve meningiomas: Is this the answer? Ophthalmology 109:833–834

44.Miller NR (2004) Primary tumours of the optic nerve and its sheath. Eye 18:1026–1037

45.Miller NR (2006) New concepts in the diagnosis and management of optic nerve sheath meningioma. J Neuroophthalmol 26:200–208

46.Miller NR, Solomon S (1991) Retinochoroidal (optociliary) shunt veins, blindness and optic atrophy: a non-specific sign of chronic optic nerve compression. Aust NZ J Ophthalmol 19:105–109

47.Moyer PD, Golnik KC, Breneman J (2000) Treatment of optic nerve sheath meningioma with three-dimensional conformal radiation. Am J Ophthalmol 129:694–696

48.Muci-Mendoza R, Arevalo JF, Ramella M et al (1999) Optociliary veins in optic nerve sheath meningioma; indocyanine green videoangiography findings. Ophthalmology 106:311–318

49.Narayan S, Cornblath WT, Sandler HM et al (2003) Preliminary visual outcomes after threedimensional conformal radiation therapy for optic nerve sheath meningioma. Int J Radiat Oncol Biol Phys 56:537–543

50.Ng KL, McDermott N, Romanowski CA et al (1995) Neurosarcoidosis masquerading as glioma of the optic chiasm in a child. Postgrad Med J 71:265–268

51.Parsa CF, Hoyt CS Lesser RL et al (2001) Spontaneous regression of optic gliomas: thirteen cases documented by serial imaging. Arch Ophthalmol 119:516–529

52.Pitz S, Becker G, Schiefer U et al (2002) Stereotactic fractionated irradiation of optic nerve sheath meningioma: a new treatment alternative. Br J Ophthalmol 86:1265–1268

53.Roberti F, Lee HH, Caputy AJ et al (2005) “Shave” biopsy of the optic nerve in isolated neurosarcoidosis. J Neurosurg Sci 49:59–63

54.Saaed P, Rootman J, Nugent RA et al (2003) Optic nerve sheath meningiomas. Ophthalmology 110:2019–2030

55.Sarkies NJC (1987) Optic nerve sheath meningioma: diagnostic features and therapeutic alternatives. Eye 1:597–602

56.Schatz H, Green WR, Talamo JH et al (1991) Clinicopathologic correlation of retinal to choroidal venous collaterals of the optic nerve head. Ophthalmology 98:1287–1293

57.Selva D, Rootman J, Crompton J (2004) Orbital lymphoma mimicking optic nerve meningioma. Orbit 23:115–120

58.Shen TT, SakaiO, Curtin HD et al (2001) Magnetic resonance imaging of primary anterior visual pathway tumours. Int Ophthalmol Clin 41:171–180

59.Smith JL, Vuksanovic MM, Yates BM et al (1981) Radiation therapy for primary optic nerve meningiomas. J Clin Neuroophthalmol 1:85–99

60.Thiagalingam S, Flaherty M, Billson F et al (2004) Neurofibromatosis type 1 and optic pathway glioma: follow-up of 54 patients. Ophthalmology 111: 568–577

61.Thorne JE, Volpe NJ, Wulc AE et al (2002) Caught by a masquerade: sclerosing orbital inflammation. Surv Ophthalmol 47:50–54

62.Tow SL, Chandela S, Miller NR et al (2003) Longterm outcome in children with gliomas of the anterior visual pathway. Pediatr Neurol 28:262–270

63.Turbin RE, Thompson CR, Kennerdell JS et al (2002) A long-term visual outcome comparison in patients with optic nerve sheath meningioma managed with observation, surgery, radiotherapy, or surgery and radiotherapy. Ophthalmology 109:890–900

64.Vaphiades MS (2001) Disk edema and cranial MRI optic nerve enhancement: how long is too long? Surv Ophthalmol 46:56–58

65.Wright JE, McDonald WI, Call NB (1980) Management of optic nerve gliomas. Br J Ophthamol 64:545–552

66.Wright JE, McNab AA, McDonald WI (1989) Primary optic nerve sheath meningioma. Br J Ophthalmol 73:960–966

Core Messages

■Traumatic optic neuropathy (TON) may result from either direct or indirect injury.

■TON can be classified into transection and compressive forms of neuropathy.

■Both forms of TON may result in acute loss of vision.

■Transection of the optic nerve is rare and currently untreatable.

■Compressive TON can be treated with steroids, surgery, or both.

■Conservative treatment has been performed with prednisolone at widely varying doses.

■Surgical treatment has been performed with transsphenoid and endoscopic decompression of the optic canal.

■However, none of the current treatments has been tested in a prospective, controlled, and randomized multicentric study, and the available reported results are no better than those when TON remains untreated.

■None of the treatments can be recommended until evidence-based data are available, and any decision on treatment should be made on an individual basis.

■Neuroprotection is still in the experimental phase, and cannot be yet recommended in the treatment of TON.

■Regeneration of the optic nerve is still in the experimental phase but may become available in the future.

■A complete ophthalmic examination should precede any treatment or the inclusion in a prospective treatment trial.

6.1 Introduction

6.1.1 Optic Nerve Anatomy

The mature optic nerve consists of about one million retinal ganglion cell axons, all of which are ensheathed by oligodendrocytes, plus astrocytes, capillaries, microglial cells, and extracellular matrix. The cellular organization of the optic nerve is similar to that of the cerebral white matter and the long intraspinal tracts of fibers. The optic nerve differs from peripheral nerves, in that the

latter contain Schwann cells, and are therefore considered as central tracts that project outside the confines of the cranial grooves.

Beginning at the optic nerve head, the optic nerve travels within the muscle conus formed by the extraocular muscles, and after about 30 mm passes into the optic canal (which is a 5- to 12-mm-long boney canal superonasally to the superior orbital fissure) and enters the cranium. Some sympathetic axons destined for the orbit and the dura-covered ophthalmic artery located at the inferolateral aspect of the optic nerve lie

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