Optic nerve glioma and the management of optic nerve tumours in the young.

Thirty-one patients presenting as orbital optic nerve glioma have been reviewed with maximum follow-up of 14 years. Sixteen of these patients have been reported on previously and further follow-up is provided. Sixteen patients had a stable clinical course with little change over a period of up to 13.5 years. Neurofibromatosis was relatively common in this group (11/16). Fifteen patients had progressive enlargement of the tumour; the incidence of neurofibromatosis in this group was low (4/15). Eleven of these patients were explored neurosurgically and the optic nerve totally excised in 10 of them. The proximal cut end was normal in six patients and the chiasm has apparently remained free of tumour in all of them. We suggest a method of management of primary optic nerve tumours, both meningiomas and gliomas, in young patients.     

Unilateral adult malignant optic nerve glioma

Introduction Adult malignant optic nerve gliomas are rare and rapidly fatal visual pathway tumours. They represent a clinical entity different from the more common childhood benign optic nerve gliomas, which are frequently associated with neurofibromatosis I.Case report A 61-year-old woman presented with rapidly progressing right vision loss, lower altitudinal visual field defect and papilloedema. MRI showed intraorbital and intracranial swelling of the right optic nerve. Resection of the intracranial part of the right optic nerve up to the chiasm revealed anaplastic astrocytoma grade III. Within 1 year, the patient died of leptomeningeal metastasis despite radiotherapy. Clinical and MRI evaluation of the left eye and optic nerve were normal at all times.Discussion Unilateral adult malignant glioma of the optic nerve is exceptional. The final diagnosis was only confirmed by optic nerve biopsy. In the literature, only one patient has been reported with a unilateral tumour manifestation; he was lost to follow-up 3 months later. All other cases were bilateral. To date, 44 case reports of adult malignant optic nerve glioma have been published, either malignant astrocytoma or glioblastoma. These tumours can mimic optic neuritis in their initial presentation. The diagnosis is seldom made before craniotomy. On MRI images, malignant glioma cannot be distinguished from optic nerve enlargement due to other causes. Although radiotherapy appears to prolong life expectancy, all presently available treatment options (radiation, surgery, radio-chemotherapy) are of limited value. Most patients go blind and die within 1 or 2 years.This paper was presented in part at the 101st Meeting of the German Ophthalmological Society (DOG).     

Optic Glioma: Long-term Follow-up of 85 Histopathologically Verified Cases

Eighty-five cases of histologically verified gliomas of the optic nerve or chiasm were studied retrospectively. Patient survival was analyzed according to location of tumor, treatment received, presence of neurofibromatosis, and degree of histologic anaplasia. Thirty-three patients had optic nerve tumors, and 52 had tumors involving the chiasm. Follow-up ranged from 6 days to 43 7 years. Of the 33 patients with optic nerve tumors, 28 (85%) survived a mean duration of 17 years, and survival was significantly associated with completeness of surgical excision. Twenty-three of the 52 patients (44%) with chiasmal tumors survived a mean duration of 19 years. Survival among patients with chiasmal tumors was unrelated to therapy received and was affected adversely by concomitant involvement of adjacent brain structures. The presence of neurofibromatosis conferred a protective benefit to patients with chiasmal tumors. No other significant factors could be statistically identified to influence the prognosis of patients with optic gliomas.     

Bilateral optic nerve sheath meningiomas in a patient with neurofibromatosis type 2.

A 34-year-old woman who presented with hearing loss and tinnitus was found to have reduced vision bilaterally. Computed tomography scan revealed bilateral acoustic neuromas and bilateral optic nerve sheath meningiomas. The presence of bilateral acoustic neuromas fulfils the criteria for the diagnosis of central neurofibromatosis (neurofibromatosis type 2). Although this is the first report of bilateral optic nerve sheath meningioma in neurofibromatosis type 2, meningiomas are commoner in this dominantly inherited disorder, than in its absence and both forms of central nervous system tumour may be caused by loss of tumour suppressor genes on chromosome 22.     

Neuro-ophthalmological findings in neurofibromatosis type 1

Objectives: To describe the neuro-ophthalmological findings in five patients with neurofibromatosis type 1 (NF-1). Methods: Retrospective case series. Results: Five patients (3 males, 2 females) with NF-1 who showed neuro-ophthalmogical findings were included in this study. Their ages ranged from one to 28 years (mean: 8 years).Two patients had glioma of the optic chiasm, one glioma of the optic nerve, one orbitotemporal plexiform neurofibroma and glioma of the optic chiasm, and one absence of the greater sphenoid wing. Conclusions: Patients with NF-1 may show different neuro-ophthalmological findings. Lesions tend to develop early in life and might have a favorable long-term natural history. Given the potential for serious visual loss, close follow-up until adolescence is recommended.     

Uveal malignant melanoma and optic nerve glioma in von Recklinghausen''s neurofibromatosis.

A case of uveal malignant melanoma and contralateral optic nerve glioma is described in a 53-year-old Caucasian male with multiple uveal melanocytic hamartomas and neurofibromatosis. The eye was enucleated, and histologically the melanoma was found to consist of 70% epithelioid cells, with many bizarre, multinucleated forms. CT scan demonstrated a non-enhancing, fusiform enlargement of the contralateral optic nerve with enlargement of the optic canal and intracranial extension. This combination of tumours has not previously been reported in a patient with neurofibromatosis and serves to emphasise the common neuroectodermal origin of tumours in this autosomal dominant condition.     

原发性开角型青光眼视神经损害进展与眼压波动及视盘旁萎缩弧扩大的关系

目的 分析原发性开角型青光眼（POAG）视神经损害进展的相关危险因素。设计 回顾性病例系列。 研究对象 北京同仁医院眼科门诊确诊的POAG、随访3年以上、眼底照片及眼压资料完整的患者115例（197眼）。方法 将患者初次就诊和末次就诊的眼底图片在计算机图像处理软件下进行图像配准,通过叠加闪烁对比观察眼底病变的细微改变。平均随访（56.6±14.8）个月。青光眼视神经损害进展的标准为盘沿丢失进展或伴有视网膜神经纤维层缺损进展。主要指标 可能导致青光眼视神经损害进展的多因素Logistic回归分析。结果 视神经损害进展98眼,未进展99眼,进展率49.75%。单因素Logistic回归分析显示视神经损害进展与眼压波动（P=0.000）、峰值眼压（P=0.001）及随访时间（P=0.041）有关;卡方检验显示视神经损害进展与盘沿出血（P=0.02）及视盘旁萎缩弧扩大（P=0.000）有关。多因素Logistic 回归分析显示视神经损害进展与眼压波动（P=0.000）及视盘旁萎缩弧扩大（P=0.000）有关。视神经损害进展组与未进展组相比,眼压波动明显大,前者眼压波动值平均为（2.87±1.29）（0.89～7.21）,后者眼压波动值平均为（2.11±0.94）（0.25～4.97）;并且视盘旁萎缩弧扩大的比例明显增高,视神经损害进展组无β区萎缩弧者5眼（5.1%）,有β区萎缩弧扩大者75眼（76.53%）。结论 除峰值眼压外,过大的眼压波动及β区萎缩弧扩大是POAG视神经损害进展的重要危险因素。（眼科,2012,21：39-42）     

Management of congenital glaucoma in neurofibromatosis type 1: a report of two cases

The most frequent ophthalmic lesions associated to neurofibromatosis type 1 include iris Lisch nodules, optic nerve gliomas, and neurofibromas located on the eyelid, conjunctiva or orbit. Glaucoma is much less frequent, and it may be difficult to diagnose and treat. We present two patients with neurofibromatosis type 1 and associated congenital glaucoma. In case 1, the glaucoma was present at birth, and was the first symptom of the disease. It was surgically treated by means of an Ahmed glaucoma valve implantation, with good intraocular pressure (IOP) control after 13 months of follow-up. In case 2, the glaucoma appeared at 5 months old, and a trabeculectomy was initially performed; it failed 2 years later and an Ahmed glaucoma valve was then implanted, with adequate IOP control after 7 years of follow-up. Both children were males, and in both cases there were orbital neurofibromas and a dysplasia of the greater wing of the sphenoid of the same side. In case 2, orbital enlargement surgery was also performed at 4 years old. Congenital glaucoma management in the context of neurofibromatosis is very complex due to the frequent association of orbital and eyelid tumors and bone dysplasia, and its prognosis is usually poor. We present two cases in which good control of IOP has been achieved with Ahmed glaucoma valve implantation after 13 months and 7 years of follow-up.     

Orbital optic nerve gliomas in children with neurofibromatosis type 1

PURPOSE: To describe the clinical course and treatment of symptomatic orbital optic nerve gliomas in children with neurofibromatosis type-1 (NF-1). METHODS: A retrospective review of the records of patients with NF-1 and symptomatic orbital optic nerve gliomas seen in a large multidisciplinary NF-1 clinic of a tertiary care children's hospital. The main outcome measures included presenting symptoms and signs, ophthalmologic examination at diagnosis, the presence of progressive disease following diagnosis, type of therapy, and the reasons therapy was instituted. RESULTS: Twelve patients with symptomatic orbital optic nerve gliomas, all of which led to proptosis (eight girls, four boys), were identified. The mean age of diagnosis of NF-1 was 20 months; the mean age of diagnosis of the orbital optic nerve glioma was 26 months. At the time of diagnosis of the tumor, 10 of 12 patients (83%) had decreased visual acuity in the affected eye. Three patients underwent optic nerve resection; eight received chemotherapy, and one was observed without therapy. Of the eight children who received chemotherapy, progressive disease prior to treatment could be documented in only three; none of these eight children had a reproducible improvement in vision following chemotherapy. There was no demonstrable improvement in vision in any treated patient with NF-1-associated orbital optic nerve gliomas. CONCLUSIONS: Although not definitively proven, our data and previous studies suggest that NF-1-associated orbital optic nerve gliomas should not be treated unless there is clear evidence of either ophthalmologic or radiographic progression. Surgical excision of tumors which have led to proptotic eyes without functional vision should be reserved for cosmetic purposes or to treat complications of exposed globes.     

Initial glaucomatous optic disk and retinal nerve fiber layer abnormalities and their progression

We attempted to identify the initial glaucomatous changes of the optic disk and retinal nerve fiber layer and to analyze how these changes subsequently progressed. Of 61 eyes of 61 patients with ocular hypertension, 23 (38%) developed glaucoma during ten years of follow-up (range, five to 15 years). The initial sign of glaucomatous damage was diffuse enlargement of the optic disk cup in ten of 23 eyes or generalized thinning of the nerve fiber layer without localized changes in 12 of 23 eyes. We found localized optic disk damage in ten of 23 patients and localized retinal nerve fiber layer damage in 11 of 23 patients alone or in combination with diffuse damage. In 13 of 23 eyes, the cupping ended up in diffuse enlargement with even more profound thinning of the neural rim in the upper and lower temporal disk margins. There seems to be great variability in the appearance and progression of the initial glaucomatous optic disk and nerve fiber layer abnormalities in patients with increased intraocular pressure.     

中国人McCune-Albright综合征的临床分析

目的 探讨McCune-Albright综合征(MAS)的眼部临床特点.方法 系列病例研究.分析从2008年1月至2011年6月就诊北京协和医院眼科的6例MAS患者最佳矫正视力、视野、色觉、视网膜神经纤维层厚度、视觉诱发电位、眼底、视神经管CT扫描,多科综合治疗方法及随访结果.结果 6例MAS患者中男性3例,女性3例,就诊年龄在4～ 43岁(中位数16岁).视神经管CT扫描发现6例(12只眼)MAS患者视神经管有不同程度的缩窄,其中全周缩窄3例(6只眼)、部分缩窄3例(6只眼),视神经管全周缩窄中有2例(3只眼)发现有视神经病变,其余9只眼均未发现有视神经病变.有4例(8只眼)MAS患者视神经被不同程度拉长.结论 MAS患者视神经管有不同程度的缩窄,部分患者出现视神经病变,应当在临床上受到高度关注.     

Optic Nerve Sheath Meningioma: Associations and Implications

The classical clinical presentation of optic nerve sheath meningiomas is painless, slowly progressive, unilateral optic neuropathy with a swollen and/or pale optic disc. It affects middle-aged women more frequently than men. Optic nerve sheath meningiomas occur frequently in patients with neurofibromatosis type 2. This association parallels the well known link between neurofibromatosis type 1 and optic gliomas. Due to advances in neuroimaging, management decisions have to be made in patients with excellent visual function. Fractionated conformal stereotactic radiotherapy holds the best potential to improve, prevent or at least delay severe visual loss in patients with optic nerve sheath meningiomas.     

Evaluation of acute radiation optic neuropathy by B-scan ultrasonography

We studied the accuracy of B-scan ultrasonography to diagnose radiation-induced optic neuropathy in 15 patients with uveal melanoma. Optic neuropathy was diagnosed by an observer masked as to clinical and photographic data. We analyzed planimetry area measurements of the retrobulbar nerve before and after irradiation. The retrobulbar area of the optic nerve shadow on B-scan was quantitated with a sonic digitizer. Increased optic nerve shadow area was confirmed in 13 of 15 patients who had radiation optic neuropathy (P less than .004). The correct diagnosis was confirmed when the results of ultrasound were compared to fundus photography and fluorescein angiography. In 13 patients there was acute radiation optic neuropathy. Two patients did not show an enlarged retrobulbar optic nerve, and the clinical appearance suggested early progression to optic atrophy. Ultrasonography documents the enlargement of the optic nerve caused by acute radiation changes.     

Clinical presentation of retinoblastoma in Eastern Nepal

BACKGROUND: The purpose of the present study was to determine modes of presentation of retinoblastoma and the association between proptosis with orbital extension and histopathologically detectable optic nerve infiltration by the tumour. METHODS: Clinical records and histopathological reports of patients with retinoblastoma were studied retrospectively. The work was undertaken at a tertiary care hospital in eastern Nepal during the period from September 1995 to August 2002. RESULTS: A total of 43 patients with retinoblastoma were studied. Among them unilateral involvement was found in 39 patients (90.70%) and bilateral involvement in four patients (9.30%). The mean age of presentation was 3.04 +/- 1.80 years (95% confidence interval = 2.49-3.59). The commonest mode of presentation was proptosis with orbital extension in 19 eyes (40.42%) followed by leucokoria in 14 eyes (29.78%). Histopathological reports of 42 eyes (one patient died shortly after admission and did not have an autopsy) confirmed the diagnosis of retinoblastoma and revealed that the optic nerve cut section had been infiltrated in 18, of which 16 had the clinical finding of proptosis with orbital extension. This was statistically significant (relative risk = 21.33, P < 0.001). CONCLUSION: The commonest mode of presentation of retinoblastoma in Nepal is proptosis. Presence of proptosis with orbital extension is associated with optic nerve cut end infiltration by the tumour. The diagnosis or presentation of retinoblastoma in Nepal is delayed and there is tremendous scope for improvement in its management.     

Optic nerve glioma in Japanese patients with neurofibromatosis 1. Case reports and literature review.

Case 1, a 6-year-old boy, had multiple café-au-lait spots, no light perception OS, Lisch nodules OU, pale optic disc OS, enlarged left optic nerve on computed tomographic scan and magnetic resonance imaging, and histopathologically verified pilocytic astrocytoma (glioma). The patient's mother had neurofibromatosis 1 (NF-1). Case 2, a 12-year-old boy, had multiple café-au-lait spots, decreased visual acuity OU, Lisch nodules OU, pale optic discs OU, enlarged optic nerves and chiasm on computed tomographic scan, and histopathologically verified pilocytic astrocytoma. We also examined 38 Japanese patients with NF-1 and found Lisch nodules in 95% and optic nerve glioma in 5%. After reviewing the recent literature, we found that the association of optic nerve glioma and NF-1 in the Japanese population was less than that reported in North America.     

Diameter of the optic nerve in idiopathic optic neuritis and in anterior ischemic optic neuropathy

Purpose: There is considerable overlap in the clinical profile of patients with idiopathic optic neuritis(ON) and anterior ischemic optic neuropathy (AION). We tested the hypothesis that the retrobulbar diameter of the optic nerve may be a criterion for the differential diagnosis between ON and AION. Methods: The diameter of the optic nerve was measured by B-scan ultrasonography with the eye in an abducted position. Only patients with a unilateral optic neuropathy were included, 16 ON patients (mean age 24years, 5 with and 11 without disc swelling) and 9patients with AION (mean age 72 years). As controls for the ON patients 10 young normal subjects (mean age25 years) and as controls for the AION patients 10elderly subjects with eye problems not related to the optic nerve (mean age 76 years) were examined. Results: In the ON patients with disc swelling the diameter of the optic nerve was 5.4 ± 0.5 mm in the affected and 3.0 ± 0.3 mm in the unaffected side. This difference was significant (Wilcoxon-test, p = 0.043). In the ON patients without disc swelling the diameter of the optic nerve was 4.4 ± 0.4 mm in the affected and 3.0 ± 0.3 mm in the unaffected side. This difference was significant (Wilcoxon-test, p = 0.003). In the AION patients the diameter of the optic nerve was 3.0 ± 0.3 mm on the affected and2.8 ± 0.4 mm on the unaffected side. This difference was not significant (Wilcoxon-test, p =0.093). Comparing the optic nerves with ON and AION to those of the controls, the diameter was significantly enlarged in the nerves with ON and normal in the nerves with AION (one factor repeated ANOVA). Conclusion: The diameter of the optic nerve is increased in ON without disc swelling and even more so in ON with disc swelling. The enlargement is probably due to edema of the nerve itself, not the surrounding subarachnoidal space. In AION, the diameter of the optic nerve is normal. Measuring the diameter of the optic nerve by B-scan ultrasonography is particularly useful in the differential diagnosis between ON with disc swelling and AION. This revised version was published online in August 2006 with corrections to the Cover Date.     

Optic glioma of childhood: clinical, histopathological, and histochemical observations.

This report documents the long-term clinical and histopathological behaviour of eight intraorbital and 16 intracranial optic nerve gliomas and relates the therapeutic data to the prognosis for both visual acuity and survival. The mean age at onset of symptoms was 8.6 years and at the diagnosis 10.9 years. It is generally held that proptosis is mild in intraorbital glioma, but we encountered marked proptosis ranging from 7 to 12 mm in six of the eight intraorbital gliomas, which contained abundant Alcian-blue-positive mucoid material. Of the patients with intracranial optic nerve gliomas 37.5% survived for a mean of eight years after treatment with radiotherapy or surgery combined with radiotherapy. At follow-up ranging from five months to 11 years only one of the six patients with intracranial gliomas had full visual acuity. Our observations emphasise that, although optic nerve gliomas are benign hamartomas, the prognosis for visual acuity and survival is unfavourable in cases which are diagnosed and treated late. Histopathological and histochemical observations suggest that increase in the amount of mucoid material may contribute to rapid enlargement of intraorbital and intracranial optic gliomas.     

Unilateral papilledema revealing an intracanalicular optic nerve sheath meningioma

A 43-year-old female is referred to our clinic for evaluation of an incidentally discovered unilateral papilledema in her right eye of unknown cause. She had no past ocular or medical history. Examination revealed a corrected-distance visual acuity of 20/20 in both eyes. Posterior segment examination showed an elevated right optic nerve head with blurred edges. Ultrasonography failed to reveal optic disc drusen. Visual field testing showed enlargement of the blind spot in the right eye. Magnetic resonance imaging of the brain and orbit was done and revealed enlargement of the intracanalicular and prechiasmatic part of the right optic nerve and a diagnosis of a presumed right intracanalicular optic nerve sheath meningioma was made. She was managed conservatively and several years later remains asymptomatic.     

Ganglioglioma of optic nerve in neurofibromatosis type 1. Case report and review of the literature

BACKGROUND: Gangliogliomas are rare tumors of the central nervous system. In only seven cases they have been found within the optic nerve. Two of these cases were associated with neurofibromatosis (NF), but a pathogenic link between gangliogliomas of the optic nerve and NF still remains controversial. PATIENT: Here we report on a 71-year-old patient with a ganglioglioma of the optic nerves and NF type 1. Post mortem examination revealed multiple neurofibromas of the vagal and left femoral nerves, multiple schwannomas of the small bowel and Lisch noduli of both irides. In addition, a spindle shaped thickening of the right optic nerve was observed in its intracranial portion. The left optic nerve was normal on gross inspection. RESULT: Histologically, tumoral tissue was found in both optic nerves. The tumor was composed of two cell types: highly differentiated, partly stellate, partly pilocytic astrocytes and, at the rim of the axon bundles of the optic nerve, fully developed synaptophysin- and neurofilament-antigen-positive ganglion-cells with short corkscrew-shaped processes. No mitosis could be found in the neuronal or in the glial cell population. In spite of the tumoral involvement of the optic nerves, there has been no evidence of visual disturbance. CONCLUSION: Optic nerve tumors in NF most often are of glial origin (astrocytomas, pilocytic astrocytomas). Our case illustrates the rare condition of a glioneuronal tumor associated with neurofibromatosis type 1.     

A case of neurofibromatosis 1 presenting with optic pathway glioma with an early onset and an aggressive course

Optic pathway glioma associated with neurofibromatosis 1 has a classically indolent course. However, involvement of the optic radiations is relatively rare and is associated with a more aggressive course. A three-year-old girl presented with strabismus and loss of vision in the left eye with relative afferent pupillary defect and optic disc pallor. She had multiple cafiota au lait spots. Visually evoked potential was suggestive of an optic nerve conduction defect and magnetic resonance imaging of the brain was suggestive of an optic pathway glioma involving the optic nerves, the optic chiasma and the optic tracts. The optic radiations and the dendate nuclei had hamartomas. Optic nerve biopsy confirmed pilocytic astrocytoma. Radical radiotherapy under general anesthesia was subsequently given. This case report aims to highlight the involvement of the optic radiations and the unusually aggressive clinical course in this case.