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Abstract：
Neurofibromatosis Type I (NF1), also termed von Recklinghausen disease, is a rare genetic disorder that is transmitted by autosomal dominant inheritance, with complete penetrance and variable expressivity. It is caused by mutation in the NF1 gene on chromosome 17 encoding for neurofibromin, a protein with oncosuppressive activity, and it is 50% sporadic or inherited. The disease is characterized by a broad spectrum of clinical manifestations, mainly involving the nervous system, the eye and skin, and a predisposition to develop multiple benign and malignant neoplasms. Ocular diagnostic hallmarks of NF1 include optic gliomas, iris Lisch nodules, orbital and eyelid neurofibromas, eyelid café-au-lait spots. Choroidal nodules and microvascular abnormalities have recently been identified as additional NF1-related ocular manifestations. The present study was designed to describe the features and clinical significance of a new sign related to the visual apparatus in NF-1, represented by hyperpigmented spots (HSs) of the fundus oculi.
HSs were detected in 60 (24.1%) out of 249 patients with NF1, with a positive predictive value of 100% and a negative predictive value of 44.2%. None of the healthy subjects (150 subjects) showed the presence of HSs. HSs were visible under indirect ophthalmoscopy, ultra-wide field (UWF) pseudocolor imaging and red-only laser image, near-infrared reflectance (NIR)-OCT, but they were not appreciable on UWF green reflectance. The location and features of pigmentary lesions matched with the already studied NF1-related choroidal nodules. No significant difference was found between the group of patients (n = 60) with ocular HSs and the group of patients (n = 189) without ocular pigmented spots in terms of age, gender or severity grading of the disease. A statistically significant association was demonstrated between the presence of HSs and neurofibromas (p = 0.047), and between the presence of HSs and NF1-related retinal microvascular abnormalities (p = 0.017).
We described a new ocular sign represented by HSs of the fundus in NF1. The presence of HSs was not a negative prognostic factor of the disease. Following multimodal imaging, we demonstrated that HSs and choroidal nodules were consistent with the same type of lesion, and simple indirect ophthalmoscopy allowed for screening of HSs in NF1.
HSs were detected in 60 (24.1%) out of 249 patients with NF1, with a positive predictive value of 100% and a negative predictive value of 44.2%. None of the healthy subjects (150 subjects) showed the presence of HSs. HSs were visible under indirect ophthalmoscopy, ultra-wide field (UWF) pseudocolor imaging and red-only laser image, near-infrared reflectance (NIR)-OCT, but they were not appreciable on UWF green reflectance. The location and features of pigmentary lesions matched with the already studied NF1-related choroidal nodules. No significant difference was found between the group of patients (n = 60) with ocular HSs and the group of patients (n = 189) without ocular pigmented spots in terms of age, gender or severity grading of the disease. A statistically significant association was demonstrated between the presence of HSs and neurofibromas (p = 0.047), and between the presence of HSs and NF1-related retinal microvascular abnormalities (p = 0.017).
We described a new ocular sign represented by HSs of the fundus in NF1. The presence of HSs was not a negative prognostic factor of the disease. Following multimodal imaging, we demonstrated that HSs and choroidal nodules were consistent with the same type of lesion, and simple indirect ophthalmoscopy allowed for screening of HSs in NF1.
摘要：
神经纤维瘤病Ⅰ型(NF1),也被称为冯·雷克林豪森病，是一种通过常染色体显性遗传传播的罕见遗传疾病，具有完整的外显率和可变的表现力。它是由17号染色体上编码神经纤维蛋白的NF1基因突变引起的，一种具有抑癌活性的蛋白质，50%是零星的或遗传的。该疾病的特点是广泛的临床表现，主要涉及神经系统，眼睛和皮肤，和发展多种良性和恶性肿瘤的倾向。NF1的眼部诊断标志包括视神经胶质瘤，虹膜Lisch结节,眼眶和眼睑神经纤维瘤，眼睑的咖啡色斑点。脉络膜结节和微血管异常最近被确定为与NF1相关的其他眼部表现。本研究旨在描述与NF-1视觉装置相关的新体征的特征和临床意义，该体征由眼底色素沉着斑（HSs）表示。
249例NF1患者中有60例（24.1％）检测到HSs，阳性预测值为100％，阴性预测值为44.2％。健康受试者(150名受试者)均未显示HSs的存在。间接检眼镜下可以看到HSs,超宽场(UWF)伪彩色成像和纯红色激光图像，近红外反射(NIR)-OCT,但它们在UWF绿色反射率上并不明显。色素性病变的位置和特征与已经研究的NF1相关脉络膜结节相匹配。眼HSs患者组(n=60)与无眼部色素斑患者组(n=189)在年龄方面无显著差异,疾病的性别或严重程度分级。在HSs和神经纤维瘤的存在之间证明了统计学上的显着关联（p=0.047）。在HSs和NF1相关的视网膜微血管异常之间（p=0.017）。
我们描述了NF1中由眼底HS代表的新眼部体征。HSs的存在不是该疾病的负面预后因素。在多模态成像之后，我们证明HSs和脉络膜结节与相同类型的病变一致，和简单的间接检眼镜允许筛查NF1中的HSs。
249例NF1患者中有60例（24.1％）检测到HSs，阳性预测值为100％，阴性预测值为44.2％。健康受试者(150名受试者)均未显示HSs的存在。间接检眼镜下可以看到HSs,超宽场(UWF)伪彩色成像和纯红色激光图像，近红外反射(NIR)-OCT,但它们在UWF绿色反射率上并不明显。色素性病变的位置和特征与已经研究的NF1相关脉络膜结节相匹配。眼HSs患者组(n=60)与无眼部色素斑患者组(n=189)在年龄方面无显著差异,疾病的性别或严重程度分级。在HSs和神经纤维瘤的存在之间证明了统计学上的显着关联（p=0.047）。在HSs和NF1相关的视网膜微血管异常之间（p=0.017）。
我们描述了NF1中由眼底HS代表的新眼部体征。HSs的存在不是该疾病的负面预后因素。在多模态成像之后，我们证明HSs和脉络膜结节与相同类型的病变一致，和简单的间接检眼镜允许筛查NF1中的HSs。
