病例14 40岁女性，发现双眼有白色沉着物1年
CASE 14 A 40-year-old female complaining of white spots in both eyes for 1 year
见图1-21。See Fig. 1-21.
图1-21 角膜前基质中央区可见颗粒状、星状混浊，混浊可呈指状排列，混浊间的角膜透明Fig. 1-21 Some granules and stellate elements located in the center of the anterior corneal stroma and often in f inger-like arrangement. There is clear space between lesions
鉴别诊断
Differential Diagnosis
◎ 颗粒状角膜营养不良：是一种常染色体显性遗传性疾病。1型角膜基质可见多量细小的面包屑样混浊，呈雪花样；2型角膜基质可见星状、环状、颗粒状、线状混浊，有些患者角膜混浊可呈指状排列。
◎ Granular corneal dystrophy (GCD): This is an autosomal dominant disease. GCD1: “snowfall appearance” of multiple small crumb-like granules. GCD2: superf icial stars, rings,granules, and lines opacities in some cases in f inger-like appearance.
◎ 斑块状角膜营养不良：常染色体隐性遗传，弥散性的全角膜基质混浊。多量、不规则的灰白色结节样病变可见于混浊区。
◎ Macular corneal dystrophy: This autosomal recessive disorder is characterized by a diffuse stromal haze extending limbus to limbus and throughout the corneal stroma.Multiple, irregular, gray-white, nodular lesions are found within the diffuse haze.
◎ 格子样角膜营养不良：1型，常染色体显性遗传，突变位点5q31染色体上TGFBI基因，主要表现为角膜玻璃丝样透明病变，通常不累及角膜缘。2型，常染色体显性遗传，9q34染色体凝胶蛋白基因突变。丝状病变主要位于周边部，密度比1型低。大部分病变位于前基质。
◎ Lattice corneal dystrophy: Type 1 corneal dystrophy,autosomal dominant inheritance of the TGFBI gene on the 5q31 locus, most typically marked by ‘glass-like’f ilamentous lesions. Typically, the limbus is not involved.Type 2 corneal dystrophy, autosomal dominant inheritance of the gelsolin gene on 9q34. Filamentous lesions are present but they are more peripheral and less dense than in Type 1. Most lesions are in the anterior stroma.
◎ Reis-Bücklers角膜营养不良：是一种原因不明、罕见的角膜上皮基底膜营养不良，表现为双眼角膜混浊，主要为上皮下和浅基质层角膜混浊，地图样混浊是该病的特点。最早可于1岁发病，4~5岁进展。为常染色体显性遗传性疾病，突变基因TGFBI。
◎ Reis-Bücklers corneal dystrophy: This is a rare corneal dystrophy of unknown cause, in which the Bowman’s layer of the cornea undergoes disintegration to produce a cloudiness in the corneas of both eyes. This disorder is characterized by subepithelial and superf icial stromal changes extending almost to the limbus. The geographiclike opacities are to be regarded as a landmark. The disorder is inherited in an autosomal dominant fashion, which may occur as early as 1 year of age, but usually develops by 4 to 5 years of age. And it is associated with mutations in the gene TGFBI.
◎ 施耐德角膜营养不良：是一种罕见的遗传性角膜疾病，突变基因UBIAD1，表现为双眼角膜中央区结晶样混浊，周边角膜脂质环。主要由于胆固醇和脂质在角膜基质内沉积引起角膜混浊，严重患者需要行角膜移植手术。
◎ Schnyder corneal dystrophy (SCD)：This is a rare form of corneal dystrophy caused by mutations in UBIAD1 gene.Stromal dystrophy characterized by progressive bilateral corneal opacif ication，with corneal crystal, midperipheral haze and arus lipoides. Cells in the cornea accumulate cholesterol and phospholipid deposits leading to the opacity,in severe cases requiring corneal transplants.
病史询问
Asking History
◎ 起病时间：早期可无症状，角膜出现明显混浊后可影响视力。
◎ Onset time and progression: Early stages of the disease may be asymptomatic and the diagnosis may be delayed until the occurrence of a distinct corneal opacity.
◎ 家族史：询问家族史和全身性疾病史。
◎ Asking family history and history of systemic diseases.
眼部检查
Examination
◎ 视力主要受角膜病变影响。角膜出现明显混浊后可影响视力。
◎ Visual acuity is associated with characteristic corneal opacities that decrease with age.
◎ 裂隙灯检查：GCD1型角膜基质可见多量细小的面包屑样混浊，呈雪花样；GCD2型角膜基质可见星状、环状、颗粒状、线状混浊，有些患者角膜混浊可呈指状排列。
◎ Slit-lamp examination: GCD1: “snowfall appearance” of multiple small crumb-like granules. GCD2: superf icial stars,rings, granules, and lines opacities in some cases in f ingerlike appearance.
实验室检查
Lab
◎ 角膜组织病理学检查：GCD1型，角膜基质可见透明样变性；GCD2型，可见角膜基质透明样变性和淀粉样沉积。◎ 基因检查：GCD1型，5q31染色体TGFBI基因（Arg555Trp突变）；GCD2型，5q31染色体TGFBI基因（Arg124His突变）。
◎ Histopathology of the cornea: Hyaline deposits are the typical histopathological feature of GCD1. The histopathology of GCD2 patients demonstrates hyaline and amyloid deposits.
◎ Genetic testing: GCD1, TGFBI gene (Arg555Trp mutation) on chromosome 5q31. GCD2, TGFBI gene(Arg124His mutation) on chromosome 5q31.
诊断
Diagnosis
颗粒状角膜营养不良。
Granular corneal dystrophy.
治疗
Management
◎ 大多数不需要治疗。
◎ Most patients do not need treatment.
◎ 可行准分子激光治疗性角膜切削术提高患者视力。对于进展期患者，可行板层角膜移植术或者穿透性角膜移植术。
◎ To increase vision, phototherapeutic keratectomy can be performed. Lamellar keratoplasty or penetrating keratoplasty can be performed in advanced stage.
患者教育和预后
Patient Education & Prognosis
◎ 该病为常染色体显性遗传性疾病，进展缓慢，早期通常不影响视力，晚期影响视力可行角膜移植，术后病变复发率较低。
◎ GCD is an autosomal dominant disease and slowly progressive disease. Vision minimally worsens with age.Keratoplasty can be performed in advanced stage. The rate of recurrence of GCD is low.