病例15　45岁女性，主诉左眼反复眼红、畏光、视力下降2年

CASE 15　A 45-year-old female complaining of multiple episodes of redness, photophobia, and vision loss in left eye for 2 years

见图1-22。See Fig. 1-22.

鉴别诊断

Differential Diagnosis

◎ 单纯疱疹病毒性角膜炎（基质型）：单纯疱疹病毒(HSV)是双链DNA病毒，单纯疱疹病毒性角膜炎(HSK)多数由HSV-1感染引起，少数因HSV-2。复发性HSV感染是由三叉神经节中潜伏HSV被重新激活引起的，尤其是在身体或情绪压力大的时候。基质型角膜炎是引起视力障碍的一种慢性的、复发性的HSK，可分为基质坏死型及非基质坏死型。坏死型基质炎病灶区角膜上皮通常缺损，角膜基质融解，穿孔风险高，该类型角膜炎病损机制包括病毒直接侵袭及免疫介导损伤。相反，非基质坏死型角膜炎（又称为免疫性角膜基质炎）病区角膜上皮完整，其病损机制主要是病毒抗原介导的宿主免疫反应。

◎ Herpes simplex keratitis (stromal type): HSV is a double-stranded DNA virus. HSV-1 infection is the most common cause of HSK, while HSV-2 infection is less. Recurrent HSV is caused by a reactivation of latent infection in the trigeminal ganglion, especially during periods of physical or emotional stress. Stromal keratitis is a chronic and recurrent disease to cause vision loss. HSK can be classif ied as either necrotizing or non-necrotizing.In necrotizing HSK, an overlying epithelial defect is often present, and the risk of stromal melting and perforation is high. Both viral and immune-mediated destruction of the cornea is implicated in necrotizing HSK. Conversely, in non-necrotizing HSK, also known as immune or interstitial HSK, the epithelium is intact, and the pathology is thought to driven primarily by the host immune response.

◎ 角膜基质炎：角膜基质炎是不累及角膜上皮及内皮的非溃疡性角膜基质炎症，主要表现为角膜基质的炎症和血管化，可导致角膜基质瘢痕及视力损害。角膜基质炎可由感染或免疫介导，最常见的病因是单纯疱疹病毒和梅毒感染。其他病因包括莱姆病、结核病、麻风病、布鲁氏菌病、钩端螺旋体病、带状疱疹、EB病毒、HIV-1、腮腺炎、麻疹、盘尾丝虫病、锥虫病、微孢子虫病和棘阿米巴感染。该病病理机制本质上被认为是免疫介导性疾病，临床上还须与Cogan综合征、结节病、霉菌性和角膜接触镜相关性角膜炎进行鉴别。

◎ Interstitial keratitis: Interstitial keratitis is any nonulcerating inf lammation of the corneal stroma without the involvement of either the epithelium or endothelium. It primarily manifest as inf lammation and vascularization of the corneal stroma, which can result in scarring of this layer and cause vision lost. The underlying causes of interstitial keratitis can broadly be either infectious or immune-mediated. The most common etiologies of interstitial keratitis are herpes simplex virus and syphilis.Other include Lyme disease, tuberculosis, leprosy,Brucellosis, leptospirosis, herpes zoster, Epstein-Barr virus,HIV-1, mumps, measles, onchocerciasis, trypanosomiasis,microsporidiosis and acanthamoeba. Finally, the diseases thought to be immune-mediated in nature including Cogan’s syndrome, sarcoidosis, mycosis fungoides, and contact lens-associated keratitis are in the differential diagnosis.

◎ 棘阿米巴性角膜炎：是由棘阿米巴原虫感染引起的角膜炎。多数有角膜接触镜配戴史或眼外伤史。典型症状为持续数周的剧烈眼痛、眼红和畏光。感染早期出现角膜上皮混浊、假树枝状或局部点状荧光素着染，部分患者可有放射状角膜神经炎。随后可见环状或片状角膜基质浸润，常伴角膜上皮缺损及溃疡。在晚期角膜溃疡可融解穿孔。确诊还须进行角膜刮片染色及共聚焦生物显微镜检查，可见典型的棘阿米巴包囊。

◎ Acanthamoeba keratitis: This kind of keratitis is caused by acanthamoeba infection. Most of patients have a history of wearing contact lenses without stander solution or with ocular trauma. Typical symptoms are severe eye pain,redness and photophobia over several weeks. The signs of early stage include corneal haze, pseudodendrites or spots on the epithelium and can be stained with f luorescein, some patients may have radial keratoneuritis. Subsequently,ring-shaped or lamellar corneal stroma inf iltration appear,accompanying with corneal epithelial defect or ulcer. In the late stage, corneal ulcer will develop to stromal melting and even perforation. For def initive diagnosis, corneal scraping staining with typical acanthamoeba cysts can be found by confocal microscope .

◎ 原发性或继发性细菌性或真菌性角膜炎：通常存在上皮缺损。当对眼部感染进行抗病毒治疗无效，感染和炎症的迹象加重，以及出现新的症状时，应考虑这些情况。

◎ Primary or secondary bacterial or fungal keratitis: There is generally an overlying epithelial defect. These conditions should be considered when there is lack of response to antiviral treatment, and when there are increased or new signs of infection and inf lammation.

病史询问

Asking History

◎ 询问眼部症状出现及持续时间，是否伴有眼痛、畏光等症状。

◎ Asking the onset and progression of ocular symptoms, such as ocular pain, photophobia, etc.

◎ 既往是否有反复发作史，有无其他眼部病史、角膜外伤史及角膜接触镜配戴史；是否有局部或全身性类固醇应用史，是否患有免疫缺陷性疾病；是否患有全身性疾病，如梅毒、结核、麻风等。

◎ How many episodes previously, other eye diseases, corneal trauma or wearing contact lenses. Immune def iciency diseases, or treatment by local or systemic steroid. Systemic diseases, such as syphilis, tuberculosis, leprosy, etc.

检查

Examination

◎ 视力：感染后视力减退。在视轴上形成的角膜基质瘢痕对视力影响很大。

◎ Visual acuity：Vision decreases during infection, and stromal scaring can severely affect vision if in the visual axis.

◎ 眼压：若前房受累，可出现眼压升高。

◎ IOP: Intraocular pressure maybe elevate if anterior chamber reaction involved in.

◎ 裂隙灯检查：明确角膜浸润的大小、部位及受累的深度；角膜荧光染色以明确上皮是否完整；检查是否有葡萄膜炎、视网膜血管炎及视网膜炎。该病可见严重的基质浸润，通常合并角膜溃疡、基质新生血管形成、瘢痕形成或穿孔。或可见角化沉淀物、前葡萄膜炎或前房积脓。

◎ Slit lamp examination: To detect the size, location and which cornea layer with inf iltration. Fluorescence staining is to detect epithelium defect. Check if there is uveitis,retinal vasculitis and retinitis. Severe stromal inf iltration can be seen in this disease, usually combined with corneal ulceration, stromal neovascularization, scarring, or perforation may develop. There may be associated keratic precipitates, anterior uveitis, or hypopyon.

◎ 角膜知觉检查：慢性、复发性病例可有角膜知觉减退或消失。

◎ Corneal sensation: Weaken or disappear in chronic and recurrent cases.

◎ 皮肤及颜面检查：带状疱疹病毒性角膜炎总伴随着单眼周围的皮肤疱疹和 / 或皮肤瘢痕，可以延伸到同侧的前额、头皮和鼻尖。皮区分布通常有助于明确诊断。

◎ Skin and face inspection: Herpes zoster keratitis always accompany with skin herpes and/or skin scars around the unilateral eye, which can extend to the ipsilateral forehead,scalp and tip of nose. The dermatomal distribution usually helps clarify the diagnosis.

◎ 先天性梅毒引起的角膜基质炎有马鞍形鼻畸形、哈钦森齿、额突或其他先天性梅毒症状。

◎ Interstitial keratitis caused by congenital syphilis has the signs of saddle nose deformity, hutchinson tooth,frontal process or other congenital syphilis symptoms.

◎ 共聚焦显微镜：病灶区角膜上皮细胞肿胀，前弹力层附近可见大量活化朗格汉斯细胞，角膜神经丛密度降低。角膜基质细胞肿胀，基质间大量炎性细胞，可见不规则片状高反光瘢痕及新生血管。角膜内皮细胞层缺乏特异性改变。

◎ Confocal microscope: Corneal epithelial cells become swollen and bigger. A large number of activated Langerhans cells and less density of corneal nerve appear subepithelially. A large number of inf lammatory cells can be found among swollen stromal cells, and irregular hyperref lective structures and vessels are found. There is no characteristic changes in endothelial layer.

实验室检查

Lab

◎ 角膜及房水病毒PCR检测：存在假阴性率，尤其对已经接受抗病毒药物及激素治疗的患者。

◎ PCR detection of corneal and aqueous viruses: False negative rate exists, especially for patients who have received antiviral drugs and steroids therapy.

◎ 角膜刮片镜检及培养：对于存在上皮缺损者，可进行该检查，有助于排除其他感染性角膜炎。

◎ Corneal scraping for microscopy and culture (if epithelial defect exists): To exclude other infectious keratitis.

◎ 血液检测：梅毒螺旋体微量血细胞凝集实验(MHATP)、结核菌素交叉试验等有助排除角膜基质炎（必要时）。

◎ Micro hemagglutination-treponema pallidum (MHATP), tuberculin tine test, etc., to exclude interstitial keratitis(if need).

诊断

Diagnosis

单纯疱疹病毒性角膜炎（基质型）。

Herpes simplex keratitis (stromal type).

治疗（图1-23、图1-24）

Management (Figs. 1-23 and 1-24)

◎ 急性期治疗原则：控制病毒在角膜内复制，减轻炎症反应引起的角膜损伤。

◎ Principles of treatment of acute phase: Control virus replication in cornea, reduce corneal injury caused by inf lammatory reaction.

◎ 局部抗病毒药物：阿昔洛韦(ACV)、更昔洛韦(GCV)滴眼液或眼膏，持续14天或更久。用药期间注意药物副作用。联合糖皮质激素类滴眼液，具有抗炎和抑制角膜免疫反应的作用。严重的HSV感染，可联合口服抗病毒药物，如阿昔洛韦、伐昔洛韦。口服阿昔洛韦400mg，每天2次，或伐昔洛韦1g，每天1次，持续半年至1年，可减少HSK复发率。

◎ Topical antivirals: Acyclovir (ACV), ganciclovir (GCV)eye drops or ointments for 14 days or longer, monitor the side effect. Combined with steroids to suppress inf lammation and immune response in cornea. Severe HSK can be combined with oral antivirals such as acyclovir and valaciclovir. Oral acyclovir 400 mg twice a day or ganciclovir 1g one time a day for half to one year can reduce the recurrence rate of HSK.

◎ 药物难以控制病情发展至角膜溃疡迁延不愈，可酌情选择病灶清创术、结膜瓣遮盖术、羊膜覆盖术；发展至角膜穿孔或角膜炎症痊愈后形成角膜瘢痕影响视力者，可选择角膜移植术。

◎ If HSK progress aggressively, debridement of the lesions, conjunctival f lap or amniotic membrane graft can be considered for severe corneal ulcer and corneal transplantation for corneal perforation. Corneal transplantation may eventually be necessary if scars on cornea signif icantly affect vision.

患者教育和预后

Patient Education & Prognosis

◎ 该病预后欠佳，易复发，治疗周期较长，须在严格随诊下规范接受治疗。

◎ The prognosis of HSK is poor. HSK tend to recur, and has a long treatment cycle, then requires standardized treatment under strict follow-up.

◎ 改善不良生活及用眼习惯，避免过度劳累和熬夜，勤于锻炼身体、增强体质，增强机体抵抗力，提高自身免疫力。

◎ Improve living and eye using habits, avoid overwork and staying up too late, proper physical exercise can enhance the body immunity.