病例15　45歲女性，主訴左眼反復眼紅、畏光、視力下降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

見圖1-22。See Fig. 1-22.

鑒別診斷

Differential Diagnosis

◎ 單純皰疹病毒性角膜炎（基質型）：單純皰疹病毒(HSV)是雙鏈DNA病毒，單純皰疹病毒性角膜炎(HSK)多數由HSV-1感染引起，少數因HSV-2。復發性HSV感染是由三叉神經節中潛伏HSV被重新激活引起的，尤其是在身體或情緒壓力大的時候。基質型角膜炎是引起視力障礙的一種慢性的、復發性的HSK，可分為基質壞死型及非基質壞死型。壞死型基質炎病灶區角膜上皮通常缺損，角膜基質融解，穿孔風險高，該類型角膜炎病損機制包括病毒直接侵襲及免疫介導損傷。相反，非基質壞死型角膜炎（又稱為免疫性角膜基質炎）病區角膜上皮完整，其病損機制主要是病毒抗原介導的宿主免疫反應。

◎ 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.

◎ 角膜基質炎：角膜基質炎是不累及角膜上皮及內皮的非潰瘍性角膜基質炎癥，主要表現為角膜基質的炎癥和血管化，可導致角膜基質瘢痕及視力損害。角膜基質炎可由感染或免疫介導，最常見的病因是單純皰疹病毒和梅毒感染。其他病因包括萊姆病、結核病、麻風病、布魯氏菌病、鉤端螺旋體病、帶狀皰疹、EB病毒、HIV-1、腮腺炎、麻疹、盤尾絲蟲病、錐蟲病、微孢子蟲病和棘阿米巴感染。該病病理機制本質上被認為是免疫介導性疾病，臨床上還須與Cogan綜合征、結節病、霉菌性和角膜接觸鏡相關性角膜炎進行鑒別。

◎ 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：是由棘阿米巴原蟲感染引起的角膜炎。多數有角膜接觸鏡配戴史或眼外傷史。典型癥狀為持續數周的劇烈眼痛、眼紅和畏光。感染早期出現角膜上皮混濁、假樹枝狀或局部點狀熒光素著染，部分患者可有放射狀角膜神經炎。隨后可見環狀或片狀角膜基質浸潤，常伴角膜上皮缺損及潰瘍。在晚期角膜潰瘍可融解穿孔。確診還須進行角膜刮片染色及共聚焦生物顯微鏡檢查，可見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 .

◎ 原發性或繼發性細菌性或真菌性角膜炎：通常存在上皮缺損。當對眼部感染進行抗病毒治療無效，感染和炎癥的跡象加重，以及出現新的癥狀時，應考慮這些情況。

◎ 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.

病史詢問

Asking History

◎ 詢問眼部癥狀出現及持續時間，是否伴有眼痛、畏光等癥狀。

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

◎ 既往是否有反復發作史，有無其他眼部病史、角膜外傷史及角膜接觸鏡配戴史；是否有局部或全身性類固醇應用史，是否患有免疫缺陷性疾病；是否患有全身性疾病，如梅毒、結核、麻風等。

◎ 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.

檢查

Examination

◎ 視力：感染后視力減退。在視軸上形成的角膜基質瘢痕對視力影響很大。

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

◎ 眼壓：若前房受累，可出現眼壓升高。

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

◎ 裂隙燈檢查：明確角膜浸潤的大小、部位及受累的深度；角膜熒光染色以明確上皮是否完整；檢查是否有葡萄膜炎、視網膜血管炎及視網膜炎。該病可見嚴重的基質浸潤，通常合并角膜潰瘍、基質新生血管形成、瘢痕形成或穿孔。或可見角化沉淀物、前葡萄膜炎或前房積膿。

◎ 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.

◎ 角膜知覺檢查：慢性、復發性病例可有角膜知覺減退或消失。

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

◎ 皮膚及顏面檢查：帶狀皰疹病毒性角膜炎總伴隨著單眼周圍的皮膚皰疹和 / 或皮膚瘢痕，可以延伸到同側的前額、頭皮和鼻尖。皮區分布通常有助于明確診斷。

◎ 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質炎有馬鞍形鼻畸形、哈欽森齒、額突或其他先天性梅毒癥狀。

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

◎ 共聚焦顯微鏡：病灶區角膜上皮細胞腫脹，前彈力層附近可見大量活化朗格漢斯細胞，角膜神經叢密度降低。角膜基質細胞腫脹，基質間大量炎性細胞，可見不規則片狀高反光瘢痕及新生血管。角膜內皮細胞層缺乏特異性改變。

◎ 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.

實驗室檢查

Lab

◎ 角膜及房水病毒PCR檢測：存在假陰性率，尤其對已經接受抗病毒藥物及激素治療的患者。

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

◎ 角膜刮片鏡檢及培養：對于存在上皮缺損者，可進行該檢查，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.

◎ 血液檢測：梅毒螺旋體微量血細胞凝集實驗(MHATP)、結核菌素交叉試驗等有助排除角膜基質炎（必要時）。

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

診斷

Diagnosis

單純皰疹病毒性角膜炎（基質型）。

Herpes simplex keratitis (stromal type).

治療（圖1-23、圖1-24）

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

◎ 急性期治療原則：控制病毒在角膜內復制，減輕炎癥反應引起的角膜損傷。

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

◎ 局部抗病毒藥物：阿昔洛韋(ACV)、更昔洛韋(GCV)滴眼液或眼膏，持續14天或更久。用藥期間注意藥物副作用。聯合糖皮質激素類滴眼液，具有抗炎和抑制角膜免疫反應的作用。嚴重的HSV感染，可聯合口服抗病毒藥物，如阿昔洛韋、伐昔洛韋。口服阿昔洛韋400mg，每天2次，或伐昔洛韋1g，每天1次，持續半年至1年，可減少HSK復發率。

◎ 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.

◎ 藥物難以控制病情發展至角膜潰瘍遷延不愈，可酌情選擇病灶清創術、結膜瓣遮蓋術、羊膜覆蓋術；發展至角膜穿孔或角膜炎癥痊愈后形成角膜瘢痕影響視力者，可選擇角膜移植術。

◎ 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.

患者教育和預后

Patient Education & Prognosis

◎ 該病預后欠佳，易復發，治療周期較長，須在嚴格隨診下規范接受治療。

◎ 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習慣，避免過度勞累和熬夜，勤于鍛煉身體、增強體質，增強機體抵抗力，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.