应用免疫荧光技术对眼瘢痕性类天疱疮的研究

目的 探讨免疫荧光技术对眼瘢痕性类天孢疮（ＯＣＰ）的实验诊断意义。方法 应用直接免疫荧光（ＤＩＦ）检测１６例ＯＣＰ患者的结膜和应用间接免疫荧光（ＨＦ）以鼠食道和正常人结膜为基质检测３４例ＯＣＰ患者的血清。结果 ＤＩＦ证实６例结膜上皮细胞基底膜上有免疫复合物（ＩｇＧ和／或ＩｇＡ）和／或Ｃ３呈线状沉积。以结膜为基质的ＨＦ证实血清中抗基底膜（ＢＭＺ）抗体４例,抗细胞间物质（ＨＳ）抗体１４例,总阳性率为５     

Ocular Cicatricial Pemphigoid: A Review of Clinical Features,Immunopathology, Differential Diagnosis,and Current Management

Ocular cicatricial pemphigoid is a devastating autoimmune blistering disorder mainly affecting the conjunctiva but frequently associated with systemic mucosal findings. This article is an update of the pathogenesis, ocular findings, differential diagnosis, and approaches to treatment.     

瘢痕性天疱疮35例临床分析

目的:探讨瘢痕性天疱疮临床特点,为临床诊治提供帮助。方法:回顾性分析2002-01/2008-01我科诊治的35例瘢痕性天疱疮临床特点。结果:瘢痕性天疱疮平均发病年龄为62.4岁,男女性别比为20∶15,病史平均3.3a,51.43%以口腔黏膜病变首发,31.43%以眼部病变首发,眼睑内翻倒睫/慢性结膜炎和干眼/角膜病变为5/4/2,17.14%以其它黏膜病变首发。经过治疗,71.43%(25/35)患者症状消失或缓解超过3mo,14.29%(5/35)患者症状反复或无明显缓解,14.29%(5/35)患者中途退出治疗。治疗过程中37.14%(13/35)患者出现全身其它异常,其中6例出现肝功能异常,2例终止治疗,肾功能异常2例,1例终止治疗,血液系统异常3例,1例退出治疗,心肌梗塞1例,退出治疗,明显血压升高1例。结论:瘢痕性天疱疮是一种慢性病,多发于老年人,男性稍多于女性,眼组织经常受累,多表现为干眼症、睑球粘连和内翻倒睫。瘢痕性天疱疮治疗复杂,经常需要多学科协作。     

Ocular cicatricial pemphigoid

A series of 17 patients with ocular cicatricial pemphigoid (OCP) is described retrospectively. The importance of early recognition, especially of disease involving the medial canthus and caruncular region, diagnosis by biopsy, and adequate immunosuppressive and surgical therapy, are emphasised.
A detailed grading scheme has been developed and this has enabled the authors to determine the success or failure of the therapy during the active treatment period. A combined ophthalmological and immunological approach to treatment can result in a successful visual outcome of this potentially blinding disease.     

Long term results of systemic chemotherapy for ocular cicatricial pemphigoid

Ocular cicatricial pemphigoid (OCP) is a chronic, progressive, blinding, autoimmune disease that scars mucous membranes. We studied the long-term outcome in 104 consecutive patients (average follow-up: 4 years) to determine whether complete remission could be achieved following a course of treatment with immunosuppressive drugs. We found that prolonged periods of remission off therapy are maintained in about one third of OCP patients. Follow-up must be continued for life as relapse occurs in approximately one third of cases. Those who relapsed regained disease control readily upon reinstitution of therapy and did not deteriorate to more advanced cicatrization. Sex, age, initial degree of inflammation and the incidence of extraocular involvement did not bear a prognostic significance. The mechanism which underlies the differing responses to therapy is not yet known.Abbreviations BMZ basement membrane zone - CP cicatricial pemphigoid - OCP ocular cicatricial pemphigoid - OD right eye - OS left eye     

Immunosuppressive Therapy for External Ocular Inflammatory Disease

Fourteen patients with progressive ocular inflammation and destructive lesions, unresponsive to conventional therapy, were treated with systemic immunosuppression. Ten patients had connective tissuelvasculitis diseases; two, cicatricial pemphigoid; and two, bilateral Mooren's corneal ulcers. Control of underlying systemic disease by immunosuppression resulted invariably in concomitant control of ocular inflammation and destruction. Encouraging results were obtained in the patients with cicatricial pemphigoid and those with bilateral Mooren's ulcers.     

眼瘢痕性类天疱疮机制及治疗研究进展

眼瘢痕性类天疱疮(ocular cicatricial pemphigoid,OCP)是黏膜类天疱疮(mucous membrane pemphigoid,MMP)在眼部的一种特殊表现形式,目前发病机制尚不明确,可由抗原抗体反应、炎细胞浸润、细胞因子作用、钙离子水平升高、易感基因等多种因素导致。病变早期表现为慢性进行性的结膜纤维化性炎症,晚期可见角膜混浊及新生血管形成,最终导致视力严重丧失。因此,及时对OCP患者进行规范的临床治疗尤为重要。例如氨苯砜、免疫球蛋白(intravenous immunoglobulin,IVIG)、利妥昔单抗(rituximab,RTX)、肿瘤坏死因子拮抗剂、肾上腺皮质激素类药物,可以有效控制炎症反应、延缓疾病进展。手术治疗可在OCP患者并发严重倒睫、角膜病变及白内障时酌情考虑。     

Immunosuppressive Therapy for Progressive Ocular Cicatncial Pemphigoid

In a controlled, nonrandomized, longitudinal cohort study, we studied the efficacy of systemic immunosuppression in treatment of progressive cicatricial pemphigoid affecting the eyes. Twenty-six patients were studied; 18 received systemic immunosuppressive drugs, and eight received conventional therapy. Three patients who received cytotoxic agents withdrew from the study with intolerable gastrointestinal distress. Fourteen of the 15 patients who were immunosuppressed successfully for prolonged periods experienced a cessation of their episodic ocular inflammation and a halting of their progressive conjunctival cicatrization. They maintained vision at least as good as that present when disease activity was brought under control; in two patients vision improved. The one patient who was adequately immunosuppressed and successfully maintained in such a state for two years but who had progressive ocular surface pathology with eventual blindness had concomitant rheumatoid arthritis and severe sicca syndrome. The three patients who withdrew from immunosuppressive therapy and the eight concomitant controls all showed continued episodic conjunctiva) inflammation and conjunctiva) cicatrization with development of severe keratopathy and profound visual loss. Complications in this series included alopecia (100%), anemia (78%), gastrointestinal distress (22%), hemorrhagic cystitis (11.1%), and severe leukopenia (5.5%). These results support the notion that abnormal immunoregulatory mechanisms are involved in the progressive disease activity in cicatricial pemphigoid and that systemic immunosuppression may have an appropriate role in the treatment of this disease.     

Ocular Cicatricial Pemphigoid

The characteristic feature of ocular cicatricial pemphigoid (OCP) is progressive shrinkage of the conjunctiva. In our series of 78 patients with OCP, 21% had cutaneous involvement and 50% had involvement of the oral mucosa. Immunoglobulins and the third component of complement are found bound to the conjunctival epithelium and basement membrane of patients with OCP. Circulating antibodies which bind to the conjunctival and corneal epithelium but not to the conjunctival basement membrane have also been demonstrated. OCP is associated with an increased prevalence of HLA-B12. The lids and conjunctiva of patients with OCP demonstrate an increased incidence of potential pathogens when compared with age- and sex-matched controls. When followed for a period averaging 22 months, the majority of patients not treated with systemic immunosuppressives or topical corticosteroids progress. However, OCP has a variable course because there were patients in all stages who did not progress. The acute manifestations of OCP may cause rapid shrinkage of the conjunctiva and may be suppressed with systemic corticosteroids.     

眼瘢痕性类天疱疮的治疗策略

眼瘢痕性类天疱疮（ OCP）是一种罕见的累及眼结膜的自身免疫病,常由于其早期的非特异性临床表现导致误诊或延误治疗,最终造成眼表结构功能损害及失明。 OCP治疗主要通过全身免疫抑制控制炎症反应及瘢痕进展,经过多年的临床探索及众多新药问世,目前治疗期前景乐观。现全身免疫抑制治疗主要包括传统免疫抑制治疗（CIST）及新型免疫抑制治疗。 CIST现主要为治疗OCP的一线用药,但由于其副作用较多、对顽固性OCP疗效不佳而有一定缺陷;新型免疫抑制药物如IVIg、抗TNF-α药及单克隆抗体等,凭借强力的免疫抑制作用及较少副反应逐渐受到重视,在今后可能可作为一线用药的更优选择。中晚期OCP患者因并发眼表畸形及角膜浑浊等严重影响生活质量,在全身炎症情况控制稳定的前提下可行手术治疗。局部治疗主要针对不同的眼表并发症行相应处理,以改善局部症状。经过科学合理的药物及手术治疗,大部分OCP患者预后良好,但仍有少量反复发作者需进一步研究,寻找最为合适的治疗策略。     

Eosinophil granule proteins expressed in ocular cicatricial pemphigoid

BACKGROUND—Blister formation and tissue damage in bullous pemphigoid have been attributed to the release of eosinophil granule proteins—namely, to eosinophil derived cationic protein (ECP) and major basic protein (MBP). In the present investigation these eosinophil granule proteins were studied in the conjunctiva of patients with ocular cicatricial pemphigoid (OCP).
METHODS—Conjunctival biopsy specimens obtained from patients with subacute (n=8) or chronic conjunctival disease (n=13) were analysed histologically and immunohistochemically using antibodies directed against EG1 (stored and secreted ECP), EG2 (secreted ECP), MBP, CD45 (common leucocyte antigen), CD3 (pan T cell marker), and HLA-DR (class II antigen).
RESULTS—Subepithelial mononuclear cells, mast cells, and neutrophils were detected in all specimens. The number of mononuclear cells, neutrophils, CD45+ cells, CD3+ cells, and the HLA-DR expression were significantly higher in the subacute than in the chronic disease group. Some eosinophils were found in specimens from five of eight patients with subacute OCP, but in none of the patients with chronic disease. The eosinophil granule proteins (ECP and MBP) were found in the epithelium and substantia propria in patients with subacute conjunctivitis.
CONCLUSIONS—Subepithelial cell infiltration in the conjunctiva greatly differs between subacute and chronic ocular cicatricial pemphigoid specimens. The findings suggest that eosinophil granule proteins may participate in tissue damage in acute phase of inflammation in OCP.

     

Cicatricial entropion and trichiasis in an urban Australian population

BACKGROUND: Cicatricial entropion and trichiasis may be caused by a variety of diseases, of which trachomatous entropion is the commonest worldwide. The spectrum of disease in the authors' community is quite different. The purpose of this study was to establish the aetiology of entropion and trichiasis in patients referred to a Melbourne-based subspecialty oculoplastics practice, excluding epiblepharon, congenital entropion and involutional entropion, and to compare the final diagnosis with the referring diagnosis. METHODS: All records of patients with cicatricial entropion and trichiasis presenting to the practice of one of the authors over the period 1990-2000 were analysed. Demographic data, referring diagnosis and final diagnosis were tabulated. RESULTS: The commonest final diagnosis was ocular cicatricial pemphigoid. In only a small proportion of cases was this diagnosis considered by the referring practitioners. In addition, two cases of undiagnosed conjunctival neoplasia presented with entropion and trichiasis. CONCLUSION: In all patients with entropion and trichiasis, a careful history and examination should be obtained and appropriate investigations performed to try and establish a firm diagnosis.     

甲氨蝶呤治疗眼瘢痕性类天疱疮的疗效

目的：探讨应用甲氨蝶呤（MTX）治疗眼瘢痕性类天疱疮（OCP）的效果及安全性。方法：回顾性系列病例研究。收集2016年9月至2019年8月于天津医科大学总医院眼科行MTX治疗的OCP患者5例（10眼），其中男2例，女3例。观察MTX治疗6个月、12个月OCP炎症的进展及药物不良反应。结果：本组患者OCP平均发病年龄51.8岁（38～66岁），开始免疫治疗年龄54.4岁（39～68岁）。MTX治疗6个月，OCP好转3例，OCP部分活跃1例，OCP活跃1例。MTX治疗12个月，OCP好转4例，OCP活跃1例。活跃患者OCP睑球粘连进展，在MTX治疗12个月后加用利妥昔单抗联合治疗。治疗过程中，1人（1眼）在MTX治疗10个月时发生角膜病毒感染。另有2例应用MTX后出现轻度胃肠道反应，1例转氨酶轻度升高。随访期间无其他严重不良反应出现。结论：对于OCP患者，MTX耐受良好，早期应用有助于控制眼部病情。     

Methotrexate in the Treatment of Ocular Cicatricial Pemphigoid

Objective: To evaluate the effectiveness and safety of methotrexate (MTX) for the treatment of patients with ocular cicatricial pemphigoid (OCP). Methods: This was a retrospective case series study. A review of patient records with OCP who received treatment with MTX in the Department of Ophthalmology of Tianjin Medical University General Hospital from September 2016 to August 2019 were analyzed. Five patients were involved, 2 males and 3 females. OCP inflammation and progression and the adverse reaction of MTX were evaluated. Results: Mean age at the onset of OCP was 51.8 years (range, 38-66 years). Mean age at the initiation of immunotherapy was 54.4 years (range, 39-68 years). Six eyes in 3 patients achieved quiescence, 2 eyes in 1 patient presented with partial activity, and 2 eyes in 1 patient presented with disease activity after being treated by MTX for 6 months. At 12 months of MTX treatment, 8 eyes in 4 patients achieved quiescence, and 2 eyes in 1 patient presented with disease activity and continuous progression over stage one of OCP. This patient received rituximab in combination with MTX at 12 months after MTX initiation. Adverse events included gastrointestinal reaction in 2 patients, mild liver enzyme elevation in 1 patient, and virus infection of the cornea of 1 eye in 1 patient after being treated with MTX for 10 months. No other severe adverse events were noted during the follow-up period. Conclusions: These retrospective data suggest that MTX is efficacious and well tolerated when included early in the treatment of OCP.     

Incidence, prevalence, and demographic characteristics of ocular cicatricial pemphigoid in Colombia: data from the National Health Registry 2009-2019

AIM: To provide an epidemiological characterization of ocular cicatricial pemphigoid (OCP) in Colombia. METHODS: We conducted a cross-sectional study using SISPRO. We applied the specific code of the International Classification of Diseases for Ocular Pemphigoid, from 2009-2019 to estimate prevalence, incidence, and the demographic status of the disease in Colombia. RESULTS: The estimated average prevalence was 0.22 per 1 000 000 inhabitants, and the estimated average incidence was 0.24 per 1 000 000 inhabitants. With a female predominance of 62.5%, and a male/female ratio of 1:1.6. The group of patients diagnosed with the disease after the age of 80 presented the highest prevalence. The departments with the highest prevalence were Antioquia, Bogotá, and Santander. CONCLUSION: There are important differences between worldwide and Colombian prevalence and incidence data, which may be related to genetic and epigenetic factors, and the possible underdiagnosis of the disease. According to the results, OCP is an extremely rare disease in Colombia. Nevertheless, it is important to encourage awareness of the disease due to its devastating consequences.     

Ocular surface impressions using cellulose acetate filter material. Ocular pemphigoid

A technique for obtaining ocular surface impressions using cellulose acetate filter material is described. A representative ocular surface impression obtained by this technique from a patient with cicatricial ocular pemphigoid is shown, and contrasted to a normal ocular surface impression.     

Outcomes of Cataract Surgery in Ocular Cicatricial Pemphigoid

Abstract

Purpose: To report the outcomes of cataract surgery in ocular cicatricial pemphigoid (OCP). Setting: L. V. Prasad Eye Institute, Hyderabad, India. Design: Retrospective, interventional case series.

Methods: Patients diagnosed with OCP who had undergone cataract surgery were included. Staging of disease, type of surgery, pre- and postoperative best-corrected visual acuity (BCVA), and number and duration of topical and systemic medications were recorded. Complications and any exacerbation or worsening of disease were noted.

Results: Nine eyes of 7 patients (3 male, 4 female) were included in the study, with mean age of 60.44?±?2.6 years (range 56–64 years). Follow-up ranged from 6 months to 10 years (mean 52.9?±?46.25 months). Surgery performed was extracapsular cataract extraction with posterior chamber intraocular lens implantation (n?=?5) or phacoemulsification with posterior chamber intraocular lens implantation (n?=?4). Best-corrected visual acuity improved by more than 2 lines in 6 of 9 (66.67%) eyes, which remained stable till the last follow-up. Three eyes had no visual improvement due to corneal scar in 2 patients and preexisting posterior staphyloma in 1 eye. Disease progression was noted in 2 of 9 operated eyes by one stage at the end of 1 year.

Conclusion: In this series, cataract surgery could be safely performed with no major intra- or postoperative complications. While the surgical intervention itself was not associated with acute exacerbations of inflammation, progression of disease was noted in some cases over time. In spite of ongoing disease, cataract surgery in OCP was associated with stable visual outcomes.     

Cicatricial entropion repair with hard palate mucous membrane graft: surgical technique and outcomes

Background:  The use of a hard palate mucous membrane graft (HPMMG) has been previously described for upper and lower eyelid cicatricial entropion repair. The objective of this paper is to review the surgical technique and postoperative complications in a large series of patient who underwent hard palate grafting for the management of cicatricial entropion.
Methods:  The medical records of 107 patients representing 147 eyelids undergoing surgical management of cicatricial entropion with HPMMG were reviewed. The surgical technique is described.
Results:  147 eyelid operations (74 upper, 73 lower) were performed on 107 patients (46 male, 61 female), with a mean age of 63 years (range 12–87). The aetiology of the cicatricial entropion included idiopathic (41%), trauma (5.6%), chronic blepharitis (16.8%), chemical injury (3.7%), ocular cicatricial pemphigoid (8.4%), trachoma (7.5%) and other (16.8%). Patients were followed postoperatively for an average of 21 months (range 6–120). Ninety-four per cent of patients noted symptomatic improvement. The postoperative complications included excess keratin (29%), recurrence of cicatricial entropion (4.1%), punctuate epithelial erosion (2.7%), graft shrinkage (0.7%) and donor site bleeding (2.0%).
Conclusions:  Cicatricial Entropion with hard palate mucous membrane grafting for both upper and lower eyelid surgery offers high symptomatic and anatomical cure rates. The requirement for further surgical intervention is low.     

Cicatricial Pemphigoid and Dry Eye

Cicatricial pemphigoid is the most common of the immunobullous disorders causing conjunctival cicatrization and is an autoimmune disease in which the ocular component of the immunopathology is directed at the conjunctival basement membrane. The disease is usually bilateral and more common in females, with most cases occurring between 30–90 years, and most often in the seventh decade. The disease occasionally occurs in children. Tear deficiency is a major cause of symptoms, although loss of vision is usually due to surface failure before the onset of aqueous tear deficiency, which occurs late in the progression of the disease. Management of the dry eye must be integrated with the management of the other components of both the ocular surface disease and inflammation. Management requires plastic surgery for the lid and lash malposition, tetracyclines and lid hygiene for the accompanying blepharitis. For the dry eye, the use of lubricants without preservatives is important, to avoid toxicity, and lubricant ointment is helpful for the relief of symptoms in terminally dry eyes without the capacity for surface wetting. Contact lenses, either large limbal diameter rigid gas permeable or gas permeable scleral lenses, are useful for treating dry eye and improving vision in some patients. Control of the conjunctival inflammation is mandatory to prevent disease progression and usually requires systemic immunosuppressive therapy.     

Conjunctival mucoepidermoid carcinoma in a patient with ocular cicatricial pemphigoid and a review of the literature

Invasive mucoepidermoid carcinoma of the conjunctiva of the left lower eyelid was diagnosed in an orbital exenteration specimen of a 57-year-old woman, after a biopsy of the same lesion was originally diagnosed as invasive squamous cell carcinoma. The woman was undergoing mitomycin C injections for ocular cicatricial pemphigoid, diagnosed in the same eye 2 years prior to identification of the neoplasm. The tumor invaded the cornea, sclera, lacrimal gland, regional small nerves, and lymphatics, but did not show intraocular involvement. The original biopsy specimen was reassessed with stains for mucin and found to be mucoepidermoid carcinoma of the conjunctiva. We reviewed 21 cases of mucoepidermoid carcinoma of the conjunctiva described to date in the English literature. We believe this number underestimates the true incidence of this condition, as it is frequently misdiagnosed both clinically and histopathologically. Evaluating suspected aggressive squamous cell carcinoma with special stains for mucin generally helps to identify mucoepidermoid carcinoma of the conjunctiva. More extensive surgical excision than that used for squamous cell carcinoma should be implemented in the management of mucoepidermoid carcinoma of the conjunctiva to prevent recurrence.