Autoimmune phenomena of the external eye.

The immunologic status of patients with ocular pemphigoid, Mooren's ulcer, chronic herpetic keratitis, and staphylococcal peripheral corneal ulcers was studied. Although tissue-fixed and circulating antibodies to the conjunctival epithelium were found in all groups, patients with Mooren's ulcer demonstrated these findings most consistently. Immunoglobulins bound to the conjunctival basement membrane were found not only in ocular pemphigoid but also in patients with Mooren's and staphylococcal ulcers. Approximately one half of the patients with ocular pemphigoid and Mooren's ulcer demonstrated elevations in serum IgA levels. An increased prevalence of HLA-B12 was found in ocular pemphigoid.     

A case of suspected drug-induced ocular pemphigoid

BACKGROUND: Lacrimal obstruction can occur as a complication of ocular cicatricial pemphigoid. We report a patient who was diagnosed as having drug-induced ocular cicatricial pemphigoid associated with acquired lacrimal canalicular obstruction in spite of relatively mild subconjunctival scar formation. CASE: The patient was a 69-year-old woman. She had been treated for glaucoma, blepharoconjunctivitis, dacryocystitis, and lacrimal canalicular obstruction for two years with topical administration including 0.5% timolol maleate, 0.1% dipivefrine hydrocholoride, 0.1% fluorometholone, and 0.3% ofloxacin. The patient had moderate conjunctival hyperemia without shortening of the inferior conjunctival sac, corneal ulceration, neovascularization, and keratinization. Lacrimal canalicular obstruction progressed further as topical ocular medications were continued. Topical anti-glaucoma medications were stopped after dacryocystorhinostomy. Although the blepharoconjunctivitis was improved, left inferior conjunctival symblepharon, and medical canthal keratinization was progressive despite the use of topical corticosteroids. The conjunctival biopsy specimen showed the lacrimal punctum covered with proliferated conjunctival epithelium. There was a moderate stromal infiltration of small lymphocytes and plasma cells. We diagnosed this patient as having drug-induced ocular cicatricial pemphigoid caused by topical anti-glaucoma medications. CONCLUSION: Lacrimal canalicular obstructions may occur with the topical anti-glaucoma medications even when subconjunctival scarring is mild.     

Pure ocular cicatricial pemphigoid: A distinct immunopathologic subset of cicatricial pemphigoid

ObjectiveTo determine whether ocular cicatricial pemphigoid (OCP) may represent a distinct immunopathologic disease when it is pure ocular cicatricial pemphigoid (POCP) (e.g., only confined to the conjunctiva) or when it is associated with skin or extraocular mucous membrane lesions or both (OCP⁺).DesignProspective, immunologic, and immunopathologic study with special emphasis on direct immunoelectron microscopy.ParticipantsSix patients with POCP and seven patients with OCP⁺.InterventionAfter informed consent was obtained, a conjunctival biopsy was performed in all patients. Skin and extraocular mucosa biopsy specimens were harvested in selected cases only.Main outcome measuresResults of direct immunofluorescence and direct immunoelectron microscopy without freezing on conjunctival and skin biopsy specimens, indirect immunofluorescence, and Western immunoblotting analysis were analyzed.ResultsResults of direct immunoelectron microscopic examination of the conjunctiva showed the presence of immune deposits in the upper lamina lucida of the basement membrane zone in the six patients with POCP, whereas the immune reactants were located in the lower part of the lamina lucida and in the lamina densa of the basement membrane zone (conjunctiva, buccal mucosa, and skin) in the seven patients with OCP⁺. Direct immunofluorescence was positive in the biopsy specimens of three patients with POCP (50%) and the seven patients with OCP⁺ (100%). Results of indirect immunofluorescence study showed circulating autoantibody levels only in two patients with OCP⁺, and results of Western immunoblot analysis were negative.ConclusionsResults of direct immunoelectron microscopic examination of the conjunctiva support the hypothesis that POCP may be a disease entity distinct from mucocutaneous cicatricial pemphigoid.     

The acute manifestations of ocular cicatricial pemphigoid: diagnosis and treatment

Seven patients with ocular cicatricial pemphigoid displayed acute inflammatory activity that could not be attributed to secondary bacterial infections, trichiasis, or lagophthalmos secondary to symblepharon. This acute inflammatory activity was manifested either as a localized conjunctival mound that was ulcerated and intensely hyperemic or as diffuse and intense conjunctival hyperemia and chemosis. Acute disease activity developed shortly after conjunctival biopsy in three patients and appeared spontaneously in the other four patients. Conjunctival biopsy specmens disclosed a heavy infiltrate of polymorphonuclear leucocytes within and beneath the conjunctival epithelium in addition to the chronic inflammatory cells typically found in this condition. The acute manifestations of ocular cicatricial pemphigoid cause rapid shrinkage and scarring of the conjunctiva. Systemic corticosteroids suppressed the acute disease activity and prevented additional scarring in all five patients treated.     

Scanning electron microscopy of conjunctival surfaces in patients with ocular cicatricial pemphigoid

The conjunctival surfaces of ten patients with active, ocular cicatricial pemphigoid, three patients with drug-controlled ocular cicatricial pemphigoid, and six patients with normal conjunctivas were studied using scanning electron microscopy. A homogeneous granular sheet of amorphous mucin-like material was observed covering extensive areas of the conjunctiva in eight of ten patients with active ocular cicatricial pemphigoid. This sheet of amorphous material was absent on drug-controlled ocular cicatricial pemphigoid and normal conjunctival specimens. Our study demonstrates that patients with active ocular cicatricial pemphigoid possess ocular surface mucus that appears thicker and more continuous than normal ocular mucus when observed with scanning electron microscopy. This observation is in agreement with clinical observations of thick mucus strands in the inferior fornix of patients with active ocular cicatricial pemphigoid.     

Exacerbation of undiagnosed ocular cicatricial pemphigoid after repair of involutional entropion

We report a case of exacerbation of undiagnosed ocular cicatricial pemphigoid after repair of involutional entropion. A lateral tarsal strip was performed to address entropion in the setting of eyelid laxity. No evidence of ocular cicatricial pemphigoid was observed before surgery. Postoperatively the patient developed intense conjunctival inflammation and diffuse symblepharon formation. Conjunctival biopsy demonstrated immunoglobulin and complement deposition at the basement membrane consistent with ocular cicatricial pemphigoid. Clinicians should be aware of the possibility of underlying ocular cicatricial pemphigoid in all patients with entropion, including those without a cicatricial component.     

Mucous membrane pemphigoid with ocular involvement. Part I: Clinical manifestations, pathogenesis and diagnosis

Mucous membrane pemphigoid is a subepidermal blistering autoimmune disorder characterized by predominant involvement of mucous membranes and the presence of autoantibodies against proteins of the dermal-epidermal junction. Lesions most frequently develop in the oral cavity followed, in descending order of frequency, by conjunctiva, nasopharynx, the anogenital region, skin, larynx, and oesophagus. When the lesions are restricted to the conjunctiva, the term ocular pemphigoid may be applied. Cicatrization of the plica is considered a pathognomonic sign in early disease. Recurrent conjunctival inflammation results in subepithelial fibrosis, which leads to fornix shortening, symblepharon formation and subsequent trichiasis and entropion. Even in the absence of conjunctival inflammation, ankyloblepharon may occur. In end stage disease, limbal stem cell deficiency, tear deficiency, and lid malpositions may occur and result in a total keratinization of the ocular surface. The diagnosis is based on clinical findings and the detection of linear deposits of IgG and/or IgA and/or C3 at the dermal-epidermal junction by direct immunofluorescence microscopy of a perilesional biopsy. Autoantibodies (against type XVII and VII collagen, laminin 5 and 6, alpha6beta4 integrin, BP230) have been detected in patient serum. In the case of ocular involvement, preferential reactivity against beta4 integrin has been described.     

Ocular cicatricial pemphigoid associated with hyperproliferation of the conjunctival epithelium

We determined the mitotic rate, measured by evaluating uptake of tritiated thymidine autoradiographically, and the frequency of goblet cells in conjunctival epithelial biopsy specimens from nine normal subjects and from 11 patients (seven women and four men ranging in age from 50 to 80 years) with ocular cicatricial pemphigoid. The mitotic rate of patients with the disease was significantly higher than that of normal subjects, 7.2 +/- 2.2 vs 1.6 +/- 0.2 labeled cells per 100 basal epithelial cells (P less than .01). The goblet cell frequency, however, was significantly less in patients than in normal subjects. This suggests that ocular cicatricial pemphigoid is associated with hyperproliferation of the conjunctival epithelium, with a concurrent failure of normal conjunctival differentiation.     

Conjunctival involvement in paraneoplastic pemphigus.

Paraneoplastic pemphigus is a recently described autoimmune inflammatory mucocutaneous disease associated with an underlying neoplasm. Although histopathologic and direct immunofluorescence findings of involved skin and mucous membranes are consistent with pemphigus vulgaris, indirect immunofluorescence and immunoprecipitation study results are unique. We treated two patients with non-Hodgkin's lymphoma and paraneoplastic pemphigus. Both patients had bilateral bulbar conjunctival hyperemia and diffuse papillary tarsal conjunctival reactions. One patient had sloughing of conjunctival epithelium and the other had tarsal conjunctival cicatrization and forniceal shortening. Histopathologic findings of conjunctivae obtained from both patients were consistent with pemphigus vulgaris. Diffuse deposition of IgG and C3 in the intercellular substance of the conjunctival epithelium was demonstrated by direct immunofluorescence. Indirect immunofluorescence testing disclosed binding of autoantibodies to rodent bladder and intestinal epithelium. Immunoprecipitation disclosed antibodies reactive to Desmoplakin I (250 kd), bullous pemphigoid (230 kd), Desmoplakin II (210 kd) and 190-kd proteins. Ophthalmologists and pathologists should be aware of the conjunctival changes in paraneoplastic pemphigus.     

Schleimhautpemphigoid mit okulärer Beteiligung

Mucous membrane pemphigoid is a subepidermal blistering autoimmune disorder characterized by predominant involvement of mucous membranes and the presence of autoantibodies against proteins of the dermal-epidermal junction. Lesions most frequently develop in the oral cavity followed, in descending order of frequency, by conjunctiva, nasopharynx, the anogenital region, skin, larynx, and oesophagus. When the lesions are restricted to the conjunctiva, the term ocular pemphigoid may be applied. Cicatrization of the plica is considered a pathognomonic sign in early disease. Recurrent conjunctival inflammation results in subepithelial fibrosis, which leads to fornix shortening, symblepharon formation and subsequent trichiasis and entropion. Even in the absence of conjunctival inflammation, ankyloblepharon may occur. In end stage disease, limbal stem cell deficiency, tear deficiency, and lid malpositions may occur and result in a total keratinization of the ocular surface. The diagnosis is based on clinical findings and the detection of linear deposits of IgG and/or IgA and/or C3 at the dermal-epidermal junction by direct immunofluorescence microscopy of a perilesional biopsy. Autoantibodies (against type XVII and VII collagen, laminin 5 and 6, α6β4 integrin, BP230) have been detected in patient serum. In the case of ocular involvement, preferential reactivity against β4 integrin has been described.     

Lichen planus and cicatrizing conjunctivitis: characterization of five cases

PURPOSE: To report the clinical and immunopathologic features and the response to therapy in a series of six patients with cicatrizing conjunctivitis due to lichen planus. DESIGN: Retrospective case series. METHODS: All six patients were seen in an ocular pemphigoid clinic. Clinical, immunopathologic, and serologic features were evaluated and therapeutic response in each patient was monitored. RESULTS: All six patients had evidence of conjunctival scarring. Five patients had lichen planus of the oral mucosa and gingiva; one patient had involvement of the skin. Histologic findings consisted of thickened epithelium and an interface lymphocytic infiltrate along the lamina propria. In three patients, electron microscopy of the conjunctiva revealed thickening, fragmentation, and duplication of the basement membrane zone. Direct immunofluorescence examination of the conjunctiva and oral mucosa demonstrated linear and shaggy fibrinogen deposition along the basement membrane zone, confirming the diagnosis of lichen planus. All six patients were placed on immunosuppressive therapy with control of the disease. However, only one patient was able to discontinue the anti-inflammatory medication and have the lichen planus remain in remission. CONCLUSIONS: Lichen planus should be included in the differential diagnosis of cicatrizing conjunctivitis. Performing appropriate investigations to distinguish conjunctival lichen planus from other autoimmune diseases such as mucous membrane pemphigoid is critical to managing the patient with cicatrizing conjunctivitis appropriately. Oral cyclosporine effectively controlled the conjunctival lichen planus in four of the six cases.     

External ocular findings in lupus erythematosus: a clinical and immunopathological study.

A selected group of 18 patients with systemic lupus erythematosus (SLE) and 30 patients with chronic cutaneous lupus erythematosus (CCLE) showed an unexpectedly high incidence of problems involving the globe or eyelids. Five SLE patients had recurrent episcleritis, two CCLE patients had lower tarsal plaques, and two further CCLE patients had erosion of the lower lid margins associated with conjunctival scarring and symblepharon. This association has not previously been reported. There was an unexpectedly high incidence of deposition of immunoreactants in a linear pattern at the basement membrane zone in normal bulbar conjunctiva, which occurred in both SLE (42%) and CCLE (50%). The significance of these findings is discussed. We believe surface ocular problems in lupus erythematosus to be under-reported and that direct immunofluorescence of bulbar conjunctival biopsy might be helpful in diagnosis.     

Mucous membrane pemphigoid and pseudopemphigoid

PURPOSE: To describe the clinical characteristics of patients with mucous membrane pemphigoid (MMP) and pseudopemphigoid. DESIGN: Retrospective cohort study. PARTICIPANTS: Two hundred eighty consecutive patients referred for the evaluation of possible ocular MMP from January 1, 1985, to December 31, 2001. METHODS: Information on patients presenting for evaluation of possible MMP was entered prospectively into a database, which was supplemented by a retrospective chart review. Mucous membrane pemphigoid was diagnosed in patients with a compatible clinical picture by the linear deposition of antibodies to the basement membrane zone (BMZ) on direct immunofluorescent analysis of a mucous membrane biopsy specimen or by the presence of circulating autoantibodies to epithelial BMZ. MAIN OUTCOME MEASURES: Demographic and clinical characteristics of MMP and pseudopemphigoid; risk of ocular MMP among patients presenting with extraocular MMP without ocular disease. RESULTS: Among patients with ocular MMP, extraocular disease was common (82.4% of patients). The risk of ocular involvement among patients with MMP seen without ocular disease was approximately 5% per year over the first 5 years of follow-up (cumulative risk at 5 years, 22%). Although immunohistologic confirmation of the diagnosis was obtained in all patients, the initial conjunctival biopsy was positive for MMP in 80% of the patients diagnosed with ocular MMP. The most frequent presumed causes of pseudopemphigoid were topical glaucoma medications (28.3%), rosacea blepharoconjunctivitis (20.0%), atopic keratoconjunctivitis (8.3%), and conjunctival lichen planus (8.3%). CONCLUSIONS: Patients with ocular MMP typically have other systemic manifestations of MMP. Patients who are initially seen with extraocular MMP without ocular involvement are at risk for ocular disease developing. The clinical characteristics of ocular MMP and pseudopemphigoid are similar; therefore, immunohistologic evaluation of biopsied tissue is needed to confirm the diagnosis of MMP.     

The cell-layer- and cell-type-specific distribution of GalNAc-transferases in the ocular surface epithelia is altered during keratinization

PURPOSE: It has been hypothesized that the biosynthesis of O-linked glycans on proteins, particularly on the highly O-glycosylated mucins, by the corneal and conjunctival epithelium is necessary for the protection and maintenance of a healthy ocular surface. The initial step in O-glycosylation is the enzymatic addition of N-acetyl galactosamine (GalNAc) to serine and threonine residues by a large family of polypeptide GalNAc-transferases (GalNAc-Ts). The purpose of this study was to determine the cellular distribution of GalNAc-Ts in the normal ocular surface epithelia and to compare their distribution with that in pathologically keratinized conjunctival epithelia. METHODS: Five conjunctival biopsy specimens and 5 corneas from normal individuals, and 14 conjunctival specimens from patients with ocular cicatricial pemphigoid (OCP) were used. Based on the histologic characteristics of their epithelia, OCP specimens were divided into two groups: less advanced, nonkeratinized (n = 6), and late-stage, keratinized (n = 8). Five monoclonal antibodies raised against the GalNAc-T1, -T2, -T3, -T4, and -T6 isoenzymes, were used for immunofluorescence microscopic localization according to standard protocols. RESULTS: Immunohistochemical studies revealed the presence of GalNAc-T2, -T3, and -T4 isoforms within the stratified epithelium of the cornea and the conjunctiva. The GalNAc-T4 isoenzyme was found in the apical cell layers, whereas GalNAc-T2 was found in the supranuclear region of the basal cell layers of both cornea and conjunctiva. GalNAc-T3 was distributed throughout the entire ocular surface epithelium, whereas GalNAc-T1 was found in scattered cells in conjunctiva only. Binding of antibody to GalNAc-T6 was restricted exclusively to conjunctival goblet cells. There were distinct alterations in expression patterns of GalNAc-T2, -T6, and -T1 in nonkeratinized OCP epithelia compared with normal epithelia. Both GalNAc-T2 and -T6 were expressed in the apical stratified epithelia, and T1 was detected in all cell layers in five of six biopsy specimens. By comparison with nonkeratinized OCP epithelia, a marked reduction in the binding of GalNAc-T antibody was observed in the late-stage keratinized conjunctival epithelia of patients with OCP. In all samples, apical GalNAc-T2 was absent, and GalNAc-T6 was entirely absent. Only one of eight samples was positive for GalNAc-T1. CONCLUSIONS: The presence of GalNAc-T isoenzymes in the human corneal and conjunctival epithelia is cell-layer and cell-type specific. The increased distribution of GalNAc-Ts observed in early stages of the keratinization process in patients with OCP suggests a compensatory attempt of the ocular surface epithelium to synthesize mucin-type O-glycans to maintain a wet-surface phenotype. This early increase in isoenzymes in nonkeratinized OCP epithelia is reduced as keratinization proceeds in the disease.     

Corneal ulcer as an atypical presentation of ocular cicatricial pemphigoid

PURPOSE: To describe three patients, each presenting noninfective corneal epithelial damage as first manifestation of ocular cicatricial pemphigoid (OCP). METHODS: Case report. RESULTS: Patients 1 and 2 were referred to the authors' clinic for corneal ulcer while Patient 3 for relapsed epithelial defects. All patients had negative history for systemic diseases and microbiological tests were negative. Topical steroid treatment induced the complete resolution of corneal damage. During the follow-up period, the onset of mild conjunctival fibrosis in the lower fornix allowed the authors to suspect OCP, confirmed by conjunctival biopsy. CONCLUSIONS: In the three patients corneal damage was an early sign of OCP, in the absence of typical signs of conjunctival fibrosis. The authors thus suggest considering conjunctival biopsy as a useful additional test in the management of idiopathic corneal ulcers.     

Mucous membrane pemphigoid: an update

PURPOSE OF REVIEW: To review articles on mucous membrane pemphigoid, published between June 2004-May 2005. RECENT FINDINGS: Decreased glycosylation of mucin was found in patients with ocular cicatricial pemphigoid. A unique antigen in oral mucous membrane pemphigoid has not yet been identified. Increased vascular cell adhesion molecule and intercellular adhesion molecule 1 expression was found in skin of patients affected by mucous membrane pemphigoid. Autoreactive T cells to an epitope of bullous pemphigoid antigen 180 kilodaltons were identified in the blood of some patients with mucous membrane pemphigoid. Circulating IgA against an antigen in mucous membrane pemphigoid was found in about 20% of patients, without prognostic significance. Enhanced sensitivity for direct immunofluorescence was reported if skin biopsy specimens were stored for 24 hours in saline. An enzyme-linked immunosorbent assay for detection of circulating autoantibodies against laminin-5 was developed. Sensitivity was higher than indirect immunofluorescence on salt-split skin and immunoblotting. Patients with younger onset (<60 years) of ocular cicatricial pemphigoid were found to have disease evolution similar to that of an older group (>70 years) but were visually impaired earlier in life. Intravenous immunoglobulin as treatment of ocular cicatricial pemphigoid was found to be superior to conventional immunosuppressants, with fewer side effects and better long-term outcome for halting disease activity. Intraoperative adjunction of mitomycin C during fornix reconstruction with amniotic membrane resulted in achieving a deeper fornix in 83% of patients with various cicatrizing conjunctivitis. Transplantation of cultured epithelial cells of oral mucosa in corneal limbal stem cell deficiency was successful in improving visual acuity and reestablishing corneal transparency in mid- to advanced ocular cicatricial pemphigoid. SUMMARY: Further advances have been achieved in the field of mucous membrane pemphigoid.     

Diagnostics and pharmacological treatment of ocular cicatrical pemphigoid

Ocular cicatricial pemphigoid (OCP) is an autoimmune disease characterize by mucous membrane fibrosis and skin changes resulting with scarring. The pathogenic mechanisms of ocular cicatricial pemphigoid are incompletely understood. Antibasement membrane antibodies which lead to subepithelial blistering, granulation tissue and inflammatory infiltrate formation in the substantia propria are thought to be the main pathophysiological mechanisms in cicatricial pemphigoid. It has been found eosinophils and increased collagen type I and III. Human leukocyte antigen HLA-DR2, HLA-DR4 and DQw7 genotypes have been identified as conferring increased susceptibility to the development of this disease. Ocular cicatrical pemphigoid (OCP) is one of the forms of bullous pemphigoid. Initial symptoms of ocular pemfigoid are not characteristic. Conjunctival fibrosis may cause severe entropion, trichiasis, symblepharon, dry eye syndrome, corneal epithelial erosions or ulceration. Secondary glaucoma is one of the most frequent complications. Ocular cicatricial pemphigoid may be chronic, acute, or subacute disease with periodic exacerbation of conjunctival inflammation. The treatment in this disease are topical drops or ointment (lubricants, corticosteroids, antibiotics, antiglaucomatous). Oral dapsone and corticosteroids may control the activity of the disease. In other progressive cases immunosuppressive drugs must be used (azathioprine, cyclophosphamide, methotrexate, mycophenolan mofetil, daclizumab, intravenous immunoglobulin therapy). To make an early diagnosis of ocular cicatricial pemphigoid, biopsy and immunohistochemical analysis of conjunctiva should be performed in every case of persistent conjunctival inflammation.     

Repeat Conjunctival Biopsy after Immunomodulatory Therapy for Ocular Mucous Membrane Pemphigoid

Purpose: To evaluate whether conjunctival biopsy findings in patients with ocular mucous membrane pemphigoid (MMP) persist as positive or revert to negative following treatment with immunomodulatory therapy (IMT).

Methods: Patients with biopsy-proven MMP were treated with IMT for at least 2 years before undergoing repeat conjunctival biopsy for immunofluorescence microscopy. Their records were reviewed and findings evaluated to ascertain which patients’ biopsies showed antibody deposition on the conjunctival basement membrane.

Results: Following 2 years of IMT, conjunctival biopsies showed persistent antibody deposition in two patients, and were negative in four patients.

Conclusions: Conjunctival biopsies in patients with ocular MMP may show reversion to inactive disease following IMT. Post-treatment biopsy might be clinically useful as a means of evaluating the efficacy of therapy in this chronic disease.     

Chronic cicatrizing conjunctivitis in a patient with ocular cicatricial pemphigoid and fatal Wegener granulomatosis

PURPOSE: To describe a case of chronic cicatrizing conjunctivitis in a patient with ocular cicatricial pemphigoid and Wegener granulomatosis. METHODS: Observational case report. A retrospective study. RESULTS: An 80-year-old man presented with chronic cicatrizing conjunctivitis, peripheral corneal thinning, and Wegener granulomatosis, which were diagnosed by his referring physician based on clinical (recurrent epistaxis, sinus congestion) and histopathologic features of nasal mucosa (granulomatous inflammation, vasculitis). A conjunctival biopsy performed by us disclosed features of active Wegener granulomatosis and ocular cicatricial pemphigoid, which indicate lack of control of both diseases with methotrexate treatment. The patient died of pulmonary complications from Wegener granulomatosis 1 week after our evaluation. CONCLUSION: Ocular cicatricial pemphigoid and Wegener granulomatosis are both potentially fatal autoimmune diseases. Ocular involvement in Wegener granulomatosis indicates poor control of the underlying systemic condition and is a marker for active vasculitis, which indicates the need for treatment with cyclophosphamide.     

Remission of antiepiligrin (laminin-5) cicatricial pemphigoid after excision of gastric carcinoma

PURPOSE: To describe a case of antiepiligrin cicatricial pemphigoid with unusual ocular manifestations and its remission after surgical removal of gastric carcinoma. METHODS: We describe a 61-year-old Japanese man with antiepiligrin cicatricial pemphigoid. RESULTS: He presented with conjunctival injection and discharge preceded by a 6-month period of erosive lesions in the oral mucosa and the truncal skin. An advanced gastric carcinoma was found and his serum immunoprecipitated laminin-5. Despite topical treatment with betamethasone, ofloxacin, and artificial tear solutions, serious symblepharon along the Meibomian line developed with little shortening of the inferior conjunctival sac. Following radical gastrectomy, the ocular and cutaneous lesions turned completely quiet. CONCLUSION: The present case differed from past cases by lacking inferior conjunctival sac shortening and by showing erosive lesions solely at the mucocutaneous junctions. The ocular involvement in this case correlated very well with the severity of gastric carcinoma.