Conjunctival intraepithelial neoplasia presenting as corneal ulcer

PURPOSE: To report a case of conjunctival intraepithelial neoplasia presenting as corneal ulcer. METHOD: Case report of a 28-year-old man who presented with sudden onset of pain, redness, and watering in the right eye. Examination of right cornea revealed deep stromal infiltrate inferonasally. Adjacent to the infiltrate and straddling the inferonasal limbus, a reddish well-defined sessible lesion with prominent blood vessels was seen. After corneal scraping for microbiological evaluation, the patient was treated with frequent instillation of ciprofloxacin hydrochloride 0.3% eyedrops. RESULTS: Corneal scraping revealed no microorganisms. Infiltrate resolved promptly after excision of the lesion. Histopathologic evaluation of the excised lesion revealed conjunctival intraepithelial neoplasia. CONCLUSIONS: This case highlights the fact that conjunctival intraepithelial neoplasia at the limbus may present as corneal ulcer. This ulcer could have occurred secondary to a dellen formation and epithelial breakdown predisposing to a corneal ulcer.     

Conjunctival Inclusion Cysts in Long-standing Chronic Vernal Keratoconjunctivitis

PURPOSE: To report a case of conjunctival inclusion cysts on the corneal limbus of a patient with chronic vernal keratoconjunctivitis during 16 months' follow up. METHODS: The patient was a 26 year old male without any specific history of surgery or trauma. Giant papillae, shield ulcers, and Horner-Trantas dots were detected. During the 16 month follow-up, Sodium cromoglycate eye drops and Prednisolone acetate 1% eye drops were given 3 times a day. During this period, conjunctival cysts were detected on the corneal limbus in both eyes. In spite of improvement of the corneal and conjunctival conditions, the conjunctival cysts did not seem to show any specific changes. For relief of foreign body sensation, excision of the conjunctival cysts and giant papillae of the left eye and histopathologic examination of the specimen was performed. RESULTS: On histopathological examination, the conjunctival cysts consisted of nonkeratinizing stratified epithelial cells filled with PAS-positive mucous substance. Inflammatory cells were not found in the vicinity. CONCLUSIONS: Conjunctival inclusion cysts can be seen as an atypical finding of long-standing vernal keratoconjunctivitis. Mechanical friction between the giant papillae and conjunctiva may be a factor in inducing the formation of the conjunctival cysts.     

角结膜缘上皮性癌前病变和恶性肿瘤的临床病理学特点

目的 分析角结膜缘上皮性癌前病变和恶性肿瘤的类型和临床病理学特点.方法 回顾性研究收集天津眼科医院从1990年至2008年间收治的69例角结膜缘上皮性癌前病变和恶性肿瘤的临床资料,按照目前病理学分类和诊断标准,重新核对所有病例的病理诊断,分析临床病理学特征.结果 所有病变包括结膜上皮内瘤变(conjunctivalintraepithelial neoplasia,CIN)45例(65.2%),日光性角化病6例(8.7%),鳞状细胞癌18例(26.1%).男性58例(84%),女性l1例(16%),发病年龄34～83岁,平均年龄53.6岁.42例发生于鼻侧角结膜缘(61%),21例发生于颞侧角结膜缘(30.4%),6例肿瘤位于角膜表面(9%).CIN和日光性角化病表现为角结膜缘扁平状或轻度隆起、灰白色或粉红色肿物,肿物周围通常有充血扩张的血管.45例CIN病例中,11例(24.4%)为低级别CIN,34例(75.6%)为高级别CIN.鳞状细胞癌通常表现为结节状或乳头状,肿瘤体积通常大于CIN和日光性角化病,其中乳头状鳞状细胞癌12例,浸润性鳞状细胞癌6例.角结膜缘CIN、日光性角化病和鳞状细胞癌容易累及邻近的角膜上皮,尤其浸润性鳞状细胞癌容易侵及角膜浅实质层,但很少穿透眼球壁侵入到眼球内.结论 睑裂部角膜缘是眼球表面CIN,日光性角化病和鳞状细胞癌好发部位,早期正确的诊断和治疗非常重要.     

The conjunctiva in corneal epithelial wound healing

BACKGROUND/AIMS—During the healing of corneal epithelial wounds with limbal involvement, conjunctival epithelium often migrates across the denuded limbus to cover the corneal surface. It is believed that, over a period of time, conjunctival epithelium covering the cornea assumes characteristics of corneal epithelium by a process referred to as conjunctival transdifferentiation. The purpose of this study was to examine, clinically, the fate of conjunctival epithelial cells covering the cornea and to assess the healing of corneal epithelial wounds when the conjunctival epithelium was removed or actively prevented from crossing the limbus and extending onto the cornea.
METHODS—10 patients with conjunctivalisation of the cornea were followed for an average of 7.5 months. Five patients in this group had their conjunctival epithelium removed from the corneal surface and allowed to heal from the remaining intact corneal epithelium. In another four patients with corneal epithelial defects, the conjunctival epithelium was actively prevented from crossing the limbus by mechanically scraping it off.
RESULTS—The area of cornea covered by conjunctival epithelium appeared thin, irregular, attracted new vessels and was prone to recurrent erosions. Conjunctivalisation of the visual axis affected vision. Removal of conjunctival epithelium from the cornea allowed cells of corneal epithelial phenotype to cover the denuded area with alleviation of symptoms and improvement of vision. It was also established that migration of conjunctival epithelium onto corneal surface could be anticipated by close monitoring of the healing of corneal epithelial wounds, and prevented by scraping off conjunctival epithelium before it reached the limbus.
CONCLUSION—This study shows that there is little clinical evidence to support the concept that conjunctival transdifferentiation per se, occurs in humans. "Replacement" of conjunctival epithelium by corneal epithelial cells may be an important mechanism by which conjunctival "transdifferentiation" may occur. In patients with partial stem cell deficiency this approach can be a useful and effective alternative to partial limbal transplantation, as is currently practised.

Keywords: corneal epithelium; conjunctiva; stem cells; transdifferentiation     

Massive intraocular invasion of conjunctiva by squamous cell carcinoma--a case report

BACKGROUND: Squamous cell carcinoma of the conjunctiva is a mostly solitary growing tumor located at the limbus region, which seldom invades the eye. We present an unusual case of conjunctival carcinoma with marked intraocular involvement, which appeared primarily as a chronic inflammation with corneal ulcer. CASE REPORT: A 89-year-old female patient was referred to our institution with a suspected ulcus rodens of the cornea. Since one year a refractory conjunctivitis persisted despite of different local treatment. At first presentation, a marked bacterial keratoconjunctivitis with circular necrosis of the conjunctiva, corneal infiltration and perforation was seen. Visual acuity of the right eye was light perception. The left eye was unremarkable. Enucleation of the right eye was performed. Histopathologic examination revealed the diagnosis of squamous cell carcinoma of the conjunctiva with intraocular involvement. There was a marked infiltration of the choroid even behind the equator. No metastases were found. CONCLUSION: Advanced squamous cell carcinoma associated with superinfection may present as a primary inflammatory process. There may be extensive involvement of the choroid. Metastases are probably rare even in advanced cases of this type of carcinoma.     

The 1998 Pan American Lecture. Intraocular invasion of conjunctival squamous cell carcinoma in five patients.

PURPOSE: To report five patients with intraocular invasion of conjunctival squamous cell carcinoma and to make recommendations regarding clinical recognition and treatment of this condition. METHODS: The authors reviewed the clinical records and pathology slides on five patients who had intraocular invasion of conjunctival squamous cell carcinoma, and they describe the presenting features and histopathology in these cases. RESULTS: Intraocular invasion of conjunctival squamous cell carcinoma occurred in older patients who had one or more recurrences of a previously excised conjunctival epithelial tumor located near the comeoscleral limbus. The intraocular recurrence often was heralded by the onset of low-grade inflammation and secondary glaucoma, simulating a granulomatous iridocyclitis. A white mass generally was observed in the anterior chamber angle. Histopathologic examination revealed an ingrowth of malignant epithelial cells through the limbus with diffuse involvement of the anterior segment of the eye. The reported patients were managed by modified enucleation (standard enucleation with excision of affected conjunctival tissue). Metastatic disease did not develop in any of the patients. CONCLUSIONS: The onset of signs of uveitis and glaucoma and a white mass in the anterior chamber angle in a patient with prior excision of a conjunctival squamous cell neoplasm tumor should raise suspicion of intraocular recurrence of conjunctival squamous cell carcinoma. Most affected patients require enucleation or subtotal orbital exenteration. The prognosis is good.     

角膜缘部干细胞对角膜上皮创伤愈合的影响

利用角膜缘上皮移植，结膜移植和非手术的方法分别对角膜上皮创伤伴随膜缘损伤的兔眼进行实验研究，结果表明角膜缘上皮移植组上皮愈合时间短（平均８．５天），且无杯状细胞，无或极少量新生血管；结膜移植组，上皮愈合时间延长（平均１１．５天），含有杯状细胞和新生血管，非手术组形成角膜血管翳性混浊。而不件随角膜缘损伤仅有角膜中央皮皮创伤的兔眼愈合时间最短（平均３．５天），愈合后无新生血管及怀状细胞。结果证实角膜部     

Conjunctival inflammation induces Langerhans cell migration into the cornea

PURPOSE: The virtual absence of Langerhans cells (LC) in donor or recipient corneal epithelium is known to be an important factor in the acceptance of orthotopic corneal allografts. Though it is well known that various types of stimulation to the cornea induce LC migration into the corneal epithelium, resulting in poor graft survival, the influence of conjunctival inflammation on LC migration into the cornea has not been elucidated. Therefore we examined whether LCs migrate into the cornea in the presence of conjunctival inflammation. METHODS: Sixteen BALB/c mice were divided into four groups. Group A: 4 mice with corneal inflammation induced by two 9-0 silk interrupted sutures in the central cornea (positive control); Group B: 4 mice with conjunctival inflammation induced by two 9-0 silk interrupted sutures in the temporal and nasal bulbar conjunctiva 1 mm from the limbus; Group C: 4 mice with conjunctival inflammation by two 10-0 nylon interrupted sutures in the temporal and nasal bulbar conjunctiva 1 mm from the limbus; and Group N: 4 mice with no inflammation (untreated, naive control). Fourteen days after suturing, the mice were sacrificed and LCs migrated into the corneal epithelium were counted by immunofluorescence assay using anti-Ia antibody. RESULTS: In Group A, Ia(+) cells in the cornea totaled 29.4 +/- 3.8 cells/mm(2); in Group B, 7.9 +/- 1.2 cells/mm(2); in Group C, 7.8 +/- 0.7 cells/mm(2); and in Group N, 1. 6 +/- 0.5 cells/mm(2). Significantly greater numbers of Ia(+) cells were detected in Groups A, B and C than in Group N (p < 0.005). CONCLUSIONS: Conjunctival inflammation caused by sutures in the bulbar conjunctiva induced LC migration into the cornea. These results indicate that conjunctival inflammation influences the corneal immunological environment, and may affect the fate of orthotopic corneal allografts.     

Histological study of a model of keratoepithelioplasty in the rat]

A model for keratoepithelioplasty (KEP) was developed using the Lewis rat, and histological studies were performed using the model. The entire corneal epithelium was removed using a spatula and a 1.5-mm-width of the conjunctiva including the limbus was excised. An oval corneal lamellar graft (3 x 1.5 mm) with an intact epithelium taken from another Lewis rat was transplanted on the denuded limbus. Biomicroscopic observation showed significantly less vascular invasion in the part of the cornea adjacent to the lenticule than in other part of cornea, and clear cornea was maintained in the cornea adjacent to the lenticule. Histologically only few vessels were recognized in the lenticule, and the epithelial cells on the lenticule showed histological characteristics of corneal epithelium. These results indicate that surgical function of KEP can be obtained because the lenticules keep distance between corneal epithelium and conjunctival vessels. And it is also confirmed that this model is useful in research on the pathophysiological mechanism of KEP.     

Keratoepithelioplasty in rat: development of a model and histological study.

A model for keratoepithelioplasty (KEP) was developed using the Lewis rat, and histological studies were performed using this model. The entire corneal epithelium was removed mechanically and a 1.5-mm width of the conjunctiva including the limbus was excised. An oval corneal lamellar graft (3 x 1.5 mm) with an intact epithelium taken from another Lewis rat was transplanted on the denuded limbus. Biomicroscopic observations showed much less vascular invasion in the part of the cornea adjacent to the lenticule than in other parts of the cornea, and the cornea remained clear adjacent to the lenticule. Histologically, a few vessels were observed in the corneal stroma under the lenticule. Epithelial cells on the lenticule specimens showed histological characteristics of the corneal epithelium. These findings indicate that one of the functions of KEP is to block neovascularization in the newly developing corneal epithelium by transplanting the lenticule between the corneal epithelium and conjunctival vessels. The present study also confirmed that this model is useful in the research of the pathophysiological mechanism of KEP.     

角膜全结膜瓣遮盖术式探讨

报告眼球萎缩及先天性小眼球１０例１０只眼行角膜上皮去除全结膜瓣遮盖术，９例９只根均获满意结果，结膜瓣一期愈合，上窝饮满，义眼活动好，１例术后４天结膜瓣裂开，７天 至角膜缘。产吩眼球萎缩及先天性小眼球患者可保留眼球，行角膜全结膜瓣遮盖术，安装义眼，改善外观。本文讨论了角膜全结膜瓣盖手术的关键步骤，手术的适应证，禁忌证及相关手术的比较。     

Surgical Excision, Cryotherapy, Autolimbal Transplantation and Mitomycin-C in Treatment of Conjunctival–corneal Intraepithelial Neoplasia

Purpose To report surgical excision, cryotherapy, autologous conjunctival–limbal transplantation and topical mitomycin C (MMC) in the patient with extensive conjunctival–corneal intraepithelial neoplasia. Methods Case report and literature review. Results A 75-year-old woman was referred to our department with the diagnosis of conjunctival–corneal neoplasia. Slit-lamp microscopic examination revealed an extensive papilliform tumoral mass invading the limbus at 360-degrees, and bulbar conjunctiva and cornea. Visual acuity was finger counting from 2 m in the right eye and 20/20 in the left eye. We performed total surgical excision, cryotherapy and autologous conjunctival–limbal transplantation in the right eye. Mitomycin-C 0.02% eye drops four times a day were prescribed for 4 weeks after the surgery. After the treatment, the visual acuity increased to 0.7 in the right eye. Corneal epithelium completely healed within 1 week after the surgery. No corneal epithelium-related problem or neoplasia recurrence were noted during the 2-year follow-up period. Conclusions This technique may be useful in reconstruction of eyes with extensive neoplastic involvement of the conjunctiva, limbus, and cornea. In addition, mitomycin C drops may be useful in preventing postoperative recurrence of conjunctival–corneal intraepithelial neoplasia.     

Autologous limbal transplantation in patients with unilateral corneal stem cell deficiency

AIM: To describe a surgical technique for autologous limbal stem cell transplantation and the outcome of a series of patients with unilateral stem cell deficiency. METHODS: A report of six consecutive patients who underwent autologous limbal stem cell transplantation is presented. The primary diagnosis included alkali burn (n=3), conjunctival intraepithelial neoplasia (CIN) (n=1), recurrent pterygium (n=1), and contact lens induced keratopathy (n=1). The autologous transplanted tissue consisted of peripheral cornea, limbus, and conjunctiva obtained from the contralateral eye. Three of the above patients underwent penetrating keratoplasty in association with auto-limbal transplantation. A significant modification to established techniques was the close monitoring of conjunctival epithelial migration in the immediate postoperative period. If conjunctival epithelium threatened to migrate on to the corneal surface, it was mechanically removed at the slit lamp and prevented from crossing the limbus. This was required in three patients. RESULTS: The mean follow up was 18.8 months. The outcome was satisfactory in all cases: a stable corneal surface was restored and there was a substantial improvement in vision and symptoms. One patient had a primary failure of the corneal allograft associated with glaucoma, and 6 months later developed a retinal detachment. No complications were noted in the donor eye with the exception of one patient who developed filamentary keratitis along the edge of the donor site. CONCLUSION: Autologous limbal transplantation with corneal, limbal, and conjunctival carriers was found to be useful for ocular surface reconstruction, over a mid-term follow up, in patients with unilateral stem cell deficiency. Close monitoring of the migration of conjunctival epithelium in the immediate postoperative period, and preventing it from crossing the limbus, ensured that the corneal surface was re-epithelialised exclusively from epithelial cells derived from the transplanted limbal tissue. This approach should improve the success of this procedure.     

Amniotic membrane transplantation with conjunctival limbal autograft for total limbal stem cell deficiency

PURPOSE: To evaluate the outcomes of corneal surface reconstruction with conjunctival limbal autograft when combined with amniotic membrane transplantation on both the donor and recipient eyes. DESIGN: Retrospective, noncomparative, interventional small case series. PARTICIPANTS: Five eyes of five patients with total limbal stem cell deficiency (LSCD) resulting from pseudopemphigoid (n = 1), chemical burns (n = 3), and extensive removal of conjunctival intraepithelial neoplasia (n = 1) were operated on by one surgeon (SCGT). INTERVENTION: After the removal of fibrovascular pannus from the corneal surface, two conjunctival limbal free grafts were harvested from the fellow eyes in all five patients with unilateral LSCD. Amniotic membrane, with the basement membrane side up, was grafted onto the defect created at the donor site and onto the recipient corneal and limbal sclera before placement of conjunctival limbal grafts. MAIN OUTCOME MEASURES: Symptomatic relief, improvement in visual acuity, fornix deepening, and rapid healing and restoration of normal cornea and limbus in the recipient and donor eyes were assessed. RESULTS: During the mean follow-up of 22 months (range, 11-48 months), all eyes experienced symptomatic relief. All recipient eyes had a mean improvement in visual acuity of nine lines (range, 7-12). The three eyes with stromal vascularization showed regression, and all recipient eyes had marked improvement in corneal clarity. Three eyes receiving simultaneous symblepharon lysis and fornix reconstruction successfully regained deep, stable fornices. The donor eyes showed rapid healing and restoration of the normal limbal landmark, even in one eye where nearly the entire limbus was removed. CONCLUSIONS: Limbal conjunctival transplantation is an effective procedure for restoring the corneal surface integrity in eyes with total LSCD. The additional use of amniotic membrane may contribute to a higher rate of success in the recipient eye and a lower rate of complications in the donor eye, as well as allow the simultaneous correction of concomitant cicatricial abnormalities.     

Management of conjunctival and corneal melanoma with surgical excision, amniotic membrane allograft, and topical chemotherapy

PURPOSE: To illustrate a novel method of management for extensive conjunctival and corneal melanoma. METHODS: Interventional case report. A 40-year-old Caucasian woman presented with a large, diffuse conjunctival melanoma involving 6 clock hours of the limbus. The remaining bulbar conjunctiva and the entire corneal epithelium were affected by diffuse, flat melanosis. RESULTS: The conjunctival melanoma was completely resected microsurgically in one piece without disrupting the tumor. The conjunctival melanosis was treated with double freeze-thaw cryotherapy. The extensive conjunctival defect, involving one-half of the bulbar conjunctiva, was reconstructed with an amniotic membrane allograft. The corneal melanosis was subsequently treated with topical mitomycin C eyedrops. At 8 months follow-up, the conjunctiva and the cornea were completely healed with resolution of all pigment and 20/20 visual acuity. CONCLUSION: Preliminary evidence suggests that combined therapeutic approaches, consisting of extensive tumor removal, cryotherapy, amniotic membrane allograft, and topical mitomyin C, can be effective in the management of diffuse conjunctival and corneal melanoma arising from primary acquired melanosis.     

The corneoscleral limbus in human corneal epithelial wound healing

We studied re-epithelialization of the ocular surface in 17 human eyes (14 patients) with large corneal and conjunctival abrasions. We focused on the healing of the limbal region. During re-epithelialization, cell movement was found to occur circumferentially along the corneoscleral limbus and centripetally from the corneoscleral limbus. In no patient did the central corneal defect close before the corneoscleral limbus had first re-epithelialized completely. Normal limbal healing was observed to occur by circumferentially migrating tongue-shaped corneal limbal epithelium. These tongue-shaped projections developed from either side of the remaining intact epithelium and advanced along the corneoscleral limbus until they met. A centripetal movement of cells from the corneoscleral limbus then completed the healing process. In three patients, however, the advancing conjunctival epithelium extended across the corneoscleral limbus before the tongue-shaped projections of corneal limbal epithelium had met. The surface of the cornea covered by conjunctival epithelium was thin and irregular, and later showed peripheral scarring, vascularization, and recurrent erosions.     

Corneally displaced malignant conjunctival melanomas

PURPOSE: To characterize and classify malignant conjunctival melanomas with exclusively corneal invasive growth. DESIGN: Population-based, nationwide retrospective cross-sectional study. PARTICIPANTS: Patients with primary malignant conjunctival melanoma diagnosed between 1967 and 2000 in Finland. METHODS: On the basis of all available clinical and histopathologic data of tumors diagnosed during the study period, malignant conjunctival melanomas that first demonstrated invasive growth on the cornea without evidence of conjunctival tumors other than primary acquired melanosis were identified, their prevalence calculated, and their characteristics reviewed. On the basis of these cases and literature data, a classification for "corneal melanoma" was developed. MAIN OUTCOME MEASURES: Frequency and type of corneal involvement, recurrence, and survival. RESULTS: Patients with exclusively corneal invasive tumor accounted for 5% (95% confidence interval, 1-12) of 85 consecutive primary conjunctival melanomas. Two were separated from the limbus by clear cornea (type I), and two paralleled but did not invade the limbal conjunctiva (type II). Two were associated with clear evidence of primary acquired melanosis. None of the tumors recurred after local excision, and no metastases were observed during a median follow-up of 2 years 5 months (range, 1 year 8 months-7 years 10 months). CONCLUSIONS: Primary malignant conjunctival melanomas can grow on the cornea without conjunctival involvement other than acquired melanosis. They are easily removed and do not cause lymphatic metastases. The term "corneally displaced malignant conjunctival melanoma" would best describe their supposed conjunctival origin and actual corneal location.     

Marginal pellucid degeneration of the cornea, or marginal keratoconus (author's transl)

Histological and ultrastructural examination of the corneas of a woman presenting with marginal pellucid degeneration, treated by bilateral perforating keratoplasty, revealed obvious analogies with keratoconus. The condition of marginal pellucid degeneration is really only an excentric keratoconus. Marginal pellucid degeneration is a rare affection but it has been clinically sell defined. Many authors seem to have recognized it under various different names (cylindrical keratoconus, corneal protusion, piriform cornea). It is a pouch-shaped deformity of the cornea overlying a thinning of the linear stroma concentric to the limbus, always inferior and bilateral, perfectly transparent, non-vascularized, and without signs of corneal of conjunctival inflammation. The affection usually occurs in young adults.     

Nevus melanocítico atípico limbar. A propósito de un caso

Case reportA 78-year-old-woman presented with a corneal non-pigmented vascularised tumour of her left eye, of 2 months onset, but with no previous ocular disorders. Surgical excision was performed, and the histopathological study showed the lesion to be an atypical melanocytic nevus of the limbus.DiscussionCorneal pigmented lesions tend to occur as a result of conjunctival or sclerocorneal limbus lesions spreading or arising de novo from melanocytic cells that have migrated following corneal injury. A biopsy should be carried out to type and distinguish benign lesions (nevus) from pre-malignant or malignant lesions (primary acquired melanosis or conjunctival melanoma).     

Epibulbar molluscum contagiosum in acquired immune deficiency syndrome. Case report and review of the literature.

BACKGROUND: While molluscum contagiosum of the eyelid skin is commonly complicated by conjunctivitis, primary involvement of the conjunctiva or cornea by molluscum lesions is exceedingly rare. The authors studied a 34-year-old man with acquired immune deficiency syndrome (AIDS) in whom multiple molluscum lesions of the lids and a single nodule of the limbus developed. METHODS: The nodular lesion was excised from the limbus and processed for histologic examination by light microscopy. Pertinent literature concerning epibulbar molluscum contagiosum was reviewed. RESULTS: Histopathology of the excised lesion showed molluscum bodies within the acanthotic, hyperkeratotic conjunctival epithelium with surrounding chronic, nongranulomatous inflammation. Only 10 previous cases of conjunctival or corneal primary lesions have been reported, half of which showed associated cutaneous involvement. Lesions tended to be single, noninflamed, dome-shaped, and umbilicated, often with a yellowish central core. Patients were otherwise well and ranged in age from 3 to 55 years. Simple excision was effective in eradicating the lesions. CONCLUSION: Primary epibulbar molluscum contagiosum is rare. Although cutaneous molluscum is common in AIDS, this report is the first to document conjunctival molluscum in a patient with AIDS.