Indocyanine Green Angiographic Assessment of Conjunctival Melanocytic Disorders.

PURPOSE: To investigate whether transvascular indocyanine green (ICG) dye leakage is associated with conjunctival malignancy. METHODS: This is a prospective interventional study. Patients presenting with circumscribed conjunctival melanocytic disorders (CMDs) were included and examined using color photography, anterior segment optical coherence tomography to measure lesion size, and fluorescein and ICG angiography to measure vascular pattern and leakage. Time to vascular leakage was measured by 2 independent observers. Lesions were characterized as benign or malignant based on histopathological features. RESULTS: Thirty patients with CMD were included: 22 lesions were benign (conjunctival nevus, n = 20; conjunctival melanocytic intraepithelial neoplasia without atypia, n = 2) and 8 were malignant (in situ conjunctival melanoma n = 2; invasive conjunctival melanoma, n = 6). Malignant lesions had larger mean maximal diameters (11.0 ± 4.5 vs. 4.2 ± 2.5 mm, P = 0.003) and more frequently showed intrinsic tumor vasculature (8 of 8 vs. 10 of 22, P = 0.007). The mean time to ICG leakage was 350.9 ± 165.9 seconds in benign and 59.6 ± 22.1 seconds (P = 0.002) in malignant lesions and was inversely correlated with lesion size and thickness. CONCLUSIONS: Time to angiographic ICG dye leakage is significantly shorter in malignant versus benign CMD.

Inflammatory juvenile compound nevi: A melanoma is not all that it appears to be. / Nevus compuesto inflamatorio juvenil: no es melanoma todo lo que parece.

An 11 year-old girl presented with a recent growth pigmented conjuntival lesion in the bulbar conjunctiva of left eye. Due to the the biomicroscopic and ultrasound findings, an excisional biopsy was performed on the lesion using the «no touch¼ technique, as well as cryo-coagulation of surgical margins. Histopathological examination revealed an inflammatory compound nevus. Melanotic conjunctival tumours are mostly benign. However, the recent growth of a lesion, its vascularisation, irregularities of the margins, and colour change must suggest it has turned malignant. In such case, excision of the lesion is mandatory. Despite all the clinical changes, especially in young patients, it can still be an inflammatory compound nevus.

Identification of Feeder Vessels in Ocular Surface Neoplasia Using Indocyanine Green Angiography.

PURPOSE: To evaluate indocyanine green angiography (ICGA) for the identification and characterization of afferent (feeding) and efferent (draining) vessels in patients with ocular surface neoplasia. MATERIALS AND METHODS: Consecutive patients with biopsy-proven benign, pre-invasive, or invasive ocular surface tumors of the bulbar conjunctiva were included. Patients underwent anterior segment optical coherence tomography, ICGA, and color photography for the evaluation of the thickness, location, number, and diameter of afferent and efferent vessels of the lesions. RESULTS: Twenty-two eyes of 22 patients with papillomas (n = 4), intra-epithelial neoplasia lesion (n = 2) in situ or invasive carcinomas (n = 6), nevus (n = 5), conjunctival melanocytic intra-epithelial neoplasia lesion (n = 1), and in situ or invasive melanomas (n = 4) were investigated. Afferent (feeder) vessels were identified in all lesions. There were fewer afferent (3.1 ± 1.6) than efferent (7.5 ± 3.5) vessels per lesion (p < 0.001) and the mean diameter was smaller for afferent (101 ± 62 µm, 28-281) than efferent vessels (137 ± 51 µm, 31-652; p = 0.017). The number of afferent and efferent vessels was associated with the thickness of the lesion (p = 0.037, p < 0.01). Lesion filling times differed between benign and invasive or pre-invasive lesions (p = 0.018). CONCLUSIONS: ICGA is a useful adjunctive in vivo imaging method for the assessment of the vasculature in patients with suspected ocular surface neoplasia.

Vascular-Associated Muc4/Vwf Co-Localization in Human Conjunctival Malignant Melanoma Specimens-Tumor Metastasis by Migration?

PURPOSE: To investigate whether vascular differentiation marker von Willebrand factor (vWf) and proliferation marker KI67 expression correlate with MUC4 localization around stromal tumor vascularization in human conjunctival malignant melanoma (CMM). MATERIALS AND METHODS: For the purposes of this study, we analyzed samples from human CMMs (n = 4), conjunctival compound nevi (n = 7), and samples from healthy conjunctiva (n = 7) for MUC1, 4, and 16 by immunohistochemistry. To test CMM vessel association of MUC4, we investigated the co-localization of MUC4 with vWf or KI67 in human CMM specimens (n = 10) by immunohistochemistry. Also, we investigated the MUC4 localization around vessels of healthy conjunctiva (n = 10). RESULTS: The immunohistochemical analysis demonstrated membrane-associated mucin expression in epithelia of CMM, nevi and healthy conjunctiva, whereas only MUC4 was localized perivascular in CMM tissue in this preliminary analysis. Co-staining analysis with vWf and KI67 demonstrated MUC4 localization around stromal vessels in human CMM specimens. In contrast, no MUC4 localization has been seen around healthy conjunctiva stroma vessels. CONCLUSIONS: MUC4 was detected around vWf/KI67-positive CMM stromal vascular tissue, but not around healthy conjunctival stroma vessels. Therefore, we assume that MUC4 might play a role in tumor cell migration toward vessels inducing metastasis.

Topical Bevacizumab for the Treatment of Ocular Surface Squamous Neoplasia.

PURPOSE: To determine the efficacy and safety of topical bevacizumab treatment in patients with ocular surface squamous neoplasia (OSSN). METHODS: Six eyes of 6 patients with primary OSSN confirmed by impression cytology received topical 5 mg/mL bevacizumab 4 times daily for a period of 8 weeks. Patients were evaluated in 2-week intervals. Digital photography images were obtained at each visit and changes in the size of the lesions were analyzed by image analysis software. RESULTS: The mean age of the patients was 66 ± 13 (± SD) years. Four tumors were nasal in origin and 2 tumors were temporal. The mean reduction observed in the lesion area was 43% ± 24.2% (range, 20%-71%) in the first month and 68% ± 29.7% (range, 42%-100%) in the second month when compared with the baseline area. Four patients required tumor excision at the end of the treatment period. Surgical treatment was not necessary in 2 patients due to complete disappearance of the tumor, which was confirmed by impression cytology. The visual acuity was stable in all patients and no systemic or visual side effects were observed during the study period. CONCLUSIONS: Topical bevacizumab is effective as a neoadjuvant therapy combined with surgical excision for the treatment of OSSN. Topical bevacizumab may be used before surgery to decrease the size of the excision. Excision may be unnecessary in responsive patients.

Use of topical bevacizumab for conjunctival intraepithelial neoplasia.

PURPOSE: To report our experience in the treatment of intraepithelial neoplasia of the conjunctiva using topical bevacizumab. METHODS: Ten eyes of 10 patients with conjunctival neoplasia received 25 mg/mL bevacizumab topically. Changes in the lesions were documented weekly using digital photography. After topical treatment, excisional biopsy was performed. RESULTS: The mean age of the patients was 60.5 ± 12 (33-77) years. The mean duration of topical treatment was 7.8 ± 1.3 (5-14) weeks. The size and vascularity of the tumors reduced weekly. All patients underwent excisional biopsy, cryotherapy, and amnion membrane transplantation. The histopathologic diagnosis of the lesions was carcinoma in situ. No recurrence was observed during the follow-up of patients for 6 months. CONCLUSIONS: Topical bevacizumab is an effective treatment to reduce the tumor size before surgery and may be a good alternative for adjuvant therapy of conjunctival neoplasms.

Subconjunctival bevacizumab injection for ocular surface squamous neoplasia.

PURPOSE: To determine the efficacy and safety of perilesional/subconjunctival bevacizumab injections in the management of ocular surface squamous neoplasia (OSSN). METHODS: Ten eyes of 10 patients with an OSSN diagnosis confirmed by impression cytology received 2 perilesional/subconjunctival injections of bevacizumab at a 2-week interval. Patients were evaluated for 3 months, during which time, changes in the lesions were documented using digital photography. After this period, excisional biopsy of the remaining tumor and cryotherapy of the conjunctival borders were performed if deemed necessary. RESULTS: The mean age of the patients was 65 ± 12 years (± SD). All of the tumors were nasal in origin and had varying degrees of vascularization. The mean lesion area before treatment was 16 ± 6.9 mm2. Two weeks after the first injection, the mean reduction observed in the tumor area was 25% ± 5.65% and ranged from 17% to 33% (P = 0.001). Two weeks after the second injection, the mean tumor area was further decreased (42% ± 33%, ranging from 15% to 100%, P = 0.049). Corneal extension of the tumor was not affected significantly in 8 of the eyes with concomitant conjunctival and corneal involvement. Complete disappearance of the tumor was demonstrated by impression cytology and occurred in 2 cases involving lesions clinically confined to the conjunctiva. No systemic or ocular side effects occurred during the study period. CONCLUSIONS: Perilesional/subconjunctival injections of bevacizumab decrease the size and vascularity of OSSN and may be curative in lesions limited to the conjunctiva. However, this treatment has no significant effect on the corneal extension of OSSN.

Immunolocalization of vascular adhesion protein-1 in human conjunctival tumors.

OBJECTIVE: We analyzed the expression and immunolocalization of vascular adhesion protein (VAP)-1 in conjunctival tumors and normal conjunctival tissue of humans. METHODS: Nine conjunctival tumors, including pyogenic granuloma and extranodal marginal zone B-cell lymphoma (EMZL), and 2 normal conjunctivas were analyzed by immunohistochemistry for VAP-1 and CD31 expression. RESULTS: Immunoreactivity for VAP-1 was detected in the lumen of microvessels in pyogenic granuloma and in EMZLs. In contrast, normal bulbar conjunctival tissues demonstrated weak cytoplasmic immunoreactivity for VAP-1 in the blood vessels. CONCLUSIONS: The immunolocalization of VAP-1 varied in the histopathology of the conjunctiva, involving the pathology of inflammatory conjunctival disorders.

Conjunctival melanomas: can the cancer stem cell hypothesis be applied?

Conjunctival melanoma patients often follow an unpredictable course with significant rates of recurrence and metastases despite optimal treatment. Can we better understand conjunctival melanomas by applying the cancer stem cell hypothesis? The cancer stem cell hypothesis posits that cancers exist as a hierarchical system where cancer stem cells generate and maintain tumors. Targeting cancer stem cells may be the key to future treatments. Directed treatments need to focus on key differences between cancer stem cells and normal tissue stem cells. These directed treatments may lead to curative therapies and decrease the number of recurrences and metastases.

Treatment of conjunctival squamous cell carcinoma with photodynamic therapy.

PURPOSE: The aim of this study was to describe the clinical and angiographic response of squamous cell carcinoma (SCC) of the conjunctiva to treatment with photodynamic therapy (PDT). DESIGN: Interventional case series. METHODS: In a prospective study, three patients (62 to 86 years old) with SCC of the conjunctiva were treated with PDT. Patients received one to three treatments of verteporfin (6 mg/m(2) body surface area, intravenously). The light dose was calculated as 50 J/cm(2). All tumors were irradiated 1 minute after injection. The mean follow-up time was 8.6 months (7 to 12 months). Main outcome measurements were clinical and angiographic response and treatment-related side effects. RESULTS: One week after treatment, angiographic occlusion of tumor vasculature and normal conjunctival vessels was observed in all patients. Tumor regression was noted in all patients 1 month after treatment. Two patients had complete regression (clinical and angiographic observation) after one or two treatments for the entire follow-up time. One tumor involved large aspects of the conjunctiva and cornea. In this case, only the treated areas showed tumor regression. PDT caused minimal temporary local irritation in two patients, and small conjunctival hemorrhages and mild transient chemosis in the three eyes directly after treatment. One patient had infusion-related back pain. CONCLUSION: The preliminary results of this study suggest that PDT may be a valuable addition to the treatment of patients with SCC of the conjunctiva. However, longer follow-up is necessary to assess the duration and degree of tumor control.

A case of conjunctival Spitz nevus: review of literature and comparison with cutaneous locations.

We report a case of Spitz nevus of the bulbar conjunctiva in a 15-year-old boy. Clinically, the lesion was juxtalimbic, nodular, red, and 6mm in diameter. Only histologic examination provided the diagnosis. Perusal of the literature revealed seven cases of Spitz nevus of the conjunctiva, but for some of them the histology was incompletely described. We compare the clinical and histologic features in cutaneous and conjunctival nevi and stress the similarity between the two. The histologic criteria which permit differentiation of melanomas and Spitz nevi in conjunctival locations are identified.