Excision combined with ocular surface reconstruction followed by topical chemotherapy for ocular surface squamous neoplasia.

PURPOSE: To investigate the visual prognosis of ocular surface squamous neoplasia (OSSN) after tumor resection and ocular surface reconstruction, and clarify factors that influence recurrence. STUDY DESIGN: Retrospective cohort study. METHODS: Medical records of all patients who underwent surgical treatment for OSSN at our hospital between January 1996 and December 2019 were reviewed. Tumor size/location, histological classification, surgical procedure, intraoperative mitomycin-C use, and postoperative topical 5-fluorouracil (5-FU) administration were examined, and pre and postoperative visual acuity (VA) were compared to elucidate factors that influence disease recurrence. RESULTS: Tumor excision was performed in 70 eyes of 70 cases (43 men, 27 women; average age: 71.6 ± 12.6 years) with dysplasia (8 eyes), carcinoma in situ (26 eyes), and invasive squamous cell carcinoma (36 eyes). Tumors were found in the limbus (N = 59 eyes), palpebral conjunctiva (N = 8 eyes), and from the bulbar to palpebral conjunctiva (N = 3 eyes). Surgical procedures performed were limbal transplantation/keratoepithelioplasty (N = 29 eyes), cultivated oral mucosal epithelial transplantation (N = 3 eyes), and auto-conjunctival epithelium transplantation (N = 2 eyes). Ocular surface was reconstructed using amniotic membrane, donor cornea, or cultivated epithelial sheet. The mean follow-up was 38.6 ± 38.6 months (range, 2 months to 13.8 years). VA postoperatively improved in 25 (61.0%) cases. Recurrence occurred in 19 (27.1%) cases at from 2 to 50 months (median: 12.5 months) postoperative. Uni- and multivariate analyses revealed that presurgical tumor size and postoperative administration of 5-FU were significantly related to recurrence. CONCLUSION: Combined surgical excision and postoperative topical 5-FU administration effectively prevented OSSN recurrence, and ocular surface reconstruction contributed to improvement of VA.

Treatment of ocular surface squamous neoplasia in an Indian rural facility: a study of 38 eyes.

PURPOSE: To report the demographic profile, clinical presentation, and management outcomes of ocular surface squamous neoplasia (OSSN) treated with primary topical chemotherapy in a limited resource secondary eye care facility in rural parts of South India. METHODS: Retrospective interventional study of 38 eyes of 37 patients with OSSN treated with topical 1% 5-Fluorouracil (5FU), over a period of two years. RESULTS: The median age at presentation with OSSN was 44 years (mean, 46 years; range 13 to 74 years). Majority (76%) were males. The most common morphological variant was placoid OSSN (18, 47%). Limbus was the most common epicenter (31, 82%). Corneal OSSN was the most initially misdiagnosed variant (n = 3). Of the 38 eyes receiving one week on and 3-weeks off cycles of 5FU regimen, complete tumor resolution was achieved in 36 (95%) eyes. The median number of topical 5FU cycles for tumor resolution was 2 (mean, 2; range, 1 to 4). Over a median follow-up period of 5 months (mean, 6 months; range, 1 to 27 months), tumor recurrence was noted in 3 eyes (8%), of which one case had xeroderma pigmentosum with bilateral multifocal recurrence. Complication rate was 5% (n = 2), which included transient conjunctival hyperemia (n = 1), and bacterial keratitis (n = 1) which resolved with fortified antibiotics. CONCLUSION: Primary chemotherapy with topical 1% 5FU is a safe and effective management modality for OSSN at limited resource settings in rural India.

Efficacy of topical 5-Fluorouracil in the management of ocular surface squamous neoplasia: a study of 101 eyes.

OBJECTIVE: To study the efficacy and side-effect profile of topical 5-Fluorouracil (5-FU) in the treatment of ocular surface squamous neoplasia (OSSN). METHODS: Retrospective study of 101 eyes of 100 patients treated with 5-FU with one week on and 3 weeks off regimen. RESULTS: Of the 100 patients (101 eyes), the mean age at diagnosis of OSSN was 49 (median, 52 years; range, 11-87 years). History of prior intervention was noted in 6 (6%) eyes. Tumor epicenter included bulbar conjunctiva (n = 54; 53%), limbus (n = 27; 27%), and cornea (n = 20;20%). Mean number of cycles of topical 5-FU administered was 3 (median, 3; range, 1-8). Complete tumor regression was achieved with topical 5-FU in 89 (88%) eyes with a mean number of 2 cycles (median, 2; range, 1-6) of 5-FU. The remaining 12 (12%) lesions underwent additional treatment including excisional biopsy (n = 7), extended enucleation (n = 3), and topical Interferon alpha 2b (n = 2) for complete tumor control. Over a mean follow-up period of 6 months (median, 5 months; range, 1-36 months) following treatment, tumor recurrence was noted in 2 (2%) patients, and side-effects were noted in 7 (7%) eyes including conjunctival hyperemia (n = 1), punctal stenosis (n = 1), sterile keratitis (n = 4), and limbal stem cell deficiency (n = 1). CONCLUSION: Topical 5-FU is an effective non-invasive therapy for OSSN with a minimal side-effect profile.

Conjunctival Intraepithelial Neoplasia Mimicking a Pigmentary Lesion in an HIV-Seropositive Indian Male.

We present the case of a 27-year-old male who presented to our ophthalmology outpatient clinic with a pigmented lesion on the conjunctiva of his right eye. There was no history of ocular trauma or familial ocular complaints, and a thorough evaluation revealed the patient's seropositive status for HIV for the past eight years. The presentation resembled a conjunctival pigmentary lesion, with typical features of ocular surface squamous neoplasia (OSSN) being absent and a demographic incongruent with typical OSSN cases as OSSN typically affects the elderly population. Given the patient's HIV status and the lesion's recent increase in size, a more aggressive treatment approach was warranted. Mass excisional biopsy surgery confirmed conjunctival intraepithelial neoplasia with one positive margin. Adjuvant treatment with mitomycin eye drops (0.04%) resulted in no lesion recurrence at the one-month follow-up. Conjunctival intraepithelial neoplasia can mimic pigmentary lesions in young HIV-positive patients with obvious signs of OSSN being absent. In such cases, the history of seropositivity should be sufficient to suspect it as OSSN and aggressive management measures should be adopted to get best possible outcomes.

Ocular Surface Squamous Neoplasia with Coexistent Pterygia: A Study of 14 Cases and Review of Literature.

PURPOSE: To report the clinical presentation, anterior segment optical coherence tomography features, treatment, and outcomes of ocular surface squamous neoplasia (OSSN) associated with pterygium. METHODS: Retrospective interventional series of 14 cases in a 28-month study period. RESULTS: OSSN was coexistent with pterygium (n = 14) in < 1% of all pterygia (n = 7384). The mean age at the presentation of OSSN with pterygium was 49 years (median, 49 years; range, 36 to 71 years). Referral diagnosis included pterygium sans OSSN (n = 7, 50%), granuloma (n = 1, 7%), actinic keratosis (n = 1, 7%), and conjunctivitis (n = 1, 7%). All OSSNs were unilateral, and six patients (43%) had bilateral pterygia. Tumors arose from the nasal (n = 8, 57%), or temporal (n = 6, 43%) quadrants. The mean tumor diameter was 4 mm (median, 4 mm; range, 2 to 6 mm), and the mean thickness was 2 mm (median, 1 mm; range, 1 to 3 mm). The delineation between OSSN and pterygium could be identified on anterior segment optical coherence tomography (AS-OCT) in all (100%) cases. All patients received 1% topical 5-fluorouracil (5-FU), and complete tumor regression was achieved in 13 (93%) cases with a mean number of 2 cycles (median, two cycles; range, 1 to 4 cycles). There were no significant adverse effects. No tumor recurrence was noted over a mean follow-up period of 11 months (median 12 months; range, 1 to 4 months). CONCLUSION: AS-OCT allows accurate detection and mapping of tumor extent in OSSN with coexistent pterygium, and topical 5-FU yields excellent tumor control.

Xeroderma Pigmentosum With Ocular Surface Squamous Neoplasia: A Case Report.

Xeroderma pigmentosum (XP) is a rare, autosomal recessive disorder characterized by defective DNA repair. Patients with this disorder are at increased risk of developing various oculocutaneous malignancies. We report a rare case of a child with XP with bilateral ocular surface squamous neoplasia (OSSN) and left eye (OS) medial canthal basal cell carcinoma (BCC). Ultrasound biomicroscopy and contrast-enhanced computed tomography (CECT) of the orbit showed intraocular extension with no orbital involvement. The patient was started on topical interferon therapy in both eyes for OSSN. Topical 5% imiquimod was started for BCC for eight hours a day and then washed off. During follow-up, there was no recurrence of tumors. Since ocular and cutaneous neoplasms tend to occur at an early age in XP with a high rate of recurrence and they tend to be more aggressive, multimodal therapy with long-term follow-up is more advantageous for these patients. Topical 5% imiquimod can be used as a treatment for periocular BCC as an alternative to excision.

Topical 5-fluorouracil 1% for moderate to extensive ocular surface squamous neoplasia in 73 consecutive patients: Primary versus secondary treatment.

IMPORTANCE: Ocular surface squamous neoplasia (OSSN) is a spectrum of malignancies that generally includes conjunctival intraepithelial neoplasia (CIN) and squamous cell carcinoma (SCC). OSSN can be treated with topical therapies including interferon α-2b (IFN), mitomycin C (MMC), or 5-fluorouracil 1% (5FU). Recently, due to unavailability of IFN and toxicity associated with MMC, therapy has shifted towards 5FU. OBJECTIVE: Herein, we compare the use of 5FU 1% as a primary versus (vs) secondary treatment regimen in eyes with moderate to extensive OSSN. DESIGN SETTING AND PARTICIPANTS: Retrospective cohort study of 73 consecutive patients with unilateral moderate to extensive OSSN treated at a single tertiary ocular oncology center from 2016 to 2023. Mean follow up time was 478.2 days overall, with 283.0 days for primary 5FU group and 860.3 days for secondary 5FU group. INTERVENTION: Topical 5FU 1% 4 times daily for 2 weeks with option for 2-weekly extension until tumor control, either as primary treatment or as secondary treatment to surgical resection, topical IFN or topical MMC, or cryotherapy. MAIN OUTCOMES: Outcome measures included tumor response, need for additional surgery, complications, and visual outcomes. RESULTS: A comparison (primary vs secondary treatment) revealed no difference in mean tumor basal dimension (19.6 vs 17.2 mm, P = 0.46), thickness (3.7 vs 3.4 mm, P = 0.64), or tumor extent (4.4 vs 4.5 clock hours, P = 0.92). The primary treatment group showed greater complete tumor control (77% vs 38%, P = 0.04). Multivariable analysis comparison (primary vs secondary treatment) showed primary treatment more likely to achieve complete tumor control (P = 0.01). There was no difference in the complication rate from 5FU treatment between the groups. There was no difference in visual outcome, and no tumor-related metastasis (0%) or death (0%). CONCLUSION AND RELEVANCE: Topical 5FU 1% is efficacious and safe as a primary or secondary treatment for moderate to extensive OSSN. Tumors treated with primary 5FU 1% demonstrated more complete resolution. In patients with moderate to extensive OSSN, primary treatment with topical 5FU 1% may be warranted.

Ocular surface squamous neoplasia masquerading as pseudoepitheliomatous hyperplasia in chronic vernal keratoconjunctivitis.

We report a rare case of ocular surface squamous neoplasia (OSSN) masquerading as pseudoepitheliomatous hyperplasia in chronic vernal keratoconjunctivitis (VKC). A 24-year-old man presented with a history of bilateral VKC since childhood with a superior limbal mass in the right eye. There was a history of use of intermittent corticosteroids in the past. He underwent impression cytology followed by excision biopsy with wide margins (no touch technique), cryotherapy and amniotic membrane transplantation. Histopathological analysis confirmed the diagnosis of OSSN with mild to moderate dysplasia. This case highlights the importance of strong clinical suspicion and detailed cytological and histopathological examination for early detection and management of OSSN.

Yes-associated protein-1 overexpression in ocular surface squamous neoplasia; a potential diagnostic marker and therapeutic target.

Yes-associated protein-1 (YAP-1) is a Hippo system transcription factor, which serves as an oncogene in squamous cell carcinoma, and several solid tumors when the Hippo pathway is dysregulated. Yet, the activity of YAP-1 in ocular surface squamous neoplasia (OSSN) has not been determined. Here, we investigate the relationship between YAP-1 overexpression and OSSN. Using a cross-sectional study design, we recruited 227 OSSN patients from the University Teaching Hospitals in Lusaka, Zambia. Immunohistochemistry was used to assess YAP-1 protein overexpression in tumor tissue relative to surrounding benign squamous epithelium. OSSN patient samples (preinvasive, n = 62, 27% and invasive, n = 165, 73%) were studied. One hundred forty-nine invasive tumors contained adjacent preinvasive tissue, bringing the total number of preinvasive lesions examined to 211 (62 + 149). There was adjacent benign squamous epithelium in 50.2% (114/227) of OSSN samples. Nuclear YAP- 1 was significantly overexpressed in preinvasive (Fisher's (F): p <.0001, Monte Carlo (MC): p <.0001) and invasive (F: p <.0001, MC: p <.0001) OSSN in comparison to adjacent benign squamous epithelium when analyzed for basal keratinocyte positive count, staining intensity, expression pattern, and Immunostaining intensity-distribution index. YAP-1 expression did not differ between preinvasive and invasive OSSN (p >.05), keratinizing and non- keratinizing cancer (p >.05), or between T1/T2 and T3/T4 stages in invasive tumors (p >.05). However, grade 2 and 3 tumors had significantly stronger nucleus YAP-1 overexpression intensity than grade 1 tumors (F: p = .0078, MC: p = .0489). By immunohistochemistry, we identified significant overexpression (upregulation of YAP-1 protein expression) in preinvasive and invasive OSSN lesions compared to neighboring benign squamous epithelium. YAP-1 expression was significantly higher in poorly and moderately differentiated invasive squamous cancer than in well-differentiated carcinomas. Overexpression of YAP-1 within the margin of preinvasive and invasive OSSN, but not in the neighboring normal epithelium, indicates that it plays a role in the development and progression of OSSN.

Promotor methylation in ocular surface squamous neoplasia development: epigenetics implications in molecular diagnosis.

INTRODUCTION: Cancer is heavily influenced by epigenetic mechanisms that include DNA methylation, histone modifications, and non-coding RNA. A considerable proportion of human malignancies are believed to be associated with global DNA hypomethylation, with localized hypermethylation at promoters of certain genes. AREA COVERED: The present review aims to emphasize on recent investigations on the epigenetic landscape of ocular surface squamous neoplasia, that could be targeted/explored using novel approaches such as personalized medicine. EXPERT OPINION: While the former is thought to contribute to genomic instability, promoter-specific hypermethylation might facilitate tumorigenesis by silencing tumor suppressor genes. Ocular surface squamous neoplasia, the most prevalent type of ocular surface malignancy, is suggested to be affected by epigenetic mechanisms, as well. Although the exact role of epigenetics in ocular surface squamous neoplasia has mostly been unexplored, recent findings have greatly contributed to our understanding regarding this pathology of the eye.

Corneal epithelial development and homeostasis.

The corneal epithelium (CE), the most anterior cellular structure of the eye, is a self-renewing stratified squamous tissue that protects the rest of the eye from external elements. Each cell in this exquisite three-dimensional structure needs to have proper polarity and positional awareness for the CE to serve as a transparent, refractive, and protective tissue. Recent studies have begun to elucidate the molecular and cellular events involved in the embryonic development, post-natal maturation, and homeostasis of the CE, and how they are regulated by a well-coordinated network of transcription factors. This review summarizes the status of related knowledge and aims to provide insight into the pathophysiology of disorders caused by disruption of CE development, and/or homeostasis.

Clinicopathological profile, management and clinical outcomes in recurrent cases of ocular surface squamous neoplasia at a tertiary care centre.

PURPOSE: This study was taken up to look into the various causes of recurrence, clinicopathological profile and final outcomes in recurrent cases of ocular surface squamous neoplasia (OSSN). METHODOLOGY: A prospective cohort study was conducted and total 18 patients were recruited. All patients were subjected to detailed history, comprehensive eye examination and imaging studies. A treatment plan was formulated based on the size and extent of the lesion. The primary outcome measure was complete response to treatment with no evidence of recurrence after12 months and secondary outcome measure was complication associated with each treatment modality. RESULTS: The common cause of recurrence in our study was misdiagnosis of the lesion as in 15 cases it was diagnosed as pterygium and in 03 cases it was actinic keratosis. Excision Biopsy with adjunctive cryotherapy was the preferred treatment modality followed by topical interferon-alpha 2b drop-in our study. We could achieve good outcomes in terms of complete response to the treatment in 16 cases. The complication associated with this treatment was minimal in our study as few patients complained redness and irritation which subsided after application of topical lubricants. There was no sign of recurrence even at 12 months of follow-up in all 18 cases. CONCLUSION: The current study provided clinicopathological characteristics and treatment outcomes in recurrent cases of OSSN. In our study, adopting appropriate treatment strategy, regular follow-up to assess the response to treatment and change over to new treatment plan in cases with inadequate response helped in achieving good outcomes in recurrent cases of OSSN.

Ocular surface squamous neoplasia with 360° limbal involvement: a study of 130 patients.

PURPOSE: To describe the risk factors, clinical features and management outcomes of ocular surface squamous neoplasia (OSSN) with 360° of limbal involvement (360-OSSN) and compare with segmental limbal involvement (SL-OSSN). METHODS: Retrospective comparative study of 360-OSSN vs SL-OSSN. All 360-OSSN and every 10th patient with SL-OSSN during the study period (2012-2020) were included. Lesions with uncertain diagnosis were excluded. RESULTS: Of 1250 patients diagnosed with OSSN during the study period, 30 (2%) had 360-OSSN. A total of 100 patients of OSSN with SL-OSSN were included for comparison. 360-OSSN patients more often had longer duration of symptoms (mean, 17 vs 8 months; p, 0.003), prior misdiagnosis (17% vs 6%, p, 0.13) and prior intervention (47% vs 13%; p, 0.0002) than patients with SL-OSSN. 360-OSSN had higher incidence of scleral fixity (57% vs 16%; p < 0.0001), corneal/scleral melt (17% vs 0%; p, 0.0005), intraocular tumor extension (17% vs 0%; p, 0.003), orbital tumor extension (33% vs 1%; p < 0.0001), and advanced T stage at presentation (Tis: 37% vs 76%, T1: 0% vs 15%; T2: 7% vs 4%; T3: 27% vs 4%; T4: 30% vs 1%; p < 0.001). Over a mean follow-up of 14 months, lymph node metastasis (8% vs 0%; p, 0.05) and distant metastasis (4% vs 0%; p, 0.23) were more common in 360-OSSN group compared to SL-OSSN group. CONCLUSION: Risk factors of 360-OSSN include prolonged symptoms, prior misdiagnosis and prior intervention. It represents an advanced form of disease with propensity for corneo-scleral melt and invasive disease which requires aggressive management.

Brachytherapy as a curative option for ocular surface squamous neoplasia.

PURPOSE: Ocular surface squamous neoplasia (OSSN) has a high recurrence rate if only treated with surgical excision, especially in cases with positive excision margins. To reduce recurrence, we used brachytherapy after surgical excision for limbal and bulbar lesions in addition to chemotherapy/immunotherapy, cryotherapy, or external beam radiotherapy as adjunctive or primary therapies. METHODS: Nine eyes with isolated OSSN lesions were included in the study. Adjunctive brachytherapy with Ruthenium106-plaques was administered. The follow-up included regular biomicroscopic slit-lamp examination and photo-documentation. Additionally, a staging check for metastasis was performed in cases with squamous cell carcinoma (SCC). RESULTS: The average age of patients at the time of presentation was 66 ± 12 years. Follow-up time was 52.8 ± 44.6 months. The maximal tumour base varied between 3 and 28 mm. SCC was confirmed by histology in all cases. No recurrences were recorded during the follow-up, and organ salvage and eye function preservation were achieved. Radiotherapy-induced complications included secondary glaucoma (n = 1) and scleral melting (n = 1). Other complications, such as radiogenic retinopathy, were not observed. CONCLUSION: Brachytherapy with Ruthenium106-plaques offers an additional option for adjunct treatment of limbal and bulbar OSSN presenting with only a focal spread. Organ salvage can be achieved with a low complication rate and recurrence-free survival. This technique offers globe salvage in patients with tumours involving intraocular infiltration.

Treatment of ocular-involving monkeypox virus with topical trifluridine and oral tecovirimat in the 2022 monkeypox virus outbreak.

Purpose: To report a case of ocular involving monkeypox infection in the United States during the 2022 outbreak, and to review the literature regarding its clinical manifestations and management known to date. Observations: A 36-year-old man with well controlled HIV presented to the emergency department with anal pain, diffuse rash, right eye pain, and right eye redness after he tested positive for monkeypox one week prior. Ocular examination showed bilateral periorbital vesicular lesions, right eye conjunctival injection, and a single white plaque on his right medial bulbar conjunctiva. Macular, vesicular, and pustular lesions were noted throughout his body, including the genital and perianal region. His ocular and systemic symptoms completely resolved after treatment with a ten-day course of 1% trifluridine and moxifloxacin drops in both eyes, as well as two weeks of oral tecovirimat. Conclusion and Importance: In July of 2022, monkeypox virus was declared a global health emergency by the World Health Organization; however, there are no standard guidelines for monkeypox treatment. Data on its clinical presentation and course, especially pertaining to ocular manifestations, is limited. We highlight the importance of recognizing ophthalmic manifestations of monkeypox virus and a possible therapeutic approach to help guide the management of these patients.

Ocular Surface Squamous Neoplasia: A 12-Month Prospective Evaluation of Incidence in Waikato, New Zealand.

Ocular surface squamous neoplasia (OSSN) has a high incidence in the southern hemisphere. This prospective study evaluated the incidence of OSSN in the Waikato region of New Zealand. All patients presenting with pterygium or conjunctival lesions in the Waikato region in 2020 were included. All surgeons in the region were asked to send all conjunctival and corneal specimens excised for histopathologic examination. The primary outcome measure was the incidence of OSSN. Eighty-eight percent of all excised specimens were sent for histopathologic examination. Of the 185 excised lesions sent for histopathological assessment, 18 (10%) were reported as OSSN. Patients were on average 69.4 years of age (standard deviation, SD = 6.9), predominantly male (78%), and of New Zealand-European ethnicity (89%). The OSSN annual incidence was 3.67/100,000/year. Histology grades included conjunctival intraepithelial neoplasia (CIN)-I (25%), CIN-II (25%), CIN-III (12.5%), carcinoma in situ (25%), and invasive squamous cell carcinoma (SCC) (12.5%). One patient with invasive SCC required exenteration. This study identified a high incidence rate of OSSN and is the first prospective study to analyze OSSN epidemiology in New Zealand.

Metastatic conjunctival squamous cell carcinoma: a study of 5 patients.

PURPOSE: To describe the risk factors, clinical features, management, and outcomes in patients with metastatic conjunctival squamous cell carcinoma (mcSCC). METHODS: Retrospective comparative study. RESULTS: Of the 1192 cases with ocular surface squamous neoplasia during the study period, 654 (55%) patients were biopsied and 223 (19%) had invasive squamous cell carcinoma (cSCC). Of these 223 patients with cSCC, locoregional metastasis developed in 4 (2%) and distant metastasis in 1 (0.4%) patient. Mean age at diagnosis of OSSN was 48 years (median, 40 years; range 35-74 years). Tumors belonged to T2 (n = 2; 40%) and T4a (n = 3; 60%) at presentation. Primary treatment modalities included topical and subconjunctival interferon α 2B immunotherapy (n = 2; 40%), extended enucleation (n = 1; 20%) and orbital exenteration (n = 2; 40%). Metastases were noted after a mean period of 22 months of onset of primary tumor (median, 18 months; range 2-46 months). Death from metastatic disease occurred in all patients over a mean follow-up period of 21 months (median, 11 months; range 1-46 months). Bivariate regression analysis revealed smoking (p = 0.037, Odds Ratio (OR) = 0.13), tumor thickness ≥ 5 mm (p = 0.015, OR = 17.78), orbital invasion (p = 0.018, OR = 1.00), and poor histopathological differentiation (p = 0.031, OR = 10.44) to be significant risk factors for mcSCC. CONCLUSION: Metastatic disease in cSCC is rare and risk factors for metastasis include smoking, thicker tumors, orbital tumor extension, and poor tumor differentiation. mcSCC is associated with high mortality.

miR-196b-5p and miR-107 Expression Differentiates Ocular Sebaceous Carcinoma from Squamous Cell Carcinoma of the Conjunctiva.

An Ocular Sebaceous Carcinoma (OSC) is a rare malignant tumor for which initial clinical and pathological diagnosis is often incorrect. OSCs can mimic Squamous Cell Carcinomas of the Conjunctiva (SCCC). The aim of this study was to find microRNA biomarkers to distinguish OSCs and SCCCs from normal tissue and from each other. Clinical OSC and SCCC case files and the corresponding histopathological slides were collected and reviewed. Micro dissected formalin-fixed paraffin-embedded tumor and control tissues were subjected to semi-high throughput microRNA profiling. MicroRNA expression distinguishes OSCs and SCCCs from corresponding control tissues. Selected differentially expressed miRNAs were validated using single RT-PCR assays. No prognostic miRNAs could be identified that reliably predict SCCC metastasis or OSC recurrence. A comparison between OSCs (n = 14) and SCCCs (n = 18) revealed 38 differentially expressed microRNAs (p < 0.05). Differentially expressed miRNAs were selected for validation in the discovery cohort and an independent validation cohort (OSCs, n = 11; SCCCs, n = 12). At least two miRNAs, miR-196b-5p (p ≤ 0.05) and miR-107 (p ≤ 0.001), displayed a statistically significant differential expression between OSCs and SCCCs with miR-196b-5p upregulated in SCCCs and miR-107 upregulated in OSCs. In the validation cohort, microRNA miR-493-3p also showed significant upregulation in SCCCs when compared to OSCs (p ≤ 0.05). ROC analyses indicated that the combined miR-196b-5p and miR-107 expression levels predicted OSCs with 90.0% sensitivity and 83.3% specificity. In conclusion, the combined testing of miR-196b-5p and miR-107, can be of additional use in routine diagnostics to discriminate OSCs from SCCCs.

Amniotic Membrane Grafting for Ocular Surface Inflammation Following Topical Interferon Alpha 2b Therapy.

We describe a rare case of a 58-year-old female with ocular surface squamous neoplasia (OSSN) in her left eye. She was treated for 12 months with topical interferon alpha-2b (IFNα-2b) eye drops and OSSN resolved completely. She presented with a whitish elevated lesion involving the cornea, limbus, and conjunctival surface after discontinuation of topical IFNα-2b. Excision biopsy along with amniotic membrane grafting was done to stabilize the ocular surface. Histopathological evaluation of the excised tissue revealed ocular surface inflammation with no evidence of malignancy.