The prevalence of human papillomavirus in ocular surface squamous neoplasia in HIV positive and negative patients in a South African population.

PURPOSE: To assess the prevalence and subtypes of Human Papillomavirus (HPV) in Ocular Surface Squamous Neoplasia (OSSN) in Human Immunodeficiency Virus (HIV) positive and negative patients in South Africa. BASIC PROCEDURES: This study was a single center retrospective cross-sectional study, conducted at Tygerberg Hospital, Western Cape, South Africa. We assessed 63 histopathologically confirmed OSSN formalin-fixed paraffin-embedded (FFPE) tissue blocks from 2015-2023. The presence of HPV was determined using the Hybrispot Direct Flow Chip Kit. Corresponding clinical data was retrieved from the National Health Laboratory Service (NHLS) central data warehouse. MAIN FINDINGS: Of the confirmed OSSN samples, 66.7% tested positive for HPV (95% confidence interval [CI] 54-77.3%). Of the 42 HPV positive samples, 38 (90.5%) had one or more known genotypes detected and 4 had unknown genotypes. The most prevalent subtypes were HPV 11, 16 and 18 (found in 61.9%, 52.4% and 33.3% of HPV positive samples respectively). 88.9% of the lesions biopsied were from HIV positive patients, of whom 56.4% had a CD4 + count of < 200 cells/µL. A lower median CD4 + count was detected among HIV positive patients with invasive squamous cell carcinoma compared to those with moderate dysplasia (p < 0.0198). CONCLUSIONS: There is a high prevalence of HPV in OSSN in South Africa. Certain subtypes namely, 11, 16, 18, 31, 33 and 35 may be more carcinogenic. HIV with HPV co-infection may be linked as a causative factor in the development of OSSN.

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.

Efficacy, safety and cost-effectiveness of 5-fluorouracil versus interferon α-2b as adjuvant therapy after surgery in ocular surface squamous neoplasia in a southern European tertiary hospital.

PURPOSE: To analyze the efficacy, safety and cost-effectiveness of adjuvant therapy with 5-fluorouracil (5-FU) compared to interferon α-2b (IFNα-2b) after surgery in ocular surface squamous neoplasia (OSSN). METHODS: Retrospective study that included patients diagnosed with OSSN, who underwent surgical excision followed by adjuvant therapy with IFN α-2b (Group A) or 5-FU (Group B), in a tertial referral hospital. Clinical data collected included: demographics, risk factors, appearance, size and location of the lesions, slit-lamp examination, anterior segment optical coherence tomography, iconography and histological classification of subtypes of OSSN. Costs derived from surgery and adjuvant therapy were noted. Resolution of the lesion, recurrences and adverse events were studied. Cost-effectiveness analysis was performed with the incremental cost-effectiveness index (CEI). RESULTS: 54 cases of 54 patients were included, with a mean age of 74.4 years (range 28-109). 30 were male (55.6%), and predominantly Caucasian (79.6%). The main risk factor was prolonged sun exposure (79.6%). Leukoplakic appearance (48.1%), location in bulbar conjunctiva (48.2%) and T3 (46.3%) stage were the most common clinical features. Histologically, the percentage of CIN I, CIN II, CIN III and SCC were 25.9%, 29.6%, 40.7% and 3.7%, respectively. Complete resolution was obtained in 74.1% and tolerance was overall positive. The cost was significantly higher for IFNα (1025€ ± 130.68€) compared to 5-FU (165.57€ ± 45.85 €) (p 0.001). The CEI was - 247.14€. CONCLUSIONS: Both 5-FU and IFN α-2b are effective and present a good security profile as adjuvant therapies after surgery in OSSN. Although presenting slightly more ocular complications, 5-FU can be considered more cost-effective than IFN α-2b.

Novel ocular immunotherapy induces tumor regression in an equine model of ocular surface squamous neoplasia.

Ocular surface squamous neoplasia (OSSN) is the major cause of corneal cancer in man and horses worldwide, and the prevalence of OSSN is increasing due to greater UVB exposure globally. Currently, there are no approved treatments for OSSN in either species, and most patients are managed with surgical excision or off-label treatment with locally injected interferon alpha, or topically applied cytotoxic drugs such as mitomycin C. A more broadly effective and readily applied immunotherapy could exert a significant impact on management of OSSN worldwide. We therefore evaluated the effectiveness of a liposomal TLR complex (LTC) immunotherapy, which previously demonstrated strong antiviral activity in multiple animal models following mucosal application, for ocular antitumor activity in a horse spontaneous OSSN model. In vitro studies demonstrated strong activation of interferon responses in horse leukocytes by LTC and suppression of OSSN cell growth and migration. In a trial of 8 horses (9 eyes), treatment with topical or perilesional LTC resulted in an overall tumor response rate of 67%, including durable regression of large OSSN tumors. Repeated treatment with LTC ocular immunotherapy was also very well tolerated clinically. We conclude therefore that ocular immunotherapy with LTC warrants further investigation as a novel approach to management of OSSN in humans.

Local ocular safety of the subconjunctival injection of cetuximab in rabbits.

BACKGROUND: To evaluate the safety of different doses of subconjunctival cetuximab in rabbits. METHODS: After general anesthesia rabbits received a subconjunctival injection of 2.5 mg in 0.5 ml, 5 mg in 1 ml, and 10 mg in 2 ml of cetuximab in their right eyes (two rabbits in each group). A similar volume of normal saline solution was injected subconjunctivally in the left eyes. The histopathologic changes were evaluated after enucleation with the aid of H&E staining. RESULTS: No significant difference were observed between the treated and control eyes in terms of conjunctival inflammation, goblet cell density, or limbal blood vessel density for all administered doses of cetuximab. CONCLUSION: Subconjunctival injection of cetuximab with the administrated doses in rabbit eyes are safe.

Safety and efficacy of topical interferon alpha 2B and mitomycin C for localized conjunctival intraepithelial neoplasia: long-term report of their pharmacological safety and efficacy.

PURPOSE: Ocular surface squamous neoplasia (OSSN) comprises a wide spectrum of squamous tumors, from which corneal/conjunctival intraepithelial neoplasia (CIN) is the most common one. The classic treatment is complete excision, but recurrence rates are high. Antineoplastic drugs such as mitomycin C (MMC) and interferon alpha 2b (IFNα2b) have been used as adjuvants or as primary treatment. To evaluate the efficacy and safety of topical IFNα2b and MMC in patients with CIN, a phase IIb double-blind clinical trial was performed. METHODS: Patients diagnosed with localized CIN were evaluated by slit lamp and impression cytology and were randomly given MMC 0.04% or INF2b (1 million IU/mL) 4 times daily until neoplasia resolution. Time of resolution and frequency of adverse effects were analyzed to determine the pharmacological efficacy and safety of both medications. RESULTS: Seventeen patients were included. Nine patients were treated with MMC and 8 with IFNα2b. All patients responded to treatment. The resolution time in days was 59.11 ± 24.02 in patients treated with MMC and 143.50 ± 47.181 in those treated with IFNα2b (p < 0.001). In the MMC group, one recurrence was reported (11%). There were no recurrences at 2 years of follow-up in the IFNα2b group. Regarding adverse effects, one or more mild adverse reaction occurred in 77% of patients managed with MMC and in 50% of patients managed with IFNα2b (p > 0.05). No serious adverse effects were reported. CONCLUSIONS: Topical chemotherapy with MMC and IFNα2b demonstrate pharmacological safety and efficacy. Therefore, these drugs could be considered as primary therapies for localized CIN .

Efficacy and safety of topical 5-fluorouracil in conjunctival intraepithelial neoplasia refractory to interferon alpha-2b.

PURPOSE: To report the efficacy and safety of 5-fluorouracil as the second line of treatment for two cases of conjunctival intraepithelial neoplasia refractive to topical interferon alpha-2b. CASE REPORT: In the first case, a 77-year-old woman was evaluated because of a fleshy vascularized lesion in the temporal conjunctiva on her right eye with leukoplakia of the corneal epithelium from 10- to 5-o'clock limbus. In the second case, an 81-year-old man, a nodular lesion in the temporal conjunctiva on his RE, with corneal adjacent opalescence, one millimeter in extent, was observed. Both patients were initially treated with excisional surgery, the samples being reported as conjunctival intraepithelial neoplasia with high-grade dysplasia. Co-adjuvant treatment with topical interferon alpha-2b 1 mIU/mL was indicated 4 times/day uninterruptedly. In the first case, there was no response despite 8 months of treatment, while in the second, the corneal lesion progressed in an arboriform pattern after 4 months of topical chemotherapy. MANAGEMENT & OUTCOME: In the absence of efficacy, the treatment was then changed to topical 5-fluorouracil (1%), 4 times/day for 7 days with a time-lapse of 21 days off, which constitutes a course. Two and four courses of treatment with 5-fluorouracil 1% were completed in both cases in the absence of important side effects. After the first course, both patients showed complete remission of the lesions. No clinical signs of relapse were noted after 1 year of follow-up. DISCUSSION: The treatment with 5-fluorouracil is a good option as the second line of treatment for conjunctival intraepithelial neoplasia who are low-responders to interferon alpha-2b, with fewer side effects than other currently available alternatives.

Therapy Failure and Resistance Mechanism in Eyelid and Ocular Surface Tumors.

Malignant tumors of the eyelids and ocular surface are common ocular malignancies. At present, surgical treatment is mostly the first choice for these types of tumors. However, postoperative tumor recurrence and metastasis are still regarded as failures in the treatment of such malignancies. Based on this, malignant tumors of the eyelid and ocular surface are sometimes accompanied by local adjuvant chemotherapy and systemic chemotherapy to treat patients with relapse, invasion of adjacent tissues, and systemic metastases. Still, drug resistance greatly affects the treatment effect. This review lists several mechanisms of recurrence and metastasis of ocular surface and eyelid tumors after surgery, as well as mechanisms that may lead to non-surgical treatment or drug resistance.

Ocular surface squamous neoplasia in Northern Thailand: a 16-year review.

PURPOSE: To evaluate clinical characteristics, treatments, and outcomes in patients with ocular surface squamous neoplasia (OSSN) at a tertiary center in Northern Thailand. METHODS: Patients diagnosed with either corneal-conjunctival intraepithelial neoplasia (CIN) or squamous cell carcinoma (SCC) from May 2000 to December 2015, were recruited. The patients' demographics, symptoms, clinical characteristics, cytopathology, treatments, and outcomes were reviewed. RESULTS: Overall 171 eyes from 168 patients, 92 eyes were CIN and 79 eyes were SCC. Males were affected in 65.5%. The mean age was 58.8 ± 16.8 (29-99) years. In most cases (60.3%), the tumors were located at the limbus. The most common clinical characteristic was papilliform appearance (46.2%). Human immunodeficiency virus (HIV) infection was found in 37 (22.0%) patients with a mean age of 40.5 ± 7.7 years. The treatments and outcomes were evaluated in 136 eyes whose main initial treatment was wide excision with adjunctive cryotherapy (47.8%), followed by topical mitomycin C (30.9%). The mean follow-up time after treatment was 20.8 ± 2.2 (3-110) months and the recurrence occurred in 18 eyes (13.2%) during the follow-up period. The mean recurrence-free time (months) for CIN was significantly longer than that of SCC (81.3 ± 10.0 [95%CI 61.5 - 101.1] vs 33.2 ± 4.6 [95%CI 24.0 - 42.3], p = 0.030). SCC was the only significant risk factor that influences the recurrence of the tumors with the adjusted hazard ratio of 5.69 (p = 0.005). CONCLUSION: OSSN in Northern Thailand usually involved a limbal area and presented as a papilliform mass. HIV infection should be suspected in young patients. CIN had better outcomes after treatments than invasive SCC.

The Management of Ocular Surface Squamous Neoplasia (OSSN).

The rise of primary topical monotherapy with chemotherapeutic drugs and immunomodulatory agents represents an increasing recognition of the medical management of ocular surface squamous neoplasia (OSSN), which may replace surgery as the standard of care in the future. Currently, there is no consensus regarding the best way to manage OSSN with no existing guidelines to date. This paper seeks to evaluate evidence surrounding available treatment modalities and proposes an approach to management. The approach will guide ophthalmologists in selecting the most appropriate treatment regime based on patient and disease factors to minimize treatment related morbidity and improve OSSN control. Further work can be done to validate this algorithm and to develop formal guidelines to direct the management of OSSN.

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.

Ocular surface squamous neoplasia in India: a study of 438 patients.

PURPOSE: To describe the clinical features, histopathology, treatment, and outcomes of patients with ocular surface squamous neoplasia (OSSN) presenting to a referral centre in India. METHODS: Retrospective interventional study. RESULTS: Of 438 patients, the mean age at presentation was 49 years. Human immunodeficiency virus infection was noted in 72 (16%), xeroderma pigmentosum in 22 (5%), hepatitis B virus infection in 14 (3%), and systemic cancer in 8 (2%) patients. Tumor pigmentation was noted in 243 (54%) tumors with a mean percentage of tumor pigmentation of 44% (median, 40%; range, 1 to 100%). Intraocular tumor extension was noted in 12 (3%), and orbital tumor extension in 16 (4%) eyes. Of the 381 treated lesions, excisional biopsy (n = 247; 65%) was the most common treatment modality. Of the 311 lesions with histopathology diagnosis of OSSN, invasive squamous cell carcinoma (n = 92; 30%) was the most common. Over a mean follow-up period of 11 months (median, 5 months; range, 1 to 108 months) in 368 patients, tumor recurrence was noted in 16 (4%) eyes, globe salvage was achieved in 341 (90%) eyes, vision salvage in 338 (89%) eyes, regional lymph node metastasis occurred in 9 (2%), and metastasis-related death in 9 (2%) patients. CONCLUSION: Pigmented OSSN is common in Asian Indian population. Appropriate management of OSSN is associated with good vision, globe, and life salvage rates in India.

Clinicopathological characteristics of ocular surface squamous neoplasia: a 10-year review form a referral tertiary centre in Nigeria.

BACKGROUND: Ocular surface squamous neoplasia (OSSN) is a heterogeneous group of proliferative squamous lesions on the ocular surface with varying biologic behaviours. This study aims to report the clinical profile and pathological characteristics of cases of OSSN seen at a tertiary referral centre in North West Nigeria. METHODS: A retrospective review of all cases of OSSN diagnosed over a 10-year period was done. RESULTS: OSSN accounted for 68 out of 91 ocular surface lesions affecting twice as many males as females and a peak incidence in the 30-39 years age group. They frequently presented as higher-grade and higher-stage lesions with invasive squamous cell carcinoma being the most frequently diagnosed OSSN. They also frequently showed an association with HIV infection and a relatively long duration of symptoms before presentation. CONCLUSION: OSSN occurs in a relatively young age group in our environment. Certain clinical and epidemiological features appear to predict the occurrence of higher-grade lesions, and this may help in the clinical prediction of likely pathologic grade and/or biologic behaviour of these lesions.

Advanced ocular surface squamous cell carcinoma (OSSC): long-term follow-up.

PURPOSE: To analyze the clinical characteristics and long-term follow-up of patients with advanced ocular surface squamous cell carcinoma (OSSC) involving periocular tissues and/or orbit. Primary outcomes were overall survival (OS), disease-free survival (DFS), and overall recurrence rate (RR). Secondary outcomes were a correlation between primary outcomes and tumor location, American Joint Committee on Cancer Classification (AJCC) staging system, histological results, surgical margins, and type of treatment. STUDY DESIGN: a retrospective case series. METHODS: The medical records of patients affected by OSSC involving periocular tissues and/or orbit referring, from 01/2011 to 01/2020, to our tertiary referral center were reviewed. RESULTS: Thirty-six eyes of 36 patients were included. The mean age was 68.2 years; 18 (50%) patients were males. The mean follow-up was 40 months. The RR was 64%. The OS at 12, 24, 36, and 60 months was respectively 97.1%, 92.7%, 92.7%, and 92.7%. The DFS at 12, 24, 36, and 60 months was respectively 62.9%, 50.8%, 41.6%, and 29.7%. Multicentric disease (p = 0.0039), inferior tarsus localization (p = 0.0428), histological diagnosis of high-risk SSCs (p = 0.0264), positive surgical margins (p = 0.0434), and excisional biopsy (EB) alone (p = 0.0005) were associated with an increased risk of recurrence. A shorter OS was observed in patients who underwent EB alone (p = 0.0049). CONCLUSION: OSCC involving periocular tissues and/or orbit is an aggressive disease with a high recurrence rate. Multicentric disease, positive surgical margins, inferior tarsus localization, and surgery without adjuvant therapies are strong predictors of recurrence and are the main factors affecting prognosis.

Anterior segment optical coherence tomography features of pseudoepitheliomatous hyperplasia of the ocular surface: a study of 9 lesions.

PURPOSE: To describe anterior segment optical coherence tomography (AS-OCT) features of pseudoepitheliomatous hyperplasia (PEH) of the ocular surface. METHODS: This is a retrospective study of 9 lesions of 8 patients with histopathologically proven PEH RESULTS: Mean age at diagnosis of PEH was 31 years (median 31 years; range 12 to 62 years). The lesion was unilateral in 7 (88%) patients and bilateral in one (12%). Two patients (25%) had xeroderma pigmentosum, who also had a history of prior surgical intervention in the same eye for conjunctival tumor excision. Referral diagnosis was ocular surface squamous neoplasia (OSSN) in all cases. Ocular surface mass (n = 4, 44%) was the most common presenting complaint. The mean duration of symptoms was 18 months (median 3 months; range < 1 to 84 months). All lesions were perilimbal, and the mean basal diameter of the tumor was 7 mm (median 6 mm; range 4 to 12 mm). Clinical diagnosis included OSSN (n = 5; 56%), PEH (n = 3; 33%), or leiomyosarcoma (n = 1; 11%). AS-OCT features included irregular hyperreflective epithelium, epithelial dipping, and subepithelial hyperreflective lesion with posterior shadowing in all cases. Histopathology confirmed the diagnosis of PEH in all cases. The underlying cause of PEH in these cases included vernal keratoconjunctivitis (n = 4; 44%), idiopathic severe blepharitis (n = 2; 22%), or prior surgical intervention (n = 2; 22%). No apparent cause could be determined in one eye (11%). CONCLUSION: Ocular surface PEH is a close mimicker of OSSN. Careful history-taking, clinical examination, and characteristic AS-OCT features aid in accurate diagnosis.

Ocular surface squamous neoplasia at a tertiary eye facility, Southwestern Nigeria: a 10-year review.

BACKGROUND: Ocular surface squamous neoplasia (OSSN) is a low-grade malignancy arising from the squamous epithelium of the ocular surface AIM: To describe the clinical presentation, histological diagnoses, treatment, and outcome of treatment in patients with OSSN managed at a tertiary health facility. METHODS: Medical records of all patients with OSSN managed using a standardized treatment protocol over a 10-year period were reviewed. RESULTS: Eighty-six patients comprising 44 (51.2%) males and mean age of 48.2 ± 15.8 years were studied. The most common presentation was a fleshy growth in the eye in all patients, and 43 (50.0%) patients tested positive to human immunodeficiency virus. The right eye was affected in 44 (51.2%) patients with no bilateral tumors, and the medial limbus was involved in 28 (32.6%) patients. Morphologically, 40 (46.5%) patients had gelatinous growth, 24 (27.9%) patients were in Tis category while 30 (34.9%) patients were in T4 category. Twenty-eight (32.6%) patients received complete course of adjuvant topical mitomycin C (0.04%) while nine (10.5%) patients completed adjuvant systemic chemotherapy and external beam radiation. Overall, 61 (70.9%) patients had no tumor recurrence, seven (8.1%) patients had recurrent tumor, while the status of 18 (20.9%) patients was not known. CONCLUSION: OSSN occurs more commonly in younger age group in our studied population and is strongly associated with HIV seropositivity. Intraoperative cryotherapy in patients with carcinoma in situ and intraoperative cryotherapy with adjuvant topical mitomycin C in those with invasive SCC that is limited to the ocular surface are associated with low tumor recurrence.

Non-malignant conjunctival epithelial masses with ocular surface squamous neoplasia-like optical coherence tomography features.

PURPOSE: To observe and describe the anterior segment optical coherence tomography features of limbally localised non-malignant epithelial mass lesions METHODS: Thirteen patients (age: 66.9 ± 16.3 years) with conjunctival mass suggesting ocular surface squamous neoplasia with biomicroscopic examination were imaged using anterior segment ocular coherence tomography (anterior segment optical coherence tomography)/Cirrus HD-OCT, Model 4000, Carl Zeiss Meditec, Inc., Dublin, CA, and Spectralis HRA + OCT system, Heidelberg Engineering, Vista, CA/. Cases with ocular surface squamous neoplasia-like anterior segment optical coherence tomography (hyperreflective, thickened epithelium and an abrupt transition from normal to abnormal) were included in the study. Maximal thickness of the epithelium was measured. Histological diagnosis was gained from an excisional or incisional biopsy or impression cytology specimens. RESULTS: In six patients (age: 68.5 ± 15.4 years) with ocular surface squamous neoplasia-like anterior segment optical coherence tomography features, the histological diagnosis was other than ocular surface squamous neoplasia (papilloma, parakeratosis and a keratotic plaque with mild dysplasia), and ocular surface squamous neoplasia in seven cases (age: 65.6 ± 18.0 years). The maximal epithelial thickness was between 250 and 859 µm in non-ocular surface squamous neoplasia cases and between 252 and 596 µm in ocular surface squamous neoplasia cases. CONCLUSION: Non-malignant epithelial lesions can mimic ocular surface squamous neoplasia on anterior segment optical coherence tomography.

Comparative evaluation of clinical characteristics of biopsy-proven conjunctival intraepithelial neoplasia and invasive squamous cell carcinoma using image processing software programs.

PURPOSE: To identify morphological parameters aiding clinical differentiation of conjunctival intraepithelial neoplasia (CIN) and invasive squamous cell carcinoma (iSCC) and to demonstrate the utility of image processing software to objectively assess ocular surface squamous neoplasia (OSSN). METHODS: This retrospective case series included all biopsy-proven cases of OSSN presenting as an ocular surface nodule. Based on histopathology, lesions were classified as CIN and iSCC. Clinical image analysis utilized 'Contour' and 'ImageJ' software. The effect of predictors demography, seropositivity, lesion dimensions, keratin, pigmentation, corneal involvement, vascularity and feeder vessels on the final histopathologic grade were assessed. RESULTS: A total of 108 OSSN lesions (74 CIN and 33 iSCC) were included. Mean age was 46.1 ± 17.2 years in CIN and 47.2 ± 13.9 years in iSCC. By univariate logistic regression analysis, significant predictors of iSCC were HIV seropositivity (p < 0.0001), maximum diameter (p = 0.003), perpendicular to maximum diameter (p = 0.003), height (p = 0.003), nodular morphology (p = 0.006) and feeder vessels (p = 0.03), whereas gelatinous morphology (p = 0.02) was predictor of CIN. By multiple logistic regression, seropositivity was the predictor of iSCC (p < 0.0001, OR 13.33 ± 8.35, 95% CI 3.90-45.53). CONCLUSION: HIV seropositivity is an important predictor of iSCC. Large, thick, nodular lesions with feeder vessels may favor the diagnosis of iSCC, whereas gelatinous, small, flatter lesions without feeder vessels may favor CIN. In a first of its kind study, simple and objective analysis of OSSN with image processing software was demonstrated.

Role of oncogenic viruses in the development ocular surface squamous neoplasia.

PURPOSE: The pathogenesis of ocular surface squamous neoplasia is not fully understood. Therefore, we evaluated the role of oncogenic viruses in the pathogenesis of ocular surface squamous neoplasia in Israel. METHODS: Patients with ocular surface squamous neoplasia were enrolled in this retrospective study. The specimens were taken during 2004-2015 from two big centers: Emek Medical Center, Afula and the Hadassah Medical Center, Jerusalem. All the specimens (totally 26) were analyzed by immunohistochemistry for evidence of oncogenic viruses that included Human Papilloma virus, Herpes Simplex virus and Cytomegalovirus infection and 14 samples were examined by polymerase chain reaction. In addition, all the samples were examined for Epstein Barr virus infection by immunohistochemistry and Epstein Barr encoding region test. RESULTS: Twenty-six patients were included with a mean age of 61.81 [Formula: see text] 3.83 years (mean [Formula: see text]. Immunohistochemistry staining and Epstein Barr encoding region test did not detect any of the oncogenic viruses in the 26 samples. Human Papilloma virus-16 and -18, and Herpes Simplex virus were detected by polymerase chain reaction in 14.2%, 7% and 7%, respectively. CONCLUSION: We conclude from our study that oncogenic viruses may play a role in the pathogenesis of ocular surface squamous neoplasia in Israel.