Anterior High-Resolution Optical Coherence Tomography in the Diagnosis and Therapeutic Monitoring of Ocular Surface Squamous Neoplasia.

Ocular surface squamous neoplasia (OSSN) is the most common tumor of the ocular surface, ranging from mild dysplasia to invasive squamous carcinoma. Traditionally, the diagnosis of OSSN relies on histopathological confirmation followed by a full-thickness biopsy. However, in the past two decades, the therapeutic approach to OSSN has shifted from surgical intervention to topical chemotherapy regimens in clinical settings. This shift emphasizes the need for less invasive or non-invasive methods to diagnose ocular surface pathologies. Among various imaging devices, commercially available high-resolution optical coherence tomography (HR-OCT) has emerged as a powerful tool for the characterization of OSSN. HR-OCT provides an in vivo, cross-sectional view of ocular surface lesions, offering an "optical biopsy" for OSSN with high sensitivity and specificity. It provides valuable information in differentiating intraepithelial or invasive OSSN from other benign lesions. Additionally, HR-OCT can be used to monitor the response to topical chemotherapy and to detect subclinical OSSN during follow-up visits. In this article, the scanning protocol for image acquisition is presented, and image interpretation for OSSN is outlined. This standardized, practical, and reproducible approach is recommended in clinical workflows and is expected to assist clinicians in the management of OSSN.

Exclusive Ru-106 brachytherapy for the management of a recurrent corneo: Conjunctival squamous cell carcinoma.

BACKGROUND: We report a case of personalized exclusive brachytherapy treatment for the management of a highly recurrent squamous cell conjunctival carcinoma with corneal invasion. CASE DESCRIPTION: This is a case of a Caucasian 81-years-old man who presented 10 years ago to our clinic with a pink-white para-limbal mass with dilated feeder arteries and mild leukoplakia. Excisional biopsy confirmed the presence of conjunctival intraepithelial neoplasia (CIN). Successively, he underwent two 4-weeks cycles of Mytomicin C topical therapy and a second excisional surgery, due to several recurrences of the lesion. At the last relapse, the pink-white peri-limbic mass which invaded the corneal limbus, determining corneal opacification from 5- to 7-clock hours, was confirmed by anterior segment optical coherence tomography (AS-OCT). Due to resistance to MMC therapy and chronic epitheliopathy, an AS-OCT guided exclusive radiotherapy plan was set: a Rhutenium-106 CCD plaque was applied directly over the afflicted corneal surface, the corneal limbus and the neighboring sclera for 24 hours. The remission of both conjunctival and corneal malignancy was complete 2 months after surgery and no signs of recurrence were highlighted at AS-OCT analysis at the 2-year follow up. CONCLUSION: Brachytherapy treatment showed optimal management of both corneal and conjunctival involvement, with a free-of-disease follow-up of 24-months. This result suggests that, in specific conditions, Ru-106 brachytherapy could be an effective option of treatment even if not associated with surgical excision.

Anterior segment optical coherence tomography in ocular surface tumours and simulating lesions.

This study aims to systematically review the reported literature on the use of anterior segment optical coherence tomography (AS-OCT) in ocular surface tumours and simulating lesions. A systematic literature search was done using PubMed, Scopus, and Web of Science databases between January 2002 and December 2021. On AS-OCT, ocular surface squamous neoplasia typically demonstrate epithelial thickening, epithelial hyperreflectivity, and an abrupt transition between normal and abnormal epithelium. Conjunctival nevi usually show mildly hyperreflective epithelium of normal thickness, internal hyperreflectivity, and intralesional cysts which is the hallmark of this tumour. Primary acquired melanosis presents with normal thickness epithelium, basal epithelial hyperreflectivity, and absence of cysts. Conjunctival melanoma demonstrates hyperreflective normal/thickened epithelium, hyperreflective basal epithelium, internal hyperreflectivity, and absence of intralesional cysts. Conjunctival lymphoma shows homogenous, low-medium reflective subepithelial lesions with smooth borders, and dot-like infiltrates. Benign reactive lymphoid hyperplasia findings are similar to lymphoma but the infiltrates are more hyperreflective compared to lymphoma. Pterygium shows thickened conjunctival epithelium, epithelial hyperreflectivity, and subepithelial wedge-shaped hyperreflective tissue separated from the overlying epithelium by a cleavage plane. Pinguecula demonstrates mildly thickened epithelium and similar findings with pterygium but does not extend beyond the corneal limbus. This review shows that AS-OCT, as a noninvasive tool, has potential uses in the differential diagnosis of ocular surface tumours and simulating lesions. Major limitations of AS-OCT include limited visualization of the posterior border of thick, keratinized, and pigmented tumours and lack of assessment of large conjunctival tumours in a single cut.

Anterior segment optical coherence tomography characteristics of conjunctival papilloma as compared to papilliform ocular surface squamous neoplasia.

PURPOSE: To describe the anterior segment optical coherence tomography (AS-OCT) appearance of conjunctival papilloma and identify differentiating features from papilliform ocular surface squamous neoplasia (OSSN). METHOD: A retrospective chart review of individuals clinically diagnosed with conjunctival papilloma (n = 10) or papilliform OSSN (n = 10) based on slit lamp features. Data on demographics, tumour characteristics, and primary treatment were collected. AS-OCT features were assessed including epithelial thickness and reflectivity, a corrugated epithelial surface, presence of an overhanging edge, presence of intrinsic spaces and posterior shadowing. Histopathology was available in 5 papilloma and 3 OSSN specimens. RESULT: Overall, the majority of individuals in both groups were white males. OSSN lesions were more likely to involve the limbus (80% vs.10%, p = 0.005) and the bulbar conjunctiva (100% vs. 20%, p < 0.001) compared to papillomas. On AS-OCT, maximum epithelial thickness was thicker in papilloma compared to OSSN (936 ± 533 vs. 637 ± 207 µm, p = 0.009). The feature that best differentiated papilloma from OSSN was an overhanging edge (100% vs. 0%, p < 0.001), where the epithelial lesion was seen on top of underlying normal epithelium. Other features more common in papilloma compared to OSSN included a corrugated epithelial surface (70% vs.10%, p = 0.02), the presence of intrinsic spaces (100% vs. 50%, p = 0.03), and posterior shadowing (100% vs. 40%, p = 0.01). CONCLUSION: AS-OCT shows differentiating features between papilloma and OSSN with an overhanging edge as a distinctive AS-OCT feature of papilloma.

Conjunctival Myxoma: High-Resolution Optical Coherence Tomography Findings of a Rare Tumor.

PURPOSE: The purpose of this study was to describe 2 cases of biopsy-proven conjunctival myxomas and present their optical signs on high-resolution optical coherence tomography (HR-OCT) with clinical and histopathological correlations. METHODS: Two middle-aged female patients with a clinical diagnosis of conjunctival cysts were referred for surgical treatment. Clinical assessment, photographs, ultrasound biomicroscopy, and HR-OCT images were obtained. Excisional biopsies were performed, and specimens were sent for histopathological and immunohistochemical analyses. RESULTS: Clinically, these patients presented with a well-circumscribed, semitranslucent, yellow-pinkish mass. Ultrasound biomicroscopy showed a dome-shaped epibulbar mass with medium-to-high internal reflectivity. No compromise of the underlying sclera was noted. HR-OCT showed a normal conjunctival epithelium, a subepithelial nonhomogeneous mass with hyperreflective and hyporeflective areas lined by a highly hyperreflective band, and mild posterior shadowing. Histopathological findings and immunoreactivity for CD34 and vimentin confirmed the diagnosis of conjunctival myxoma. CONCLUSIONS: The HR-OCT optical signs found in our 2 cases strongly correlated with the microscopic findings. Disclosing the optical signs observed on HR-OCT can help clinicians diagnose and differentiate this lesion, guiding its management. However, more studies with a larger number of patients comparing conjunctival myxoma and other ocular surface tumors are needed to enlighten readers about the unique pattern observed by HR-OCT.

Anterior segment optical coherence tomography and ultrasound biomicroscopy for measuring thickness of corneal and bulbar conjunctival tumours.

BACKGROUND/OBJECTIVE: Anterior segment optical coherence tomography (AS-OCT) and ultrasound biomicroscopy (UBM) are two non-invasive imaging techniques used for the measurement of tumour thickness in corneal and bulbar conjunctival tumours. Histopathology (HP), however, remains the gold standard for the measurement of tumour thickness. The aim of this study was to determine whether AS-OCT and UBM are as accurate as HP for measuring tumour thickness. METHODS: Forty-two corneal and bulbar conjunctival tumours were imaged using AS-OCT and UBM. Images were assessed and tumour thickness was measured. Eleven patients subsequently underwent surgical excision. All specimens were measured during histopathological analysis. The correlation of the thickness measurement on HP to AS-OCT and UBM was then statistically analysed. In cases where the tumour was not excised, thickness measurement comparisons between AS-OCT and UBM were analysed. RESULTS: AS-OCT and UBM measurements of tumour thickness were found to be significantly positively correlated (p=<0.001), as were UBM and HP thickness measurements (p=0.031). HP and AS-OCT measurements, however, only showed a mild but non-significant positive correlation. CONCLUSION: Both AS-OCT and UBM are useful techniques to image and measure the thickness of corneal and conjunctival bulbar tumours. While AS-OCT provides better details than UBM, it was more limited in visualising the posterior boundary of the tumour, particularly in malignant tumours. While thickness measurements of both methodologies were correlated, neither should yet be considered as replacements to the gold standard of HP.

Case Series: High-resolution Optical Coherence Tomography as an Optical Biopsy in Ocular Surface Squamous Neoplasia.

SIGNIFICANCE: Ocular surface squamous neoplasias are superficial tumors of the cornea and conjunctiva that can be sight threatening if neglected. Therefore, accurate noninvasive diagnostic modalities are needed. PURPOSE: The purpose of this case series was to describe the hallmark features of ocular surface squamous neoplasia on high-resolution optical coherence tomography (HR-OCT) imaging and its use in the evaluation and management of superficial ocular tumors. CASE SERIES: Five eyes of four patients with ocular surface squamous neoplasia are described. Whereas two eyes displayed the classic clinical features of ocular surface squamous neoplasia, three of the five eyes had more subtle atypical features. However, all shared features on HR-OCT of epithelial thickening and hyperreflectivity with abrupt transitions between normal and abnormal tissue, classic features of ocular surface squamous neoplasia. All lesions ultimately underwent incisional or excisional biopsy and were confirmed to be ocular surface squamous neoplasia on histopathology. CONCLUSIONS: Ocular surface squamous neoplasia may present as a classic tumor but can also have subtle features or masquerade. Accurate methods to diagnose and manage patients with ocular surface squamous neoplasia are necessary. With recent advancements in technology, HR-OCT has been demonstrated to accurately identify ocular surface squamous neoplasia with the repeatable optical findings of (1) epithelial thickening, (2) epithelial hyperreflectivity, and (3) abrupt transition zone between normal and abnormal tissue. This case series demonstrates how HR-OCT can help provide an optical biopsy to guide appropriate diagnosis and management of this neoplastic lesion.

The Evaluation of the Malignant Characteristics of Conjunctival Lesions Based on the Dermatoscopic Algorithm.

BACKGROUND/AIM: This study analysed the prevalence of the characteristics evaluated in dermatoscopy for melanocytic infiltrations of the conjunctiva with various degrees of malignancy. PATIENTS AND METHODS: A total of 160 conjunctival pigmented lesions were studied. Each lesion was scored using dermatoscopic patterns and the characteristics of malignancy described by Kittler. Also, the Authors' own clues were added to the evaluation. RESULTS: In melanomas, the following characteristics were identified: asymmetry of the pattern and colour, larger average number of colours, the presence of grey colour, structureless area, polymorphic vessels and feeder vessels. A pattern of black dots and a black colour was typical of malignant lesions and pre-cancerous (premalignant) lesions - primary acquired melanosis (PAM) with atypia. Cysts were observed only in the group of naevi. CONCLUSION: The patterns evaluated with dermatoscopy are present in pigmented lesions of the conjunctiva. There are, however, some characteristics which allow differentiation between melanoma and pigmented naevus and melanosis and also between PAM.

In-vivo imaging for assessing tumor growth in mouse models of ocular melanoma.

Uveal melanoma (UM) and conjunctival melanoma (CM) are ocular malignancies that give rise to life-threatening metastases. Although local disease can often be treated successfully, it is often associated with significant vision impairment and treatments are often not effective against metastatic disease. Novel treatment modalities that preserve vision may enable elimination of small tumors and may prevent subsequent metastatic spread. Very few mouse models of metastatic CM and UM are available for research and for development of novel therapies. One of the challenges is to follow tumor growth in-vivo and to determine the right size for treatment, mainly of the posterior, choroidal melanoma. Hence, the purpose of this study was to establish a simple, noninvasive imaging tool that will simplify visualization and tumor follow-up in mouse models of CM and UM. Tumors were induced by inoculation of murine B16LS9 cells into the sub-conjunctival or the choroidal space of a C57BL/6 mouse eye under a surgical microscope. Five to ten days following injection, tumor size was assessed by Phoenix MicronIV™ image-guided Optical Coherence Tomography (OCT) imaging, which included a real-time camera view and OCT scan of the conjunctiva and the retina. In addition, tumor size was evaluated by ultrasound and histopathological examination of eye sections. Tumor growth was observed 5-9 days following sub-conjunctival or sub-retinal injection of seven-thousand or seventy-thousand cells, respectively. A clear tumor mass was detected at these regions using the MicronIV™ imaging system camera and OCT scans. Histology of eye sections confirmed the presence of tumor tissue. OCT allowed an accurate measurement of tumor size in the UM model and a qualitative assessment of tumor size in the CM model. Moreover, OCT enabled assessing the success rate of the choroidal tumor induction and importantly, predicted final tumor size already on the day of cell inoculation. In conclusion, by using a simple, non-invasive imaging tool, we were able to follow intraocular tumor growth of both CM and UM, and to define, already at the time of cell inoculation, a grading scale to evaluate tumor size. This tool may be utilized for evaluation of new mouse models for CM and UM, as well as for testing new therapies for these diseases.

Uveal Melanoma Metastasis to the Contralateral Eye Structures: A Retrospective Comparative Analysis of 13 Consecutive Patients.

PURPOSE: To report uveal melanoma (UM) metastasis to the contralateral ocular and periocular structures. DESIGN: Retrospective study. PARTICIPANTS: Thirteen patients with UM metastasis to the contralateral ocular and periocular structures were included. METHODS: Clinical records were reviewed retrospectively. MAIN OUTCOME MEASURES: The development and time to onset of contralateral ocular and periocular metastasis, systemic metastasis, and death. RESULTS: Of the 13 000 treated UM patients, 13 patients were diagnosed with UM metastasis to the contralateral ocular and periocular structures. Mean patient age at primary UM diagnosis was 60 years (median, 60 years; range, 37-87 years). The primary uveal melanoma was in the choroid (n = 11) or ciliary body (n = 2) and was treated with brachytherapy (n = 11), proton beam radiotherapy (n = 1), or enucleation (n = 1). Systemic metastasis developed in 11 patients (85%) at a mean of 66 months (median, 34 months; range, 12-216 months) after diagnosis of the primary UM. All 11 patients (100%) showed liver metastasis and 8 patients (62%) also showed extrahepatic metastasis. The sites of metastasis to the contralateral ocular or periocular structures included the choroid in 4 patients (31%), the orbit in 7 patients (54%), and the eyelid in 2 patients (15%). One patient with eyelid metastasis demonstrated concurrent conjunctival nodule. Mean time to diagnosis of contralateral ocular or periocular metastasis was 94 months (median, 48 months; range, 9-375 months). Contralateral choroidal metastasis was multifocal in 3 of 4 patients (75%). Of 7 patients with orbital metastasis, 5 showed extraocular muscle involvement with restricted ocular motility. Treatment for contralateral choroidal metastasis included brachytherapy (n = 2), transpupillary thermotherapy (n = 1), and observation (n = 1). Treatment for contralateral periocular (orbit or eyelid) metastasis was excision (n = 5), external beam radiotherapy (n = 2), and observation (n = 2). Of 13 patients, death was documented in 11 patients at a mean of 17 months (median, 9 months; range, 3-54 months) as a result of systemic UM metastasis (n = 10) or unrelated cause (n = 1). CONCLUSIONS: Metastasis resulting from UM to the contralateral ocular and periocular structures is rare and generally occurs in patients with disseminated metastasis. Orbital tissue is the most common site of involvement, and these patients have short life expectancy.

F-18 fluorodeoxyglucose positron emission tomography/computed tomography in conjunctival melanoma with recurrence.

Ocular melanoma is classified under the category of noncutaneous melanomas. Noncutaneous melanomas are relatively rare. Ocular melanoma commonly arises from choroid. Conjunctival melanoma is a rare but potentially lethal form of ocular melanoma. It can invade locally. Systemic spread is seen in up to 25% of cases, often associated with lymph node involvement. Metastatic sites include the lungs, liver, gastrointestinal tract, and the central nervous system. F-18 fluorodeoxyglucose positron emission tomography/computed tomography (F-18 FDG PET-CT) scanning is indicated for staging cutaneous melanoma patients. However, few studies have evaluated its role in the management of conjunctival melanoma. This case highlights the use of F-18 FDG PET/CT for imaging, preoperative staging, and evaluation for metastasis in conjunctival melanoma.

Dermolipoma conjuntival / Conjunctival dermolipoma

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Successful treatment of recurrent benign fibrous histiocytoma by complete surgical removal and appropriate ocular surface reconstruction: A case report.

INTRODUCTION: Ocular benign fibrous histiocytoma can involve corneoscleral limbus and adjacent cornea and usually has a good prognosis after surgical removal. Despite the low recurrence rate, we reported a rare case of ocular benign fibrous histiocytoma with twice recurrences after excision. PATIENT CONCERNS: A 12-year-old Chinese girl presented with two painless progressively enlarging masses in the right eye for 6 years. She once had the lesions excised 1 year ago. However, the primary lesions relapsed again. DIAGNOSIS: Histopathologic and immunohistochemical examinations of the excised samples supported the diagnosis of benign fibrous histiocytomas of the corneoscleral limbus. INTERVENTIONS: The patient underwent mass resection with limbal stem cell transplantation and amniotic membrane transplantation at first. As for the tumors' second recurrence, we performed extended excision combined with lamellar keratoplasty and amniotic membrane implantation. OUTCOMES: The corneal graft remained clear with no sign of tumor recurrence 3 years after the second surgery. CONCLUSION: Complete surgical resection with tumor-free margins is critical to reduce the recurrence of benign fibrous histiocytoma and appropriate ocular surface reconstruction is necessary to remedy tissue defect and maintain epithelial integrity.

Tomografía de coherencia óptica de segmento anterior de alta resolución como método de diagnóstico diferencial entre neoplasia intraepitelial córneo-conjuntival y pterygium / High resolution anterior segment optical coherence tomography for differential diagnosis between corneo-conjunctival intraepithelial neoplasia and pterygium

OBJETIVO: Valorar si la tomografía de coherencia óptica de segmento anterior (OCT-SA) es un método de diagnóstico no invasivo adecuado para diferenciar lesiones córneo-conjuntivales benignas (pterygium) de las premalignas (neoplasia intraepitelial córneo-conjuntival [CIN]). MATERIAL Y MÉTODOS: Estudio observacional, analítico y transversal de 22 ojos con diagnóstico de sospecha de pterygium y CIN durante 2 años. Con la OCT-SA se estudiaron las características morfológicas y se compararon espesores epiteliales (EE) y grado de extensión sobre la superficie corneal (GIC). Posteriormente se confirmó el diagnóstico con el estudio histopatológico tras exéresis quirúrgica. RESULTADOS: La edad media de los pacientes con pterygium (n = 18) fue de 52,67 ± 15 años y 74 ± 12 años en los sujetos con CIN (n = 4) (p < 0,021). En los pterygium, la OCT-SA mostró EE normal, adelgazado o levemente aumentado (77,4 ± 26 μm), además de aumento del tejido subepitelial en forma de cuña. Los CIN presentaron un aumento del EE (262,5 ± 124 μm), que era fuertemente hiperreflectivo, con transición abrupta entre epitelio sano y patológico. El análisis de los EE en OCT-SA entre pterygium y CIN reveló diferencias estadísticamente significativas (p < 0,002). La curva ROC reveló una sensibilidad y especificidad del 100% de la OCT-SA en la diferenciación entre CIN y pterygium, utilizando EE de 141μm como punto de corte. CONCLUSIÓN: La OCT-SA es una herramienta útil para la diferenciación entre pterygium y CIN, ya que proporciona características morfológicas típicas. Un aumento del espesor del EE córneo-conjuntival mayor de 141 μm en OCT-SA sugiere una sensibilidad y especificidad del 100% para diagnosticar CIN

OBJECTIVE: To assess if anterior segment optical coherence tomography (AS-OCT) is a noninvasive diagnostic method suitable to differentiate benign corneo-conjunctival lesions (pterygium) from premalignant lesions (corneo-conjunctival intraepithelial neoplasia, CIN). MATERIAL AND METHODS: An observational, analytical and cross-sectional study was conducted in 22 eyes with conjunctival lesions clinically suspicious for pterygium and CIN during two years. Morphological differences between both lesions were studied with AS-OCT; epithelial thicknesses (EE) and extension length on corneal surface (GIC) were compared between both groups. A surgical excision of the lesion was performed for histopathological diagnosis. RESULTS: Mean age of patients with pterygium (n = 18) was 52.67 ± 15 y.o and 74 ± 12 y.o in subjects with CIN (n = 4) (p < 0.021). In pterygia, AS-OCT showed typical features (normal, thinning or slightly thickened EE; 77.4 ± 26 μm), in addition to an increase in wedge-shaped subepithelial tissue. Patients with CIN had a mean thickened EE (262.5 ± 124μm) and strongly hyperreflective, with abrupt transition between normal and pathological epithelium. Analysis of EE between subjects with pterygium and CIN revealed statistically significant differences (p < 0.002). ROC curve revealed a 100% sensitivity and specificity of OCT-SA in differentiation between CIN and pterygium, using 141μm as cutoff point of EE. CONCLUSION: AS-OCT is a useful tool for the differentiation between pterygium and CIN able to provide typical morphological characteristics. An EE greater than 141 μm in AS-OCT suggests a sensitivity and specificity of 100% for the diagnosis of CIN