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.

A Novel Melanin-Targeted 18F-PFPN Positron Emission Tomography Imaging for Diagnosing Ocular and Orbital Melanoma.

OBJECTIVE: 18F-N-(2-(Diethylamino)ethyl)-5-(2-(2-(2-fluoroethoxy)ethoxy)ethoxy) picolinamide (18F-PFPN) is a novel positron emission tomography (PET) probe designed to specifically targets melanin. This study aimed to evaluate the diagnostic feasibility of 18F-PFPN in patients with ocular or orbital melanoma. MATERIALS AND METHODS: Three patients with pathologically confirmed ocular or orbital melanoma (one male, two females; age 41-59 years) were retrospectively reviewed. Each patient underwent comprehensive 18F-PFPN and 18F-fluorodeoxyglucose (18F-FDG) PET scans. The maximum standardized uptake value (SUVmax) of the lesion and the interference caused by background tissue were compared between 18F-PFPN and 18F-FDG PET imaging. In addition, the effect of intrinsic pigments in the uvea and retina on the interpretation of the results was examined. The contralateral non-tumorous eye of each patient served as a control. RESULTS: All primary tumors (3/3) were detected using 18F-PFPN PET, while only two primary tumors were detected using 18F-FDG PET. Within each lesion, the SUVmax of 18F-PFPN was 2.6 to 8.3 times higher than that of 18F-FDG. Regarding the quality of PET imaging, the physiological uptake of 18F-FDG PET in the brain and periocular tissues limited the imaging of tumors. However, 18F-PFPN PET minimized this interference. Notably, intrinsic pigments in the uvea and retina did not cause abnormal concentrations of 18F-PFPN, as no anomalous uptake of 18F-PFPN was detected in the healthy contralateral eyes. CONCLUSION: Compared to 18F-FDG, 18F-PFPN demonstrated higher detection rates for ocular and orbital melanomas with minimal interference from surrounding tissues. This suggests that 18F-PFPN could be a promising clinical diagnostic tool for distinguishing malignant melanoma from benign pigmentation in ocular and orbital melanomas.

Imaging in Ocular Surface Squamous Cell Carcinoma: There's More to PET/CT Than Meets the Eye.

ABSTRACT: A 56-year-old woman presenting with swelling, redness, and pain in the left eye, initially treated with topical therapy for conjunctival squamous neoplasia, developed visual loss with progression of swelling in the left eye over the next year. Patient was referred for imaging as she also had significant weight loss and palpable neck swellings. Whole-body 18 F-FDG PET/CT revealed hypermetabolic left eye lesion; metastases in bilateral submandibular glands; cervical, mediastinal, and axillary lymph nodes; and a right lung nodule. Patient was diagnosed with ocular surface squamous cell carcinoma with metastases and started on systemic chemotherapy (cisplatin, paclitaxel, and 5-fluorouracil).

Uncertainties in ocular proton planning and their impact on required margins.

PURPOSE: To review required margins in ocular proton therapy (OPT) based on an uncertainty estimation and to compare them with widely used values. Further, uncertainties when using registered funduscopy images in the 3D model is investigated. METHODS: An uncertainty budget in planning and delivery was defined to determine required aperture and range margins. Setup uncertainties were considered for a cohort of treated patients and tested in a worst-case estimation. Other uncertainties were based on a best-guess and knowledge of institutional specifics, e.g. range reproducibility. Margins for funduscopy registration were defined resulting from scaling, rotation and translation of the image. Image formation for a wide-field fundus camera was reviewed and compared to the projection employed in treatment planning systems. RESULTS: Values for aperture and range with margins of 2.5 mm as reported in literature could be determined. Aperture margins appear appropriate for setup uncertainties below 0.5 mm, but depend on lateral penumbra. Range margins depend on depth and associated density uncertainty in tissue. Registration of funduscopy images may require margins of >2 mm, increasing towards the equator. Difference in the projection may lead to discrepancies of several mm. CONCLUSIONS: The commonly used 2.5 mm aperture margin was validated as an appropriate choice, while range margins could be reduced for lower ranges. Margins may however not include uncertainties in contouring and possible microscopic spread. If a target base is contoured on registered funduscopy images care must be taken as they are subject to larger uncertainties. Multimodal imaging approach in OPT remains advisable.

Prediction model of radiotherapy outcome for Ocular Adnexal Lymphoma using informative features selected by chemometric algorithms.

BACKGROUND: Ocular Adnexal Lymphoma (OAL) is a non-Hodgkin's lymphoma that most often appears in the tissues near the eye, and radiotherapy is the currently preferred treatment. There has been a controversy regarding the prognostic factors for systemic failure of OAL radiotherapy, the thorough evaluation prior to receiving radiotherapy is highly recommended to better the patient's prognosis and minimize the likelihood of any adverse effects. PURPOSE: To investigate the risk factors that contribute to incomplete remission in OAL radiotherapy and to establish a hybrid model for predicting the radiotherapy outcomes in OAL patients. METHODS: A retrospective chart review was performed for 87 consecutive patients with OAL who received radiotherapy between Feb 2011 and August 2022 in our center. Seven image features, derived from MRI sequences, were integrated with 122 clinical features to form comprehensive patient feature sets. Chemometric algorithms were then employed to distill highly informative features from these sets. Based on these refined features, SVM and XGBoost classifiers were performed to classify the effect of radiotherapy. RESULTS: The clinical records of from 87 OAL patients (median age: 60 months, IQR: 52-68 months; 62.1% male) treated with radiotherapy were reviewed. Analysis of Lasso (AUC = 0.75, 95% CI: 0.72-0.77) and Random Forest (AUC = 0.67, 95% CI: 0.62-0.70) algorithms revealed four potential features, resulting in an intersection AUC of 0.80 (95% CI: 0.75-0.82). Logistic Regression (AUC = 0.75, 95% CI: 0.72-0.77) identified two features. Furthermore, the integration of chemometric methods such as CARS (AUC = 0.66, 95% CI: 0.62-0.72), UVE (AUC = 0.71, 95% CI: 0.66-0.75), and GA (AUC = 0.65, 95% CI: 0.60-0.69) highlighted six features in total, with an intersection AUC of 0.82 (95% CI: 0.78-0.83). These features included enophthalmos, diplopia, tenderness, elevated ALT count, HBsAg positivity, and CD43 positivity in immunohistochemical tests. CONCLUSION: The findings suggest the effectiveness of chemometric algorithms in pinpointing OAL risk factors, and the prediction model we proposed shows promise in helping clinicians identify OAL patients likely to achieve complete remission via radiotherapy. Notably, patients with a history of exophthalmos, diplopia, tenderness, elevated ALT levels, HBsAg positivity, and CD43 positivity are less likely to attain complete remission after radiotherapy. These insights offer more targeted management strategies for OAL patients. The developed model is accessible online at: https://lzz.testop.top/.

[The value of dynamic contrast-enhanced MRI in the differentiation between benign and malignant lacrimal epithelial tumors].

Objective: To investigate the diagnostic performance of multiparametric dynamic contrast-enhanced MRI(DCE-MRI) for the differentiation between benign and malignant larcrimal gland epithelial tumors. Methods: The clinical and imaging data of 104 patients with epithelial tumors of the lacrimal gland who underwent orbital MRI scan and met the inclusion criteria in Beijing Tongren Hospital from January 2011 to December 2017 were retrospectively collected, including 48 males and 56 females, aged from 12 to 77 (43±7) years. Sixty-three cases of benign epithelial tumors and 41 cases of malignant epithelial tumors were examined by DCE-MRI. The parameters of semiquantitative analysis including: time to peak enhancement (Tpeak), maximum enhancement ratio (ERmax), Slope, washout ratio (WR) and time-signal intensity curve (TIC) types. The parameters of quantitative analysis including: volume transfer constant (Ktrans), the extravascular extracellular volume fraction (Ve) and rate constant (Kep). Receiver operating characteristic (ROC) curve analysis was performed for DCE-MRI parameters with statistically significant differences, the area under the curve (AUC) was calculated, the diagnostic threshold was determined, and the diagnostic performance was evaluated. Logistic regression analysis was used to determine the best parameters for differential diagnosis of benign and malignant epithelial tumors of the lacrimal gland. Results: For the semiquantitative analysis of DCE-MRI, malignant lacrimal gland epithelial tumor had a significantly shorter Tpeak than benign masses [(103.77±57.87) s vs (187.80±77.01) s,P<0.001)], while had a higher value in ERmax, Slope [M(Q1,Q3)] and WR in malignant masses compared with benign one [1.55±0.39 vs 1.36±0.33; 1.76 (0.97,2.27) vs 0.62 (0.50,0.93); 7.70%(1.40%, 21.60%)% vs 0(0, 0),all P<0.05)].The TICs of benign lacrimal tumors mainly showed a persistent type (49/63),while most malignant lacrimal tumors mainly showed a plateau type (25/41). For the quantitative analysis of DCE-MRI, the values of Ktrans and Kep[M(Q1,Q3)] in malignant tumors were significantly greater than those of benign tumors (0.99±0.52/min vs 0.43±0.23/min, P<0.001; 1.33(0.83, 1.55)/min vs 0.55(0.46, 0.68)/min, P<0.001). No significant difference in Ve was found between the groups (0.76±0.20 vs 0.73±0.22,P=0.467). Through the statistical analysis, TIC types (OR=3.887,95%CI: 1.409-10.725) and Ktrans(OR=50.979,95%CI: 6.046-429.830) can provide superior diagnostic performance for predicting malignant lacrimal gland epithelial tumors, with a sensitivity of 78.05%, specificity of 77.78%,and sensitivity of 70.73%, specificity of 95.24%, respevtively. Furthermore, the comprehensive diagnostic performance of Ktrans in AUC was proven to be significantly better than that of TIC [0.875 (0.796-0.932) vs 0.798 (0.708-0.870),P=0.049]. Conclusions: Multiparametric DCE-MRI is helpful for the differential diagnosis of benign and malignant epithelial tumors of lacrimal gland. TIC type and Ktrans have higher diagnostic value, and the diagnostic performance of Ktrans is better than that of TIC.

Clinical and Optical Coherence Tomography Comparison Between Ocular Surface Squamous Neoplasia and Squamous Metaplasia.

PURPOSE: The purpose of this study was to compare the clinical characteristics and high-resolution optical coherence tomography (HR-OCT) findings between corneal squamous metaplasia and ocular surface squamous neoplasia (OSSN). METHODS: A retrospective case-control study of 8 patients, 4 with histologically confirmed squamous metaplasia and 4 with histologically confirmed OSSN, who presented to the Miami Veterans Administration Medical Center and Bascom Palmer Eye Institute between 2016 and 2020 was performed. Clinical characteristics, HR-OCT findings, and pathology were evaluated and compared. RESULTS: Four patients with squamous metaplasia and 4 with OSSN were evaluated. In the metaplasia group, 75% were male, 2 were White, and 2 were Black. In the OSSN group, all 4 were White males. All lesions were opalescent and occurred at the limbus; however, the borders were more smooth and rounded in the metaplastic lesions compared with OSSN. HR-OCT findings were indistinguishable between the 2 groups. CONCLUSIONS: There is overlap in clinical characteristics and HR-OCT findings between corneal squamous metaplasia and OSSN, highlighting one limitation of HR-OCT. As such, if a corneal opacity has some but not all HR-OCT findings of OSSN, squamous metaplasia should also be considered. A biopsy may be indicated to further evaluate and guide treatment.

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.

Individualized dosimetry in Ru-106 ophthalmic brachytherapy based on MRI-derived ocular anatomical parameters.

PURPOSE: To estimate ocular geometry-related inaccuracies of the dosimetric plan in Ru-106 ophthalmic brachytherapy. METHODS AND MATERIALS: Thirty patients with intraocular lesions were treated with brachytherapy using a Ru-106 plaque-shell of inner radius of 12 mm. Magnetic resonance imaging was employed to determine the external scleral radius at tumor site and the tumor margins. A mathematical model was developed to determine the distance between the external sclera and the internal surface of the plaque associated with the tangential application of the plaque on the treated eye. Differences in delivered dose to the tumor apex, sclera and tumor margins as derived by considering the default eye-globe of standard size (external sclera radius = 12 mm) against the individual-specific eye globe were determined. RESULTS: The radius of external sclera at the tumor site was found to range between 10.90 and 13.05 mm for the patient cohort studied. When the patient specific eye-globe/tumor geometry is not taken into account, the delivered dose was found to be overestimated by 8.1% ± 4.1% (max = 15.3%) at tumor apex, by 1.5% ± 2.8% (max = 5.7%) at anterior tumor margin, by 16.6% ± 7.5% (max = 36.4%) at posterior tumor margin and 8.1% ± 3.8% (max = 13.2%) at central sclera of eyes with lower than the default radius. The corresponding dose overestimations for eyes with higher than the default radius was 13.5% ± 4.3% (max = 22.3%), 1.5% ± 2.8% (max = 5.7%), 12.6% ± 4.5% (max = 20.0%), and 15.1% ± 5.0% (max = 24.4%). CONCLUSIONS: The proposed patient-specific approach for Ru-106 brachytherapy treatment planning may improve dosimetric accuracy. Individualized treatment planning dosimetry may prevent undertreatment of intraocular tumors especially for highly myopic or hyperopic eyes.

The forgotten lacrimal gland and lacrimal drainage apparatus: pictorial review of CT and MRI findings and differential diagnosis.

The lacrimal gland is a bilobed serous gland located in the superolateral aspect of the orbit. Lacrimal system pathologies can be broadly divided into pathologies of the lacrimal gland and those of the nasolacrimal drainage apparatus. These include distinct congenital, infectious, inflammatory, and benign, indeterminate, and malignant neoplastic lesions. Trauma and resultant fractures affecting lacrimal drainage apparatus is not part of this review; only non-traumatic diseases will be discussed. CT is the initial modality of choice because of its ability to delineate lacrimal system anatomy and demonstrate most lacrimal drainage system abnormalities and their extent. It also assesses bony architecture and characterizes any osseous changes. MRI is helpful in further characterizing these lesions and better assessing involvement of the surrounding soft tissue structures. In this pictorial review, we will review the anatomy of the lacrimal system, describe CT/MRI findings of the common and uncommon lacrimal system abnormalities and discuss relevance of imaging with regards to patient management.

Squamous carcinoma ex pleomorphic adenoma of the lacrimal gland.

We present a very rare case of squamous cell carcinoma (SCC) ex pleomorphic adenoma of the lacrimal gland. Our patient presented with a 12 month history of painful proptosis of his left eye associated with severe headache. Imaging showed a left lacrimal gland lesion with extensive orbital disease extending into lateral and superior rectus muscles, cavernous sinus and the greater wing of the sphenoid. A lacrimal gland biopsy showed a combination of small bland glandular structures and sclerotic, elastin-containing stroma showing that the SCC had arisen on a background of a probable pleomorphic adenoma. Treatment with cisplatin and 5-Fluorouracil proved efficacious with a significant reduction of orbital and post-orbital disease on interval scanning.

Cutaneous pleomorphic adenoma of the periocular region - a case series.

Mixed tumour of the skin is a rare entity also known as chondroid syringoma and pleomorphic adenoma. These usually present as slow-growing skin nodules with a smooth surface, clear boundaries, and no ulceration. Case series exist describing pleomorphic adenomas in the periocular region including the lids and orbit, separate to the more familiar lacrimal gland pleomorphic adenoma. These may arise from accessory or ectopic lacrimal gland tissue but in the eyelids are more likely to arise from sweat glands in the skin. Histopathological analysis of these lesions is important to identify complete excision, minimising recurrences and in identifying rare but potential malignant transformation. We describe the clinical features and outcomes in three cases of pleomorphic adenoma with two at the medial canthus (including one recurrence) and one in the brow region.

Adenoid cystic carcinoma of the palpebral lobe of the lacrimal gland - case report and literature review.

Epithelial tumors of the lacrimal gland are rare and usually develop in the orbital lobe. We report the exceedingly rare occurrence of a primary adenoid cystic carcinoma in the palpebral lobe of the lacrimal gland. A 26-year-old female was referred for evaluation of a gradually enlarging mass in the lateral upper eyelid, previously diagnosed as a chalazion. Computed tomography revealed a heterogeneous round lesion anterior to the orbital rim. Excisional biopsy was compatible with an adenoid cystic carcinoma. After excluding distant metastasis, and as the patient refused adjuvant radiotherapy, a second surgical procedure, with wide local excision, was indicated. Follow-up showed no recurrence. This case highlights the importance of performing a thorough clinical examination when diagnosing any lateral upper eyelid mass. A high index of suspicion for malignant tumors of the lacrimal gland should always be maintained, and a complete excision with histological analysis should be preferred whenever possible.

Lacrimal gland pleomorphic adenoma with extensive necrosis.

Lacrimal gland pleomorphic adenomas (LGPA) are benign mixed tumors. Diagnosis is based on clinical and radiological findings which usually prompts complete excision of the lesion to minimise recurrence and a cumulative risk of malignant transformation. Necrosis in pleomorphic adenoma has been rarely reported in salivary gland PA, either spontaneously or due to iatrogenic interventions. Necrosis is suggestive of a malignant process and makes interpretation of histology specimens difficult. A 23 year old woman, while awaiting biopsy for a mass in the left lacrimal gland, which had been symptomatic for only several months, presented with acute pain and swelling of the left lateral lid. An incisional biopsy showed an inflamed lacrimal gland with focal necrosis and atypia of adjacent cytology and gland architecture. Subsequent excisional biopsy confirmed an LGPA with some inflammation but no necrosis. Necrosis may occur as an atypical presentation in LGPA.

The role of 18F-FDG PET/CT in diagnosis and treatment evaluation for ocular adnexal mucosa-associated lymphoid tissue lymphoma.

OBJECTIVE: The purpose of this study is to evaluate the value of fluorine-18-fludeoxyglucose positron emission tomography (18F-FDG PET)/CT in the diagnosis and treatment evaluation of ocular adnexal mucosa-associated lymphoid tissue (MALT) lymphoma. METHODS: 70 patients with OAML who received radiotherapy were recruited in our study. All the patients had the 18F-FDG PET/CT examination before the treatment. We retrospectively reviewed the medical records, pathological reports, laboratory results, and imaging features of all patients. The associations between 18F-FDG PET/CT parameters and Epstein-Barr virus antibodies, treatment response, MRI data, and Ki-67 expression were investigated. RESULTS: The PET/CT scan indicated that 80% (56/70) of the patients showed orbital FDG avidity. The median level of maximum standardized uptake value (SUVmax) of the lesions was 4.65 ± 3.00 (range:1.2-13.5). 92.0% (46/50) of the mass-forming lesions showed 18F-FDG avidity, while only 50.0% (10/20) of the non-massive lesions had 18F-FDG avidity (χ2 = 13.23, p=0.01). The SUVmax in orbit, conjunctiva, and lacrimal gland lymphoma were 5.6, 2.9, and 3.7, respectively. A significant difference was identified of SUVmax among the three locations' lymphoma using one-way ANOVA analysis (F = 5.039, p = 0.01). After completion of radiotherapy, the complete remission rate was achieved in 30.8% (4/13) of the patients without 18F-FDG avidity, and 70.4% (38/54) in cases with 18F-FDG avidity (χ2 = 5.43, p = 0.02). The correlation between high Ki-67 score and 18F-FDG avidity was confirmed (χ2 = 3.916, p = 0.048); however, no significant correlation was found between the SUVmax and Ki-67 score of the lesions (p = 0.971). Three patients (3/70, 4.3%) were upregulated the stage via PET/CT. CONCLUSION: 18F-FDG PET/CT had some potential values in the diagnosis and assessment of treatment response in patients with OAML. ADVANCES IN KNOWLEDGE: The value of 18F-FDG PET/CT for patients with OAML.

A case of pleomorphic adenoma of the lacrimal gland invading the lower orbit.

Pleomorphic adenoma is a benign tumor that originates from the lacrimal gland and typically develops in the upper orbit. There is a risk of postoperative recurrence due to capsule damage by biopsy or incomplete tumor resection. Here, we report a case of primary lacrimal gland pleomorphic adenoma that extended to the lower orbit. A 76-year-old man visited a nearby clinic with swelling of the right eyelid, and was referred to our department because of decreased vision in the right eye and marked chemosis. At the initial presentation, external eye findings showed swelling of the right eyelid, and elastic hard masses were palpable beneath the skin of the upper and lower eyelids. Magnetic resonance imaging revealed a multinodular tumor in the upper and lower orbits, measuring about 2 cm in the long axis. Excision was attempted by a transcutaneous approach from the upper eyelid, and the tumor was totally removed as a mass without damage to the capsule. The orbital mass was histologically diagnosed as pleomorphic adenoma of the lacrimal gland. We encountered a rare morphological variation of pleomorphic adenoma of the lacrimal gland that extended to the lower orbit. When diagnosing large tumors extending to the upper and lower orbits, total tumor resection should be attempted without biopsy due to the possibility of pleomorphic adenoma.