Conjunctival Melanoma: Features Based on the Fitzpatrick Skin Type (FST) in 540 Patients at a Single Ocular Oncology Center

Background: The Fitzpatrick skin type (FST) is a classification system for skin pigmentation that has been used to stratify risk for cutaneous melanoma; however, it has not yet been explored in the context of conjunctival melanoma. Herein, we examine FST and its association with the clinical features of conjunctival melanoma. Methods: A retrospective review was conducted on 540 medical records of patients with pathologic diagnosis of conjunctival melanoma. The patients were categorized according to the FST classification based on their external facial photographs at presentation. This includes: Type I (white skin color), Type II (fair skin color), Type III (average skin color), Type IV (light-brown skin color), Type V (brown skin color), and Type VI (black skin color). Other clinical features (namely tumor characteristics, tumor location, and tumor color) were also noted. Results: The FST included Types I (n=126, 23%), II (n=337, 62%), III (n=56, 10%), IV (n=8, 2%), V (n=12, 2%), and VI (n=1, \u3c1%). Statistical analysis (FST I vs. FST II vs. FST III, IV, V, and VI) revealed FST I and II tumors had smaller tumor thickness (2.1 vs. 2.8 vs. 3.6 mm, p=0.01) and less eyelid involvement (13% vs. 13% vs. 28%, p=0.02). Discussion: In this analysis, we found that the majority of patients with conjunctival melanoma are FST I or II; they also had smaller tumor thickness and less eyelid involvement than FST III, IV, V, and VI. Thus, patients with FST I and II should be considered a phenotype at risk for conjunctival melanoma and be observed accordingly

Postenucleation adjuvant chemotherapy with vincristine, etoposide, and carboplatin for the treatment of high-risk retinoblastoma.

BACKGROUND: Analysis of 52 eyes with high-risk retinoblastoma managed with postenucleation adjuvant chemotherapy using vincristine sulfate, etoposide phosphate, and carboplatin showed no evidence of systemic metastasis in any case during a mean (range) follow-up of 66 (12-202) months. PURPOSE: To determine the efficacy of postenucleation adjuvant chemotherapy with vincristine, etoposide, and carboplatin in the prevention of metastasis for patients with high-risk retinoblastoma. METHODS: Retrospective, nonrandomized, interventional case series of 52 eyes in 51 patients with high-risk retinoblastoma consisting of tumor invasion into the anterior segment, posterior uvea 3 mm or greater, postlaminar optic nerve, or any combination of posterior uvea and optic nerve involvement. RESULTS: Of 51 consecutive patients with high-risk retinoblastoma, there were 30 males (59%) and 21 females (41%), with a median age of 28 months at diagnosis. All 52 eyes were classified as group E. The main histopathologic risk factors included anterior segment invasion (7 [13%]), isolated massive posterior uveal invasion of 3 mm or greater (6 [12%]), isolated postlaminar optic nerve invasion (15 [29%]), or any posterior uveal invasion with any optic nerve involvement (24 [46%]). There was additional invasion into the sclera (3 [6%]) and extrascleral structures, including the orbit (1 [2%]). A single histopathologic high-risk factor was present in 32 eyes (62%), whereas 20 eyes (38%) manifested 2 or more high-risk characteristics. Based on previously published series, untreated high-risk retinoblastoma carries at least a 24% risk for metastatic disease. In the present series, using vincristine, etoposide, and carboplatin in all cases, there was no metastasis during a mean follow-up of 66 months (median [range], 55 [12-202] months). CONCLUSIONS: Retinoblastoma with invasion into the postlaminar optic nerve and/or posterior uvea is at high risk for metastasis and death. In this study, postenucleation chemotherapy using vincristine, etoposide, and carboplatin was effective in preventing metastasis in every case (100%)

Melanoma of the Choroid in a Dog

Intraocular tumors are rare in the dog. Of the reported neoplasms, melanomas are the most common. These tumors characteristically arise in the anterior uvea and secondarily infiltrate posteriorly into the choroid and/or anteriorly into the corneoscleral region. Advanced tumors may extend extraocularly. In the dog, isolated choroidal melanomas are extremely uncommon; to the authors\u27 knowledge, only two cases have been previously reported. This report describes a pigmented choroidal tumor in a dog with clinical and histopathologic features resembling a benign melanoma

Photodynamic Therapy in Ocular Oncology

Over the past two decades, we have witnessed the increasing use of photodynamic therapy (PDT) in the field of ocular oncology. Based on a review of the literature and our own experience, we herein review the role of PDT for the management of intraocular tumors. The discussion includes two main topics. First, we discuss the application of PDT for benign tumors, including circumscribed choroidal hemangioma, choroidal osteoma, retinal astrocytoma, retinal capillary hemangioma (retinal hemangioblastoma), and retinal vasoproliferative tumor. Second, we assess the role of PDT for malignant tumors, including choroidal melanoma and choroidal metastasis

Effects of capecitabine treatment on the uptake of thymidine analogs using exploratory PET imaging agents: 18F-FAU, 18F-FMAU, and 18F-FLT

Patient Image Data. (XLSX 19 kb

Predicting Choroidal Nevus Transformation to Melanoma Using Machine Learning

PURPOSE: To develop and validate machine learning (ML) models to predict choroidal nevus transformation to melanoma based on multimodal imaging at initial presentation. DESIGN: Retrospective multicenter study. PARTICIPANTS: Patients diagnosed with choroidal nevus on the Ocular Oncology Service at Wills Eye Hospital (2007-2017) or Mayo Clinic Rochester (2015-2023). METHODS: Multimodal imaging was obtained, including fundus photography, fundus autofluorescence, spectral domain OCT, and B-scan ultrasonography. Machine learning models were created (XGBoost, LGBM, Random Forest, Extra Tree) and optimized for area under receiver operating characteristic curve (AUROC). The Wills Eye Hospital cohort was used for training and testing (80% training-20% testing) with fivefold cross validation. The Mayo Clinic cohort provided external validation. Model performance was characterized by AUROC and area under precision-recall curve (AUPRC). Models were interrogated using SHapley Additive exPlanations (SHAP) to identify the features most predictive of conversion from nevus to melanoma. Differences in AUROC and AUPRC between models were tested using 10 000 bootstrap samples with replacement and results. MAIN OUTCOME MEASURES: Area under receiver operating curve and AUPRC for each ML model. RESULTS: There were 2870 nevi included in the study, with conversion to melanoma confirmed in 128 cases. Simple AI Nevus Transformation System (SAINTS; XGBoost) was the top-performing model in the test cohort [pooled AUROC 0.864 (95% confidence interval (CI): 0.864-0.865), pooled AUPRC 0.244 (95% CI: 0.243-0.246)] and in the external validation cohort [pooled AUROC 0.931 (95% CI: 0.930-0.931), pooled AUPRC 0.533 (95% CI: 0.531-0.535)]. Other models also had good discriminative performance: LGBM (test set pooled AUROC 0.831, validation set pooled AUROC 0.815), Random Forest (test set pooled AUROC 0.812, validation set pooled AUROC 0.866), and Extra Tree (test set pooled AUROC 0.826, validation set pooled AUROC 0.915). A model including only nevi with at least 5 years of follow-up demonstrated the best performance in AUPRC (test: pooled 0.592 (95% CI: 0.590-0.594); validation: pooled 0.656 [95% CI: 0.655-0.657]). The top 5 features in SAINTS by SHAP values were: tumor thickness, largest tumor basal diameter, tumor shape, distance to optic nerve, and subretinal fluid extent. CONCLUSIONS: We demonstrate accuracy and generalizability of a ML model for predicting choroidal nevus transformation to melanoma based on multimodal imaging. FINANCIAL DISCLOSURES: Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article

Conditional Metastasis of Uveal Melanoma in 8091 Patients over Half-Century (51 Years) by Age Group: Assessing the Entire Population and the Extremes of Age

PURPOSE: To evaluate cumulative incidence of metastasis at specific timepoints after treatment of uveal melanoma in a large cohort of patients and to provide comparison of conditional outcomes in the youngest and oldest cohorts (extremes of age). METHODS: Retrospective analysis of 8091 consecutive patients with uveal melanoma at a single center over a 51-year period. The patients were categorized by age at presentation (0-29 years [n = 348, 4%], 30-59 years [n = 3859, 48%], 60-79 years [n = 3425, 42%], 80 to 99 years [n = 459, 6%]) and evaluated for nonconditional (from presentation date) and conditional (from specific timepoints after presentation) cumulative incidence of metastasis at five, 10, 20, and 30 years. RESULTS: For the entire population of 8091 patients, five-year/10-year/20-year/30-year nonconditional cumulative incidence of metastasis was 15%/23%/32%/36%, and the conditional incidence improved to 6%/15%/25%/30% for patients who did not develop metastasis in the first three years. For the extremes of age (0-29 years and 80-99 years), the nonconditional cumulative incidence of metastasis revealed the younger cohort with superior outcomes at 8%/15%/19%/27% and 21%/29%/29%/29%, respectively (P \u3c 0.001). The conditional incidence (at one-year and two-year timepoints with metastasis-free survival) showed persistent superior younger cohort survival (P \u3c 0.001, P = 0.001), but no further benefit for patients with three-year metastasis-free survival at 4%/12%/16%/24% and 7%/18%/18%/18%, respectively (P = 0.09). CONCLUSIONS: Non-conditional metastasis-free survival analysis for patients with uveal melanoma revealed the youngest cohort to have significantly better survival than the oldest cohort, and this persisted into one-year and two-year conditional metastasis-free survival but diminished at the three-year conditional timepoint

Likelihood of Germline Mutation with Solitary Unilateral Retinoblastoma Based on Patient Age at Presentation. A Real-World Analysis of 482 Consecutive Patients.

Introduction: Retinoblastoma due to germline mutation has a greater risk of bilateral presentation, and multifocal or extraocular involvement. In solitary unilateral retinoblastoma, the inheritance pattern is less understood and assumed to be somatic. We assessed the likelihood of germline inheritance in children with unilateral retinoblastoma and whether it varies based on age at presentation. Methods: This was a retrospective case study assessing 482 consecutive patients with solitary unilateral retinoblastoma at Wills Eye Hospital between 1972 and 2020 for the likelihood of germline inheritance based on age at presentation (≤1 year vs. \u3e1 year). Germline inheritance was deemed likely if there was a family history of retinoblastoma, positive genetic testing, and/or progression to bilateral retinoblastoma. Only patients with \u3e1-month follow-up were included. Chi-square test and Odds Ratio analyses were performed. Results: 465 of the 482 patients had sufficient follow-up data. 16% (n=72) of all patients, and 29% (n=37) of patients ≤1 year of age with unilateral retinoblastoma were likely to have germline disease (p=0.001). When compared to patients \u3e1 year of age (n=339), patients ≤1 year (n=126) demonstrated a greater likelihood of germline inheritance with a 2.96 odds ratio ([1.55 – 5.65]). Discussion: The inheritance of unilateral retinoblastoma is poorly understood. We found that 16% of children with unilateral retinoblastoma likely have germline inheritance, with a greater likelihood in children ≤1 year of age. Therefore, early assessment of inheritance and genetic testing of unilateral retinoblastoma may uncover germline disease and potential bilateral progression, for which a more conservative management approach to preserve vision should be considered