Ocular Oncology and Pathology最新文献

Introduction: Uncontrolled elevated intraocular pressure (IOP) during brachytherapy for posterior choroidal tumors is unreported. We present 2 patients who both experienced intractable elevated IOP during plaque brachytherapy.

Case presentation: Both patients experienced persistent elevated IOP unresponsive to all pressure-lowering agents following surgery that included transvitreal retinochoroidal biopsy and ruthenium-106 plaque application for posterior choroidal tumors in the superior quadrants. During plaque placement in patient 1, a large, dilated vortex vein was observed in the area where the plaque was to be placed. After plaque removal in both patients, IOP normalized without the need for additional pressure-lowering therapy.

Conclusion: We hypothesize that the clinical presentation in both patients was primarily attributable to two factors: first, pre-existing venous congestion and, second, the application of a plaque, which obstructed a superior vortex vein. This left the remaining vortex veins unable to compensate for the obstruction, leading to intractable IOP during plaque brachytherapy.

Introduction: We aim to describe 2 patients with metastatic uveal melanoma who developed metastases to the contralateral rectus muscles and review the literature on this rare presentation.

Case presentations: Patient 1 was a woman in her 60s with a history of cirrhosis who presented with a medium-sized choroidal melanoma in the right eye that was treated with plaque brachytherapy. She underwent regular hepatic imaging for surveillance post-treatment. Two-and-a-half years later, she developed diplopia, and a left medial rectus muscle lesion was found on MRI imaging. Biopsy was consistent with metastatic uveal melanoma. Systemic therapy with tebentafusp was initiated. The lesion slowly progressed over 2 years. The patient passed away from complications from her cirrhosis. Patient 2 was a man in his 70s with a large choroidal melanoma in the left eye treated with enucleation. He had metastatic disease at the time of diagnosis that was treated with multiple systemic therapies. Metastases to the right superior and lateral rectus muscles were noted on MRI imaging and were initially observed. He developed painful proptosis and was found to have acute enlargement of the lesions. Treatment with 30 Gy external beam radiation to the right orbit was performed with good local response. He passed away from tumor progression.

Conclusion: Metastasis to rectus muscles from uveal melanoma has historically been exceedingly rare. These cases highlight new challenges in treating symptomatic intraorbital metastasis as surgical outcomes and survival improve in patients due to advances in systemic therapy.

Introduction: Chronic macular edema is a well-recognized complication of radiation-induced maculopathy (RM). Current treatment methods vary in efficacy and clinical benefit. The potential of fluocinolone acetonide (FAc) slow-release intravitreal implants (Iluvien® implant) remains unclear. We hypothesized that local continuous delivery of low-dose corticosteroids may improve RM symptoms.

Methods: This study included 8 patients who presented with RM after ¹⁰⁶-Ru-plaque brachytherapy (n = 3), proton beam therapy (n = 2), or stereotactic radiation therapy (n = 3) with photons. All eyes were initially treated with triamcinolone injections but proved refractory to steroids. The Iluvien® implant was injected, and patients were followed to monitor clinical improvement.

Results: After 5 years, visual acuity improved in 3 patients, remained stable in 2 patients, and decreased in 2 patients. One patient progressed to no light perception following treatment. One patient was lost to follow-up after 5 years. Central macular thickness was reduced in 5 patients, stable in 1 patient, and increased in 1 patient.

Discussion: Slow-release FAc implants are a promising treatment option to improve the anatomical structure of the fovea and visual function. They may also reduce the frequency of intravitreal injections and the overall therapeutic burden.

Introduction: Mirvetuximab soravtansine is an antibody-drug conjugate approved for the treatment of folate receptor alpha-expressing ovarian cancer and is associated with ocular adverse events. Patients treated with mirvetuximab soravtansine often develop moderate to severe keratopathy, requiring topical steroids. Recent studies suggest a higher incidence of cataract formation than initially reported. This case series describes the rapid development of visually significant cataracts in 3 patients receiving mirvetuximab therapy.

Case presentations: Three female patients undergoing treatment with mirvetuximab soravtansine for platinum-resistant serous ovarian cancer experienced significant visual decline after 11, 18, and 19 treatment cycles, in 1 case progressing from 20/25 to counting fingers in both eyes within 10 weeks. All patients had baseline ophthalmic examinations and were treated with prophylactic topical corticosteroids to mitigate corneal complications. Despite standard management, each patient developed bilateral posterior subcapsular cataracts with substantial loss of visual acuity. Patients underwent sequential or same-day bilateral cataract extraction without complication. Postoperatively, all patients regained their baseline vision, and oncologic therapy was continued.

Conclusion: Rapidly progressing posterior subcapsular cataracts may occur in patients receiving prolonged mirvetuximab soravtansine therapy and may reflect drug-related toxicity, steroid exposure, or a synergistic interaction. Given that these patients did not develop cataracts until later cycles, ophthalmologic monitoring may be warranted beyond the duration specified in current treatment protocols. Early recognition and cataract surgery can restore vision without requiring cessation of oncologic therapy.

Introduction: Evidence-based medicine relies on publicly available research findings, and the non-publication of studies may predispose to incomplete evidence on intervention efficacy or redundant funding for re-attempting unpublished studies. This study investigated non-publication rates among US-registered interventional studies for uveal melanoma.

Methods: In April 2025, ClinicalTrials.gov was searched for interventional uveal melanoma studies. Interventional studies were included if completed at least 3 years prior to the database search, excluding completed trials awaiting results publication. Studies were labeled as having publicly available results if data were posted through ClinicalTrials.gov or in a journal publication. For published studies, we determined whether their primary study endpoint result was statistically significant. For all records, we collected study characteristics, including phase, sponsor, country of study, year of study initiation, enrollment, melanoma type, treatment type, and randomization status. The primary outcome was the overall rate of non-publication among all records. Second, we provided descriptive characteristics of included records and compared rates of non-publication between sublevels of primary endpoint significance status and study characteristics. Wherever applicable, the Fisher-exact, Wilcox rank-sum, and binomial exact tests analyzed these comparisons. Analysis was completed in RStudio (v2022.02 + 433).

Results: From 102 records, we identified 98 trials (N = 4,669) for final inclusion. Overall, 38% of records did not have an identifiable online publication on any platform. Whether published or unpublished, 23% and 16% of trials were terminated, respectively, and the reasons for termination were heterogeneous. Trials with industry sponsorship were significantly more often published than those without industry sponsorship (p = 0.024). No significant association was found between publication status and study phase, enrollment size, study duration, or randomization status. Among the 60 studies published online, 64% had reported significant primary study endpoints. Given this, the calculated probability of publication to ClinicalTrials.gov or in a journal was 65% [95% CI: 51.60-76.87%; p = 0.03]. No significant association was found between significant positive primary outcome results and randomization status or sponsor type.

Conclusion: About one-third of US-registered uveal melanoma interventional studies were not published online. Greater transparency of results or reasons for non-publication is needed.

Introduction: Uveal melanoma (UM) is a challenging malignancy, in terms of diagnosis, risk stratification, and treatment associated with high morbidity and mortality rates. It has been demonstrated that E2F-related pathways play a significant role in the tumorigenesis and distant metastasis of UM. In this study, the E2F target-related genes were utilized to construct and validate a prognostic risk score for patients with UM.

Methods: Using the TCGA-UVM cohort (n = 80), 192 E2F target genes were screened using gene set enrichment analysis (GSEA) to identify survival-associated genes. Prognostic genes were filtered using Kaplan-Meier analysis, univariate Cox regression, and LASSO, followed by multivariate Cox regression to construct a risk score model. The model was validated using the GSE22138 cohort (n = 63). Functional annotations of the risk score and its impact on stratifying tumor immune microenvironment components were assessed.

Results: A total of 9 genes (CDC25B, NME1, RFC2, PRDX4, NASP, UBE2S, PRKDC, MCM6, and LBR) passed the model construction pipeline. The risk score categorization system showed an independent prognostic power (HR: 2.34, 95% CI: 1.11-4.90, p = 0.025) and a good predictability of the survival outcome (receiver operating characteristic curve analysis: area under the curve = 0.730, 95% CI: 0.60-0.86, p = 0.002). When analyzing the most frequently mutated gene cohorts, the risk score was significantly lower in the mutated subgroups of GNAQ, SF3B1, and EIF1AX. In contrast, the risk score was notably higher in the BAP1 mutated subgroup. Copy number analysis of chromosomal arms showed significant correlations between the risk score and 1q, 3q, 3p, 6p, 8q. The high-risk group showed significant infiltration for NK cells, plasma B cells, gamma delta T cells, follicular T cells, M1 and M2 macrophages with lower infiltration of common myeloid progenitor cells. In addition, the high-risk group showed higher immune and microenvironment scores.

Conclusion: The developed E2F target-related gene model offers a robust tool for predicting the prognosis of UM patients. As a potential risk stratification method for UM, this model could have clinical applications pending further evaluation.

Introduction: Iris metastases are a rare initial presentation of a systemic malignancy, managed with chemotherapy and radiotherapy in most cases. These cases provide visual documentation of iris metastasis resolution following chemotherapy and radiotherapy and illustrate potential adverse effects associated with treatment response, including intraocular pressure variations and development of iris synechiae.

Case presentation: Two cases presented to metropolitan hospitals with ocular pain, which on ophthalmic review, revealed the presence of vascularised iris lesions. One case had a history of lung adenocarcinoma, on maintenance chemotherapy in addition to palliative radiotherapy to other metastatic deposits (case 1), whilst the other had no known history of malignancy (case 2). Case 2 required extensive investigations to obtain a histopathological diagnosis and stage the malignancy, after which he received chemotherapy followed by radiotherapy. In contrast, case 1 proceeded with immediate management with radiotherapy, followed by chemotherapy. Following the commencement of either treatment modality, tumour response was noted, with corresponding elevations in intraocular pressure, which was managed with topical glaucoma eye drops in addition to systemic acetazolamide. Both cases experienced complete remission of their iris metastases, though case 1 had extensive iris synechiae and case 2 passed away due to a rapid decline in their systemic malignancy.

Conclusion: Our case offers a unique visual insight into the impact of both systemic chemotherapy and localised radiotherapy on uncommon iris metastases, with sequential images taken at each stage of treatment. We underscore the importance of continual monitoring of the intraocular pressure during treatment, as tumour response was associated with elevated intraocular pressures in both of these cases. We hypothesise that this may be due to a combination of tumour liquefaction and hyphaema blocking trabecular meshwork outflow. Finally, despite treatment of the iris metastasis, patients may be left with residual iris synechiae, requiring additional surgical intervention to manage the intraocular pressure.

Introduction: Uveal melanomas are rare and usually detected in adults over 60 years old. We presented herein an unusual intraocular melanocytic tumor that does not fit into any known category in a child with 10-year follow-up data. The clinical findings, course, ultrasound, MRI, and pathology, including immunohistochemistry and gene profiling, of a child with pigmented intraocular masses simulating uveal melanoma are described. The tumor is provisionally called "endopapillary uveal melanocytic tumor of childhood" based on its unusual pathology and molecular biology. Comprehensive molecular testing, including MSK-IMPACT, which interrogates 468 known cancer genetic alterations, and Archer fusion testing (RNA sequence analysis) revealed no abnormalities.

Case presentation: Our patient was a 7-month-old white boy with a suspected mass in the left eye. There was no family history of melanoma. An MRI scan revealed a 1.9 × 1.7-cm well-circumscribed, heterogeneously T1 pre-contrast hyperintense mass, which demonstrated heterogeneous low signal intensity on T2-weighted imaging. A needle biopsy using a 25-gauge needle revealed a pigmented tumor, so we performed an enucleation. Upon histopathologic examination after enucleation, the tumor was densely pigmented, without significant necrosis or internal cavitation. Tumor cells grew around vascular "papillae." Six years later, the patient is alive and shows no evidence of local or systemic recurrence.

Conclusion: Our case exhibited unique features and pathology, without any of the known genetic abnormalities associated with uveal melanoma and does not match the descriptions in the existing literature. Thus, we have named these masses "endopapillary uveal melanocytic tumor of childhood."

Background: Ophthalmic pathology has been of paramount importance for the development of medical and surgical ophthalmology. Unfortunately, many laboratories are being closed down due to short-sighted financial reasons. This lecture aims at demonstrating the continuing significance of this subspecialty even in modern times.

Summary: Various examples from different structures of the eye (conjunctiva, cornea, retina) are illustrated to document the relevance of a profound knowledge of ophthalmic pathology for the advancement of both medical and surgical treatment.

Key message: The impact of ophthalmic pathology even in the era of genetics and molecular biology continues to advance our knowledge substantially on behalf of the best possible treatment of our patients.

Introduction: Uveal melanoma (UM) metastasis follows variable temporal trajectories, with recurrences ranging from rapid onset to decades post primary therapy. Outcomes after metastasis also vary significantly. Predicting high-risk "early" progressors from "late" recurring phenotypes would facilitate tailored approaches to management.

Methods: A literature review was conducted to synthesise clinicopathologic and molecular predictors of metastatic latency and their impact on survival outcomes in patients with UM.

Results: Early dissemination is associated with older age, male sex, larger basal dimensions, and ciliary body involvement. Genetically, monosomy 3, 8q gain, and BAP1 loss drives a rapid-progression phenotype and poor survival. Conversely, SF3B1 mutations define a distinct late-onset cohort (median: >6 years) with persistent lifetime risk. PRAME expression significantly accelerates metastatic kinetics, even in gene expression profiling class 1 tumours. While early recurrence correlates with dismal outcomes, late-onset disease is associated with extended post-metastasis survival and greater eligibility for interventions like liver-directed therapy.

Conclusion: Metastatic timing is related to biologic rather than stochastic determinants. Integrating molecular profiling with clinical staging and patient factors allows for more precise temporal risk stratification. These insights are essential for tailoring surveillance intensity and selecting candidates for emerging adjuvant therapies, such as tebentafusp and protein kinase C inhibitors.