Dalvin, Lauren A.

Purpose: To describe a case of locally invasive conjunctival squamous cell carcinoma (SCC) refractory to plaque radiotherapy. Case Description: A 69-year-old man presented with a recurrent conjunctival tumor after 6 previous cycles of topical 5-fluorouracil chemotherapy and excisional biopsy showing invasive SCC with positive margins. There was a mild anterior chamber reaction. By the time of repeat excisional biopsy, the conjunctiva had ulcerated with underlying scleralysis associated with histopathologic evidence of scleral involvement by SCC. After subsequent tectonic scleral patch grafting, plaque radiotherapy was applied after which the disease appeared to be controlled for 9 months. The eye then developed progressive conjunctival ulceration and scleralysis with progressive ectropion. Exenteration was performed, revealing locally invasive SCC into palpebral conjunctiva, ciliary body, and choroid. Conclusions: Conjunctival SCC can be locally invasive with destruction of the globe, despite plaque radiotherapy. Clinicians should be suspicious of invasive diseases in cases of ocular surface squamous neoplasia that are poorly responsive to topical chemotherapy. Associated anterior chamber cell and progressive scleralysis should also raise concern for invasive malignancy.

Purpose To investigate the clinical features, treatments, and outcomes of patients with secondary orbital lymphoma. Major Findings In this cohort of 31 patients, 15 (48.4%) were female and 27 (87.1%) were white. Follicular lymphoma was the most common subtype (n = 13, 41.9%) and was more associated with unilateral disease compared to other subtypes (p = 0.01). Common presenting symptoms included a palpable mass (n = 17, 54.8%), eyelid swelling (n = 16, 51.6%), and ptosis (n = 12, 38.7%). Patients were most often diagnosed with Ann Arbor Stage IV lymphoma (n = 17, 54.8%) via incisional biopsy (n = 13, 41.9%). Radiation therapy (n = 9, 29.0%) was the most common initial treatment, and most patients received radiation (n = 19, 61.3%) and/or chemotherapy (n = 21, 67.7%). A majority of patients had final best corrected visual acuity (BCVA) within 1 line of initial BCVA (n = 19, 82.6%) and had no local recurrences (n = 21, 67.7%). However, complete remission was rare (n = 3, 9.7%), and systemic recurrence occurred in over half of patients (n = 18, 58.1%). Conclusions Follicular lymphoma was the predominant subtype of secondary orbital lymphoma in this cohort. Most patients with secondary orbital lymphoma presented with advanced disease where few achieved complete remission and more than half of the patients developed systemic recurrence despite majority retaining visual acuity.

Novel systemic anticancer therapies, including immune checkpoint inhibitors (ICIs), antibody-drug conjugates (ADCs), bispecific antibodies, and next-generation targeted agents, have improved survival, expanded into earlier disease settings, and created a growing population of long-term survivors. However, these therapies introduce toxicity profiles that differ substantially from those of traditional cytotoxic chemotherapy, including differences in organs affected, timing of onset, management strategies, and long-term sequelae. Tailored approaches to monitoring, diagnosis, and treatment are therefore required, along with stronger evidence to guide strategies that reduce morbidity and mortality while maintaining antitumor efficacy. Importantly, patients' lived experiences of toxicity often do not align with clinician-graded Common Terminology Criteria for Adverse Events classifications. Nonobservable symptoms, daily functioning, and quality of life must also be taken into account. Here, ocular and cutaneous adverse events are used as illustrative examples of how toxicities that may appear mild can become unacceptable when they impair function, quality of life, or treatment sustainability. Interdisciplinary collaboration between oncologists and organ specialists is essential for optimal recognition and management. At the same time, the evidence base for toxicity risk and management must continue to evolve through registries such as Side Effect Registry Immuno-Oncology and prospective comparative studies. Better tailored treatment strategies, particularly for immune-related adverse events, are needed to preserve both tumor response and organ function while reducing reliance on corticosteroids and broad immunosuppression. Although these therapies are highly effective, their risks must be better understood and managed to maximize patient benefit.

The objective of this study was to compare drug response of uveal melanoma patient-derived cell lines (PDLs) and patient-derived organoids (PDOs) with response of commercially available cell lines and contextualize laboratory outputs in terms of clinical trial results. Uveal melanoma commercial cell lines, PDLs, and PDOs were treated with drugs that were ultimately utilized in clinical trials. Four treatments were chosen for promising laboratory results that failed to yield clinical response, while darovasertib was a surrogate positive control given initial favorable clinical trial data in the neoadjuvant setting. Drug concentrations were matched to laboratory work that supported progression to clinical trials. Viability was measured using PrestoBlueHS Cell Viability Reagent. Commercial cell lines showed promising viability reduction similar to prior laboratory results with treatments, including 5-μM darovasertib, 700-nM selumetinib, 700-nM selumetinib + 1000-nM MK-2206, 500-nM sotrastaurin + 1000-nM alpelisib, and 100-nM trametinib, with overall viability reduced to 32.5% for all drugs. However, PDLs (viability 52.8%) and PDOs (viability 80.4%) showed more treatment resistance ( P < 0.05), better simulating ultimate lack of efficacy found in clinical trials. While uveal melanoma with BAP1 loss demonstrated greater treatment resistance under some conditions, other factors such as cell morphology or culture in a three-dimensional environment appeared to be more consistent drivers of therapeutic sensitivity. PDLs and PDOs may more accurately represent uveal melanoma clinical response. Demonstrating efficacy of novel therapeutics in these models could improve the likelihood of successful translation for future clinical trials, but future studies are needed to define clinically meaningful in-vitro response thresholds.

Purpose To explore the relationship between systemic comorbidities and presenting tumor T category in patients with uveal melanoma. Methods Single-center, retrospective cohort study of patients with posterior uveal melanoma initially diagnosed between January 2000 and December 2016. Univariate and multivariate ordinal logistic regression analyses were performed to identify comorbidities associated with presenting tumor T category, as classified by AJCC criteria. Results Initial presenting AJCC T category was T1 in 190 (43%), T2 in 130 (29%), T3 in 89 (20%), and T4 in 38 (9%). The most common comorbidities present were hypertension (250 patients, 56%), hyperlipidemia (211, 47%), obesity (137, 31%), and diabetes mellitus (87, 19%). Of these, obesity ( p = 0.034), hypertension ( p = 0.017), and diabetes mellitus ( p < 0.001) were associated with earlier presenting T category on univariate ordinal logistic regression. After multivariate regression, only diabetes mellitus ( p = 0.01) and obesity ( p = 0.04) remained significantly associated with earlier T category on initial presentation. Conclusion Among patients presenting with uveal melanoma, diabetes mellitus and obesity were associated with earlier presenting T category, which could reflect earlier detection of uveal melanoma in patients undergoing annual diabetic retinopathy screening examinations or having more frequent contact with the healthcare system. Larger studies should further explore this association and examine the utility of increased ocular screening in early detection of uveal melanoma.

ABSTRACT Intraocular lymphomas, including vitreoretinal and choroidal lymphoma, can simulate the clinical presentation of other benign and malignant ocular diseases resulting in diagnostic delays. Multimodal imaging features can raise early clinical suspicion to support appropriate subspecialty referrals and treatment for patients affected by these conditions. This review synthesises current evidence on the diagnostic and prognostic value of characteristic imaging features of these rare malignancies. Findings are reviewed based on imaging modality, including fundus photography, optical coherence tomography, fundus autofluorescence, fluorescein angiography, indocyanine green angiography, optical coherence tomography angiography, and ultrasound. We emphasise discriminative biomarkers that heighten suspicion for either vitreoretinal or choroidal lymphoma, as well as key findings to discriminate between lymphoma and alternative diagnoses. We further describe longitudinal changes in multimodal imaging features that can facilitate tracking disease progression or treatment response. By consolidating modality‐specific findings, this review aims to facilitate early referral and accurate diagnosis of these rare malignancies.

Radiation exposure to the eye during cancer treatment can lead to ocular radiation injury (ORI), a devastating condition that can have a profound and permanent impact on vision-related quality of life. Rodent models do not have adequate ocular anatomy to accurately simulate human ORI, and modeling in non-human primates is limited by logistical and ethical concerns. To improve future translational research investigating ways to treat or prevent ORI, we developed protocols for a tree shrew model of ORI. Northern tree shrews (Tupaia belangeri) were obtained by our laboratory. Custom housing and handling methods were developed, including custom body suits to maintain the tree shrew’s body temperature during procedures. Radiation delivery was optimized to accurately deliver radiation, and imaging was performed to observe fundus changes from ORI. Optimization of tree shrew handling, housing, anesthesia approaches, radiation delivery, and clinically-relevant ocular imaging permitted successful induction and assessment of ORI in tree shrews. With these protocols, tree shrews can be used as a highly relevant model organism with key anatomic features similar to humans to study ORI.