PURPOSE:To explore the safety of high-dose intravitreal topotecan for recurrent retinoblastoma management in human eyes. METHODS:There were 81 consecutive injections of high-dose intravitreal topotecan (90 μ g/0.18 cc‒100 µ g/0.20 cc on a monthly basis) in 25 eyes with recurrent retinoblastoma. Tumor control and injection-related complications were assessed at each visit. Each tissue was reviewed for complication-associated alterations, and systemic evaluation for myelosuppression, infection, metastasis, and death was assessed. RESULTS:At the time of injection, the mean patient age was 26 months, and in all cases, the injection was for recurrent retinoblastoma (n = 24 eyes, 100%) involving intraretinal tumor (n = 6 eyes, 24%), vitreous seeds (n = 3 eyes, 12%), subretinal seeds (n = 13 eyes, 52%), or multiple tumor types (n = 3 eyes, 12%). The mean intraretinal tumor thickness was 2.2 mm, vitreous seed thickness varied from pinpoint to confluent seeds, and subretinal seed was 0.9 mm. The total number of high-dose intravitreal topotecan injections was 81 (mean 3.2 per eye) with 39 (48%) injections given without concurrent chemotherapy and 42 (52%) given with concurrent intravenous or intra-arterial chemotherapy. At mean follow-up of 10 months after first injection, tumor control was achieved in all cases (n = 81 injections, 100%), and there was no local or systemic complication in any of the 81 injections. There was no case of extraocular tumor extension, myelosuppression, infection, metastasis, or death. CONCLUSION:Based on this analysis, high-dose intravitreal topotecan is safe and effective in the management of recurrent small retinoblastoma in humans. Further investigation of the limits of this therapy is warranted.

TPS9607 Background: Uveal melanoma (UM) is the most common intraocular malignant tumor in adults. Primary UM are effectively treated by plaque radiotherapy or enucleation; however, up to 50% of UM patients ultimately succumb to advanced disease. Tebentafusp-tebn is a bispecific gp100 peptide human leukocyte antigen (HLA)-directed cluster of differentiation 3 (CD3) T-cell engager that became the first FDA approved treatment for unresectable or metastatic UM. Among the metastatic UM patients who received tebentafusp on clinical trial (IMCgp100-01 (n=19), IMCgp100-102 (n=146), and IMCgp100-202 (n=245)), 12 patients had recurrent orbital tumors. All orbital lesions were stable or had achieved shrinkage with tebentafusp. The best percentage changes from baseline were reported as -3 to -40% reduction in intra-ocular target lesions. All intra-ocular non-target lesions were stable or achieved a complete response after tebentafusp treatments. These preliminary data indicate that tebentafusp may have potential for treating surgically unresectable primary UM. Methods: This is an investigator-initiated, prospective, single arm phase II trial evaluating neoadjuvant tebentafusp in patients with locally advanced primary UM [NCT06414590]. Patients must be 18 years or older, HLA-A*02:01 with a primary UM with T3 or T4 category tumor size. Patients cannot have a symptomatic UM that requires immediate ophthalmological intervention such as enucleation. Patients will be treated with up to 8 weeks of neoadjuvant tebentafusp, followed by radioactive plaque or enucleation. Tebentafusp will be administered as follows: 20mcg on Day 1, 30mcg on Day 8, 68 mcg on Day 15, and weekly doses of 68 mcg thereafter. The first three treatments will require inpatient hospitalization for overnight observation. The primary endpoint of the study is regression (defined as ≥ 20% reduction in tumor volume) of primary UM after tebentafusp treatment in 20% of treated patients. Secondary endpoints include toxicity assessment and ctDNA analysis in both blood and aqueous humor. Exploratory endpoints include changes to visual acuity, radiation dose to the fovea, and treatment (enucleation to plaque brachytherapy). The efficacy of this combination treatment will be assessed using the Simon’s two stage design. In stage I, a total number of 8 patients are accrued and if there are 0 responses among these 8 patients, further enrollment of patients may be stopped. Otherwise, an additional 11 patients will be accrued in stage II, resulting in a total sample size of 19 patients. Enrollment began in September 2025 at Thomas Jefferson University Hospital, in conjunction with Wills Eye Hospital. Clinical trial information: NCT06414590 .

Purpose: To evaluate the impact of radiation dose to the optic disc and foveola on ≥15-letter visual acuity loss following plaque radiotherapy of posterior uveal melanoma (PUM) in the pre-anti-vascular endothelial growth factor (anti-VEGF) era. Methods: We reviewed data on 4000 consecutive patients to assess radiation dose and dose rate to the optic disc and foveola on ≥15-letter visual acuity loss. Results: The (median) patient age was 60 years, tumor diameter was 11.0 mm and thickness 4.5 mm, and distance to the optic disc was 4.0 mm and foveola 3.0 mm. The (median) dose (centiGray (cGy)) (dose rate (cGy/hour)) to the tumor apex was 8079 cGy (85 cGy/hour (cGy/hr)), to the optic disc was 3346 cGy (34 cGy/hr), and the foveola was 4021 cGy (40 cGy/hr). By Kaplan-Meier analysis, eyes that received ≤4000 cGy to optic disc developed ≥15-letter vision loss at 3 years with foveal dose 0-2000 cGy in 41%, 2001-4000 cGy in 60%, and 4001-6000 cGy in 68% ( p <0.01). For eyes that received >4000 cGy to optic disc, ≥15-letter vision loss at 3 years was poorer ( p nonsignificant). For those with optic disc dose ≤4000 cGy, a comparison (foveal dose 0-2000 versus (vs.) 2001-4000 cGy) led to hazard ratio (HR) of 1.71 ( p <0.01) and (foveal dose 2001-4000 vs. 4001-6000 cGy) showed HR of 1.21 ( p <0.03) for ≥15-letter vision loss. Conclusions: In the pre-anti-VEGF days, following treatment of PUM with plaque radiotherapy, higher radiation doses to the optic disc and foveola demonstrated greater ≥15-letter vision loss.

PURPOSE:To evaluate clinical factors that lead to ≥15-letter visual acuity loss following plaque radiotherapy of posterior uveal melanoma (PUM) in the pre-anti-vascular endothelial growth factor (anti-VEGF) era. METHODS:The authors reviewed data on 4,000 consecutive patients with plaque-irradiated PUM managed between May 1976 and November 2008 to identify parameters predictive of ≥15-letter vision loss. RESULTS:Data included median patient age (60 years), diabetes mellitus (11%), median tumor diameter (11.0 mm) and thickness (4.5 mm), and median distance to optic disk (4.0 mm) and foveola (3.0 mm). Kaplan-Meier analyses revealed ≥15-letter loss at 1 versus 3 versus 5 versus 10 years in 30% versus 60% versus 73% versus 82% of patients. Multivariate analyses revealed factors predictive of ≥15-letter loss included greater tumor thickness ( P < 0.01, hazard ratio [HR] 1.14), shorter distance to foveola ( P < 0.01, HR 0.93), greater radiation dose to foveola ( P < 0.01, HR 1.01) and lens ( P < 0.01, HR 1.01), and presence of diabetes mellitus ( P < 0.01, HR 1.11). For small PUM, multivariate risk factors included older age ( P < 0.01), diabetes mellitus ( P < 0.01), and shorter distance to foveola ( P < 0.02); for medium PUM, risk factors included greater tumor thickness ( P < 0.01), shorter distance to foveola ( P < 0.01), and less (but shorter) radiation dose to foveola ( P < 0.01); for large PUM, risk factors included greater tumor thickness ( P < 0.01) only. CONCLUSION:In the pre-anti-VEGF days, following treatment of PUM with plaque radiotherapy, clinical and treatment factors predictive of ≥15-letter visual acuity loss included greater tumor thickness, shorter distance to foveola, greater radiation dose to foveola and lens, and presence of diabetes mellitus.

PURPOSE:To evaluate ≥15-letter visual acuity loss after plaque radiotherapy of posterior uveal melanoma (PUM) in the pre-anti-vascular endothelial growth factor era. METHODS:We reviewed data on 4,000 consecutive patients managed between 1976 and 2008 regarding patient demographics, tumor features, treatment factors, and ≥15-letter visual acuity loss over time based on tumor size category of small (0-3.0 mm thickness), medium (3.1-8.0 mm), and large (>8.0 mm). RESULTS:Of the 4,000 patients, there were small (n = 1,011 eyes, 25%), medium (n = 2,445, 61%), and large (n = 544, 14%) tumor categories. The PUM touched the optic disc (n = 560, 14%) and/or extended under the foveola (n = 644, 16%). Comparative analysis (small vs. medium versus large PUM) showed small tumor category with demographics of younger age ( P < 0.01) and greater White race ( P < 0.05), presenting features of visual acuity ≥20/40 ( P < 0.01) and closer proximity to the optic disc ( P < 0.01) and foveola ( P < 0.01), and radiation treatment parameters most intense at the foveola ( P < 0.01). The median radiation dose to the optic disc (3,100 vs. 3,257 vs. 4,336 cGy, P < 0.01) and the foveola (3,964 vs. 3,864 vs. 4,598 cGy, P < 0.01) was noted. Overall, ≥15-letter loss was found in 62% patients at median 16 months. By Kaplan-Meier analysis of all cases, ≥15-letter loss at 1 versus 2 versus 3 versus 5 versus 10 years was present in 30% versus 48% versus 60% versus 73% versus 82%. CONCLUSION:In the pre-anti-vascular endothelial growth factor days, after treatment of PUM with plaque radiotherapy, visual acuity showed ≥15-letter loss in 62% of patients at median 16 months.

Objective To evaluate and compare epidemiology, clinical and histopathologic features, and outcomes of conjunctival papilloma in historical and modern cohorts. Design Retrospective comparative cohort study. Participants Patients with conjunctival papilloma at a tertiary referral center between 2015 and 2024. Methods A retrospective review of Oncology and Pathology records was conducted to identify all patients with conjunctival papilloma over a 10-year period (2015–2024). Data collected included demographics, HPV vaccination status, clinical tumor characteristics, treatment modalities, outcomes, and histopathologic findings of excised lesions. Patients were stratified by age (≤20 vs.> 20 years). Findings were compared with a historical cohort managed at the same institution (1970–2012). Results Fifty-six conjunctival lesions were identified in 40 patients (mean age, 50 years; range, 8–89). Those older than 20-years-old demonstrated thicker tumors (4.6 vs. 2.2 mm, p = 0.03) with a predilection for the fornix (36%vs 0%; p = 0.02), whereas younger patients more commonly had bulbar lesions (46%vs 13%; p = 0.03). There was no difference in configuration (sessile vs. pedunculated, p > 0.99) between the age groups. The most common primary treatments included excision with cryotherapy (38%) or excision with cryotherapy plus interferon alfa-2b (38%). A combination of excision, cryotherapy and adjuvant oral cimetidine and interferon alfa-2b was significantly more common in the children and adolescent cohort compared to adults (56%vs. 0%, p < 0.01). Three tumors (9%) recurred following treatment. None of the lesions underwent malignant transformation. Compared with the historical cohort, patients in this study were older (mean 50 vs 43 years, p = 0.04), with a higher proportion of diffuse lesions (14%vs 3%, p < 0.01). Historically, most papillomas were treated with excision and cryotherapy alone (62%vs. 38%, p < 0.01), whereas, in our modern cohort there was a significantly increased use of excision and cryotherapy with adjuvant interferon alfa-2b (38%vs. 18%, p < 0.001). Conclusion This study demonstrates evolving demographic, clinical characteristics, and treatment trends in conjunctival papilloma over the past decade, including a shift toward an older patient population. Despite these changes, treatment outcomes remain favorable.

PURPOSE:To better define the frequency and types of retinal pigment epithelial (RPE) tumors. METHODS:Retrospective review of all computer-coded RPE tumors over a five-decade period. RESULTS:Of 926 consecutive patients with RPE tumors, the specific diagnosis included solitary congenital hypertrophy of the retinal pigment epithelium (n = 727, 79%), multifocal congenital hypertrophy of the RPE (n = 42, 4%), torpedo maculopathy (n = 7, 1%), RPE hamartomas associated with familial adenomatous polyposis (n = 10, 1%), congenital simple hamartoma of the RPE (n = 5, 1%), combined hamartoma of the retina and RPE (n = 99, 11%), benign RPE adenoma (n = 34, 3%), and malignant RPE adenocarcinoma (n = 2, <1%). There were differences in RPE tumors regarding patient age (P < 0.01), race (P < 0.01), sex (P < 0.01), presenting visual acuity (P < 0.01), number of tumors (P < 0.01), tumor basal diameter (P < 0.01), tumor thickness (P < 0.01), and distance to the optic disc (P < 0.01) and foveola (P < 0.01). There were differences in RPE tumors regarding imaging with ultrasonography (P < 0.01), optical coherence tomography (P < 0.01), and prevalence of macular epiretinal membrane, cystoid macular, edema, and subretinal fluid on optical coherence tomography (P < 0.01). By autofluorescence and fluorescein angiography, nearly all lesions that were imaged were hypoautofluorescent/hypofluorescent except for combined hamartoma of the retina and RPE (P < 0.01). Outcomes revealed visual acuity loss ≥3 lines (≥15 letters) at 10 years more often in combined hamartoma of the retina and RPE (20%), adenoma (21%), and adenocarcinoma (100%) (P < 0.01) and 10-year nodular growth in congenital hypertrophy of the RPE (1%), adenoma (9%), and adenocarcinoma (100%) (P < 0.01). CONCLUSION:Retinal pigment epithelial tumors comprise a spectrum in demographics, clinical features, and outcomes. Most remain stable over time with little impact on visual acuity except for combined hamartoma of the retina and RPE, adenoma, and adenocarcinoma.

PURPOSE:To evaluate outcomes of single-stage posterior lamellar reconstruction using buccal mucosal grafts after posterior lamellar resection (PLR) for eyelid sebaceous carcinoma. METHODS:Retrospective consecutive case series at an academic center (2020-2025). Patients with histopathologically confirmed sebaceous carcinoma who underwent PLR with immediate buccal mucosal grafting, without other posterior lamellar substitutes, were included. Outcomes included graft integration, eyelid position, ocular surface morbidity, complications, and change in visual acuity (VA). RESULTS:Thirteen eyelids in 12 patients were included (mean age 72.1 ± 10.3 years; 61.5% female). Tumors involved the upper eyelid in nine cases (69.2%) and lower eyelid in four (30.8%). Pagetoid spread was present in 10/11 cases with available data (90.9%). All patients underwent conjunctival cryotherapy following PLR. Grafts were harvested from lip mucosa in 12 cases (92.3%) and cheek mucosa in 1 (7.7%), with mean graft area 946.9 ± 448.5 mm2 (range 300-1600). Graft integration was successful in 100%. No entropion, ectropion, or new ptosis occurred; lower-lid retraction occurred in one case (7.7%), mild lagophthalmos in two (15.4%). Ocular surface morbidity included neurotrophic keratopathy in three cases (23.1%) and limbal stem cell deficiency in three (23.1%); two (15.4%) required permanent lateral tarsorrhaphy and one underwent evisceration (7.7%). Among nine eyes with paired data, three (33.3%) lost > three Snellen lines. No local recurrence or distant metastasis occurred during follow-up. CONCLUSION:Buccal mucosal grafting provided reliable single-stage posterior lamellar reconstruction after PLR with complete graft integration and generally stable eyelid position; morbidity was driven primarily by ocular surface disease, supporting proactive corneal protection.

9515 Background: Surgical resection of locally advanced basal cell carcinoma of the head and neck (BCCHN) often carries significant morbidity. This phase II study seeks to investigate the response to neoadjuvant cemiplimab on surgical morbidity in BCCHN patients. Methods: In this prospective, nonrandomized, multicenter, phase II trial (NCT05929664), anti-PD1 and HHI-naive patients with resectable BCCHN received 2 to 6 cycles of cemiplimab (350mg IV Q21 days), followed by surgical resection or biopsy. Surgical plan at enrollment required functional organ sacrifice (orbit, eyelid, ear, nose, lip, or facial nerve). RECISTv1.1 tumor measurements were performed every 2 cycles to determine primary endpoints of ORR and DCR. Patients with PD (>20% growth) or SD with 5 to 20% growth at any assessment were offered HHI or surgery. Patients with CR at any assessment proceeded to surgery or directed biopsy. Secondary endpoints included: surgical benefit rate (SBR, defined as rate of functional organ preservation, determined by the investigator, comparing surgical resection to surgical plan at time of enrollment), rate of pCR, safety (CTCAEv5.0), and quality of life (FHNSI, FACE-Q and VFQ-25). Correlative studies include examination of the tumor immune microenvironment related to functional changes in immune cell composition. Results: Between August 2023 and September 2025, 33 patients were enrolled: 40-89 yo; 22 M/11 F; sites of disease included eyelid (n=17), orbit (n=4), nose(n=5), lip (n=1), facial nerve (n=1), ear (n=1), and scalp or cheek (n=5). 30 were evaluable: 23 (76.7%) completed 6 cycles. Among the remaining 7 patients, 1 experienced CR after 4 cycles; 1 was taken off therapy for grade 3 myalgia; 1 had SD with 5-20% growth and 2 had PD, and were taken to surgery per protocol; 2 chose surgery due to stagnant response after initial PR. 12 patients (40%) experienced a grade 1-2 treatment-related AE. 1 patient (3.33%) experienced a grade 3 treatment-related AE as above. The ORR was 66.67%. The DCR was 90.0%. Based on RECISTv1.1 criteria, 3.33% (n=1) had CR, 63.33% (n=19) had PR, 23.33% (n=7) had SD, and 10.0% (n=3) had PD as best overall response 8 patients (26.67%) achieved pCR. The SBR was 43.3%, with functional preservation of the eyelid (n=7), nose (n=2), lip (n=1), ear (n=1), or orbit (n=1). Conclusions: Neoadjuvant cemiplimab had an acceptable safety profile and shows promising efficacy in the treatment of advanced, surgically-resectable BCCHN. This novel approach may alleviate the morbidity of subsequent surgical resection. (NCT05929664 supported by Regeneron Pharmaceuticals, Inc.). Clinical trial information: NCT05929664 .

PURPOSE:To evaluate tissue glue-assisted plaque placement regarding accuracy, stability, and longer-term outcomes for choroidal tumors with scleral thinning. METHODS:All patients with tissue glue-assisted plaque radiotherapy at a single ocular oncology center were evaluated for patient demographics, tumor features, surgical details, tumor response, and glue-related complications. RESULTS:There were 13 patients (mean age 72 years) treated with tissue glue-assisted plaque radiotherapy for choroidal melanoma (n = 12) or choroidal metastasis (n = 1). At presentation, the tumor was mean 4.3 mm to the optic disk and 2.0 mm to the foveola with a mean basal diameter of 9.5 mm and a thickness of 4.2 mm. In all cases, the tissue glue-assistance was used due to extreme scleral thinning in the bed of proposed radiation. The plaque size was 15 mm (n = 5), 18 mm (n = 7), or 20 mm (n = 1). At application, there was no immediate glue hypersensitivity, ultrasonography confirmed accuracy of placement, and the glue remained adherent for the entire treatment duration (mean 113 hours) with stable plaque location at removal. At removal, the plaque-glue composite was peeled off the globe without need for glue dissolvent and without scleral disruption. At 12 months, mean melanoma thickness was 2.7 mm (regression 36%). There were no conjunctival, corneal, or scleral complications. CONCLUSION:Tissue glue-assisted plaque radiotherapy is safe and effective for treatment of choroidal tumors with thin sclera.

TPS9606 Background: Surgical resection of locally advanced basal cell carcinoma of the head and neck (laBCCHN) is often not feasible due to tumor size and proximity to vital structures with risk of significant deformity. Prior data suggest that neoadjuvant therapy could have a major impact on preserving critical structures, especially in the head and neck. The PD-1 inhibitor cemiplimab (REGN2810) has shown significant response rates for metastatic BCC after progression or intolerance of Hedgehog inhibitor (HHI) therapy. However, cemiplimab has not been investigated in the neoadjuvant setting for laBCCHN. To address this gap, this multi-center phase II study seeks to assess the response to neoadjuvant cemiplimab in the treatment of HHI-naïve laBCCHN. Methods: Patients with HHI-naive laBCCHN will receive response-adaptive, neoadjuvant IV cemiplimab 350mg every 3 weeks for an initial 2 cycles. The primary endpoint is the fraction of patients demonstrating clinical response after 2 cycles. All patients will undergo RECIST v1.1 response assessment by CT or MRI, and if not radiographically measurable, caliper measurement will be utilized to evaluate the primary endpoint. Those with RECIST v1.1 progression or stable disease with >5% growth will be considered non-responders and will proceed with surgery or other standard of care (e.g. HHI). Patients with stable disease (+5% to -20%) and RECIST v1.1 response will be considered responders and will continue to additional cycles of therapy and clinical assessment (imaging every 2 cycles, total cycles = 6). Patients with complete clinical response prior to completing 6 cycles may proceed to surgery for resection or biopsy of tumor site. Secondary endpoints include rate of functional organ preservation, pathologic response, safety, and quality of life. Correlative analyses will be performed on pre- and post-cemiplimab tumor specimens and peripheral blood samples to assess treatment-related changes in the immune microenvironment related to functional changes in immune cell composition. This study is open with 22 patients enrolled at the time of submission, with a planned total enrollment of 35 patients. Clinical trial information: NCT05929664 .

Purpose: This article explores the application of artificial intelligence (AI) in the differentiation of choroidal melanocytic lesions, specifically choroidal nevi and small melanomas, within the field of ocular oncology. The primary topic highlights the significance of accurately diagnosing these lesions to enhance patient outcomes and management strategies. Design: The study reviews of the role of AI in differentiating choroidal melanocytic lesions, particularly choroidal nevi from small melanomas, examining clinical and imaging risk factors. It explores deep learning (DL) applications for image classification and assesses AI's potential impact on patient care, diagnostic accuracy, and regulatory concerns in ocular oncology. Methods: To achieve this, the methods discussed in this paper revolve around employing DL techniques, which utilize artificial neural networks to analyze high-dimensional medical images. This approach enables automated classification and image analysis of ophthalmic data, allowing for the identification of intricate patterns and features that may be imperceptible to clinicians. Additionally, the text reviews existing clinical and imaging risk factors associated with the growth of choroidal nevi into melanoma, leveraging this information to inform and enhance AI algorithms. Results: The anticipated results of integrating AI into clinical practice include increased diagnostic accuracy, which can lead to earlier identification of high-risk lesions and, consequently, timely interventions. This proactive approach has the potential to improve patient care significantly by facilitating better management strategies, thus enhancing patient outcomes. Artificial intelligence may also uncover subtle imaging features that would otherwise be overlooked, providing a more comprehensive assessment of lesions. Conclusion: In conclusion, the paper emphasizes the transformative potential of AI in ocular oncology, advocating for its integration with existing imaging technologies. While AI offers promising advancements in diagnostic practices and patient care, the paper also acknowledges the necessity of addressing regulatory and implementation challenges to fully harness these benefits. Overall, the incorporation of AI technologies into the diagnostic workflow has the potential to not only save vision but also improve survival rates, marking a significant step forward in the management of choroidal melanocytic lesions. Financial Disclosure(s): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

Purpose:To evaluate the efficacy and safety of high-dose intravitreal topotecan (IvitTopo) for recurrent retinoblastoma.Methods:There were 13 patients with recurrent retinoblastoma treated with high-dose IvitTopo (90 micrograms [mu g]/0.18cc-100 mu g/0.20cc). The primary outcome measures were tumor control, globe salvage, and treatment complications.Results:At date first seen, median patient age was 9 months, and the affected eye was classified as International Classification of Retinoblastoma Group B (n = 2, 15%), Group C (n = 3, 23%), or Group D (n = 8, 62%) retinoblastoma with initial therapy of intravenous chemotherapy (n = 9, 69%) or intraarterial chemotherapy (n = 4, 31%). Recurrent tumor was detected at median 10 months as solid tumor (n = 3), subretinal seeds (n = 10), and/or vitreous seeds (n = 3) and high-dose IvitTopo (median three injections) delivered at monthly intervals. Additional chemotherapy was delivered by intraarterial (n = 8, 62%) or intravenous (n = 1, 8%) routes, and one eye received additional cryotherapy (n = 1, 8%). In three cases (23%), there was no additional therapy. At mean follow-up of 9 months, regression of solid tumor, subretinal seeds, and vitreous seeds was achieved in 12 cases (92%), and globe salvage was achieved in all cases (n = 13, 100%). Of those three eyes treated with high-dose IvitTopo alone, tumor control was initially achieved in all cases (100%), but one case that previously demonstrated massive vitreous seeding showed late recurrence of a solitary vitreous seed at 8 months. There were no complications.Conclusion:High-dose IvitTopo is an effective and safe therapy for recurrent retinoblastoma, in conjunction with other therapy, and possibly as a stand-alone therapy.

BACKGROUND:There is limited literature on tumor location of uveal melanoma (UM) and the relative impact on metastasis-free survival (MFS). METHODS:A review of 1001 consecutive eyes with UM was performed and precise tumor location was identified according to quadrant (5 zones), clock hour (13 zones), anteroposterior (5 zones), and a combination of clock hour and anteroposterior regions (49 zones). Heat maps were constructed for frequency in each zone and Kaplan-Meier estimates for 5- and 10-year MFS was calculated. RESULTS:The UM quadrant regions included central (macula and juxtapapillary) (18%), superior (19%), nasal (18%), inferior (18%), and temporal (27%). The central region demonstrated smaller UM thickness (p < .01) and diameter (p < .01). The MFS (5- and 10-years) for central region (90%, 86%) was more favorable than other quadrants (p < .01).The UM clock hour regions included central (18%), 1:00 (6%), 2:00 (6%), 3:00 (10%), 4:00 (6%), 5:00 (7%), 6:00 (7%), 7:00 (5%), 8:00 (7%), 9:00 (9%), 10:00 (6%), 11:00 (5%), and 12:00 (8%). The central region demonstrated smaller UM thickness (p < .01) and diameter (p < .01). The MFS (5- and 10-years) for central region (90%, 86%) was more favorable than any clock hour region (p = .03).The UM anteroposterior regions included central (18%), post-equatorial (28%), equatorial (26%), peripheral (13%), and ciliary body (15%). Increasing UM thickness (p < .01) and diameter (p < .01) stepwise were noted with increasing anterior location. The MFS (5- and 10-years) for central region (90%, 86%) was more favorable than other anteroposterior regions (p < .01).A combination of clock hour and anteroposterior regions (49 zones) revealed random distribution with no preferential location. Multivariate regression analysis adjusted for tumor thickness/diameter and proximity to foveola/optic disc showed no benefit of any location. CONCLUSIONS:Across all fundus regions, UM occurred most often in the central region. Uveal melanoma in the central region was smaller in thickness and base and demonstrated more favorable MFS compared to other quadrants, clock hours, and anteroposterior zones. Analysis of the 49 zones showed no benefit of tumor location alone after adjusting for tumor size and proximity to foveola and optic disc.

Purpose To evaluate the safety profile of aqueous humor (AH) liquid biopsy in pediatric patients with retinoblastoma and retinoblastoma-simulating lesions through a multicenter analysis of paracentesis procedures. Design Retrospective multicenter study. Participants A total of 1203 paracentesis procedures were performed on 484 eyes of 425 pediatric patients, including 352 patients with retinoblastoma and 73 patients with retinoblastoma-simulating lesions. Methods Medical records were reviewed retrospectively to identify complications from anterior chamber paracentesis performed to obtain AH for liquid biopsy. Procedures were conducted during routine examination under anesthesia. Aqueous humor samples were extracted using a 32-gauge needle and underwent cell-free DNA analysis. Complications were classified as mild, moderate, or severe based on clinical impact and required interventions. Main Outcome Measures Incidence and severity of complications related to the paracentesis procedure. Results Among 1203 procedures, 1 mild complication was identified, representing an overall complication rate of 0.08%. No moderate or severe complications, including vision, eye loss, extraocular tumor spread, or death, were observed at a median follow-up of 16 months. The procedure demonstrated an excellent safety profile across multiple centers, with no permanent adverse outcomes. Conclusions Aqueous humor liquid biopsy via anterior chamber paracentesis is a safe and well-tolerated procedure in pediatric patients with retinoblastoma when performed by trained ocular surgeons under general anesthesia. This large-scale analysis supports the procedure’s use as a minimally invasive diagnostic tool with minimal risk, providing valuable molecular insights for retinoblastoma management. These findings offer reassurance to clinicians and parents regarding the safety of AH liquid biopsy for retinoblastoma. Financial Disclosure(s) Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

BACKGROUND:Genetic testing for uveal melanoma and tumour size is important in prognostication. METHODS:A review of 1 585 patients with uveal melanoma who had cytogenetic testing and classification, according to The Cancer Genome Atlas (TCGA), was performed. Kaplan-Meier (KM) metastasis-free survival at 1-, 3-, 5-, and 10-years were explored. RESULTS:The findings revealed TCGA Group A (n = 781; 49%), Group B (n = 215; 14%), Group C (n = 329; 21%), or Group D (n = 260; 16%). The median patient age at diagnosis was 60 years, sex was male in 51%, and race was White in 95%. A comparison (TCGA Group A vs Group B vs Group C vs Group D) revealed a difference in median patient age at tumour diagnosis (59 vs 59 vs 63 vs 65 years; p < 0.01), and initial visual acuity (20/20-20/50: 80% vs 68% vs 69% vs 64%; p < 0.01). The median tumour thickness was 4 mm, and the median diameter was 12 mm. A comparison (TCGA Group A vs Group B vs Group C vs Group D) revealed differences in median tumour thickness (3 vs 5 vs 6 vs 7 mm; p < 0.01), tumour diameter (10 vs 13 vs 13 vs 16 mm; p < 0.01), distance to foveola (3 vs 3 vs 4 vs 5 mm; p < 0.01), and distance to optic disc (3 vs 4 vs 5 vs 4 mm; p < 0.01). The KM metastasis-free survival estimates (TCGA Group A vs Group B vs Group C vs Group D) revealed differences at 1 year, 3 years, 5 years, and 10 years (p < 0.01) for any metastasis and specific survival rates at 5 years (96% vs 86% vs 62% vs 37%; p < 0.01), and 10 years (93% vs 78% vs 50% vs not available; p < 0.01) significantly decreased from Group A to Group D. By multivariate analysis, the hazard ratio for metastasis-free survival revealed differences in Groups B vs A (3.67), Groups C vs B (5.73), and Groups D vs C (3.20) (p < 0.01), as well as differences per tumour thickness (1.06) and diameter (1.13) (p < 0.01). CONCLUSIONS:Genetic prognostication for metastatic risk from uveal melanoma using TCGA in this large cohort revealed that increasing TCGA category reduced the rate for metastasis-free survival.