PURPOSE:Choroidal melanoma arising from an optic disk melanocytoma is rare but has been previously described at an incidence of 1-2%. Evaluating these cases for pathology and genetics is relevant for determining metastatic risk. METHODS:Case report. RESULTS:A 73-year-old man with a history of optic disk melanocytoma of the left eye presented with blurred vision after being lost to follow-up at an outside clinic for 5 years. The melanocytoma was found to have undergone transformation to a choroidal melanoma suggested by fundus examination, optical coherence tomography, and B scan ultrasonography. The patient underwent enucleation because the tumor was circumpapillary and technically unable to undergo plaque brachytherapy. Pathologic evaluation after enucleation demonstrated peripapillary choroidal melanoma of mixed cellularity with areas of intrascleral extension. Genetic analysis revealed mutations in guanine nucleotide-binding protein G(q) subunit alpha (GNAQ) and exon 1 of eukaryotic translation initiation factor 1A, X-linked (EIF1AX), and a Class 1A molecular signature. CONCLUSION:Our case of a choroidal melanoma of low metastatic risk arising from an optic disk melanocytoma may suggest that these cases have a lower metastatic risk than melanomas not derived from melanocytomas, though further studies including cases with genetic profiling and long-term systemic follow-up to detect metastatic disease rates are necessary to establish such a pattern.

IntroductionMelanoma-associated retinopathy (MAR) is a rare paraneoplastic ocular manifestation of cutaneous or mucocutaneous melanoma. We describe a novel case of MAR that mimicked an inflammatory or infiltrative retinopathy.Patient presentationA 68-year-old female developed bilateral, painless, floaters over six months with accompanying photopsia. Bilateral posterior uveitis was noted, and bilateral vitrectomies were non-diagnostic for malignancy. A systemic evaluation revealed a subcutaneous lesion on the medial aspect of her right thigh. Biopsy of the lesion was consistent with melanoma. The patient was diagnosed with melanoma-associated retinopathy (MAR).Conclusion and importanceMAR is a vision-threatening paraneoplastic disorder that more commonly arises in patients with an existing diagnosis of melanoma. Most cases of MAR have normal or near normal fundus examinations at onset. Our case is interesting because the fundus presentation mimicked a posterior uveitis and vitrectomy was non-diagnostic. Clinicians should be aware of paraneoplastic MAR and the potential for “masquerade syndrome.” Systemic search for underlying neoplasms including occult melanoma or carcinoma is warranted in such cases.

Uveal melanoma (UM) is an aggressive eye cancer that frequently results in metastatic death despite successful primary tumor treatment. Subclinical micrometastasis is thought to occur early, when tumors are small and difficult to distinguish from benign nevi. However, the early genetic evolution of UM is poorly understood, and biomarkers for malignant transformation are lacking. Here, we perform integrated genetic profiling of 1140 primary UMs, including 131 small tumors. A clinically available 15-gene expression profile (15-GEP) prospectively validated by our group is more accurate than driver mutations for predicting patient survival. Small tumors are significantly more likely to be in earlier stages of genetic evolution than larger tumors. Further, the 15-GEP support vector machine discriminant score predicts small tumors undergoing transformation from low-risk Class 1 to high-risk Class 2 profile. These results shed light on the early genetic evolution of UM and move us closer to a molecular definition of malignant transformation in this cancer type.

The reported rate of pathogenic germline mutations in the BAP1 gene range from 2% in unselected population to up to 50% in patients with familial uveal melanoma (UM) and are associated with an increased risk of developing BAP1-Tumor Predisposition Syndrome (TPDS)-related cancers. The primary objective of this study was to determine more accurately the rate of germline BAP1 mutations in a clinically representative sample population of UM patients with a known somatic mutation in BAP1, using clinically available 7-gene UM next-generation sequencing (NGS) panel DecisionDx-UMSeq. Blood and buccal swab samples were prospectively collected from 45 adult participants (median age at diagnosis 63 y.o., range 35-92) at a single center under an IRB-approved protocol. All participants had a prior diagnosis of primary UM and had at least one reportable BAP1 mutation previously identified in their tumors. Both samples (blood and buccal swab) were analyzed using the DecisionDx-UMSeq test. Results of all 3 assays (tumor, blood, and buccal swab) were analyzed for the presence of BAP1 mutations. All reportable germline mutations detected in blood and buccal swab samples were previously identified in the primary tumor samples by DecisionDx-UMSeq, with 100% concordance in mutation calls between blood and swab samples and allele frequencies (AFs) within a 5% range. Out of 45 samples analyzed, 11 (24.4%) had reportable germline mutations classified as either Variants of Uncertain Significance (VUS) or pathogenic according to the ClinVar database. The remaining 34 samples had no reportable germline mutations. When comparing the AFs of BAP1 mutations in blood and buccal swab to those in tumor samples, 4/11 (36.4%) had matching AFs, while 7/11 (63.6%) exhibited higher AFs in the tumor samples than in blood or buccal swabs. Among the detected mutations, four were classified as pathogenic and seven as VUS. Tumors in this cohort tended to be large, consistent with a high-risk molecular profile, with an average diameter of 14.5±3.53 mm and average tumor thickness of 6.14±3.48 mm. The DecisionDx-UMSeq panel accurately identified reportable germline BAP1 mutations in both buccal swab and blood samples from patients with previously reported somatic BAP1 mutations. A quarter of patients in this cohort had a reportable germline mutation, including patients without a family history suggestive of typical BAP1-TPDS cancers, thus indicating that the rate of BAP1 germline mutations may be higher in this cohort than reported elsewhere. This study supports the routine implementation of the DecisionDx-UMSeq panel for BAP1 germline testing in all patients with a somatic BAP1 mutation, enabling improved critical clinical decision-making and genetic counseling for patients and family members at risk of BAP1-related TPDS. Amy C. Schefler, Julia Litvinov, Jason Maarsing, Kasia Wozny, Olga Zolochevska. Detection of reportable germline BAP1 mutations in patients with uveal melanoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 1 (Regular Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_1):Abstract nr 1014.

PURPOSE:Patients who present with high risk choroidal nevi, typically with thickness <2.0 mm, are thought to have a better prognosis than patients who present with larger tumors. Large scale studies have not explored the differences in genetics between melanocytic lesions that were initially observed (IO) and those immediately treated (IT). The primary objective of this study is to compare genetics and metastatic rate between high risk nevi IO and treated upon growth vs IT uveal melanoma (UM). The secondary objective is to evaluate the growth rate of high-risk lesions in the IO group that eventually triggered treatment, and to assess whether this growth rate threshold was sufficient to maintain a low rate of metastasis. DESIGN:Retrospective clinical cohort study. SUBJECTS:A total of 272 patients with UM who underwent treatment at a large ocular oncology practice in Houston, Texas between 2013 and 2022 with at least 18 months follow-up. MAIN OUTCOME MEASURES:Tumor Gene Expression Profile (GEP), Tumor PReferentially Expressed Antigen in MElanoma (PRAME) status, Tumor height and largest base diameter (LBD) growth rate [millimeters (mm)/year], presence of metastasis (yes or no). METHODS:Patients were categorized as IO or IT. Patients in the IO group were initially diagnosed with high risk choroidal nevi and monitored until clinical criteria for UM were met. In contrast, patients in the IT group were diagnosed with UM upon their first visit by the ocular oncologist. Metastatic outcomes, genetic expression, and tumor growth rates were analyzed. RESULTS:A total of 213 patients in IT and 59 in IO were included. Compared to IO patients, IT patients had higher percentages of metastasis (p = .009), Gene Expression Profile (GEP) Class 2 tumors (p = .010), and PReferentially Expressed Antigen in MElanoma (PRAME) expression (p = .044). Mean tumor growth rate in the IO group increased just before treatment decision by 0.65 and 1.00 mm/y for height and LBD, respectively (p < .01). CONCLUSIONS:Genetic profiles and metastatic potential evolve alongside tumor growth, indicating a transition from high risk nevi to UM. Monitoring the growth rate of high risk nevi serves as a reliable noninvasive biomarker for identifying nevus transformation to UM and for guiding clinical decision-making, without resulting in a high rate of Class 2 tumors and metastatic disease.

9590 Background: Uveal melanocytic tumors of indeterminate malignant potential (UMTIMP) are usually managed by a “watch and wait” approach before the decision to treat. Although the aggressiveness of these lesions can be assessed by tumor-biopsy based molecular testing, serial tumor biopsies may be impractical and not always feasible for routine clinical management of UMTIMPs. In contrast, aqueous humor (AH) sampling can be safely performed as an outpatient procedure and is repeatable. AH protein biomarkers strongly associated with aggressive UM could be used as a sensitive and objective biological marker of malignant transformation, facilitating earlier tumor biopsy and treatment when clinically indicated. The purpose of this study was to validate a previously developed 16-protein algorithmic test for identification of high-risk tumor biology in AH sample. Methods: All study participants were clinically diagnosed with UM and had the 15-GEP, PRAME and 7-gene UM panel next-generation sequencing (NGS) test results available. AH samples (N=71) were prospectively collected at 3 independent sites under IRB approved protocols. The samples were analyzed with the Olink Target 96 Oncology II panel. The low-risk group included Class 1 and BAP1 wild type samples, and the high-risk group included Class 1 BAP1-mutant samples and all Class 2. Algorithmic analyses were performed in R and demographics analysis was performed in GraphPad Prism (version 10). Results: The sample distribution was representative of a typical UM patient cohort: average age was 62.4±15.1 years, tumor diameter 11.16±3.56 mm, and tumor thickness 4.85± 2.94 mm. The 15-GEP identified 48/71 of tumors as Class 1, and 23/71 tumors as Class 2. There was a significant difference in tumor diameter (P=0.003) and tumor thickness (P=0.001) between Class 1 and Class 2 patients. The proteins primarily belonged to Signal Transduction, Disease, and Cytokine Signaling pathways, based on Olink’s Pathway Browser. The 16-protein test had a sensitivity of 92%, specificity 52%, NPV 92%, and PPV 51%. Conclusions: A novel 16-protein algorithmic test for predicting high-risk tumor biology of the uveal melanocytic lesions was independently validated in a multi-center study. This high sensitivity test would help to accurately identify high-risk melanocytic lesions based on AH sample and provide a clinically useful ancillary approach for guiding decisions for definitive tumor biopsy and treatment.

PURPOSE:Eye plaque brachytherapy (EPBT) is not routinely performed on large uveal melanomas (UM) as commercially available plaques often cannot ensure adequate coverage of the tumor with high doses of 85 Gy. The purpose of this study is to report our institution's experience with a clinically novel approach of staged EPBT in treating large UM in 2 treatments, 45 Gy in each treatment. METHODS AND MATERIALS:Patients were included if they underwent staged EPBT at our institution between 2020 and 2023. RESULTS:A total of 13 patients with a median age of 65 were included in this study. All patients were treated with Iodine-125 with a first-stage prescription dose of 45 Gy and with a second-stage treatment occurring at median 13 weeks after with prescription dose of 45 Gy. Median follow-up was 42 months, and local control was 100% with no patients requiring an enucleation for a local recurrence or other radiation-related toxicities. At last follow-up, all tumors were decreased in size. Visual acuity worsened in 11 patients, and other radiation-related toxicities included cataract, cystoid macular edema, radiation retinopathy, and neovascular glaucoma. Three patients developed metastases, one of whom died shortly after, while all other patients were alive at last follow-up. CONCLUSIONS:Staged EPBT for large UM is a novel and feasible globe-preserving treatment with a high rate of local control. Ocular toxicities are expected but do not require enucleation. Further prospective randomized trials should be performed to validate this treatment approach.

There are few investigations into low-penetrance heritable retinoblastoma (RB) mutations and sparse reports of identical twins with RB. To our knowledge, this is the first report of monozygotic twins with molecularly proven discordant RB and the largest pedigree published describing a low-penetrance RB1 mutation with multiple successive generations of silent carriers.

Purpose: The purpose of this study is to present a case series of patients with co-occurrence of either BRCA1 associated protein-1 (BAP1), eukaryotic translation initiation factor 1A, X-chromosomal (EIF1AX), or splicing factor 3B subunit 1 (SF3B1) in the detection and treatment of a uveal melanoma (UM) prior to the development of metastatic disease. Observations: This is a retrospective case series of ten patients with UM demonstrating co-occurrence of either BAP1, EIF1AX, or SF3B1 variants treated at a single ocular oncology clinic by a senior ocular oncologist between 2020 and 2024. Charts were reviewed and data on medical history, demographics, tumor characteristics, genetic testing, follow up, as well as fundus photo and B-scan ocular ultrasound were collected. The average age of the patients was 58.5 years old. The mean length of follow up was 18.2 months. Four patients had guanosine nucleotide-binding protein alpha-11 (GNA11) variants and six had guanosine nucleotide-binding protein Q (GNAQ) variants. Four patients had germline BAP1 variants. Four patients had a combination of EIF1AX and BAP1 variants. Three patients had a combination of EIF1AX and SF3B1 variants. Three patients had a combination of SF3B1 and BAP1 variants. Eight UM were gene expression profile (GEP) Class 1A and two UM were GEP Class 1B. Seven UM were preferentially expressed antigen in melanoma (PRAME) negative and three UM were PRAME positive. All patients had cytologic confirmation of the diagnosis of UM: seven had cytology results of spindle cells and three had results of mixed spindle and epithelioid cells. All patients were treated with Iodine-125 (I-125) plaque brachytherapy. Conclusions and importance: We present a case series of patients with the co-occurrence of EIF1AX, SF3B1, or BAP1. With distinct genomic aberrations, transcriptional features, and clinical outcomes, EIF1AX, SF3B1, and BAP1 are thought to be mutually exclusive. The present case series demonstrates rare exceptions to this general pattern and speculates on the early molecular steps of UM which may lead to these rare mutation combinations.

Purpose: To report an unusual case of vitreoretinal lymphoma (VRL) in which a glaucoma drainage implant (GDI) likely functioned as a sanctuary site for relapsing disease. Observations: A 54-year-old female with recently diagnosed CNS diffuse large B-cell lymphoma (DLBCL) was referred for evaluation of VRL. Ocular history at an outside center included a 4-year reported history of uveitis complicated by glaucoma and a GDI in the left eye (OS). Initial examination revealed keratic precipitates (KP), vitreous haze with clumps of white cells OS, and vitreous biopsy revealed DLBCL OS. Intravitreal methotrexate injections were initiated for primary VRL alongside systemic chemotherapy for CNS involvement with resolution of disease. One year later, the patient returned with 2+ anterior chamber (AC) and vitreous cells OS, and vitreous biopsy again revealed DLBCL OS. External radiation treatment was administered for recurrent VRL in the left eye, followed also by the right eye due to the high risk of fellow eye involvement. Autologous stem cell transplantation was then performed. Five months later, the patient returned with worsening KPs and new vitreous cells OS, and vitreous biopsy again revealed DLBCL OS. Enucleation was performed, and histopathology revealed DLBCL cells lining the GDI fibrous capsule, consistent with the GDI likely having served as a sanctuary site and source for continued local relapse. Conclusions and Importance: We report a case in which a GDI functioned as a probable sanctuary site for VRL. Sanctuary sites of malignancy should be considered in patients with pre-existing ocular hardware, particularly when recurrent relapses occur despite complete treatment.

With a prevalence of approximately 5% in the U.S., uveal melanocytic tumors of indeterminate malignant potential (UMTIMP) are primarily managed by observation for growth prior to treatment. While the malignant potential of these lesions can be assessed by intraocular tumor biopsy and genetic testing, serial tumor biopsy in the operating room is not feasible for routine management of UMTIMPs. On the other hand, the aqueous humor (AH) from the anterior chamber of the eye can be easily and safely obtained by an office-based procedure that can be repeated periodically. Proteomic signatures in aqueous fluid could potentially allow early detection of UMTIMPs at high risk of having undergone malignant transformation, thus identifying patients who would benefit from a definitive tumor biopsy and earlier treatment as indicated. AH was collected via paracentesis from 79 patients with clinically diagnosed UM at three independent sites under IRB-approved protocols. Immediately thereafter, all patients underwent a tumor biopsy for the standard-of-care molecular prognostic testing with DecisionDx-UM, -PRAME, and -UMSeq. Proteomic profiling was carried out with the Olink Explorer panel, which analyzes 3072 proteins. Statistical analysis was performed in R (version 4.3.3). Algorithm development and accuracy estimation were based on 4x 10-fold cross-validation. The sample distribution was representative of a typical UM cohort: mean age 64.8±14.5 years, mean tumor diameter 11.02±3.40 mm, mean tumor thickness 4.61±3.14 mm. DecisionDx-UM identified 57/79 (72%) of tumors as Class 1 and 22/79 (28%) of tumors as Class 2. Approximately 1400 out of 3072 proteins were detected in AH samples. Proteins with statistically significant differences between Class 1 and 2 (N=386, p<0.0001) were included in further analyses. The best fitting models were k-nearest neighbor, random forest, and neural networks with accuracies of 76%, 83%, and 83%, and kappa 0.25, 0.40, and 0.36, respectively. Within the Explorer3072 panel, proteins grouped into the Immune Response and Oncology subpanels achieved an average accuracy of 81-85% and 77-89%, respectively. Several promising risk prediction models were identified by proteomic profiling of AH from UM patients. The proteins from the highest-performing models will be utilized in the development and validation of a testing platform that is feasible for office-based clinical testing to identify high-risk UMTIMPs that would benefit from definitive risk assessment using tumor biopsy-based testing. Olga Zolochevska, Julia Litvinov, Kyle R. Covington, David A. Reichstein, Amy C. Schefler, Zelia M. Correa, Jason Maarsing, Kasia Wozny, Katherina M. Alsina, J. William Harbour. Development of a clinically feasible aqueous proteomic signature to assess the malignant potential of small uveal melanocytic tumors [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 2 (Late-Breaking, Clinical Trial, and Invited Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_2):Abstract nr LB262.

PURPOSE: Eye plaque brachytherapy (EPBT) is the most common treatment for uveal melanoma with high local control rates of 95-100%. When local recurrences occur following EPBT, salvage options include enucleation, transpupillary thermotherapy (TTT), external beam radiation, or reirradiation with EPBT. The purpose of this study is to report our institution's experience with EPBT re-irradiation for locally recurrent uveal melanoma. METHODS AND MATERIALS: Patients were included if they were previously treated for uveal melanoma with EPBT, experienced local recurrence, and were subsequently treated at our institution with EPBT from 2016- 2020. RESULTS: A total of 5 patients with median age 68 years were included. All patients were initially treated at an outside institution (OSI) with Iodine-125 or Ruthenium-106 EPBT. Mean time between EPBT at the OSI and EPBT at our facility was 130 months (range 28-231 months). Patients were re-irradiated with Iodine-125 EPBT prescribed to 85 Gy over 168 hours. Median follow up after re-treatment at our center was 24 months. Local control among this cohort was 100%. Metastasis occurred in two patients after re-treatment, at 8 months and 7 months. At last follow up, all treated lesions were decreased in size. Four patients experienced worsening visual acuity. Four patients developed cataracts, while two patients developed radiation retinopathy with cystoid macular edema requiring anti-VEGF injections. One patient developed radiation retinopathy but did not require injections. No patients required enucleation. CONCLUSIONS: Re-treatment of locally recurrent uveal melanomas with EPBT is a feasible alternative to enucleation with a high local control rate. Ocular toxicities have not been significant enough to require enucleation. (c) 2024 American Brachytherapy Society. Published by Elsevier Inc. All rights are reserved, including those for text and data mining, AI training, and similar technologies.

Background/Purpose: To determine and compare the efficacy of a surgical internal limiting membrane (ILM) flap technique with the traditional ILM peel on long-term visual and anatomical outcomes for large (>400 µ m) full-thickness macular holes. Methods: From October 2016 to July 2022, patients undergoing initial full-thickness macular hole repair with the ILM flap or ILM peel technique were reviewed. Final outcomes were recorded and based on size in microns: 401 to 800, 801 to 1,200, and >1,200. Results: Patients treated with ILM flap (n = 52, 94.2% closure rate) or ILM peel (n = 407, 93.6% closure rate) were followed with a mean follow-up time of 15.0 ± 10.2 and 20.0 ± 13.4 months, respectively. Success rates for ILM flaps and ILM peels were compared for full-thickness macular holes of 401 to 800 (100%, 95.8%, P = 0.39), 801 to 1,200 (95%, 93%, P = 0.74), and >1,200 (86.7%, 86.7%, P = 1.0) µ m. Mean best-recorded logarithm of the minimal angle of resolution visual acuity for ILM flaps and ILM peels, respectively, was 1.02 ± 0.46 and 0.87 ± 0.47 preoperatively, with follow-up acuity of 0.48 ± 0.32 ( P < 0.03) and 0.39 ± 0.42 ( P < 0.01) at Year 3. Conclusion: Both techniques provide a similar anatomical closure rate and functional improvement in vision. Comparisons should be cautiously made based on difference in preoperative hole size.

Introduction Primary vitreoretinal lymphoma (PVRL) is a rare manifestation of primary central nervous system lymphoma, with most cases classified as diffuse large B-cell lymphoma (DLBCL). Local therapies aimed at restoration of vision and prevention of central nervous system dissemination typically have excellent response rates, but local recurrence and fatal brain relapse is common. With an estimated 50 new cases per year in the United States, epidemiological data and standardized treatment guidelines are lacking. Herein, we report outcomes of one of the largest single institutional populations of PVRL patients with or without brain involvement. Methods/Materials Patients with histologically confirmed PVRL (DLBCL), with or without brain involvement and diagnosed between 2016-2024 were included. Demographics, genomics, and treatment patterns were assessed. Differences in median or mean overall survival (OS) and relapse free survival (RFS) with 95% confidence interval (CI) based on treatment modality (local, systemic, local+systemic), brain involvement at diagnosis, and consolidative therapies was estimated by Kaplan-Meier methodology and compared by the Log-Rank test. P-value <0.05 was considered statistically significant. Results A total of 31 patients were diagnosed. Median age was 68 (50-85) years, 20 (64.5%) were female, and 18 (58%) were non-Hispanic white. There were 10 (32.2%) patients with at least one genomic alteration, with MYD88 reported in 5 (50.0%). There were 27 patients with available treatment data. Of these, 10 (37.0%) had unilateral disease, 10 (37.0%) had bilateral ocular involvement, and 7 (18.9%) had unilateral ocular and brain involvement. Upfront therapy included local therapy in 7 (18.9%), systemic therapy in 5 (18.5%), and systemic+local therapy in 15 (55.6%). Overall response rate (ORR) with local therapy was 85.7%, relapse rate was 47.8%, and 1 (14.7%) patient died. ORR with systemic therapy was 80%, relapse rate was 60%, and 40% died. ORR with local+systemic therapy was 80%, relapse rate was 53.3%, and 20% died. Of the 15 (55.6%) total relapses, 7 (46.7%) had brain dissemination; 6 (40.0%) had isolated ocular lymphoma at diagnosis, 8 (53.3%) had received systemic+local therapy, and 4 (26.7%) received systemic therapy only. Of the 12 (44.4%) with no relapse, all 12 (100%) had ocular disease only, 7 (53.8%) received local+systemic therapy, and 1 (8.3%) received systemic therapy. Median RFS and OS for all patients was 12.8 (95% CI 0.59, 64.99) months and 31.9 (95% CI 0.59, 101.85) months, respectively. Mean RFS for ocular only vs ocular+brain disease was 46.9 (95% CI 32.7, 61.2) vs 24.6 (95% CI 33.0, 58.9) (p=0.538) months, respectively, whereas mean OS was 60.1 (95% CI 48.8, 71.4) and 80.6 (95% CI 55.3, 105.9) (p=0.845) months, respectively. Mean RFS for local, systemic, and local+systemic was 35.7 (95% CI 24.0, 47.4) vs 18.2 (95% CI5.4, 31.0) vs 47.6 (95% CI 31.4, 63.8) (p=0.337) months, and OS was 57.6 (95% CI 39.0, 76.2), 53.7 (95% CI 31.4, 76.1), and 77.1 (95% CI 55.2, 98.9) (p=0.772) months, respectively. Receipt of autologous stem cell transplantation at any time during their disease course had RFS of 52.6 (95% CI 37.3, 67.9) vs 35.5 (95% CI 25.5, 45.5) (p=0.784) and OS of 82.4 (95% CI 60.3, 104.5) vs 54 (95% CI 40.3, 68.9) (p=0.387) months, respectively. Conclusion In one of the largest real-world studies of PVRL, patients with or without brain involvement had an ORR of 81.4%, but 55.6% relapsed and 22.2% died. Further studies are needed to assess the benefit of applying a local+systemic therapy approach including in those with localized disease to improve ocular morbidity and reduce ocular and brain relapse.

This case series reports on two patients who developed macular holes while on prostaglandin analogs (PGA) therapy. The first case involves a 63-year-old woman with a history of a macular hole of the left eye that had spontaneously closed. After starting PGA therapy for elevated intraocular pressure, cystoid macular edema formed, which resulted in reopening of the macular hole. The second case involves a 64-year-old man with primary open-angle glaucoma, on PGA therapy, with a newly diagnosed small macular hole of the right eye that closed after cessation of the PGA therapy. These cases demonstrate an association between prostaglandin analogs and the formation or reopening of full-thickness macular holes. [ Ophthalmic Surg Lasers Imaging Retina 2024;55:112–115.]

BACKGROUND AND OBJECTIVE:Our objective was to monitor variables via spectral-domain optical coherence tomography (SD-OCT) and identify the most relevant biomarkers related to best-corrected visual acuity (BCVA) in radiation retinopathy (RR). PATIENTS AND METHODS:A post-hoc analysis of the two-year Ranibizumab for Radiation Retinopathy (RRR) trial analyzed vision and OCT parameters including intraretinal fluid, ellipsoid zone (EZ) disruption, retinal pigment epithelium atrophy, hard exudates, retinal hemorrhage, retinal neovascularization, and subfoveal fluid. BCVA and SD-OCT parameters were evaluated by univariate analysis and a mixed-effects model. RESULTS:Forty eyes from the RRR trial were included. Intraretinal cyst vertical size (week 24: P = 0.032; week 48: P = 0.021), neovascularization (week 48: P = 0.028; week 72: P = 0.025), and EZ disruption (week 72: P = 0.029; week 104: P = 0.019) were the clinical parameters most relevant to BCVA by univariate analysis in at least two time points. The mixed-effects model confirmed the relevance of intraretinal cyst vertical size (P = 0.001) and neovascularization (P = 0.001) but not EZ disruption (P = 0.119) over the course of the study. CONCLUSIONS:This study characterizes the course of visual loss in RR by identifying intraretinal cyst vertical size, neovascularization, and EZ disruption as biomarkers of poor BCVA over a span of two years. Larger multicenter studies are needed to confirm these findings. [Ophthalmic Surg Lasers Imaging Retina 2024;55:255-262.].