Objective Therapy for vision-threatening CMV retinitis is often limited by drug resistance or systemic toxicity. Maribavir, a novel UL97 kinase inhibitor that has been FDA-approved for refractory CMV viremia, is a potential alternative to traditional antiviral therapy but remains understudied for CMV retinitis. The objective of this series is to describe the clinical courses and outcomes of patients with CMV retinitis after initiation of maribavir therapy. Design Retrospective case series. Subjects Six patients (11 eyes) with CMV retinitis from two tertiary uveitis centers. All were immunocompromised due to chemotherapy, immunotherapy, or AIDS and were initially treated with standard therapy (systemic and/or intravitreal ganciclovir, valganciclovir, or foscarnet) before developing drug resistance, toxicity, or intolerance prompting a transition to maribavir as alternative therapy. Intervention Oral maribavir 400mg twice daily. Main Outcome Measures Time to retinitis quiescence, visual acuity (VA), and adverse effects of therapy. Results 4/11 eyes had active retinitis upon initiation of maribavir and all achieved quiescence within 6 weeks. The remaining 7/11 eyes were already quiescent and remained so. VA remained stable or improved in all eyes. Notable clinical courses included (1) rapid decline in aqueous CMV titer and resolution of retinitis in a patient with multidrug-resistant CMV failing intravitreal ganciclovir/foscarnet; (2) a patient with UL54-resistant CMV and bilateral macula-involving retinitis rapidly achieving inactivity and preserved visual acuity on maribavir; and (3) successful substitution of maribavir in patients who were unable to continue conventional antiviral therapy due to drug-induced neutropenia or nephrotoxicity. Maribavir was generally well-tolerated, and only mild adverse effects were reported (dysgeusia, myalgia). Review of the literature identified 2 additional cases of patients with similar clinical courses achieving resolution of retinitis on maribavir. Conclusions In this descriptive case series, patients with multidrug-resistant CMV retinitis or intolerance to traditional antiviral therapy were observed to achieve or maintain quiescence of retinitis following initiation of maribavir. These findings suggest maribavir as a potential novel systemic option for challenging cases of CMV retinitis. Prospective studies are necessary to further characterize the efficacy and safety of maribavir for the treatment of CMV retinitis, as well as optimal duration of therapy after quiescence.
TPS9608 Background: Uveal melanoma (UM) is the most common intraocular malignancy and has high risk of metastatic progression and poor long-term survival. Standard treatment of the primary tumor includes enucleation (eye-removal), and radiation therapy including plaque brachytherapy (PB) and proton beam therapy, which can result in vision loss or removal of the eye. No approved neoadjuvant therapies exist that shrink the tumor or improve visual outcomes. Almost all UM tumors harbor GNAQ/GNA11 initiating mutations with downstream constitutive activation of protein kinase C (PKC). Darovasertib, a first-in-class oral PKC inhibitor tested in study OptimUM-09, has demonstrated the ability to reduce UM tumor size resulting in enucleation sparing in patients with large tumors, and radiation reduction in patients with medium sized tumors requiring PB. In addition, visual improvements have been observed not only during neoadjuvant therapy but also in the predicted risk of legal blindness post PB using a vision prognostication tool. Methods: OptimUM-10 is an ongoing phase 3, randomized, multicenter, open-label trial enrolling patients with primary non-metastatic UM. Eligible patients must have high metastatic risk (class 2 gene-expression profile, monosomy 3, or AJCC stage 3). Additionally, for the PB cohort, moderate to high risk of vision loss (> 30Gy predicted radiation dose to key visual structures) is required for eligibility. Major exclusion criteria include metastatic disease or extraocular tumor extension, prior UM primary treatment, attributes necessitating immediate enucleation, and relevant ocular comorbidities. The trial has two cohorts: Cohort 1 (n=330) includes patients with medium UM tumors where PB is the standard treatment. Cohort 2 (n=120) includes patients with large UM tumors where enucleation is the standard treatment. In each cohort, eligible patients are randomized 2:1 to receive neoadjuvant darovasertib (300 mg twice daily for up to six 28-day cycles) or standard-of-care treatment with PB (cohort 1) or enucleation (cohort 2). The primary endpoint for cohort 1 is the proportion of patients with loss of Early Treatment Diabetic Retinopathy Study Best-Corrected Visual Acuity of ≥15 letters (%VL15) from randomization, while in cohort 2 it is eye preservation rate. Across cohorts, the key secondary objective is to evaluate response rate with neoadjuvant darovasertib. Additional secondary endpoints include event-free survival and safety, as assessed by treatment-emergent adverse events and serious adverse events. Enrollment is ongoing, and results will determine whether OptimUM-10 may establish darovasertib prior to definitive PB as the first neoadjuvant treatment for primary UM to meaningfully reduce tumor burden and expand vision- and eye-preserving treatment options for patients. Clinical trial information: NCT07015190 .
Purpose: To assess the impact of repeated intravitreal (IVT) antivascular endothelial growth factor (anti-VEGF) injections on the vitreomacular interface in eyes with cystoid macular edema secondary to central retinal vein occlusion (CRVO). Methods: This retrospective cohort study included 45 treatment-naïve eyes with CRVO with 12 or more months of follow-up. The cohort had a mean age of 62 ± 12 years, was 40% male, and was racially diverse (60% White, 29% Black). All eyes received more than 1 anti-VEGF injection. Vitreomacular status was staged at baseline and 12 months using optical coherence tomography. Eyes with complete posterior vitreous detachment (PVD) at presentation or previous treatment for CRVO were excluded. Twenty-seven untreated fellow eyes served as controls. Results: PVD progression occurred in 42% of eyes with CRVO, with 4% reaching complete PVD. The eyes with CRVO received more injections (8.4 ± 2.4) than CRVO nonprogressors (6.2 ± 2.8; P = .01). Only 18.5% of fellow eyes progressed. Paired analysis showed greater change in vitreomacular staging in eyes with CRVO vs fellow eyes (mean, 0.44; P = .047). Conclusions: Eyes with CRVO receiving multiple IVT injections showed significantly greater progression toward complete PVD than untreated fellow eyes.
Purpose:To describe methods for improving visualization of the port delivery system (PDS) with ranibizumab (Susvimo) during the refill-exchange procedure when visualization of the implant septum is compromised. Methods:Multiple methods of PDS visualization using external illumination were evaluated. Results:Transpupillary and transscleral illumination of the PDS reservoir body using various light sources improved visualization of the implant septum during the refill-exchange procedure. Conclusions:Indirect internal illumination of the PDS implant can facilitate visualization of the implant septum during the refill-exchange procedure, particularly when visualization is compromised by conjunctival edema, thickened Tenon capsule, or fibrous capsule formation.
Anti-vascular endothelial growth factor (anti-VEGF) therapies are standards of care for vision-threatening retinal diseases. This retrospective observational study describes demographics, utilization, best recorded visual acuity (BRVA), and safety among eyes with neovascular age-related macular degeneration (nAMD), diabetic retinopathy (DR), diabetic macular edema (DME), or retinal vein occlusion (RVO) treated with the biosimilar aflibercept-ayyh (PAVBLU®) in routine clinical practice. Electronic medical records from the Retina Consultants of America database of patients receiving aflibercept-ayyh (12/1/2024–10/31/2025) were analyzed, focusing on eyes with ≥ 84 days of follow-up. The index date was defined as the first documented aflibercept-ayyh injection. Post-index data were used to evaluate treatment patterns, changes in BRVA, and adverse events of special interest (AESIs). Within-eye changes in BRVA were assessed using the Wilcoxon signed rank test and summarized as mean change in logarithm of the minimum angle of resolution (ΔlogMAR). A total of 1000 consecutive eyes from 989 patients (55
