Purpose To evaluate the safety and efficacy of DS-7080a in eyes with neovascular age-related macular degeneration (nAMD) and diabetic macular edema (DME) alone or in combination with ranibizumab. Design This was a Phase I dose-escalation-and-expansion study registered on clinicaltrials.gov (NCT02530918) and conducted in three parts. Parts one (P1) and two (P2) involved dose-escalation-and-expansion for nAMD patients while Part three (P3) involved dose-expansion-only for DME subjects. Subjects Patients with nAMD or DME. Methods In P1, eligible patients were randomized into three sequential dose-level cohorts to establish a maximum tolerated dose (MTD) for DS-7080a as 4.0 mg and assess its safety and tolerability. The study then proceeded to P2 where 27 nAMD subjects were randomized to one of the three treatment arms: DS-7080a-4.0-mg-only, ranibizumab-0.5 mg-only, or DS-7080a-4.0-mg-plus-ranibizumab-0.5 mg. In P3, 20 subjects with DME were randomized to one of the two arms: DS-7080a-4.0-mg or ranibizumab-0.3-mg injected thrice. The treatment period was 12 weeks. Outcomes Primary endpoints were treatment-emergent adverse events (TEAEs) and serious adverse events (SAEs). Secondary endpoints were changes in central retinal thickness (CST) and best corrected visual acuity (BCVA). Results A total of 56 patients were enrolled. DS-7080a, administered as monotherapy or in combination with ranibizumab, was generally well tolerated. Six drug-related TEAEs were observed, four of which were ocular events that led to treatment discontinuation. No drug-related SAEs or deaths occurred. As expected, ranibizumab was associated with improvements in BCVA and CST, whereas DS-7080a, alone or in combination, did not show clinically meaningful functional or anatomical benefit. Conclusions DS-7080a was generally well tolerated in eyes with nAMD and DME; however, drug-related TEAEs, including ocular events leading to discontinuation, were observed. In terms of efficacy outcomes, DS-7080a does not show BCVA improvement and CST decrease when administered alone or in conjunction with ranibizumab. These findings are inconsistent with non-clinical studies supporting DS-7080a as a therapeutic agent for nAMD and DME.

Secondary intraocular lymphoma is an uncommon manifestation of systemic lymphoma and may relapse in immune-privileged sites years after apparent remission. We report the case of a 67-year-old man with a history of right testicular diffuse large B-cell lymphoma (DLBCL) treated with orchiectomy and systemic chemotherapy who presented five years later with painless progressive vision loss in the left eye. Examination revealed visual acuity of 20/80, fibrinoid material with hemorrhage in the anterior chamber, and yellow-white choroidal infiltrates extending from the optic disc toward the periphery with associated subretinal fluid. Multimodal imaging demonstrated subretinal infiltrates and diffuse choroidal thickening. Diagnostic pars plana vitrectomy was performed during repair of an associated retinal detachment. Routine cytology was nondiagnostic, MYD88 L265P testing was negative, and flow cytometry using a limited panel identified an abnormal lambda-restricted B-cell population comprising 45.2% of CD45+ events, without definitive morphologic confirmation. In the context of the patient's prior lymphoma history, supportive multimodal ocular findings, and exclusion of major infectious and inflammatory etiologies, the overall clinicopathologic impression favored secondary intraocular lymphoma with choroidal involvement. Systemic restaging showed no active extraocular or central nervous system disease. Treatment with oral ibrutinib 560 mg daily was associated with clinical stability over 24 months, improvement of visual acuity to 20/40, resolution of subretinal fluid, stable residual choroidal changes, and no evidence of systemic recurrence. This case highlights the importance of long-term ophthalmic surveillance in patients with testicular DLBCL and the integration of multimodal imaging, ocular fluid analysis, and systemic restaging in the evaluation of suspected ocular relapse.

Purpose To report a case of severe refractory surgically induced scleral necrosis (SISN) with pan-uveitis and retinal detachment following pterygium excision, highlighting the challenges in differentiating infectious versus autoimmune mechanisms and demonstrating successful restoration of ocular structure with combined surgical and immunosuppressive therapy in a patient with poor initial prognosis. Observation: An 80-year-old man presented one year after pterygium surgery with severe pain, redness, and vision loss in the right eye. Examination revealed nasal necrotizing scleritis with purulent discharge, extensive scleral thinning and uveal exposure, pan-uveitis, serous retinal detachment, and choroidal folds. Co-infection was suspected, and systemic autoimmune predisposition was suggested by p-ANCA positivity and history of cutaneous lupus. The patient underwent urgent scleral debridement and biopsy, along with topical and systemic antibiotics, followed by weekly rituximab infusions and mycophenolate mofetil under steroid taper. After eight cycles of active treatment, scleral inflammation improved significantly, scleral thickness restored, and retinal detachment and subretinal fluid completely resolved. At last follow-up, visual acuity improved from counting fingers to 20/100 with restoration of ocular structural integrity. Conclusion The index case highlights the challenge of distinguishing infection from autoimmunity in SISN. Early debridement, prompt antimicrobial treatment, and immunosuppressive therapy are crucial in the management of SISN. Rituximab infusion is safe and effective for rapidly controlling severe scleral inflammation once infection is ruled out or is under control.

Purpose To describe the clinicopathological study of severe bilateral intraocular inflammation following intravitreal (IVT) injection of faricimab in a patient with neovascular age-related macular degeneration (nAMD). Observation An 80-year-old Caucasian female with bilateral nAMD presented with blurry vision and ocular pain after receiving bilateral IVT injections of faricimab on separate days from different lots. The patient experienced significant reduction in her visual acuity, from 20/40 to counting-fingers in the right eye and from 20/50 to hand-motion in the left eye; intraocular pressure (IOP) was elevated in both eyes at 48 mmHg and 49 mmHg. Anterior segment examination revealed bilateral diffuse mutton-fat keratic precipitates and fundus examination revealed bilateral vitreous opacities. Fluorescein angiography demonstrated optic disc leakage and bilateral hemorrhagic occlusive vasculitis. Following initial management with systemic corticosteroid, a subsequent unilateral subconjunctival dexamethasone implant, and pars plana vitrectomy, ocular inflammation subsided significantly along with the normalization of IOP. Cytology examination of vitreous samples showed the presence of chronic inflammatory cells in the vitreous. Conclusion The case highlights the clinical presentation, detailed findings, and successful treatment strategy for hemorrhagic occlusive retinal vasculitis and panuveitis induced by IVT injection of faricimab. Cytopathology analysis of vitreous samples provides novel insights regarding inflammatory mechanisms underlying this rare but potentially sight-threatening complication.

Purpose: To report a case of acute anterior uveitis occurring shortly after influenza vaccination in a patient with HLA-B27 positivity, highlighting the potential role of genetic susceptibility in vaccine-related ocular inflammation. Case Summary: A 35-year-old Asian male experienced progressive unilateral ocular redness, pain, and blurred vision starting from three days after receiving the trivalent influenza vaccine. Ophthalmic examination afterwards demonstrated conjunctival injection, fine keratic precipitates, anterior chamber flare and cells, and posterior synechiae with normal intraocular pressure. Diagnostic workup was unremarkable except for HLA-B27 positivity. The patient was diagnosed with unilateral acute non-granulomatous anterior uveitis and successfully treated with topical corticosteroids and cycloplegics, with resolution of inflammation and no recurrence over six months of follow-up. Conclusions and Importance: The index report highlights that HLA-B27 positive individuals may be particularly vulnerable to diverse systemic triggers, including vaccines.

To elucidate changes of full-field electroretinography (ffERG) tests in active unilateral retinal vasculitis, using the unaffected fellow eye as an internal control. Despite no significant differences in best corrected visual acuity (p=0.100) or central subfield macular thickness (p=0.084) at baseline, ffERG showed significant reductions in five of eight amplitudes (i.e. DA10 a-wave, p<0.001) and delays in six of eight implicit times (i.e. light-adapted Flicker, p=0.002). At follow-up ffERG, following management for retinal vasculitis, the implicit times normalised, coinciding with inflammation reduction. However, the amplitude reductions persisted. In ffERG, the implicit time might be a sensitive biomarker for retinal vasculitis activity and the amplitude might be one for permanent functional loss.

INTRODUCTION:Pathogenic variants in FZD4 have been implicated in the pathogenesis of familial exudative vitreoretinopathy (FEVR). We present a family with a novel FZD4 variant and provide functional evidence supporting its pathogenic relevance. MATERIALS AND METHODS:This family-based study included three affected individuals who underwent comprehensive ophthalmic examinations, including best-corrected visual acuity, slit-lamp biomicroscopy, fundus examination, optical coherence tomography, and wide-field retinal imaging. Genetic testing was performed using whole-exome sequencing, followed by Sanger sequencing for variant confirmation and segregation analysis. Functional studies included in vitro cellular expression assays comparing wild-type and mutant FZD4 protein levels, Western blotting analysis, and proteasome inhibition experiments. Protein structural modeling was conducted to assess the impact of the missense variant on FZD4 domain integrity. RESULTS:Proband and three family members underwent comprehensive clinical evaluation. The proband presented with nystagmus, amblyopia, and acute angle-closure glaucoma in the left eye. Intraocular pressure normalized 1 month after lens extraction with intraocular lens implantation and goniosynechialysis. The proband's clinically asymptomatic sister and mother demonstrated peripheral retinal nonperfusion on imaging, consistent with subclinical manifestations of familial exudative vitreoretinopathy. The heterozygous FZD4 c.428T > C (p.Leu143Pro) variant segregated with FEVR-related phenotypes within the family, showing variable expressivity. The variant was classified as a likely pathogenic allele under ACMG/AMP criteria based on its location in the conserved cysteine-rich domain, absent from population databases, consistent with the in silico predictions, phenotype specificity, and functional evidence. Western blotting demonstrated a reduction of mutant FZD4 protein levels when compared with wild-type protein, also partially rescued by the proteasome inhibitor MG132. Structural modeling suggests that p.Leu143Pro substitution disrupts a conserved α-helical region, potentially affecting Wnt ligand binding. CONCLUSIONS:This family-based study identifies a novel FZD4 missense variant associated with FEVR and provides integrated clinical, genetic, functional, and structural evidence, supporting its likely pathogenic relevance. Surgical management of secondary complications, such as angle-closure glaucoma, might stabilize visual outcomes in patients with FZD4-associated FEVR.

We propose MAE-SAM2, a novel foundation model based framework for retinal vascular leakage segmentation in fluorescein angiography images. Due to the small size and dense distribution of the leakage areas, along with the limited availability of labeled clinical data, this segmentation task is significant challenge. To address these challenges, we integrate a self-supervised pre-training strategy based on Masked Autoencoders (MAE) with the foundation model MedSAM2. We further investigate several loss functions and identify a task-specific combined loss that yields the best performance. Extensive experiments and ablation studies demonstrate that MAE-SAM2 consistently outperforms multiple state-of-the-art methods, achieving the highest Dice score and Intersection-over-Union (IoU). These results highlight the potential of combining self-supervised pre-training with foundation models for challenging clinical image segmentation tasks.

Purpose:To evaluate the safety, tolerability, and effectiveness of the Everads Injector, a novel suprachoroidal drug delivery device, for administration of triamcinolone acetonide (TA) in patients with diabetic macular edema (DME). Design:A prospective, open-label pilot study. Subjects:Ten adult patients (10 eyes) with center-involved DME and inadequate response to prior anti-VEGF therapy. Methods:Each participant received a single suprachoroidal injection of 4 mg of TA in 100 μL using the injector. The device enables rapid, tangential delivery into the suprachoroidal space (SCS) by creating a channel from the sclera into the choroid via blunt dissection. Follow-up assessments were conducted on injection day and on days 3, 14, 28, and 42. Safety was assessed by adverse events monitoring, intraocular pressure (IOP) measurements, and comprehensive ocular examinations. Suprachoroidal delivery was confirmed through clinical evaluation and thermal imaging, verifying successful localization of TA within the SCS. Efficacy was measured by changes in central macular thickness and best-corrected visual acuity (BCVA). Main Outcome Measures:Safety, device performance, central macular thickness, and BCVA. Results:Triamcinolone acetonide was successfully delivered into the SCS in all participants, with no serious adverse events reported. Over 5 to 7 seconds, 100 μL of TA was injected. Mild subconjunctival hemorrhages occurred in 7 eyes and resolved without intervention IOP remained stable within the normal physiological range (12-18 mmHg) throughout all follow-up visits. Statistically significant reductions in central macular thickness were observed by day 42 (mean change: -134.9 μm; P = 0.0039). Best-corrected visual acuity improved in most participants (8 eyes), with a mean gain of +11.4 letters on the ETDRS chart from baseline to visit 6. Conclusions:Suprachoroidal delivery of TA in patients with DME using the injector demonstrated favorable safety and tolerability. The procedure was well tolerated under topical anesthesia and performed successfully in an office-based setting. These findings support the feasibility of this delivery technology and highlight its potential clinical benefit in reducing macular edema and improving visual function. Further studies are warranted to confirm these results in larger, controlled trials. Financial Disclosures:Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

Purpose:To describe spectral-domain optical coherence tomography (SD-OCT) morphological characteristics in patients with cone dysfunction disorders. Methods:This retrospective, single-center observational study was conducted at a tertiary referral university eye hospital between July 2018 and September 2020. Forty-two patients (84 eyes) with cone dysfunction disorders, diagnosed based on clinical findings and electroretinogram evidence of severely reduced or non-recordable cone responses with preserved rod function, were included in our study. SD-OCT imaging was performed, and images were evaluated regarding the integrity and pattern of hyper-reflective outer retinal bands. The relationship between these findings, age, central retinal thickness (CRT), and best-corrected visual acuity (BCVA) was assessed. Results:SD-OCT images of 82 eyes showed outer retinal abnormalities. Five SD-OCT morphological categories were found, including outer retinal atrophy (24.4%), poorly delineated outer retinal bands (22.0%), ellipsoid zone (EZ) disruption (19.5%), outer foveal defect (17.1%), and prominent outer retinal layers (17.1%). Additionally, five isolated OCT findings were detected, including foveal hypoplasia (14.6%), trans-retinal hyperreflective dots (THD) (29.3%), outer plexiform layer (OPL) schisis (11.0%), subretinal drusenoid-like deposits (9.8%), and EZ bowing (13.4%). Age and CRT were significantly different across the morphological categories (p<0.001). Eyes with prominent outer retinal layers had the best visual acuity, whereas those with outer retinal atrophy had the worst visual acuity; however, differences in BCVA among the morphological categories were not statistically significant in the univariate GEE analysis (p = 0.09) or after multivariable adjustment (p = 0.32). Conclusion:SD-OCT imaging demonstrates diverse outer retinal morphological patterns in patients with cone dysfunction disorders. These patterns were associated with age and CRT but were not significantly associated with BCVA. The proposed morphological classification may help characterize disease morphology and warrants prospective evaluation in longitudinal, genetically characterized cohorts to determine its potential utility as a biomarker.

PURPOSE:To investigate the potential impact of ocular inflammation on development of AAAs in patients with systemic autoimmune diseases treated with adalimumab. DESIGN:Retrospective case-control study. PARTICIPANTS:Patients who were treated with adalimumab for various autoimmune conditions for at least 6 months and were tested for adalimumab levels, antiadalimumab antibodies (AAAs), or both from June 2005 through May 2024. METHODS:The Stanford Research Repository database, a clinical data warehouse that aggregates electronic health records from Stanford Health Care, Stanford Children's Health, and affiliated clinics, was used to identify eligible participants. Demographic data, systemic diagnoses, ocular involvement, and prior and concurrent treatment also were collected. Subsequently, univariable and multivariable logistic regression analyses were conducted to identify factors associated with AAA development. MAIN OUTCOME MEASURES:The correlation of AAAs with ocular inflammation and the proportion of patients with positive AAA findings in the study cohort. RESULTS:Among 704 patients, 151 patients (21.5%) demonstrated AAAs. The group was predominantly female compared with the AAA-negative group (60.9% vs. 47.0%; adjusted odds ratio [aOR], 1.75; 95% confidence interval [CI], 1.07-2.85; P = 0.024). On multivariable analysis, ocular inflammation (aOR, 2.19; 95% CI, 1.19-4.02; P = 0.011), female sex (aOR, 1.75; 95% CI, 1.08-2.85; P = 0.024), and adalimumab interruption (aOR, 1.74; 95% CI, 1.03-2.94; P = 0.038) remained independent risk factors for AAA formation. Prior biologic therapy other than tumor necrosis factor (TNF)-α inhibitors was protective (aOR, 0.27; 95% CI, 0.08-0.98; P = 0.046), although prior TNF-α inhibitor exposure remained a risk factor (aOR, 2.11; 95% CI, 1.25-3.55; P = 0.005). CONCLUSION:Ocular inflammation in patients with autoimmune disorders is associated with an increased risk of AAA formation, prospective studies are needed to determine whether this reflects a mechanistic relationship and whether TDM in this subgroup improves clinical outcomes. Notably, more than one-fifth of patients receiving adalimumab in this cohort demonstrated AAAs. FINANCIAL DISCLOSURE(S):Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

PURPOSE:To develop imaging-based statements and consensus recommendations for the application of multimodal imaging in tubercular choroiditis (TBC). DESIGN:International expert committee-led consensus agreement using a modified nominal group technique with further refinement from literature review and full task force voting. PARTICIPANTS:International expert committee of uveitis and retina specialists from the Multimodal Imaging in Uveitis (MUV) task force. METHODS:The MUV task force convened a group of international experts to develop a set of standardized imaging criteria for TBC. Cases with focus on tubercular serpiginous-like choroiditis (TB SLC) and tuberculomas/tubercles were provided by expert members to develop a review case portfolio of both active and inactive disease with longitudinal follow-up. Cases included color fundus photography, fundus autofluorescence, fundus fluorescein angiography, indocyanine green angiography, OCT, and OCT angiography. The case portfolio was reviewed by all members, and through a structured nominal group technique and guided by a literature review, the group refined descriptive statements characterizing active, evolving, and inactive lesions until consensus was achieved. MAIN OUTCOME MEASURES:Imaging statements and consensus guidelines describing features of TB SLC and tuberculoma/tubercle in relation to diagnosis, monitoring, and detection of disease complications. RESULTS:The case portfolio included 31 cases, and the group achieved consensus on defining distinct imaging features of TB SLC and choroidal tuberculomas/tubercles. For TB SLC, key features of active lesions included yellow-white multifocal or placoid lesions with hyperautofluorescent edges on fundus autofluorescence, outer retinal hyperreflectivity, and focal choroidal thickening on OCT. Both indocyanine green angiography and OCT angiography highlight lesions that are often more extensive than those seen clinically. Choroidal tuberculomas were defined as solitary, lobulated masses often associated with subretinal fluid and retinal neovascularization, whereas tubercles appear as multiple small lesions associated with disseminated tuberculosis. Consensus-based guidelines were established to use these multimodal imaging features for diagnosis, monitoring response to treatment, and detecting complications. CONCLUSIONS:The MUV imaging guidelines for TBC extend existing diagnostic frameworks by systematically integrating multimodal imaging features for disease characterization and monitoring. These consensus-based recommendations enhance phenotypic classification, improve assessment of disease activity, and provide clinically relevant endpoints for evaluating treatment response. FINANCIAL DISCLOSURE(S):Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

Purpose:To determine whether significant changes in best-corrected visual acuity (BCVA) precede or coincide with increases in central retinal thickness (CRT) in diabetic macular edema (DME) during a treat-and-extend (T&E) regimen following initial edema resolution. Methods:This post-hoc analysis included 60 eyes (60 participants) from the READ-3 clinical trial that achieved CRT <250 µm and were followed until edema recurrence. Following a six-month ranibizumab loading phase, patients were monitored through 24 months with as-needed retreatment. Significant changes were defined as ≥4 Early Treatment Diabetic Retinopathy Study (ETDRS) letters and ≥30 µm on time-domain optical coherence tomography (TD-OCT). The temporal relationship between functional (BCVA) and anatomical (CRT) changes was analyzed. Results:Median time to edema resolution was 10 months (IQR: 6-16) and to recurrence was 3 months (IQR: 2-3). 52 eyes (86.7%) had functional worsening and 43 (71.7%) had anatomical worsening. In 39 eyes exhibiting both types of deterioration, changes were concurrent in 24 (61.5%). Vision loss preceded anatomical recurrence (BCVA-led) in 23.1% of eyes, with a lead time of 1-4 months. Conversely, anatomical thickening preceded vision loss (OCT-led) in 15.4% of eyes, by a maximum of 2 months. Conclusions:BCVA fluctuations frequently mirror CRT changes and can precede structural relapse, suggesting that BCVA is a sensitive indicator of DME activity. In resource-limited settings, BCVA may allow for earlier detection of recurrence than OCT alone. Translational Relevance:Functional vision loss can precede structural edema recurrence, supporting the potential for home-based BCVA monitoring as a validated bridge for timely clinical intervention in DME.

Purpose:To evaluate the safety, tolerability, and distribution of laquinimod (LAQ) eye drops as a potential steroid-sparing anti-inflammatory therapy. Design:Phase I clinical trial conducted at the Byers Eye Institute, Stanford University. NCT06161415. Participants:Patients scheduled for elective pars plana vitrectomy for various noninfectious indications. Methods:Enrolled subjects were instructed on proper LAQ storage and administration and received the drops for 14 days prior to surgery. Patients were sequentially assigned into 3 groups receiving daily LAQ doses of 0.6, 1.2, and 1.8 mg, with dose escalation permitted only in the absence of safety concerns in the preceding cohort. A preoperative visit was performed following 7 days of LAQ administration. On the day of surgery, aqueous, vitreous, and plasma samples were collected for LAQ quantification. Two postoperative follow-up visits were conducted. Main Outcome Measures:Tolerability; safety of the LAQ eye drop, assessed via ophthalmic examination, multimodal imaging, laboratory tests, and electrocardiogram; and LAQ concentrations in aqueous, vitreous, and plasma. Results:Ten participants completed the 14-day topical LAQ and all study visits, except one where pars plana vitrectomy was canceled; however, subject completed LAQ course and safety follow-up. The mean age was 59.9 ± 15 years, with a female predominance (70%). Given there were no dose-limiting toxicities, participants sequentially received daily doses of 0.6 mg (n = 4), 1.2 mg (n = 3), and 1.8 mg (n = 3). Following the exclusion of insufficient samples, LAQ levels were analyzed in 8 vitreous and 7 aqueous specimens. Laquinimod was well tolerated at all doses, with 3 adverse events unrelated to the study drug. Laquinimod was detected in aqueous, vitreous, and plasma with dose-dependent levels across all doses. Mean total LAQ level was significantly higher in aqueous rising from 508.5 to 3640.0 ng/mL, exceeding vitreous levels that rose from 6.89 to 38.50 ng/mL. Notably, unbound LAQ levels remained significant. Plasma concentrations remain within established safety ranges, with mean LAQ levels increasing from 153.4 to 563.5 ng/mL. Conclusions:Topical LAQ was safe and well tolerated at daily doses of 0.6, 1.2, and 1.8 mg, with measurable penetration into the posterior segment. Dose-dependent drug levels were detected in vitreous, aqueous, and plasma. These findings support investigation of LAQ's therapeutic potential for inflammatory eye diseases. Financial Disclosures:Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

Purpose:To evaluate the safety and efficacy of agonistic monoclonal antibody against roundabout receptor 4 (DS-7080a) in eyes with neovascular age-related macular degeneration (nAMD) and diabetic macular edema (DME) alone or in combination with ranibizumab. Design:This was a phase I dose escalation and expansion study registered on clinicaltrials.gov (NCT02530918) and conducted in 3 parts. Parts 1 (first phase of the study [P1]) and 2 (second phase of the study [P2]) involved dose escalation and expansion for patients with nAMD, while part 3 (third phase of the study [P3]) involved dose expansion only for DME subjects. Subjects:Patients with nAMD or DME. Methods:In P1, eligible patients were randomized into 3 sequential dose-level cohorts to establish a maximum tolerated dose for DS-7080a as 4.0 mg and assess its safety and tolerability. The study then proceeded to P2, where 27 nAMD subjects were randomized to one of the 3 treatment arms: DS-7080a, 4.0 mg only; ranibizumab, 0.5 mg only; or DS-7080a, 4.0 mg plus ranibizumab, 0.5 mg. In P3, 20 subjects with DME were randomized to one of the 2 arms: DS-7080a, 4.0 mg or ranibizumab, 0.3 mg injected thrice. The treatment period was 12 weeks. Main Outcome Outcomes:The primary endpoints were treatment-emergent adverse events (TEAEs) and serious adverse events (SAEs). The secondary endpoints were changes in central retinal thickness (central subfield thickness [CST]) and best-corrected visual acuity (BCVA). Results:A total of 56 patients were enrolled. Agonistic monoclonal antibody against Robo4, administered as monotherapy or in combination with ranibizumab, was generally well tolerated. Six drug-related TEAEs were observed, 4 of which were ocular events that led to treatment discontinuation. No drug-related SAEs or deaths occurred. As expected, ranibizumab was associated with improvements in BCVA and CST, whereas DS-7080a, alone or in combination, did not show clinically meaningful functional or anatomical benefit. Conclusions:Agonistic monoclonal antibody against Robo4 was generally well tolerated in eyes with nAMD and DME; however, drug-related TEAEs, including ocular events leading to discontinuation, were observed. In terms of efficacy outcomes, DS-7080a does not show BCVA improvement and CST decrease when administered alone or in conjunction with ranibizumab. These findings are inconsistent with nonclinical studies supporting DS-7080a as a therapeutic agent for nAMD and DME. Financial Disclosures:Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

PURPOSE:Ocular toxoplasmosis (OT) is the most common cause of posterior uveitis globally, with a significant risk of visual impairment. However, the lack of standardized data collection hinders meaningful comparisons across studies. This study aimed to develop a consensus-based set of Common Data Elements (CDEs) for observational studies in OT using a Delphi approach. DESIGN:A set of CDEs was developed through a combination of a comprehensive literature review, a hybrid workshop, and a Delphi consensus process. This effort was led by an international panel of experts in OT to define a standardized CDE set for research and clinical purposes. METHODS:A multidisciplinary steering committee identified an initial list of candidate CDEs through a targeted literature review. A panel of 30 international experts participated in a structured, one-round Delphi process to evaluate and refine these CDEs. Consensus was determined based on predefined thresholds for inclusion, exclusion, and modification. RESULTS:A total of 139 CDEs were categorized across nine domains: Demographic and Background Information, Medical and Ocular History, Clinical Presentation, Clinical Findings, Lesion Characteristics, Diagnostics, Imaging Findings, Treatment and Interventions, and Outcomes. All 139 CDEs met the inclusion criteria, with 79.8% rated as "very important". The consensus underscores the importance of a comprehensive, standardized dataset for OT research. CONCLUSIONS:This study establishes the first expert-derived standardized dataset requested for reporting OT outcomes, providing a framework to standardize data collection for future observational studies. Adopting these CDEs will enhance data comparability, improve meta-analyses, and strengthen the evidence base for clinical decision-making in OT. Future work will focus on real-world validation and refinement of this dataset.

Purpose:This proof-of-concept study aimed to evaluate the feasibility of targeted, image-guided microperimetry (IGMP) by integrating optical coherence tomography (OCT) and fundus autofluorescence (FAF) for lesion mapping and functional assessment in retinal atrophic diseases. Methods:Twenty-two eyes were identified, of which 17 had early geographic atrophy (GA) and 5 had Stargardt disease (SD). Disease transition zones (TZs) on OCT and FAF were annotated onto en face infrared images. These were then exported with microperimetry (MP) assessments to custom MATLAB applications. IGMP patterns were thereafter created and imported using macular integrity assessment (MAIA) system and Nidek-MP3/S microperimeters for subsequent scans. Mean procedure and examination times (minutes), retinal sensitivity (decibel [dB]), approach feasibility, and algorithm compatibility of targeted IGMP were reported as outcomes. Results:Targeted IGMP was quicker than the standard 10-2 grid for both SD and GA lesion assessments. SD cases showed longer mean procedure and examination times and lower mean retinal sensitivity in all zones compared with GA lesions. The targeted IGMP procedure was lengthier for Nidek-MP3/S (29.2 ± 7.1 minutes) than MAIA (17.4 ± 4.3 minutes), although the examination took longer on MAIA (4.0 ± 1.0 minutes) than on Nidek-MP3/S (3.6 ± 1.2 minutes). Overall, the IGMP approach is feasible (100.0%) and the algorithm is compatible (100.0%) on both MP devices for all subjects tested. Conclusions:This study establishes the feasibility of an IGMP workflow in providing targeted functional assessments in retinal degenerative diseases. Further validation in larger cohorts is needed to assess its broader clinical applicability. Translational Relevance:Our approach may help enhance structure-function correlation and optimize the efficiency of MP integration for clinical trials.

Purpose: To report a case of cobalt-induced retinopathy from a knee prosthesis and to outline the diagnostic challenges and management approach. Observation: A 67-year-old female presented with chronic bilateral visual disturbances, including blurred vision and photopsia, which began shortly after receiving a cobalt-containing knee prosthesis (DePuy Sigma Total Knee System, recalled by FDA in 2014, Recall No. Z-0423-2014). Ophthalmic evaluation revealed bilateral chorioretinitis, cystoid macular edema, and optic disc inflammation. Removal of the cobalt-containing prosthesis, along with aggressive immunosuppressive therapy, led to significant improvement in visual acuity and retinal function, as confirmed by fluorescein angiography, electroretinography, and Goldmann visual field testing. Conclusion: This case adds to the limited literature on cobalt-induced retinopathy by demonstrating that even small prosthetic implants, such as knee prostheses, can lead to systemic cobalt toxicity with significant ocular complications. Early diagnosis, combined with prompt removal of the affected prosthesis and management of inflammation, is crucial for restoring vision and preventing further damage.