Faculty Bibliography

PURPOSE/OBJECTIVE:To characterize and classify different forms of peripapillary retinoschisis (PPRS), and to clarify the nomenclature of this condition. METHODS:A retrospective, multicenter, multinational case series of PPRS was performed from August 2021 to September 2024. Cases were included if they demonstrated retinoschisis contiguous with and thought to be originating from the optic disc. Demographic and clinical data collected included age, gender, visual acuity, intraocular pressure, axial length, refraction and referring symptoms. Mandatory investigations included optical coherence tomography of the optic disc and macula with radial scans, colour fundus photography, and fundus autofluorescence. Select cases underwent fundus fluorescein and/or indocyanine green angiography. Retinoschisis was characterised by the meridian in relation to the optic disc, layer(s) of the retina affected and associated conditions. A literature review was performed to identify all causes of PPRS. RESULTS:A total of 47 eyes from 41 patients with PPRS were identified, comprising of 22 (54%) females and a mean age of 56 years (range 14-92 years). These were classified into nine aetiologies: Congenital Disc Abnormalities (CDA, n=16 eyes), peripapillary chorioretinal coloboma (n=1), peripapillary atrophy (n=3), glaucoma (n=7), Peripapillary Pachychoroid Syndrome (PPS, n=4), peripapillary choroidal neovascularization (PP-CNV, n=3), high/ pathological myopia (n=5), vitreopapillary traction (VPT, n=4) and idiopathic (n=4). CONCLUSION/CONCLUSIONS:The nine aetiologies of peripapillary retinoschisis can be classified into five groups: non-glaucomatous optic disc abnormalities (CDA, PP-coloboma, PP-atrophy), glaucomatous optic disc abnormalities, peripapillary choroidal diseases (PPS and PP-CNV), vitreous optic disc interface abnormalities and idiopathic. A new entity, "Focal Optic Disc Dome" (FODD) was identified. Understanding the full spectrum of PPRS can assist in correct diagnosis and management.

PURPOSE/OBJECTIVE:To establish consensus-based guidelines on the diagnosis, classification, and management of central serous chorioretinopathy (CSC) through a structured expert panel initiated by the Asia-Pacific Vitreo-retina Society (APVRS), the Academy of Asia-Pacific Professors of Ophthalmology (AAPPO), and the Academia Retina Internationalis (ARI), addressing the existing clinical controversies. METHODS:An international panel of 26 experts from 13 countries collaboratively drafted consensus statements spanning five key areas: disease definition, pathophysiology, investigations, current management, and future developments. Consensus was reached through an iterative Delphi process and anonymous voting using a five-point Likert scale. Statements were accepted when >75 % agreement ('agree' & 'strongly agree') was achieved. RESULTS:Consensus was achieved for all 25 statements, reflecting strong alignment among experts. Key agreements included defining CSC as a pachychoroid-driven chorioretinal disorder characterized by neurosensory retinal and/or RPE detachment, with multimodal imaging (optical coherence tomography, fundus autofluorescence, fluorescein angiography, and indocyanine green angiography) recognized as essential for diagnosis. Half-dose photodynamic therapy (PDT) was unanimously endorsed as the first-line treatment for chronic CSC. Oral mineralocorticoid receptor antagonists (MRAs) lacked consensus for therapeutic benefit, aligning with evidence from the VICI and SPECTRA trials. Anti-vascular endothelial growth factor receptor therapy was recommended solely for CSC complicated by a macular neovascularization. Future priorities highlighted standardizing disease classification and exploring targeted therapies through genetic and nanomedicine research. CONCLUSION/CONCLUSIONS:This consensus initiative provides a robust, evidence-based framework for the diagnosis and management of CSC, promoting standardization across clinical practices and guiding future research directions to address persistent gaps in CSC care.

Inflammation drives various diseases, including cardiovascular, neurodegenerative, and oncological disorders, by altering immune cell dynamics in hematopoietic niches. The bone marrow is the primary site for hematopoietic stem and progenitor cell activity. Here, we present a novel, noninvasive approach using multispectral optoacoustic tomography (MSOT) to track oxygenation dynamics in the murine calvarial bone marrow during acute systemic inflammation induced by lipopolysaccharide (LPS). Our MSOT system provided real-time, label-free imaging of hemoglobin oxygen saturation (sO₂), revealing significant reductions in sO₂ levels in lipopolysaccharide-treated mice, indicative of increased oxygen consumption. Co-registration with microCT enabled precise vascular mapping. Hypoxia was confirmed by ex vivo Pimonidazole staining and optical imaging and was associated with elevated neutrophil counts and enhanced hematopoietic activation. These findings demonstrate MSOT's potential for noninvasive imaging of marrow oxygenation, offering insights into inflammation-driven hematopoietic activation and supporting the development of therapies targeting oxygen-sensitive pathways.

BACKGROUND:Delayed diagnosis of venous thromboembolism (VTE) is prevalent among hospitalized patients, yet case identification is challenging and feedback limited. OBJECTIVE:To develop a large language model (LLM)-based electronic-trigger to identify VTE diagnostic delays. METHODS:All admissions to internal medicine (IM) residents at NYU Langone Health between January 2022 and December 2023 (n = 20,843) were included. Using an open-source LLM, prompts were validated to detect (1) residents considering VTE in admission notes and (2) VTE confirmation in five types of imaging reports (n = 100 for each prompt validation set). The validated prompts were applied to determine discordance between admission note differential omitting VTE and imaging report confirming VTE. Two hospitalists reviewed discordant cases using a validated tool to identify diagnostic delays. Hospitalizations were labeled as diagnostic delays, in-hospital complication, or false-positive. Based on in-hospital complication and false-positive patterns, exclusion criteria were implemented. Positive predictive value (PPV) and negative predictive value (NPV) were calculated. RESULTS:The LLM prompts correctly classified admission notes and VTE imaging studies with high accuracy (range 98%-100%, n = 699 VTE cases identified). Of the 137 diagnostic delays the LLM-based electronic-trigger identified, 31 were true-positives, 60 in-hospital complications, and 46 false-positives. 4.4% of all VTE hospitalizations had a diagnostic delay. With the exclusion criteria, the PPV was 48% (95% confidence interval [CI], 35%-62%) and NPV was 95% (95% CI, 87%-98%). CONCLUSIONS:We developed the first LLM-based electronic-trigger to identify VTE diagnostic delays, with higher performance than existing non-LLM electronic-triggers. LLM-based approaches can facilitate diagnostic performance feedback and are scalable to other conditions and institutions.

BACKGROUND:In ELM-2, the human CD20 × CD3 bispecific antibody odronextamab was associated with deep, durable responses and a generally manageable safety profile in patients with relapsed/refractory follicular lymphoma (r/r FL). PATIENTS AND METHODS/METHODS:Prespecified analyses reported herein examined patient-reported outcomes in ELM-2 among 140 patients with r/r FL. RESULTS:Using the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30), patients reported good global health status/quality of life (GHS/QoL), functioning, and low symptom burden at baseline, which were generally maintained. Emotional functioning improved significantly overall, with a clinically meaningful change at week 42. Patients were more likely to report clinically meaningful improvement or maintenance than worsening on QLQ-C30 scales. Median time to definitive deterioration (TTDD) was 22.4 months for GHS/QoL, 22.6 months for role functioning, 19.8 months for social functioning, 16.4 months for cognitive functioning, and not reached for physical functioning or emotional functioning. For each QLQ-C30 symptom scale, median TTDD was > 15 months or not reached. On the Functional Assessment of Cancer Therapy-Lymphoma (FACT-Lym) questionnaire, Lymphoma Subscale (LymS) scores improved significantly overall, with clinically meaningful improvement at weeks 26 and 42, and FACT-G, Trial Outcome Index, and Total Score were maintained. Most patients reported either limited or no bother related to side effects of treatment. Visual analog scale scores of the EQ-5D-3L questionnaire improved significantly overall. CONCLUSION/CONCLUSIONS:In this heavily pretreated, highly refractory population, maintenance or improvement of health-related quality of life, functioning, and symptoms support odronextamab as a potential treatment option in R/R FL.

IMPORTANCE/OBJECTIVE:Belantamab mafodotin (belamaf)-containing regimens are effective treatment options for patients with relapsed and/or refractory multiple myeloma. Ocular events are a common adverse effect of belamaf treatment, which can be managed by physicians, following appropriate training, to minimize their impact on the patient. OBJECTIVE:To develop clinical recommendations for the identification, monitoring, and management of ocular events associated with belamaf therapy, and guidance for any required dose modification. EVIDENCE REVIEW/METHODS:A systematic literature review was conducted and an international group of hematologists and ophthalmologists reviewed clinical trial data, real-world evidence, and published literature on belamaf-associated ocular events. This literature review and the collective experience and expertise of the panel of experts informed the recommendations. FINDINGS/RESULTS:Belamaf-associated ocular events are common side effects of treatment, which are managed primarily with appropriate dose modification and decreased frequency of dosing, as well as the use of artificial tears. These events affect the corneal epithelium, are mainly Grade 1 and 2 per the Keratopathy and Visual Acuity scale and are reversible in almost all patients. In general, before initiating belamaf therapy, all patients should undergo a baseline ophthalmic evaluation with an eye specialist. However, if there are delays in obtaining ophthalmic evaluation, or if a patient is rapidly progressing, treatment should be initiated, and ophthalmic evaluation should be undertaken as soon as possible. Patients should be also evaluated by an eye specialist before administering the next three belamaf doses (i.e., before Cycles 2, 3, and 4); dose modifications, as described in this paper, may apply if required. Importantly, modifying the belamaf dose in response to an ocular event is not associated with any reductions in treatment efficacy. After Cycle 4, the treating physician may use the Vision-Related Anamnestic tool, alongside clinical judgment, to decide whether to administer the next dose of belamaf or to refer the patient to an eye specialist (i.e., if the patient experiences new worsening of vision or if the ocular events have neither improved after 8 weeks nor resolved after 12 weeks). CONCLUSIONS AND RELEVANCE/CONCLUSIONS:The expert panel developed recommendations for managing belamaf-associated ocular events, with the aim of contributing to the ease of clinical use of belamaf and improving patient outcomes.

PURPOSE/OBJECTIVE:In this study, we further evaluated a unique early biomarker that has been demonstrated to be correlated with primary open-angle glaucoma in a pilot study. This novel biomarker correlated an increased ratio of pigmentation in the inferior trabecular meshwork (TM) compared to the superior TM with a greater degree of visual field loss in a small subset of patients. We evaluated this association in a larger group of patients. METHODS:This is a retrospective single-center analysis of Black and Afro-Latino patients that make up the local New York inner-city community of Advanced Eyecare of New York in Queens Village and Harlem, New York City with a diagnosis of primary open-angle glaucoma. We reviewed 335 consecutive glaucoma and glaucoma suspect patients with imaging of the TM via the GS-1 gonioscope. The degree of pigmentation was then quantified using ImageJ software to measure the ratio of pigmentation in the superior to inferior TM. We then created a ratio based on these superior to inferior TM measurements for each patient and compared this ratio to the patient's mean deviation of the visual field. RESULTS:Results from 529 eyes in 335 patients demonstrated a positive correlation between the superior-inferior ratio (SIR) of pigmentation and visual field loss. The greater the degree of pigmentation asymmetry between the superior and inferior angle, the greater the extent of visual field deterioration. There was also a positive correlation between the SIR and age. CONCLUSION/CONCLUSIONS:In a larger cohort of patients with glaucoma or glaucoma suspects, on TM pigment assessment with Image J, there was a positive correlation between SIR and worsening visual field mean deviation. Further research is required to evaluate a greater number of normal patients, glaucoma suspects, and glaucoma patients. Further research is also necessary to produce automated TM images and to develop automated assessment of TM pigment density with artificial intelligence to compare with other clinical factors such as age, IOP, OCT, and retinal nerve fiber layer thickness. Since the TM is where damage initially occurs to cause glaucoma, this can potentially lead to earlier detection before IOP elevation and retinal ganglion cell loss.

PURPOSE/OBJECTIVE:To characterize the clinical and multimodal imaging features of central bouquet hemorrhage (CBH) with Henle fiber layer (HFL) involvement in highly myopic eyes, and to investigate the relationships between hemorrhage characteristics, reabsorption time, and visual outcomes. METHODS:Multicenter, retrospective analysis of highly myopic eyes with CBH involving the HFL, confirmed by optical coherence tomography (OCT). RESULTS:Eighteen eyes from 18 subjects were included for analysis. The mean age of the cohort was 39 ± 13.7 years (range: 17-69) and 61% of subjects were female. Mean refractive error was -14.8 ± 3.14 diopters (range: -9 D to -22 D). All eyes demonstrated a combined CBH with HFL component, while a subretinal component was present in 83.3% of cases. Myopic choroidal neovascularization (CNV) was excluded in all eyes using optical coherence tomography angiography (OCTA) or dye-based angiography (fluorescein or indocyanine green). No correlation was observed between hemorrhage size and visual outcomes or reabsorption time. Hemorrhage cleared after a mean of 2.63 months, and the radial HFL hemorrhage component resolved first. All eyes showed improvement in visual acuity from baseline. Persistent OCT alternations after resolution of hemorrhage included ellipsoid zone disruption (88.9%) and hyperreflective changes in HFL (77.8%). Anti-VEGF injections were administered to 6 eyes (33.3%) and did not correlate with a significant visual or anatomical benefit. CONCLUSION/CONCLUSIONS:CBH with HFL involvement in high myopia was associated with significantly improved visual outcomes from baseline but structural alterations can persist after clinical resolution. The size of the hemorrhage did not correlate with resorption time, and anti-VEGF treatment did not affect outcome. These findings provide new insights into the natural history and management of nonneovascular CBH in highly myopic eyes.

PURPOSE/UNASSIGNED:To validate an existing finite element model (FEM) for predicting the flattening effect of corneal cross-linking (CXL) in a clinical scenario and to use this model to investigate the parameters that most influence CXL-induced flattening effects. METHODS/UNASSIGNED:Retrospective data were collected from two clinical cohorts, each with 20 patients receiving either standard or customized CXL. Data were collected before surgery and at the six-month follow-up. Both CXL treatments were simulated with a FEM calibrated on experimental data. Standard anterior corneal geometry indexes (e.g., sphere, cylinder), as well as the curvature changes observed at follow-up were compared to those predicted by FEM simulations. RESULTS/UNASSIGNED:At follow-up, patients who underwent customized CXL exhibited more corneal flattening compared to those who received standard CXL (Kmax-t: -2.28 ± 1.4 D vs. -0.81 ± 1.5 D; P < 0.001). The FEM-predicted curvature reduction in the central CXL regions showed a significant correlation with the follow-up data for both standard (R2 = 0.48, P < 0.01) and customized CXL (R2 = 0.59, P < 0.01). Compared to follow-up data, standard CXL model showed concordance correlation coefficients > 0.9 for nine corneal geometry parameters and customized CXL model for three. Sensitivity analysis demonstrated that a 3 mm Hg increase in intraocular pressure (IOP) combined with a 10% weaker keratoconus region alters flattening outcomes by up to 20%. CONCLUSIONS/UNASSIGNED:Customized CXL induces a flattening of about 2 diopters in the cone region six months after surgery. The model adequately captured the curvature corrections induced by the treatment in the keratoconus cone region, but showed reduced accuracy in predicting global corneal metrics, particularly for customized CXL. The induced flattening effects depend on the IOP, keratoconus-induced biomechanical weakening, and the fluence delivered to the cone.