Faculty Bibliography

PURPOSE/OBJECTIVE:To assess the biomechanical strength of a new transepithelial corneal cross-linking (epi-on CXL) protocol without iontophoresis and additional oxygen, and to compare it to the most broadly used accelerated epithelium-off (epioff) CXL protocol. METHODS:). Stress-strain extensiometry was performed to determine corneal biomechanics. RESULTS:= .005, respectively). CONCLUSIONS:.

Targeted cancer therapies have transformed the landscape of cancer treatments but are often associated with off-target adverse drug reactions due to overlapping molecular pathways in healthy tissues, including those in the eye. Fibroblast growth factor receptors (FGFRs), expressed across various parts of the eye, can become unintended targets of FGFR inhibitors such as erdafitinib, infigratinib, and pemigatinib, leading to ocular adverse events (AEs) affecting the ocular surface and retina. AEs across clinical trials are graded using the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE), which may not completely capture the ocular sequelae resulting from the use of emerging therapies. As CTCAE grading is mainly through the description of symptoms and their impact on visual acuity, it is imperative to use a tool that relies more on objective findings from ophthalmologic evaluations. The novel ocular adverse reaction severity grading scale developed by Amgen in collaboration with expert ophthalmologists, accounts for the anatomical regions impacted by ocular adverse reactions and anchors each severity grade to objective observable criteria from ophthalmologic evaluations. This grading scale is being used across the clinical development program for bemarituzumab to precisely characterize the ocular safety profile, enabling cross-specialty collaboration between oncologists and eye care providers to implement appropriate management strategies. This commentary article highlights the efforts led by Amgen in collaboration with regulatory, medical, and academic fields to develop tools that facilitate early recognition of adverse reactions and appropriate interventions for patient care.

PURPOSE/OBJECTIVE:To develop imaging and consensus-based guidelines on the application of multimodal imaging in multiple evanescent white dot syndrome (MEWDS). DESIGN/METHODS:Consensus agreement guided by literature, and an expert committee using a nominal group technique (NGT). METHODS:The expert committee employed a structured NGT with multiple rounds of discussion, conflict resolution, and anonymous voting to: (1) establish imaging criteria for diagnosing and monitoring MEWDS using color fundus photography (CFP), optical coherence tomography (OCT), fundus autofluorescence (FAF), fundus fluorescein angiography (FFA), indocyanine green angiography (ICGA), and OCT angiography (OCTA); and (2) develop consensus-based recommendations for assessing specific characteristics in patients with MEWDS. These formal recommendations were derived from a structured NGT using illustrative cases of MEWDS and were further voted upon by the entire task force. RESULTS:The diagnosis of acute MEWDS is supported by distinct multimodal features on CFP, multi-focal disruption of the ellipsoid/interdigitation zone with overlying outer retinal hyper-reflectivity with OCT, and hyper-autofluorescent spots with FAF (short-wave blue/green). In complex cases, wreath-like lesions on FFA and the absence of early hypofluorescence on ICGA help differentiate MEWDS from other chorioretinopathies. The lack of specific choroidal changes on OCT and preserved signal on OCTA on retinal and inner choroidal slabs also aid in diagnosis. CONCLUSIONS:Multimodal imaging is essential for diagnosing MEWDS and differentiating it from other non-infectious uveitis types, extending the Standardization of Uveitis Nomenclature (SUN) classification. These imaging criteria enable detailed assessment of disease activity and offer valuable insights into MEWDS pathogenesis.

PURPOSE/UNASSIGNED:To assess areas of mechanical instability in the fovea based on a review of artifactual separations of histological sections. METHODS/UNASSIGNED:A collection of annotated high-resolution retinal histological sections of aged donors was assessed for tissue disruptions in the fovea. Sections belong to Project MACULA (https://projectmacula.org). RESULTS/UNASSIGNED:Sections (mean length, 7467 ± 491 µm) through 75 foveas were analyzed (61% [46/75] from females; mean age at death, 81.3 years). Of these, 68% (51/75) were normal-aged, and 32% (24/75) showed early non-neovascular AMD. Separation of the neurosensory retina from the RPE occurred in 96% of sections (72/75). A break between the photoreceptor inner and outer segments was observed in 57% of cases (41/72), and bacillary layer detachment was observed in 15% (11/72), primarily involving the subfoveal region. Henle fiber layer disruptions were observed in 64% of sections (48/75), being around the Müller cell cone (MCC) in 90% of cases (43/48) and extending to cone photoreceptor cell bodies in 58% (28/48). Cystic changes at the MCC occurred in 50% of sections (38/75), with partial or complete disinsertion of the MCC in 47% of these (18/38). CONCLUSIONS/UNASSIGNED:Histological sections from normal-aged and early AMD eyes exhibit frequent tissue disruptions from post mortem handling, corresponding with regions of separation observed on OCT scans of various vitreoretinal diseases. Findings suggest that foveal areas of low mechanical stability may manifest as common ex vivo artifactual disruptions. Observing how foveal tissue breaks down post mortem may provide greater insight into the pathophysiology of different vitreoretinal diseases.

PURPOSE/UNASSIGNED:The purpose of this study was to assess the utility of artificial intelligence (AI) assisted analysis of anterior segment optical coherence tomography (AS-OCT) imaging of the device-cornea joint in predicting outcomes of an intrastromal synthetic cornea device in a rabbit model. METHODS/UNASSIGNED:Sixteen rabbits underwent intrastromal synthetic cornea implantation. Baseline anterior lamellar thickness was established using AS-OCT intraoperatively. Monthly postoperative clinical examinations and AS-OCT imaging were performed, focusing on the peri-optic zone. A convolutional neural network was trained using a subset of manually marked images to automatically detect anterior lamellar tissue. Images were aligned manually using reference coordinates. The tissue volume data were evaluated as both absolute volume and percentage change from baseline using AI. RESULTS/UNASSIGNED:Sixteen rabbits were observed for 6 (n = 8) and 12 (n = 8) months. Mild focal anterior lamella thinning without retraction was seen near tight sutures in 2 rabbits (2/8) in the 6-month cohort, whereas 2 rabbits (2/8) in the 12-month cohort showed mild focal retraction from the optic stem with thinning. AI-assisted AS-OCT image analyses detected tissue volume reduction up to 3 months before clinical examination, with a reliable threshold of 5% change in tissue volume. CONCLUSIONS/UNASSIGNED:AI-assisted AS-OCT can detect peri-prosthetic tissue loss and predicting postoperative complications following an intrastromal synthetic cornea implantation in a rabbit model. Further studies are warranted to explore its clinical utility in human patients. TRANSLATIONAL RELEVANCE/UNASSIGNED:AI-assisted monitoring of peri-optic corneal tissue volume may be a useful screening modality to detect subclinical thinning after artificial corneal implantation and inform clinical decision making.

PURPOSE/OBJECTIVE:To assess whether slit-scanning specular microscopy (CellChek C; Konan Medical) can repeatedly image the same corneal location using anatomic landmarks (posterior corneal rings and corneal undulations) and unique cells identified during imaging. METHODS:A total of 203 eyes (113 patients) with and without corneal pathology were imaged to assess the prevalence of anatomic landmarks. A subcohort of 20 healthy eyes was used to identify unique cells adjacent to anatomic landmarks. Landmarks were then used to locate the same cells on repeat imaging approximately 1 week later. Endothelial cell density (ECD), coefficient of variation, and percent hexagonality were calculated. Intraclass correlation coefficient and 95% limits of agreement were used to measure variability and reproducibility of imaging. RESULTS:Approximately 91% of eyes had either posterior corneal rings or undulations present. Undulations were more common than posterior corneal rings in both healthy and diseased corneas. Among subcohort eyes, unique cells were found adjacent to anatomic landmarks in 100% of eyes. Landmarks were used to reimage the same cells in 75% of eyes. There was minimal variation in ECD, coefficient of variation, and hexagonality; intraclass correlation coefficient and 95% confidence intervals were 0.891 [0.715-0.962], 0.612 [0.179-0.849], and 0.793 [0.499-0.925], respectively. The 95% limits of agreement for ECD was -359.9-260.98. CONCLUSIONS:Landmarks identified with slit-scanning specular microscopy allowed reliable reimaging of the same endothelial location, providing a powerful tool to better understand the role of the peripheral endothelium in health and disease.

PRECISE/UNASSIGNED:In this article, we describe the development of validated software that automates cost-effectiveness analyses of minimally invasive glaucoma surgeries based on modifications to robust mathematical models of glaucoma progression and management discussed in previous literature. PURPOSE/OBJECTIVE:To develop a validated application to streamline use of cost-effectiveness (CE) in clinical management and investigations of minimally invasive glaucoma surgeries (MIGS) in the United States. DESIGN/METHODS:Automated cost-utility analysis adapted from Markov models described in prior literature. PARTICIPANTS/METHODS:Patients of ages 65 years and greater with mild to moderate primary open-angle glaucoma irrespective of concurrent visually significant cataract. METHODS:Markov models simulating glaucoma progression through 37 states and death were constructed based on previous CE models of minimally invasive trabecular meshwork stents. These states represent combinations of various glaucoma severity (mild, moderate, advanced, and severe/blind) with differences in clinical management, including use of up to 4 medications, selective laser trabeculoplasty, or incisional surgery. These are not mutually exclusive and are based on decisions related to the rate of thinning of the retinal nerve fiber layer. Rather than using fixed sets of transition probabilities for specific surgical interventions, new transition probabilities are dynamically derived based on the expected reduction in intraocular pressure related to visual field mean deviation decline. In addition to the generic MIGS arm, two comparison arms (cataract-surgery or medications-only) are included. Medication reduction, whole costs, and utilities are modifiable inputs in the model. Optimal and worst-case results are determined by uncomplicated or complicated (secondary surgical intervention required/medication nonadherence) intervention outcomes. The model was entirely re-implemented in R and validated by comparing results to TreeAge data. MAIN OUTCOME MEASURES/METHODS:Total costs, quality adjusted life years (QALY), and incremental cost-effectiveness ratio (ICER). RESULTS:An optimal-case 35-year CE-analysis of the implantation of Hydrus and iStent inject devices provided values of costs and QALY that were similar to prior data (R vs. TreeAge): Hydrus (Cost: $50446.53 vs. $48026.13; QALY: 12.18 vs. 12.26), iStent inject (Cost: $52323.43 vs. $49599.86; QALY: 12.13 vs. 12.21), cataract (Cost: $54150.56 vs. $54409.25; QALY: 12.03 vs. 12.04). Trends of ICER over time were also very similar. CONCLUSIONS:Novel software is available to aid in CE analyses of MIGS with modifiable inputs and outcomes of interest. Such a tool makes CE more accessible for use in clinical management decisions and may guide future investigation.

BACKGROUND AND OBJECTIVE/OBJECTIVE:The increasing use of retinal diagnostic imaging necessitates a standardized viewing technique. This study investigates visual search patterns among ophthalmologists at various experience levels using eye-tracking technology. PATIENTS AND METHODS/METHODS:Participants included postgraduate year 2, 3, and 4 residents, retina fellows, and attending ophthalmologists, who analyzed fundus images while their eye movements were tracked. RESULTS:Results indicated that attendings had shorter fixation durations (0.15 ± 0.04 seconds) and saccade lengths (0.06° ± 0.01°), indicating faster image information processing than novice physicians. Experts also analyzed a higher proportion of the image area (49.43% ± 7.34%) and possessed a global-focal search pattern, suggesting increased thoroughness. CONCLUSION/CONCLUSIONS:.