Commotio retinae (CR) resulting from retinal trauma can lead to focal photoreceptor degeneration and permanent vision loss. Currently no therapies exist for CR-induced retinal degeneration, in part because of the lack of a large-animal model that replicates human injury pathology and allows testing of therapeutics. Severe CR is clinically characterized by subretinal fluid and focal photoreceptor outer nuclear layer thinning. To develop a porcine CR model, we developed a laser-guided projectile apparatus and optimized projectile delivery procedure using porcine cadaveric eyes embedded in a 3D-printed porcine skull. Scleral and corneal impacts resulted in retinal damage consistent with patient injury, but corneal impacts also led to cornea damage and opacification, which precluded follow-up imaging. In live porcine eyes, scleral impacts of 39.5 m/s induced transient blood-retinal barrier breakdown evidenced by subretinal fluid on optical coherence tomography (OCT), leakage observed on fluorescein and indocyanine green angiography, and transient photoreceptor outer segment disruption seen by OCT and multifocal electroretinography. Impacts above 39.5 m/s induced longer-lasting photoreceptor degeneration but only transient blood-retinal barrier breakdown. This porcine model, combined with clinically relevant imaging and diagnostic modalities, will be valuable for testing the safety and efficacy of therapies to restore vision after focal photoreceptor degeneration.
PURPOSE. Rod-mediated dark adaptation delays are among the earliest functional abnormalities in age-related macular degeneration (AMD), preceding photoreceptor loss. This study evaluated whether parafoveal fundus-tracked dark adaptometry at 2 degrees detects earlier rod dysfunction than mid-macular loci (4 degrees and 6 degrees) and assessed the diagnostic performance of dynamic and steady-state parameters across eccentricities. METHODS. In this cross-sectional study, 35 patients with predominantly early/intermediate AMD and 35 healthy volunteers across a broad range of ages underwent funduscontrolled dark adaptometry (S-MAIA-2; iCare/CenterVue) and multimodal imaging. After standardized bleaching, Goldmann III sized (0.43 degrees) cyan stimuli were presented 2 degrees, 4 degrees, and 6 degrees temporal to the fovea. Dark-adaptation curves were modeled to derive rod intercept time (RIT), final (rod) threshold (FT), and cone threshold (CT), each compared with normative data. Diagnostic accuracy was quantified using covariate-adjusted receiver operating characteristic (ROC) analyses, to account for age. RESULTS. Among 70 analyzed eyes, RIT was abnormal in 86% of AMD eyes at 2 degrees, 69% at 4 degrees, and 60% at 6 degrees, whereas FT and CT were less frequently abnormal (29% to 51% and 17% to 26%, respectively). Median RIT at 2 degrees reached 60 minutes in the AMD cohort, indicating absence of rod function within the test duration in many eyes. RIT achieved the highest diagnostic accuracy, with covariate-adjusted area under the curve (AUC) values of 0.91 (95% credible intervals [CrI] = 0.80-0.97) at 2 degrees, 0.88 (95% CrI = 0.77-0.96) at 4 degrees, and 0.87 (95% CrI = 0.76-0.95) at 6 degrees. CONCLUSIONS. Fundus-tracked dark adaptometry enables spatially precise assessment of parafoveal rod recovery. Parafoveal RIT prolongation represents the earliest and most frequent functional abnormality in AMD and demonstrates excellent diagnostic performance, supporting its potential as a sensitive functional biomarker for early disease and therapeutic trials.
Ophthalmic immune-related adverse events (Eye-irAEs) from immune checkpoint inhibitors can cause visual morbidity. The absence of standardized definitions for Eye-irAEs not only impedes the development of evidence-based treatments but also progress in translational research. The objective of this study was to develop consensus guidance for an approach to Eye-irAEs.Four ophthalmic physicians (uveitis specialists and neuro-ophthalmologists) drafted Eye-irAE consensus guidance and definitions, which were reviewed by the multidisciplinary Eye-irAE definition panel. The panel was divided into Group A (Neuro-ophthalmology/Orbital Disease) and Group B (Uveitis/Ocular Surface Disease). A modified Delphi consensus process was used, with two rounds of anonymous ratings by panelists and two meetings to discuss areas of controversy. For each disorder, five diagnostic components were evaluated: symptoms, examination findings, laboratory studies/imaging findings, diagnostic criteria, and treatment. Panelists rated content for usability, appropriateness and accuracy on 9-point scales in electronic surveys and provided free-text comments. Aggregated survey responses were incorporated into revised definitions. Consensus was based on numeric ratings using the RAND Corporation/ University of California Los Angeles Health Services Utilization Study (RAND/UCLA) Appropriateness Method with prespecified definitions.29 panelists from 25 academic medical centers voted on 114 rating scales (66 neuro-ophthalmic/orbital disease components, 48 uveitis/ocular surface disease components); of these, 86.3% (57/66) in Group A and 89.6% (43/48) in Group B reached first-round consensus. After revisions, all items except 6.1% (4/66) in Group A and 1.6% (1/60) in Group B received second-round consensus. Consensus definitions were achieved for 10/11 neuro-ophthalmic/orbital disorders: optic neuritis, inflammatory optic disc edema, arteritic ischemic optic neuropathy, optic perineuritis, orbital inflammation, thyroid eye disease-like orbital inflammation, cavernous sinus syndrome, oculomotor mononeuritis, trochlear mononeuritis, and abducens mononeuritis. Consensus definitions were achieved for 9/10 uveitis/ocular surface disorders: anterior uveitis, intermediate uveitis, posterior uveitis, panuveitis, Vogt-Koyanagi-Harada-like syndrome, sarcoidosis-like syndrome, acute macular neuroretinopathy, dry eye disease, and scleritis.These disease definitions establish a standardized classification for Eye-irAE, highlighting differences between irAEs and other inflammatory disorders. Importantly, diagnostic certainty does not always align directly with the need to treat as an Eye-irAE. Given the consensus from this representative panel group, it is anticipated the definitions will be used broadly across clinical and research settings.
