Faculty Bibliography

Neurofibroma can present in a myriad of body tissues, including, very rarely, in the sclera; a unique presentation that is described herein. We describe a case of a 21-year-old man with neurofibromatosis type 1, who presented with 2 weeks of a blue-gray scleral discoloration overlying a protrusion of the sclera. His presentation was initially concerning for scleritis; however, histopathological analysis revealed an epibulbar neurofibroma. Recognition of rare manifestations of neurofibromatosis is essential to properly diagnose and manage ocular findings in this condition.

IMPORTANCE/UNASSIGNED:The current ocular Common Terminology Criteria for Adverse Events (CTCAE) mix eye signs with symptoms and lack standardized clinical photographs and experimental oncology drug dose modification recommendations. Robust reporting of ocular adverse events (AEs) is important to maintain patient safety and to guide the development of novel efficacious drugs. OBJECTIVE/UNASSIGNED:To develop improved ocular AE grading scales to reliably evaluate and grade ocular AEs in patients on experimental oncology drug therapy and to provide clear drug dose modification recommendations. DESIGN, SETTING, AND PARTICIPANTS/UNASSIGNED:A collaborative multicenter interspecialty working group consisting of oncologists and academic ophthalmologists from 11 academic centers in the US and ophthalmologists from the US Food and Drug Administration was assembled in February 2023 to form a consensus on new experimental oncology drug-related ocular AE grading scales. The grading scales were released in June 2023. MAIN OUTCOMES AND MEASURES/UNASSIGNED:Expert consensus on novel experimental oncology drug-related ocular AE grading scales. RESULTS/UNASSIGNED:Six experimental oncology drug-related ocular AE grading scales were developed with agreement from ophthalmologists and oncologists for use in antibody-drug conjugate clinical trials: visual acuity, eye symptoms, cornea, conjunctiva/sclera, anterior chamber, and retina/posterior segment. CONCLUSIONS AND RELEVANCE/UNASSIGNED:The new experimental oncology drug-related ocular AE grading scales developed by the consensus panel were developed to be more concise, containing photographs where applicable, and to provide clear drug dose modification recommendations compared with the previous CTCAE. Use of these ocular AE grading scales may allow for more objective and consistent incidence measurements of ocular AEs throughout clinical trials and postmarketing, potentially facilitating safe testing of novel agents that may cause eye toxicity.

Monitoring intracellular calcium is central to understanding cell signaling across nearly all cell types and organisms. Fluorescent genetically encoded calcium indicators (GECIs) remain the standard tools for in vivo calcium imaging, but require intense excitation light, leading to photobleaching, background autofluorescence and phototoxicity. Bioluminescent GECIs, which generate light enzymatically, eliminate these artifacts but have been constrained by low dynamic range and suboptimal calcium affinities. Here we show that CaBLAM ('calcium bioluminescence activity monitor'), an engineered bioluminescent calcium indicator, achieves an order-of-magnitude improvement in signal contrast and a tunable affinity matched to physiological cytosolic calcium. CaBLAM enables single-cell and subcellular activity imaging at video frame rates in cultured neurons and sustained imaging over hours in awake, behaving animals. These capabilities establish CaBLAM as a robust and general alternative to fluorescent GECIs, extending calcium imaging to regimes where excitation light is undesirable or infeasible.

PURPOSE/OBJECTIVE:To describe the clinical features, multimodal imaging findings, natural history, and treatment outcomes of acute outer retinopathy (AOR), which represents an expanded spectrum of acute annular outer retinopathy (AAOR). DESIGN/METHODS:Retrospective, observational, longitudinal, multicenter case series. PARTICIPANTS/METHODS:Twenty-three patients (15 female, 8 male) with a mean age of 41.8 ± 18.6 years (range: 14-86 years) and a mean follow-up duration of 3.7 ± 1.5 years (range: 1-12 years). METHODS:Clinical characteristics, multimodal imaging findings, laboratory evaluations, genetic testing, natural history, therapeutic management, and outcomes were reviewed and analyzed. MAIN OUTCOMES MEASURES/METHODS:Specific multimodal imaging signatures of AOR were identified, including findings from ophthalmoscopy, fundus autofluorescence (FAF), fluorescein angiography (FA), indocyanine green angiography (ICGA), and optical coherence tomography (OCT). Humphrey visual field testing, full-field electroretinography (ERG), and multifocal ERG were analyzed. Baseline features and the natural course of the disease were delineated. RESULTS:Thirty-eight eyes from 23 patients were analyzed. Presenting symptoms included photopsia (87%), blurred vision (57%), and scotoma (57%). On ophthalmoscopy, AOR was acutely characterized by yellow-greyish outer retinal lesions corresponding to hyperautofluorescent changes on FAF and the angular sign of Henle fiber layer hyperreflectivity (ASHH) on OCT. FAF imaging revealed ring-like hyperautofluorescent lesions surrounding the optic disc in 18% of eyes. Additional lesion patterns on FAF included perivenular (53%), sectoral (16%), and spot-like distributions (13%). FA and ICGA findings were mostly unremarkable. Lesion progression primarily occurred within the initial weeks following presentation and stabilized in size beyond this period in the majority of eyes. Over time, affected areas progressed to outer retinal atrophy with pigmentary changes. Foveal sparing was observed in 68% of the eyes. None of the therapeutic interventions appeared effective in halting the progression to complete outer retinal atrophy or preventing lesion enlargement. CONCLUSIONS:AOR is characterized by early photoreceptor disruption, evidenced by ASHH on OCT, leading to rapid outer retinal atrophy and subsequent degeneration of the retinal pigment epithelium within the damaged zones. Although distinct patterns of lesion distribution were observed, their consistent features on multimodal imaging support their inclusion within a unified disease spectrum termed acute outer retinopathy.

PURPOSE/OBJECTIVE:To evaluate anti-vascular endothelial growth factor (VEGF) treatment patterns and long-term visual acuity (VA) outcomes in retinal vein occlusion (RVO) in routine clinical practice. DESIGN/METHODS:Retrospective observational study of the Vestrum Health Retina database. SUBJECTS/METHODS:Treatment-naïve eyes with a diagnosis of macular edema secondary to branch RVO (BRVO) or central RVO (CRVO) between January 2014 and November 2021. METHODS:Patient eyes were identified in the database using International Classification of Diseases, Clinical Modification codes, and free text searches of Vestrum's 'Exam Findings' field for macular edema. Eyes included for analysis were required to have ≥ 1 intravitreal anti-VEGF injection and ≥ 3 months of follow-up. MAIN OUTCOME MEASURES/METHODS:Treatment patterns and VA outcomes up to 60 months (5 years) of follow-up. Mean VA change stratified by the tertile of the number of anti-VEGF injections received over 60 months. RESULTS:22 365 BRVO and 18 064 CRVO eyes were included in the analysis; ∼70% had ≥ 12 months follow-up and ∼10% had ≥ 60 months follow-up. The mean number of anti-VEGF injections for BRVO and CRVO, respectively, were 6.9 and 7.0 in year 1 and 3.7 and 3.9 in year 5. Mean VA gains from baseline for BRVO and CRVO, respectively, were 11.5 and 9.7 Early Treatment Diabetic Retinopathy Study letters at month 12 and 8.2 and 5.3 letters at month 60. BRVO and CRVO eyes with fewer injections (tertile 1) tended to have lower VA gains compared with eyes that received more injections (tertile 3). Of available eyes at 60 months, 68% of BRVO and 71% of CRVO eyes had received ≥ 1 anti-VEGF injection in year 5 of follow-up. Overall, 24% of BRVO and 5% of CRVO eyes received focal/grid-pattern laser, whereas 14% of both BRVO and CRVO eyes received intravitreal corticosteroids at any time during follow-up over 60 months. CONCLUSIONS:In this retrospective analysis of the Vestrum database, VA gains were observed after anti-VEGF treatment. These were lower in patients with longer follow-up times and higher in patients who received a higher number of injections, suggesting a need for long-term monitoring of eyes with RVO.

In this retrospective cohort study of 5,690 adults ≥ 65 years with non-traumatic corneal perforations, Black and older patients were less likely to receive keratoplasty, while older and lower-income patients more often underwent enucleation/evisceration.

BACKGROUND:Despite the high potential of transcranial ultrasound stimulation (TUS) for non-invasive brain therapy and interrogation, real-time monitoring of brain responses to TUS remains a challenge. Traditional methods to monitor direct neural responses are invasive and mostly incompatible with precise TUS delivery while other non-invasive approaches to visualize the induced responses suffer from poor penetration depth, lack of sensitivity, or low temporal resolution. OBJECTIVE:We present an integrated approach for high precision delivery of ultrasound into the mouse brain and simultaneous whole-brain oximetry with functional optoacoustic tomography to characterize the hemodynamic response elicited by TUS. METHODS:A spherically focused ultrasound array was employed to non-invasively deliver holographic TUS and simultaneously detect multispectral optoacoustic signals from the brains of anesthetized mice. Ultrasound pressure and pulse duration were varied, while the number of stimuli (5), stimulation duration (15 s), and ultrasound frequency (3 MHz) were kept constant. The acquired optoacoustic data were tomographically reconstructed and spectrally unmixed to render three-dimensional maps of oxygenated and deoxygenated hemoglobin in real time. RESULTS:TUS-evoked brain-wide hemodynamics were efficiently monitored via spectroscopic optoacoustic imaging with high spatial and temporal resolution. Holographic TUS targeted to the somatosensory cortex elicited distinct hemodynamic responses, which extended beyond the stimulated region, involving subcortical arteries and pial veins. CONCLUSIONS:Our method provides new transformative non-invasive capabilities to study the effects of ultrasound on a living brain thus help unleash the strong potential of TUS in neuroscience and medicine.

Keratoconus (KC) is a progressive corneal disorder that typically manifests during adolescence characterized by corneal thinning and irregularity. Recent studies have revealed that pathoanatomical abnormalities may not be limited to the anterior segment. Posterior segment alterations may also occur in KC patients. This study aims to provide a comprehensive review of the posterior segment changes in KC and assess the role of optical coherence tomography (OCT) in detecting these alterations. An initial systematic search of PubMed, EMBASE, and Web of Science was conducted on November 28, 2024. To identify any newly published literature, the search was updated on September 1, 2025. Random-effects models were employed to calculate pooled effect estimates. A total of 38 studies involving 4584 eyes were reviewed and 26 studies (3124 eyes) met our eligibility criteria for meta-analysis. The remaining 12 studies, although not included in the quantitative synthesis, were reviewed and their findings integrated. Our systematic analysis revealed significant reductions in several macular measurements, including average and temporal parafoveal (inner ring) thickness as well as temporal and superior perifoveal (outer ring) thickness. Peripapillary parameters also showed notable decreases, specifically in lamina cribrosa thickness, average retinal nerve fiber layer (RNFL) thickness, and RNFL thickness in the superior, temporal, and inferior quadrants. By contrast, subfoveal choroidal thickness was significantly increased in KC patients. Additionally, optic nerve head parameters, including cup area and cup volume, showed significantly greater values. When comparing different stages of the disease, patients with moderate KC exhibited significantly higher superotemporal RNFL thickness than those with severe disease. This meta-analysis underscores the concept that keratoconus, primarily a corneal disease, is associated with retinal and choroidal structural abnormalities. Changes in the posterior segment were similar across mild and advanced stages of the corneal disease. OCT monitoring in KC patients can facilitate detection of these alterations.

PURPOSE/UNASSIGNED:The purpose of this study was to introduce and evaluate the femtosecond laser enhanced refractive outcome (FLERO) prediction method, an intraocular lens (IOL) calculator that augments Barrett Universal II (BUII) by integrating novel anterior segment optical coherence tomography (OCT) biometric predictors obtained during femtosecond laser-assisted cataract surgery (FLACS). METHODS/UNASSIGNED:Two thousand, three hundred sixty-three (2363) eyes of 1720 patients (mean age = 71.33 years, 60.26% women) undergoing FLACS were analyzed. FLERO was developed by selecting the most predictive subset of OCT-derived biometry features using a "genetic algorithm" and combining them with BUII predictions in a linear model. Internal validation was performed through cross-validation, and prediction errors (PEs) were compared with BUII and Kane errors. RESULTS/UNASSIGNED:Compared to BUII, FLERO increased the proportion of eyes achieving postoperative refraction within ±0.25 diopter (D), ±0.50 D, and ±1.00 D of target from 0.470 to 0.507, 0.781 to 0.824, and 0.962 to 0.970, respectively. Mean absolute error decreased from 0.345 D for BUII and 0.338 D for Kane to 0.315 D for FLERO. FLERO outperformed BUII and Kane across (short, medium, and long) eyes, where proportions of eyes achieving refraction within ±0.50 D were 0.696, 0.831, and 0.782 for FLERO, 0.468, 0.796, and 0.718 for BUII, and 0.595, 0.798, and 0.718 for Kane. Wilcoxon Signed-Rank testing indicated significant reductions in absolute PEs for FLERO versus BUII and Kane (P < 0.0001). PE regression revealed FLERO made significantly smaller errors. CONCLUSIONS/UNASSIGNED:FLERO enhances BUII by incorporating novel OCT-derived FLACS biometric parameters across short, medium, and long eyes. TRANSLATIONAL RELEVANCE/UNASSIGNED:FLERO combines advanced FLACS-derived intraoperative biometry with established IOL formulae to refine refractive outcome prediction.