Faculty Bibliography

PURPOSE/OBJECTIVE:To characterize private equity (PE) acquisition of ophthalmology and optometry practices and compare procedural utilization before and after acquisition. METHODS:Ophthalmologists and optometrists in practices acquired from 2012 to 2016 were identified and characterized using an internet archive with an additional search in 2017 to characterize doctor turnover. United States Census Bureau and Internal Revenue Service Data were used to determine population health insurance and adjusted gross income (AGI). Healthcare Common Procedure Coding System codes were drawn from the Medicare database. RESULTS:Six platform companies acquired 36 practices between 2012 and 2016, including 518 optometrists and 136 ophthalmologists with a net doctor decrease of 3% and 7%, respectively (years 2016 to 2017). PE firm-owned practices were primarily located in metropolitan core areas with above-average AGI and insurance coverage. Diagnostic procedures, total encounters, cataract surgery, and yttrium aluminum garnet (YAG) capsulotomy volume increased per physician 1-year post-acquisition. In adjusted difference-in-difference comparisons, cataract surgery (13.3% relative increase, P<0.001) and YAG capsulotomy (35.6% relative increase, P<0.001) remained significant. PE practices demonstrated an increase in cataract surgery procedures (28,813/platform pre-acquisition to 33,930/platform post-acquisition, P=0.015). CONCLUSION/CONCLUSIONS:PE acquisitions of ophthalmology and optometry practices were centered in metropolitan core areas with above-average AGI and insurance coverage. PE acquisition led to less optometrists and ophthalmologists employed at the practice. Overall, they exhibited doctor turnover with a net doctor decrease. When compared to non-PE doctors, PE-acquired doctors demonstrated an increase in cataract surgery and YAG capsulotomy volume. Overall, cataract surgery volume increased among PE practices after acquisition.

SIGNIFICANCE/CONCLUSIONS:Optimal meibography utilization and interpretation are hindered due to poor lid presentation, blurry images, or image artifacts and the challenges of applying clinical grading scales. These results, using the largest image dataset analyzed to date, demonstrate development of algorithms that provide standardized, real-time inference that addresses all of these limitations. PURPOSE/OBJECTIVE:This study aimed to develop and validate an algorithmic pipeline to automate and standardize meibomian gland absence assessment and interpretation. METHODS:A total of 143,476 images were collected from sites across North America. Ophthalmologist and optometrist experts established ground-truth image quality and quantification (i.e., degree of gland absence). Annotated images were allocated into training, validation, and test sets. Convolutional neural networks within Google Cloud VertexAI trained three locally deployable or edge-based predictive models: image quality detection, over-flip detection, and gland absence detection. The algorithms were combined into an algorithmic pipeline onboard a LipiScan Dynamic Meibomian Imager to provide real-time clinical inference for new images. Performance metrics were generated for each algorithm in the pipeline onboard the LipiScan from naive image test sets. RESULTS:Individual model performance metrics included the following: weighted average precision (image quality detection: 0.81, over-flip detection: 0.88, gland absence detection: 0.84), weighted average recall (image quality detection: 0.80, over-flip detection: 0.87, gland absence detection: 0.80), weighted average F1 score (image quality detection: 0.80, over-flip detection: 0.87, gland absence detection: 0.81), overall accuracy (image quality detection: 0.80, over-flip detection: 0.87, gland absence detection: 0.80), Cohen κ (image quality detection: 0.60, over-flip detection: 0.62, and gland absence detection: 0.71), Kendall τb (image quality detection: 0.61, p<0.001, over-flip detection: 0.63, p<0.001, and gland absence detection: 0.67, p<001), and Matthews coefficient (image quality detection: 0.61, over-flip detection: 0.63, and gland absence detection: 0.62). Area under the precision-recall curve (image quality detection: 0.87 over-flip detection: 0.92, gland absence detection: 0.89) and area under the receiver operating characteristic curve (image quality detection: 0.88, over-flip detection: 0.91 gland absence detection: 0.93) were calculated across a common set of thresholds, ranging from 0 to 1. CONCLUSIONS:Comparison of predictions from each model to expert panel ground-truth demonstrated strong association and moderate to substantial agreement. The findings and performance metrics show that the pipeline of algorithms provides standardized, real-time inference/prediction of meibomian gland absence.

PURPOSE/OBJECTIVE:To report the multimodal imaging features of hyperpigmented chorioretinal lesions originating from the retinal pigment epithelium (RPE) within punched-out lesions of punctate inner choroidopathy (PIC). METHODS:Retrospective case report. Multimodal imaging findings including fundus photography, optical coherence tomography (OCT), and OCT-angiography (OCTA) were analyzed. RESULTS:A 49-year-old female with myopic degeneration developed progressive lesions of PIC requiring immunosuppressive therapy with adalimumab. Within areas of punched-out chorioretinal atrophic lesions, the occurrence of hyperpigmented lesions were observed which enlarged and extended into the choroid over a multiyear follow-up. CONCLUSION/CONCLUSIONS:This case illustrates the development of pigmented choroidal lesions appearing to originate from the RPE through transdifferentiation following previous chorioretinal inflammatory lesions. The introduction of adalimumab treatment may have activated the cellular migration of the RPE. To the best of our knowledge, this is the first report of intrachoroidal RPE migration in PIC.

OBJECTIVES/OBJECTIVE:To systematically review the safety and efficacy of nonbiological (NBAL) or biological artificial liver support systems (BAL) and whole-organ extracorporeal liver perfusion (W-ECLP) systems, in adults with acute liver failure (ALF) and acute-on-chronic liver failure (ACLF). DATA SOURCES/METHODS:Eligible NBAL/BAL studies from PubMed/Embase searches were randomized controlled trials (RCTs) in adult patients with ALF/ACLF, greater than or equal to ten patients per group, reporting outcomes related to survival, adverse events, transplantation rate, and hepatic encephalopathy, and published in English from January 2000 to July 2023. Separately, we searched for studies evaluating W-ECLP in adult patients with ALF or ACLF published between January1990 and July 2023. STUDY SELECTION AND DATA EXTRACTION/METHODS:Two researchers independently screened citations for eligibility and, of eligible studies, retrieved data related to study characteristics, patients and interventions, outcomes definition, and intervention effects. The Cochrane Risk of Bias 2 tool and Joanna Briggs Institute checklists were used to assess individual study risk of bias. Meta-analysis of mortality at 28-30 days post-support system initiation and frequency of at least one serious adverse event (SAE) generated pooled risk ratios (RRs), based on random (mortality) or fixed (SAE) effects models. DATA SYNTHESIS/RESULTS:Of 17 trials evaluating NBAL/BAL systems, 11 reported 28-30 days mortality and five reported frequency of at least one SAE. Overall, NBAL/BAL was not statistically associated with mortality at 28-30 days (RR, 0.85; 95% CI, 0.67-1.07; p = 0.169) or frequency of at least one SAE (RR, 1.15; 95% CI, 0.99-1.33; p = 0.059), compared with standard medical treatment. Subgroup results on ALF patients suggest possible benefit for mortality (RR, 0.67; 95% CI, 0.44-1.03; p = 0.069). From six reports of W-ECLP (12 patients), more than half (58%) of severe patients were bridged to transplantation and survived without transmission of porcine retroviruses. CONCLUSIONS:Despite no significant pooled effects of NBAL/BAL devices, the available evidence calls for further research and development of extracorporeal liver support systems, with larger RCTs and optimization of patient selection, perfusion durability, and treatment protocols.

PURPOSE/OBJECTIVE:We developed human cornea organoids (HCOs) from induced pluripotent stem cells (iPSCs) where single-cell RNA-sequence (scRNA-seq) analysis suggested similarity with developing rather than mature human corneas. We performed immunohistology to determine the presence of corneal glycosaminoglycans as an assessment of maturity. We undertook a detailed comparison of the HCO scRNA-seq data with a recent scRNA-seq study of human fetal corneas at different stages to gauge the HCO's maturity. METHODS:We generated HCOs from a second iPSC line, NCRM-1, to assess the reproducibility of HCO development. We stained sections from both HCO lines with Alcian blue and picrosirius red to determine deposition of sulfated glycosaminoglycans and fibrillar collagens. We immunolocalized glycosaminoglycan biosynthetic enzymes and proteoglycan core proteins. The scRNA-seq data from IMR90.4 HCOs were compared to that of fetal corneas using MetaNeighbor analysis to assess the similarity of HCOs to different stages of human corneal development. RESULTS:The MetaNeighbor analysis suggests closer alignment of the IMR90.4 HCOs with 17-18 post-conception week fetal human corneas. HCOs from both iPSC lines deposit sulfated glycosaminoglycans and fibrillar collagens. Immunohistology showed chondroitin/dermatan sulfate (CS/DS) and keratan sulfate in the presumptive stromal and some epithelial layers. The NCRM-1-derived HCOs show increased CS/DS staining compared to the IMR90.4 derived HCOs. CONCLUSIONS:Both HCO lines show similar developmental patterns and timeline. The NCRM-1 HCO line may have more glycosaminoglycan deposition. Overall, the glycosaminoglycan deposition pattern is consistent with an immature tissue. Optimizations based on our current findings may yield more mature stromal cells and cornea-typical proteoglycans.

The existence of a previously unrecognized subarachnoid lymphatic-like membrane (SLYM) was reported in a recent study. SLYM is described as an intermediate leptomeningeal layer between the arachnoid and pia mater in mouse and human brains, which divides the subarachnoid space (SAS) into two functional compartments. Being a macroscopic structure, having missed detection in previous studies is surprising. We systematically reviewed the published reports in animals and humans to explore whether prior descriptions of this meningeal layer were reported in some way. A comprehensive search was conducted in PubMed/Medline, EMBASE, Google Scholar, Science Direct, and Web of Science databases using combinations of MeSH terms and keywords with Boolean operators from inception until 31 December 2023. We found at least eight studies that provided structural evidence of an intermediate leptomeningeal layer in the brain or spinal cord. However, unequivocal descriptions for this layer all along the central nervous system were scarce. Obscure names like the epipial, intermediate meningeal, outer pial layers, or intermediate lamella were used to describe it. Its microscopic/ultrastructural details closely resemble the recently reported SLYM. We further examined the counterarguments in current literature that are skeptical of the existence of this layer. The potential physiological and clinical implications of this new meningeal layer are significant, underscoring the urgent need for further exploration of its structural and functional details.

BACKGROUND/UNASSIGNED:Attention Deficit Hyperactivity Disorder (ADHD) among children younger than 6 years is quite impairing, nearly half these youth with ADHD experience school exclusion from mainstream preschool classes due to related emotional and behavioral outbursts. While a range of behavior rating scales and subjective measures are used to assess these youth, objective methods of assessment and prediction derived from technology have potential to improve therapeutic and academic interventions outcomes for these youths. We hypothesized that biometric sensors would provide objective, highly sensitive and specific information regarding the physiological status of children prior to an impulsive outburst and could be feasibly implemented using a wearable device in the special education classroom. METHODS/UNASSIGNED: = 5 youth from the first grade) of a specialized therapeutic day-school for youth with ADHD and other psychiatric and developmental disorders to examine feasibility of obtaining continuous physiological data associated with behavioral and emotional outbursts through smartwatch use. Children wore a sensor watch during their daily classroom activities for two weeks and trained observers collected data using behavioral logs. Using Ecological Momentary Assessment methodology, to examine correlations between objective sensor data and observer observation. Data collected from parents regarding prior night's sleep was also examined. RESULTS/UNASSIGNED:All participants completed the study. With a few tolerability or palatability issues. Associations were found between physiological and behavioral/questionnaire data. The methodology holds promise for reliably measuring behavioral and emotional outbursts in young children. CONCLUSIONS/UNASSIGNED:among severely dysregulated pre-school aged youth throughout a full school day. This study established the feasibility of utilizing sensor derived physiological data as an objective biomarker of ADHD within the special education therapeutic classroom. Further research with larger samples is required to build a more robust and personalized AI predictive model.

The XEN®45 Glaucoma Treatment System (gel stent; Allergan, an AbbVie company, Irvine, CA, USA) is a minimally invasive bleb-forming surgical device that was originally approved to lower intraocular pressure by diverting the aqueous humor from the anterior chamber to the subconjunctival space (like trabeculectomy) following ab-interno placement. Since approval of the gel stent in multiple countries, the implantation technique has evolved considerably, being performed ab interno or ab externo with open or closed conjunctiva, based on patients' needs and/or surgeons' preferences. Additional technical variations that can facilitate gel stent placement and/or improve outcomes have also emerged. This article aims to increase awareness of these developments to facilitate informed decision-making and improve surgical success and outcomes for patients.

We report the case of a 33-year-old woman with a history of hypothyroidism and ocular history of mild myopia who presented with a spontaneous filtering bleb. Extensive systemic rheumatologic evaluation was unrevealing. The bleb was observed for many months, until the patient's vision declined secondary to the development of hypotony maculopathy. The filtering bleb was closed using an allogenic scleral patch graft, resulting in normotensive intraocular pressure and improved best-corrected visual acuity. A unilateral, spontaneous filtering bleb is a rare occurrence and is typically associated with systemic or ocular conditions. Complications such as hypotony can lead to visual impairment, and intervention is required. Early diagnosis and repair with donor scleral patch graft can prevent complications and provide an excellent cosmetic outcome.

PURPOSE/UNASSIGNED:To determine the efficacy and safety of repetitive transorbital alternating current stimulation (rtACS) treatment by assessing vision-related quality of life and visual function outcome in subjects treated with rtACS versus sham-control. STUDY DESIGN/UNASSIGNED:Double masked, randomized, sham-controlled clinical trial (NCT03188042). SUBJECTS/UNASSIGNED:Sixteen subjects with moderate-to-advanced glaucoma (visual field [VF] mean deviation [MD] ≤-6.00 decibels) randomized into sham (9 subjects) or rtACS intervention (7 subjects) groups. METHODS/UNASSIGNED:Subjects underwent 10 rtACS sessions over 2 weeks. All subjects had comprehensive ocular examination at baseline, 1-week, and 4-weeks posttreatment. MAIN OUTCOME MEASURES/UNASSIGNED:Visual acuity (VA), contrast sensitivity (CS), VF MD, number of threshold sensitivity points that changed or were unchanged, and vision-related quality of life (VR-QoL) questionnaire scores. RESULTS/UNASSIGNED: = 0.04). No significant changes were detected with VA, CS, and VF analyses for either group. No serious adverse events were noted in either study group. CONCLUSIONS/UNASSIGNED:Repetitive transorbital alternating current stimulation therapy showed a significant beneficial effect on several domains of VR-QoL. Further studies will determine its utility in glaucoma. FINANCIAL DISCLOSURES/UNASSIGNED:Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.