Faculty Bibliography

Clinical manifestations of liver inflammation in alcohol-associated liver disease (ALD) can range from asymptomatic to severe alcoholic hepatitis. While biopsy is the gold standard for identifying liver inflammation, it is an invasive procedure with risks of bleeding, visceral damage, and infection. We aim to establish the state of the current literature on non-invasive markers of inflammation in ALD. We searched Ovid MEDLINE, Embase, and the Cochrane Library for original studies on the association between one or more non-invasive biomarker(s) and histological inflammation or hepatitis in ALD patients. Exclusion criteria were lack of histological data, abstract only, non-English-language articles, and animal studies. Two independent reviewers screened abstracts, reviewed full texts, and extracted data from included papers. Our search identified 8051 unique studies. Title and abstract screening resulted in 563 studies, and full-text screening resulted in 31 studies for final inclusion. The majority were single-center observational cohorts with an average sample size of 124. Review of these studies identified 44 unique biomarkers and 8 calculated scores associated with histological inflammation and/or hepatitis, in addition to a metabolomic panel of 468 metabolites. Six studies examined diagnostic accuracy for histological inflammation and/or hepatitis. The highest area under the receiver operating characteristic curve was 0.932 using a model based on four metabolites. This review highlights the available literature on non-invasive markers of inflammation in ALD. There is a dearth of studies that evaluate the diagnostic accuracy of these biomarkers, and larger studies are needed to confirm findings identified in small cohorts.

Monitoring brain responses to ultrasonic interventions is becoming an important pillar of a growing number of applications employing acoustic waves to actuate and cure the brain. Optical interrogation of living tissues provides a unique means for retrieving functional and molecular information related to brain activity and disease-specific biomarkers. The hybrid optoacoustic imaging methods have further enabled deep-tissue imaging with optical contrast at high spatial and temporal resolution. The marriage between light and sound thus brings together the highly complementary advantages of both modalities toward high precision interrogation, stimulation, and therapy of the brain with strong impact in the fields of ultrasound neuromodulation, gene and drug delivery, or noninvasive treatments of neurological and neurodegenerative disorders. In this review, we elaborate on current advances in optical and optoacoustic monitoring of ultrasound interventions. We describe the main principles and mechanisms underlying each method before diving into the corresponding biomedical applications. We identify areas of improvement as well as promising approaches with clinical translation potential.

PURPOSE/OBJECTIVE:To analyze ophthalmology workforce supply and demand projections from 2020 to 2035. DESIGN/METHODS:Observational cohort study using data from the National Center for Health Workforce Analysis (NCHWA). METHODS:Data accessed from the Department of Health and Human Services, Health Resources and Services Administration (HRSA) website were compiled to analyze the workforce supply and demand projections for ophthalmologists from 2020 to 2035. MAIN OUTCOME MEASURES/METHODS:Projected workforce adequacy over time. RESULTS:From 2020 to 2035, the total ophthalmology supply is projected to decrease by 2650 full-time equivalent (FTE) ophthalmologists (12% decline) and total demand is projected to increase by 5150 FTE ophthalmologists (24% increase), representing a supply and demand mismatch of 30% workforce inadequacy. The level of projected adequacy was markedly different based on rurality by year 2035 with 77% workforce adequacy versus 29% workforce adequacy in metro and nonmetro geographies, respectively. By year 2035, ophthalmology is projected to have the second worst rate of workforce adequacy (70%) of 38 medical and surgical specialties studied. CONCLUSIONS:The HRSA's Health Workforce Simulation Model forecasts a sizeable shortage of ophthalmology supply relative to demand by the year 2035, with substantial geographic disparities. Ophthalmology is one of the medical specialties with the lowest rate of projected workforce adequacy by 2035. Further dedicated workforce supply and demand research for ophthalmology and allied professionals is needed to validate these projections, which may have significant future implications for patients and providers. FINANCIAL DISCLOSURE(S)/BACKGROUND:Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

PURPOSE/OBJECTIVE:The purpose of the study was to describe the rationale and design of Project FOREVER (Finding Ophthalmic Risk and Evaluating the Value of Eye exams and their predictive Reliability). DESIGN/METHODS:Project FOREVER will build a comprehensive database of clinical eye and vision data collected from ~280 000 adults at 100 optician stores across Denmark. The FOREVER database (FOREVERdb) includes detailed data from refraction, visual acuity, intraocular pressure, corneal thickness, visual field assessments and retinal fundus images. Linkage to the comprehensive Danish national registries with, that is diagnostic and prescribing data permits investigation of rare associations and risk factors. 30 000 individuals over 50 also provide a saliva sample for later genetic studies and blood pressure measurements. Of these 30 000, 10 000 will also get optical coherence tomography (OCT) nerve and retinal scans. This subpopulation data is reviewed by ophthalmologists for disease detection. All participants will be asked to complete a questionnaire assessing lifestyle, self-perceived eye health and general health. Enrolment of participants began in April 2022. PERSPECTIVE/CONCLUSIONS:The FOREVERdb is a powerful tool to answer a wide range of research questions that can pave the way for better eye health. This database will provide valuable insights for future studies investigating the correlations between eye and general health in a Danish population cohort, enabling research to identify potential risk factors for a range of diseases.

INTRODUCTION/BACKGROUND:Cenegermin is approved for treatment of neurotrophic keratopathy (NK) and has been studied in patients with stage 2 or 3 NK. This study evaluated the efficacy and safety of cenegermin in adults with stage 1 NK. METHODS:This was a phase IV, multicenter, prospective, open-label, uncontrolled trial. Adults with stage 1 NK (Mackie criteria) and decreased corneal sensitivity (≤ 4 cm) received 1 drop of cenegermin 20 mcg/ml in the affected eye(s) 6 times/day for 8 weeks with a 24-week follow-up. RESULTS:Of 37 patients, corneal epithelial healing was observed in 84.8% (95% confidence interval [CI] 68.1-94.9%; P < 0.001) at week 8; 95.2% (95% CI 76.2-99.9%; P < 0.001) of those patients remained healed at the end of the 24-week follow-up (week 32). At week 8, 91.2% (95% CI 76.3-98.1%; P < 0.001) of patients experienced improved corneal sensitivity; this improvement was observed in 82.1% (95% CI 63.1-93.9%; P < 0.001) of patients at week 32. Mean best-corrected distance visual acuity change from baseline at week 8 was - 0.10 logMAR (standard deviation [SD], 0.15; 95% CI - 0.16 to - 0.05; P < 0.001) and at week 32 was - 0.05 logMAR (SD, 0.16; 95% CI - 0.11 to 0.01; P = 0.122). At weeks 8 and 32, 15.2% (95% CI 5.1-31.9%; P < 0.001) and 10.7% (95% CI 2.3-28.2%; P < 0.001) of patients, respectively, had a 15-letter gain from baseline. At least one adverse event (AE) was reported by 73.0% and 45.7% of patients during the treatment and follow-up periods, respectively. The most common treatment-related, treatment-emergent AEs were eye pain (37.8%), blurred vision (10.8%), and eyelid pain (8.1%); these were mostly mild or moderate and were only reported during the treatment period. CONCLUSIONS:These results support the potential use of cenegermin for treating patients with stage 1 NK, and future confirmatory studies would be beneficial to elaborate on these findings. TRIAL REGISTRATION/BACKGROUND:DEFENDO; NCT04485546.

PURPOSE/UNASSIGNED:Mohs micrographic surgery (MMS) is a highly efficacious, tissue sparing method of skin cancer removal. Nevertheless, in the months to years after MMS, psychosocial distress has been described. The present study addressed the immediate period after MMS and assessed the frequency and risk factors for development of depressive symptoms. METHODS/UNASSIGNED:Subjects undergoing MMS at two physician practices (JL, FS) were included in this prospective cohort study. Preoperatively, a standardized depression screening, the Patient Health Questionnaire-8 (PHQ-8), was administered. After MMS, the PHQ-8 was readministered at weeks 1, 2, 4, 6, and 12. Average PHQ-8 score by week and change from baseline PHQ-8 score were the primary outcomes. RESULTS/UNASSIGNED: = 0.02) than all other age groups. There were no differences in scores between location groups. CONCLUSIONS/UNASSIGNED:One-third of subjects had some increase in score during the follow-up period. Those in the oldest age cohort were at highest risk of increased score. In contrast to prior literature, those with facial sites were not at higher risk. This difference may be explained by increased masking during the ongoing COVID-19 pandemic. Ultimately, consideration of patients' psychologic status in the immediate postoperative period after MMS, particularly in the elderly population, may enhance perceived patient outcomes.

Central serous chorioretinopathy (CSC) is a relatively common disease that causes vision loss due to macular subretinal fluid leakage and is often associated with reduced vision-related quality of life. In CSC, the leakage of subretinal fluid through defects in the retinal pigment epithelial layer's outer blood-retina barrier appears to occur secondary to choroidal abnormalities and dysfunction. The treatment of CSC is currently the subject of controversy, although recent data obtained from several large randomized controlled trials provide a wealth of new information that can be used to establish a treatment algorithm. Here, we provide a comprehensive overview of our current understanding regarding the pathogenesis of CSC, current therapeutic strategies, and an evidence-based treatment guideline for CSC. In acute CSC, treatment can often be deferred for up to 3-4 months after diagnosis; however, early treatment with either half-dose or half-fluence photodynamic therapy (PDT) combined with the photosensitive dye verteporfin may be beneficial in selected cases. In chronic CSC, half-dose or half-fluence PDT, which targets the abnormal choroid, should be considered the preferred treatment. If PDT is unavailable, chronic CSC with focal, non-central leakage on angiography may be treated using conventional laser photocoagulation. CSC with concurrent macular neovascularization should be treated with half-dose/half-fluence PDT and/or intravitreal injections of an anti-vascular endothelial growth factor compound. Given the current shortage of verteporfin and the paucity of evidence supporting the efficacy of other treatment options, future studies-ideally, well-designed randomized controlled trials-are needed in order to evaluate new treatment options for CSC.

The cellular-level visualization of retinal microstructures such as blood vessel wall components, not available with other imaging modalities, is provided with unprecedented details by dark-field imaging configurations; however, the interpretation of such images alone is sometimes difficult since multiple structural disturbances may be present in the same time. Particularly in eyes with retinal pathology, microstructures may appear in high-resolution retinal images with a wide range of sizes, sharpnesses, and brightnesses. In this paper we show that motion contrast and phase gradient imaging modalities, as well as the simultaneous acquisition of depth-resolved optical coherence tomography (OCT) images, provide additional insight to help understand the retinal neural and vascular structures seen in dark-field images and may enable improved diagnostic and treatment plans.