Restoration of neuronal progenitors by partial reprogramming in the aged neurogenic niche.

Partial reprogramming (pulsed expression of reprogramming transcription factors) improves the function of several tissues in old mice. However, it remains largely unknown how partial reprogramming impacts the old brain. Here we use single-cell transcriptomics to systematically examine how partial reprogramming influences the subventricular zone neurogenic niche in aged mouse brains. Whole-body partial reprogramming mainly improves neuroblasts (cells committed to give rise to new neurons) in the old neurogenic niche, restoring neuroblast proportion to more youthful levels. Interestingly, targeting partial reprogramming specifically to the neurogenic niche also boosts the proportion of neuroblasts and their precursors (neural stem cells) in old mice and improves several molecular signatures of aging, suggesting that the beneficial effects of reprogramming are niche intrinsic. In old neural stem cell cultures, partial reprogramming cell autonomously restores the proportion of neuroblasts during differentiation and blunts some age-related transcriptomic changes. Importantly, partial reprogramming improves the production of new neurons in vitro and in old brains. Our work suggests that partial reprogramming could be used to rejuvenate the neurogenic niche and counter brain decline in old individuals.

TOWARD AN IMAGING-CENTRIC DEFINITION OF NONPARANEOPLASTIC AUTOIMMUNE RETINOPATHY.

PURPOSE: To explore characteristic imaging features of nonparaneoplastic autoimmune retinopathy (npAIR) to augment diagnostic criteria. METHODS: This is a retrospective cohort study of patients with npAIR evaluated at the Emory Eye Center between 2013 and 2019. Multimodal fundus images were evaluated to characterize the evolution of the disease. RESULTS: Twenty-one eyes of 12 patients were classified as having npAIR. Five patients (42%) were female, with median (range) age of 59 years (45-85 years). Median baseline visual acuity was 20/30 (20/20 to hand motions). Disease was asymmetric in 11 patients (92%). Common imaging findings included absence of bone spicules (86% of affected eyes), presence of attenuated vessels (86%), and speckled hypoautofluorescence in perimacular and perivenular regions. Three eyes were noted to present early with subtle splotchy fundus autofluorescence abnormality, ultimately developing characteristic speckled perimacular hypoautofluorescence. On optical coherence tomography, 18 eyes (86%) had loss of outer retinal bands with relative foveal sparing and a tapered transition zone. CONCLUSION: Many eyes with npAIR exhibit a subacute, asymmetric, generalized photoreceptor degeneration featuring outer retinal atrophy with relative foveal sparing, retinal vascular attenuation, absence of bone spicules, and speckled hypoautofluorescence often in a perimacular and perivenular distribution. Findings of this study augment diagnostic criteria to improve specificity and accessibility of testing for npAIR.

Trends in Response Rate to US News & World Report Best Hospitals Reputation Survey, 2015 to 2023.

Reputation score has been shown to be the strongest predictor of ranking in the US News & World Reports (USNWR) Best Hospitals report. However, the extent to which physicians participate in the underlying USNWR reputation survey is not well-characterized. We conducted a retrospective cross-sectional study of USNWR public methodology reports from 2015 to 2023 to characterize trends in physician response rates by specialty, region, and Doximity membership. Overall response rates declined between 2015 (24.0%) and 2023 (8.9%). In 2023, rates ranged from 4.7% (psychiatry) to 13.9% (otolaryngology). Otolaryngology had the highest response rate among all specialties between 2017 and 2023. Within otolaryngology, both response rates (25.0% to 13.9%) and count (2106 to 1724 physicians) declined between 2015 and 2023. Among Doximity members, response rates were consistently higher for otolaryngologists in the Northeast and Midwest compared to other regions. Though hospital rankings often influence where patients seek care, our findings suggest USNWR reputation scores may not be reliable or representative.

Outcomes of a Multicenter 10-Year Review of Postinjection Endophthalmitis and Associated Systemic Medical Comorbidities.

Purpose: To investigate whether any systemic medical conditions may be associated with a higher risk for developing postinjection endophthalmitis. Methods: This case-control study is a retrospective review within the Emory Eye Center from 2009 to 2019 and The Cleveland Clinic Foundation from 2012 to 2019. Each case was matched in a 1:4 case-to-control ratio. The associations between medical comorbidities and endophthalmitis were explored using multivariable logistic regression models on the combined sample. Results: Sixty-six individuals were diagnosed with injection-associated endophthalmitis. Systemic immunocompromised status was found to be a risk factor associated with developing endophthalmitis with an adjusted odds ratio (aOR) of 3.17 (P = .009). Other conditions with increased risk approaching statistical significance included a history of pulmonary disease (aOR, 1.74; P = .08) and a history of smoking (aOR, 1.72; P = .06). Conclusions: This is the first report to our knowledge demonstrating that immunocompromised status is associated with an increased risk for developing postinjection endophthalmitis. While this study may be limited due to its retrospective nature, the result may nevertheless serve as a guidance for risk counseling. Future analysis using a large-scale database will be needed.

Opioid-Sparing Pain Control after Rhinoplasty: Updated Review of the Literature.

Rhinoplasty is one of the most performed elective surgeries, and given the opioid crisis, increasing research and studies are focused on successful pain control with multimodality opioid-sparing techniques, such as acetaminophen, nonsteroidal anti-inflammatory drugs (NSAIDs), and gabapentin. Although limiting overuse of opioids is critical, this cannot be at the expense of inadequate pain control, particularly as insufficient pain control can be correlated with patient dissatisfaction and the postoperative experience in elective surgery. There is likely significant opioid overprescription, as patients often report taking less than 50% of their prescribed opioids. Furthermore, excess opioids provide opportunities for misuse and opioid diversion if not disposed of properly. To optimize postoperative pain control and minimize opioid requirements, interventions must occur at the preoperative, intraoperative, and postoperative time points. Preoperative counseling is imperative to set expectations for pain and to screen for predisposing factors for opioid misuse. Intraoperatively, use of local nerve blocks and long-acting analgesia in conjunction with modified surgical techniques can lead to prolonged pain control. Postoperatively, pain should be managed with a multimodal approach, incorporating acetaminophen, NSAIDs, and potentially gabapentin with opioids reserved for rescue analgesia. Rhinoplasty represents a category of short-stay, low/medium pain, and elective procedures highly susceptible to overprescription and consequently, are readily amenable to opioid minimization through standardized perioperative interventions. Recent literature on regimens and interventions to help limit opioids after rhinoplasty are reviewed and discussed here.

Patient and Visit Characteristics Associated With Otolaryngology Telemedicine Care.

BACKGROUND: Clinicians are increasingly adopting telemedicine in an effort to expand patient access and efficiently deliver care. The degree of health disparities among patients receiving otolaryngologic telemedical care is unclear. AIMS: We performed a retrospective cross-sectional study to explore disparities in telemedicine delivery. METHODS: We evaluated otolaryngology clinical visits from January 2019 to November 2022. We obtained patient demographics and visit characteristics (e.g., subspecialty, telemedicine vs in-person). Our primary outcome was demographic characteristics of otolaryngology patients who received telemedicine vs in-person care during the study timeframe. RESULTS: A total of 231,384 otolaryngology clinical visits were reviewed, of which 26,895 (11.6%) were telemedicine visits. Rhinology (36.5%) and facial plastics (28.4%) subspecialties performed the most telemedicine visits. On multivariate analysis, individuals who identified as Asian, non-English speaking, and with Medicare insurance were statistically significantly less likely to use telemedicine than in-person services. CONCLUSION: Our findings suggest that expanding telemedicine care may not improve access for all populations, and socioeconomic factors are important considerations to ensure patients are receiving equally accessible care. Futures studies are warranted to understand how these disparities may impact health outcomes and patient satisfaction with care.

The Impact of Gender on Long-Term Quality of Life After Sinus Surgery for Chronic Rhinosinusitis.

OBJECTIVE: To identify the impact of gender on the clinical outcomes of endoscopic sinus surgery (ESS) through the comparison of quality of life measures in female and male patients who undergo surgical treatment for chronic rhinosinusitis (CRS). STUDY DESIGN: Prospective observational cohort study. METHODS: Patients with CRS completed the 22-item Sino-Nasal Outcome Test (SNOT-22) and EuroQol 5-Dimension Survey (EQ-5D) preoperatively and annually for 5 years following ESS. Health utility values (HUV) were calculated from EQ-5D scores. Comparisons of cohort characteristics were performed with chi-square and t-tests. A multivariable linear mixed effects model evaluated changes in SNOT-22 and HUV over time by gender. RESULTS: Among the 1268 patients (54% female) enrolled, 789 and 343 completed postoperative surveys at one and 5 years, respectively. Preoperatively, females experienced more severe symptoms: mean SNOT-22 score (51.1 ± 20.9 female vs. 44.7 ± 20.0 male, p < 0.001) and HUV (0.80 ± 0.14 female vs. 0.84 ± 0.11 male, p < 0.001). These gender differences were resolved by year one postoperatively (SNOT-22: p = 0.083; HUV: p = 0.465). Two years after surgery, however, females reported more severe symptoms (SNOT-22: 25.6 ± 20.7 female vs. 21.5 ± 17.4 male, p = 0.005; HUV: 0.88 ± 0.12 female vs. 0.90 ± 0.11 male, p = 0.018), a difference that persisted at year five. These gender-related differences remained after adjusting for age, race, ethnicity, nasal polyps, history of prior ESS, and smoking status (p < 0.001). Within-subject improvement was comparable between genders (SNOT-22: p = 0.869; HUV: p = 0.611). CONCLUSION: Females with CRS reported more severe symptoms both before and 5 years after surgery compared to their male counterparts. Understanding the mechanism behind these gender-related differences is important for optimizing CRS treatment. LEVEL OF EVIDENCE: 2 Laryngoscope, 133:3319-3326, 2023.

Cell-type-specific aging clocks to quantify aging and rejuvenation in neurogenic regions of the brain.

The diversity of cell types is a challenge for quantifying aging and its reversal. Here we develop 'aging clocks' based on single-cell transcriptomics to characterize cell-type-specific aging and rejuvenation. We generated single-cell transcriptomes from the subventricular zone neurogenic region of 28 mice, tiling ages from young to old. We trained single-cell-based regression models to predict chronological age and biological age (neural stem cell proliferation capacity). These aging clocks are generalizable to independent cohorts of mice, other regions of the brains, and other species. To determine if these aging clocks could quantify transcriptomic rejuvenation, we generated single-cell transcriptomic datasets of neurogenic regions for two interventions-heterochronic parabiosis and exercise. Aging clocks revealed that heterochronic parabiosis and exercise reverse transcriptomic aging in neurogenic regions, but in different ways. This study represents the first development of high-resolution aging clocks from single-cell transcriptomic data and demonstrates their application to quantify transcriptomic rejuvenation.

Physician Turnover Among Otolaryngologists in the United States, 2014-2021.

Using publicly available Medicare data, we performed a retrospective cross-sectional analysis of separation between otolaryngologists and affiliated medical groups between 2014 and 2021. During this period, the cumulative turnover rate among otolaryngologists was 36.4%, with annual turnover rates ranging between 6.2%-10.2%. Otolaryngologist turnover rates varied by career stage and group size.

Twelve tips for teaching neuroanatomy, from the medical students' perspective.

Neuroanatomy is a complex and fascinating subject that is often a daunting prospect for medical students. In fact, the fear of learning neuroanatomy has gained its own name - "neurophobia." This widespread phenomenon among medical students poses a challenge to medical teachers and educators. To tackle "neurophobia" by summarising tips for dynamic and engaging neuroanatomy teaching formulated based on our experiences as medical students and evidence-based techniques.Focusing on the anatomical, physiological, and clinical aspects of neurology and their integration, here we present 12 tips which are [1] Teach the basic structure before fine details, [2] Supplement teaching with annotated diagrams, [3] Use dissections for haptic learning, [4] Teach form and function together, [5] Group anatomy into systems, [6] Familiarise students with neuroimaging, [7] Teach from clinical cases, [8] Let the patient become the teacher, [9] Build from first principles, [10] Try working in reverse, [11] Let the student become the teacher, [12] Let the student become the examiner. These 12 tips can be used by teachers and students alike to provide a high-yield learning experience.

Cell death in cancer chemotherapy using taxanes.

Cancer cells evolve to be refractory to the intrinsic programmed cell death mechanisms, which ensure cellular tissue homeostasis in physiological conditions. Chemotherapy using cytotoxic drugs seeks to eliminate cancer cells but spare non-cancerous host cells by exploring a likely subtle difference between malignant and benign cells. Presumably, chemotherapy agents achieve efficacy by triggering programmed cell death machineries in cancer cells. Currently, many major solid tumors are treated with chemotherapy composed of a combination of platinum agents and taxanes. Platinum agents, largely cis-platin, carboplatin, and oxaliplatin, are DNA damaging agents that covalently form DNA addicts, triggering DNA repair response pathways. Taxanes, including paclitaxel, docetaxel, and cabazitaxel, are microtubule stabilizing drugs which are often very effective in purging cancer cells in clinical settings. Generally, it is thought that the stabilization of microtubules by taxanes leads to mitotic arrest, mitotic catastrophe, and the triggering of apoptotic programmed cell death. However, the precise mechanism(s) of how mitotic arrest and catastrophe activate the caspase pathway has not been established. Here, we briefly review literature on the involvement of potential cell death mechanisms in cancer therapy. These include the classical caspase-mediated apoptotic programmed cell death, necroptosis mediated by MLKL, and pore forming mechanisms in immune cells, etc. In particular, we discuss a newly recognized mechanism of cell death in taxane-treatment of cancer cells that involves micronucleation and the irreversible rupture of the nuclear membrane. Since cancer cells are commonly retarded in responding to programmed cell death signaling, stabilized microtubule bundle-induced micronucleation and nuclear membrane rupture, rather than triggering apoptosis, may be a key mechanism accounting for the success of taxanes as anti-cancer agents.

Protein re-surfacing of E. coli L-Asparaginase to evade pre-existing anti-drug antibodies and hypersensitivity responses.

The optimal use of many biotherapeutics is restricted by Anti-drug antibodies (ADAs) and hypersensitivity responses which can affect potency and ability to administer a treatment. Here we demonstrate that Re-surfacing can be utilized as a generalizable approach to engineer proteins with extensive surface residue modifications in order to avoid binding by pre-existing ADAs. This technique was applied to E. coli Asparaginase (ASN) to produce functional mutants with up to 58 substitutions resulting in direct modification of 35% of surface residues. Re-surfaced ASNs exhibited significantly reduced binding to murine, rabbit and human polyclonal ADAs, with a negative correlation observed between binding and mutational distance from the native protein. Reductions in ADA binding correlated with diminished hypersensitivity responses in an in vivo mouse model. By using computational design approaches to traverse extended distances in mutational space while maintaining function, protein Re-surfacing may provide a means to generate novel or second line therapies for life-saving drugs with limited therapeutic alternatives.

Multimodal diagnostic imaging in primary vitreoretinal lymphoma.

BACKGROUND: Primary vitreoretinal lymphoma (PVRL) is an aggressive lymphoma that may present with protean features and represents a diagnostic challenge. Given that patients with PVRL are at high risk of CNS involvement with a high mortality and morbidity rate, prompt diagnosis is crucial to initiate treatment early in the disease course. A multimodality imaging approach including fundus photography, fundus autofluorescence (FAF), optical coherence tomography (OCT), fluorescein and indocyanine angiography, and electroretinography (ERG) can provide information to establish a diagnosis and provide objective measures for management. We review key findings seen via these imaging modalities in patients with PVRL. OBSERVATIONS: Fundus photography can highlight commonly seen patterns of PVRL including vitritis, subretinal disease, retinal pigment epithelial (RPE) abnormalities, optic nerve edema, retinal detachment, and less typical retinitis-like lesions. FAF can identify characteristic patterns of hyper- and hypoautofluorescent signal abnormalities in the macula. Spectral-domain OCT will demonstrate vitreous cells, RPE nodularity, and hyperreflectivity of the outer retina. The presence of a hyper-reflective band in the subretinal space and infiltrates between the RPE and Bruch's membrane can assist in distinguishing PVRL from choroidal lymphoma. Vertical hyperreflective columns (VHRLs) are another pertinent finding that may represent microinfiltrates of the tumor. OCT has proven to be a particularly useful modality in assessing the progress of treatment in PVRL. Fluorescein angiography can show RPE changes, which include granularity, late staining at the RPE level, and blockage. Indocyanine green angiography (ICGA) primarily shows hypocyanescence, which corresponds to PVRL lesions on fundus photography and may occur secondary to loss of RPE and choriocapillaris. CONCLUSION: While PVRL remains a challenging disease to diagnose and follow, the use of a multimodality imaging approach may assist in establishing a diagnosis. Because of the anatomic spaces PVRL may affect, fundus photography, OCT, FAF, angiography, and ERG can identify key characteristics of the disease, differentiate PVRL from other diseases, and provide baseline information for targeted systemic and local therapies. Further assessment of anatomic and functional targets will aid our clinical application of multimodal imaging in the management of PVRL.

Management of an atypical case of post-operative endophthalmitis presenting as angle-closure glaucoma.

BACKGROUND/PURPOSE: To report an atypical presentation of postoperative endophthalmitis after cataract surgery that initially presented as angle-closure glaucoma and to discuss challenges with the case management due to the unusual presentation and patient non-compliance. METHODS: Observational case report. B-scan ultrasound and ultrasound biomicroscopy. RESULTS: A 69-year-old Caucasian male with a 1-week history of uncomplicated cataract surgery was referred to our glaucoma clinic due to vision loss and concern for angle closure glaucoma. Anterior segment exam showed 360 degrees of flat anterior chamber (AC) with no hypopyon. A diagnosis of postoperative endophthalmitis was established when a B-scan ultrasound showed dense vitreous opacities. The patient underwent a pars plana vitrectomy (PPV), AC reformation, peripheral iridectomy, and intravitreal injection of antibiotics for treatment of endophthalmitis in the presence of an angle-closure glaucoma with good visual recovery. CONCLUSION: A low threshold for suspicion of endophthalmitis is needed after any routine intraocular procedure. An atypical presentation may masquerade as another pathology that delays the true diagnosis and treatment. Timely intervention in postoperative endophthalmitis is crucial in preserving vision.

Patient Satisfaction With Otolaryngology Care: Stratification by Race, Age, Gender, Income, and Language.

OBJECTIVE: To understand how race, gender, income, and language are correlated with patient satisfaction scores. STUDY DESIGN: Cross-sectional analysis of patient satisfaction data. SETTING: An urban/suburban academic otolaryngology practice. METHODS: Patients presenting for outpatient otolaryngology visits from 2017 to 2020 were surveyed for patient satisfaction following a visit with their otolaryngology provider. Categorical responses and numerical responses were collected regarding overall satisfaction as well as a variety of more specific satisfaction questions. Responses were matched to both provider characteristics and patient demographic data. Differences in satisfaction by demographic data were assessed with descriptive statistics as well as a multivariable mixed-effect model to adjust for repeated responder data and control for confounding factors. RESULTS: In total, 55,469 surveys were included, the majority of which were from white, English-speaking patients. Overall satisfaction levels were very high across all questions. The individual provider was associated highly with satisfaction, but provider gender was not. Race, age, and gender of the patient had a statistically significant impact on patient satisfaction, with higher levels of satisfaction among patients who were older, white, and male; income and language did not. CONCLUSION: Patient factors including race, age, and gender had a significant impact on ratings on outpatient otolaryngology patient satisfaction surveys, with nonwhite, younger, female patients reporting lower scores.

Risk Factors for Retinal Detachment in Acute Retinal Necrosis.

PURPOSE: Retinal detachment (RD) is associated with poor visual outcomes in patients with acute retinal necrosis (ARN). This research was undertaken to assess the risk factors for RD in ARN. DESIGN: Retrospective cohort study. SUBJECTS: Patients diagnosed with ARN at a tertiary referral center from 2010 to 2020. METHODS: A chart review was performed for all clinical and surgical encounters. Univariate and multivariate logistic analyses of demographic and clinical variables associated with RD were performed. Survival analyses with Kaplan-Meier estimates were performed to compare the time to RD in herpes simplex virus (HSV)- and varicella zoster virus (VZV)-associated ARN. MAIN OUTCOME MEASURES: Demographic information, clinical information (including visual acuity [VA]), intraocular pressure (IOP), intraocular inflammation level, the extent of retinitis, incidence and timing of retinal detachment, date of diagnosis, and treatments performed (including intravitreal injections of antiviral medications). RESULTS: Fifty-four eyes of 47 patients who were diagnosed with ARN were included, with equal proportions of eyes (n = 27; 50%) with VZV-ARN and HSV-ARN. Patients with VZV-ARN were, on average, older, more likely to be men, and more likely to be immunosuppressed compared with patients with HSV-ARN. The clinical characteristics, including the initial VA, initial IOP, anterior segment inflammation, clock hours, and posterior extent of retinitis, were similar between eyes with VZV- and HSV-ARN. In the univariate analysis of clinical and demographic variables associated with the development of RD, initial VA (P = 0.0083) and greater clock hours of retinitis (P = 0.009) were significantly associated with RD. These 2 variables remained significant in the multivariate logistic regression; worse VA at presentation had an odds ratio of 2.34 (95% confidence interval [CI], 1.01-5.44; P = 0.042), and greater clock hours of retinitis had an odds ratio of 1.23 (95% CI, 1.02-1.47; P = 0.025). A Kaplan-Meier survival analysis demonstrated no statistical difference in RD-free survival between HSV- and VZV-ARN. CONCLUSIONS: Patients with VZV-ARN were more likely to be older, male, and immunosuppressed compared with those with HSV-ARN, although no clear difference was observed in RD by viral etiology. Poor initial VA and clock hours of retinitis were significantly associated with RD development and may be relevant for patient counseling and prognosis.

Spending and Utilization on Drugs Prescribed by Otolaryngologists to Medicare Beneficiaries, 2013 to 2017.

OBJECTIVES: The significant and rising cost of prescription drugs is a pressing concern for patients and payers. However, little is known about spending on and utilization of drugs prescribed by otolaryngologists. METHODS: Utilizing publicly available Medicare Part D Prescriber Public Use data, we conducted a retrospective cross-sectional analysis of 34 small-molecule drugs commonly prescribed by otolaryngologists (defined as 2017 Medicare Part D spending ≥$500 000) to Medicare beneficiaries. Prescription data was characterized by drug type (brand name vs generic). Primary outcomes for each prescription drug included the total annual cost and the total annual number of days supplied. RESULTS: From 2013 to 2017, spending on drugs prescribed by otolaryngologists to Medicare beneficiaries decreased by $32.1 million ($131.7-$99.5 million; relative decrease 24.4%; compound annual growth rate [CAGR] -5.4%), while total utilization increased by 24.9 million days supplied (74.6-99.5 million; relative increase 33.3%; CAGR 5.9%). For brand name drugs, there was a decrease in spending ($71.1-$26.7 million; relative decrease -62.4%; CAGR -17.8%) and utilization (11.2-3.1 million days supplied; relative decrease -72.5%; CAGR -22.8%). In contrast, generic drugs demonstrated increased spending ($60.6-$72.8 million; relative increase 20.2%; CAGR 3.7%) and utilization (63.5-96.4 million days supplied; relative increase 51.9%; CAGR 8.7%). CONCLUSIONS: Spending on drugs prescribed by otolaryngologists to Medicare Part D beneficiaries declined between 2013 and 2017 in part due to a transition from brand name drugs to lower-cost generic equivalents.

Diagnostic retinal biopsy in the management of secondary non-CNS vitreoretinal lymphoma masquerading as viral retinitis: a case report.

BACKGROUND: Intraocular lymphoma accounts for fewer than 1% of intraocular tumors. When the posterior segment is involved, it can be further classified as vitreoretinal or choroidal lymphoma. Vitreoretinal lymphoma (VRL) can rarely masquerade as an infectious retinitis making diagnosis and management challenging. RESULTS: A 73-year-old woman with a history of non-central nervous system (CNS) involving diffuse large B-cell lymphoma (DLBCL) was referred for worsening blurry vision-visual acuity of count figures at 2 ft-in her right eye for 8 months. Dilated fundus examination of the right eye was significant for retinal whitening and dot-blot hemorrhages, which was concerning for a viral retinitis and guided initial management. Secondary intraocular lymphoma was also considered. The retinal disease continued to progress despite intravitreal and systemic antiviral therapy, and a diagnostic vitrectomy was inconclusive. A retinal biopsy was then performed, which showed DLBCL, confirming a diagnosis of secondary VRL. Three subsequent treatments with intravitreal methotrexate led to regression of the VRL. CONCLUSIONS: Our case highlights the utility of a retinal biopsy after an inconclusive diagnostic vitrectomy in a challenging scenario of VRL to establish a diagnosis and initiate successful treatment. A multidisciplinary team of providers was essential for diagnosis, comprehensive workup, medical and surgical management of the patient.

Retinopathy and Systemic Disease Morbidity in Severe COVID-19.

PURPOSE: To assess the prevalence of retinopathy and its association with systemic morbidity and laboratory indices of coagulation and inflammatory dysfunction in severe COVID-19. DESIGN: Retrospective, observational cohort study. METHODS: Adult patients hospitalized with severe COVID-19 who underwent ophthalmic examination from April to July 2020 were reviewed. Retinopathy was defined as one of the following: 1) Retinal hemorrhage; 2) Cotton wool spots; 3) Retinal vascular occlusion. We analyzed medical comorbidities, sequential organ failure assessment (SOFA) scores, clinical outcomes, and laboratory values for their association with retinopathy. RESULTS: Thirty-seven patients with severe COVID-19 were reviewed, the majority of whom were female (n = 23, 62%), Black (n = 26, 69%), and admitted to the intensive care unit (n = 35, 95%). Fourteen patients had retinopathy (38%) with retinal hemorrhage in 7 (19%), cotton wool spots in 8 (22%), and a branch retinal artery occlusion in 1 (3%) patient. Patients with retinopathy had higher SOFA scores than those without retinopathy (8.0 vs. 5.3, p = .03), higher rates of respiratory failure requiring invasive mechanical ventilation and shock requiring vasopressors (p < .01). Peak D-dimer levels were 28,971 ng/mL in patients with retinopathy compared to 12,575 ng/mL in those without retinopathy (p = .03). Peak CRP was higher in patients with cotton wool spots versus those without cotton wool spots (354 mg/dL vs. 268 mg/dL, p = .03). Multivariate logistic regression modeling showed an increased risk of retinopathy with higher peak D-dimers (aOR 1.32, 95% CI 1.01-1.73, p = .04) and male sex (aOR 9.6, 95% CI 1.2-75.5, p = .04). CONCLUSION: Retinopathy in severe COVID-19 was associated with greater systemic disease morbidity involving multiple organs. Given its association with coagulopathy and inflammation, retinopathy may offer insight into disease pathogenesis in patients with severe COVID-19.