Frequency and correlates of subjective cognitive complaints and objective cognitive screening results in African American adults following COVID-19 infection.

Background: Subjective cognitive complaints are frequent following COVID-19 infection, but assessment of whether these complaints map onto objective cognitive findings may not be routine in busy clinical settings. Consequently, opportunities to confirm these complaints and to provide follow-up referrals and appropriate care may be missed, thereby impacting patients' functional independence and quality of life. African Americans are vulnerable to poor outcomes from COVID-19, and thus represent a minority group in whom subjective concerns are especially important to investigate. Towards this end, we examined the frequency and correlates of subjective complaints and objective screening results of African American patients referred to the Post-Acute Sequelae of SARS-CoV-2 (PASC) Clinic at Grady Memorial Hospital, a large county teaching hospital in Atlanta, Georgia. Methods: Eighty seven African American patients (mean age = 52.5, SD = 10.5, range = 30-73) were evaluated between January 28, 2021-October 14, 2021 in the Grady PASC clinic. They ranged from 1 to 17 months post positive SARS-COV-2 antigen testing. Patients were administered a subjective cognitive complaint questionnaire (PROMIS Cognitive Function Scale Short Form 8a) as well as cognitive screening measures including the Mini-Cog (3 item recall, clock) and the Digit Symbol Substitution Test (timed visuomotor sequencing). Mood was assessed via the Patient Health Questionnaire-9, and anxiety via the Generalized Anxiety Disorders Scale. Published norms were used to identify clinically elevated scores. Results: Sixty six (76%) patients denied experiencing meaningful cognitive concerns, and of these, 25 (38%) had positive cognitive screens indicating impaired performance on objective testing. Of 21 patients with subjectively elevated cognitive concerns, 17 (81%) also had positive cognitive screens. There were no significant differences in sociodemographic factors (p values = .07-.71), days post-acute positive SARS-COV-2 Antigen Test (p = .99), disease severity (p values = .67-.75), or COVID-19 comorbidity indices (medical conditions (p values = .20-.77), substance abuse (p = .79), psychiatric history (p values = .11-.99) in those with or without subjective complaints and objective cognitive findings. However, patients with subjective complaints and objective cognitive findings reported more post-COVID-19 anxiety (p = .02) and depression (p = .001). Conclusions: Findings indicate a high concordance between subjective complaints on the PROMIS Cognitive Scale and objectively confirmed cognitive impairments in African Americans. Further, almost 40% who reported no cognitive complaints screened positive for cognitive impairment. Although depression and anxiety are associated with subjective complaints, they do not account for positive cognitive screening results, as those patients without depressive complaints also had similar rates of positive objective screens. The findings suggest that cognitive screening using assessment tools should be routinely performed in African Americans, especially those reporting cognitive symptoms on outcome scales. While future studies are needed to assess long-term outcomes, we highly recommend follow-ups in those with positive screens to characterize the specific domains that are impacted and that could affect activities of daily living and quality of life.

Chronic inflammation, neutrophil activity, and autoreactivity splits long COVID.

While immunologic correlates of COVID-19 have been widely reported, their associations with post-acute sequelae of COVID-19 (PASC) remain less clear. Due to the wide array of PASC presentations, understanding if specific disease features associate with discrete immune processes and therapeutic opportunities is important. Here we profile patients in the recovery phase of COVID-19 via proteomics screening and machine learning to find signatures of ongoing antiviral B cell development, immune-mediated fibrosis, and markers of cell death in PASC patients but not in controls with uncomplicated recovery. Plasma and immune cell profiling further allow the stratification of PASC into inflammatory and non-inflammatory types. Inflammatory PASC, identifiable through a refined set of 12 blood markers, displays evidence of ongoing neutrophil activity, B cell memory alterations, and building autoreactivity more than a year post COVID-19. Our work thus helps refine PASC categorization to aid in both therapeutic targeting and epidemiological investigation of PASC.

Mild antecedent COVID-19 associated with symptom-specific post-acute sequelae.

BACKGROUND: The impact of COVID-19 severity on development of long-term sequelae remains unclear, and symptom courses are not well defined. METHODS: This ambidirectional cohort study recruited adults with new or worsening symptoms lasting ≥3 weeks from confirmed SARS-CoV-2 infection between August 2020-December 2021. COVID-19 severity was defined as severe for those requiring hospitalization and mild for those not. Symptoms were collected using standardized questionnaires. Multivariable logistical regression estimated odds ratios (OR) and 95% confidence intervals (CI) for associations between clinical variables and symptoms. RESULTS: Of 332 participants enrolled, median age was 52 years (IQR 42-62), 233 (70%) were female, and 172 (52%) were African American. Antecedent COVID-19 was mild in 171 (52%) and severe in 161 (48%). In adjusted models relative to severe cases, mild COVID-19 was associated with greater odds of fatigue (OR:1.83, CI:1.01-3.31), subjective cognitive impairment (OR:2.76, CI:1.53-5.00), headaches (OR:2.15, CI:1.05-4.44), and dizziness (OR:2.41, CI:1.18-4.92). Remdesivir treatment was associated with less fatigue (OR:0.47, CI:0.26-0.86) and fewer participants scoring >1.5 SD on PROMIS Cognitive scales (OR:0.43, CI:0.20-0.92). Fatigue and subjective cognitive impairment prevalence was higher 3-6 months after COVID-19 and persisted (fatigue OR:3.29, CI:2.08-5.20; cognitive OR:2.62, CI:1.67-4.11). Headache was highest at 9-12 months (OR:5.80, CI:1.94-17.3). CONCLUSIONS: Mild antecedent COVID-19 was associated with highly prevalent symptoms, and those treated with remdesivir developed less fatigue and cognitive impairment. Sequelae had a delayed peak, ranging 3-12 months post infection, and many did not improve over time, underscoring the importance of targeted preventative measures.

Development of a Definition of Postacute Sequelae of SARS-CoV-2 Infection.

Importance: SARS-CoV-2 infection is associated with persistent, relapsing, or new symptoms or other health effects occurring after acute infection, termed postacute sequelae of SARS-CoV-2 infection (PASC), also known as long COVID. Characterizing PASC requires analysis of prospectively and uniformly collected data from diverse uninfected and infected individuals. Objective: To develop a definition of PASC using self-reported symptoms and describe PASC frequencies across cohorts, vaccination status, and number of infections. Design, Setting, and Participants: Prospective observational cohort study of adults with and without SARS-CoV-2 infection at 85 enrolling sites (hospitals, health centers, community organizations) located in 33 states plus Washington, DC, and Puerto Rico. Participants who were enrolled in the RECOVER adult cohort before April 10, 2023, completed a symptom survey 6 months or more after acute symptom onset or test date. Selection included population-based, volunteer, and convenience sampling. Exposure: SARS-CoV-2 infection. Main Outcomes and Measures: PASC and 44 participant-reported symptoms (with severity thresholds). Results: A total of 9764 participants (89% SARS-CoV-2 infected; 71% female; 16% Hispanic/Latino; 15% non-Hispanic Black; median age, 47 years [IQR, 35-60]) met selection criteria. Adjusted odds ratios were 1.5 or greater (infected vs uninfected participants) for 37 symptoms. Symptoms contributing to PASC score included postexertional malaise, fatigue, brain fog, dizziness, gastrointestinal symptoms, palpitations, changes in sexual desire or capacity, loss of or change in smell or taste, thirst, chronic cough, chest pain, and abnormal movements. Among 2231 participants first infected on or after December 1, 2021, and enrolled within 30 days of infection, 224 (10% [95% CI, 8.8%-11%]) were PASC positive at 6 months. Conclusions and Relevance: A definition of PASC was developed based on symptoms in a prospective cohort study. As a first step to providing a framework for other investigations, iterative refinement that further incorporates other clinical features is needed to support actionable definitions of PASC.

An innovative approach to career development and promotion of diverse faculty.

Women and persons from racial and ethnic populations underrepresented in medicine (URiM) comprise a substantially lower proportion of academic internal medicine faculty, particularly at senior ranks (associate professors and professors). Numerous factors lead to this inequity which has broad implications for medical education and healthcare. The Emory University Division of General Internal Medicine Grady Section (GIMG) formed the Faculty Review Committee (FRC) in 2013 to address low promotion rates to senior ranks as part of a strategy to foster a more inclusive, equitable environment. The FRC systematically and proactively reviews all GIMG faculty years prior to possible promotion to provide tailored recommendations to bolster professional development and with a goal to expedite successful advancement to senior ranks. Deidentified GIMG academic rank data was compared with aggregate data from Emory University School of Medicine and the American Association of Medical Colleges. In 2020, GIMG had significantly more senior faculty compared with pre-FRC intervention (odds ratio [OR]: 3.94, 95% confidence interval [CI]: 1.65-9.42). Subgroup analyses of non-URiM women GIMG senior faculty compared with preintervention (OR: 11.6, 95% CI: 2.52-53.7), showed a significant increase. A trend toward increased URiM women faculty was also seen. Descriptive analysis suggests that the GIMG group had a higher promotion to senior ranks among women and URiM compared with national and institutional comparators. The FRC is associated with significant increases in the promotion of all faculty and non-URiM women faculty, and an increasing trend of URiM women faculty, effects which help contribute to an equitable academic medicine environment, fostering a more diverse workforce and improved patient outcomes.

Dysregulated naive B cells and de novo autoreactivity in severe COVID-19.

Severe SARS-CoV-2 infection1 has been associated with highly inflammatory immune activation since the earliest days of the COVID-19 pandemic2-5. More recently, these responses have been associated with the emergence of self-reactive antibodies with pathologic potential6-10, although their origins and resolution have remained unclear11. Previously, we and others have identified extrafollicular B cell activation, a pathway associated with the formation of new autoreactive antibodies in chronic autoimmunity12,13, as a dominant feature of severe and critical COVID-19 (refs. 14-18). Here, using single-cell B cell repertoire analysis of patients with mild and severe disease, we identify the expansion of a naive-derived, low-mutation IgG1 population of antibody-secreting cells (ASCs) reflecting features of low selective pressure. These features correlate with progressive, broad, clinically relevant autoreactivity, particularly directed against nuclear antigens and carbamylated proteins, emerging 10-15 days after the onset of symptoms. Detailed analysis of the low-selection compartment shows a high frequency of clonotypes specific for both SARS-CoV-2 and autoantigens, including pathogenic autoantibodies against the glomerular basement membrane. We further identify the contraction of this pathway on recovery, re-establishment of tolerance standards and concomitant loss of acute-derived ASCs irrespective of antigen specificity. However, serological autoreactivity persists in a subset of patients with postacute sequelae, raising important questions as to the contribution of emerging autoreactivity to continuing symptomology on recovery. In summary, this study demonstrates the origins, breadth and resolution of autoreactivity in severe COVID-19, with implications for early intervention and the treatment of patients with post-COVID sequelae.

Preparing Residents for Fellowship: A Novel Mock Interview Program.

OBJECTIVES: Although high-stakes interviews are critically important for residents to obtain competitive fellowships, few formalized programs targeting interviewing skills exist. Previous studies demonstrate that mock interviews increase medical students' and healthcare professionals' confidence and improve match rates, but little research has been conducted among medical residents. The objective of our study was to increase trainees' confidence entering fellowship interviews and prepare them for commonly encountered questions via a mock interview program. METHODS: Emory Internal Medicine residency leaders designed a voluntary mock interview program focused on 103 residents (64% of the overall cohort) pursuing fellowship training (median 36, range 30-37/year) from 2018 to 2020. Administrative staff scheduled eight associate program director interviewers for 75 hours of interviews for 3 years (mean 3.6 hours per interviewer per year), ensuring program feasibility. Interviewers underwent faculty development and used a standardized tool with commonly asked interview questions to conduct mock interviews. Interviewers provided feedback on verbal communication, nonverbal communication, professionalism, and, given recent shifts to virtual interviews, camera readiness. We conducted resident surveys to understand their perceptions of mock interview program experiences. RESULTS: Ninety-nine residents pursuing fellowship (96%) enrolled. Fifty (51%) completed the survey (median 20, range 14-22/year); 46 (92%) reported that the mock interviews were helpful or increased their confidence for interview season. CONCLUSIONS: Residents perceived that this high-fidelity mock interview program successfully prepared them at a critical career juncture. This program is feasible, sustainable, adaptable, and scalable, and may be adopted to benefit trainees in any graduate medical education program.

Reactive arthritis incidence in a community cohort following a large waterborne campylobacteriosis outbreak in Havelock North, New Zealand.

OBJECTIVES: In August 2016, Campylobacter spp contaminated an untreated reticulated water supply resulting in a large-scale gastroenteritis outbreak affecting an estimated 8320 people. We aimed to determine the incidence of probable reactive arthritis (ReA) cases in individuals with culture-confirmed campylobacteriosis (CC), self-reported probable campylobacteriosis (PC) and those reporting no diarrhoea (ND). DESIGN: We conducted a retrospective cohort study to identify incidence of probable ReA cases. We identified cases with new ReA symptoms using an adapted acute ReA (AReA) telephone questionnaire. Those reporting ≥1 symptom underwent a telephone interview with the study rheumatologist. Probable ReA was defined as spontaneous onset of pain suggestive of inflammatory arthritis in ≥1 previously asymptomatic joint for ≥3 days occurring ≤12 weeks after outbreak onset. SETTING: Population-based epidemiological study in Havelock North, New Zealand. PARTICIPANTS: We enrolled notified CC cases with gastroenteritis symptom onsets 5 August 2016-6 September 2016 and conducted a telephone survey of households supplied by the contaminated water source to enrol PC and ND cases. RESULTS: One hundred and six (47.3%) CC, 47 (32.6%) PC and 113 (34.3%) ND cases completed the AReA telephone questionnaire. Of those reporting ≥1 new ReA symptom, 45 (75.0%) CC, 13 (68.4%) PC and 14 (82.4%) ND cases completed the rheumatologist telephone interview. Nineteen CC, 4 PC and 2 ND cases developed probable ReA, resulting in minimum incidences of 8.5%, 2.8% and 0.6% and maximum incidences of 23.9%, 12.4% and 2.15%. DISCUSSION: We describe high probable ReA incidences among gastroenteritis case types during a very large Campylobacter gastroenteritis outbreak using a resource-efficient method that is feasible to employ in future outbreaks.

Respiratory Syncytial Virus-Associated Hospitalizations Among Adults With Chronic Medical Conditions.

BACKGROUND: In contrast with respiratory disease caused by influenza, information on the risk of respiratory syncytial virus (RSV) disease among adults with chronic medical conditions (CMCs) is limited. METHODS: We linked population-based surveillance of acute respiratory illness hospitalizations to national administrative data to estimate seasonal RSV hospitalization rates among adults aged 18-80 years with the following preexisting CMCs: chronic obstructive pulmonary disease (COPD), asthma, congestive heart failure (CHF), coronary artery disease (CAD), cerebrovascular accidents (CVA), diabetes mellitus (DM), and end-stage renal disease (ESRD). Age- and ethnicity-adjusted rates stratified by age group were estimated. RESULTS: Among 883 999 adult residents aged 18-80 years, 281 RSV-positive hospitalizations were detected during 2012-2015 winter seasons. Across all ages, RSV hospitalization rates were significantly higher among adults with COPD, asthma, CHF, and CAD compared with those without each corresponding condition. RSV hospitalization rates were significantly higher among adults with ESRD aged 50-64 years and adults with DM aged 18-49 years and 65-80 years compared with adults in each age group without these conditions. No increased risk was seen for adults with CVA. The CMC with the highest risk of RSV hospitalization was CHF (incidence rate ratio [IRR] range, 4.6-36.5 across age strata) and COPD (IRR range, 9.6-9.7). Among RSV-positive adults, CHF and COPD were independently associated with increased length of hospital stay. CONCLUSIONS: Adults with specific CMCs are at increased risk of RSV hospitalizations. Age affects this relationship for some CMCs. Such populations maybe relevant for future RSV prevention strategies.

Risk of Severe Influenza Among Adults With Chronic Medical Conditions.

BACKGROUND: Severe influenza illness is presumed more common in adults with chronic medical conditions (CMCs), but evidence is sparse and often combined into broad CMC categories. METHODS: Residents (aged 18-80 years) of Central and South Auckland hospitalized for World Health Organization-defined severe acute respiratory illness (SARI) (2012-2015) underwent influenza virus polymerase chain reaction testing. The CMC statuses for Auckland residents were modeled using hospitalization International Classification of Diseases, Tenth Revision codes, pharmaceutical claims, and laboratory results. Population-level influenza rates in adults with congestive heart failure (CHF), coronary artery disease (CAD), cerebrovascular accidents (CVA), chronic obstructive pulmonary disease (COPD), asthma, diabetes mellitus (DM), and end-stage renal disease (ESRD) were calculated by Poisson regression stratified by age and adjusted for ethnicity. RESULTS: Among 891 276 adults, 2435 influenza-associated SARI hospitalizations occurred. Rates were significantly higher in those with CMCs compared with those without the respective CMC, except for older adults with DM or those aged <65 years with CVA. The largest effects occurred with CHF (incidence rate ratio [IRR] range, 4.84-13.4 across age strata), ESRD (IRR range, 3.30-9.02), CAD (IRR range, 2.77-10.7), and COPD (IRR range, 5.89-8.78) and tapered with age. CONCLUSIONS: Our findings support the increased risk of severe, laboratory-confirmed influenza disease among adults with specific CMCs compared with those without these conditions.

Recognition of Azole-Resistant Aspergillosis by Physicians Specializing in Infectious Diseases, United States.

Infections caused by pan-azole-resistant Aspergillus fumigatus strains have emerged in Europe and recently in the United States. Physicians specializing in infectious diseases reported observing pan-azole-resistant infections and low rates of susceptibility testing, suggesting the need for wider-scale testing.

Nosocomial transmission of Ebola virus disease on pediatric and maternity wards: Bombali and Tonkolili, Sierra Leone, 2014.

BACKGROUND: In the largest Ebola virus disease (EVD) outbreak in history, nosocomial transmission of EVD increased spread of the disease. We report on 2 instances in Sierra Leone where patients unknowingly infected with EVD were admitted to a general hospital ward (1 pediatric ward and 1 maternity ward), exposing health care workers, caregivers, and other patients to EVD. Both patients died on the general wards, and were later confirmed as being infected with EVD. We initiated contact tracing and assessed risk factors for secondary infections to guide containment recommendations. METHODS: We reviewed medical records to establish the index patients' symptom onset. Health care workers, patients, and caregivers were interviewed to determine exposures and personal protective equipment (PPE) use. Contacts were monitored daily for EVD symptoms. Those who experienced EVD symptoms were isolated and tested. RESULTS: Eighty-two contacts were identified: 64 health care workers, 7 caregivers, 4 patients, 4 newborns, and 3 children of patients. Seven contacts became symptomatic and tested positive for EVD: 2 health care workers (1 nurse and 1 hospital cleaner), 2 caregivers, 2 newborns, and 1 patient. The infected nurse placed an intravenous catheter in the pediatric index patient with only short gloves PPE and the hospital cleaner cleaned the operating room of the maternity ward index patient wearing short gloves PPE. The maternity ward index patient's caregiver and newborn were exposed to her body fluids. The infected patient and her newborn shared the ward and latrine with the maternity ward index patient. Hospital staff members did not use adequate PPE. Caregivers were not offered PPE. CONCLUSIONS: Delayed recognition of EVD and inadequate PPE likely led to exposures and secondary infections. Earlier recognition of EVD and adequate PPE might have reduced direct contact with body fluids. Limiting nonhealth-care worker contact, improving access to PPE, and enhancing screening methods for pregnant women, children, and inpatients may help decrease EVD transmission in general health care settings.

Notes from the field: Fatal gastrointestinal mucormycosis in a premature infant associated with a contaminated dietary supplement--Connecticut, 2014.

In October 2014, a hospital in Connecticut notified CDC and the Connecticut Department of Public Health of a fatal case of gastrointestinal mucormycosis in a preterm infant. The infant, born at 29 weeks' gestation and weighing 1,400 grams (about 3 pounds), had developed signs and symptoms initially consistent with necrotizing enterocolitis approximately 1 week after birth. Exploratory laparotomy revealed complete ischemia of the gastrointestinal tract from the esophagus to the rectum; a portion of necrotic cecum was sent for microscopic examination. Following surgery, the infant developed multiple areas of vascular occlusion, including a large clot in the aorta, findings not usually associated with necrotizing enterocolitis. The infant died soon after. Histopathology results from the resected cecum revealed an angioinvasive fungal infection consistent with mucormycosis. Gastrointestinal mucormycosis is an extremely rare fungal infection caused by mold in the order Mucorales. It occurs predominantly in low birth weight infants, patients with diarrhea and malnutrition, and those receiving peritoneal dialysis; mortality is 85%. Local investigation revealed that the infant had received a dietary supplement, ABC Dophilus Powder, for 7 days, beginning on day 1 of life.

Tauroursodeoxycholic acid preservation of photoreceptor structure and function in the rd10 mouse through postnatal day 30.

PURPOSE: Retinitis pigmentosa (RP) is a progressive neurodegenerative disease resulting in blindness for which there is no current treatment. Although the members of the family of RP diseases differ in etiology, their outcomes are the same: apoptosis of rods and then by cones. Recently, the bile acid tauroursodeoxycholic acid (TUDCA) has been shown to have antiapoptotic properties in neurodegenerative diseases, including those of the retina. In this study the authors examined the efficacy of TUDCA on preserving rod and cone function and morphology at postnatal day 30 (P30) in the rd10 mouse, a model of RP. METHODS: Wild-type C57BL/6J and rd10 mice were systemically injected with TUDCA (500 mg/kg) every 3 days from P6 to P30 and were compared with vehicle (0.15 M NaHCO(3)). At P30, retinal function was measured with electroretinography, and morphologic preservation of the rods and cones was assessed with immunohistochemistry. RESULTS: Dark-adapted electroretinographic (ERG) responses were twofold greater in rd10 mice treated with TUDCA than with vehicle, likewise light-adapted responses were twofold larger in TUDCA-treated mice than in controls at the brightest ERG flash intensities. TUDCA-treated rd10 retinas had fivefold more photoreceptors than vehicle-treated retinas. TUDCA treatments did not alter retinal function or morphology of wild-type mice when administered to age-matched mice. CONCLUSIONS: TUDCA is efficacious and safe in preserving vision in the rd10 mouse model of RP when treated between P6 and P30. At P30, a developmental stage at which nearly all rods are absent in the rd10 mouse model of RP, TUDCA treatment preserved rod and cone function and greatly preserved overall photoreceptor numbers.

Nanotechnology as an adjunct tool for transplanting engineered cells and tissues.

Laboratory and clinical studies have provided evidence of feasibility, safety and efficacy of cell transplantation to treat a wide variety of diseases characterized by tissue and cell dysfunction ranging from diabetes to spinal cord injury. However, major hurdles remain and limit pursuing large clinical trials, including the availability of a universal cell source that can be differentiated into specific cellular phenotypes, methods to protect the transplanted allogeneic or xenogeneic cells from rejection by the host immune system, techniques to enhance cellular integration of the transplant within the host tissue, strategies for in vivo detection and monitoring of the cellular implants, and new techniques to deliver genes to cells without eliciting a host immune response. Finding ways to circumvent these obstacles will benefit considerably from being able to understand, visualize, and control cellular interactions at a sub-micron level. Cutting-edge discoveries in the multidisciplinary field of nanotechnology have provided us a platform to manipulate materials, tissues, cells, and DNA at the level of and within the individual cell. Clearly, the scientific innovations achieved with nanotechnology are a welcome strategy for enhancing the generally encouraging results already achieved in cell transplantation. This review article discusses recent progress in the field of nanotechnology as a tool for tissue engineering, gene therapy, cell immunoisolation, and cell imaging, highlighting its direct applications in cell transplantation therapy.

Structural and functional MRI reveals multiple retinal layers.

MRI is a noninvasive diagnostic modality that reveals anatomy, physiology, and function in vivo without depth limitation or optical interference. MRI application to the retina, however, remains challenging. We improved spatial resolution to resolve layer-specific structure and functional responses in the retina and confirmed the laminar resolution in an established animal model of retinal degeneration. Structural MRI of normal rat retinas revealed three bands corresponding histologically to (i) the combined ganglion cell layer/inner nuclear layer plus the embedded retinal vessels, (ii) the avascular outer nuclear (photoreceptor) layer and its photoreceptor segments, and (iii) the choroidal vascular layer. Imaging with an intravascular contrast agent (gadolinium-diethylene-tri-amine-pentaacetic acid) enhanced the retinal and choroidal vascular layers bounding the retina, but not the avascular outer nuclear layer and the vitreous. Similarly, blood-oxygen-level-dependent (BOLD) functional MRI revealed layer-specific responses to hyperoxia and hypercapnia. Importantly, layer-specific BOLD responses in the two vascular layers were divergent, suggesting the two vasculatures are differentially regulated. To corroborate sensitivity and specificity, we applied layer-specific MRI to document photoreceptor degeneration in Royal College of Surgeons rats. Consistent with histology, layer-specific MRI detected degeneration of the outer nuclear layer. Surprisingly, MRI revealed increased thickness in the choroidal vascular layer and diminished BOLD responses to hyperoxia and hypercapnia in the Royal College of Surgeons rat retinas, suggesting perturbation of vascular reactivity secondary to photoreceptor loss. We conclude that MRI is a powerful investigative tool capable of resolving lamina-specific structures and functional responses in the retina as well as probing lamina-specific changes in retinal diseases.

Status of the feline retina 5 years after subretinal implantation.

Retinal prosthetics are designed to restore functional vision to patients with photoreceptor degeneration by detecting light and stimulating the retina. Since devices are surgically implanted into the eye, long-term biocompatibility and durability are critical for viable treatment of retinal disease. To extend our previous work, which demonstrated the biocompatibility of a microphotodiode array (MPA) for 10 to 27 months in the normal feline retina, we implanted normal cats with an MPA implant backed with either an iridium oxide or platinum electrode and examined retinal function and biocompatibility for 3 to 5 years. All implants functioned throughout the study period. Retinal function remained steady and normal with a less than 15 percent decrease in electroretinogram response. The retinas had normal laminar structure with no signs of inflammation or rejection in areas adjacent to or distant from the implants. Directly over the implants, a loss of photoreceptor nuclei and remodeling of inner retinal layers existed. These results indicate that the subretinal MPA device is durable and well tolerated by the retina 5 years postimplantation.