Quantitative Autofluorescence at AMD's Beginnings Highlights Retinal Topography and Grading System Differences: ALSTAR2 Baseline.

INTRODUCTION: The aims of the study were to describe baseline quantitative (short-wavelength) autofluorescence (qAF) findings in a large pseudophakic cohort at age-related macular degeneration (AMD)'s beginnings and to assess qAF8 as an outcome measure and evaluate Age-Related Eye Disease Study (AREDS) and Beckman grading systems. METHODS: In the ALSTAR2 baseline cohort (NCT04112667), 346 pseudophakic eyes of 188 persons (74.0 ± 5.5 years) were classified as normal (N = 160 by AREDS, 158 by Beckman), early AMD (eAMD) (N = 104, 66), and intermediate AMD (iAMD) (N = 82, 122). Groups were compared via mean qAF intensities in a 6°-8° annulus (qAF8) and maps of differences between observations and the overall mean, divided by standard deviation (Z-score). RESULTS: qAF8 did not differ significantly among diagnostic groups by either stratification (p = 0.0869 AREDS; p = 0.0569 by Beckman). Notably, 45 eyes considered eAMD by AREDS became iAMD by Beckman. For AREDS-stratified eyes, Z-score maps showed higher centrally located qAF for normal, near the mean in eAMD, and lower values for iAMD. Maps deviated from this pattern for Beckman-stratified eyes. CONCLUSIONS: In a large sample of pseudophakic eyes, qAF8 does not differ overall from normal aging to iAMD but also does not capture the earliest AMD activity in the macula lutea. AREDS classification gives results more consistent with a slow decline in histologic autofluorescence than Beckman classification.

Compensatory Growth Is Accompanied by Changes in Insulin-Like Growth Factor 1 but Not Markers of Cellular Aging in a Long-Lived Seabird.

AbstractDeveloping organisms often plastically modify growth in response to environmental circumstances, which may be adaptive but is expected to entail long-term costs. However, the mechanisms that mediate these growth adjustments and any associated costs are less well understood. In vertebrates, one mechanism that may be important in this context is the highly conserved signaling factor insulin-like growth factor 1 (IGF-1), which is frequently positively related to postnatal growth and negatively related to longevity. To test this idea, we exposed captive Franklin's gulls (Leucophaeus pipixcan) to a physiologically relevant nutritional stressor by restricting food availability during postnatal development and examined the effects on growth, IGF-1, and two potential biomarkers of cellular and organismal aging (oxidative stress and telomeres). During food restriction, experimental chicks gained body mass more slowly and had lower IGF-1 levels than controls. Following food restriction, experimental chicks underwent compensatory growth, which was accompanied by an increase in IGF-1 levels. Interestingly, however, there were no significant effects of the experimental treatment or of variation in IGF-1 levels on oxidative stress or telomeres. These findings suggest that IGF-1 is responsive to changes in resource availability but is not associated with increased markers of cellular aging during development in this relatively long-lived species.

Retinal electrophysiologic response to IOP elevation in living human eyes.

PURPOSE: The relationships between intraocular pressure (IOP), ocular perfusion pressure (OPP), retinal perfusion, and retinal electrophysiologic responses have been explored experimentally across several animal models. These studies have demonstrated that elevated IOP reduces OPP, and when this reduction in OPP exceeds the autoregulatory capacity of the retina vasculature, retinal perfusion and electrophysiologic responses are reduced. This study aimed to evaluate these interactions for the first time in the living human eye. METHODS: Five eyes from three research-consented brain-dead organ donors underwent optical coherence tomography with angiographic (OCT/A; Spectralis, Heidelberg Engineering) and electroretinographic (ERG, Diagnosys LLC) measurements while IOP was manometrically-elevated stepwise to pressures of 10, 30 and 50 mmHg. Systemic blood pressure (BP) was monitored continuously during testing. Correlation analysis was applied to assess association between ERG and OPP changes. In a single eye, prolonged IOP elevation was induced with viscoelastic injection and serial ERG measurements were obtained. RESULTS: Reductions in inner retinal function defined by photopic ERG were observed with elevation in IOP and concomitant reduction in OPP. Reductions, especially in b-wave, and photopic negative response (PhNR) amplitudes and implicit times were significantly correlated with elevation in IOP and reduction in OPP. There were more appreciable changes in perfusion and functional responses in eyes tested while systemic blood pressure was lower. With prolonged IOP elevation, selective loss of the PhNR response was observed. CONCLUSIONS: In the living human eye, retinal perfusion and inner retinal function are acutely impacted by elevation of IOP, and this impact is related to systemic BP and OPP. This novel approach provides a viable model to study the autoregulatory responses to IOP elevation in the living human eye.

Sporadic Creutzfeldt-Jakob disease.

Being considered among the most fatal neurological conditions, Creutzfeldt-Jakob disease is a transmissible spongiform encephalopathy characterized by its unknown etiology and rapidly progressive neurodegenerative symptoms that often lead to a mean survival of 6 to 12 months. The accumulation of the prionic protein causes brain matter degeneration, which leads to a set of clinical findings that include rapidly progressive dementia, myoclonus, tremors, cerebellar ataxia, and extrapyramidal signs. This clinical presentation is non-specific, which makes CJD a very difficult condition to diagnose, due to the low level of clinical suspicion. However, combining this clinical presentation with neuroimaging, a lumbar puncture and an encephalogram will help us make the correct diagnosis. We present the case of a 57-year-old male presenting to the Emergency department with complaint of personality change and intermittent memory loss. The patient's physical exam was significant for resting pill roll tremor, bilateral cogwheel rigidity, dysmetria, and shuffling gait. Magnetic resonance imaging of his brain showed symmetric bilateral diffusion signal abnormality involving the cortex, bilateral caudate heads and putamina. Continuous electroencephalogram revealed multiple bifrontal delta discharges with triphasic morphology. Lumbar puncture was significant for presence of 14-3-3 protein in cerebrospinal fluid. The multiple examinations performed in conjunction with the previous findings supported the diagnosis of acute encephalopathy secondary to sporadic CJD.

Patients as team members: Factors affecting involvement in treatment decisions from the perspective of patients with a chronic condition.

BACKGROUND: Active patient involvement in treatment decisions is seen as a feature of patient-centred care that will ultimately lead to better healthcare services and patient outcomes. Although many factors have been identified that influence patient involvement in treatment decisions, little is known about the different views that patients have on which factors are most important. OBJECTIVE: This study explores the views of patients with a chronic condition on factors influencing their involvement in treatment decisions. DESIGN: Q-methodology was used to study the views of patients. Respondents were asked to rank a set of 42 statements from the least important to the most important for active patient involvement in treatment decision-making. The set of 42 statements was developed based on a literature search and a pilot in which two external researchers, 15 patients and four healthcare professionals participated. A total of 136 patients with one of three major chronic conditions were included: diabetes types 1 and 2, respiratory disease (i.e., chronic obstructive pulmonary disease and asthma) and cancer (i.e., breast cancer and prostate cancer). Data were collected in a face-to-face interview setting in the Netherlands. RESULTS: Four distinct views on the factors influencing active patient involvement were identified among patients with a chronic condition. (1) Enabled involvement: the extent to which patients are facilitated and empowered to participate will lead to patient involvement. (2) Relationship-driven involvement: the relationship between patients and healthcare professionals drives patient involvement. (3) Disease impact-driven involvement: the severity of disease drives patient involvement. (4) Cognition-driven involvement: knowledge and information drive patient involvement. DISCUSSION AND CONCLUSION: From the patients' perspective, this study shows that there is no one-size-fits-all approach to involving patients more actively in their healthcare journey. Strategies aiming to enhance active patient involvement among patients with a chronic condition should consider this diversity in perspectives among these patients. PATIENT CONTRIBUTION: Patients are the respondents as this study researches their perspective on factors influencing patient involvement. In addition, patients were involved in pilot-testing the statement set.

Otoliths suggest lifespans more than 30 years for free-living bowfin Amia calva: Implications for fisheries management in the bowfishing era.

The bowfin Amia calva is an amiid (Amiiformes) relict native to North America. It is the last surviving member of the Halecomorphi, a group of fishes that evolved more than 250 million years ago. Despite the phylogenetic significance of the amiids in vertebrate evolution, little has been published about their age and growth. Recreational bowfin harvest is currently unregulated throughout most of the USA, yet new recreational fisheries are emerging. As such, bowfin are increasingly harvested by sport bowfishing without limit, in addition to their growing commercial harvest for caviar. From 2017 to 2021 we studied a total of 81 bowfin from 11 populations across the east-west gradient of Minnesota within a narrow latitudinal margin (<50 km) of the 46th parallel north. We compared the allometry and translucence of bowfin asteriscus, lapillus and sagittal otoliths and found the lapillus otoliths provide consistent readability for age estimation despite being the smallest of the set. Size-at-age data derived from otoliths indicated that bowfin are sexually dimorphic in asymptotic length and may live up to 33 years, which is 15 years longer than previously estimated in wild populations, but comparable to what has been reported in captivity. Overall, 28% of the otolith-aged fish were estimated as older than the previously reported maximum age for wild bowfin populations. Our findings suggest that the bowfin life history may exhibit slower growth, greater longevity, and more variable recruitment than previously recognized, which sets the stage for more otolith-derived population demographics across their range and age validation study. Our results have direct implications for conservation of bowfin, especially amidst the increasing rates of exploitation during the bowfishing era.

Preserving Patient Privacy During Computation over Shared Electronic Health Record Data.

Patient Electronic Health Records (EHRs) contain valuable clinical data that is useful for medical research and public health inquires. However, patient privacy regulation and improper resource sharing risks limit access to EHR medical data for research and public health purposes. In this paper, we introduce an end-to-end security solution that addresses both concerns and facilitates the sharing of patient EHR data over an unsecured third-party server using a leveled homomorphic encryption (LHE) scheme. Time testing for aggregating queries and linear computations was carried out using an HPE ProLiant DL580 Gen 10 server with an Intel Xeon Platinum 8280 Processor.

Challenges and opportunities for sustaining coastal wetlands and oyster reefs in the southeastern United States.

Formed at the confluence of marine and fresh waters, estuaries experience both the seaside pressures of rising sea levels and increasing storm severity, and watershed and precipitation changes that are shifting the quality and quantity of freshwater and sediments delivered from upstream sources. Boating, shoreline hardening, harvesting pressure, and other signatures of human activity are also increasing as populations swell in coastal regions. Given this shifting landscape of pressures, the factors most threatening to estuary health and stability are often uncertain. To identify the greatest contemporary threats to coastal wetlands and oyster reefs across the southeastern United States (Mississippi to North Carolina), we summarized recent population growth and land-cover change and surveyed estuarine management and science experts. From 1996 to 2019, human population growth in the region varied from a 17% decrease to a 171% increase (mean = +43%) with only 5 of the 72 SE US counties losing population, and nearly half growing by more than 40%. Individual counties experienced between 999 and 19,253 km2 of new development (mean: 5725 km2), with 1-5% (mean: 2.6%) of undeveloped lands undergoing development over this period across the region. Correspondingly, our survey of 169 coastal experts highlighted development, shoreline hardening, and upstream modifications to freshwater flow as the most important local threats facing coastal wetlands. Similarly, experts identified development, upstream modifications to freshwater flow, and overharvesting as the most important local threats to oyster reefs. With regards to global threats, experts categorized sea level rise as the most pressing to wetlands, and acidification and precipitation changes as the most pressing to oyster reefs. Survey respondents further identified that more research, driven by collaboration among scientists, engineers, industry professionals, and managers, is needed to assess how precipitation changes, shoreline hardening, and sea level rise are affecting coastal ecosystem stability and function. Due to the profound role of humans in shaping estuarine health, this work highlights that engaging property owners, recreators, and municipalities to implement strategies to improve estuarine health will be vital for sustaining coastal systems in the face of global change.

Functionally validated imaging endpoints in the Alabama study on early age-related macular degeneration 2 (ALSTAR2): design and methods.

BACKGROUND: Age-related macular degeneration (AMD), a leading cause of irreversible vision impairment in the United States and globally, is a disease of the photoreceptor support system involving the retinal pigment epithelium (RPE), Bruch's membrane, and the choriocapillaris in the setting of characteristic extracellular deposits between outer retinal cells and their blood supply. Research has clearly documented the selective vulnerability of rod photoreceptors and rod-mediated (scotopic) vision in early AMD, including delayed rod-mediated dark adaptation (RMDA) and impaired rod-mediated light and pattern sensitivity. The unifying hypothesis of the Alabama Study on Early Macular Degeneration (ALSTAR2) is that early AMD is a disease of micronutrient deficiency and vascular insufficiency, due to detectable structural changes in the retinoid re-supply route from the choriocapillaris to the photoreceptors. Functionally this is manifest as delayed rod-mediated dark adaptation and eventually as rod-mediated visual dysfunction in general. METHODS: A cohort of 480 older adults either in normal macular health or with early AMD will be enrolled and followed for 3 years to examine cross-sectional and longitudinal associations between structural and functional characteristics of AMD. Using spectral domain optical coherence tomography, the association between (1) subretinal drusenoid deposits and drusen, (2) RPE cell bodies, and (3) the choriocapillaris' vascular density and rod- and cone-mediated vision will be examined. An accurate map and timeline of structure-function relationships in aging and early AMD gained from ALSTAR2, especially the critical transition from aging to disease, will identify major characteristics relevant to future treatments and preventative measures. DISCUSSION: A major barrier to developing treatments and prevention strategies for early AMD is a limited understanding of the temporal interrelationships among structural and functional characteristics while transitioning from aging to early AMD. ALSTAR2 will enable the development of functionally valid, structural biomarkers for early AMD, suitable for use in forthcoming clinical trials as endpoint/outcome measures. The comprehensive dataset will also allow hypothesis-testing for mechanisms that underlie the transition from aging to AMD, one of which is a newly developed Center-Surround model of cone resilience and rod vulnerability. TRIAL REGISTRATION: ClinicalTrials.gov Identifier NCT04112667, October 7, 2019.

The ARMS2 A69S Polymorphism Is Associated with Delayed Rod-Mediated Dark Adaptation in Eyes at Risk for Incident Age-Related Macular Degeneration.

PURPOSE: To examine the association between sequence variants in genetic risk factors for age-related macular degeneration (AMD) and delayed rod-mediated dark adaptation (RMDA), the first functional biomarker for incident AMD, in older adults with normal macular health and early AMD. DESIGN: Cross-sectional. PARTICIPANTS: Adults 60 years of age or older showing normal macular health (defined as both eyes at step 1 on the Age-Related Eye Disease Study 9-step AMD classification system) and those with AMD in one or both eyes (defined as steps 2-9). METHODS: Single nucleotide polymorphisms were genotyped in the complement factor H (CFH) and ARMS2 genes using a Taqman assay. Rod-mediated dark adaptation was assessed in 1 eye after photobleach with targets centered at 5° on the inferior vertical meridian. Rate of dark adaptation was defined by rod intercept time (RIT), duration (in minutes) required for sensitivity to reach a criterion sensitivity level in the latter half of the second component of rod recovery. Associations between CFH and ARMS2 polymorphisms and RMDA were adjusted for age and smoking. MAIN OUTCOME MEASURE: Rod intercept time. RESULTS: The sample consisted of 543 participants having both genotype and RIT determination; 408 showed normal macular health and 135 demonstrated AMD, most having early AMD (124 of 135). For the combined sample, higher RIT (slower RMDA) was observed for both the A69S variant in ARMS2 and the Y402H variant in CFH (adjusted P = 0.0001 and P = 0.0023, respectively). For healthy participants, the A69S variant in ARMS2 was associated with higher RIT (adjusted P = 0.0011), whereas the Y402H variant in CFH was not (adjusted P = 0.2175). For AMD patients, the A69S variant of ARMS2 and the Y402H variant of CFH were associated with higher RIT (adjusted P = 0.0182 and P = 0.0222, respectively). Those with a larger number of high-risk ARMS2 and CFH alleles showed higher RIT, in both healthy and AMD groups (adjusted P = 0.0002 and P < 0.0001, respectively). CONCLUSIONS: We report a novel association wherein older adults with high-risk ARMS2 and CFH genotypes are more likely to demonstrate delayed RMDA, the first functional biomarker for incident early AMD. Before the AMD clinical phenotype is present, those showing normal macular health with the ARMS2 A69S allele demonstrate delayed RMDA. Understanding ARMS2 function is a research priority.

Diversity of Cryptosporidium in common voles and description of Cryptosporidium alticolis sp. n. and Cryptosporidium microti sp. n. (Apicomplexa: Cryptosporidiidae).

Fecal samples from wild-caught common voles (n = 328) from 16 locations in the Czech Republic were screened for Cryptosporidium by microscopy and PCR/sequencing at loci coding small-subunit rRNA, Cryptosporidium oocyst wall protein, actin and 70 kDa heat shock protein. Cryptosporidium infections were detected in 74 voles (22.6%). Rates of infection did not differ between males and females nor between juveniles and adults. Phylogenetic analysis revealed the presence of eight Cryptosporidium species/genotypes including two new species, C. alticolis and C. microti. These species from wild-caught common voles were able to infect common and meadow voles under experimental conditions, with a prepatent period of 3-5 days post-infection (DPI), but they were not infectious for various other rodents or chickens. Meadow voles lost infection earlier than common voles (11-14 vs 13-16 DPI) and had significantly lower infection intensity. Cryptosporidium alticolis infects the anterior small intestine and has larger oocysts (5.4 × 4.9 µm), whereas C. microti infects the large intestine and has smaller oocysts (4.3 × 4.1 µm). None of the rodents developed clinical signs of infection. Genetic and biological data support the establishment of C. alticolis and C. microti as separate species of the genus Cryptosporidium.

What Do Program Directors Look for in an Applicant?

Program directors (PDs) are faced with an increasing number of applicants to emergency medicine (EM) and a limited number of positions. This article will provide candidates with insight to what PDs look for in an applicant. We will elaborate on the performance in the emergency medicine clerkship, interview, clinical rotations (apart from EM), board scores, Alpha Omega Alpha membership, letters of recommendation, Medical Student Performance Evaluation or dean's letter, extracurricular activities, Gold Humanism Society membership, medical school attended, research and scholarly projects, personal statement, and commitment to EM. We stress the National Resident Matching Program process and how, ultimately, selection of a residency is equally dependent on an applicant's selection process.

Differential role of pannexin-1/ATP/P2X7 axis in IL-1ß release by human monocytes.

IL-1ß release is integral to the innate immune system. The release of mature IL-1ß depends on 2 regulated events: the de novo induction of pro-IL-1ß, generally via NF-κB-dependent transduction pathways; and the assembly and activation of the NLRP3 inflammasome. This latter step is reliant on active caspase-1, pannexin-1, and P2X7 receptor activation. Pathogen-associated molecular patterns in gram-positive and gram-negative bacteria activate IL-1ß release from immune cells via TLR2 and TLR4 receptors, respectively. We found that pro-IL-1ß and mature IL-1ß release from human monocytes is stimulated by the TLR2 agonists Pam3CSK4 or FSL-1, as well as the TLR4 agonist LPS in the absence of additional ATP. TLR2 agonists required pannexin-1 and P2X7 receptor activation to stimulate IL-1ß release. In contrast, IL-1ß release stimulated by the TLR4 agonist LPS is independent of both pannexin-1 and P2X7 activation. In the absence of exogenous ATP, P2X7 activation requires endogenous ATP release, which occurs in some cells via pannexin-1. In line with this, we found that LPS-stimulated human monocytes released relatively low levels of ATP, whereas cells stimulated with TLR2 agonists released high levels of ATP. These findings suggest that in human monocytes, both TLR2 and TLR4 signaling induce pro-IL-1ß expression, but the mechanism by which they activate caspase-1 diverges at the level of the pannexin-1/ATP/P2X7 axis.-Parzych, K., Zetterqvist, A. V., Wright, W. R., Kirkby, N. S., Mitchell, J. A., Paul-Clark, M. J. Differential role of pannexin-1/ATP/P2X7 axis in IL-1ß release by human monocytes.

Cryptosporidium infecting wild cricetid rodents from the subfamilies Arvicolinae and Neotominae.

We undertook a study on Cryptosporidium spp. in wild cricetid rodents. Fecal samples were collected from meadow voles (Microtus pennsylvanicus), southern red-backed voles (Myodes gapperi), woodland voles (Microtus pinetorum), muskrats (Ondatra zibethicus) and Peromyscus spp. mice in North America, and from bank voles (Myodes glareolus) and common voles (Microtus arvalis) in Europe. Isolates were characterized by sequence and phylogenetic analyses of the small subunit ribosomal RNA (SSU) and actin genes. Overall, 33·2% (362/1089) of cricetids tested positive for Cryptosporidium, with a greater prevalence in cricetids from North America (50·7%; 302/596) than Europe (12·1%; 60/493). Principal Coordinate analysis separated SSU sequences into three major groups (G1-G3), each represented by sequences from North American and European cricetids. A maximum likelihood tree of SSU sequences had low bootstrap support and showed G1 to be more heterogeneous than G2 or G3. Actin and concatenated actin-SSU trees, which were better resolved and had higher bootstrap support than the SSU phylogeny, showed that closely related cricetid hosts in Europe and North America are infected with closely related Cryptosporidium genotypes. Cricetids were not major reservoirs of human pathogenic Cryptosporidium spp.

DYNAMISM OF DOT SUBRETINAL DRUSENOID DEPOSITS IN AGE-RELATED MACULAR DEGENERATION DEMONSTRATED WITH ADAPTIVE OPTICS IMAGING.

PURPOSE: To investigate the natural history of dot subretinal drusenoid deposits (SDD) in age-related macular degeneration, using high-resolution adaptive optics scanning laser ophthalmoscopy. METHODS: Six eyes of four patients with intermediate age-related macular degeneration were studied at baseline and 1 year later. Individual dot SDD within the central 30° retina were examined with adaptive optics scanning laser ophthalmoscopy and optical coherence tomography. RESULTS: A total of 269 solitary SDD were identified at baseline. Over 12.25 ± 1.18 months, all 35 Stage 1 SDD progressed to advanced stages. Eighteen (60%) Stage 2 lesions progressed to Stage 3 and 12 (40%) remained at Stage 2. Of 204 Stage 3 SDD, 12 (6.4%) disappeared and the rest remained. Twelve new SDD were identified, including 6 (50%) at Stage 1, 2 (16.7%) at Stage 2, and 4 (33.3%) at Stage 3. The mean percentage of the retina affected by dot SDD, measured by the adaptive optics scanning laser ophthalmoscopy, increased in 5/6 eyes (from 2.31% to 5.08% in the most changed eye) and decreased slightly in 1/6 eye (from 10.67% to 10.54%). Dynamism, the absolute value of the areas affected by new and regressed lesions, ranged from 0.7% to 9.3%. CONCLUSION: Adaptive optics scanning laser ophthalmoscopy reveals that dot SDD, like drusen, are dynamic.

EXPLORING PHOTORECEPTOR REFLECTIVITY THROUGH MULTIMODAL IMAGING OF OUTER RETINAL TUBULATION IN ADVANCED AGE-RELATED MACULAR DEGENERATION.

PURPOSE: To investigate the microscopic structure of outer retinal tubulation (ORT) and optical properties of cone photoreceptors in vivo, we studied ORT appearance by multimodal imaging, including spectral domain optical coherence tomography (SD-OCT) and adaptive optics scanning laser ophthalmoscopy. METHODS: Four eyes of four subjects with advanced age-related macular degeneration underwent color fundus photography, infrared reflectance imaging, SD-OCT, and adaptive optics scanning laser ophthalmoscopy with a high-resolution research instrument. Outer retinal tubulation was identified in closely spaced (11 µm) SD-OCT volume scans. RESULTS: Outer retinal tubulation in cross-sectional and en face SD-OCT was a hyporeflective area representing a lumen surrounded by a hyperreflective border consisting of cone photoreceptor mitochondria and external limiting membrane, per previous histology. In contrast, ORT by adaptive optics scanning laser ophthalmoscopy was a hyporeflective structure of the same shape as in en face SD-OCT but lacking visualizable cone photoreceptors. CONCLUSION: Lack of ORT cone reflectivity by adaptive optics scanning laser ophthalmoscopy indicates that cones have lost their normal directionality and waveguiding property due to loss of outer segments and subsequent retinal remodeling. Reflective ORT cones by SD-OCT, in contrast, may depend partly on mitochondria as light scatterers within inner segments of these degenerating cells, a phenomenon enhanced by coherent imaging. Multimodal imaging of ORT provides insight into cone degeneration and reflectivity sources in optical coherence tomography.

ASSOCIATION BETWEEN VISUAL FUNCTION AND SUBRETINAL DRUSENOID DEPOSITS IN NORMAL AND EARLY AGE-RELATED MACULAR DEGENERATION EYES.

PURPOSE: To examine the association between subretinal drusenoid deposits (SDDs) identified by multimodal retinal imaging and visual function in older eyes with normal macular health or in the earliest phases of age-related macular degeneration (AMD). METHODS: Age-related macular degeneration status for each eye was defined according to the Age-Related Eye Disease Study (AREDS) 9-step classification system (normal = Step 1, early AMD = Steps 2-4) based on color fundus photographs. Visual functions measured were best-corrected photopic visual acuity, contrast and light sensitivity, mesopic visual acuity, low-luminance deficit, and rod-mediated dark adaptation. Subretinal drusenoid deposits were identified through multimodal imaging (color fundus photographs, infrared reflectance and fundus autofluorescence images, and spectral domain optical coherence tomography). RESULTS: The sample included 1,202 eyes (958 eyes with normal health and 244 eyes with early AMD). In normal eyes, SDDs were not associated with any visual function evaluated. In eyes with early AMD, dark adaptation was markedly delayed in eyes with SDDs versus no SDD (a 4-minute delay on average), P = 0.0213. However, this association diminished after age adjustment, P = 0.2645. Other visual functions in early AMD eyes were not associated with SDDs. CONCLUSION: In a study specifically focused on eyes in normal macular health and in the earliest phases of AMD, early AMD eyes with SDDs have slower dark adaptation, largely attributable to the older ages of eyes with SDD; they did not exhibit deficits in other visual functions. Subretinal drusenoid deposits in older eyes in normal macular health are not associated with any visual functions evaluated.

Delayed Rod-Mediated Dark Adaptation Is a Functional Biomarker for Incident Early Age-Related Macular Degeneration.

PURPOSE: To examine whether slowed rod-mediated dark adaptation (DA) in adults with normal macular health at baseline is associated with the incidence of age-related macular degeneration (AMD) 3 years later. DESIGN: Prospective cohort. PARTICIPANTS: Adults aged ≥60 years were recruited from primary care ophthalmology clinics. Both eyes were required to be step 1 (normal) on the Age-Related Eye Disease Study 9-step AMD classification system based on color fundus photographs graded by experienced and masked evaluators. METHODS: Rod-mediated DA was assessed at baseline in 1 eye after a photobleach using a computerized dark adaptometer with targets centered at 5° on the inferior vertical meridian. Speed of DA was characterized by the rod-intercept value, with abnormal DA defined as rod-intercept ≥12.3 minutes. Demographic characteristics, best-corrected visual acuity, and smoking status were also assessed. Log-binomial regression was used to calculate unadjusted and adjusted risk ratios (RRs) and associated 95% confidence intervals (CIs) for the association between baseline DA and incident AMD. MAIN OUTCOME MEASURES: Presence of AMD at the 3-year follow-up visit for the eye tested for DA at baseline. RESULTS: Both baseline and follow-up visits were completed by 325 persons (mean age, 67.8 years). At baseline, 263 participants had normal DA with mean rod-intercept of 9.1 (standard deviation [SD], 1.5), and 62 participants had abnormal DA with mean rod-intercept of 15.1 (SD, 4.0). After adjustment for age and smoking, those with abnormal DA in the tested eye at baseline were approximately 2 times more likely to have AMD in that eye (RR, 1.92; 95% CI, 1.03-3.62) by the time of the follow-up visit, compared with those who had normal DA at baseline. CONCLUSIONS: Delayed rod-mediated DA in older adults with normal macular health is associated with incident early AMD 3 years later, and thus is a functional biomarker for early disease. The biological relevance of this test is high, because it assesses translocation of vitamin A derivatives across the retinal pigment epithelium and Bruch's membrane, 2 tissues with prominent age- and AMD-related pathology.

Prevalence of Subretinal Drusenoid Deposits in Older Persons with and without Age-Related Macular Degeneration, by Multimodal Imaging.

PURPOSE: To assess the prevalence of subretinal drusenoid deposits (SDD) in older adults with healthy maculas and early and intermediate age-related macular degeneration (AMD) using multimodal imaging. DESIGN: Cross-sectional study. PARTICIPANTS: A total of 651 subjects aged ≥60 years enrolled in the Alabama Study of Early Age-Related Macular Degeneration from primary care ophthalmology clinics. METHODS: Subjects were imaged using spectral domain optical coherence tomography (SD OCT) of the macula and optic nerve head (ONH), infrared reflectance, fundus autofluorescence, and color fundus photographs (CFP). Eyes were assessed for AMD presence and severity using the Age-Related Eye Disease Study (AREDS) 9-step scale. Criteria for SDD presence were identification on ≥1 en face modality plus SD OCT or on ≥2 en face modalities if absent on SD OCT. Subretinal drusenoid deposits were considered present at the person level if present in 1 or both eyes. MAIN OUTCOME MEASURES: Prevalence of SDD in participants with and without AMD. RESULTS: Overall prevalence of SDD was 32% (197/611), with 62% (122/197) affected in both eyes. Persons with SDD were older than those without SDD (70.6 vs. 68.7 years, P = 0.0002). Prevalence of SDD was 23% in subjects without AMD and 52% in subjects with AMD (P < 0.0001). Among those with early and intermediate AMD, SDD prevalence was 49% and 79%, respectively. After age adjustment, those with SDD were 3.4 times more likely to have AMD than those without SDD (95% confidence interval, 2.3-4.9). By using CFP only for SDD detection per the AREDS protocol, prevalence of SDD was 2% (12/610). Of persons with SDD detected by SD OCT and confirmed by at least 1 en face modality, 47% (89/190) were detected exclusively on the ONH SD OCT volume. CONCLUSIONS: Subretinal drusenoid deposits are present in approximately one quarter of older adults with healthy maculae and in more than half of persons with early to intermediate AMD, even by stringent criteria. The prevalence of SDD is strongly associated with AMD presence and severity and increases with age, and its retinal topography including peripapillary involvement resembles that of rod photoreceptors. Consensus on SDD detection methods is recommended to advance our knowledge of this lesion and its clinical and biologic significance.

Cryptosporidium galli and novel Cryptosporidium avian genotype VI in North American red-winged blackbirds (Agelaius phoeniceus).

Proventriculus and intestinal samples from 70 North American red-winged blackbirds (Agelaius phoeniceus; order Passeriformes) were examined for the presence of Cryptosporidium by PCR amplification and sequence analysis of the 18S ribosomal RNA (18S rRNA), actin, and 70-kDa heat shock protein (HSP70) genes. Twelve birds (17.1 %) were positive for the Cryptosporidium 18S rRNA gene: six birds were positive at the proventriculus site only and six birds were positive at the proventriculus and intestinal sites. Sequence analysis of the 18S rRNA, actin and HSP70 genes showed the presence of the gastric species Cryptosporidium galli in a single proventriculus sample and a closely related genotype, which we have named Cryptosporidium avian genotype VI, in all other positive samples. These findings contribute to our understanding of Cryptosporidium diversification in passerines, the largest avian order.