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The phosphonate group is a key pharmacophore in many anti-viral, anti-microbial, and anti-neoplastic drugs. Due to its high polarity and short retention time, detecting and quantifying such phosphonate-containing drugs with LC/MS-based methods is challenging and requires derivatization with hazardous reagents. Given the emerging importance of phosphonate-containing drugs, developing a practical, accessible, and safe method for their quantitation in pharmacokinetics (PK) studies is desirable. NMR-based methods are often employed in drug discovery but are seldom used for compound quantitation in PK studies. Here, we show that proton-phosphorous (1H-31P) heteronuclear single quantum correlation (HSQC) NMR allows for quantitation of the phosphonate-containing enolase inhibitor HEX in plasma and tissue at micromolar concentrations. Although mice were shown to rapidly clear HEX from circulation (over 95% in 1H-31P HSQC method to quantify phosphonate-containing drugs in complex biological samples and illustrates an important limitation of mice as preclinical model species for phosphonate-containing drugs.

Purpose To identify disparities in the use of telemedicine during the coronavirus disease 2019 (COVID-19) pandemic. Design A cross-sectional study of completed clinical encounters in an academic ophthalmology center from March 2020, through August 2020. Participants A total of 5023 patients comprising 8116 ophthalmic clinical encounters. Methods Medical charts were abstracted for demographic information. We identified zip code-level socioeconomic characteristics, which were drawn from the 2019 American Community Survey 5-year estimates. Main Outcome Measures The completion of a synchronous video encounter, the completion of a telephone (audio-only) encounter in the absence of any video encounters, or the completion of in-person encounters only. Results During the study period, 8116 total clinical encounters were completed for 5023 unique patients. Of these patients, 446 (8.9%) participated in a video encounter, 642 (12.8%) completed a telephone encounter, and 3935 (78.3%) attended clinical appointments in person only. In adjusted analysis, patients who were Black (odds ratio [OR], 0.65; 95% confidence interval [CI], 0.52–0.80; P < 0.001) or Hispanic/Latino (OR, 0.65; 95% CI, 0.49–0.85; P = 0.002) were significantly less likely to complete a video or telephone appointment. Older patients (OR, 0.99; 95% CI, 0.98–0.99; P < 0.001), patients whose primary language was not English (OR, 0.49; 95% CI, 0.28–0.82; P = 0.01), Black patients (OR, 0.45; 95% CI, 0.32–0.62; P < 0.001), and Hispanic/Latino patients (OR, 0.56; 95% CI, 0.37–0.83; P = 0.005) were significantly less likely to complete a video encounter. Finally, among patients completing any type of telemedicine encounter, older age, (OR, 1.02; 95% CI, 1.01–1.03; P < 0.001), Medicare insurance (OR, 1.55; 95% CI, 1.11–2.17; P = 0.01), and Black race (OR, 1.97; 95% CI, 1.33–2.94; P < 0.001) were associated with using only phone visits. Conclusions Ethnic/racial minorities, older patients, and non–English-speaking individuals were significantly less likely to complete a video telehealth encounter. With the expansion of telemedicine and the need to reduce the disparate impact of COVID-19 on minorities, it will be increasingly important to identify barriers to telehealth use and opportunities to improve access.

Introduction This study determines the prevalence and associated correlates of people unaware of their diabetic retinopathy diagnosis in the U.S. Methods Participants unaware of diabetic retinopathy from the National Health and Nutrition Examination Survey from 2005 to 2008 were identified. The prevalence of those unaware of their diabetic retinopathy diagnosis was determined. Descriptive statistics and logistic regression were used to determine correlates associated with being unaware of one's diabetic retinopathy diagnosis (completed in 2018‒2020). Results Among 5,563 participants aged ≥40 years who underwent fundus photography, the prevalence of those unaware of their diabetic retinopathy diagnosis was 10.6% (9.8 million). This included 23.1% of those with self-reported diabetes (2.9 million) and 6.8% of those who reported not having diabetes (6.9 million). Among participants reporting diabetes with photographic evidence of retinopathy, 70.1% were unaware. Among individuals with self-reported diabetes, correlates of being unaware of one's diabetic retinopathy diagnosis included diabetes diaganosis for ≥10 years (OR=3.15, 95% CI=1.78, 5.56), HbA1c ≥6.5% (OR=2.92, 95% CI=1.65, 5.18), and treatment with insulin only (OR=4.04, 95% CI=1.43, 11.39). Self-reported hypertension was associated with decreased odds of undiagnosed diabetic retinopathy (OR=0.48, 95% CI=0.28, 0.82). Among those without self-reported diabetes, correlates of being unaware of diabetic retinopathy included older age (OR=1.02, 95% CI=1.01, 1.04), male sex (OR=1.83, 95% CI=1.31, 2.56), Black race (OR=1.81, 95% CI=1.12, 2.92), Hispanic race/ethnicity (OR=1.60, 95% CI=1.14, 2.25), elevated blood pressure (OR=1.54, 95% CI=1.23, 1.93), current smoking (OR=1.74, 95% CI=1.21, 2.51), and history of stroke (OR=2.20, 95% CI=1.06, 4.58). Conclusions A substantial proportion of individuals with diabetic retinopathy are unaware of the diagnosis. These data provide a path toward refining efforts to diagnose and treat diabetic retinopathy to decrease the burden of preventable blindness.

Purpose To estimate temporal trends in total and out-of-pocket (OOP) expenditures for ophthalmic prescription medications among adults in the United States. Design Retrospective, longitudinal cohort study. Participants Participants in the 2007 through 2016 Medical Expenditure Panel Survey (MEPS) 18 years of age or older. The MEPS is a nationally representative survey of the noninstitutionalized, civilian United States population. Methods We estimated trends in national and per capita annual ophthalmic prescription expenditures by pooling data into 2-year cycles and using weighted linear regressions. We also identified characteristics associated with greater total or OOP expenditures with multivariate weighted linear regression. Costs were adjusted to 2016 United States dollars using the gross domestic product price index. Main Outcome Measures Trends in total and OOP annual expenditures for ophthalmic medications from 2007 through 2016 as well as factors associated with greater expenditures. Results From 2007 through 2016, 9989 MEPS participants (4.2%) reported ophthalmic medication prescription use. Annual ophthalmic medication use increased from 10.0 to 12.2 million individuals from 2007 and 2008 through 2015 and 2016. In this same period, national expenditures for ophthalmic medications increased from $3.39 billion to $6.08 billion and OOP expenditures decreased from $1.34 to $1.18 billion. Per capita expenditure increased from $338.72 to $499.42 (P Conclusions Total ophthalmic medication expenditure in the United States increased significantly over the last decade, whereas OOP expenses decreased. Increases in coverage, copayment assistance, and use of expensive brand drugs may be contributing to these trends. Policy makers and physicians should be aware that rising overall drug expenditures ultimately may increase indirect costs to the patient and offset a decline in OOP prescription drug spending.

Adults with diabetes are at an increased risk of atherosclerotic cardiovascular disease (ASCVD), and food insecurity may be a major and underappreciated risk compounder in this population. We sought to analyze the prevalence of food insecurity and its association with ASCVD in adults with diabetes.A total of 6424 participants with diabetes were included from the 2019 and 2020 National Health Interview Survey. Food insecurity was determined with a 10-question U.S. Adult Food Security Survey Module, and classified as high, marginal, low, and very low. ASCVD was defined as a self-reported history of coronary artery disease, myocardial infarction, or stroke.Of the 6424 included participants (weighted: n = 21 690 217), 5 405 543 (24.4%) reported a history of ASCVD and 2 946 061 (13.3%) were identified as food insecure (low or very low food security). Adults with food insecurity were more likely to have ASCVD than adults who were food secure (28.9% vs 23.7%; P = 0.008). In the multivariate analyses adjusted for traditional cardiovascular risk factors, all levels of food insecurity were associated with ASCVD compared with food-secure adults (marginal security: odds ratio [OR]: 1.60; 95% confidence interval [CI], 1.18-2.18]; P = 0.003; low security: OR: 2.09; 95% CI, 1.58-2.74]; P0.001; very low security: OR: 1.69; 95% CI, 1.22-2.34]; P = 0.001). The association persisted when adjusted for income, location, education, and insurance status. In adults with diabetes and ASCVD, income was a negative factor for food insecurity (OR: 0.71; 95% CI, 0.62-0.80; P0.001), but female sex and smoking were positive factors (OR: 1.90; 95% CI, 1.29-2.80; P = 0.001; and OR: 1.97; 95% CI, 1.23-3.18; P = 0.005; respectively). At younger ages, the prevalence of food insecurity increased, especially in adults with ASCVD.We showed that 13% of U.S. adults with diabetes are food insecure, which was associated with ASCVD independent of traditional and socioeconomic risk factors. Our findings emphasize the importance of recognizing food insecurity as a driver of ASCVD in adults with diabetes, and encourage future efforts at reducing this disparity.

Purpose The current demographics of the ophthalmology workforce do not reflect the diverse United States population, which has implications for addressing health disparities. The demographics of ophthalmology department faculty may influence the recruitment of underrepresented students into the field. This study sought to determine how the racial and ethnic demographics of ophthalmology department faculty compare with those of other clinical departments at United States medical schools. Design Secondary data analysis of medical school faculty demographic data from the 2019 American Association of Medical Colleges (AAMC) Faculty Roster. Participants Clinical faculty and department chairs at United States medical schools. Methods We analyzed the racial and ethnic demographics of clinical department faculty and department chairpersons using data from the 2019 AAMC Faculty Roster. We calculated the proportion of underrepresented minority (URM) faculty in ophthalmology and in 17 other clinical departments. We analyzed these data for statistically significant differences between ophthalmology and other clinical departments. In addition, we compared the percentage of URM ophthalmology faculty with the proportion of URM persons among graduating United States medical students and in the United States population using data from the Medical School Graduation Questionnaire and the United States census, respectively. Main Outcome Measures The proportion of URM persons, defined as Black, Hispanic or Latino, Native American, or Native Hawaiian or Pacific Islander among clinical faculty and department chairs. Results Ophthalmology faculty are less racially and ethnically diverse than graduating medical students and the general United States population. When compared with 17 other clinical departments, ophthalmology has the third-lowest proportion of URM faculty, with only radiology and orthopedic surgery having a smaller proportion of URM faculty. These differences were statistically significant in most departments (12 of 18). No statistically significant difference was found in the proportion of URM department chairs in ophthalmology compared with most other clinical departments, although the absolute number of URM chairs in ophthalmology is low at only 8 chairpersons. Conclusions More work must be done to increase the recruitment of URM physicians into ophthalmology faculty positions to obtain parity with other clinical departments and with the diverse patient populations that physicians serve.

PURPOSE: To describe follow-up rates for patients referred for outpatient ophthalmic care after emergency department (ED) discharge and identify patient and visit characteristics associated with loss to follow-up (LTFU). DESIGN: Single-institution retrospective cohort study. METHODS: We analyzed the medical records of 2,206 patients seen in the ED for an eye-related issue who were subsequently scheduled for ophthalmology follow-up between 2013-2019 at a single tertiary health system. The main outcome measures were the frequency of and risk factors for LTFU and ED revisits. RESULTS: In total, 1649 (74.8%) completed follow-up within 2-months of an index ED visit. On multivariable analysis, younger age (p5 days after the ED visit (p

Residence within a disadvantaged US neighborhood was significantly associated with adherence to initial diabetic retinopathy screening. Composite measures of community-level socioeconomic status have the potential to be utilized to inform patient-specific care and policy interventions.

BACKGROUND: Diabetic retinopathy (DR) is among the leading causes of vision loss in the US, yet an estimated 50% of patients with diabetes do not receive recommended annual screening eye exams. Patients with diabetes and low socioeconomic status or who are racial/ethnic minorities are at increased risk for vision loss. METHODS: Qualitative interviews were conducted with 24 patients with diabetes at a federally qualified community health center in an urban area regarding factors influencing their use of screening. The interviews were recorded, transcribed, and analyzed line by line to identify themes. The themes were organized in a theoretical framework of factors influencing receipt of screening. RESULTS: The median age of participants was 57.5 (range 44 −73). Ten participants identified as female and 14 as male. Participants identified as Black (14), White (4), Hispanic (3), and Other/no answer (3). Twenty-three had health insurance. Twenty-three had received an eye exam within in the past year and 17 reported that they receive eye exams at least yearly. 415 comments were analyzed, 22 concepts were identified under 7 broader themes and two overarching categories of individual and structural factors. Themes included vision status, competing concerns, emotional context, resource availability, in-clinic experience, cues to action, and knowledge about diabetes. CONCLUSIONS: The factors that influence diabetic retinopathy screening utilization are complex. Visual symptoms and the need for glasses are important facilitators of screening. Many patients lack knowledge about diabetic retinopathy and the utility of preventative eye care. New strategies for engaging high-risk populations are necessary.

Purpose To report a case of idiopathic retinal vasculitis, aneurysms and neuroretinitis (IRVAN) in a young woman. Observations A 21-year-old white female patient was referred to retina clinic with decreased vision in the left eye. On examination, best corrected visual acuity was 20/20 in the right eye and counting fingers in the left eye. Fundus examination revealed bilateral optic disc edema, peripapillary and macular exudates, retinal arterial aneurysms, and venous beading. In the left eye, there was a large focus of exudative material in the central macula. Examination of the peripheral retina was unremarkable, bilaterally. Fluorescein angiography demonstrated arterial aneurysms and venous beading in both eyes, with optic nerve activity and vascular sheathing noted on late frames in both eyes. In the left eye, there was a large central area of blockage corresponding to hard exudates surrounding a more central area of hyperfluorescence with leakage, representing retinal neovascularization. Review of systems and extensive laboratory workup were negative. The patient was diagnosed with IRVAN. She was observed, and her exam at 6-month follow-up revealed low grade inflammation for which the patient was started on oral prednisone. Conclusions and Importance Management of IRVAN remains challenging because of its idiopathic nature and the lack of controlled clinical trials for such a rare entity. Bilateral involvement in IRVAN is variable and close follow up is crucial.

Hemorrhagic occlusive retinal vasculitis (HORV) is a condition associated with intraocular vancomycin during surgical intervention, most frequently following bilateral sequential cataract surgery. Because of the high rate of ophthalmic vascular complications in this condition, gonioscopic evaluation for identification of neovascularization of the angle and iris is essential. Careful examination can reveal previously asymptomatic and unassociated lesions of the iris or ciliary body. We present the case of a 71-year-old female who was diagnosed with a ciliary body melanoma secondary to complete ophthalmic examination associated with HORV. She reported decreased vision to light perception in the left eye (OS) following sequential, bilateral cataract surgery. Fundus examination OS demonstrated diffuse retinal vasculitis, retinal ischemia, and extensive hemorrhage. Evaluation included inflammatory and coagulopathy laboratory evaluation, carotid ultrasonography and magnetic resonance imaging (MRI) of the brain and orbits, all of which proved unrevealing, except for an enhancing mass OS on MRI. Further evaluation revealed a pigmented mass with features of melanoma in the anterior chamber angle extending into the ciliary body. Fine needle aspiration biopsy revealed high risk cytogenetic characteristics, and plaque radiotherapy was successfully employed. Keywords: Ciliary body, Hemorrhagic occlusive retinal vasculitis, Intracameral vancomycin, Malignant melanoma, Plaque radiotherapy, Uvea

Problem Health disparities among racial and ethnic groups exist in the United States despite improvements in health status and access to care. These inequalities may be reduced by increasing minority physician recruitment; however, how best to recruit these physicians remains unclear. Approach Near-peer teachers are not professionally trained, but have recently learned material that they themselves teach. Near-peer teaching in minority student outreach programs may be effective in increasing minority physician recruitment. The authors used a near-peer teaching model to promote interest in medicine, specifically ophthalmology, as a potential career path for both volunteer near-peer teachers and minority high school students participating in an educational outreach program. Twenty-one college and graduate-school near-peer teachers of various racial and ethnic backgrounds participated to teach 31 inner-city high school students. The program was evaluated using pre- and posttest surveys assessing students' knowledge about and interest in science, medicine, and ophthalmology; analysis used pairwise t-test comparisons. Qualitative responses and an end-of-training survey also assessed students' and near-peer teachers' satisfaction with the program and perceptions about medicine as a career. Outcomes Students' knowledge about and interest in medicine and ophthalmology increased significantly after participation. Near-peer teachers agreed that teaching in the program was beneficial to their careers and made it more likely that they would enter medicine and ophthalmology. Next Steps The authors will track the near-peer teachers' career paths and, in the next iteration, will increase the number of program days. This intervention may serve as a model for outreach for other specialties beyond ophthalmology.

OBJECTIVE Identifying individuals most at risk for diabetic retinopathy progression and intervening early can limit vision loss and reduce the costs associated with managing more advanced disease. The purpose of this study was to identify factors associated with progression from nonproliferative diabetic retinopathy (NPDR) to proliferative diabetic retinopathy (PDR). RESEARCH DESIGN AND METHODS This was a retrospective cohort analysis using a claims database of all eye care recipients age ≥30 years enrolled in a large managed-care network from 2001 to 2009. Individuals with newly diagnosed NPDR were followed longitudinally. Multivariable Cox regression analyses identified factors associated with progression to PDR. Three- and five-year probabilities of retinopathy progression were determined. RESULTS Among the 4,617 enrollees with incident NPDR, 307 (6.6%) developed PDR. After adjustment for confounders, every 1-point increase in HbA1c was associated with a 14% (adjusted hazard ratio 1.14 [95% CI 1.07–1.21]) increased hazard of developing PDR. Those with nonhealing ulcers had a 54% (1.54 [1.15–2.07]) increased hazard of progressing to PDR, and enrollees with nephropathy had a marginally significant increased hazard of progressing to PDR (1.29 [0.99–1.67]) relative to those without these conditions. The 5-year probability of progression for low-risk individuals with NPDR was 5% (range 2–8) and for high-risk patients was 38% (14–55). CONCLUSIONS Along with glycemic control, nonophthalmologic manifestations of diabetes mellitus (e.g., nephropathy and nonhealing ulcers) are associated with an increased risk of diabetic retinopathy progression. Our retinopathy progression risk score can help clinicians stratify patients who are most at risk for disease progression.

Introduction: Community-engaged research (CEnR) allows researchers and community organizations to partner together to improve health outcomes and to decrease health disparities. While prevalent in other fields of medicine, it is rarely used in ophthalmology.Areas covered: A comprehensive search of Ovid MEDLINE, NLM PubMed, Ovid Embase, Scopus and the Cochrane Library for the Medical Subject Headings (MeSH) ‘Community-based participatory research’ and text word variations including participatory research, community engagement, community research, partnered research, community–institutional relations, CEnR, CBPR in addition to variations on ophthalmology, eye diseases, vision disorders and eye injuries yielded 451 unique references. Two ophthalmologists (KHN, PANC) reviewed the titles and abstracts and identified 37 relevant studies. Expert consultation yielded an additional reference. After reviewing the full texts and excluding non-English texts, 18 articles met the necessary criteria. The eightee...

Using artifacts of teachers' practices, classroom observations, and interviews, we explore how 2 novice history teachers use writing in their middle school classrooms. Both teachers focused on evidence-based, interpretive writing in their preservice work, an approach promoted by their methods courses. After graduation, one teacher continued this focus and improved his ability to scaffold his students' essay writing. The second teacher emphasized summary of content and proper formatting in her use of writing, although some of her assignments integrated evidence-based interpretive writing. These case studies illustrate how 2 similarly prepared teachers convey entirely different notions of history through their use of writing. These teachers' school contexts and disciplinary understandings influence their use of writing. Their experiences make the case for integrating general literacy skills with disciplinary literacy and practicing historical writing instruction in different contexts during teacher ...

The escalating amount of kidney transplant recipients (KTRs) represents a significant dilemma for primary care providers. As the number of physician assistants (PAs) has been steadily increasing in primary care in the United States, the utilization of these healthcare professionals presents a solution for the care of post-kidney transplant recipients. A physician assistant (PA) is a state licensed healthcare professional who practices medicine under physician supervision and can alleviate some of the increasing demands for primary patient care. Here we provide an outline of the crucial components and considerations for PAs caring for kidney transplant recipients. These include renal function and routine screenings, drug monitoring (both immunosuppressive and therapeutic), pre-existing and co-existing conditions, immunizations, nutrition, physical activity, infection, cancer, and the patient’s emotional well-being. PAs should routinely monitor renal function and blood chemistry of KTRs. Drug monitoring of KTRs is a crucial responsibility of the PA because of the possible side-effects and potential drug-drug interactions. Therefore, PAs should obtain a careful and detailed patient history from KTRs. PAs should be aware of pre- and co-existing conditions of KTRs as this impacts treatment decisions. Regarding immunization, PAs should avoid administering vaccines containing live or attenuated viruses to KTRs. Because obesity following kidney transplantation is associated with decreased allograft survival, PAs should encourage KTRs to maintain a balanced diet with limited sugar. In addition, KTRs should be urged to gradually increase their levels of physical activity over subsequent years following surgery. PAs should be aware that immunosuppressive medications diminish immune defenses and make KTRs more susceptible to bacterial, viral, and fungal infections. Moreover, KTRs should be screened routinely for cancer due to the higher risk of development from immunosuppressive therapy. PAs must remain cognizant of the emotional well-being of the KTR, as many transplant patients struggle with fear, frustration, and acceptance.

Diabetic retinopathy affects 4.2 million people in the United States and is the leading cause of blindness in working-aged people. As the prevalence of diabetes continues to rise, cost-effective interventions to decrease blindness from diabetic retinopathy will be paramount. While HbA1c and duration of disease are known risk factors, they account for only 11% of the risk of developing microvascular complications from the disease. The assessment of environmental risk factors for diabetic eye disease allows for the determination of modifiable population-level challenges that may be addressed to facilitate the end of blindness from diabetes.

Cigarette smoking is the most common addictive behaviour co-occurring with problem gambling. Based on classical conditioning, smoking and gambling cues may acquire conditioned stimulus properties that elicit cravings for both behaviours. This study examined cross-cue reactivity in 75 men who were regular smokers, poker players or cigarette-smoking poker players. Participants were exposed to discrete cigarette, poker and neutral cues while skin conductance and psychological urges to smoke and gamble were measured. Results showed evidence of cross-cue reactivity based on skin conductance, and subjective response to smoking cues; subjective response to gambling cues was less clear. Smoking gamblers showed greater skin conductance reactivity to cues, and stronger subjective urges to smoke to smoking and gambling cues, compared to individuals who only smoked or only gambled. This study demonstrates evidence for cross-cue reactivity between a substance and a behavioural addiction, and the results encourage further research.

Data inside enterprises is exploding. Routinely key decision makers state, “one of the most valuable assets of our organization is actionable information.” Paradoxically, it is often challenging to gather the necessary metrics to build a business case to justify a Linked Data initiative for improved data quality in the face of the well-documented shortcomings of traditional enterprise approaches to data management. Internet standards have matured considerably in the last decade. The number of linked data sets is growing daily and already exceeds well in excess of ten thousand data sets, over 400 of which are published via the US Government at gov as of April 2010. Many of these linked data sets are high quality. Best practices for linking data within the enterprise are increasingly being published in articles, blogs and technical books. One of the pioneering linked enterprise data projects was undertaken by a Fortune 500 company in the early 2000 timeframe. The lessons learned about how to navigate the management and organizational dynamics are relevant today. This chapter outlines the successful strategies for a linked enterprise data initiative, including a consistent metadata management strategy across lines of business, definition and documentation of data ownership and the value of cross-functional teams in the definition, development and deployment of the project.

MMPI-2 maintains an extensive empirical base with psychiatric populations, although more recently, neurologically compromised patients have documented unique elevation patterns. This study examined mild-moderate TBI patients, Alzheimer's Dementia patients, and Psychiatric controls on MMPI-2 scales. Participants included 160 outpatients (TBI n = 26, AD n = 74, Psychiatric n = 60). Controlling for family-wise-error, five ANCOVAs were conducted on five MMPI-2 scales, correcting for age and education. TBI and Psychiatric group means were significantly higher than AD group means for scales Hypochondriasis, Depression, and Hysteria at an alpha of .01. Results support previous research with mild TBI patients, and further document a unique pattern of elevations in this population.

We assessed recent trends in the use of diagnostic testing for neovascular age-related macular degeneration (NVAMD) and macular edema (ME).Claims data from a managed-care network were analyzed on patients with NVAMD (n = 22,954) or ME (n = 31,810) to assess the use of fluorescein angiography (FA), fundus photography (FP), and optical coherence tomography (OCT) from 2001 to 2009. Repeated-measures logistic regression was performed to compare patients' odds of undergoing these procedures in 2001, 2005, and 2009. In addition, the proportions of patients with an incident NVAMD or ME diagnosis in 2003 or 2008 who underwent FA, FP, and OCT were compared.From 2001 to 2009, among patients with NVAMD, the odds of undergoing OCT increased 23-fold, whereas the odds of receiving FA and FP decreased by 68% and 79%, respectively. Similar trends were observed for ME. From 2003 to 2008, the proportion of patients undergoing OCT within 1 year of initial diagnosis increased by 315% for NVAMD and by 143% for ME; the proportion undergoing OCT without FA within 1 year increased by 463% for NVAMD and by 216% for ME.Use of OCT increased dramatically during the past decade, whereas use of FA and FP declined considerably, suggesting that OCT may be replacing more traditional diagnostic testing in patients with NVAMD or ME. Future studies should evaluate whether this increased reliance on OCT instead of FA and FP affects patient outcomes.

It has long been hypothesized that changes in dendritic spine structure may modify the physiological properties of synapses located on them. Due to their small size, large number, and highly variable shapes, standard light microscopy of Golgi impregnations and electron microscopy (EM) of single thin sections have not proved adequate to identify most spines in a sample or to quantify their structural dimensions and composition. Here we describe a new approach, the series sample, that was developed to classify by shape and subcellular composition all of the spines and synapses in a sample of neuropil by viewing them through serial EM sections. Spines in each class are then randomly selected for serial reconstruction and measurement in three dimensions. This approach was used to assess whether structural changes in hippocampal CA1 spines could contribute to the enhanced synaptic transmission and the greater endurance of long-term potentiation (LTP) that occur with maturation. Our results show a near doubling in the total density of synapses in the neuropil and along reconstructed dendrites between postnatal day 15 (PND 15) and adult ages. However, this doubling does not occur uniformly across all spine and synapse morphologies. Thin spines, mushroom spines containing perforated postsynaptic densities (PSDs) and spine apparatuses, and branched spines increase by about four-fold in density between PND 15 and adult ages. In contrast, stubby spines decrease by more than half and no change occurs in mushroom spines with macular PSDs or in dendritic shaft synapses. The stubby spines that remain are smaller in adults than at PND 15 and the mushroom spines are larger, while no change occurs in the three-dimensional structure of thin spines. Only a few spine necks at either age are constricted or long enough to attenuate charge transfer; therefore, the doubling in synapses should mediate the enhancement of synaptic transmission that occurs with maturation. In addition, LTP is not likely to be mediated by widening of spine necks at either age. However, the constricted spine necks could serve to concentrate specific molecules at activated synapses, thereby enhancing the specificity and endurance of LTP with maturation. These results demonstrate that the new series sample method combined with three- dimensional reconstruction reveals quantitative changes in the frequency and structure of spines and synapses that are not discernable by other methods and are likely to have dramatic effects on synaptic physiology and plasticity.