Relationship between glaucoma and admixture in postmenopausal African American women.

OBJECTIVE: To investigate the association between African admixture and glaucoma prevalence among African American women. DESIGN, SETTING, PARTICIPANTS: Participants included 11616 African American women from the Women's Health Initiative Study (WHI) for whom admixture information was available and included 2548 who self-reported a diagnosis of glaucoma. MAIN OUTCOME MEASURES: Glaucoma. RESULTS: Significant association was observed between self-identified glaucoma status and admixture. However, this association was not significant in a model that included neighborhood socioeconomic status (NSES), hypertension, diabetes and body mass index (BMI). Self-identified glaucoma status was associated with diabetes that persisted after adjustment for admixture, NSES, hypertension, and BMI. Lower NSES was also associated with higher glaucoma risk but this association was marginal in the fully adjusted model and neither hypertension nor BMI showed association. When glaucoma status was limited to those reporting use or no use of appropriate ophthalmologic medication, no associations were observed in any of the models. CONCLUSION: This study failed to find an independent association of glaucoma status and African admixture and these findings suggest that the higher frequency glaucoma in African Americans may be largely due to other factors.

Parallel rarebits: a novel, large-scale visual field screening method.

BACKGROUND: Rarebit perimetry (RBP) is a computer-based perimetric testing program with sensitivity and specificity for detection of visual field defects comparable to traditional automated perimetry. To make large-scale screening more efficient, we developed a parallel rarebit perimetric method to screen groups of subjects simultaneously. We then used this method to report the mean hit rate (MHR) among subjects aged 13 to 19 years. METHODS: Rarebit perimetry was installed on computers in an existing school computer laboratory. All subjects provided medical and demographic information and underwent a basic visual examination. Testing instructions were provided to groups of up to 35 subjects and rarebit perimetry was subsequently administered. Two or three test supervisors answered questions and ensured that subjects were well aligned with their test screens. Mean hit rate, reaction times, error rates and testing time were calculated, and time estimates for rarebit, frequency doubling perimetry and Humphrey 24-2 Swedish Interactive Thresholding Algorithm (SITA) fast test were compared. RESULTS: A total of 364 rarebit perimetric tests were conducted on 182 subjects. Of these, 154 subjects met our inclusion criteria for the reference range (three testing errors or less and visual acuity 6/9 or better). The average mean hit rate was 94.3 ± 4.63 per cent. Screening of 500 subjects using this parallel rarebit perimetric method would require approximately nine hours, which is far less than an estimated 77 hours required for frequency doubling perimetry C-20 screening tests or an estimated 127 hours required for Humphrey 24-2 SITA fast tests. CONCLUSION: Using our methods, rarebit perimetry can be administered in parallel to groups of subjects. The mean hit rate was comparable to that reported in previously published studies. This parallel technique may improve the efficiency of large-scale visual field screenings.

Active aspiration of suprachoroidal hemorrhage using a guarded needle.

BACKGROUND AND OBJECTIVE: To describe a novel technique using a guarded needle to drain suprachoroidal hemorrhage. PATIENTS AND METHODS: A guarded needle is used to drain suprachoroidal hemorrhage under direct microscope visualization. A scleral buckling sleeve is used to create a guarded 26-gauge needle to avoid over-penetration of the needle beyond the suprachoroidal space. Active extrusion can be used to drain suprachoroidal blood. RESULTS: The authors report two cases in which active aspiration using a guarded needle was successful in draining suprachoroidal hemorrhage without complications. In both cases, the vitreous cavity could be restored, allowing for subsequent pars plana vitrectomy. CONCLUSION: The technique of active aspiration using a guarded needle optimizes surgeon control of suprachoroidal hemorrhage drainage and also has the added benefit of easy transition to secondary vitrectomy after drainage has been completed.

Oxidized low-density-lipoprotein-induced injury in retinal pigment epithelium alters expression of the membrane complement regulatory factors CD46 and CD59 through exosomal and apoptotic bleb release.

Genetic and immunohistochemical studies have identified the alternative complement pathway as an important component of age-related macular degeneration (AMD). The objective of this chapter is to review the impact of complement regulators on complement activation in the macula as it relates to AMD. Our laboratory and other investigators have identified CD46 and CD59 as important retinal pigment epithelium (RPE) cell membrane complement regulators, which are decreased in AMD. Using oxidized low-density lipoproteins (oxLDLs), which are found in Bruch's membrane in AMD, we found that CD46 and CD59 were decreased in RPE cells in part, by their release in exosomes and apoptotic particles. The release of complement regulators could potentially impair complement regulation on RPE cells and contribute to lesion formation in the outer retina and Bruch's membrane during the development of AMD.

Stanford University Network for Diagnosis of Retinopathy of Prematurity (SUNDROP): five years of screening with telemedicine.

BACKGROUND AND OBJECTIVE: To report the 5-year results of the Stanford University Network for Diagnosis of Retinopathy of Prematurity (SUNDROP) telemedicine initiative. PATIENTS AND METHODS: Infants requiring retinopathy of prematurity (ROP) screening at six neonatal intensive care units from December 1, 2005, to November 30, 2010, were evaluated with remote retinal photography by an ROP specialist. Every infant received outpatient binocular indirect ophthalmoscope examinations until termination criteria were achieved or until treatment. Outcomes were treatment-warranted ROP (TW-ROP, ETROP type 1) and adverse anatomical events. RESULTS: Five hundred eleven infants (1,022 eyes) were screened. Fifteen infants had TW-ROP and underwent laser photocoagulation. The TW-ROP cohort had significantly lower birth weight and gestational age (both P < .001). No patient progressed to adverse anatomical outcomes and no case of TW-ROP was missed. Tele-medicine had 100% sensitivity, 99.8% specificity, 93.8% positive predictive value, and 100% negative predictive value for detection of TW-ROP. CONCLUSION: Telemedicine demonstrates high diagnostic accuracy for detection of TW-ROP and can complement ROP screening.

Mediastinal kaposiform hemangioendothelioma and Kasabach-Merritt phenomenon in a patient with no skin changes and a normal chest CT.

A 16-month-old previously healthy boy was admitted to the hospital with respiratory distress and thrombocytopenia. Initial workup demonstrated large pleural and pericardial effusions. The patient had no cutaneous abnormality on physical examination, and his initial chest CT (computed tomography) was nondiagnostic. He required multiple platelet transfusions, chest tube placement, and pericardiocentesis. Sixteen days after admission, a chest MRI (magnetic resonance imaging) revealed a large infiltrative mass of the superior mediastinum, consistent with kaposiform hemangioendothelioma (KHE). The patient's thrombocytopenia was due to associated Kasabach-Merritt phenomenon (KMP). The patient now has complete resolution of KMP after medical treatment with prednisolone, aminocaproic acid, vincristine, and aspirin.

Validation of a grading system for lateral nasal wall insufficiency.

This study was designed to validate a grading scheme for lateral nasal wall insufficiency with interrater and intrarater reliability measures. Representative endoscopic videos depicting varied degrees of lateral nasal wall insufficiency were collated into a 30-clip video (15 clips in duplicate). This was rated by five reviewers for a total of 150 observations. Interrater and intrarater reliability were determined using Fleiss kappa and intraclass correlation coefficient (ICC) statistics, respectively. Good agreement was established between reviewers (interrater reliability), with a Fleiss kappa of 0.7733 (p < 0.01). Analysis of intrarater variability with the ICC revealed a very strong agreement (ICC = 0.88; p < 0.01). The proposed grading system is shown to have good interrater and intrarater reliability. It provides a reliable instrument for assessing lateral wall insufficiency.

Academic productivity and its relationship to physician salaries in the University of California Healthcare System.

OBJECTIVES: To evaluate whether physicians with higher academic productivity, as measured by the number of publications in Scopus and the Scopus Hirsch index (h-index), earn higher salaries. METHODS: This was a cross-sectional study. Participants were ophthalmologists, otolaryngologists, neurosurgeons, and neurologists classified as "top earners" (>$100,000 annually) within the University of California (UC) healthcare system in 2008. Bibliometric searches on Scopus were conducted to retrieve the total number of publications and Hirsch indices (h-index), a measure of academic productivity. The association between the number of publications and h-index on physicians' total compensation was determined with multivariate regression models after controlling for the four specialties (ophthalmology, otolaryngology, neurosurgery, and neurology), the five institutions (UC San Francisco, UC Los Angeles, UC San Diego, UC Irvine, and UC Davis), and academic rank (assistant professor, associate professor, and professor). RESULTS: The UC healthcare system departments reported 433 faculty physicians among the four specialties, with 71.6% (n = 310) earning more than $100,000 in 2008 and classifying as top earners. After controlling for the specialty, institution, and ranking, there was a significant association between the number of publications on salary (P < 0.000001). Scopus number of publications and h-index were correlated (P < 0.001). Scopus h-index was of borderline significance in predicting physician salary (P = 0.12). Physicians with higher Scopus publications had higher total salaries across all four specialties. Every 10 publications were associated with a 2.40% increase in total salary after controlling for specialty, institution, rank, and chair. CONCLUSIONS: Ophthalmologists, otolaryngologists, neurosurgeons, and neurologists in the UC healthcare system who are more academically productive receive greater remuneration.

The importance of keeping a broad differential in retina clinic: the spectrum of ophthalmic disease seen by retina specialists in a tertiary outpatient clinic setting.

BACKGROUND AND OBJECTIVE: To describe the new patient population referred to retina specialists at tertiary ophthalmic academic centers in the United States. STUDY DESIGN AND METHODS: Retrospective chart review of all new patients seen by retina specialists at Stanford University from 2008 to 2011. RESULTS: Retina specialists saw 7,197 new patients during the study period, with a mean age of 52.2 ± 25.6 years (range: 0 to 108 years). Younger patients (0 to 10 years) were more likely male (P < .001) while older patients were more likely female (P < .01 for 61 to 70, 81+ years). The most common diagnoses were diabetic eye disease (17.0%), retinopathy of prematurity (9.9%) and age-related macular degeneration (9.5%). CONCLUSION: Retina specialists treat patients of all ages, and the most common diagnoses vary with age and gender. Patients present to retinal clinic with a vast spectrum of disease from various ophthalmic and systemic etiologies; therefore, it is important to maintain a broad differential diagnosis.

Fever literacy and fever phobia.

OBJECTIVE: To identify the percentage of parents who define the threshold for fever between 38.0°C and 38.3°C, which has not been reported previously, and to describe parental attitudes toward fever and antipyretic use. STUDY DESIGN: Thirteen-question survey study of caregivers. RESULTS: Overall, 81% of participants defined the threshold for fever as <38.0°C, 0% correctly defined fever between 38.0°C and 38.3°C, and 19% defined fever as >38.3°C. Twenty percent of children brought to clinic for a chief complaint of fever were never truly febrile. Ninety-three percent of participants believed that high fever can cause brain damage. For a comfortable-appearing child with fever, 89% of caregivers reported that they would give antipyretics and 86% would schedule a clinic visit. CONCLUSION: Our finding that 0% of parents correctly defined fever is both surprising and unsettling, and it should inform future discussions of fever between parents and clinicians.

Stanford University Network for Diagnosis of Retinopathy of Prematurity (SUNDROP): four-years of screening with telemedicine.

PURPOSE: To report the four-year experience of the Stanford University Network for Diagnosis of Retinopathy of Prematurity (SUNDROP) telemedicine initiative, which was developed to reduce the risk of blindness from retinopathy of prematurity (ROP). MATERIALS AND METHODS: A retrospective analysis of the SUNDROP archival data between 12/1/2005 and 11/30/2009. A total of 410 consecutively enrolled infants meeting ROP screening criteria had nurse-obtained fundoscopic images evaluated remotely by an ROP specialist. Every infant then received at least one dilated bedside binocular indirect ophthalmoscope (BIO) examination within one week of discharge. All infants were then followed with both telemedicine images and bedside evaluation in clinic according to recommended screening timelines. Primary outcomes were treatment-warranted ROP (TW-ROP), defined as Early Treatment of ROP Type 1, and adverse anatomical outcomes. RESULTS: The SUNDROP telemedicine screening initiative has not missed any TW-ROP in its four-year evaluation period. A total of 410 infants (820 eyes) were imaged, resulting in 1486 examinations and 18,097 unique images. An average of 12.2 images were obtained per patient. Fourteen infants met TW-ROP criteria on telemedicine examination. After bedside evaluation, 13 infants required laser photocoagulation and one was followed until he spontaneously regressed. Infants with TW-ROP had a significantly lower gestational age (24.9 weeks), birth weight (658.7 grams), and were more likely to be male than the no TW-ROP cohort (all p values <0.00001). Telemedicine had a calculated sensitivity of 100%, specificity of 99.8%, positive predicative value of 92.9% and negative predictive value of 100% for the detection of TW-ROP. No patient progressed to retinal detachment or any adverse anatomical outcome. CONCLUSIONS: The SUNDROP initiative demonstrated a high degree of diagnostic reliability and was able to capture all infants with TW-ROP. Telemedicine offers a cost-effective, reliable and accurate screening methodology for identifying infants with TW-ROP without sacrificing quality of care.

Decreased membrane complement regulators in the retinal pigmented epithelium contributes to age-related macular degeneration.

Dysregulated complement is thought to play a central role in age-related macular degeneration (AMD) pathogenesis, but the specific mechanisms have yet to be determined. In maculae of AMD specimens, we found that the complement regulatory protein, CD59, was increased in regions of uninvolved retinal pigmented epithelium (RPE) of early AMD, but decreased in the RPE overlying drusen and in geographic atrophy, an advanced form of AMD. While CD46 immunostaining was basolaterally distributed in the RPE of unaffected controls, it was decreased in diseased areas of early AMD samples. Since oxidized low-density lipoproteins (oxLDL) collect in drusen of AMD and are a known complement trigger, we treated ARPE-19 cells with oxLDL and found that cellular CD46 and CD59 proteins were decreased by 2.9- and nine-fold (p < 0.01), respectively. OxLDLs increased complement factor B mRNA and Bb protein, but not factor D, I or H. OxLDLs increased C3b, but not C3a, C5 or C5b-9. C5b-9 was increased by 27% (p < 0.01) when the medium was supplemented with human serum, which was sufficient to induce poly(ADP-ribose) polymerase cleavage, a marker of apoptosis. The decreased levels of CD46 and CD59 were in part explained by their release in exosomal and apoptotic membranous particles. In addition, CD59 was partially degraded through activation of IRE1α. Collectively, these results suggest that a combination of impaired complement regulators results in inadequately controlled complement by the RPE in AMD that induces RPE damage.

Advanced glycation endproduct changes to Bruch's membrane promotes lipoprotein retention by lipoprotein lipase.

Lipoprotein particles accumulate in Bruch's membrane before the development of basal deposits and drusen, two histopathologic lesions that define age-related macular degeneration (AMD). We therefore, sought to determine which molecules could participate in lipoprotein retention. Wild-type or lipoprotein lipase-deficient mice were injected with low-dose D-galactose or PBS subcutaneously for 8 weeks to induce advanced glycation endproduct (AGE) formation. Some mice were also injected with the AGE breaker phenacylphiazolium bromide and D-galactose. Rhodamine-labeled low-density lipoproteins were injected into mice, and the fluorescence was measured up to 72 hours later. AGEs, proteoglycans, and other lipid-retaining molecules were evaluated by IHC. Lipoprotein lipase distribution was assessed in AMD samples by IHC. D-galactose-treated mice retained lipoproteins in the retinal pigment epithelial and Bruch's membrane to a greater extent than either PBS- or phenacylphiazolium bromide/D-galactose-treated mice at 24 and 72 hours after injection (P ≤ 0.04). Immunolabeling for carboxymethyllysine, biglycan, and lipoprotein lipase was found in D-galactose-treated mice only. Mice deficient for lipoprotein lipase treated with D-galactose did not retain lipoproteins to any measureable extent. Human AMD samples had lipoprotein lipase labeling within drusen, basal deposits, and the choroid. Mice treated with D-galactose to induce AGE formation in Bruch's membrane retain intravenously injected lipoproteins. Our results suggest that lipoprotein retention in Bruch's membrane is mediated by lipoprotein lipase.