CENTRAL RETINAL VEIN OCCLUSION ASSOCIATED WITH USE OF AMYL NITRITE "POPPERS".

PURPOSE: To report a case of central retinal vein occlusion in a young patient after the use of amyl nitrate "poppers." METHODS: Description of the patient's clinical history, ophthalmic examination, retinal imaging, and treatment. RESULTS: A 38-year-old man presented with a central retinal vein occlusion in his right eye after inhaling amyl nitrite "poppers." There appeared to be a definitive temporal association between poppers use and both the onset of the vein occlusion and the patient's visual scotomata, which recurred immediately after drug use multiple times. Optical coherence tomography displayed cystic macular edema, which was treated with intravitreal bevacizumab. The patient's hypercoagulable laboratory workup was negative. CONCLUSION: This is the first report of a central retinal vein occlusion associated with poppers inhalation. A high index of suspicion for poppers use should be maintained in young patients who present with retinal vein occlusion, particularly in homosexual patients with a normal laboratory workup that fails to reveal a hypercoagulable etiology.

The long-term effects of anti-vascular endothelial growth factor therapy on the optical coherence tomography angiographic appearance of neovascularization in age-related macular degeneration.

BACKGROUND: The short-term effects of anti-vascular endothelial growth factor (anti-VEGF) treatment on macular neovascularization (MNV) morphology is well described, but long-term studies on morphologic changes and correlation of such changes to the type of MNV have not been conducted. This study aims to determine if different types of MNVs in neovascular AMD (nAMD) behave differently with anti-VEGF treatment as visualized on optical coherence tomography angiography (OCTA). METHODS: Treatment-naïve nAMD patients were retrospectively screened for baseline and follow-up OCTA imaging 10 or more months after initial treatment. Images were graded for MNV type, area, activity, mature versus immature vessels, vessel density, presence of atrophy, atrophy location and area. Growth rate was calculated as the percent change in lesion area from baseline over the years of follow-up. In addition, the occurrence of complete regression and the percent of lesions that grew, remained stable, and shrunk per type was also evaluated. RESULTS: Forty-three eyes from 43 patients with a mean follow-up of 2 years were evaluated. On structural OCT, 26 lesions were classified as pure type 1 MNVs, 12 MNVs had a type 2 component, and 5 MNVs had a type 3 component. Of these cases, 2 mixed-type MNVs were considered to have completely regressed. There was no significant differences in MNV area and growth rate between type 1 and type 2 lesions, but all cases of type 3 lesions shrunk in the follow-up period. There was no correlation between the number of injections per year and growth rate, endpoint MNV area or endpoint activity status for any MNV type. There was no significant association between the development of atrophy and the number of injections, baseline MNV area, baseline vessel density, or lesion growth rate. CONCLUSIONS: In nAMD, complete regression of an MNV network exposed to anti-VEGF is rare. This work emphasizes the role of anti-VEGF as anti-leakage rather than vascular regression agents in nAMD.

A Phase I/II Placebo-Controlled Randomized Pilot Clinical Trial of Recombinant Deoxyribonuclease (DNase) Eye Drops Use in Patients With Dry Eye Disease.

PURPOSE: To determine whether DNase eye drops have the potential to reduce signs and symptoms of dry eye disease (DED). METHODS: A placebo-controlled, randomized clinical trial was performed to compare the safety and efficacy of DNase eye drops 0.1% four times a day for 8 weeks in patients with severe tear deficient DED. The change in safety outcome measures (drug tolerability and proportion of adverse events) and efficacy outcome measures (Ocular Surface Disease Index [OSDI] score, corneal and conjunctival staining) were analyzed between baseline and week 8. RESULTS: Tolerability and adverse events were similar in placebo group and DNase group. Within the DNase group (but not placebo group), corneal staining showed a statistically significant and clinically meaningful reduction at week 8 compared with baseline. The OSDI score also showed a significant median reduction of 27.3 at week 8 compared with baseline within the DNase group. The median reduction in corneal staining and mucoid debris/strands was significantly greater in the DNase group as compared with the placebo group. In the DNase group, the median reduction in OSDI (-20.75) was more than placebo group (-8.43); however, the difference between groups was borderline significant. CONCLUSIONS: In this pilot study, treatment of severe tear deficient DED patients with DNase eye drops appears safe, well tolerated, and has the potential to reduce the severity of signs and symptoms. TRANSLATIONAL RELEVANCE: Data from this pilot clinical trial demonstrate the therapeutic potential of DNase eye drops in dry eye disease, possibly due to degradation neutrophil extracellular traps (NETs) from the ocular surface.

Thomas A. Swift's Electric Rifle Injuries to the Eye and Ocular Adnexa: The Management of Complex Trauma.

PURPOSE: To report the ocular and adnexal injuries sustained by patients with Thomas A. Swift's electric rifles (TASER; TASER International, Scottsdale, AZ), review the literature, and discuss the management of this complex trauma. DESIGN: Multicenter, retrospective case series and literature review. PARTICIPANTS: Seventeen eyes of 16 patients (5 eyes of 5 patients treated at 3 institutions, and 12 eyes of 11 previously reported cases). METHODS: The clinical data of 17 eyes were pooled. Spearman's correlation coefficient was used to assess the association between the extent of TASER injury and patient outcomes. MAIN OUTCOME MEASURES: Extent of TASER injury (zone of injury, penetrating vs. perforating) and association with patient outcomes (visual acuity [VA] and retinal detachment [RD]). RESULTS: In our cohort, 4 patients were transported by law enforcement and 1 was transferred from a community hospital. Four patients were taken to the operating room for TASER removal and globe repair; 1 patient underwent removal in the emergency room. Of 17 pooled cases, 12 (71%) involved open-globe injury. Of these, there was a high rate of zone 3 injuries (100%; n = 12) and a high incidence of RD (73%; 8 of 11, eviscerated eye excluded). Among patients with closed-globe injury (n = 5), 1 patient demonstrated exudative RD and 1 patient demonstrated retinal dialysis with RD. Of 10 patients with RD, 1 (10%) achieved resolution with monitoring (exudative RD); 1 (10%) underwent cryopexy and pneumatic retinopexy; 3 (30%) underwent vitrectomy, and 5 (50%) with poor prognosis did not undergo vitreoretinal surgery. In the 3 patients who underwent vitrectomy, all 3 (100%) demonstrated redetachment resulting from proliferative vitreoretinopathy and required additional surgery. Visual acuity on presentation was significantly correlated with final VA (ρ = 0.783; P = 0.02). Men (94%) were more likely than women (6%) to sustain TASER trauma. Median age was 26 years. There was a 50% rate of loss to follow-up. CONCLUSIONS: Thomas A. Swift's electric rifle injuries to the eyes or ocular adnexa represent complex trauma. Zone 3 injuries are common. The visual prognosis is guarded, and eyes may require multiple surgeries to preserve vision. Patients are at high risk for loss to follow-up by way of incarceration.

Neutrophil extracellular traps (NETs) contribute to pathological changes of ocular graft-vs.-host disease (oGVHD) dry eye: Implications for novel biomarkers and therapeutic strategies.

PURPOSE: To investigate the role of neutrophil extracellular traps (NETs) and NET-associated proteins in the pathogenesis of oGVHD and whether dismantling of NETs with heparin reduces those changes. METHODS: Ocular surface washings from oGVHD patients and healthy subjects were analyzed. Isolated peripheral blood human neutrophils were stimulated to generate NETs and heparinized NETs. We performed in vitro experiments using cell lines (corneal epithelial, conjunctival fibroblast, meibomian gland (MG) epithelial and T cells), and in vivo experiments using murine models, and compared the effects of NETs, heparinized NETs, NET-associated proteins and neutralizing antibodies to NET-associated proteins. RESULTS: Neutrophils, exfoliated epithelial cells, NETs and NET-associated proteins (extracellular DNA, Neutrophil Elastase, Myeloperoxidase, Oncostatin M (OSM), Neutrophil gelatinase-associated lipocalin (NGAL) and LIGHT/TNFSF14) are present in ocular surface washings (OSW) and mucocellular aggregates (MCA). Eyes with high number of neutrophils in OSW have more severe signs and symptoms of oGVHD. NETs (and OSM) cause epitheliopathy in murine corneas. NETs (and LIGHT/TNFSF14) increase proliferation of T cells. NETs (and NGAL) inhibit proliferation and differentiation of MG epithelial cells. NETs enhance proliferation and myofibroblast transformation of conjunctival fibroblasts. Sub-anticoagulant dose Heparin (100 IU/mL) dismantles NETs and reduces epithelial, fibroblast, T cell and MG cell changes induced by NETs. CONCLUSION: NETs and NET-associated proteins contribute to the pathological changes of oGVHD (corneal epitheliopathy, conjunctival cicatrization, ocular surface inflammation and meibomian gland disease). Our data points to the potential of NET-associated proteins (OSM or LIGHT/TNFSF14) to serve as biomarkers and NET-dismantling biologics (heparin eye drops) as treatment for oGVHD.

Ocular Pharmacology of Tear Film, Dry Eye, and Allergic Conjunctivitis.

Dry Eye Disease (DED) is "a multifactorial disease of the tears and ocular surface that results in symptoms of discomfort, visual disturbance, and tear-film instability with potential damage to the ocular surface." DED comprises two etiologic categories: aqueous-deficient dry eye (ADDE) and evaporative dry eye (EDE). Diagnostic workup of DED should include clinical history, symptom questionnaire, fluorescein TBUT, ocular surface staining grading, Schirmer I/II, lid and meibomian pathology, meibomian expression, followed by other available tests. New diagnostic tests employ the Oculus Keratograph, which performs non-invasive tear-film analysis and a bulbar redness (BR). The TearLab Osmolarity Test enables rapid clinical evaluation of tear osmolarity. Lipiview is a recently developed diagnostic tool that uses interferometry to quantitatively evaluate tear-film thickness. In DED, epithelial and inflammatory cells produce a variety of inflammatory mediators. A stagnant tear film and decreased concentration of mucin result in the accumulation of inflammatory factors that can penetrate tight junctions and cause epithelial cell death. DED treatment algorithms are based on severity of clinical signs and symptoms, and disease etiology. Therapeutic approaches include lubricating artificial tears and immunomodulatory agents.

A New Master's Degree in Global Health: Reflections on a 5-year Experience.

BACKGROUND: The University of California-San Francisco's (UCSF) Master of Science (MS) degree in global health sciences, a 1-year degree program started in 2008, is the first accredited master's degree in global health in the country. OBJECTIVE: The aim of this study was to review the genesis and structure of the MS degree program, and describe its progress over its first 5 years. METHODS: We reviewed the program's teaching methods, academic curriculum, course evaluations, and backgrounds and outcomes of the first 127 graduates. Student opinions were gathered from anonymous course evaluations. Student outcome data and graduates' perspectives were gathered through a voluntary, anonymous, online survey. We reflect on student demand, program strengths and weaknesses, and future academic directions. FINDINGS: The program's structure arose from three learning objectives identified by the Curriculum Committee: a multidisciplinary approach to the foundations of global health, an emphasis on research design and methods, and an application of theory to international fieldwork. The resulting broad curriculum has attracted students of diverse backgrounds, which has enriched classroom discussions. Over the first 5 years, the program revised its fieldwork project criteria to allow more flexibility in design, leading to a higher rate of publication and enabling students to graduate with an academic portfolio. Students have reported that the high faculty-to-student ratio has fostered strong mentorship relationships; this is vital as 66% of graduates work in academics. Graduates have reflected that group work in the program appropriately prepared them for their work environment. The program's experience has guided its response to: pressure to focus on medical aspects of global health; students' needs for career skill-building; financial challenges; and trends toward online didactics. CONCLUSIONS: The recent surge in interest in global health careers has created demand for academic programs. UCSF has designed the MS degree program to balance breadth and depth of learning in a multidisciplinary curriculum, and combine career preparation and theoretical learning in a one-year academic degree. The challenges of balancing breadth and depth of learning in a multidisciplinary program, and combining career preparation and theoretical learning in a one-year academic degree, have informed UCSF's MS program design.

Effect of gestational age and birth weight on the risk of strabismus among premature infants.

IMPORTANCE: Strabismus causes irreversible vision loss if not detected and treated early. It is unclear whether birth weight (BW) and gestational age (GA) are risk factors for strabismus. OBJECTIVE: To estimate the effect of BW and GA on the likelihood of premature infants developing strabismus. DESIGN, SETTING, AND PARTICIPANTS: In this longitudinal cohort analysis, we monitored a group of premature children from birth to determine the proportion that developed strabismus and the timing of the first strabismus diagnosis. Multivariable Cox regression analyses assessed the relationships of BW and GA with the development of strabismus. Regression models were adjusted for other risk factors for strabismus, sociodemographic factors, and ocular comorbidities. The analysis included 38,055 otherwise healthy children born prematurely who were enrolled for more than 6 months in a nationwide US managed care network between 2001 and 2011 in communities throughout the United States. EXPOSURES: Birth weight less than 2000 g or GA of 32 weeks or less. MAIN OUTCOMES AND MEASURES: Hazard ratios (HRs) for strabismus with 95% CIs. RESULTS: Of 38,055 otherwise healthy children who were born prematurely, 583 received a diagnosis of strabismus later in life. The cumulative incidence of strabismus was 3.0% at 5 years. Controlling for GA and other covariates, infants born with BW less than 2000 g had a 61% increased hazard (HR, 1.61; 95% CI, 1.22-2.13) of developing strabismus. Controlling for BW and other covariates, there was no significant association between strabismus and GA (HR, 0.98; 95% CI, 0.69-1.38). Among premature infants with BW of less than 2000 g, a GA of 32 weeks or less conveyed no additional increased risk for developing strabismus relative to infants born after 32 weeks (HR, 1.27; 95% CI, 0.86-1.88). In contrast, among infants with a GA of 32 weeks or less, BW of less than 2000 g conveyed a 14-fold increase in the risk of strabismus relative to BW of 2000 g or more (HR, 14.39; 95% CI, 1.99-104.14). CONCLUSIONS AND RELEVANCE: Independent of GA, very low BW conferred a large increase in strabismus risk among premature infants. In contrast, independent of BW, GA did not significantly affect the risk of strabismus. Updates to existing guidelines in the pediatric and ophthalmic literature should be considered, highlighting the importance of BW rather than GA and alerting clinicians about the need for careful monitoring of premature infants with low BW for strabismus.

Fetal ascites and hydrometrocolpos due to persistent urogenital sinus and cloaca: a rare congenital anomaly and review of literature.

Fetal ascites can occur due to many heterogeneous disorders. Its association with hydrometrocolpos because of persistent urogenital sinus and cloaca is extremely rare. A 29-year-old primigravida presented at 32 weeks of gestation with ultrasonographic evidence of fetal ascites, a cystic pelvic mass, hydronephrosis and oligohydramnios. Fetal ascites in this case was due to fetal urine draining through fallopian tubes into the abdomen as a result of vesicovaginal fistula and distal vaginal atresia. The antenatal ultrasound results along with autopsy findings are discussed. Though rare, a persistent urogenital sinus is to be suspected in isolated fetal ascites cases where the viral tests are negative and there is no evidence of cardiac anomalies as this is a treatable anomaly if diagnosed at early gestational age.

Febrile illness management in children under five years of age: a qualitative pilot study on primary health care workers' practices in Zanzibar.

BACKGROUND: In Zanzibar, malaria prevalence dropped substantially in the last decade and presently most febrile patients seen in primary health care facilities (PHCF) test negative for malaria. The availability of rapid diagnostic tests (RDTs) allows rural health workers to reliably rule out malaria in fever patients. However, additional diagnostic tools to identify alternative fever causes are scarce, often leaving RDT-negative patients without a clear diagnosis and management plan. This pilot study aimed to explore health workers' practices with febrile children and identify factors influencing their diagnostic and management decisions in non-malarial fever patients. METHODS: Semi-structured key informant interviews were conducted with 12 health workers in six PHCFs in North A district, Zanzibar, April to June 2011. Interviews were coded using Atlas.ti to identify emerging themes that play a role in the diagnosis and management of febrile children. RESULTS: The following themes were identified: 1) health workers use caregivers' history of illness and RDT results for initial diagnostic and management decisions, but suggest caregivers need more education to prevent late presentation and poor health outcomes; 2) there is uncertainty regarding viral versus bacterial illness and health workers feel additional point-of-care diagnostic tests would help with differential diagnoses; 3) stock-outs of medications and limited caregivers' resources are barriers to delivering good care; 4) training, short courses and participation in research as well as; 5) weather also influences diagnostic decision-making. CONCLUSIONS: This pilot study found that health workers in Zanzibar use caregiver history of fever and results of malaria RDTs to guide management of febrile children. However, since most febrile children test negative for malaria, health workers believe additional training and point-of-care tests would improve their ability to diagnose and manage non-malarial fevers. Educating caregivers on signs and symptoms of febrile illness, as well as the introduction of additional tests to differentiate between viral and bacterial illness, would be important steps to get children to PHCFs earlier and decrease unnecessary antibiotic prescribing without compromising patient safety. More research is needed to expand an understanding of what would improve fever management in other resource-limited settings with decreasing malaria.

Interleukin-6 as a predictor of subclinical chorioamnionitis in preterm premature rupture of membranes.

PROBLEM: One of the major challenges faced by the clinicians in preterm premature rupture of the membranes (PPROM) is to correctly identify when a significant chorioamnionitis is evolving and decide timely delivery of the fetus. Measuring interleukin-6 levels in maternal serum can be useful for the identification of asymptomatic intrauterine infections in subjects with PPROM. METHOD OF STUDY: A total of 75 pregnant women, of which 45 pregnant women presenting with PPROM between 24 and 34 weeks gestation and 30 healthy pregnant women without PPROM, were included in the study. Serum IL-6 levels were determined by solid-phase sandwich enzyme-linked immunosorbent assay (Diaclone Research, Besancon, France). RESULTS: The mean serum IL-6 value at admission in the control group was 2.48 ± 2.7 pg/mL and in the study group was 11.86 ± 14.5 pg/mL (P = 0.001). Mean serum IL-6 concentrations at admission in subjects without histological chorioamnionitis were 3.98 ± 3.9 pg/mL and in those who had histological chorioamnionitis were 20.09 ± 16.8 pg/ml (P < 0.001). CONCLUSION: Maternal serum IL-6 levels were significantly elevated in subjects with PPROM with infectious morbidity as compared to those without infectious morbidity in the present study. There was a significant rise in maternal serum IL-6 levels with increased duration of rupture of membranes and with evidence of histological chorioamnionitis and funisitis in the placenta.

Maternal serum interleukin-6 and its association with clinicopathological infectious morbidity in preterm premature rupture of membranes: a prospective cohort study.

OBJECTIVE: To analyze the association of maternal serum interleukin-6 (IL-6) with fetomaternal outcome in preterm premature rupture of membranes (PPROM). METHODS: Serial serum IL-6 levels were measured in 45 women with PPROM at gestation 24-34 weeks. The women were followed till pueperium and fetomaternal outcome as well as the histopathology of the placenta and the umbilical cord was studied. The data were analyzed using t test and χ(2) test. RESULTS: IL-6 levels ≥ 8 pg/ml were significantly associated with puerperal sepsis and neonatal sepsis. Histological chorioamnionitis and funisitis were demonstrated in 48.8% and 13.3% women respectively and significantly correlated with elevated serum IL-6 levels and fetomaternal infection. A cut-off value of IL-6 of 8 pg/ml was found to correctly diagnose 19 out of 23 patients with infectious morbidity and showed the best sensitivity (82.6%) and specificity (86.3%) as compared to the total leucocycte count (TLC) and C-reactive protein (CRP) in diagnosing infection in PPROM. CONCLUSION: Maternal serum IL-6 can be used as a biomarker to predict preclinical asymptomatic infection in PPROM with good sensitivity and specificity.