Pharmacotherapies for Diabetic Retinopathy: Present and Future

Diabetic retinopathy remains a major cause of worldwide preventable blindness. Measures to avoid blindness include medical management (control of blood sugar, blood pressure, and serum lipids) and ocular management (laser photocoagulation and pars plana vitrectomy). Adjunctive pharmacologic therapies (intravitreal triamcinolone acetonide and anti-vascular endothelial growth factor agents) have shown early promise in the treatment of both diabetic macular edema and proliferative diabetic retinopathy. Other medications under investigation include the fluocinolone acetonide implantable device, extended-release dexamethasone implant, oral ruboxistaurin, and intravitreal hyaluronidase

Lipemia Retinalis, Macular Edema, and Vision Loss in a Diabetic Patient with a History of Type IV Hypertriglyceridemia and Pancreatitis

Background: Lipemia retinalis is a rare but known complication of elevated serum triglycerides. This case describes the clinical course of a diabetic patient who presented with lipemia retinalis and macular edema, which responded to systemic and local treatments. Case Report: A 40-year-old female with a history of type II diabetes mellitus, hypertriglyceridemia, and pancreatitis presented with decreased vision in the left eye. She had peripapillary and macular edema, intraretinal hemorrhages, and prominent exudates in the setting of lipemia retinalis due to type IV hypertriglyceridemia. She was treated with serial intravitreal bevacizumab injections for macular edema and systemic lipid lowering therapy, and her visual acuity improved back to baseline. Conclusions: In the setting of lipemia retinalis and hypertriglyceridemia, the current patient developed macular edema and vision loss. The macular edema was treated with intravitreal injections of bevacizumab, and the patient experienced a rapid recovery of visual acuity

Delayed-onset endophthalmitis associated with corneal suture infections

BACKGROUND: The purpose of the current study was to report the microbiology, risk factors, and treatment outcomes in patients with delayed-onset endophthalmitis associated with corneal suture infections. For this retrospective consecutive case series, a search of the ocular microbiology department database was performed to identify all patients with positive corneal and intraocular cultures (anterior chamber and/or vitreous) between 01 January 1995 and 01 January 2010. A subset of patients with a history of corneal suture infections and delayed-onset endophthalmitis was identified. RESULTS: Over the 15-year period of the study, 68 patients were identified to have both positive corneal and intraocular cultures. Among them, six patients were identified to have a culture-proven, delayed-onset endophthalmitis that developed from a culture-positive corneal suture infection. All of the patients in the current study were using topical corticosteroids at the time of diagnosis. In four of six patients, there was documented manipulation of a suture before the development of endophthalmitis. Streptoccocus was identified as the causative organism in five of six patients in the current study. All of the Streptoccocus isolates were sensitive to vancomycin. The single case of Serratia marcescens endophthalmitis was sensitive to amikacin, ceftazidime, ciprofloxacin, gentamicin, and tobramycin. Treatment modalities varied and were guided by the attending ophthalmologist depending upon clinical presentation. One patient with severe Streptococcus pyogenes keratitis and endophthalmitis underwent a primary enucleation after developing a wound dehiscence. Of the remaining five patients, all received topical and intravitreal antibiotics. Therapeutic penetrating keratoplasty was performed in three patients. Pars plana vitrectomy was performed in two patients. Visual acuity outcomes ranged from 20/150 to no light perception. CONCLUSIONS: In the current study, Streptococcus was isolated in nearly all patients with delayed-onset endophthalmitis associated with corneal suture infections. Topical steroid use and suture manipulation were identified as associated factors for developing endophthalmitis. Visual acuity outcomes were poor despite the prompt recognition of endophthalmitis and appropriate antibiotic therapy

Phacoemulsification, pars plana vitrectomy and intraocular lens implant in eyes with proliferative diabetic retinopathy

PURPOSE: To evaluate the outcomes and the best technique for a combined phacoemulsification (PHACO), pars plana vitrectomy (PPV) and posterior chamber intraocular lens insertion (PCIOL) in one single procedure for patients with proliferative diabetic retinopathy. METHODS: We reviewed charts of 47 (53 eyes) patients with proliferative diabetic retinopathy who underwent combined phacoemulsification with posterior chamber intraocular lens implant and pars plana vitrectomy performed between January 1991 and September 1998 at the Bascom Palmer Eye Institute, eye hospital affiliated with the University of Miami. The study was done in conjunction with the Federal University of São Paulo. A total of 43 eyes from 40 patients were elected to participate in the study. RESULTS: The follow-up range was three to 60 months (mean 20 months). The age ranged from 37 to 77 years with a mean of 59. Preoperative visual acuity improved two lines or more in 26 (60.4%) eyes, remained the same in 9 (20.9%) and got worse in 8 (18.6%). In 10 (23.2%) eyes visual acuity improved to 20/40. The study showed to be statistically significant for the improvement of the final visual acuity. Recurrent vitreous hemorrhage was the most frequent postoperative complication found in 12 (27.9%) eyes and it was followed by transient anterior chamber reaction in 9 (20.9%) eyes. Intraoperative and postoperative complications related to phacoemulsification were rare. IOL capture was found in 2 (4.6%) eyes and intraocular lens subluxation in 1 (2.3%) eye. CONCLUSION: Combined phacoemulsification with posterior chamber intraocular lens implant and pars plana vitrectomy in proliferative diabetic retinopathy is a feasible procedure, well-tolerated and usually presents significant visual acuity improvement. One single procedure, to remove the cataract and to perform pars plana vitrectomy, instead of performing a second surgery that would be only to remove the cataract after the pars plana vitrectomy is safe, improves visual acuity and is also less aggressive for the patient. The potential for improving final visual acuity is limited by the severity of retinopathy.OBJETIVO: Avaliar a viabilidade da técnica de facoemulsificação para a extração da catarata com implante de lente intra-ocular combinada à vitrectomia via pars plana em olhos com retinopatia diabética proliferativa, em um único procedimento cirúrgico. MÉTODOS: Foram revisados os prontuários de 47 pacientes (53 olhos) com retinopatia diabética proliferativa e catarata que foram submetidos ao procedimento combinado de vitrectomia via pars plana, facoemulsificação e implante de lente intra-ocular no mesmo ato cirúrgico, entre janeiro de 1991 e setembro de 1998 no Bascom Palmer Eye Institute, hospital de olhos filiado à Universidade de Miami. O estudo foi realizado em conjunto com a Universidade Federal de São Paulo (UNIFESP). Participaram do estudo 43 olhos de 40 pacientes. RESULTADOS: O tempo de seguimento variou de três a 60 meses com média de 20 meses. A idade dos pacientes variou de 37 a 77 anos com média de 59 anos. A acuidade visual melhorou duas linhas ou mais em relação ao pré-operatório em 26 (60,4%) olhos, permaneceu a mesma em 9 (20,9%) e piorou em 8 (18,6%). Em (23,2%) 10 olhos a acuidade visual aumentou para 20/40. O teste estatístico chamado de teste do sinal mostrou-se estatisticamente significante na melhora da acuidade visual final. A complicação mais observada foi a hemorragia vítrea recorrente, ocorrendo em 12 (27,9%) olhos, seguida pela inflamação transitória da câmara anterior em 9 olhos (20,9%). Complicações intra-operatórias relacionadas à extração do cristalino foram raras. No pós-operatório observaram-se captura da lente intra-ocular em 2 (4,6 %) olhos e lente intra-ocular subluxada em 1 (2,3%) olho. CONCLUSÕES: A cirurgia combinada de facoemulsificação, implante de lente intra-ocular e vitrectomia via pars plana em olhos com retinopatia diabética é procedimento bem tolerado e geralmente apresenta bons resultados com relação à acuidade visual. Um único procedimento para remover a catarata e realizar a vitrectomia via pars plana, ao invés de se realizar uma segunda cirurgia, que seria somente para a remoção da catarata após a vitrectomia pars plana, é técnica segura e capaz de promover a melhora da acuidade visual além de ser menos agressiva para o paciente. O potencial para melhora da acuidade visual final é limitado pela gravidade da retinopatia diabética.Universidade Federal de São Paulo (UNIFESP)Universidade de Miami Bascom Palmer Eye InstituteUNIFESP, EPMSciEL

Ariel - Volume 2 Number 3

Editors Delvyn C. Case, Jr. Paul M. Fernhoff News Editors Richard Bonanno Daniel B. Gould Robin A. Edwards Lay-Out Editor Carol Dolinskas Sports Editor James J. Nocon Contributing Editors Michael J. Blecker Lin Sey Edwards Jack Guralnik W. Cherry Light Features Editor Steven A. Ager Donald A. Bergman Stephen P. Flynn Business Manager Nick Greg

Quantitative Serial MRI of the Treated Fibroid Uterus

There are no long-term medical treatments for uterine fibroids, and non-invasive biomarkers are needed to evaluate novel therapeutic interventions. The aim of this study was to determine whether serial dynamic contrast-enhanced MRI (DCE-MRI) and magnetization transfer MRI (MT-MRI) are able to detect changes that accompany volume reduction in patients administered GnRH analogue drugs, a treatment which is known to reduce fibroid volume and perfusion. Our secondary aim was to determine whether rapid suppression of ovarian activity by combining GnRH agonist and antagonist therapies results in faster volume reduction.Forty women were assessed for eligibility at gynaecology clinics in the region, of whom thirty premenopausal women scheduled for hysterectomy due to symptomatic fibroids were randomized to three groups, receiving (1) GnRH agonist (Goserelin), (2) GnRH agonist+GnRH antagonist (Goserelin and Cetrorelix) or (3) no treatment. Patients were monitored by serial structural, DCE-MRI and MT-MRI, as well as by ultrasound and serum oestradiol concentration measurements from enrolment to hysterectomy (approximately 3 months).A volumetric treatment effect assessed by structural MRI occurred by day 14 of treatment (9% median reduction versus 9% increase in untreated women; P = 0.022) and persisted throughout. Reduced fibroid perfusion and permeability assessed by DCE-MRI occurred later and was demonstrable by 2-3 months (43% median reduction versus 20% increase respectively; P = 0.0093). There was no apparent treatment effect by MT-MRI. Effective suppression of oestradiol was associated with early volume reduction at days 14 (P = 0.041) and 28 (P = 0.0061).DCE-MRI is sensitive to the vascular changes thought to accompany successful GnRH analogue treatment of uterine fibroids and should be considered for use in future mechanism/efficacy studies of proposed fibroid drug therapies. GnRH antagonist administration does not appear to accelerate volume reduction, though our data do support the role of oestradiol suppression in GnRH analogue treatment of fibroids.ClinicalTrials.gov NCT00746031

Формирование эмоциональной культуры как компонента инновационной культуры студентов

Homozygosity has long been associated with rare, often devastating, Mendelian disorders1 and Darwin was one of the first to recognise that inbreeding reduces evolutionary fitness2. However, the effect of the more distant parental relatedness common in modern human populations is less well understood. Genomic data now allow us to investigate the effects of homozygosity on traits of public health importance by observing contiguous homozygous segments (runs of homozygosity, ROH), which are inferred to be homozygous along their complete length. Given the low levels of genome-wide homozygosity prevalent in most human populations, information is required on very large numbers of people to provide sufficient power3,4. Here we use ROH to study 16 health-related quantitative traits in 354,224 individuals from 102 cohorts and find statistically significant associations between summed runs of homozygosity (SROH) and four complex traits: height, forced expiratory lung volume in 1 second (FEV1), general cognitive ability (g) and educational attainment (nominal p<1 × 10−300, 2.1 × 10−6, 2.5 × 10−10, 1.8 × 10−10). In each case increased homozygosity was associated with decreased trait value, equivalent to the offspring of first cousins being 1.2 cm shorter and having 10 months less education. Similar effect sizes were found across four continental groups and populations with different degrees of genome-wide homozygosity, providing convincing evidence for the first time that homozygosity, rather than confounding, directly contributes to phenotypic variance. Contrary to earlier reports in substantially smaller samples5,6, no evidence was seen of an influence of genome-wide homozygosity on blood pressure and low density lipoprotein (LDL) cholesterol, or ten other cardio-metabolic traits. Since directional dominance is predicted for traits under directional evolutionary selection7, this study provides evidence that increased stature and cognitive function have been positively selected in human evolution, whereas many important risk factors for late-onset complex diseases may not have been

Search for gravitational waves from Scorpius X-1 in the second Advanced LIGO observing run with an improved hidden Markov model

We present results from a semicoherent search for continuous gravitational waves from the low-mass x-ray binary Scorpius X-1, using a hidden Markov model (HMM) to track spin wandering. This search improves on previous HMM-based searches of LIGO data by using an improved frequency domain matched filter, the J-statistic, and by analyzing data from Advanced LIGO's second observing run. In the frequency range searched, from 60 to 650 Hz, we find no evidence of gravitational radiation. At 194.6 Hz, the most sensitive search frequency, we report an upper limit on gravitational wave strain (at 95% confidence) of h095%=3.47×10-25 when marginalizing over source inclination angle. This is the most sensitive search for Scorpius X-1, to date, that is specifically designed to be robust in the presence of spin wandering. © 2019 American Physical Society

Search for gravitational waves from Scorpius X-1 in the second Advanced LIGO observing run with an improved hidden Markov model

We present results from a semicoherent search for continuous gravitational waves from the low-mass x-ray binary Scorpius X-1, using a hidden Markov model (HMM) to track spin wandering. This search improves on previous HMM-based searches of LIGO data by using an improved frequency domain matched filter, the J-statistic, and by analyzing data from Advanced LIGO’s second observing run. In the frequency range searched, from 60 to 650 Hz, we find no evidence of gravitational radiation. At 194.6 Hz, the most sensitive search frequency, we report an upper limit on gravitational wave strain (at 95% confidence) of h95%0=3.47×10−25 when marginalizing over source inclination angle. This is the most sensitive search for Scorpius X-1, to date, that is specifically designed to be robust in the presence of spin wandering