Sofia Androudi

Global, regional, and national age-sex specific mortality for 264 causes of death, 1980-2016

The last 37 years have featured declining rates of communicable, maternal, neonatal, and nutritional diseases across all quintiles of SDI, with faster than expected gains for many locations relative to their SDI. A global shift towards deaths at older ages suggests success in reducing many causes of early death. YLLs have increased globally for causes such as diabetes mellitus or some neoplasms, and in some locations for causes such as drug use disorders, and conflict and terrorism. Increasing levels of YLLs may reflect outcomes from conditions that required high levels of care but for which effective treatments remain elusive, potentially increasing costs to health systems.Summary Background Monitoring levels and trends in premature mortality is crucial to understanding how societies can address prominent sources of early death. The Global Burden of Disease 2016 Study (GBD 2016) provides a comprehensive assessment of cause-specific mortality for 264 causes in 195 locations from 1980 to 2016. This assessment includes evaluation of the expected epidemiological transition with changes in development and where local patterns deviate from these trends. Methods We estimated cause-specific deaths and years of life lost (YLLs) by age, sex, geography, and year. YLLs were calculated from the sum of each death multiplied by the standard life expectancy at each age. We used the GBD cause of death database composed of: vital registration (VR) data corrected for under-registration and garbage coding; national and subnational verbal autopsy (VA) studies corrected for garbage coding; and other sources including surveys and surveillance systems for specific causes such as maternal mortality. To facilitate assessment of quality, we reported on the fraction of deaths assigned to GBD Level 1 or Level 2 causes that cannot be underlying causes of death (major garbage codes) by location and year. Based on completeness, garbage coding, cause list detail, and time periods covered, we provided an overall data quality rating for each location with scores ranging from 0 stars (worst) to 5 stars (best). We used robust statistical methods including the Cause of Death Ensemble model (CODEm) to generate estimates for each location, year, age, and sex. We assessed observed and expected levels and trends of cause-specific deaths in relation to the Socio-demographic Index (SDI), a summary indicator derived from measures of average income per capita, educational attainment, and total fertility, with locations grouped into quintiles by SDI. Relative to GBD 2015, we expanded the GBD cause hierarchy by 18 causes of death for GBD 2016. Findings The quality of available data varied by location. Data quality in 25 countries rated in the highest category (5 stars), while 48, 30, 21, and 44 countries were rated at each of the succeeding data quality levels. Vital registration or verbal autopsy data were not available in 27 countries, resulting in the assignment of a zero value for data quality. Deaths from non-communicable diseases (NCDs) represented 72·3% (95% uncertainty interval [UI] 71·2–73·2) of deaths in 2016 with 19·3% (18·5–20·4) of deaths in that year occurring from communicable, maternal, neonatal, and nutritional (CMNN) diseases and a further 8·43% (8·00–8·67) from injuries. Although age-standardised rates of death from NCDs decreased globally between 2006 and 2016, total numbers of these deaths increased; both numbers and age-standardised rates of death from CMNN causes decreased in the decade 2006–16—age-standardised rates of deaths from injuries decreased but total numbers varied little. In 2016, the three leading global causes of death in children under-5 were lower respiratory infections, neonatal preterm birth complications, and neonatal encephalopathy due to birth asphyxia and trauma, combined resulting in 1·80 million deaths (95% UI 1·59 million to 1·89 million). Between 1990 and 2016, a profound shift toward deaths at older ages occurred with a 178% (95% UI 176–181) increase in deaths in ages 90–94 years and a 210% (208–212) increase in deaths older than age 95 years. The ten leading causes by rates of age-standardised YLL significantly decreased from 2006 to 2016 (median annualised rate of change was a decrease of 2·89%); the median annualised rate of change for all other causes was lower (a decrease of 1·59%) during the same interval. Globally, the five leading causes of total YLLs in 2016 were cardiovascular diseases; diarrhoea, lower respiratory infections, and other common infectious diseases; neoplasms; neonatal disorders; and HIV/AIDS and tuberculosis. At a finer level of disaggregation within cause groupings, the ten leading causes of total YLLs in 2016 were ischaemic heart disease, cerebrovascular disease, lower respiratory infections, diarrhoeal diseases, road injuries, malaria, neonatal preterm birth complications, HIV/AIDS, chronic obstructive pulmonary disease, and neonatal encephalopathy due to birth asphyxia and trauma. Ischaemic heart disease was the leading cause of total YLLs in 113 countries for men and 97 countries for women. Comparisons of observed levels of YLLs by countries, relative to the level of YLLs expected on the basis of SDI alone, highlighted distinct regional patterns including the greater than expected level of YLLs from malaria and from HIV/AIDS across sub-Saharan Africa; diabetes mellitus, especially in Oceania; interpersonal violence, notably within Latin America and the Caribbean; and cardiomyopathy and myocarditis, particularly in eastern and central Europe. The level of YLLs from ischaemic heart disease was less than expected in 117 of 195 locations. Other leading causes of YLLs for which YLLs were notably lower than expected included neonatal preterm birth complications in many locations in both south Asia and southeast Asia, and cerebrovascular disease in western Europe. Interpretation The past 37 years have featured declining rates of communicable, maternal, neonatal, and nutritional diseases across all quintiles of SDI, with faster than expected gains for many locations relative to their SDI. A global shift towards deaths at older ages suggests success in reducing many causes of early death. YLLs have increased globally for causes such as diabetes mellitus or some neoplasms, and in some locations for causes such as drug use disorders, and conflict and terrorism. Increasing levels of YLLs might reflect outcomes from conditions that required high levels of care but for which effective treatments remain elusive, potentially increasing costs to health systems. Funding Bill & Melinda Gates Foundation.

Primary pars plana vitrectomy versus scleral buckle surgery for the treatment of pseudophakic retinal detachment: a randomized clinical trial.

Objective: To compare the anatomical and functional outcome of scleral buckle (SB) surgery with that of pars plana vitrectomy (PPV) alone in the treatment of primary rhegmatogenous pseudophakic retinal detachment (RD). Methods: In this prospective, randomized clinical trial, 150 eyes of 150 patients with pseudophakic RD and proliferative vitreoretinopathy (PVR) stage B or less were randomized to SB surgery (75 eyes) or primary PPV (75 eyes). SB surgery involved break localization, cryotherapy, placement of a circumferential 240 style 2.5-mm solid silicone band, combined with a local buckle when indicated, and transscleral drainage of subretinal fluid. PPV included extensive vitreous removal, perfluoro-n-octane injection or endodrainage of subretinal fluid to flatten the retina, cryopexy treatment of breaks, and fluid/air exchange with injection of 20% SF6. Postoperative follow-up was 1 year. Break diagnosis, operating time, intraoperative and postoperative complications, retinal reattachment rate for single as well as multiple surgeries, axial length changes, and best-corrected visual acuity at 1 year after surgery were the main outcome measures. Results: The number of eyes that were diagnosed with additional breaks interoperatively was higher in the PPV group (P = 0.004, &khgr;2 test). Mean operating time was significantly less (P = 0.0001, t-test) in the PPV group. With a single surgery, the retina was reattached in 62 eyes (83%) in the SB surgery group and in 71 eyes (94%) in the PPV group (P = 0.037, Fisher exact test). With subsequent surgeries, final anatomical reattachment was achieved in 71 cases in the SB surgery group and in 74 cases in the PPV group (P = 0.37, Fisher exact test). Mean axial length change at 1 year was 0.95 mm in the SB surgery group and 0.1 mm in the PPV group (P = 0.0001, t-test). Mean final best-corrected visual acuity (logMAR) was 0.40 in the SB surgery group and 0.33 in the PPV group (P = 0.26, t-test). Conclusions: Primary PPV offers potential advantages over SB surgery in the treatment of pseudophakic RD, including less operating time, accurate diagnosis of breaks, higher reattachment rate with a single surgery, and no postoperative axial length changes. Retinal reattachment rate with multiple surgeries and final visual acuity at 1 year were similar for SB surgery and PPV.

Secukinumab in the Treatment of Noninfectious Uveitis: Results of Three Randomized, Controlled Clinical Trials

PURPOSE To determine the efficacy and safety of different doses of secukinumab, a fully human monoclonal antibody for targeted interleukin-17A blockade, in patients with noninfectious uveitis. DESIGN Three multicenter, randomized, double-masked, placebo-controlled, dose-ranging phase III studies: SHIELD, INSURE, and ENDURE. PARTICIPANTS A total of 118 patients with Behçets uveitis (SHIELD study); 31 patients with active, noninfectious, non-Behçets uveitis (INSURE study); and 125 patients with quiescent, noninfectious, non-Behçets uveitis (ENDURE study) were enrolled. METHODS After an initial subcutaneous (s.c.) loading phase in each treatment arm, patients received s.c. maintenance therapy with secukinumab 300 mg every 2 weeks (q2w), secukinumab 300 mg monthly (q4w), or placebo in the SHIELD study; secukinumab 300 mg q2w, secukinumab 300 mg q4w, secukinumab 150 mg q4w, or placebo in the INSURE study; or secukinumab 300 mg q2w, secukinumab 300 mg q4w, secukinumab 150 mg q4w, or placebo in the ENDURE study. MAIN OUTCOME MEASURES Reduction of uveitis recurrence or vitreous haze score during withdrawal of concomitant immunosuppressive medication (ISM). Other end points included best-corrected visual acuity, ISM use (expressed as a standardized ISM score), and safety outcomes. RESULTS After completion or early termination of each trial, there were no statistically significant differences in uveitis recurrence between the secukinumab treatment groups and placebo groups in any study. Secukinumab was associated with a significant reduction in mean total post-baseline ISM score (P = 0.019; 300 mg q4w vs. placebo) in the SHIELD study. Likewise, secukinumab was associated with a greater median reduction in ISM score versus placebo in the INSURE study, although no statistical analysis of the difference was conducted because of the small sample size. Overall, there was no loss in visual acuity reported in any treatment group during follow-up in all 3 studies. According to descriptive safety statistics, the frequencies of ocular and nonocular adverse events seemed to be slightly higher among secukinumab groups versus placebo across the 3 studies. CONCLUSIONS The primary efficacy end points of the 3 studies were not met. The secondary efficacy data from these studies suggest a beneficial effect of secukinumab in reducing the use of concomitant ISM.

Safety and efficacy of intravitreal triamcinolone acetonide for uveitic macular edema.

Background: To evaluate the safety and efficacy of intravitreal triamcinolone acetonide (TA) for treating macular edema secondary to non-infectious uveitis. Methods: Retrospective review of sixteen patients (20 eyes) with chronic cystoid macular edema (CME) as a consequence of controlled intermediate uveitis, posterior uveitis, or panuveitis who received at least one intravitreal injection of TA. Main outcome measures were visual acuity (VA), intraocular pressure (IOP), formation or progression of an existing cataract, and CME resolution during the follow-up period. Results: At last follow-up, VA showed improvement (compared to baseline) in 11 eyes (55%), deterioration in three eyes (15%), remained completely unchanged in one eye (5%), and showed improvement initially but returned to baseline levels in five eyes (25%). At last follow-up, CME had relapsed or was still present in 10 of the eyes (50%). The remaining eyes showed complete resolution of the CME, without evidence of recurrence during the follow-up time. Mean VA at last follow-up showed statistically significant improvement (p = 0.02) in nonvitrectomized eyes (mean baseline VA: 1.14 ± 0.58; mean final VA: 0.96 ± 0.66) compared to the almost unaltered mean visual acuity for vitrectomized eyes (mean baseline VA: 0.76 ± 0.41; mean final VA: 0.71 ± 0.48)(p = 0.40, paired samples t-test). Elevation of IOP was transient in all cases and responded well to topical medications, except for one patient who required placement of an Ahmed valve. Preexisting cataract progressed in three of the 15 phakic eyes (20%). One patient developed a retinal detachment and required additional surgery to reattach it. Patients were followed for a mean of 34 weeks (median: 32 weeks; range: 19–56 weeks). Conclusions: Intravitreal TA may play a role in the treatment of uveitis-related CME. Further controlled studies are necessary to test this hypothesis.

Intravitreal adalimumab for refractory uveitis-related macular edema.

OBJECTIVE To evaluate the safety and efficacy of intravitreal adalimumab injections on refractory cystoid macular edema (CME) secondary to noninfectious uveitis. DESIGN Prospective, noncomparative, interventional case series. PARTICIPANTS Eight consecutive patients with controlled uveitis and chronic, refractory CME who had failed steroid treatment. INTERVENTION Intravitreal adalimumab injections were given monthly for 3 months. MAIN OUTCOME MEASURES Mean change in central retinal thickness (CRT) on optical coherence tomography (OCT); secondary objective was the mean change in best-corrected visual acuity (BCVA). RESULTS Five of the eight patients completed the 6-month follow-up. For all 5 patients, the changes in BCVA from baseline to 3 months were not statistically significant (P=0.070). Similarly, the change in BCVA from baseline to 6 months was not statistically significant (P=1.0). The mean CRT at baseline was 692 microm. The changes from baseline to 3 months were not statistically significant (P=0.466); the changes from baseline to 6 months were also not statistically significant (P=0.808). We did not observe any ocular or systemic adverse effects. CONCLUSIONS Intravitreal adalimumab showed no efficacy in improving BCVA or reducing CRT in patients with chronic uveitic macular edema.

Combined pars plana vitrectomy and phacoemulsification to restore visual acuity in patients with chronic uveitis

Purpose: To report the outcomes of combined phacoemulsification and pars plana vitrectomy (PPV) to restore visual acuity in patients with cataract and posterior segment involvement secondary to chronic uveitis. Setting: Ocular Immunology and Uveitis Service, Massachusetts Eye and Ear Infirmary, Harvard Medical School, Boston, Massachusetts, USA. Methods: This study comprised 34 patients (20 women, 14 men; 36 eyes) with posterior segment involvement secondary to chronic uveitis who had combined phacoemulsification and PPV from 1998 to 2002. The main outcome measures were visual acuity, intraocular pressure, and cystoid macular edema. Results: The mean patient age was 45 years ± 16.09 (SD). The mean duration of uveitis before surgery was 56 ± 44.17 months. In 24 eyes (66.7%), an intraocular lens (IOL) was implanted during surgery; 12 eyes (33.3%) were left aphakic. Five eyes (13.8%) received an intraocular steroid injection intraoperatively. Visual acuity improved in 26 eyes (72.2%), deteriorated in 5 (13.9%), and was unchanged in 5 (13.9%). The main reason for decreased visual acuity was refractory macular edema. During the follow‐up, 2 IOLs were explanted secondary to lens intolerance. One IOL was repositioned because of iris capture by the haptics, and 1 dislocated inferiorly, causing monocular diplopia. The mean follow‐up was 23.4 ± 16.7 months. Conclusions: Results indicate that combined phacoemulsification and PPV is a feasible technique for the removal of cataract and pathologic vitreous in eyes with chronic uveitis. Although the exact role of vitrectomy in patients with uveitis remains to be determined, the combined surgery successfully restored useful vision in most cases.

Angiogenic Growth Factors and their Inhibitors in Diabetic Retinopathy

Diabetic retinopathy is considered one of the vision-threatening diseases among working-age population. The pathogenesis of the disease is regarded multifactorial and complex: capillary basement membrane thickening, loss of pericytes, microaneuryms, loss of endothelial cells, blood retinal barrier breakdown and other anatomic lesions might contribute to macular edema and/or neovascularization the two major and sight threatening complications of diabetic retinopathy. A number of proangiogenic, angiogenic and antiangiogenic factors are involved in the pathogenesis and progression of diabetic retinal disease, Vascular Endothelial Growth Factor (VEGF) being one of the most important. Other growth factors, which are known to participate in the pathogenesis of the disease, are: Platelet Derived Growth Factor (PDGF), Fibroblast Growth Factor (FGF), Hepatocyte Growth Factor (HGF), Transforming Growth Factor (TGF), Placental Endothelial Cell Growth Factor (PlGF), Connective Tissue Growth Factor (CTGF). Other molecules that are involved in the disease mechanisms are: intergrins, angiopoietins, protein kinase C (PKC), ephrins, interleukins, leptin, angiotensin, monocyte chemotactic protein (MCP), vascular cell adhesion molecule (VCAM), tissue plasminogen activator (TPA), and extracellular matrix metalloproteinases (ECM-MMPs). However, the intraocular concentration of angiogenic factors is counterbalanced by the ocular synthesis of several antioangiogenic factors such as pigment epithelial derived factor (PEDF), angiostatin, endostatin, thrombospondin, steroids, atrial natriuretic peptide (ANP), inteferon, aptamer, monoclonal antibodies, VEGF receptor blocker, VEGF gene suppressors, intracellular signal transduction inhibitors, and extracellular matrix antagonists. Growth stimulation or inhibition by these factors depends on the state of development and differentiation of the target tissue. The mechanisms of angiogenesis factor action are very different and most factors are multipotential; they stimulate proliferation or differentiation of endothelial cells. This review attempts to briefly outline the knowledge about peptide growth factor involvement in diabetic retinopathy. Further ongoing research may provide better understanding of molecular mechanisms, disease pathogenesis and therapeutic interactions.

Lamellar macular holes: tomographic features and surgical outcome.

PURPOSE To categorize tomographically the distinct entity of lamellar macular holes (MH) and present the surgical outcomes in our patient cohort. DESIGN Prospective observational and interventional study. METHODS All cases were clinically diagnosed initially with slit-lamp biomicroscopy and confirmed with the use of optical coherence tomography (OCT)-3. Cases either were observed or underwent surgical intervention with a 25-gauge pars-plana vitrectomy (PPV) technique. Follow-up was at least 12 months for all cases and ranged from 12 to 46 months. Main outcome measures included closure of the lamellar MH following surgical intervention; best-corrected visual acuity (BCVA) preoperatively and postoperatively for the cases that underwent surgery. RESULTS We identified 32 eyes of 30 patients with lamellar MH diagnosed by OCT-3. Lamellar MHs were classified into 3 different categories: 1) associated with macular epiretinal membrane (ERM) (20 eyes), 2) secondary to cystoid macular edema (8 eyes), and 3) attributable to partial-thickness macular avulsion after acute posterior vitreous detachment (PVD) (4 eyes). Visual acuity was less affected in cases with an associated ERM. Surgery included PPV and ERM removal (when present), followed by internal limiting membrane (ILM) removal and 16% C(3)F(8) injection. Postoperatively, BCVA improved in 17 out of the 20 cases (85%) operated from the first group of patients; 3 cases retained the same BCVA preoperatively and postoperatively. Mean BCVA improvement in the first group was 2.6 Snellen lines, which was statistically significant (P = .002, paired t test). CONCLUSIONS Surgical treatment of lamellar MH associated with an ERM may result in preservation or improvement of visual acuity, by relieving the tangential traction caused by the ERM.

Vitreous and serum levels of vascular endothelial growth factor and platelet-derived growth factor and their correlation in patients with non-proliferative diabetic retinopathy and clinically significant macula oedema.

Purpose:  To investigate possible correlations between vitreous and/or serum levels of platelet‐derived growth factor isoforms (PDGF‐AA, ‐AB and ‐BB) with parameters associated with non‐proliferative diabetic retinopathy (NPDR) and clinically significant macula oedema (CSMO); to compare the results to relevant results regarding vascular endothelial growth factor (VEGF), which is an established growth factor affecting NPDR.

Rituximab Treatment for Persistent Scleritis Associated with Rheumatoid Arthritis

Purpose: To report a clinical case of a patient with severe scleritis associated with rheumatoid arthritis (RA) refractive to conventional treatment that was treated effectively with rituximab. Methods and Results: A 55-year-old man with RA, on etanercept and oral methotrexate, was referred with diagnosis of acute stromal keratitis, anterior uveitis, and anterior nodular scleritis in his right eye. Cyclophosphamide induced complete regression of acute stromal keratitis and anterior uveitis, but scleritis was still active and persistent. After two 1000-mg infusions of rituximab, scleritis regressed completely and is still in remission 9 months after the second rituximab infusion, without any concomitant use of oral steroids. Conclusion: Rituximab may be a treatment alternative in severe scleritis that is refractive to conventional therapy. Considering its safety profile, further studies are needed to refine its mechanism of action, optimal indications, and dosing in ocular inflammation.