Proof of concept, randomized, placebo-controlled study of the effect of simvastatin on the course of age-related macular degeneration

BACKGROUND: HMG Co-A reductase inhibitors are ubiquitous in our community yet their potential role in age-related macular degeneration (AMD) remains to be determined. METHODOLOGY/PRINCIPAL FINDINGS: OBJECTIVES: To evaluate the effect of simvastatin on AMD progression and the effect modification by polymorphism in apolipoprotein E (ApoE) and complement factor H (CFH) genes. DESIGN: A proof of concept double-masked randomized controlled study. PARTICIPANTS: 114 participants aged 53 to 91 years, with either bilateral intermediate AMD or unilateral non-advanced AMD (with advanced AMD in fellow eye), BCVA ≥ 20/60 in at least one eye, and a normal lipid profile. INTERVENTION: Simvastatin 40 mg/day or placebo, allocated 1:1. MAIN OUTCOME MEASURES: Progression of AMD either to advanced AMD or in severity of non-advanced AMD. Results. The cumulative AMD progression rates were 70% in the placebo and 54% in the simvastatin group. Intent to treat multivariable logistic regression analysis, adjusted for age, sex, smoking and baseline AMD severity, showed a significant 2-fold decrease in the risk of progression in the simvastatin group: OR 0.43 (0.18-0.99), p = 0.047. Post-hoc analysis stratified by baseline AMD severity showed no benefit from treatment in those who had advanced AMD in the fellow eye before enrolment: OR 0.97 (0.27-3.52), p = 0.96, after adjusting for age, sex and smoking. However, there was a significant reduction in the risk of progression in the bilateral intermediate AMD group compared to placebo [adjusted OR 0.23 (0.07-0.75), p = 0.015]. The most prominent effect was observed amongst those who had the CC (Y402H) at risk genotype of the CFH gene [OR 0.08 (0.02-0.45), p = 0.004]. No evidence of harm from simvastatin intervention was detected. CONCLUSION/SIGNIFICANCE: Simvastatin may slow progression of non-advanced AMD, especially for those with the at risk CFH genotype CC (Y402H). Further exploration of the potential use of statins for AMD, with emphasis on genetic subgroups, is warranted. TRIAL REGISTRATION: Australian New Zealand Clinical Trial Registry (ANZCTR) ACTRN1260500032065

Differential White Blood Cell Count and Type 2 Diabetes: Systematic Review and Meta-Analysis of Cross-Sectional and Prospective Studies

Objective: Biological evidence suggests that inflammation might induce type 2 diabetes (T2D), and epidemiological studies have shown an association between higher white blood cell count (WBC) and T2D. However, the association has not been systematically investigated.Research Design and Methods: Studies were identified through computer-based and manual searches. Previously unreported studies were sought through correspondence. 20 studies were identified (8,647 T2D cases and 85,040 non-cases). Estimates of the association of WBC with T2D were combined using random effects meta-analysis; sources of heterogeneity as well as presence of publication bias were explored.Results: The combined relative risk (RR) comparing the top to bottom tertile of the WBC count was 1.61 (95% CI: 1.45; 1.79, p = 1.5*10(-18)). Substantial heterogeneity was present (I-2 = 83%). For granulocytes the RR was 1.38 (95% CI: 1.17; 1.64, p = 1.5*10(-4)), for lymphocytes 1.26 (95% CI: 1.02; 1.56, p = 0.029), and for monocytes 0.93 (95% CI: 0.68; 1.28, p = 0.67) comparing top to bottom tertile. In cross-sectional studies, RR was 1.74 (95% CI: 1.49; 2.02, p = 7.7*10(-13)), while in cohort studies it was 1.48 (95% CI: 1.22; 1.79, p = 7.7*10(-5)). We assessed the impact of confounding in EPIC-Norfolk study and found that the age and sex adjusted HR of 2.19 (95% CI: 1.74; 2.75) was attenuated to 1.82 (95% CI: 1.45; 2.29) after further accounting for smoking, T2D family history, physical activity, education, BMI and waist circumference.Conclusions: A raised WBC is associated with higher risk of T2D. The presence of publication bias and failure to control for all potential confounders in all studies means the observed association is likely an overestimate

Remove, rotate, and reimplant: a novel technique for the management of exposed porous anophthalmic implants in eviscerated patients

PURPOSE: To describe and to evaluate a new and relatively easy technique for porous implant exposure repair. METHODS: Eleven patients with exposed porous orbital implants after evisceration were included in this study. Five patients with large exposures (diameter>7 mm) and six patients with small exposures of orbital implants (diameter<7 mm) that persisted despite posterior vaulting of the prosthesis and usage of antibiotics and steroids for more than 6 weeks, underwent revision surgery with the remove-rotate-reimplant technique (3R technique). Negative microbiological culture taken from the exposed socket surface before surgery was the major inclusion criterion. Five patients with insufficient conjunctival tissue also underwent additional mucosa or hard palate grafting of the defect in addition to the remove-rotate-reimplant procedure. RESULTS: Patients have been followed up for more than 18 months (ranging from 18–30 months). None of them received motility peg insertion after repair. Implant reexposure was detected in one patient during the follow-up period, which was managed by dermis fat grafting with implant removal. CONCLUSION: The remove-rotate-reimplant technique is an effective surgical method for repairing exposed porous anophthalmic implants after evisceration with a 90% success in this study. It avoids the removal of the implant from the sclera, which is a traumatic procedure that may lead to the tearing and loss of scleral tissue covering the implant. Saving the porous implant and scleral cover reduces the surgical time and cost

Orbital Implants and Wrapping Materials

Following globe removal, the surgeon must determine the best orbital implant to place into the anophthalmic socket. A decision on appropriate implant size, whether to place a porous or nonporous implant, and a patient’s total clinical picture must be considered to prevent future complications. Other considerations, including whether to wrap an implant and place a motility peg, must also be made. The modern implant is built on the foundation of anophthalmic socket reconstruction—implant retention, volume replacement, and adequate prosthetic motility. This chapter will review the special considerations the ophthalmic surgeon must weigh when choosing an orbital implant following enucleation and evisceration surgeries