LIGHTSITE III: 13-Month Efficacy and Safety Evaluation of Multiwavelength Photobiomodulation in Nonexudative (Dry) Age-Related Macular Degeneration Using the LumiThera Valeda Light Delivery System.

PURPOSE The LIGHTSITE III study evaluated multiwavelength photobiomodulation (PBM) therapy in nonexudative (dry) AMD using the LumiThera Valeda® Light Delivery System. METHODS LIGHTSITE III is a randomized, controlled trial to assess the safety and effectiveness of PBM in dry AMD. Subjects were treated with multiwavelength PBM (590, 660 and 850 nm) or Sham treatment delivered 9 treatments over 3-5 weeks every four months over 24 months. Subjects were assessed for efficacy and safety outcomes. Data from the 13-month analysis are presented in this report. RESULTS A total of 100 subjects (148 eyes) with dry AMD were randomized. LIGHTSITE III met the primary efficacy BCVA endpoint with a significant difference between PBM (n = 91 eyes) and Sham (n = 54 eyes) groups (Between group difference: 2.4 letters (SE 1.15), CI: -4.7 - -0.1, p = 0.02)(PBM alone: 5.4 letters (SE 0.96), CI: 3.5 - 7.3, p < 0.0001; Sham alone: 3.0 letters (SE 1.13), CI: 0.7 - 5.2, p < 0.0001). The PBM group showed a significant decrease in new onset GA (p = 0.024, Fisher exact test, odds ratio 9.4). A favorable safety profile was observed. CONCLUSIONS LIGHTSITE III provides a prospective, randomized controlled trial showing improved clinical and anatomical outcomes in intermediate dry AMD following PBM

X-chromosome and kidney function:evidence from a multi-trait genetic analysis of 908,697 individuals reveals sex-specific and sex-differential findings in genes regulated by androgen response elements

X-chromosomal genetic variants are understudied but can yield valuable insights into sexually dimorphic human traits and diseases. We performed a sex-stratified cross-ancestry X-chromosome-wide association meta-analysis of seven kidney-related traits (n = 908,697), identifying 23 loci genome-wide significantly associated with two of the traits: 7 for uric acid and 16 for estimated glomerular filtration rate (eGFR), including four novel eGFR loci containing the functionally plausible prioritized genes ACSL4, CLDN2, TSPAN6 and the female-specific DRP2. Further, we identified five novel sex-interactions, comprising male-specific effects at FAM9B and AR/EDA2R, and three sex-differential findings with larger genetic effect sizes in males at DCAF12L1 and MST4 and larger effect sizes in females at HPRT1. All prioritized genes in loci showing significant sex-interactions were located next to androgen response elements (ARE). Five ARE genes showed sex-differential expressions. This study contributes new insights into sex-dimorphisms of kidney traits along with new prioritized gene targets for further molecular research.</p

Adolescent Brain Development and the Risk for Alcohol and Other Drug Problems

Dynamic changes in neurochemistry, fiber architecture, and tissue composition occur in the adolescent brain. The course of these maturational processes is being charted with greater specificity, owing to advances in neuroimaging and indicate grey matter volume reductions and protracted development of white matter in regions known to support complex cognition and behavior. Though fronto-subcortical circuitry development is notable during adolescence, asynchronous maturation of prefrontal and limbic systems may render youth more vulnerable to risky behaviors such as substance use. Indeed, binge-pattern alcohol consumption and comorbid marijuana use are common among adolescents, and are associated with neural consequences. This review summarizes the unique characteristics of adolescent brain development, particularly aspects that predispose individuals to reward seeking and risky choices during this phase of life, and discusses the influence of substance use on neuromaturation. Together, findings in this arena underscore the importance of refined research and programming efforts in adolescent health and interventional needs

An assessment of prevalence of Type 1 CFI rare variants in European AMD, and why lack of broader genetic data hinders development of new treatments and healthcare access

PurposeAdvanced age-related macular degeneration (AAMD) risk is associated with rare complement Factor I (FI) genetic variants associated with low FI protein levels (termed ‘Type 1’), but it is unclear how variant prevalences differ between AMD patients from different ethnicities.MethodsCollective prevalence of Type 1 CFI rare variant genotypes were examined in four European AAMD datasets. Collective minor allele frequencies (MAFs) were sourced from the natural history study SCOPE, the UK Biobank, the International AMD Genomics Consortium (IAMDGC), and the Finnish Biobank Cooperative (FINBB), and compared to paired control MAFs or background population prevalence rates from the Genome Aggregation Database (gnomAD). Due to a lack of available genetic data in non-European AAMD, power calculations were undertaken to estimate the AAMD population sizes required to identify statistically significant association between Type 1 CFI rare variants and disease risk in different ethnicities, using gnomAD populations as controls.ResultsType 1 CFI rare variants were enriched in all European AAMD cohorts, with odds ratios (ORs) ranging between 3.1 and 7.8, and a greater enrichment was observed in dry AMD from FINBB (OR 8.9, 95% CI 1.49–53.31). The lack of available non-European AAMD datasets prevented us exploring this relationship more globally, however a statistical association may be detectable by future sequencing studies that sample approximately 2,000 AAMD individuals from Ashkenazi Jewish and Latino/Admixed American ethnicities.ConclusionsThe relationship between Type 1 CFI rare variants increasing odds of AAMD are well established in Europeans, however the lack of broader genetic data in AAMD has adverse implications for clinical development and future commercialisation strategies of targeted FI therapies in AAMD. These findings emphasise the importance of generating more diverse genetic data in AAMD to improve equity of access to new treatments and address the bias in health care.</p

Surgical Management of Posteriorly Dislocated Silicone Plate Haptic Intraocular Lenses

To report a large series of delayed posterior dislocation of silicone plate haptic intraocular lenses after Nd:YAG laser capsulotomy and discuss the surgical management of this complication. We reviewed the records of 11 consecutive patients (11 eyes) with delayed onset of posterior dislocation of a plate haptic silicone intraocular lens. The cause of the posterior capsular defect, time to dislocation, surgical management techniques, complications, and visual outcome were recorded. In eight of the 11 eyes, the silicone plate haptic intraocular lens dislocated an average of 1.8 months (range, 0 to 6.5 months) after Nd:YAG posterior capsulotomy. The other three eyes had surgical complications at the time of cataract extraction that compromised posterior capsular or zonular integrity and led to silicone plate haptic intraocular lens dislocation from 9 weeks to 6 months (mean, 3.6 months) postoperatively. Surgical management consisted of pars plana vitrectomy with intraocular lens repositioning (six eyes) or exchange (five eyes). The average follow-up period after intraocular lens repositioning or exchange was 6.5 months (range, 1 to 14 months). Best-corrected visual acuity at the last follow-up examination measured 20/40 or better in all but one eye that had preexisting macular disease. Cataract surgeons and patients should be aware of the potential for plate haptic silicone intraocular lenses to undergo delayed posterior dislocation through capsular defects. This complication can be managed effectively with vitrectomy and either repositioning or exchange of the implant. Postoperative visual acuity is generally excellent, and complications are minimal

Gender Identity, Hormone Therapy, and Cardiovascular Disease Risk

Transgender individuals represent a medically underserved and under researched population. There is a growing number of studies illustrating the importance of hormone therapy treatments in transgender men and women to assist ameliorating gender dysphoria and promoting well-being. However, the cardiovascular effects of these hormones are controversial. Large longitudinal epidemiological studies of cardiovascular event outcomes in these populations do not exist. In addition, studies of cardiovascular complications of transgender hormone therapy are limited in number and complicated by poor control of medication regimen, presence of gender confirming surgery, use of prescribed medications for prevailing conditions, and alcohol, smoking or illicit substance use, and comorbidities, such as HIV infection. The following provides an overview of current guidelines for hormone therapy regimens used by transgender individuals, as well as what is known about the use of exogenous hormones on the cardiovascular system and cardiovascular disease risk. Several gaps in our understanding of the cardiovascular effects of endogenous and exogenous hormones in treated transgender individuals are identified, which provide direction for future study

Impact of Prenatal Cocaine Exposure on Attention and Response Inhibition as Assessed by Continuous Performance Tests

OBJECTIVE: This study examined the influence of prenatal cocaine exposure on attention and response inhibition measured by continuous performance tests (CPTs) at ages 5 and 7 years. METHODS: The baseline sample consisted of 253 cocaine-exposed and 223 non–cocaine-exposed children enrolled prospectively at birth and assessed comprehensively through age 7 years in the longitudinal Miami Prenatal Cocaine Study. This report includes a subsample of 415 children (219 cocaine-exposed, 196 non–cocaine-exposed) who completed at least one CPT assessment at ages 5 and/or 7 years. Prenatal cocaine exposure was measured by maternal self-report and maternal and infant bioassays. Deficits in attention and response inhibition are estimated in relation to prenatal cocaine exposure using generalized estimating equations within the general linear model. RESULTS: Results indicate cocaine-associated increases in omission errors at ages 5 and 7 as well as increases in response times for target tasks (i.e., slower reaction times) and decreased consistency in performance at age 7. There were no demonstrable cocaine-associated deficits in commission errors. Estimates did not change markedly with statistical adjustment for selected prenatal and postnatal covariates. CONCLUSION: Evidence supports cocaine-associated deficits in attention processing through age 7 years