Association of systemic medication use with glaucoma and intraocular pressure: the E3 Consortium

PURPOSE: To investigate the association of commonly used systemic medications with glaucoma and intraocular pressure (IOP) in the European population. DESIGN: Meta-analysis of eleven population-based cohort studies of the European Eye Epidemiology (E3) consortium. PARTICIPANTS: A total of 143240 participants were included in the glaucoma analyses and 47177 participants in the IOP analyses. METHODS: We examined associations of four categories of systemic medications (antihypertensive medications: beta-blockers, diuretics, calcium channel blockers [CCBs], alpha-agonists, angiotensin-converting-enzyme inhibitors, angiotensin II receptor blockers; lipid-lowering medications; antidepressants; antidiabetic medications) with glaucoma prevalence and IOP. Glaucoma ascertainment and IOP measurement method were according to individual study protocols. Multivariable regression analyses were carried out in each study and results were pooled using random effects meta-analyses. Associations with antidiabetic medications were examined in diabetic participants only. MAIN OUTCOME MEASURES: Glaucoma prevalence and IOP. RESULTS: In the meta-analyses of our maximally-adjusted multivariable models, use of CCBs was associated with a higher prevalence of glaucoma (odds ratio [OR] with corresponding 95% confidence interval [95% CI]: 1.23 [1.08 to 1.39]). This association was stronger for monotherapy of CCBs with direct cardiac effects (OR [95% CI]: 1.96 [1.23 to 3.12]). The use of other antihypertensive medications, lipid-lowering medications, antidepressants or antidiabetic medications were not clearly associated with glaucoma. Use of systemic beta-blockers was associated with a lower IOP (Beta [95% CI]: -0.33 [-0.57 to -0.08] mmHg). Monotherapy of both selective (Beta [95% CI]: -0.45 [-0.74 to -0.16] mmHg) and non-selective (Beta [95% CI]: -0.54 [-0.94 to -0.15] mmHg) systemic beta-blockers was associated with lower IOP. There was a suggestive association between use of high-ceiling diuretics and lower IOP (Beta [95% CI]: -0.30 [-0.47; -0.14] mmHg), but not when used as monotherapy. Use of other antihypertensive medications, lipid-lowering medications, antidepressants, or antidiabetic medications were not associated with IOP. CONCLUSIONS: We identified a potentially harmful association between use of CCBs and glaucoma prevalence. Additionally, we observed and quantified the association of lower IOP with systemic beta-blocker use. Both findings are potentially important given that glaucoma patients frequently use systemic antihypertensive medications. Determining whether the CCB association is causal should be a research priority

Evaluation of the current knowledge limitations in breast cancer research: a gap analysis

BACKGROUND A gap analysis was conducted to determine which areas of breast cancer research, if targeted by researchers and funding bodies, could produce the greatest impact on patients. METHODS Fifty-six Breast Cancer Campaign grant holders and prominent UK breast cancer researchers participated in a gap analysis of current breast cancer research. Before, during and following the meeting, groups in seven key research areas participated in cycles of presentation, literature review and discussion. Summary papers were prepared by each group and collated into this position paper highlighting the research gaps, with recommendations for action. RESULTS Gaps were identified in all seven themes. General barriers to progress were lack of financial and practical resources, and poor collaboration between disciplines. Critical gaps in each theme included: (1) genetics (knowledge of genetic changes, their effects and interactions); (2) initiation of breast cancer (how developmental signalling pathways cause ductal elongation and branching at the cellular level and influence stem cell dynamics, and how their disruption initiates tumour formation); (3) progression of breast cancer (deciphering the intracellular and extracellular regulators of early progression, tumour growth, angiogenesis and metastasis); (4) therapies and targets (understanding who develops advanced disease); (5) disease markers (incorporating intelligent trial design into all studies to ensure new treatments are tested in patient groups stratified using biomarkers); (6) prevention (strategies to prevent oestrogen-receptor negative tumours and the long-term effects of chemoprevention for oestrogen-receptor positive tumours); (7) psychosocial aspects of cancer (the use of appropriate psychosocial interventions, and the personal impact of all stages of the disease among patients from a range of ethnic and demographic backgrounds). CONCLUSION Through recommendations to address these gaps with future research, the long-term benefits to patients will include: better estimation of risk in families with breast cancer and strategies to reduce risk; better prediction of drug response and patient prognosis; improved tailoring of treatments to patient subgroups and development of new therapeutic approaches; earlier initiation of treatment; more effective use of resources for screening populations; and an enhanced experience for people with or at risk of breast cancer and their families. The challenge to funding bodies and researchers in all disciplines is to focus on these gaps and to drive advances in knowledge into improvements in patient care

Retinal Vascular Occlusion after COVID-19 Vaccination : More Coincidence than Causal Relationship? Data from a Retrospective Multicentre Study

Background: To investigate whether vaccination against SARS-CoV-2 is associated with the onset of retinal vascular occlusive disease (RVOD). Methods: In this multicentre study, data from patients with central and branch retinal vein occlusion (CRVO and BRVO), central and branch retinal artery occlusion (CRAO and BRAO), and anterior ischaemic optic neuropathy (AION) were retrospectively collected during a 2-month index period (1 June–31 July 2021) according to a defined protocol. The relation to any previous vaccination was documented for the consecutive case series. Numbers of RVOD and COVID-19 vaccination were investigated in a case-by-case analysis. A case– control study using age- and sex-matched controls from the general population (study participants from the Gutenberg Health Study) and an adjusted conditional logistic regression analysis was conducted. Results: Four hundred and twenty-one subjects presenting during the index period (61 days) were enrolled: one hundred and twenty-one patients with CRVO, seventy-five with BRVO, fifty-six with CRAO, sixty-five with BRAO, and one hundred and four with AION. Three hundred and thirty-two (78.9%) patients had been vaccinated before the onset of RVOD. The vaccines given were BNT162b2/BioNTech/Pfizer (n = 221), followed by ChadOx1/AstraZeneca (n = 57), mRNA1273/Moderna (n = 21), and Ad26.COV2.S/Johnson & Johnson (n = 11; unknown n = 22). Our case–control analysis integrating population-based data from the GHS yielded no evidence of an increased risk after COVID-19 vaccination (OR = 0.93; 95% CI: 0.60–1.45, p = 0.75) in connection with a vaccination within a 4-week window. Conclusions: To date, there has been no evidence of any association between SARS-CoV-2 vaccination and a higher RVOD risk

Systematic review of instruments for the assessment of patient reported outcomes and quality of life in childhood glaucoma patients

Topic To identify patient-reported outcome measures (PROMs), that have been used in children and adolescents with glaucoma, and to evaluate their methodological quality. Clinical relevance Childhood glaucoma impairs vision and quality of life throughout all stages of life. Thus, a PROM needs to cover many different age groups and topics. Various instruments have been used to evaluate patient-reported outcomes in patients with childhood glaucoma, however it is unclear which PROM has the highest methodological quality and complies best with the needs of childhood glaucoma patients. Methods A systematic literature review was performed searching MEDLINE (PubMed), The Cochrane Library, Web of Science and PsycINFO (EBSCO). We included peer-reviewed full-text articles of the past ten years in English, German or Spanish language that reported PROMs in children with glaucoma. The study selection and methodological quality assessment of the identified PROMs was performed by two independent reviewers using a seven-point checklist. The content was mapped onto the World Health Organization International Classification of Functioning, Disability and Health. The systematic review was prospectively registered in PROSPERO (ID CRD42022353936). Results The search strategy retrieved 3295 matches. 2901 studies were screened, and 11 relevant articles were identified using ten different instruments. The instruments addressed functional visual ability (FVA), vision-related quality of life (VRQoL), health-related QoL (HRQoL), and life satisfaction (LS). Six instruments were applicable for the use in children. Seven of the questionnaires received the highest number of positive ratings (5/7). None of the instruments considered the views of childhood glaucoma patients during their development. Conclusion This systematic review provides a descriptive catalogue of vision-specific and generic health PRO instruments that have been used in childhood glaucoma cohorts. An instrument specifically developed for childhood glaucoma is lacking which might result in missing important factors, such as permanent treatment with eye drops, repeated surgeries and heritability of the disease, when investigating the quality of life in children with glaucoma

Intraocular Pressure Measurement in Childhood Glaucoma under Standardized General Anaesthesia: The Prospective EyeBIS Study

Objective: We aimed to compare intraocular pressure (IOP) measurements using iCare® PRO rebound tonometry (iCare) and Perkins applanation tonometry (Perkins) in childhood glaucoma subjects and healthy children and the influence of anaesthesia depth, age and corneal thickness. Material: Prospective clinical, case-control study of children who underwent an ophthalmologic examination under general anaesthesia according to our protocol. Children were 45.45 ± 29.76 months old (mean ± SD (standard deviation)). Of all children, 54.05% were female. IOP was taken three times (T1–T3), according to duration and the depth of anaesthesia. The order of measurement alternated, starting with iCare. Agreement between the device measurements was evaluated using Bland–Altman analysis. Results: 53 glaucoma subjects and 22 healthy controls. Glaucoma subjects: IOP measured with iCare was at T1: 27.2 (18.1–33.8), T2: 21.6 (14.8–30.6), T3: 20.4 mmHg (14.5–27.0) and Perkins 17.5 (12.0–23.0), 15.5 (10.5–20.5), 15.0 mmHg (10.5–21.0) (median ± IQR (interquartile range)). Healthy controls: IOP with iCare: T1: 13.3 (11.1–17.0), T2: 10.6 (8.1–12.4), T3: 9.6 mmHg (7.7–11.7) and Perkins 10.3 (8.0–12.0), 7.0 (5.5–10.5), 7.0 mmHg (5.5–8.5) (median ± IQR). The median IOP was statistically significantly higher with iCare than with Perkins (p < 0.001) in both groups. The mean difference (iCare and Perkins) was 6.0 ± 6.1 mmHg for T1–T3, 7.3 at T1, 6.0 at T2, 4.9 mmHg at T3. Conclusion: The IOP was the highest in glaucoma subjects and healthy children at T1 (under sedation), independently of the measurement method. iCare always leads to higher IOP compared to Perkins in glaucoma and healthy subjects, regardless of the duration of anesthesia

Long-Term Efficacy and Safety of Modified Canaloplasty Versus Trabeculectomy in Open-Angle Glaucoma

Background: To evaluate the long-term efficacy and safety of modified canaloplasty versus trabeculectomy in open-angle glaucoma. Methods: In total, 210 subjects with open-angle glaucoma were included. 70 were treated with Mitomycin C-augmented modified canaloplasty with enhanced subconjunctival filtration and 140 with Mitomycin C-augmented trabeculectomy. Cases were matched 1:2 by sex and age. Results: In canaloplasty and trabeculectomy groups, 61.4% and 57.9% of participants were female. Mean age was 60.0 ± 13.9 and 63.0 ± 12.2 years, median follow-up time was 4.6 [IQR 4.3, 5.05] years and 5.8 [IQR 5.4, 6.3]. Strict success was achieved in 20.0% and 56.4%, complete success in 24.3% and 66.4%, and qualified success in 34.3% and 73.6% (each p p p p = 0.002), use of AGM (50.0% vs. 10.7%, p p = 0.004). Occurrence of complications was similar in both groups (14.5% vs. 7.5%, p = 0.19). Conclusions: Trabeculectomy showed superiority in efficacy and equality in safety compared to modified canaloplasty

Citalopram-induced pathways regulation and tentative treatment-outcome-predicting biomarkers in lymphoblastoid cell lines from depression patients

Antidepressant therapy is still associated with delays in symptomatic improvement and low response rates. Incomplete understanding of molecular mechanisms underlying antidepressant effects hampered the identification of objective biomarkers for antidepressant response. In this work, we studied transcriptome-wide expression followed by pathway analysis in lymphoblastoid cell lines (LCLs) derived from 17 patients documented for response to SSRI antidepressants from the Munich Antidepressant Response Signatures (MARS) study upon short-term incubation (24 and 48 h) with citalopram. Candidate transcripts were further validated with qPCR in MARS LCLs from responders (n = 33) vs. non-responders (n = 36) and afterward in an independent cohort of treatment-resistant patients (n = 20) vs. first-line responders (n = 24) from the STAR*D study. In MARS cohort we observed significant associations of GAD1 (glutamate decarboxylase 1; p = 0.045), TBC1D9 (TBC1 Domain Family Member 9; p = 0.014–0.021) and NFIB (nuclear factor I B; p = 0.015–0.025) expression with response status, remission status and improvement in depression scale, respectively. Pathway analysis of citalopram-altered gene expression indicated response-status-dependent transcriptional reactions. Whereas in clinical responders neural function pathways were primarily up- or downregulated after incubation with citalopram, deregulated pathways in non-responders LCLs mainly involved cell adhesion and immune response. Results from the STAR*D study showed a marginal association of treatment-resistant depression with NFIB (p = 0.068) but not with GAD1 (p = 0.23) and TBC1D9 (p = 0.27). Our results propose the existence of distinct pathway regulation mechanisms in responders vs. non-responders and suggest GAD1, TBC1D9, and NFIB as tentative predictors for clinical response, full remission, and improvement in depression scale, respectively, with only a weak overlap in predictors of different therapy outcome phenotypes