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Purpose Genetic and epidemiologic studies have shown that lipid genes and high-density lipoproteins (HDLs) are implicated in age-related macular degeneration (AMD). We studied circulating lipid levels in relationship to AMD in a large European dataset. Design Pooled analysis of cross-sectional data. Participants Individuals (N = 30 953) aged 50 years or older participating in the European Eye Epidemiology (E3) consortium and 1530 individuals from the Rotterdam Study with lipid subfraction data. Methods AMD features were graded on fundus photographs using the Rotterdam classification. Routine blood lipid measurements, genetics, medication, and potential confounders were extracted from the E3 database. In a subgroup of the Rotterdam Study, lipid subfractions were identified by the Nightingale biomarker platform. Random-intercepts mixed-effects models incorporating confounders and study site as a random effect were used to estimate associations. Main Outcome Measures AMD features and stage; lipid measurements. Results HDL was associated with an increased risk of AMD (odds ratio [OR], 1.21 per 1-mmol/l increase; 95% confidence interval [CI], 1.14–1.29), whereas triglycerides were associated with a decreased risk (OR, 0.94 per 1-mmol/l increase; 95% CI, 0.91–0.97). Both were associated with drusen size. Higher HDL raised the odds of larger drusen, whereas higher triglycerides decreases the odds. LDL cholesterol reached statistical significance only in the association with early AMD (P = 0.045). Regarding lipid subfractions, the concentration of extra-large HDL particles showed the most prominent association with AMD (OR, 1.24; 95% CI, 1.10–1.40). The cholesteryl ester transfer protein risk variant (rs17231506) for AMD was in line with increased HDL levels (P = 7.7 × 10–7), but lipase C risk variants (rs2043085, rs2070895) were associated in an opposite way (P = 1.0 × 10–6 and P = 1.6 × 10–4). Conclusions Our study suggested that HDL cholesterol is associated with increased risk of AMD and that triglycerides are negatively associated. Both show the strongest association with early AMD and drusen. Extra-large HDL subfractions seem to be drivers in the relationship with AMD, and variants in lipid genes play a more ambiguous role in this association. Whether systemic lipids directly influence AMD or represent lipid metabolism in the retina remains to be answered.

This article describes the role of outcomes and health services research in the field of ophthalmology in Germany. First, the need for more information and data on the performance of ophthalmic care in Germany is explored. The concept, goals and methods of outcomes and health services research are explained and illustrated by examples of already existing research projects in ophthalmology. Future topics for research projects are highlighted. The article also describes how the field of outcomes and health services research can become a more important part within the scientific ophthalmological community in Germany.

Contains fulltext : 167190.pdf (Publisher’s version ) (Open Access) Myopia, currently at epidemic levels in East Asia, is a leading cause of untreatable visual impairment. Genome-wide association studies (GWAS) in adults have identified 39 loci associated with refractive error and myopia. Here, the age-of-onset of association between genetic variants at these 39 loci and refractive error was investigated in 5200 children assessed longitudinally across ages 7-15 years, along with gene-environment interactions involving the major environmental risk-factors, nearwork and time outdoors. Specific variants could be categorized as showing evidence of: (a) early-onset effects remaining stable through childhood, (b) early-onset effects that progressed further with increasing age, or (c) onset later in childhood (N = 10, 5 and 11 variants, respectively). A genetic risk score (GRS) for all 39 variants explained 0.6% (P = 6.6E-08) and 2.3% (P = 6.9E-21) of the variance in refractive error at ages 7 and 15, respectively, supporting increased effects from these genetic variants at older ages. Replication in multi-ancestry samples (combined N = 5599) yielded evidence of childhood onset for 6 of 12 variants present in both Asians and Europeans. There was no indication that variant or GRS effects altered depending on time outdoors, however 5 variants showed nominal evidence of interactions with nearwork (top variant, rs7829127 in ZMAT4; P = 6.3E-04).

Introduction The efficacy, safety and tolerability of the preservative-free (PF) fixed combination (FC) of tafluprost 0.0015% and timolol 0.5% (once daily) were compared to those of the individual components (PF tafluprost 0.0015% once daily and PF timolol 0.5% twice daily) in patients with open-angle glaucoma or ocular hypertension inadequately controlled on prior timolol or prostaglandin monotherapy for 6 months. Methods A stratified, double-masked, randomized, multicenter phase III study was conducted. A total of 189 prior timolol users were randomized within the timolol stratum (TS) to receive either FC (n = 95) or timolol 0.5% (TIM; n = 94). Furthermore, a total of 375 prior prostaglandin analog (PGA) users were randomized within the prostaglandin stratum (PS) to receive either FC (n = 188) or tafluprost 0.0015% (TAF; n = 187). To be eligible for participation in the study, the patients were required to have an intraocular pressure (IOP) of ≥22 mmHg when on timolol (TIM) or of ≥20 mmHg when on PGA in either treated eye at the screening and end-of-run-in visits. In addition to these, the study included visits at baseline, 2 and 6 weeks, 3 and 6 months and at a post-study visit. IOP was measured at 8 a.m., 10 a.m., 4 p.m., and 8 p.m. Results In the TS, a significant reduction from baseline IOP was seen with FC and TIM throughout the study. Average diurnal IOP change from baseline at month 3 was −8.55 mmHg (32%) for FC and −7.35 mmHg (28%) for TIM. The model-based treatment difference (FC–TIM) was −0.885 mmHg [95% confidence interval (CI) −1.745 to −0.024; p = 0.044] demonstrating the superiority of FC over TIM. In the PS, a significant reduction in IOP was seen with both FC and TAF throughout the study. The average diurnal IOP change from baseline at month 3 was −8.61 mmHg (33%) for FC and −7.23 mmHg (28%) for TAF. The model-based treatment difference (FC–TAF) was −1.516 mmHg (95% CI −2.044 to −0.988; p

Objective: To evaluate the predictive factors of open-angle glaucoma (OAG) in patients affected by ocular hypertension enrolled in the European Glaucoma Prevention Study (EGPS). Design: Randomized, double-masked, controlled clinical trial. Participants: One thousand seventy-seven patients, ≥30 years old, were enrolled at 18 European centers. The patients met inclusion criteria: intraocular pressure, 22 to 29 mmHg; 2 normal and reliable visual fields (VFs) (on the basis of mean deviation and corrected pattern standard deviation [PSD]); and a normal optic disc, as determined by an optic disc reading center. Intervention: Treatment with dorzolamide or a placebo (the vehicle of dorzolamide) in one or both eyes. Main Outcome Measures: Efficacy end points were VF and/or optic disc changes. Baseline demographic and clinical data were collected before randomization, except for corneal thickness measurements, which were determined during follow-up. Proportional hazards models were used to identify factors that predicted which participants in the EGPS had developed OAG. Results: In multivariate analyses, factors that predicted the development of OAG included older age (hazard ratio [HR], 1.32; 95% confidence interval [CI], 1.04-1.69), larger vertical cup-to-disc (C/D) ratio (HR, 1.34; 95% CI, 1.14-1.58), larger vertical C/D ratio asymmetry (HR, 1.46; 95% CI, 1.11-1.93), higher PSD (HR, 1.66; 95% CI, 1.15-2.38), and lesser central corneal thickness (HR, 1.32; 95% CI, 1.05-1.67). Conclusions: Baseline age, vertical C/D ratio, vertical C/D ratio asymmetry, and PSD were good predictors of the onset of OAG in the EGPS. Central corneal thickness was found to be a powerful predictor of the development of OAG. The EGPS results agree with the findings of the Ocular Hypertension Treatment Study and support the need for a thorough evaluation of patients with ocular hypertension. © 2007 American Academy of Ophthalmology.

Objectives The European Glaucoma Prevention Study seeks to evaluate the efficacy of reducing intraocular pressure (IOP), with dorzolamide to prevent or delay patients affected by ocular hypertension from developing primary open-angle glaucoma. Design Randomized, double-blinded, controlled clinical trial. Participants Patients (age > or =30 years) were enrolled from 18 European centers. The patients fulfilled a series of inclusion criteria including the measurements of IOP (22-29 mmHg), two normal and reliable visual fields (VFs) (on the basis of mean defect and corrected pattern standard deviation/corrected loss of variance of standard 30/II Humphrey or Octopus perimetry), and normal optic disc as determined by the Optic Disc Reading Center (vertical and horizontal cup-to-disc ratios; asymmetry between the two eyes Intervention Patients were randomized to the treatment with dorzolamide or a placebo. Main outcome measures End points are VF and/or optic disc changes. A VF change during the follow-up must be confirmed by two further positive tests. Optic disc change is defined by the agreement of two out of three independent observers evaluating optic disc stereo-slides. Results One thousand seventy-seven subjects were randomized between January 1, 1997 and May 31, 1999. The mean age was 57.03 +/- 10.3 years; 54.41% were women and 99.9% were Caucasian. Mean IOP was 23.6 +/- 1.6 mmHg in both eyes. Mean visual acuity was 0.97 +/- 0.11 in both eyes; mean refraction was 0.23 +/- 1.76 diopters in the right eye and 0.18 +/- 1.79 diopters in the left eye. Previous use of medication for ocular hypertension was reported by 38.4% of the patients, systemic hypertension by 28.1%, cardiovascular diseases by 12.9%, and diabetes mellitus by 4.7%. The qualifying VFs were normal and reliable according to protocol criteria. Conclusions The mean IOP of the patients enrolled in the European Glaucoma Prevention Study is consistent with the estimated mean IOP (within the range of 22-29 mmHg) found in a large sample of the European population. The European Glaucoma Prevention Study should be able to better address the clinical question of whether pharmacological reduction of IOP (by means of dorzolamide) in ocular hypertension patients at moderate risk for developing primary open-angle glaucoma effectively lowers the incidence of primary open-angle glaucoma.

PURPOSE To determine the reproducibility of the assessment for glaucomatous change in serial optic disc stereo-slides. DESIGN Masked interobserver variability study. PARTICIPANTS Serial optic disc stereo-slides from 40 patients. METHODS Three independent ophthalmologists evaluated for change a set of two serial 20 degrees optic disc color stereo-slides of 40 patients. This test set was not from European Glaucoma Prevention Study (EGPS) patients. Each observer performed two evaluations at least 30 days apart and was masked from the temporal sequence of the slides and his or her previous evaluation. Each patient was graded as changed or stable by two-out-of-three agreement. A kappa statistic was used to calculate the intra- and interobserver reproducibility as well as the assignment reproducibility (first consensus versus second consensus). The same procedure was followed to test the reproducibility when another experienced ophthalmologist was added to one of the three reading centers. MAIN OUTCOME MEASURES Reproducibility in evaluating glaucomatous optic disc change. RESULTS The intraobserver reproducibility (95% confidence interval [CI]) in the evaluation of change ranged between 0.79 (0.45-1.14) and 1.00 (0.69-1.31). The interobserver reproducibility (95% CI) in the evaluation of change ranged between 0.45 (0.15-0.75) and 0.75 (0.44-1.06). The assignment reproducibility (first consensus versus second consensus in the evaluation of change) between the senior EGPS readers was 0.94 (0.63-1.25). The assignment reproducibility when another experienced ophthalmologist replaced one of the readers was 0.94 (0.63-1.25). CONCLUSIONS The assignment reproducibility of three expert readers looking for glaucomatous change in serial optic disc stereo-slides was excellent. It remained so when one of the three experts was replaced by another experienced reader.

Current management of glaucoma entails the medical, laser, or surgical reduction of intraocular pressure (IOP) to a predetermined level of target IOP, which is commensurate with either stability or delayed progression of visual loss. In the published literature, the hypothesis is often made that IOP control implies a single IOP measurement over time. Although the follow-up of glaucoma patients with single IOP measurements is quick and convenient, such measurements often do not adequately reflect the untreated IOP characteristics, or indeed the quality of treated IOP control during the 24-h cycle. Since glaucoma is a 24-h disease and the damaging effect of elevated IOP is continuous, it is logical that we should aim to understand the efficacy of all treatment options throughout the 24-h period. This article first reviews the concept and value of diurnal and 24-h IOP monitoring. It then critically evaluates selected available evidence on the 24-h efficacy of medical, laser and surgical therapy options. During the past decade several controlled trials have significantly enhanced our understanding on the 24-h efficacy of all glaucoma therapy options. Nevertheless, more long-term evidence is needed to better evaluate the 24-h efficacy of glaucoma therapy and the precise impact of IOP characteristics on glaucomatous progression and visual prognosis. Electronic supplementary material The online version of this article (doi:10.1007/s12325-016-0302-0) contains supplementary material, which is available to authorized users.

Purpose: To describe the study design and baseline factors of the Heidelberg Retina Tomograph ancillary study within the EGPS. Furthermore, to examine the relationship between HRT optic disc topographic measurements and baseline demographic and ocular factors. Methods: Four hundred and eighty-nine ocular hypertensive participants were included. Each participant completed HRT imaging at least annually. The associations between HRT measurements and IOP, central corneal thickness (CCT), baseline photographic estimates of vertical CDR ratio (CDR), asymmetry between the two eyes in CDR ratio and baseline visual field indices were assessed using regression analysis. Results: Associations between HRT measurements and vertical CDR by photographs were found for almost all stereometric optic disc parameters in both univariate and multivariate analysis. The strongest association was found between vertical CDR measurements and disc, cup and rim area; cup and rim volume, CDR area, linear CDR, mean and maximum cup depth and cup shape measure (all p < 0.0001). In multivariate analysis, pattern standard deviation (PSD) and HRT disc area had significant associations with several HRT optic disc measurements. Furthermore, CCT was significantly associated with reference height and the glaucoma probability score (GPS, outside normal limits). Conclusions: The EGPS is the first multicentre, placebo-controlled randomized clinical trial to use HRT for monitoring optic disc changes in participants with ocular hypertension. We found strong associations between stereophotographic vertical CDR estimates, HRT disc area, PSD and several HRT parameters. We found, furthermore, that the parameters reference height and GPS were significantly related to central corneal thickness. © 2013 Acta Ophthalmologica Scandinavica Foundation. Published by John Wiley & Sons Ltd.