Comparing the effectiveness and costs of Bevacizumab to Ranibizumab in patients with Diabetic Macular Edema: a randomized clinical trial (the BRDME study)

Contains fulltext : 154839.pdf (publisher's version ) (Open Access)BACKGROUND: The effectiveness of ranibizumab in the treatment of diabetic macular edema has been proven with large clinical trials. For bevacizumab only two clinical trials have been published and a head-to-head comparison is lacking to date. However, if proved non-inferior to ranibizumab, use of the off-label bevacizumab could reduce costs enormously without a loss in visual acuity. A cost-effectiveness study has been designed to substantiate this hypothesis. AIM: To compare the effectiveness and costs of 1.25 mg of bevacizumab to 0.5 mg ranibizumab given as monthly intravitreal injections during 6 months in patients with diabetic macular edema. It is hypothesized that bevacizumab is non-inferior to ranibizumab regarding its effectiveness. DESIGN: This is a randomized, controlled, double masked, clinical trial in 246 patients in seven academic trial centres in The Netherlands. OUTCOMES: The primary outcome measure is the change in best-corrected visual acuity (BCVA) in the study eye from baseline to month 6. Secondary outcomes are the proportions of patients with a gain or loss of 15 letters or more or a BCVA of 20/40 or more at 6 months, the change in leakage on fluorescein angiography and the change in foveal thickness by optical coherence tomography at 6 months, the number of adverse events in 6 months, and the costs per quality adjusted life-year of the two treatments

Antiplatelet and anticoagulant drugs do not affect visual acuity in the comparing bevacizumab to ranibizumab in age-related macular degeneration (BRAMD) trial

Ophthalmic researc

Antiplatelet and anticoagulant drugs do not affect visual acuity in the comparing bevacizumab to ranibizumab in age-related macular degeneration (BRAMD) trial

Ophthalmic researc

Mature enzymatic collagen cross-links, hydroxylysylpyridinoline and lysylpyridinoline, in the aging human vitreous

Purpose. The vitreous body of the human eye undergoes progressive morphologic changes with aging. Since the enzymatic collagen cross-links hydroxylysylpyridinoline (HP) and lysylpyridinoline (LP) are known to be important for the integrity of the collagen matrix, the presence in the vitreous on aging was studied. Methods. Vitreous bodies (VBs; n = 143) from 119 donors (age 4-80 years; mean ± SD, 54.3 ± 17.0 years) were carefully dissected. After weighing and freeze-drying, all samples were analyzed by high performance liquid chromatography. Left and right eyes of 24 donors were compared and, for age-related phenomena, 119 single eyes were used. Results. Within one donor, no significant differences were found between left and right eyes. On aging, VB wet weight (4.42 ± 0.84 g) accumulates until 35 years and decreases thereafter. Collagen content (0.30 ± 0.14 mg), HP per triple helix (TH; 0.55 ± 0.18), and (HP plus LP)/TH (0.61 ± 0.19) increase until 50 years followed by a decrease, whereas LP/TH (0.057 ± 0.018) accumulates until 50 years and remains constant thereafter. The ratio between HP and LP (range, 0.42-31.0; median, 10.0) is constant over time. Conclusions. The accumulation of enzymatic collagen cross-links until 50 years is consistent with collagen maturation and possible collagen synthesis in the human vitreous body. The decline of collagen cross-links after 50 years is consistent with collagen breakdown

The incidence of rhegmatogenous retinal detachment in The Netherlands

Item does not contain fulltextOBJECTIVE: To estimate the incidence and characteristics of rhegmatogenous retinal detachment (RRD) in The Netherlands in 2009. DESIGN: Retrospective, observational case series. PARTICIPANTS: All patients with RRD in the Dutch population in 2009. METHODS: By reviewing surgical logs, cases of primary RRD repair in 2009 were identified. Exclusion criteria included RRD before 2009 and exudative, tractional, or traumatic retinal detachments. Patient demographics, date of surgery, and lens status were documented. Incidence of RRD and 95% confidence intervals (CIs) were calculated based on the Poisson distribution. Age distribution, male-to-female ratio, and proportion of RRD patients with prior cataract extraction (CE) were determined. A Student t test was used to examine differences in the incidence of RRD between groups. MAIN OUTCOME MEASURES: Annual RRD incidence in the population and per gender-adjusted age category and proportion of RRD patients with prior CE. RESULTS: The annual RRD incidence was 18.2 per 100 000 people (95% CI, 11.4-18.8), with a peak incidence of 52.5 per 100 000 people (95% CI, 29.4-56.8) between 55 and 59 years of age. The Bilateral RRD rate was 1.67%. Macula-off presentation occurred in 54.5% of all RRD patients. Prior CE was noted in 33.5% of RRD eyes. The male-to-female ratio was 1.3:1, and RRD incidence was statistically significantly more frequent in males (P<0.0001). CONCLUSIONS: Rhegmatogenous retinal detachment is predominantly a disease of the population older than 50 years, and males are more susceptible to RRD. The annual RRD incidence is highly dependent on demographic characteristics

Comparing the Efficacy of Bevacizumab and Ranibizumab in Patients with Retinal Vein Occlusion: The Bevacizumab to Ranibizumab in Retinal Vein Occlusions (BRVO) study, a Randomized Trial

Contains fulltext : 220891.pdf (Publisher’s version ) (Open Access)PURPOSE: Comparing the efficacy of intravitreal injections of bevacizumab to ranibizumab in the treatment of macular edema (ME) resulting from retinal vein occlusion (RVO). DESIGN: Comparative, randomized, double-masked, multicenter, noninferiority clinical trial. The noninferiority margin was 4 letters. PARTICIPANTS: Patients with vision loss resulting from ME secondary to a branch or (hemi) central RVO who might benefit from anti-vascular endothelial growth factor treatment were eligible for participation. METHODS: From June 2012 through February 2018, 277 participants were randomized to receive injections of 1.25 mg bevacizumab (n = 139) or 0.5 mg ranibizumab (n = 138). The follow-up was 6 months with a monthly dosing interval. MAIN OUTCOME MEASURES: The primary outcome was a change in visual acuity from baseline at 6 months. Changes in the central area thickness and safety were studied as secondary outcomes. RESULTS: The mean visual acuity (±standard deviation) improved, with 15.3±13.0 letters for bevacizumab and 15.5±13.3 letters for ranibizumab after 6 months of monthly treatment. The lower limit of the 2-sided 90% confidence interval was -1.724 letters, which is within the noninferiority margin of 4 letters. Even in the branch and (hemi-)central RVO subgroups, minimal differences were found in visual acuity outcomes between treatment arms. Changes in central area thickness on OCT at 6 months did not differ significantly between treatment groups, with a decrease of 287.0±231.3 μm in the bevacizumab group and 300.8±224.8 μm in the ranibizumab group. Severe adverse events (SAEs) were also distributed equally over both treatment groups: 10 participants (7.1%) in the bevacizumab group and 13 participants (9.2%) in the ranibizumab group experienced SAEs. CONCLUSIONS: This study showed, based on the change in visual acuity, that bevacizumab is noninferior to ranibizumab for patients with ME resulting from RVO of either subtype when receiving monthly injections for a period of 6 months. In addition, anatomic and safety outcomes did not differ between treatment groups. Based on our findings, bevacizumab may be an effective alternative to ranibizumab

Overview of the mutation spectrum in familial exudative vitreoretinopathy and Norrie disease with identification of 21 novel variants in FZD4, LRP5, and NDP.

Contains fulltext : 89871.pdf (publisher's version ) (Closed access)Wnt signaling is a crucial component of the cell machinery orchestrating a series of physiological processes such as cell survival, proliferation, and migration. Among the plethora of roles that Wnt signaling plays, its canonical branch regulates eye organogenesis and angiogenesis. Mutations in the genes encoding the low density lipoprotein receptor protein 5 (LRP5) and frizzled 4 (FZD4), acting as coreceptors for Wnt ligands, cause familial exudative vitreoretinopathy (FEVR). Moreover, mutations in the gene encoding NDP, a ligand for these Wnt receptors, cause Norrie disease and FEVR. Both FEVR and Norrie disease share similar phenotypic characteristics, including abnormal vascularization of the peripheral retina and formation of fibrovascular masses in the eye that can lead to blindness. In this mutation update, we report 21 novel variants for FZD4, LRP5, and NDP, and discuss the putative functional consequences of missense mutations. In addition, we provide a comprehensive overview of all previously published variants in the aforementioned genes and summarize the phenotypic characteristics in mouse models carrying mutations in the orthologous genes. The increasing molecular understanding of Wnt signaling, related to ocular development and blood supply, offers more tools for accurate disease diagnosis that may be important in the development of therapeutic interventions.1 juni 201