Correction to: Consent requirements for research with human tissue: Swiss ethics committee members disagree.

It has come to our attention that in the original article [1] information regarding dates was omitted. The data in this study were obtained in Switzerland four years before the entering into force of the new Swiss Human Research Act in 2014, when the guidelines of the Swiss Academy of Medical Sciences (SAMS) ceased to apply. It is important for readers to know that at the time of the study there was no binding law in Switzerland, only the more open SAMS guidelines that have a different legal status. We would expect to find less variation of opinions among research ethics committee members if the study were repeated after the federal law came into force.

MACULAR ATROPHY INCIDENCE IN ANTI-VASCULAR ENDOTHELIAL GROWTH FACTOR-TREATED NEOVASCULAR AGE-RELATED MACULAR DEGENERATION: Risk Factor Evaluation for Individualized Treatment Need of Ranibizumab or Aflibercept According to an Observe-and-Plan Regimen.

PURPOSE: To investigate factors associated with macular atrophy (MA) incidence in neovascular age-related macular degeneration treated with either ranibizumab or aflibercept in an Observe-and-Plan variable dosing regimen. METHODS: Information was obtained from two identical prospective treatment protocols using ranibizumab or aflibercept in a variable dosing regimen termed "Observe and Plan." Eyes without MA at baseline were included. New atrophy at the final 2-year visit was investigated with univariate and multivariate analysis to identify associated risk factors, focusing on treatment factors. RESULTS: De novo MA developed in 63 (42%) of 149 eyes/patients (mean age 79.0 years), in 70 eyes treated using aflibercept and 79 eyes using ranibizumab. The univariate analysis showed multiple associations of MA with baseline factors, of which the following were confirmed as independent risk factors after multivariate stepwise logistic regression: lower number of anti-vascular endothelial growth factors injections (P = 0.011), depigmentation (P = 0.0004), reticular pseudodrusen (P = 0.0005), lower baseline visual acuity (P = 0.0006), and retinal angiomatous proliferation (P = 0.001). The drug type showed no significant association with MA incidence (P = 0.21). CONCLUSION: Within the variable dosing regimen, MA incidence was higher when fewer injections were required. More injections, if required by disease activity, did not increase the risk for MA.

Factors influencing macular atrophy growth rates in neovascular age-related macular degeneration treated with ranibizumab or aflibercept according to an observe-and-plan regimen.

BACKGROUND/AIMS: To investigate the factors associated with macular atrophy (MA) growth rates in neovascular age-related macular degeneration treated with either ranibizumab or aflibercept. METHODS: We obtained data from two identical prospective studies using ranibizumab or aflibercept under observe-and-plan variable dosing regimens. We analysed eyes that presented MA within 2 years. After applying square root transformations to MA sizes, we calculated MA growth rate from baseline to the year 2 endpoint and used univariate and multivariate analyses to detect ocular and treatment factors associated with the MA growth rate. RESULTS: Included were 109 eyes from 101 patients (mean age 80.6 years). The mean square-root-transformed MA growth rate was 0.54±0.34 mm/year. The univariate analyses revealed that MA growth rates were significantly associated with lower baseline visual acuities (p=0.001) and thicker subretinal tissue complexes (p=0.006) and near-significantly associated with the presence of pigment epithelium detachment (p=0.057) and choroidal neovascularisation subtypes (p=0.069). Our multivariate analysis confirmed the significance of lower baseline visual acuities (p=0.008) and pigment epithelium detachments higher than 200 µm (p=0.035). Furthermore, MA growth rates in neovascular eyes significantly correlated with MA growth rates in non-neovascular fellow eyes (n=61; p=0.003). CONCLUSION: MA growth rates were associated with ocular factors in the study eyes and the fellow eyes but not with the drug or the number of injections within this variable dosing regimen.

Consent requirements for research with human tissue: Swiss ethics committee members disagree.

BACKGROUND: In Switzerland, research with identifiable human tissue samples, and/or its accompanying data, must be approved by a research ethics committee (REC) before it can be allowed to take place. However, as the demand for such tissue has rapidly increased in recent years, and biobanks have been created to meet these needs, committees have had to deal with a growing number of such demands. Detailed instructions for evaluating every kind of tissue request are scarce. Committees charged with evaluating research protocols therefore sometimes face uncertainty in their decision-making. METHODS: We examine how a pool of Swiss REC members deal with a number of cases involving human tissue, in order to determine the standards they adhere to, and their understanding and implementation of existing laws and guidelines. RESULTS: There is considerable divergence in the approaches and decisions of Swiss REC members regarding human tissue sample requests, particularly concerning the issue of informed consent. Despite recent trends towards less strict consent requirements for biosample research, many of our respondents continue to employ demanding standards for researchers. The question of informed consent, and the circumstances in which it is required, continues to result in differences of opinion. CONCLUSIONS: While room for local and cultural interpretation is essential to the workings of an REC, misunderstanding of existing guidelines, or an absence of regulation in sensitive areas, will only lead to suboptimal functioning of the REC itself. Our data suggests that there is uncertainty and disagreement on the question of consent for human tissue sample, which existing laws and guidelines may not fully clarify. Methods to address these uncertainties should be implemented in order to ensure efficient and harmonious review of research protocols.

GOOD VISUAL OUTCOME AT 1 YEAR IN NEOVASCULAR AGE-RELATED MACULAR DEGENERATION WITH PIGMENT EPITHELIUM DETACHMENT: Factors Influencing the Treatment Response.

PURPOSE: To evaluate baseline and treatment factors influencing the response of pigment epithelial detachment (PED) in patients with treatment-naive neovascular age-related macular degeneration after 1 year of intravitreal anti-vascular endothelial growth factor treatment. METHODS: This retrospective consecutive case series study included 104 eyes (94 patients) with treatment-naive neovascular age-related macular degeneration and associated PED >150 µm treated with aflibercept (n = 41) or ranibizumab (n = 63) for at least 1 year. Stepwise linear regression was used to assess factors influencing best-corrected visual acuity and PED response. RESULTS: At 1 year, the best-corrected visual acuity improved from 20/63 (60.8 ± 15.9 Early Treatment of Diabetic Retinopathy Study letters) at baseline to 20/40 (69.0 ± 15.0 letters) (P = 0.001), and PED maximal height decreased from 370.8 ± 205.6 µm to 238.8 ± 178.5 µm (P = 0.001). Multivariate analysis revealed an association of the visual improvement with lower best-corrected visual acuity at baseline (P = 0.001), the presence of foveal subretinal fluid (P = 0.001), and female gender (P = 0.047). Pigment epithelial detachment height reduction was dependent on higher baseline PED height (P = 0.001) and treatment drug (P = 0.008). CONCLUSION: Visual improvement in neovascular age-related macular degeneration with PED was equally achieved with ranibizumab and aflibercept, influenced mainly by baseline best-corrected visual acuity and foveal subretinal fluid. Pigment epithelial detachment height reduction was influenced by baseline height and the treatment drug, favoring aflibercept for a stronger effect. The clinical significance of this result warrants further studies.

PIGMENT EPITHELIAL DETACHMENT RESPONSE TO AFLIBERCEPT IN NEOVASCULAR AGE-RELATED MACULAR DEGENERATION REFRACTORY TO RANIBIZUMAB: Time Course and Drug Effects.

PURPOSE: To investigate the time course of pigment epithelium detachment (PED) height and its change after anti-vascular endothelial growth factor switch from ranibizumab to aflibercept in neovascular age-related macular degeneration. METHODS: This retrospective study included 60 eyes of 50 consecutive patients with neovascular age-related macular degeneration who showed refractory intraretinal or subretinal fluid (≥9 months) despite monthly ranibizumab treatment and an associated PED (height ≥150 µm). The treatment was switched to aflibercept, and patients were followed-up for at least 9 months. Data on the height and type of PED, exudative fluid, and best-corrected visual acuity were collected at four different time points (two before and two after the drug switch). RESULTS: The maximal PED height was significantly decreased over time, both under ranibizumab and aflibercept treatment. However, the reduction was significantly greater during the 3 months after the switch to aflibercept, due to two outliers. Visual acuity remained stable. Complete resolution of intraretinal or subretinal fluid was observed in 9 cases (15%) at 3 months after switch, allowing for treatment interval extension. CONCLUSION: Maximal PED height continuously decreased over time. Switching the intravitreal anti-vascular endothelial growth factor medication from ranibizumab to aflibercept had a significantly stronger short-term effect on PED height reduction, without changes in visual acuity.