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Purpose: The aim of this study was to investigate the influence of dietary supplementation using Age-Related Eye Disease Study 2 (AREDS2) on complement activation in patients with neovascular age-related macular degeneration (nAMD) under ongoing treatment., Methods: In this prospective, single-center, controlled, open-label investigator-initiated trial, eligible nAMD patients were randomized at a ratio of 1:1 in 2 groups: those with and without dietary AREDS2 supplementation for 4 weeks. Zinc, plasma, and aqueous humor (AH) complement levels were quantified via enzyme-linked immunosorbent assays., Results: Fifty of 62 enrolled patients completed the trial (AREDS2 n = 27, controls n = 23). Systemic zinc and complement levels were not different at baseline between the 2 groups (p > 0.1). At the final visit, systemic zinc levels were significantly higher in the AREDS2 group (10.16 ± 2.08 μmol/L; 8.66 ± 1.17 μmol/L; p = 0.007), whereas systemic and AH complement levels were not different (p > 0.1). In both groups, no significant change was observed in systemic levels of C3, C3a, FH, FI, and sC5b-9 (p > 0.1). Only systemic complement component Ba showed an increase from baseline to the end visit (p = 0.01). This increase was higher in the control group (p = 0.02) than in the AREDS2 group (p = 0.23)., Conclusions: Short-term dietary AREDS2 supplementation leads to a significant increase in systemic zinc levels without any influence on complement activation levels., (© 2021 S. Karger AG, Basel.)

Introduction: We present a prediction model for progression from early/intermediate to advanced age-related macular degeneration (AMD) within 5.9 years., Objectives: To evaluate the combined role of genetic, nongenetic, and phenotypic risk factors for conversion from early to late AMD over ≥5 years., Methods: Baseline phenotypic characteristics were evaluated based on color fundus photography, spectral-domain optical coherence tomography, and infrared images. Genotyping for 36 single-nucleotide polymorphisms as well as systemic lipid and complement measurements were performed. Multivariable backward logistic regression resulted in a final prediction model., Results and Conclusions: During a mean of 5.9 years of follow-up, 22.4% (n = 52) of the patients (n = 232) showed progression to late AMD. The multivariable prediction model included age, CFH variant rs1061170, pigment abnormalities, drusenoid pigment epithelial detachment (DPED), and hyperreflective foci (HRF). The model showed an area under the curve of 0.969 (95% confidence interval 0.948-0.990) and adequate calibration (Hosmer-Lemeshow test, p = 0.797). In addition to advanced age and carrying a CFH variant, pigment abnormalities, DPED, and HRF are relevant imaging biomarkers for conversion to late AMD. In clinical routine, an intensified monitoring of patients with a high-risk phenotypic profile may be suitable for the early detection of conversion to late AMD., (© 2020 S. Karger AG, Basel.)

Purpose: The aim of this study was to evaluate risk factors for the development of retinal pigment epithelium (RPE) atrophy in patients with neovascular age-related macular degeneration (nAMD)., Procedures: This post hoc analysis of the prospective RESPONSE study includes 52 therapy-naive nAMD patients without baseline RPE atrophy, who were treated with ≥9 anti-vascular endothelial growth factor (VEGF) injections for ≥3 years. RPE atrophy was assessed via multimodal imaging. Baseline aqueous VEGF and serum complement levels (C3d/C3) were measured. Risk factors for atrophy development were evaluated via logistic regression analysis., Results: Atrophy onset was significantly associated with the duration of nAMD (mean 5.34 years; odds ratio = 1.83, p = 0.012). Anti-VEGF injection number, age, C3d/C3 ratio, baseline intraocular VEGF, or delay to the first treatment had no influence on RPE atrophy., Conclusions: The duration of treatment-requiring nAMD was identified as primary risk factor for the onset of concomitant RPE atrophy after commencing therapy. Targeting concomitant atrophy in nAMD patients might improve the long-term prognosis of the disease., (© 2018 S. Karger AG, Basel.)

Purpose: To compare changes of retinal morphology in the first weeks following injection of anti-VEGF agents for neovascular age-related macular degeneration (nAMD)., Procedures: In a prospective study 50 patients with active choroidal neovascularization secondary to nAMD were monitored weekly by spectral-domain optical coherence tomography for 3 weeks after treatment. Twenty-two patients received bevacizumab, 15 ranibizumab, and 13 aflibercept. Morphological parameters of retinal compartments were compared., Results: Mean central retinal thickness (391.22 ± 123.41 µm) was reduced by -26.15 µm (p < 0.001) after 1 week, by -12.54 µm (p < 0.001) after 2 weeks, and by -3.52 µm (p = 0.09) after 3 weeks. Mean intraretinal layer thickness changed only significantly between baseline and week 1 (p < 0.001). Mean subretinal thickness also decreased between weeks 1 and 2 (p = 0.01)., Conclusions: Early morphological changes occur primarily in the first 14 days after treatment. This information could be clinically helpful to evaluate early non-response., (© 2017 S. Karger AG, Basel.)

Purpose: To analyze peripapillary retinal nerve fiber layer thickness (RNFLT) change after long-term intravitreal anti-VEGF therapy. Patients with regular anterior chamber paracentesis (ACP) prior to intravitreal injections (IVIs) were compared to those without ACP., Methods: Neovascular age-related macular degeneration (nAMD) was treated in a pro re nata regimen with a minimum of 9 IVIs. RNFLT change was determined in spectral domain optical coherence tomography., Results: In 32 patients without ACP, mean RNFLT loss (-2.16 ± 3.60 µm) was significantly higher than in 44 patients with regular ACP (0.16 ± 3.60; p = 0.029). Both groups were comparable in age (75.0 vs. 76.8 years; p = 0.35), number of IVIs (16.2 vs. 16.6; p = 0.98), and observational time (30.0 vs. 32.3 months; p = 0.32). In patients without ACP, RNFLT loss was higher compared to IVI-naive fellow eyes (p = 0.005), whereas in ACP patients, no difference was detected (p = 0.5)., Conclusions: A moderate RNFLT loss is found in nonglaucomatous patients after injection therapy for nAMD. As it is decreased with regular ACP, tight management of intraocular pressure seems advisable., (© 2017 S. Karger AG, Basel.)