Intraocular and systemic inflammation-related cytokines during one year of ranibizumab treatment for neovascular age-related macular degeneration.

PURPOSE: To determine inflammation-related intraocular and systemic cytokine concentrations in neovascular age-related macular degeneration (nAMD) compared with controls and to assess the influence of long-term intravitreal ranibizumab treatment over 1 year. METHODS: Aqueous humour and blood plasma of 21 controls and 17 treatment-naive nAMD patients were collected prior to cataract surgery or ranibizumab treatment. Follow-up specimens in nAMD patients were acquired immediately prior to subsequent ranibizumab injections as needed. Multiplex bead assays were conducted for ten inflammation-related cytokines and vascular endothelial growth factor (VEGF). p-values were Holm-Bonferroni-corrected for multiple comparisons. RESULTS: Prior to ranibizumab treatment, initiation aqueous humour levels of monocyte chemo-attractant protein (MCP)-1/CCL2 (p = 0.005) and vascular cell adhesin molecule (VCAM) (p = 0.002) were elevated in nAMD compared with controls. Other intraocular cytokines did not differ, including VEGF. In plasma, no differences between nAMD patients and controls were found at baseline. Pro re nata ranibizumab treatment over 12 months with 8 ± 2 injections reduced aqueous VEGF (p < 0.0001) with a trend to reduced VEGF plasma concentrations (p = 0.046), with all specimens taken at least 28 days after the previous injection. All other local and systemic cytokines remained unchanged. CONCLUSION: Neovascular age-related macular degeneration is associated with local ocular MCP-1/CCL2 and VCAM elevations, suggesting a local inflammatory involvement in the pathophysiology of nAMD. We did not detect systemic differences. Ranibizumab treatment does not result in local or systemic changes of these cytokines, in contrast to VEGF suppression. MCP-1/CCL2 and VCAM may be potential additional treatment targets for nAMD.

Adherence to ranibizumab treatment for neovascular age-related macular degeneration in real life.

BACKGROUND: To identify factors and problems influencing treatment adherence in patients undergoing anti-VEGF therapy for neovascular age-related macular degeneration (AMD) under real-life conditions. METHODS: Cross-sectional study was conducted of 95 patients receiving ranibizumab therapy on a pro re nata (PRN) regimen with monthly controls in a tertiary health care clinic. Monthly controls included best corrected visual acuity, slit-lamp examination and spectral-domain optical coherence tomography. Adherence was measured using Kaplan-Meier time-to-discontinuation analysis. Patients were asked to respond to a 16-item questionnaire covering items such as anxiety, subjective benefit, and financial issues of therapy. RESULTS: Forty-two men and 53 women were included. After a mean follow-up time of 675 days (range 63-1008), adherence was 81.1% (77/95). The mean number of follow-up visits was 19 (3-30), the mean number of intravitreal injections was ten (3-23). Seven patients withdrew from treatment due to subjective dissatisfaction with benefit. Other reasons for loss to follow-up were death in one case, serious general disease in three patients, and treatment options closer to home in five cases. Two patients cancelled further follow-up after treatment cessation due to terminal fibrosis. 62.1% of patients were afraid of a negative examination result, whereas 19.0% were afraid of intravitreal injections. A major problem was travel to and from the hospital (46.3%), with 61.5% of patients requiring escort. CONCLUSION: Despite necessary monthly visits, patients showed a high adherence to therapy. The major problem was travel to and from the hospital. From the patients' point of view, anxiety of a negative examination result was more pronounced than fear of intraocular injections, which would be an argument for continuous injections rather than for a PRN regimen.

Vascular endothelial growth factor in patients with exudative age-related macular degeneration treated with ranibizumab.

OBJECTIVES: To analyze the temporal correlations of vascular endothelial growth factor (VEGF) suppression, morphologic recurrence of choroidal neovascularization (CNV), and visual acuity loss in eyes with exudative age-related macular degeneration (AMD) treated with ranibizumab. DESIGN: Nonrandomized, prospective, clinical study. PARTICIPANTS: Forty-seven eyes of 47 patients with exudative AMD undergoing intravitreal ranibizumab injections. METHODS: Aqueous humor specimens were taken before each intravitreal ranibizumab injection. Visual acuity testing, spectral domain optical coherence tomography (SD-OCT), and fundoscopy were performed before each injection. Vascular endothelial growth factor A was measured by Luminex multiplex bead analysis (Luminex Inc., Austin, TX). MAIN OUTCOME MEASURES: Intraocular VEGF concentration, recurrence of CNV activity shown by SD-OCT, and vision loss. RESULTS: Ranibizumab resulted in complete VEGF suppression within a mean period of 37.8 days (standard deviation [SD] ± 4.8 days; range, 26-49 days). Recurrences of CNV activity as determined by SD-OCT occurred 93.7 days (SD ± 69.9 days; range, 57-368 days) after the last ranibizumab treatment. The VEGF levels were never suppressed when a recurrence occurred. Functional recurrence (visual acuity) occurred 114.3 days (SD ± 81.4 days; range, 57-398 days) after previous treatment. The VEGF levels did not differ significantly between baseline and recurrence (69.3 pg/ml vs. 74.14 pg/ml; 95% confidence interval, -18.87 to 9.12). CONCLUSIONS: A monthly intravitreal injection of 0.5 mg ranibizumab yields a durable VEGF inhibition. The recurrences of CNV as determined by SD-OCT are always preceded by a loss of intraocular VEGF suppression and usually followed by loss of visual acuity in the further course.