Association of CD11b+ Monocytes and Anti-Vascular Endothelial Growth Factor Injections in Treatment of Neovascular Age-Related Macular Degeneration and Polypoidal Choroidal Vasculopathy.

Importance: CD11b+ immune cells have been implicated in the formation of choroidal neovascularization in experimental studies on animals and disease-association studies on humans. However, the clinical importance of such observations remains unknown. Objective: To investigate whether the proportion of CD11b+ circulating monocytes is associated with the number of anti-vascular endothelial growth factor (anti-VEGF) injections in neovascular age-related macular degeneration (AMD) and polypoidal choroidal vasculopathy (PCV). Design, Setting, and Participants: These observational cohort studies collected data from January 1, 2010, through December 31, 2013, and from January 1, 2015, through December 31, 2018. Fresh venous blood samples were acquired for flow cytometric immune studies in patients with neovascular AMD or PCV receiving treatment with aflibercept or ranibizumab as needed for 36 months. Patients (n = 81) without immune diseases were consecutively recruited from a single center in Denmark. Exposures: Proportion of CD11b+ circulating monocytes. Main Outcomes and Measures: The estimation of the number of intravitreal anti-VEGF injections given at 12, 24, and 36 months by the proportion of CD11b+ circulating monocytes and the correlation between these values. The angiogenic role of CD11b+ circulating monocytes was further evaluated by investigating the expression of the known proangiogenic receptor CCR2. Results: Eighty-one patients were included in the analysis (54% women; mean [SD] age, 76 [7] years). The proportion of CD11b+ monocytes at baseline positively estimated the future number of anti-VEGF injections at 12 (ρ = 0.77; 95% CI, 0.35-0.93; P = .004), 24 (ρ = 0.82; 95% CI, 0.44-0.95; P = .002), and 36 (ρ = 0.78; 95% CI, 0.34-0.94; P = .005) months. This association was also found retrospectively in a larger sample of patients with neovascular AMD at 12 (ρ = 0.46; 95% CI, 0.16-0.68; P = .004), 24 (ρ = 0.49; 95% CI, 0.20-0.70; P = .002), and 36 (ρ = 0.65; 95% CI, 0.41-0.80; P < .001) months and patients with PCV at 12 (ρ = 0.27; 95% CI, -0.28 to 0.68; P = .30), 24 (ρ = 0.60; 95% CI, 0.12-0.85; P = .02), and 36 (ρ = 0.70; 95% CI, 0.27-0.90; P = .005) months, suggesting that this association is not specific to AMD but rather reflects VEGF activity in neovascularization. CD11b+ monocytes highly coexpressed CCR2, an important monocytic marker of proangiogenic activity. Conclusions and Relevance: Results of this study demonstrated that the proportion of circulating CD11b+ monocytes estimated and correlated with the number of anti-VEGF injections in patients with neovascular AMD and PCV. Additional longitudinal studies are needed to determine whether these findings have clinical relevance to influence treatment algorithms or provide novel targets for medical therapy.

Age-related macular degeneration is associated with increased proportion of CD56(+) T cells in peripheral blood.

PURPOSE: To examine the association between age-related changes in the T-cell compartment and prevalence of age-related macular degeneration (AMD). DESIGN: Case-control study. PARTICIPANTS: A total of 117 AMD cases and 106 controls were included prospectively. METHODS: Fresh-drawn peripheral blood samples were processed for flow cytometric analysis of T-cell populations. Plasma samples were analyzed for anti-cytomegalovirus (CMV) immunoglobulin (Ig)G and complement factor H (CFH) Y402H genotype. The diagnosis of AMD was made according to the Clinical Age-Related Maculopathy Staging System. MAIN OUTCOME MEASURES: Association between frequency of aged T cells and prevalence of AMD. RESULTS: The prevalence of AMD was associated with distinct age-related changes in the T-cell compartment. Specifically, the patients with AMD had an increased frequency of CD28(-) T cells that expressed the CD56 surface marker (patients, 34.9% vs. aged controls, 25.8%; P = 0.002). Participants in the highest tertile of CD56(+) CD28(-) T cells had an odds ratio (OR) for the presence of AMD of 3.2 (95% confidence interval [CI], 1.2-8.8) after adjustment for CFH genotype, anti-CMV IgG positivity, age, sex, and smoking history. The adjusted OR of the presence of AMD for persons having at least 1 CFH H402 risk allele increased from 3.5 (95% CI, 1.5-8.1) to 13.3 (95% CI, 3.3-53.6) for persons with at least 1 CFH H402 risk allele and above the median level of CD56(+) CD28(-) T cells. CONCLUSIONS: We found increased levels of circulating aged CD56(+) CD28(-) T cells in patients with AMD. Although this supports the notion of AMD as a systemic disease, it also suggests that the adaptive immune system is implicated in its pathogenesis.

Four-year treatment results of neovascular age-related macular degeneration with ranibizumab and causes for discontinuation of treatment.

PURPOSE: To evaluate 4-year treatment results of neovascular age-related macular degeneration with ranibizumab using a variable dosing regimen. DESIGN: Retrospective, single-center chart review. METHODS: This was a retrospective single-center study that included 855 patients with neovascular age-related macular degeneration receiving treatment with ranibizumab during a 4-year period. Included in the study were patients with a minimum follow-up of 15 months and all patients who terminated treatment regardless of follow-up. RESULTS: A total of 1321 patients were treated over the 4-year period, and 855 patients were eligible for inclusion. Of those, 456 patients were still receiving active treatment, whereas 399 patients had discontinued treatment. Overall treatment results showed a significant decrease in vision from 53.2 Early Treatment Diabetic Retinopathy Study letters (range, 1 to 85 letters) to 50.5 letters (range, 1 to 87 letters; P < .001). Mean follow-up was 23.3 months (range, 4 to 48 months). The reason for discontinuing treatment in 181 patients was no signs of activity, whereas 113 patients were judged to be nontreatable. Thirty-six patients declined further treatment for various reasons. CONCLUSIONS: This report shows that when follow-up extends beyond 2 to 3 years, visual acuity does seem to decrease. Our data show that different responder groups can be identified: bad or nonresponders (approximately 15% of all patients) and good responders (approximately 21% of all patients). These 2 groups in general can be identified within the first 2 years of treatment, whereas the third group of regular responders (approximately 64% of all patients) require continuous monitoring and treatment for years.